fluticasone-propionate--salmeterol-xinafoate-drug-combination and Asthma

Compared with the adult population, fewer clinical studies have investigated the efficacy of FP/SAL in paediatric patients with moderate and moderate-to-severe asthma. In this review, we synthesise the available evidence for the efficacy and safety of FP/SAL in the paediatric population, compared with other available therapies indicated for asthma in children.. A literature review identified randomised controlled trials and observational studies of FP/SAL in the paediatric population with moderate-to-severe asthma.. The Medline database was searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/), with no publication date restrictions. Search strategies were developed and refined by authors.. Selected articles were screened for clinical outcome data (exacerbation reduction, nocturnal awakenings, lung function, symptom control, rescue medication use and safety) and a table of key parameters developed.. Improvements in asthma outcomes with FP/SAL include reduced risk of asthma-related emergency department visits and hospitalisations, protection against exercise-induced asthma and improvements in measures of lung function. Compared with FP monotherapy, greater improvements in measures of lung function and asthma control are reported. In addition, reduced incidence of exacerbations, hospitalisations and rescue medication use is observed with FP/SAL compared with ICS and leukotriene receptor antagonist therapy. Furthermore, FP/SAL therapy can reduce exposure to both inhaled and oral corticosteroids.. FP/SAL is a reliable treatment option in patients not achieving control with ICS monotherapy or a different ICS/LABA combination. Evidence shows that FP/SAL is well tolerated and has a similar safety profile to FP monotherapy. Thus, FP/SAL provides an effective option for the management of moderate-to-severe asthma in the paediatric population.

Topics: Adult; Asthma; Child; Databases, Factual; Emergency Service, Hospital; Fluticasone-Salmeterol Drug Combination; Hospitalization; Humans

This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting beta-agonists (LABA) treatments, including when administered using maintenance and reliever therapy (MART) regimens, in terms of improvements in health-related quality of life (HRQoL). The relationship between changes in asthma control and HRQoL was assessed.. Articles published between 2001 and 2021, reporting change from baseline (CFB) in Asthma Quality of Life Questionnaire (AQLQ) in patients with moderate-to-severe asthma, were identified by a systematic review. Random effects Bayesian NMAs derived estimates of the mean difference in CFB in AQLQ vs. other interventions connected to the network (included 15 studies). Sensitivity analyses explored the impacts of differences in follow-up duration, baseline asthma control, the inclusion of observational studies, adjusting for baseline FEV. Mean CFB in AQLQ with FP/Sal vs. comparators demonstrated expected ranked effects: mean difference 0.65 [95% credible interval: 0.54, 0.78] versus placebo, 0.58 [ 0.33, 0.84] versus LABA, 0.21 [ 0.13, 0.31] versus ICS alone, 0.06 [-0.04, 0.19] versus other ICS/LABA, and 0.00 [-0.13, 0.14] versus ICS/formoterol MART. Sensitivity analyses largely showed consistent results. Improvements in AQLQ and ACQ were strongly correlated (R = 0.94).. This NMA demonstrates that HRQoL is responsive to treatment, is strongly related to asthma control and that it can be well-managed in patients with moderate-to-severe asthma using regular treatment with inhaled FP/Sal.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bayes Theorem; Bronchodilator Agents; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Network Meta-Analysis; Quality of Life

An inhaled corticosteroid (ICS)-long-acting beta-2 agonist (LABA) combination has become the standard of care in asthma. Various ICS-LABAs are commercially available providing the clinician with many choices. A thorough understanding of the clinical efficacy and safety of various formulations will immensely benefit the prescribing doctor to decide the choice of agent. The present systematic review was undertaken to compare the clinical efficacy and safety of formoterol fluticasone (FF) to other ICS/LABA combinations in asthmatics.. The review adhered to the general principles mentioned in the CRD guidance and the PRISMA statement. We searched Medline, Embase, and Cochrane Controlled Trials Register databases on the efficacy of FF in treating asthma compared with other ICS-LABAs. A total of 138 trials identified initially. Only trials comparing the efficacy and safety of FF in comparision with Salmeterol/fluticasone (SF) or Budesonide/Formoterol (BF) were selected. The outcomes compared were onset of bronchodilator action, improvement in lung function, asthma control, asthma-related quality of life and risk of pneumonia.. Sixteen studies were included in the final analysis. FF therapy provided faster onset of bronchodilatation than SF. A better improvement in lung function was seen with FF inhaler use as compared with comparators in two studies. Patients using the FF inhaler had a non-inferior asthma control and asthma-related quality of life. Pneumonia risk was least with FF usage.. FF provides faster onset of action, numerically superior improvement in lung function and comparable asthma control than other ICS-LABA formulations. FF has better safety evidenced by lower occurrence of pneumonia.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Androstadienes; Asthma; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Pneumonia; Quality of Life

Topics: Asthma; Bronchodilator Agents; Drug-Related Side Effects and Adverse Reactions; Drugs, Generic; Dry Powder Inhalers; Fluticasone-Salmeterol Drug Combination; Humans; Treatment Outcome

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Drugs, Generic; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Health Services Needs and Demand; Humans; Nebulizers and Vaporizers; Powders; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Standard of Care; Therapeutic Equivalency

Pressurized metered dose inhalers (pMDIs) are evolving to be a very effective drug delivery option in patients with airway diseases. They offer comparable lung deposition and reduced oropharyngeal deposition similar with the dry powder inhalers. As recommended by the Global Initiative for Asthma guidelines, the ideal maintenance treatment for asthma is a combination of long acting β2-agonists (LABAs) and inhaled corticosteroids (ICSs). One of the available LABA/ICS combinations is the salmeterol/fluticasone propionate combination (SFC) and a plethora of evidence supports its clinical efficacy and safety.. This article focuses on the SFC hydrofluroalkane pMDI and compares the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI. Also discussed is the efficacy and tolerability of the SFC delivered via a pMDI, as compared to the SFC via Diskus.. pMDIs play an important role in inhalation therapy given the low price, low maintenance and convenience of use. LABA/ICS combinations are the preferred choice of medication for asthma treatment and will remain the mainstay for the decades to come. In our opinion, pMDI should be the choice of device to administer LABA/ICS maintenance therapy, as it is already being used by the patients for reliever therapy, which may eventually improve patient adherence and compliance.

Topics: Albuterol; Androstadienes; Asthma; Beclomethasone; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Lung; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols

Chronic obstructive pulmonary disease (COPD) and asthma are common airway disorders characterized by chronic airway inflammation and airflow obstruction, and are a leading cause of morbidity and mortality in the People's Republic of China. These two diseases pose a high economic burden on the family and the whole of society. Despite evidence-based Global Initiative for Chronic Obstructive Lung Disease and Global Initiative for Asthma guidelines being available for the diagnosis and management of COPD and asthma, many of these patients are not properly diagnosed or managed in the People's Republic of China. The value of combination therapy with inhaled corticosteroids and long-acting β2-agonists has been established in the management of asthma and COPD globally. Combinations of inhaled corticosteroids and long-acting β2-agonists such as fluticasone and salmeterol, have been shown to be effective for improving symptoms, health status, and reducing exacerbations in both diseases. In this review, we discuss the efficacy and safety of this combination therapy from key studies, particularly in the People's Republic of China.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Asian People; Asthma; Bronchodilator Agents; China; Cost-Benefit Analysis; Drug Costs; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Lung; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

To evaluate the cost-utility of the treatment with a long acting beta-agonist (LABA) and inhaled corticosteroid (ICS) combination inhaler [salmeterol xinafoate (SAL)/fluticasone propionate (FP) combination inhaler (SFC) (Advair(®))] to continuing on current ICS dose (no ICS dose change) or increased ICS dose [fluticasone propionate (FP)] in patients with uncontrolled asthma in Canada.. A cost-utility analysis was conducted from a Canadian public healthcare perspective with a one year time horizon. In the no FP dose change scenarios, remaining on daily low (FP 100 ug BID) or medium (FP 200-250 ug BID) or high dose (FP 500 ug BID) was considered. In the increased FP dose scenarios, doubling the FP dose from low to medium dose and from medium to high dose regimens were considered. A decision model was developed with two health states: "symptom free" or "with symptoms". Clinical efficacy was based on a meta-analysis of relevant randomized controlled trials. Over the one year time horizon the percentage with symptom free days (SFD) was used as the measure of differential treatment scenario effectiveness. Drug costs and non-drug costs were incorporated into the analysis. Utilities, derived from EQ5D scores and health services resource use based on patient diaries for 'symptom free' and 'with symptoms' were based on regression analyses of individual patient data from the Gaining Optimal Asthma controL (GOAL) trial. Costs were assessed by assigning unit cost for each health services resource use for each patient. The incremental cost-utility ratios (ICUR) for SFC vs no FP dose change or increased FP dose were estimated using descriptive statistics. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis (PSA).. Over one year, SFC resulted in an incremental cost per patient of $544-$655 compared to no FP dose change and $47-$380 per year compared to increased FP dose. SFC results in incremental QALYs per patient of 0.0100-0.0149 compared to no FP dose change and 0.0136-0.0152 compared to increased FP dose. The one year ICURs were $43,000 to $54,400 per QALY gained for SFC compared to no FP dose change and $25,000 to $3500 per QALY gained compared to increased FP dose scenarios. The probability of SFC being cost-effective at $50,000 per QALY gained was greater than 75% compared to increased FP dose scenarios and compared to no dose change for patients on low or medium dose FP. The results were robust to changes in assumptions within the model.. In Canadian patients with inadequately controlled asthma on FP, it is cost-effective to use SFC for patients 12 years and over compared to doubling their FP dose. It is also cost-effective to use SFC for patients on low or medium dose FP compared to remaining on the current FP dose in patients with uncontrolled asthma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Canada; Child; Cost-Benefit Analysis; Decision Support Techniques; Dose-Response Relationship, Drug; Drug Combinations; Drug Costs; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Health Care Costs; Humans; Male; Middle Aged; Quality-Adjusted Life Years; Treatment Outcome; Young Adult

The combination of an inhaled corticosteroid and a long acting beta-2 agonist is indicated for the regular treatment of persistent moderate-to-severe asthmatics whose asthma is not controlled by inhaled corticosteroids and the occasional use of a short acting beta-2 agonist. The aim of this review is to give an overview of the rationale of combining formoterol and fluticasone and to analyze the clinical data concerning a new fixed combination of fluticasone and formoterol in a pressurised metered-dose inhaler with a dose counter (Flutiform(®)) that was approved for the treatment of asthma in France in 2013. The clinical studies provide evidence that combined fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone, and provides similar improvements in lung function to fluticasone (Flixotide(®)) and formoterol (Foradil(®)) administered concurrently. The combination of fluticasone/formoterol gave a more rapid bronchodilatation than the combination fluticasone/salmeterol. As a whole, the combination of fluticasone/formoterol had similar efficacy and tolerability profiles to the combinations of either budesonide/formoterol or fluticasone/salmeterol.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Ethanolamines; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Metered Dose Inhalers

Inhaled corticosteroids (ICS) are drugs of choice for persistent asthma. Less than 500 µg/d of fluticasone are believed to be safe. We found 92 cases of adrenal suppression in PubMed; among these cases there were 13 children who took 500 µg/d or less of fluticasone. Adrenal insufficiency was diagnosed in a 7-year-old boy on 460 µg ICS for 16 months, with a diagnosis of chronic persistent asthma. A random cortisol was nondetectable as was an early morning cortisol. ICS have greatly improved the day-to-day lives of children with chronic persistent asthma. Parents of children younger than 12 years, who use at least 400 µg of inhaled fluticasone (or bioequivalent), must be given oral and written instructions about warning symptoms of hypocortisolism. Major stress such as surgery, gastrointestinal, bronchopulmonary, or other systemic infections, and heat stress may mandate a written plan of action for use by hospital physicians.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocortisone; Male; Off-Label Use

Fixed-dose combinations of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) have been used to manage asthma for several years. They are the preferred therapy option for patients who do not achieve optimal control of their asthma with low-dose ICS monotherapy. In Europe, four ICS/LABA products are commercially available for asthma maintenance therapy (fluticasone propionate/formoterol fumarate, fluticasone propionate/salmeterol xinafoate, budesonide/formoterol fumarate and beclometasone dipropionate/formoterol fumarate), and other combinations are likely to be developed over the next few years (e.g. mometasone/formoterol fumarate, fluticasone furoate/vilanterol, mometasone/indacaterol). Data from randomized, controlled, clinical trials do not demonstrate a clear overall efficacy difference among ICS/LABA combinations approved for asthma therapy. Conversely, pharmacological data indicate that there may be certain advantages to using one ICS or LABA over another because of the specific pharmacodynamic and pharmacokinetic profiles associated with particular treatments. This review article summarizes the pharmacological characteristics oft he various ICSs and LABAs available for the treatment of asthma, including the potential for ICS and LABA synergy, and gives an insight into the rationale for the development of the latest ICS/LABA combination approved for asthma maintenance therapy.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Time Factors; Treatment Outcome

We studied the relationship between body mass index (BMI) on responses to asthma therapy using a retrospective analysis of four previously reported clinical trials. Fluticasone propionate (FP)/salmeterol via Diskus 100/50 microg twice daily and montelukast (MON) 10 mg daily were compared. BMI was classified as underweight (less than 20 kg/m(2)), normal (20-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), obese-1 (30-34.9 kg/m(2)), obese-2 (35-39.9 kg/m(2)), or obese-3 (at least 40 kg/m(2)). Outcomes assessed included forced expiratory volume in one second (FEV(1)), asthma symptom score, and albuterol use. FP/salmeterol produced greater improvements compared to MON in each of the asthma outcomes studied over the entire BMI range at the week-12 endpoint, with statistically significant differences noted among normal, overweight, obese-1, and obese-3 subjects. The within-treatment responses to FP/salmeterol across BMI ranges at the week-12 endpoint was statistically significantly greater in normal compared to obese-3 for FEV(1) and albuterol use, and in overweight compared to the obese-3 for each outcome studied. The within-treatment comparisons of MON across BMI ranges were significant for albuterol use in normal and underweight compared to obese-3 at the week-12 endpoint. Compared to subjects with normal BMI, the onset to peak FEV(1) may require longer treatment exposure in the very obese. Treatment responses to FP/salmeterol were consistently greater compared to MON and persisted at higher BMI.

Topics: Acetates; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Mass Index; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Multicenter Studies as Topic; Obesity; Overweight; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Time Factors; Treatment Outcome

Current asthma guidelines recommend the use of long-acting beta-agonists (LABAs) in combination with inhaled corticosteroids (ICSs) for long-term control and prevention of symptoms in persistent asthma. Data on the risk of asthma exacerbations of LABAs in combination with ICSs, as prescribed in typical clinical practice, are very scarce.. The authors conducted a systematic literature review and meta-analysis of observational studies to examine the risk of asthma exacerbations, measured as asthma-related hospitalization and/or asthma-related emergency room (ER) visits, in adults receiving LABAs plus ICSs in a fixed-dose combination compared with patients receiving ICSs alone.. Seven studies, all retrospective cohort studies conducted in the United States, representing approximately 96,000 patients, were included in the meta-analysis. The meta-analysis found that the use of ICSs plus LABAs was associated with a lower risk of asthma-related hospitalizations and/or ER visits than ICSs alone (odds ratio: 0.82; 95% confidence interval: 0.72-0.94). Sensitivity analyses to explore heterogeneity of endpoint definition, duration of follow-up, and patient characteristics did not significantly alter the findings.. Overall, this systematic meta-analysis suggests that patients in clinical practice treated with a single inhaler containing ICSs plus LABAs experience fewer asthma exacerbations than similar patients treated with ICSs alone.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Delayed-Action Preparations; Drug Administration Schedule; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Humans; Metered Dose Inhalers; Randomized Controlled Trials as Topic; Respiratory Function Tests

Salmeterol/fluticasone propionate (Seretide/Advair Diskus [dry powder inhaler] or Seretide/Advair inhalation aerosol [metered-dose inhaler]) is a fixed-dose combination inhalation agent containing a long-acting beta2-adrenoceptor agonist (LABA) plus a corticosteroid. In patients with symptomatic asthma, twice-daily salmeterol/fluticasone propionate maintenance therapy improves lung function and asthma symptoms to a greater extent than monotherapy with inhaled corticosteroids (ICS), such as fluticasone propionate, oral montelukast with or without fluticasone propionate, or sustained-release theophylline plus fluticasone propionate. The greater efficacy achieved with salmeterol/fluticasone propionate versus fluticasone propionate alone was sustained for 1 year in a well designed trial. Salmeterol/fluticasone propionate is also associated with a corticosteroid-sparing effect. Results of studies comparing fixed dosages of salmeterol/fluticasone propionate with formoterol/budesonide in adults and adolescents are equivocal. Twice-daily salmeterol/fluticasone propionate is associated with clinically meaningful improvements from baseline in health-related quality of life (HR-QOL), and improvements were greater than those reported with fluticasone propionate alone. Salmeterol/fluticasone propionate is generally well tolerated in adults, adolescents and children aged 4-11 years, and the fixed-combination inhaler ensures the appropriate use of a LABA in combination with an ICS. In cost-utility analyses in patients with uncontrolled asthma, salmeterol/fluticasone propionate compares favourably with fluticasone propionate alone or oral montelukast. Thus, salmeterol/fluticasone propionate provides an effective, well tolerated and cost-effective option for maintenance treatment in patients with asthma.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans

Inhaled corticosteroids (ICSs) and long-acting inhaled beta(2)-agonists (LABAs) are recommended treatment options for asthma.. This review compares the clinical effectiveness and tolerability of the ICSs fluticasone propionate and budesonide and the LABAs formoterol fumarate and salmeterol xinafoate administered alone or in combination.. A systematic review of the clinical studies available on MEDLINE (database period, 1950-September 2009) was conducted to assess English-language randomized controlled trials in children and adults with asthma. Treatment outcomes included lung function, symptom-free days (SFDs), use of rescue/reliever medications, asthma exacerbations, and tolerability profile.. Use of fluticasone was associated with significantly greater improvement in lung function and better asthma symptom control than budesonide. Similarly, formoterol was associated with significantly greater improvement in lung function and better asthma symptom control (as measured by less rescue medication use and more SFDs) compared with salmeterol. Single inhaler combination regimens (budesonide/ formoterol and fluticasone/salmeterol) were frequently more effective in improving all treatment outcomes than either monotherapy alone. Across all comparisons, a review of studies in adults and children did not find statistically significant differences in outcomes between the ICS and LABA therapies considered in this research. In general, no differences in tolerability profiles were reported between the ICS and LABA options, although the risk for growth retardation was lower with fluticasone than budesonide and with budesonide/formoterol than with budesonide monotherapy.. In this systematic review, fluticasone and formoterol appear to provide improved therapeutic benefits versus budesonide and salmeterol, respectively. Both fluticasone/salmeterol and budesonide/ formoterol combination therapies appeared to be associated with greater improvements in outcomes measures than the corresponding ICS and LABA monotherapies.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Combinations; Ethanolamines; Evidence-Based Medicine; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Lung; Nebulizers and Vaporizers; Practice Guidelines as Topic; Respiratory Function Tests; Risk Assessment; Salmeterol Xinafoate; Time Factors; Treatment Outcome

The costs of asthma and chronic obstructive pulmonary disease (COPD), the two most common chronic respiratory illnesses, are substantial and rising. The fixed-dose combination of fluticasone and salmeterol has been a safe and effective therapy for these diseases.. To review the pharmacoeconomic impact of the fixed-dose combination of inhaled fluticasone and salmeterol in asthma and COPD.. A systematic review of the literature was carried out to identify pharmacoeconomic studies with fixed-dose salmeterol and fluticasone (Seretide, Advair, Viani). In addition, abstracts from recent respiratory meetings were sought, and any unpublished data were requested from the manufacturer.. For asthma, when compared to treatment with inhaled corticosteroid monotherapy and antileukotrienes, alone or combined, salmeterol/fluticasone inhalation produced a higher proportion of successfully treated weeks, improvement in lung function and quality of life, and fewer treatment failures. The costs per quality-adjusted life year (QALY) for fluticasone/salmeterol have been favourable not only in patients with moderate to severe disease but also in patients with mild disease or patients not previously treated with a maintenance therapy. The excess cost per QALY varied from US$2,670 to US$26,445. For COPD, a clear reduction in exacerbation rates and improvement in quality of life has been demonstrated with salmeterol/fluticasone along with a likely improvement in survival rates. The incremental cost per QALY ratio for fluticasone/salmeterol against placebo ranged from US$9,512 to US$64,038.. The data currently available suggest that the cost effectiveness of combination therapy with fluticasone and salmeterol is favourable for asthma and COPD in a variety of clinical settings.

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Quality-Adjusted Life Years

In the recent years, considerable insight has been gained in to the optimal management of adult asthma. Most adult patients with asthma have mild intermittent and persistent disease, and it is acknowledged that many patients do not reach full control of all symptoms and signs of asthma. Those with mild persistent asthma are usually not well controlled without inhaled corticosteroids (ICS). Studies have provided firm evidence that these patients can be well controlled when receiving ICS, especially when disease is of recent onset. This treatment should be given on a daily basis at a low dose and when providing a good response should be maintained to prevent severe exacerbations and disease deterioration. Intermittent ICS treatment at the time of an exacerbation has also been suggested as a strategy for mild persistent asthma, but it is less effective than low-dose regular treatment for most outcomes. Adding a long-acting beta-agonist (LABA) to ICS appears to be unnecessary in most of these patients for optimising control of their asthma. Patients with moderate persistent asthma can be regarded as those who are not ideally controlled on low-dose ICS alone. The combination of an ICS and LABA is preferred in these patients, irrespective of the brand of medicine, and this combination is better than doubling or even quadrupling the dose of ICS to achieve better asthma control and reduce exacerbation risks. An ICS/LABA combination in a single inhaler represents a safe, effective and convenient treatment option for the management of patients with asthma unstable on inhaled steroids alone. Ideally, once asthma is under full control, the dose of inhaled steroids should be reduced, which is possible in many patients. The duration of treatment before initiating this dose reduction has, however, not been fully established. One of the combinations available to treat asthma (budesonide and formoterol) has also been assessed as both maintenance and rescue therapy with a further reduction in the risk for a severe exacerbation. Clinical effectiveness in the real world now has to be established, since this approach likely improves compliance with regular maintenance therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Severity of Illness Index; Treatment Outcome

To determine where in the treatment steps recommended by the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) Asthma Guideline it is cost-effective to use salmeterol xinafoate/fluticasone propionate combination inhaler (SFC) (Seretide) compared with other inhaled corticosteroid (ICS) containing regimens (with and without a long acting beta-2 agonist (LABA)) for chronic asthma in adults and children.. Meta-analyses of percentage symptom-free days (%SFD) were used within a cost-effectiveness model. Time spent in two asthma control health states, 'symptom-free' and 'with-symptoms' was used as the measure of differential treatment effectiveness. SFC was compared with varying doses of fluticasone propionate (FP) and beclometasone dipropionate (BDP) with or without a separate salmeterol inhaler, and with the budesonide/formoterol combination inhaler (BUD/FORM) (Symbicort). Drug costs, non-drug costs and quality adjusted life years (QALY) were incorporated into the analyses. Results are presented as cost per QALY ratios and uncertainty explored using probabilistic sensitivity analysis.. Compared with an increased dose of FP in adults, SFC either 'dominates' (i.e. cheaper and more effective) FP or the cost per QALY is 6852 pounds sterling. The cost per QALYs estimated in sensitivity analyses using BDP costs range from 5679 pounds sterling to 15,997 pounds sterling. For children the cost per QALY for SFC 50 Evohaler compared with an increased dose of FP is pound 15,739 pounds sterling. SFC is similarly clinically effective in improving %SFDs compared with FP plus salmeterol delivered in separate inhalers (mean differences for each dose comparison of -3.9 (low) (with a 95% confidence interval (CI): -12.96; 5.16); 4.10 (medium) (95% CI: -3.01; 11.21); -0.4 (high) (95% CI: -8.88; 8.08)) and BUD/FORM (mean difference of 0.40 (95% CI -3.69; 4.49)) in adults, and a cheaper SFC option is available at all doses (annual cost savings range from 18 pounds sterling-427 pounds sterling per patient). SFC was similarly effective compared with FP plus salmeterol in separate inhalers in children under 12 and also resulted in annual cost savings of between 47 pounds sterling and 77 pounds sterling. A number of other comparisons were also made and the results are available as electronic supplementary data.. This is the first analysis to estimate the cost-effectiveness of SFC in chronic asthma compared with multiple comparators and based on a systematic identification of relevant trials and data on %SFDs. The findings suggest that for adults and children uncontrolled on BDP 400 microg/day or equivalent it is a cost-effective option to switch to SFC (at an equivalent ICS dose) compared with increasing the dose of ICS. For adults and children aged 12 years and over who have passed this point and are uncontrolled on BDP 800 microg/day or equivalent, switching to SFC remains a cost-effective approach. Where an adult or child requires an ICS and a LABA to be co-prescribed, SFC is a cost-effective option compared with FP or BDP plus salmeterol delivered in separate inhalers. In adults who require combination therapy, SFC is a cost-effective option compared with BUD/FORM.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Chronic Disease; Cost-Benefit Analysis; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Health Services; Hospitals, State; Humans; Models, Econometric; Nebulizers and Vaporizers

The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Gene Expression Regulation; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Receptors, Glucocorticoid

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Topics: Acetates; Administration, Inhalation; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Economics, Pharmaceutical; Ethanolamines; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Quinolines; Salmeterol Xinafoate; Sulfides; Therapeutic Equivalency

Combination therapy with inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is a recognized treatment for adults with moderate to severe asthma. The introduction of inhalers containing both an ICS and a LABA simplifies treatment and improves asthma control. This review discusses clinical evidence that budesonide/formoterol and salmeterol/fluticasone are effective and well tolerated in asthma treatment. Moreover, the rapid onset of effect and long duration of action of budesonide and formoterol make once-daily dosing, adjustable maintenance dosing, and the novel treatment strategy of using budesonide/formoterol for maintenance and as needed for symptom relief, valuable treatment options for patients with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Humans; Nebulizers and Vaporizers; Treatment Outcome

Chronic-obstructive pulmonary disease (COPD) is a global public health problem and its impact is increasing. Although only smoking cessation has been shown to alter the natural history of the disease, current treatment guidelines recommend the use of inhaled bronchodilators to decrease symptoms, improve lung function and quality of life and to prevent exacerbations. For a subset of patients with more severe disease, inhaled corticosteroids may also have a role in achieving these goals. Fluticasone propionate/salmeterol (Advair) or Seretide), GlaxoSmithKline) is a combination inhaled steroid and long-acting bronchodilator that is delivered by a dry-powder inhaler and was recently approved for use in COPD in the US. Fluticasone propionate/salmeterol is a potent bronchodilator and also appears to have important effects on the frequency of exacerbations and overall quality of life for some patients with COPD. Issues of patient selection as well as the pharmacology, efficacy and safety of the drug are discussed.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive

The introduction of combination products, for the coadministration of an inhaled corticosteroid (ICS) with a long-acting beta2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort (budesonide/formoterol in a single inhaler) and Seretide (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting beta2-agonist to ICS in patients who are inadequately controlled on ICS alone. Importantly, combination inhalers ensure that patients cannot neglect their ICS maintenance therapy in favour of the long-acting beta2-agonist--which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting beta2-agonists may interact beneficially when they are administered via one inhaler. The efficacy and tolerability of budesonide/formoterol and salmeterol/fluticasone have been demonstrated. There are currently two approaches for treating asthma using combination therapy--fixed and adjustable dosing. Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals. However, given the inherent variability of asthma, there is increasing evidence that adjusting the dose of ICS according to fluctuations in symptoms is beneficial. Findings from a series of studies comparing fixed and adjustable symptom-guided dosing regimens demonstrate that adjustable dosing may improve asthma control at an overall lower steroid dose. Ultimately, if adjustable dosing proves to be an effective treatment option, it may be possible to use budesonide/formoterol for both maintenance therapy and symptom relief, thereby overcoming the need for a separate reliever inhaler. This is because formoterol has a more rapid onset and greater dose-related effects than salmeterol in salmeterol/fluticasone. Given that all patients are different, with different disease severities and treatment preferences, both fixed and adjustable dosing strategies are likely to be important in the long-term management of asthma. It is possible that different treatment options will be used for different patients, depending on their disease severity, personality and ability to adhere to therapy.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Tolerance; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Metered Dose Inhalers; Salmeterol Xinafoate

Maintenance treatment for mild asthma frequently comprises both a regular inhaled corticosteroid and an 'as required' inhaled short-acting beta 2-agonist. Where such treatment fails, additional regular treatment with an inhaled long-acting beta 2-agonist is increasingly recommended. In the UK, combination inhalers containing salmeterol + fluticasone ([symbol: see text] Seretide--Allen & Hanburys) or formoterol + budesonide ([symbol: see text] Symbicort--AstraZeneca) are licensed for use either in "patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short-acting beta 2-agonists" or in "patients already adequately controlled on both inhaled corticosteroids and long-acting beta 2-agonists". Here we review the efficacy of Seretide and Symbicort and discuss their place in asthma management.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Costs; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Randomized Controlled Trials as Topic

Several classes of medications are available for the treatment of asthma, and often they must be taken concurrently to achieve asthma control. Based on the understanding of asthma as an inflammatory disease, the National Heart Lung and Blood Institute guidelines provide a stepwise approach to pharmacologic therapy. Corticosteroid therapy, principally inhaled corticosteroid (ICS) therapy, is considered the most effective anti-inflammatory treatment. In cases of moderate-to-severe persistent asthma, the addition of a second long-term control medication to ICS therapy is one recommended treatment option. A combination-product inhaler (Advair, Seretide) was developed to treat both the inflammatory and bronchoconstrictive components of asthma by delivering a dose of the ICS, fluticasone propionate, and a dose of the long-acting beta2-adrenergic (LABA) bronchodilator, salmeterol. The Advair Diskus is available in 3 strengths of fluticasone propionate (100, 250, and 500 microg) and a fixed dose (50 microg) of salmeterol. Combination treatment with both ICS and LABA provides greater asthma control than increasing the ICS dose alone, while at the same time reducing the frequency and perhaps the severity of exacerbations. Furthermore, salmeterol added to ICS therapy provides superior asthma control compared with the addition of leukotriene modifiers or theophylline. The superior control is likely a consequence of the complementary actions of the drugs when taken together, including the activation of the glucocorticoid receptor by salmeterol. By combining anti-inflammatory treatment with a long-acting beta2-agonist in a single inhaler (1 inhalation twice daily), physicians can provide coverage for both the inflammatory and bronchoconstrictive aspects of asthma without introducing any new or unexpected adverse consequences. The most common drug-related adverse events were those known to be attributable to the constituent medications (ICS therapy and/or LABA therapy). Although the benefits of combined ICS plus LABA therapy can be achieved with separate inhalers, the convenience of the combination product may improve patient adherence and may therefore reduce the morbidity of asthma.

Topics: Administration, Inhalation; Adrenergic Agents; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Practice Guidelines as Topic; Salmeterol Xinafoate

Topics: Adolescent; Age Factors; Albuterol; Androstadienes; Anticonvulsants; Asthma; Atovaquone; Attention Deficit Disorder with Hyperactivity; Beclomethasone; Carbamazepine; Child; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Approval; Drug Combinations; Drug Delivery Systems; Drug Therapy; Epilepsies, Partial; Fluticasone-Salmeterol Drug Combination; HIV Protease Inhibitors; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Lopinavir; Methylphenidate; Naphthoquinones; Nebulizers and Vaporizers; Oxcarbazepine; Pediatrics; Proguanil; Pyrimidinones; Ritonavir; United States

In 2019, the U.S. Food and Drug Administration (FDA) approved the first generic maintenance inhaler for asthma and chronic obstructive pulmonary disease (COPD). The inhaler, Wixela Inhub (fluticasone-salmeterol; Viatris), is a substitutable version of the dry powder inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline). When approving complex generic products like inhalers, the FDA applies a special "weight-of-evidence" approach. In this case, manufacturers were required to perform a randomized controlled trial in patients with asthma but not COPD, although the product received approval for both indications.. To compare the effectiveness and safety of generic (Wixela Inhub) and brand-name (Advair Diskus) fluticasone-salmeterol among patients with COPD treated in routine care.. A 1:1 propensity score-matched cohort study.. A large, longitudinal health care database.. Adults older than 40 years with a diagnosis of COPD.. Incidence of first moderate or severe COPD exacerbation (effectiveness outcome) and incidence of first pneumonia hospitalization (safety outcome) in the 365 days after cohort entry.. Among 45 369 patients (27 305 Advair Diskus users and 18 064 Wixela Inhub users), 10 012 matched pairs were identified for the primary analysis. Compared with Advair Diskus use, Wixela Inhub use was associated with a nearly identical incidence of first moderate or severe COPD exacerbation (hazard ratio [HR], 0.97 [95% CI, 0.90 to 1.04]) and first pneumonia hospitalization (HR, 0.99 [CI, 0.86 to 1.15]).. Follow-up times were short, reflecting real-world clinical practice. The possibility of residual confounding cannot be completely excluded.. Use of generic and brand-name fluticasone-salmeterol was associated with similar outcomes among patients with COPD treated in routine practice.. National Heart, Lung, and Blood Institute.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchodilator Agents; Cohort Studies; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pneumonia; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Improvement of the delivery method of inhaled corticosteroids and subsequent dose reduction can minimize the risk of unfavorable outcomes while providing optimal asthma control.. This randomized, multi-center, non-inferiority, phase IV clinical study compared the efficacy and safety of a new formulation of fluticasone propionate/salmeterol (250 μg/50 μg, twice daily) administered in a metered-dose inhaler hydrofluoroalkane (MDI HFA) with a dry-powder inhaler (DPI) containing fluticasone propionate/salmeterol (500 μg/50 μg, twice daily).. Adults with asthma (n = 231) were randomly assigned to either the study group (treated for 12 weeks with fluticasone propionate/salmeterol MDI HFA) or a control group (treated for 12 weeks with fluticasone propionate/salmeterol DPI). Asthma symptoms, exacerbations, short-acting β. Compared with the reference drug, the study drug decreased the incidence of daytime and night-time asthma symptoms, asthma exacerbations, self-administration of SABA, and the limitation of physical activity. Comparable improvement in peak expiratory flow ([MDI HFA] from 6.2 ± 0.2 to 6.6 ± 0.2 l/s vs. [DPI] from 6.0 ± 0.2 to 6.9 ± 0.2 l/s; p > 0.05), forced expiratory volume in one second, and forced vital capacity were obtained in both groups. Significantly lower incidence of hoarseness was observed in the study group ([MDI HFA] 0.0% vs. [DPI] 2.8%; p = 0.0267); no major differences were found for other adverse events.. Fluticasone propionate/salmeterol (250 μg/50 μg, twice daily) MDI HFA provides optimal asthma control and is non-inferior to fluticasone propionate/salmeterol (500 μg/50 μg, twice daily) DPI.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Drug Tapering; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Metered Dose Inhalers; Middle Aged; Treatment Outcome; Young Adult

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Quinolones; Young Adult

Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β. This 52-week, double-blind, triple-dummy, parallel-group, phase 3 study recruited patients from 316 centres across 24 countries. Patients aged 12 to 75 years with a documented diagnosis of asthma for at least 1 year, percentage of predicted FEV. Between Dec 29, 2015, and May 4, 2018, 2216 patients were randomly assigned (high-dose MF-IND, n=445; medium-dose MF-IND, n=439; high-dose MF, n=442; medium-dose MF, n=444; high-dose FLU-SAL, n=446), of which 1973 (89·0%) completed the study treatment and 234 (10·6%) prematurely discontinued study treatment. High-dose MF-IND (treatment difference [Δ] 132 mL [95% CI 88 to 176]; p<0·001) and medium-dose MF-IND (Δ 211 mL [167 to 255]; p<0·001) showed superiority in improving trough FEV. Once-daily FDC of ICS and LABA (MF-IND) significantly improved lung function over ICS monotherapy (MF) at week 26; high-dose MF-IND was non-inferior to twice-daily combination of ICS and LABA (high-dose FLU-SAL) for improvement in trough FEV. Novartis Pharmaceuticals.

Topics: Adolescent; Adult; Aged; Asthma; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Quinolones; Treatment Outcome; Young Adult

Patients with asthma who are inadequately controlled on inhaled corticosteroid-long-acting β. In this 52-week, double-blind, double-dummy, parallel-group, active-controlled phase 3 study, patients were recruited from 415 sites across 41 countries. Patients aged 18 to 75 years with symptomatic asthma despite treatment with medium-dose or high-dose ICS-LABA, at least one exacerbation in the previous year, and a percentage of predicted FEV. Between Dec 8, 2015, and Jun 14, 2019, 3092 of 4851 patients screened were randomly assigned (medium-dose MF-IND-GLY, n=620; high-dose MF-IND-GLY, n=619; medium-dose MF-IND, n=617; high-dose MF-IND, n=618; high-dose FLU-SAL, n=618). 2747 (88·8%) patients completed the 52-week treatment and 321 (10·4%) started but discontinued study treatment prematurely. Medium-dose MF-IND-GLY (treatment difference [Δ] 76 mL [95% CI 41-111]; p<0·001) and high-dose MF-IND-GLY (Δ 65 mL [31-99]; p<0·001) showed superior improvement in trough FEV. Once-daily, single-inhaler MF-IND-GLY improved lung function versus ICS-LABA combinations (MF-IND and FLU-SAL) in patients with inadequately controlled asthma. The safety profile was similar across treatment groups. MF-IND-GLY therefore constitutes a good treatment option in these patients.. Novartis Pharmaceuticals.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Muscarinic Antagonists; Nebulizers and Vaporizers; Quinolones; Treatment Outcome; Young Adult

The Asthma Salford Lung Study demonstrated the effectiveness of initiating once-daily fluticasone furoate/vilanterol (FF/VI) versus continuing usual care in asthma patients in UK primary care [ 1 ]. Here, we report a secondary analysis in a subset of patients with fluticasone propionate/salmeterol (FP/Salm) as their baseline intended maintenance therapy, to evaluate the relative effectiveness of initiating FF/VI versus continuing FP/Salm.. Adults with symptomatic asthma were randomised to initiate FF/VI 100[200]/25 µg or continue FP/Salm. The Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), Work Productivity and Activity Impairment Asthma questionnaire, severe exacerbations, salbutamol inhaler prescriptions and serious adverse events (SAEs) were recorded throughout the 12-month treatment period.. One thousand two hundred and sixty-four patients (FF/VI 646; FP/Salm 618) were included in this subset analysis; 978 had baseline ACT score <20 and were included in the primary effectiveness analysis (PEA) population. At week 24, odds of patients being ACT responders (total score ≥20 and/or improvement from baseline ≥3) were significantly higher with FF/VI versus FP/Salm (71% vs. 56%; odds ratio 2.03 [95% CI: 1.53, 2.68]; p < 0.001 [PEA]). Significant benefit with FF/VI versus FP/Salm was also observed for AQLQ responders, activity impairment due to asthma, exacerbation rates, and salbutamol inhalers prescribed. No significant between-group differences were observed for impairment while working or work absenteeism due to asthma.. For patients in primary care, initiating FF/VI was significantly better than continuing with FP/Salm for improving asthma control and quality of life, and reducing asthma exacerbations, with no notable difference in SAEs. ClinicalTrials.gov: NCT01706198.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult

Fluticasone propionate 50 μg/salmeterol xinafoate 25 μg (FP/SAL) is widely used in adults and children with asthma, but there is sparse information on its use in very young children.. This was a randomized, double-blind, multicentre, controlled trial conducted in children aged 8 months to 4 years. During a 2-week run-in period, they all received FP twice daily. At randomization, they commenced FP/SAL or FP twice daily for 8 weeks. All were then given FP/SAL only, in a 16-week open-label study continuation. Medications were inhaled through an AeroChamber Plus with attached face mask. The primary end-point was mean change in total asthma symptom scores from baseline to the last 7 days of the double-blind period. Analyses were undertaken in all children randomized to treatment and who received at least one dose of study medication.. Three hundred children were randomized 1:1 to receive FP/SAL or FP. Mean change from baseline in total asthma symptom scores was -3.97 for FP/SAL and -3.01 with FP. The between-group difference was not statistically significant (P = 0.21; 95% confidence interval: -2.47, 0.54). No new safety signals were seen with FP/SAL.. This is the first randomized, double-blind study of this size to evaluate FP/SAL in very young children with asthma. FP/SAL did not show superior efficacy to FP; no clear add-on effect of SAL was demonstrated. No clinically significant differences in safety were noted with FP/SAL usage.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Child, Preschool; Double-Blind Method; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Humans; Infant; Japan; Severity of Illness Index; Treatment Outcome

To assess the efficacy and safety of fluticasone propionate (Fp) and Fp/salmeterol (FS) administered via a novel multidose dry powder inhaler (MDPI) that is easy to use correctly in asthma patients.. This phase-3, multicenter, double-blind, parallel-group study evaluated asthmatic patients (≥12 years of age) previously treated with either low- or mid-dose inhaled corticosteroids (ICSs) or ICS/long-acting beta agonists. After a 14- to 21-day run-in, patients were randomized to Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI 50/12.5 mcg, FS MDPI 100/12.5 mcg, or placebo twice daily for 12 weeks. Change from baseline in forced expiratory volume in 1 second (FEV. The full analysis and serial spirometry subset included 640 and 312 patients, respectively. At week 12, FS MDPI significantly improved FEV. Pulmonary function was significantly improved with Fp MDPI and FS MDPI vs placebo and FS MDPI vs Fp MDPI. Active treatments had a safety profile comparable to placebo.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Dry Powder Inhalers; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Spirometry; Treatment Outcome; Young Adult

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Asthma; Benzyl Alcohols; Bronchodilator Agents; Child; Chlorobenzenes; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Equivalence Trials as Topic; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Young Adult

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Biological Assay; Breath Tests; Cross-Over Studies; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Pilot Projects; Young Adult

The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients.. This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared.. The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Linear Models; Male; Middle Aged; Severity of Illness Index; Taiwan

Asthma is the most chronic inflammatory disease of the airways worldwide. Combination therapy with inhaled fluticasone and salmeterol is a common practice for the long-term management of asthma. Seretide® and Fluticort plus® are two available generic and brand name products of salmeterol/fluticasone. This study aimed to compare the efficacy and safety of these two drugs.. In this randomized comparative, clinical trial, 80 asthmatic patients were allocated to Fluticort plus® (n=40) or Seretide® (n=40) for a period of 4 weeks. Patients with mild asthma were instructed to inhale one puff each 12 hours and those with moderate asthma two puffs every 12 hours. Respiratory volumes (assessed using spirometry), quality of life (assessed using St. George's Respiratory Questionnaire [SGRQ]) and control of asthmatic symptoms (assessed using asthma control test [ACT]) were evaluated at baseline and at the end of the study.. ACT score improved only in the Fluticort plus® group (p=0.012) while it was not significantly changed in the Seretide® group (p=0.178). In both treatment groups, FEV1, FEV1/FVC, and total as well as subscale SGRQ scores were significantly improved by the end of the study (p<0.05). Seretide® more efficiently improved respiratory volumes and SGRQ score in comparison with Fluticort plus® (p<0.05).. Our comparative trial indicated that generic fluticasone/salmeterol product could improve respiratory volumes, quality of life but its efficacy is lower than the brand-name product. However, Fluticort plus® improved asthma control more efficiently compared with Seretide®.

Topics: Asthma; Bronchodilator Agents; Drugs, Generic; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pilot Projects; Quality of Life; Vital Capacity

Education on inhaler technique is critical for effective asthma treatment. However, traditionally used face-to-face education is time-consuming, costly, and often laborious. The current study evaluated the efficacy of a newly developed video-based inhaler technique education method.. A total of 184 subjects with well-controlled or partly-controlled asthma were enrolled from 12 hospitals in South Korea from 30 November 2015 to 01 June 2016. Subjects were randomly divided into two groups in a 1:1 ratio; a control group that received face-to-face education, and a study group that received video education. All subjects received fluticasone propionate plus salmeterol xinafoate (Fluterol® 250/50 inhalation capsules) for 12 weeks. The primary outcome measure was forced expiratory volume in the 1st second (FEV1) at 12 weeks. The secondary outcome measures were change in FEV1 at 4 weeks, change in asthma control test (ACT) score, and changes in various inhaler technique parameters. These measures were assessed with a non-inferiority margin of 10% between the control group and the study group.. FEV1 was significantly improved at 12 weeks in the control group and the study group. After adjustment, FEV1 improvement was not significantly inferior in the study group compared to the control group. The secondary outcome measures, including change in FEV1 at 4 weeks, ACT score, and various parameters pertaining to inhaler technique and satisfaction at 4 and 12 weeks did not differ significantly in the two groups. In subgroup analysis of elderly subjects and subjects with well-controlled asthma, FEV1 was significantly improved at 12 weeks in the study group but not the control group.. The newly developed video education technique investigated functioned as a suitable substitute for face-to-face education on inhaler technique (dry powder inhalation capsule) in patients with stable asthma, particularly in elderly patients and patients with well-controlled asthma.

Topics: Administration, Inhalation; Aged; Asthma; Bronchodilator Agents; Drug Administration Schedule; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Patient Education as Topic; Republic of Korea; Respiratory Function Tests; Treatment Outcome

A novel multidose dry powder inhaler (MDPI) that is breath actuated, easy, and intuitive to use has been developed for administering fluticasone propionate (Fp) and Fp/salmeterol (FS).. To assess the safety and efficacy of Fp MDPI versus Fp hydrofluoroalkane (HFA) and FS MDPI versus FS dry-powder inhaler (DPI).. This phase III, 26-week, open-label, active drug-controlled study enrolled subjects ≥12 years old with persistent asthma. Based on entry controller medication (inhaled corticosteroid [ICS] or ICS/long-acting beta-agonist), the subjects were randomized to twice-daily mid-strength Fp MDPI 100 μg or Fp HFA 220 μg, high-strength Fp MDPI 200 μg or Fp HFA 440 μg, mid-strength FS MDPI 100/12.5 μg or FS DPI 250/50 μg, or high-strength FS MDPI 200/12.5 μg or FS DPI 500/50 μg in a 3:1 MDPI to Fp HFA or FS DPI ratio. Safety and efficacy were assessed by adverse events (AE) and pulmonary function and asthma symptoms, respectively.. A total of 674 subjects were randomized. The AE incidence was similar across treatment groups (upper respiratory tract infections, sinusitis, and nasopharyngitis were most frequent). A higher percentage of subjects in the Fp HFA 440 μg and FS DPI 500/50 μg groups had oral candidiasis versus those who received Fp MDPI 200 μg or FS MDPI 200/12.5 μg, respectively. Serious AEs were similar between the treatments, with no unexpected findings. The incidence of asthma exacerbations was low and generally similar between the groups. Noninferiority was established for all Fp MDPI and FS MDPI doses compared with Fp HFA and FS DPI, respectively, for forced expiratory volume in 1 second. Changes in peak expiratory flow, rescue albuterol use, and symptoms were similar between treatments.. The safety and efficacy profiles of Fp MDPI and FS MDPI administered at lower doses were generally comparable with those of Fp HFA and FS DPI, respectively, after 26 weeks of treatment.The ClinicalTrials.gov identifier is NCT02175771.

Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Lung; Male; Middle Aged; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to test the systemic pharmacodynamic effects of the salmeterol component of two pressurized metered dose inhalers that delivered a combination of salmeterol and fluticasone propionate (SM/FP).. This was a six-way crossover study in 43 adult subjects, using a single blind design (subject blinded to product and clinical assessor blinded for all measurements). Each subject received single doses of two, six, and twelve inhalations from test and reference products that delivered SM/FP as 25/125 mcg per inhalation. Heart rate, QTcB, and plasma potassium and glucose were monitored over 6 h.. Safety equivalence was shown by relative potency analysis for primary endpoints of maximum heart rate and maximum QTcB, since the 90% confidence intervals for both endpoints were within the acceptance limit of (0.67, 1.50). There were six secondary analyses for relative potency and equivalence was met for five of these endpoints. There were also 18 pairwise comparisons performed at each dose level. No statistical differences (95% confidence intervals included zero) among these pairwise comparisons were seen at the two-inhalation dose (therapeutic dose) or the six-inhalation dose. At the supratherapeutic dose of twelve inhalations, the test product was either comparable to or statistically less than that of the reference product for all comparisons. Overall, the results demonstrated comparable systemic safety. No differences were seen between the products in reported adverse events.. The safety equivalence of the systemic pharmacodynamic effects of the SM component of the test and reference SM/FP products was demonstrated.

Topics: Administration, Inhalation; Adolescent; Adult; Area Under Curve; Asthma; Bronchodilator Agents; Cross-Over Studies; Electrocardiography; Female; Fluticasone-Salmeterol Drug Combination; Healthy Volunteers; Heart Rate; Humans; Male; Metered Dose Inhalers; Middle Aged; Single-Blind Method; Young Adult

A novel, inhalation-driven, multidose dry powder inhaler (MDPI) has been developed, which allows for lower doses of fluticasone propionate (Fp) and Fp/salmeterol (FS) for the treatment of patients with asthma.. This phase III, multicenter, double-blind, parallel-group study (NCT02141854) evaluated the efficacy and safety of Fp MDPI and FS MDPI versus placebo MDPI.. Patients aged ≥12 years with persistent asthma who previously took an inhaled corticosteroid with or without a long-acting beta-agonist entered a 14- to 21-day run-in period, during which they received single-blind, low-dose Fp MDPI 50 μg (1 inhalation twice daily [b.i.d.]) and used albuterol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) for rescue. The patients who continued to meet eligibility criteria (N = 728) were randomized to Fp MDPI (100 or 200 μg), FS MDPI (100 μg/12.5 μg or 200 μg/12.5 μg), or placebo (1 inhalation b.i.d.). Primary efficacy end points were the change from baseline in forced expiratory volume in 1 second (FEV1) and the baseline-adjusted area under the FEV1 curve 12 hours after the dose at week 12. Secondary efficacy end points were A.M. peak expiratory flow, asthma symptom scores, albuterol HFA MDI use, time to patient withdrawal, Asthma Quality of Life scores, and time to 15% and 12% improvement from baseline in FEV1. Safety end points were monitored.. Fp MDPI and FS MDPI significantly improved both primary end points compared with placebo (p < 0.05). FS MDPI significantly improved both end points versus the corresponding Fp MDPI dose (p < 0.05), with improvement also greater for FS MDPI 100 μg/12.5 μg versus Fp MDPI 200 μg (p < 0.05). Both active treatments improved a variety of secondary end points and exhibited a safety profile consistent with the drug classes.. Delivery of Fp and FS via the novel MDPI provided significant clinical benefits and was well tolerated in patients with persistent asthma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Child; Dry Powder Inhalers; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Respiratory Function Tests; Retreatment; Risk Factors; Treatment Outcome; Young Adult

The salmeterol/fluticasone combination (SFC) inhaler is currently the most widely used maintenance drug for asthmatics worldwide. Although the effectiveness of SFC as either a dry powder inhaler (DPI) or a pressurized metered dose inhaler (pMDI) is well documented, there is limited data comparing the clinical efficacies of the two devices. To address this issue, we carried out a randomized crossover trial in which asthmatic patients (n = 47; mean age, 62.5 ± 16.5 years old) received a 12-week treatment of SFC DPI (50/250 μg twice daily) or SFC pMDI (four puffs of 25/125 μg daily). After a 4-week washout period, patients received another crossover treatment for 12 weeks. Respiratory resistance and reactance were measured by forced oscillation technique (MostGraph-01), spirometry, fractional exhaled nitric oxide (FeNO), and an asthma control test (ACT) every 4 weeks. The mean forced expiratory volume1.0 at the baseline was 2.16 ± 0.86 (L). Respiratory system resistance at 5 Hz (R5), the difference between R5 and R at 20 Hz (R5 - R20), and FeNO improved in both treatment groups, while reactance at 5 Hz (X5) and ACT score improved only in the pMDI group. In patients >70 years old (n = 21), R5, R5 - R20, ΔX5, and FeNO improved only in the pMDI group. These results suggest that SFC by pMDI produces a stronger anti-inflammatory and bronchodilatory effect even in patients whose asthma is well controlled by SFC delivered by DPI.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cross-Over Studies; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Prospective Studies; Spirometry; Treatment Outcome; Young Adult

The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate.. In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation.. Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001).. Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Severity of Illness Index

Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count.. We did this randomised, double-blind, placebo-controlled, parallel-group, pivotal phase 2b clinical trial at 174 study sites across 16 countries or regions. Adults (aged ≥18 years) with an asthma diagnosis for 12 months or more based on the Global Initiative for Asthma 2009 Guidelines receiving treatment with medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist were eligible for participation. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks or every 4 weeks, or placebo, over a 24-week period. The primary endpoint was change from baseline at week 12 in forced expiratory volume in 1 s (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per μL assessed in the intention-to-treat population. Safety outcomes were assessed in all patients that received at least one dose or part of a dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT01854047, and with the EU Clinical Trials Register, EudraCT number 2013-000856-16.. 769 patients (158 in the placebo group and 611 in the dupilumab groups) received at least one dose of study drug. In the subgroup with at least 300 eosinophils per μL, the greatest increases (200 mg every 2 weeks, p=0·0008; 300 mg every 2 weeks, p=0·0063) in FEV1 compared with placebo were observed at week 12 with doses every 2 weeks in the 300 mg group (mean change 0·39 L [SE 0·05]; mean difference 0·21 [95% CI 0·06-0·36; p=0·0063]) and in the 200 mg group (mean change 0·43 L [SE 0·05]; mean difference 0·26 [0·11-0·40; p=0·0008]) compared with placebo (0·18 L [SE 0·05]). Similar significant increases were observed in the overall population and in the fewer than 300 eosinophils per μL subgroup (overall population: 200 mg every 2 weeks, p<0·0001; 300 mg every 2 weeks, p<0·0001; <300 eosinophils per μL: 200 mg every 2 weeks, p=0·0034; 300 mg every 2 weeks, p=0·0086), and were maintained to week 24. Likewise, dupilumab every 2 weeks produced the greatest reductions in annualised rates of exacerbation in the overall population (70-70·5%), the subgroup with at least 300 eosinophils per μL (71·2-80·7%), and the subgroup with fewer than 300 eosinophils per μL (59·9-67·6%). The most common adverse events with dupilumab compared with placebo were upper respiratory tract infections (33-41% vs 35%) and injection-site reactions (13-26% vs 13%).. Dupilumab increased lung function and reduced severe exacerbations in patients with uncontrolled persistent asthma irrespective of baseline eosinophil count and had a favourable safety profile, and hence in addition to inhaled corticosteroids plus long-acting β2-agonist therapy could improve the lives of patients with uncontrolled persistent asthma compared with standard therapy alone.. Sanofi-Genzyme and Regeneron Pharmaceuticals.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Breath Tests; Budesonide, Formoterol Fumarate Drug Combination; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Injections, Subcutaneous; Male; Middle Aged; Mometasone Furoate, Formoterol Fumarate Drug Combination; Nitric Oxide; Treatment Outcome

The present study was conducted to assess the efficacy, safety and tolerability of fluticasone propionate/formoterol fumarate combination therapy (FP/FORM; Flutiform®) compared with fluticasone propionate/salmeterol xinafoate (FP/SAL; Seretide® Evohaler®) in children with asthma.. This was an open-label, randomized, controlled, phase III trial and extension. Patients aged 4-12 years with reversible asthma [% predicted forced expiratory volume in 1 second (FEV1) 60-100%; documented reversibility of ⩾15% in FEV1] were randomized to receive FP/FORM (100/10 µg b.i.d.) or FP/SAL (100/50 µg b.i.d.) for 12 weeks. Eligible patients completing the 12-week core phase entered a 24-week extension phase with FP/FORM (100/10 µg b.i.d.). The primary efficacy endpoint was the change in predose FEV1 from day 0 to day 84. Secondary efficacy endpoints included change in predose to 2-hours postdose FEV1 from day 0 to day 84, peak expiratory flow rate (PEFR), patient-reported outcomes, rescue-medication use and asthma exacerbations.. In total, 211 patients were randomized and 210 completed the core phase; of these patients, 208 entered and 205 completed the extension phase of the study. Predose FEV1 increased from day 0 to day 84 [FP/FORM, 182 ml; 95% confidence interval (CI), 127, 236; FP/SAL, 212 ml, 95% CI, 160, 265] and FP/FORM was noninferior to FP/SAL: least squares (LS) mean treatment difference: -0.031 (95% CI, -0.093, 0.031; p = 0.026). Secondary efficacy analyses indicated similar efficacy with both therapies. There were no notable differences observed in the safety and tolerability profile between treatments. No safety concerns were identified with long-term FP/FORM therapy, and there was no evidence of an effect of FP/FORM on plasma cortisol.. FP/FORM improved lung function and measures of asthma control with comparable efficacy to FP/SAL, and demonstrated a favourable safety and tolerability profile in children aged 4-12 years.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Peak Expiratory Flow Rate; Respiratory Function Tests; Treatment Outcome

New inhalation devices with improved lung delivery may allow the use of lower salmeterol doses for treatment of asthma.. To determine the dose of salmeterol administered from a novel fluticasone propionate/salmeterol (FS) inhalation-driven, multidose dry powder inhaler (MDPI), which provides comparable efficacy and safety to FS dry powder inhaler (DPI).. This double-blind, six-period crossover, dose-ranging study randomized 72 patients (ages ≥12 years; with persistent asthma and predose maximum forced expiratory volume in 1 second [FEV1] of 40-85% of the predicted normal) to treatment sequences (one dose per treatment), which consisted of FS MDPI 100/6.25, 100/12.5, 100/25, 100/50 μg; fluticasone propionate (Fp) MDPI 100 μg; and open-label FS DPI 100/50 μg. The primary efficacy variable was the baseline-adjusted FEV1 area under the curve over 12 hours after the dose (AUC0-12). Pharmacokinetics and tolerability were also assessed.. FEV1 AUC0-12 was significantly higher with all FS MDPI doses and FS DPI versus Fp MDPI (p < 0.0001), and with FS MDPI 100/50 μg versus FS DPI (least squares [LS] mean, 57.88 mL; p = 0.0017). FEV1 AUC0-12 trended toward higher efficacy with FS MDPI 100/25 μg (LS mean, 34.14 mL; p = 0.0624) and was comparable with FS MDPI 100/12.5 μg (LS mean, 3.42 mL; p = 0.8503) versus FS DPI. Salmeterol area under the plasma concentration-versus-time curve from time 0 to the time of the last measurable concentration (AUC0-t) for FS MDPI 100/12.5 μg and 100/25 μg was lower versus FS DPI 100/50 μg; AUC0-t for FS MDPI 100/50 μg was higher than FS DPI 100/50 μg. All FS MDPI doses were generally well tolerated.. All FS MDPI doses produced greater efficacy versus Fp MDPI. FS MDPI 100/12.5 μg demonstrated similar efficacy to FS DPI 100/50 μg with less salmeterol exposure. Clinicaltrials.gov NCT02139644, NCT02175771, and NCT02141854.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Child; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Treatment Outcome; Young Adult

Unambiguously for inhaled products, PK measures are best suited for ensuring that the total systemic exposure is equivalent for two products but cannot provide regional information about lung deposition and structural changes. Functional respiratory imaging (FRI) has been demonstrated to be sensitive for distinguishing small but imperative differences related to a single treatment.. In this study FRI is used in 16 asthmatic patients to assess equivalence in regional deposition for two products (fluticasone/salmeterol, test and reference) by directly measuring regional functional and structural changes within the lungs following its administration.. No differences were observed between the lung deposition patterns and the effects on lung structure and function of two products, having the same formulation and manufactured by different organizations using FRI.. Results using FRI complement PK assessments. The added value of this approach to the conventional clinical methods could be significant.

Topics: Aged; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Tomography, X-Ray Computed

Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma.. To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 μg/day) and fluticasone propionate (100 μg/day), in infants and preschool children with asthma.. The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 μg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE).. Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs.. SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child, Preschool; Dose-Response Relationship, Drug; Female; Fluticasone-Salmeterol Drug Combination; Humans; Infant; Male; Treatment Outcome

Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.. We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis.. Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01).. In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).

Topics: Administration, Inhalation; Adrenergic beta-1 Receptor Agonists; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Child; Child, Preschool; Delayed-Action Preparations; Double-Blind Method; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Metered Dose Inhalers; Proportional Hazards Models

This phase III trial had two treatment periods (P): P1, patients with well-controlled asthma on FP/SAL 250/50 μg BD equivalent stepped across to once daily (OD) FF/VI 100/25 μg (open-label, eight weeks); P2, patients remaining 'well controlled' after P1 stepped down to FF 100 μg OD/FP 100 μg BD/FP 250 μg BD (randomized 1:1:1, double-blind, 12 weeks). Co-primary P2 endpoints: percentage of patients with well-controlled asthma; time to withdrawal due to poorly controlled asthma requiring step-up therapy. Adverse events (AEs) were monitored.. At the end of P1 (n = 430), 373 (90.5%; 95% confidence interval 87.29-93.18) patients' asthma remained well controlled with FF/VI; in P2 (n = 371), control was maintained in 89.5% (FF 100 μg)/79.5% (FP 100 μg)/83.8% (FP 250 μg) of patients. In P2, 4.9-7.3% of patients were withdrawn due to worsening asthma (time-to-withdrawal cumulative incidence curves were comparable). AEs were reported by 37% of patients during P1; and by 36% (FF 100 μg)/48% (FP 100 μg)/49% (FP 250 μg) of patients in P2.. For patients with well-controlled asthma on mid dose ICS/LABA (equivalent to FP/SAL 250/50 μg BD), control can be maintained when they are stepped across to FF/VI 100/25 μg OD. FF 100 μg OD is an effective step-down therapy from FF/VI 100/25 μg OD with similar efficacy to FP 100 μg BD and FP 250 μg BD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Asthma; Benzyl Alcohols; Chlorobenzenes; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Peak Expiratory Flow Rate; Prevalence; Smoking; Treatment Outcome

Cough variant asthma (CVA) is an important cause of chronic cough, and pathophysiological features of the disease appear to be similar to typical asthma. Because CVA is recognized as a precursor of asthma, early intervention with long-term anti-inflammatory agents may be recommended. However, the role of combination therapy with inhaled corticosteroid and β2-agonist in the treatment of CVA has not been elucidated. To evaluate the effectiveness of the combination therapy, we investigated the clinical impact of regular treatment with salmeterol/fliticasone propionate combination (SFC) and inhaled salmeterol (SAL) alone in patients with CVA.. The study was a randomized, controlled, parallel-group multi-center trial. Forty-three CVA patients were assigned to SFC (50/100 µg once daily) or SAL (50 µg twice daily) for 12 weeks. Then, these medications were stopped for the next 24 weeks. Main outcome measures were cough symptoms, pulmonary function and airway inflammation.. Treatment with each of SFC and SAL significantly decreased cough scores and increased FEV1 and PEF, where the efficacy was more pronounced with SFC than SAL. SFC also decreased sputum eosinophil counts and eosinophil cationic protein contents, whereas SAL had no effect. After discontinuation of the treatment, cough scores increased, pulmonary function and eosinophilic airway inflammation were aggravated and returned to the baseline levels.. Maintenance therapy with SFC provides further improvements in cough symptoms, pulmonary function and airway inflammation, and discontinuation of the therapy causes worsening of the disease, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with CVA.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Cough; Drug Combinations; Eosinophils; Female; Fluticasone-Salmeterol Drug Combination; Humans; Inflammation; Male; Middle Aged; Peak Expiratory Flow Rate; Respiratory Function Tests; Salmeterol Xinafoate

Phase III/IV clinical trials are expensive and time consuming and often suffer from poor enrollment and retention rates. Pediatric trials are particularly difficult because scheduling around the parent, participant and potentially other sibling schedules can be burdensome. We are evaluating using the internet and mobile devices to conduct the consent process and study visits in a streamlined pediatric asthma trial. Our hypothesis is that these study processes will be non-inferior and will be less expensive compared to a traditional pediatric asthma trial.. Parents and participants, aged 12 through 17 years, complete the informed consent process by viewing a multi-media website containing a consent video and study material in the streamlined trial. Participants are provided an iPad with WiFi and EasyOne spirometer for use during FaceTime visits and online twice daily symptom reporting during an 8-week run-in followed by a 12-week study period. Outcomes are compared with participants completing a similarly designed traditional trial comparing the same treatments within the same pediatric health-system. After 8 weeks of open-label Advair 250/50 twice daily, participants in both trial types are randomized to Advair 250/50, Flovent 250, or Advair 100/50 given 1 inhalation twice daily. Study staff track time spent to determine study costs.. Participants have been enrolled in the streamlined and traditional trials and recruitment is ongoing.. This project will provide important information on both clinical and economic outcomes for a novel method of conducting clinical trials. The results will be broadly applicable to trials of other diseases.

Topics: Adolescent; Asthma; Bronchodilator Agents; Child; Computers, Handheld; Data Collection; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Informed Consent; Internet; Male; Multimedia; Research Design; Spirometry

Salmeterol/fluticasone combination (SFC) formulated in a breath-actuated inhaler (BAI) overcomes the co-ordination problem associated with the pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and the safety of SFC given through the BAI versus the conventional pMDI in moderate-to-severe asthmatics.. In this randomized, double-blind, double-dummy, prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150 asthmatics were randomized to receive SFC (25/125 mcg) through either BAI or pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR value at 12 weeks and the secondary efficacy endpoints included, mean change in FEV(1), pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also assessed.. At 12 weeks, the mean change in pre-dose morning PEFR in BAI and pMDI groups was 50.72 L/min and 48.82 L/min, respectively (p < 0.0001; both groups) and the difference between the two groups was not significant. Both the treatment groups showed a statistically significant improvement in secondary endpoints at all-time points compared with baseline. The usability questionnaire assessment results showed that the BAI device was preferred by 75% of patients as compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to be safe and well tolerated.. This is the first study to demonstrate that SFC given through the BAI produces comparable efficacy and safety endpoints as pMDI. Additionally, BAI was the preferred inhaler by patients compared to conventional pMDI.

Topics: Adult; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Preference; Prospective Studies; Respiratory Function Tests

A seasonal peak in asthma exacerbations in the fall has previously been reported. The association between fall exacerbations and viral respiratory tract infections (RTI) remains uncertain.. To investigate the number of fall exacerbations and the incidence of RTIs in a pediatric asthmatic population using an at-home mucus collection methodology.. This was a 16-week, multicenter, randomized, double-blind, parallel-group exploratory study. Children, 4-11 years of age with a clinical diagnosis of asthma requiring use of an inhaled corticosteroid, a morning peak expiratory flow ≥70% predicted and a history of ≥1 asthma exacerbation during the previous respiratory viral season were eligible for enrollment. Subjects were randomized (1:1) to receive fluticasone propionate/salmeterol (FP/SAL) 100/50 mcg or FP 100 mcg prior to starting school. Subjects collected mucus samples using an at-home kit when they experienced respiratory symptoms. Mucus samples obtained during symptomatic periods were analyzed for common respiratory viruses by multiplex polymerase chain reaction. The number of exacerbations requiring systemic corticosteroids was recorded.. In total, 339 (FP/SAL, n = 171; FP, n = 168) subjects were randomized and included in the intent-to-treat population; 292 (86%) completed the study. Of the 537 mucus samples collected, 64% tested positive for viruses, but only 6% of positive samples were associated with an asthma exacerbation. Exacerbations were infrequent, with only 41 subjects reporting 49 exacerbations in total. Adverse events were reported in 66% of subjects.. In a susceptible population, the fall asthma exacerbation rates in children were low despite frequent detection of viral RTIs. NCT01192178; GSK ID: ADA113872.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Mucus; Peak Expiratory Flow Rate; Polymerase Chain Reaction; Prospective Studies; Respiratory Tract Infections; Rhinovirus; Seasons; Treatment Outcome

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is important because patients with ACOS have significantly worse outcomes compared with those with asthma or chronic obstructive pulmonary disease (COPD) alone. Inhaled corticosteroids (ICS), together with a long-acting β2 agonist (LABA), are recommended, but no therapeutic studies for ACOS have been conducted. Recently, fluticasone furoate/vilanterole (FF/VI) has been approved as the first once-daily ICS/LABA combination therapy for asthma and COPD.. A 12-week, randomized, open-label cross-over study was conducted in 16 patients with ACOS to compare the effectiveness of once-daily FF/VI 200/25 μg vs. twice-daily fluticasone propionate/salmeterol (FP/SAL) 500/50 μg. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, including forced expiratory volume in 1 s (FEV1) and respiratory impedance using the forced oscillation technique (FOT), were measured, as was fractional exhaled nitric oxide (FeNO). A COPD assessment test (CAT) scores and asthma control test (ACT) scores were recorded 0, 4, and 8 weeks after randomization.. The mean values for the FEV1 were 1.33 (±0.29) L in the run-in period, 1.38 (±0.39) L after the FP/SAL treatment period, and 1.47 (±0.38) L after the FF/VI treatment period. The FEV1 value after the FF/VI treatment was significantly greater than the value after the run-in period (p < 0.01). FOT parameters, FeNO levels, CAT scores, ACT scores, and other blood tests were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period.. FF/VI, the first once-daily ICS/LABA, can provide substantial improvement in lung functions, indicating that FF/VI should be considered for the regular treatment of ACOS.

Topics: Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Benzyl Alcohols; Chlorobenzenes; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in a single inhaler is the mainstay of asthma management. We previously showed that switching from salmeterol/fluticasone combination (SFC) 50/250 μg bid to a fixed-dose formoterol/budesonide combination (FBC) 9/320 μg bid improved asthma control and pulmonary functions, but not fractional exhaled nitric oxide (FeNO), in patients with asthma not adequately controlled under the former treatment regimen.. To assess whether switching from SFC to FBC improves peripheral airway/alveolar inflammation in asthma (UMIN000009619).. Subjects included 66 patients with mild to moderate asthma receiving SFC 50/250 μg bid for more than 8 weeks. Patients were randomized into FBC 9/320 μg bid or continued the same dose of SFC for 12 weeks. Asthma Control Questionnaire, 5-item version (ACQ5) score, peak expiratory flow, spirometry, FeNO, alveolar NO concentration (CANO), and maximal NO flux in the conductive airways (J'awNO) were measured.. Sixty-one patients completed the study. The proportion of patients with an improvement in ACQ5 was significantly higher in the FBC group than in the SFC group (51.6% vs 16.7%, respectively, p = 0.003). A significant decrease in CANO was observed in the FBC group (from 8.8 ± 9.2 ppb to 4.0 ± 2.6 ppb; p = 0.007) compared to the SFC group (from 7.4 ± 7.8 ppb to 6.4 ± 5.0 ppb; p = 0.266) although there was no significant difference in the changes in pulmonary functions between the 2 groups. Similar significant differences were found in the CANO corrected for the axial back diffusion of NO (FBC, from 6.5 ± 8.2 ppb to 2.3 ± 2.5 ppb; and SFC, from 4.3 ± 5.3 ppb to 3.9 ± 4.3 ppb). There was no difference in the changes in FeNO or J'awNO between the 2 groups.. Switching therapy from SFC to FBC improves asthma control and peripheral airway/alveolar inflammation even though there is no improvement in pulmonary functions, and FeNO in asthmatic patients.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Prospective Studies; Pulmonary Alveoli; Severity of Illness Index; Spirometry; Surveys and Questionnaires; Treatment Outcome

The object of this study was to assess whether a capsule-based and multidose dry powder inhaler containing salmeterol (as xinafoate salt) 50 μg plus fluticasone propionate (FP) 250 μg [combination (SFC 50/250)] could be equivalent in terms of in vivo drug delivery and systemic exposure.. This was a randomized, double-blind, double-dummy, replicate treatment design comparative bioavailability study of SFC 50/250 delivered in a capsule-based inhaler (Rotahaler®) and a multidose dry powder inhaler (Diskus®). Subjects with asthma or chronic obstructive pulmonary (COPD) disease (n=60) were randomized to receive twice-daily SFC 50/250 via a Rotahaler and via Diskus each for two 10-day treatment periods (GlaxoSmithKline Protocol ASR114334).. For FP and salmeterol, the in vitro aerodynamic particle size profiles were within±15% of Diskus for the fine particle mass (FPM) and emitted dose (ED) using the Andersen Cascade Impactor, and ED, mass median aerodynamic diameter, and geometric standard deviation using the New Generation Impactor (NGI). This was also the case for FP but not salmeterol for FPM and fine particle dose using the NGI. For the combined asthma and COPD subjects, the plasma AUC and Cmax for FP and salmeterol were higher for Rotahaler:Rotahaler/Diskus geometric mean ratios (90% confidence intervals) for FP AUC0-τ of 1.52 (1.37-1.67) and Cmax of 1.94 (1.75-2.10) and salmeterol AUC0-τ of 1.15 (1.09-1.21) and Cmax of 1.56 (1.42-1.67). Corresponding values for the primary pharmacodynamic endpoint, weighted mean (0-12 hr) serum cortisol, were 0.928 (0.886-0.971). Inhaled FP/salmeterol via both inhalers was well-tolerated. One serious adverse event, considered possibly related to study medication, resulted in subject withdrawal from the study.. The in vitro tests and systemic pharmacodynamic endpoints revealed no major differences between the two inhalers, but lacked predictive power and sensitivity to guide in vivo drug delivery performance and systemic exposure. Based on pharmacokinetic endpoints, the inhalers were not considered bioequivalent in terms of systemic exposure. Further studies to refine the Rotahaler performance are ongoing.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aerosols; Aged; Albuterol; Androstadienes; Area Under Curve; Asthma; Biological Availability; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Dry Powder Inhalers; Equipment Design; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Male; Middle Aged; New South Wales; New Zealand; Particle Size; Powders; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Young Adult

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility.. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials.. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial.. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial).. In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment.

Topics: Acetates; Adolescent; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, adding a long-acting β2 agonist (LABA) is the preferred treatment. We aimed to compare the effect of two widely available ICS/LABA combinations in these patients in real-life conditions: budesonide/formoterol (BUD/FM; Symbicort(®)) for maintenance and reliever therapy (SMART) and a fixed dose of fluticasone propionate/salmeterol (FP/SM).. Inadequately controlled asthma patients treated with a medium dose of ICS alone, with an Asthma Control Questionnaire (ACQ) score >0.75 and using a short-acting β2-agonist (SABA) 2-6 occasions/week, were enrolled. Patients were randomized into two groups and treated with two inhalation twice-daily BUD/FM 160/4.5 μg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation twice-daily FP/SM 250/50 μg plus as-needed procaterol (FP/SM group, n = 15) for 8 weeks.. Both groups showed significant improvement in airway inflammation, pulmonary functions and symptoms from baseline. The SMART group showed significant improvement in the fraction of nitric oxide, ACQ score, rescue medication use and small airway parameter R5-R20 measured by impulse oscillometry compared with the FP/SM group.. For stepping up treatment from ICS alone to an ICS/LABA combination, SMART is preferable for controlling asthma symptoms by suppressing airway inflammation and improving small airway impairment compared with a fixed dose of FP/SM. It may be achieved by the property of BUD/FM itself and as-needed use, but the degree of each contribution must be investigated further.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Treatment Outcome

There are several inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combinations currently used to treat asthmatic patients, but the differences in the clinical effects of these ICS/LABAs are currently unknown. We herein evaluated the effects of two currently available ICS/LABA combinations in a real-world setting.. A fluticasone propionate/salmeterol combined Discus inhaler (FP/SM; 250/50 μg bid) was switched to a budesonide/formoterol Turbuhaler inhaler (BUD/FM; 160/4.5 μg two inhalations bid) and FP/SM (500/50 μg bid) was also switched to BUD/FM (160/4.5 μg four inhalations bid) in symptomatic asthmatic patients treated with FP/SM over 20 years of age.. Sixty patients were enrolled in this study, and the scores of the asthma control test (ACT) and asthma control questionnaire-5 item version (ACQ5) were significantly improved 4 and 8 weeks after the switch to ICS/LABA treatments, and well-controlled asthma (ACQ5 score <0.75) and good control (ACT score >20) was achieved in 54 (90%) and 40 (66.7%) patients, respectively, at 8 weeks. The spirometric analysis revealed significant improvements of the values of the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) after switching from FP/SM to BUD/FM, and significantly improved small airway impairments ([Formula: see text]50 and [Formula: see text]25) were observed in patients treated with high-dose ICS/LABA. These subjective and objective improvements were also seen in patients aged over 65 years old.. These data demonstrated that changing the combined ICS/LABA inhaler from FP/SM to BUD/FM can lead to more effective management of symptomatic patients with asthma, especially in patients treated with high-dose ICS/LABA.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Longitudinal Studies; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Surveys and Questionnaires

Little is known about the effect of inhaled corticosteroids (ICS)/long-acting beta2 agonists (LABA) in combination on inflammatory markers in asthma. In addition, therapeutic equivalence of generic salmeterol/fluticasone combination (SFC) and original SFC is as yet unknown.. To determine the effects of SFC and the effects of generic and original SFC on airway inflammation in patients with mild-to moderate stable asthma.. A randomized double-blinded, crossover non-inferiority study was conducted to compare the antiinflammatory effects of generic SFC and original SFC on sputum eosinophils as a primary outcome and fractional exhaled nitric oxide (FENO) as a secondary outcome.. The authors studied 51 mild-to-moderate asthmatic patients who ranged from 18 to 80 years of age and were treated with ICS or ICS/LABA of any dose, and whose asthma was stable without an exacerbation episode for at least 3 months prior to study entry.. Both sputum eosinophils percentage and absolute eosinophil counts well correlated with FENO levels at baseline prior to the initiation of study medications. Significant reduction in sputum eosinophil percentage was observed following generic SFC and original SFC treatment. The degree of sputum eosinophil suppression by generic SFC was not inferior to original SFC, and this was not affected by treatments with the sequence of generic SFC first vs. original SFC second or original SFC first vs. generic SFC. In addition, there was no significant difference between treatments in terms of normalized gain in asthma control scores, including the number of patients found to have improved asthma control, irrespective of sequence, as change from baseline. However, this was not the case for the magnitude of FENO reduction that occurred after generic SFC treatment to a significantly larger extent than original SFC treatment.. This short-term study demonstrated that there was no significant difference between generic SFC and original SFC in terms of anti-inflammatory activity and the control of asthma symptoms. However, it is completely unknown whether generic SFC could effectively prevent the development of asthma exacerbations on a long-term basis. Therefore, longer-term studies are indicated to evaluate generic SFC's relative efficacy on asthma exacerbations.

Topics: Adult; Aged; Airway Obstruction; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Cross-Over Studies; Double-Blind Method; Drug Combinations; Drugs, Generic; Eosinophils; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Leukocyte Count; Male; Middle Aged; Sputum

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Black or African American; Child; Cross-Over Studies; Cyclopropanes; Drug Combinations; Drug Monitoring; Eczema; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Hispanic or Latino; Humans; Male; Quinolines; Sulfides; White People

Poor adherence contributes to uncontrolled asthma. Pragmatic adherence interventions for primary care settings are lacking.. To test the effectiveness of 2 brief general practitioner (GP)-delivered interventions for improving adherence and asthma control.. In a 6-month cluster randomized 2 × 2 factorial controlled trial, with GP as unit of cluster, we compared inhaler reminders and feedback (IRF) and/or personalized adherence discussions (PADs) with active usual care alone; all GPs received action plan and inhaler technique training. GPs enrolled patients prescribed combination controller inhalers, with suboptimal Asthma Control Test (ACT) scores (ACT score ≤19). Inhaler monitors recorded fluticasone propionate/salmeterol adherence (covertly for non-IRF groups) and, in IRF groups, provided twice-daily reminders for missed doses, and adherence feedback. PAD GPs received communication training regarding adherence. Outcomes collected every 2 months included ACT scores (primary outcome) and severe exacerbations. Intention-to-treat mixed-model analysis incorporated cluster effect and repeated measures.. A total of 43 GPs enrolled 143 patients with moderate-severe asthma (mean age, 40.3 ± 15.2 years; ACT score, 14.6 ± 3.8; fluticasone propionate dose, 718 ± 470 μg). Over 6 months, adherence was significantly higher in the IRF group than in non-IRF groups (73% ± 26% vs 46% ± 28% of prescribed daily doses; P < .0001), but not between PAD and non-PAD groups. Asthma control improved overall (mean change in ACT score, 4.5 ± 4.9; P < .0001), with no significant difference among groups (P = .14). Severe exacerbations were experienced by 11% of the patients in IRF groups and 28% of the patients in non-IRF groups (P = .013; after adjustment for exacerbation history; P = .06).. Inhaler reminders offer an effective strategy for improving adherence in primary care compared with a behavioral intervention or usual care, although this may not be reflected in differences in day-to-day asthma control.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; General Practitioners; Glucocorticoids; Humans; Male; Medication Adherence; Middle Aged; Nebulizers and Vaporizers; Primary Health Care; Professional-Patient Relations; Young Adult

Bacillus Calmette-Guérin and other mycobacterial vaccines are important therapeutic methods in a series of chronic inflammatory disorders characterized by Th1/Th2 imbalance in which Th2 type cells and cytokines often increase. However, few studies have investigated whether it can reduce or prevent the symptoms and attacks in children with asthma. This study evaluated the effect of inactivated Mycobacterium phlei inhaled by an atomizing device placed on asthmatic children. In this randomized, single-center, Seretide-controlled study, children aged 4-12 years with newly diagnosed, moderate, persistent asthma were treated with either inhaled inactivated M. phlei or inhaled Seretide patch. The efficacy of inhaled inactivated M. phlei was related with the alleviation of asthma symptoms, improvement of lung function and reduction of bronchial hyper-responsiveness and total serum IgE, which was similar with Seretide. These findings may have important clinical value in confirming inhaled inactivated M. phlei as a new therapeutic method in moderately asthmatic children.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bacterial Vaccines; Child; Child, Preschool; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Immunoglobulin E; Immunotherapy; Male; Mycobacterium phlei; Respiratory Function Tests; Treatment Outcome; Vaccines, Inactivated

Asthma management focuses on achieving and maintaining asthma control. Few studies have assessed whether complete and sustained asthma control is maintained in clinical practice after stepping-across ICS/LABA fixed combinations. Aim of this double-blind, double-dummy, randomized, parallel group, controlled study was to demonstrate clinical equivalence between equipotent doses of extrafine beclometasone/formoterol (BDP/F) pMDI and fluticasone/salmeterol (FP/S) Diskus® in maintaining lung function and asthma control.. A total of 416 asthmatic patients already controlled with FP/S 500/100 μg/day (Diskus®, pMDI or separate inhalers) were randomized to a 12-week treatment with extrafine BDP/F 400/24 μg/day pMDI or FP/S 500/100 μg/day Diskus®. Pre-dose 1-s forced expiratory volume (FEV(1)) was the primary efficacy variable; secondary variables included asthma control questionnaire (ACQ-7) and FEV(1)0-1 h area under the curve (FEV(1)AUC(0-1h)). Safety was assessed through adverse events monitoring and vital signs.. After 12 weeks of treatment, pre-dose FEV(1) did not differ between treatments (difference between means 0.01 L; 95% CI -0.03-0.06 L) with no significant changes from baseline in both groups (p = 0.726 and p = 0.783 in BDF/F arm and FP/S, respectively). ACQ-7 score showed that control was maintained after stepping-across to extrafine BDP/F. FEV(1)AUC(0-1h) was significantly higher in BDP/F arm at the beginning (p = 0.004) and at the end of the 12-week treatment period (p = 0.019). No safety issues were reported in both groups.. Patients previously controlled with FP/S in any device formulation can effectively step-across to extrafine BDP/F pMDI, maintaining lung function and asthma control with a 5-min onset of action.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Particle Size; Respiratory Function Tests; Time Factors; Treatment Outcome

Asthma is an increasing pathology with poor compliance. Achievement of control is possible but under intensive treatment. In this setting, fluticasone/salmeterol association delivered by dry powder inhalers is a valuable and proved option. A prospective, parallel, open-label, phase IV, multicentre non-inferiority study was conducted to determine therapeutic similarity between 2 different inhalers: Generic DPI and Diskus®, which both deliver a fluticasone/salmeterol association (CAS 80474-14-2/CAS 89365-50-4). A 103 uncontrolled asthmatic patients were randomly assigned in 2 groups, Generic (G) and Diskus® (D), and received the association for 18 weeks through the appropriate device. They were evaluated according to Asthma Quality of Life Questionnaire and GINA/NIH guidelines. To demonstrate non-inferiority, the estimation of the Relative Risk between the Global Score Rate per group with its 95% confidence interval was calculated and compared against a non-inferiority margin obtained from a previous study. The Global Score Rate was 82% for G Group and 83% for D Group. The RR was 1.0124 (95% CI: 0.847-1.210). The margin set at 0.832 was not reached by the lower 95% CI (z=-2.097; p=0.018) pointing out non-inferiority. The results have demonstrated non-inferiority between groups. Thus, the 2 products are therapeutically similar.

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged

In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it.. We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders".. On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/μL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04).. Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; C-Reactive Protein; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Particle Size; Quality of Life; Spirometry; Statistics, Nonparametric; Treatment Outcome

The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS.. In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment.. Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (-37 mL; 95% CI, -88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events.. The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Benzyl Alcohols; Child; Chlorobenzenes; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Young Adult

GINA guideline recommends stepping down treatment of asthma patients where control is achieved. The aim of this analysis was to estimate the costs and health outcomes associated with step down of controlled patients on high dose fluticasone/salmeterol (FP/S 1000/100 μg daily) to either medium dose FP/S (500/100 μg) dry powder or extrafine beclometasone/formoterol (BDP/F 400/24 μg) pMDI in three European countries.. A patient-level simulation Markov model was constructed to enable the simulation of three comparative arms (FP/S 1000/100, FP/S 500/100, BDP/F 400/24). Transition probabilities and healthcare resources consumption were derived from a multinational clinical trial comparing BDP/F 400/24 μg vs. FP/S 500/100 μg as step down therapy in asthma. Direct costs and health state utilities were sourced from public source and published literature. The analysis was conducted from a health system perspective, based on six months horizon. Probabilistic sensitivity analyses were conducted.. The ICER (Incremental Cost-Effectiveness Ratio) associated with high dose dry powder FP/S 1000/100 μg vs. extrafine BDP/F 400/24 μg was above 70,000 GBP and 200,000 €/QALY (Quality Adjusted Life Years). An ICER of 29,000 GBP/QALY and above 30,000 €/QALY was associated with medium dose dry powder FP/S 500/100 μg vs. BDP/F 400/24 μg.. It was found that maintaining controlled patients on high dose FP/S is not cost-effective. Extrafine BDP/F 400/24 μg daily can be considered to be a cost-effective option in the countries analyzed to maintain control of asthmatic patients stepped down from high dose FP/S 1000/100 μg daily dry powder or suspension formulations.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Costs; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Humans; Markov Chains; Models, Econometric; Netherlands; Quality-Adjusted Life Years; Spain; United Kingdom

The effects of mometasone furoate and fluticasone propionate on the hypothalamic-pituitary-adrenal axis were compared when administered from combination metered-dose inhaler (MDI) products.. In a randomized, open-label, placebo-controlled, parallel group study, 66 patients with mild to moderate asthma received one of the following four treatments bid through an MDI for 42 days: mometasone furoate/formoterol (MF/F) 200 μg/10 μg, MF/F 400 μg/10 μg, fluticasone propionate/salmeterol (FP/S) 460 μg/42 μg, or placebo. Plasma cortisol concentrations were measured over 24 h on days -1 (baseline) and 42. Geometric mean ratio (GMR) and 90% CI for mean change from baseline to day 42 in 24-h plasma cortisol area under the curve (AUC) were calculated for each treatment. If the 90% CI for the GMRs fell within 70% to 143%, treatments were deemed comparable.. Mean baseline cortisol AUCs were similar across groups. Mean cortisol effects (change from baseline) were similar for MF/F 400 μg/10 μg and FP/S 460 μg/42 μg (GMR, 119%; 90% CI, 101%-140%). Effects of MF/F 200 μg/10 μg on cortisol AUC were similar to placebo (GMR, 92%; 90% CI, 78%-110%), whereas MF/F 400 μg/10 μg and FP/S 460 μg/42 μg lowered cortisol AUC vs placebo (GMR, 78% [90% CI, 66%-92%] and 66% [90% CI 56%-78%], respectively). All treatments were generally well tolerated.. MF/F 400 μg/10 μg or FP/S 460 μg/42 μg bid through an MDI led to similar reductions from baseline in mean cortisol AUC (22% and 34% lower than placebo, respectively), whereas the effect of MF/F 200 μg/10 μg was similar to placebo.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Pregnadienediols; Treatment Outcome; Young Adult

To investigate Salmeterol/Fluticasone Propionate and Totropiumi treatment of Sillicosis merger Asthma.. 30 patients with Sillicosis merger Asthma were randomly divided into group Salmeterol/Fluticasone Propionate( Single group) ( n=14) and group Salmeterol/Fluticasone Propionate and Totropiumi (Joint group) ( n= 16), patient in single group were only given Salmeterol/Fluticasone Propionate (50 f.Lg Bid) inhaling,and those in Joint group were given Salmeterol/Fluticasone Propionate (50 f.Lg Bid) and Totropiumi ( 18 f.Lg Qd) inhaling. The treatment was last for 6 months.Before the treatment,evaluation of the two groups of Sillicosis installment,determination their foungation lung function and ACT score .. After the cause of treatment, lung function FEV10/FVC(% ), FEV10 pred%, FEV10(ml), ACT score, the incidence of side effects of two groups were compared and analyzed.. The two groups before the treatment of lung fuction and ACT score had no statistically significant difference. The two groups after treatment of lung fuction FEV10/FVC (% ),FEV10 pred%, ACT score obviously higher than before treatment (P<0.05), Joint group in FEV1/FVC(% ), ACT score significantly higher than in Single group (?<0.05), Joint group acute attack times(0.98±0.79)/time lower than Single group (2.10 ± 0.81 )/time (t=3.86,P<0.05). There were no significant side effect in two groups.. Salmeterol/Fluticasone Propionate or the combination of Salmeterol/Fluticasone Propionate and Totropiumi can improve lung function and clinical symptoms of patients with Sillicosis merger Asthma. It is also better that the combination of Salmeterol/Fluticasone Propionate and Totropiumi obviously improve clinical symptoms of patients and reduice acute attack times.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Silicosis; Treatment Outcome

The long-acting β2-agonist salmeterol in combination with the corticosteroid fluticasone propionate is used in clinical practice for the treatment of mild persistent asthma. Although the effect of fluticasone propionate alone in asthmatic patients is well documented, the effect of fluticasone propionate/salmeterol (FSC) combination therapy on airway inflammation and airway hyperresponsiveness (AHR) is not well characterized. Thus, we evaluated AHR, exhaled nitric oxide (FE(NO)), and nitrite and nitrate in exhaled breath condensates (EBCs) from mild persistent asthmatic patients treated with a low-dose FSC (100/50).. In this open label study, 18 mild persistent, steroid-naïve asthmatics (age, 22-62 years, forced expiratory volume in 1 s (FEV(1)) > 70% predicted, provocative dose resulting in 20% reduction (PD(20)) < 10 mg/mL) were treated with FSC 100/50 for 4 weeks. PD(20) to methacholine, FEV(1), FE(NO), and EBC nitrite and nitrate was measured before and after treatment.. After 4 weeks of therapy with FSC 100/50, FE(NO) decreased from 74 ppb (SD = 37) to 34 ppb (SD = 15) (p < .001). FEV(1) (% predicted) increased from 89.4 (SD = 10.7) to 93.3 (SD = 9.5) (p < .01). The PD(20) for methacholine increased from 3.0 (±3.2) to 10.3 (±8.4) mg/mL (p < .01) in 3 of 18 patients reaching the maximum allowable dose (25 mg/mL). FE(NO) correlated with the log of the methacholine dose. There was no statistically significant change in EBC nitrite and nitrate before and after treatment.. Treatment of mild persistent, steroid-naïve asthmatics with low-dose combination therapy is effective in rapidly reducing airway inflammation and AHR. Our results suggest different metabolic origins for nitrite, nitrate, and FE(NO) in this group of patients.

Topics: Adult; Albuterol; Androstadienes; Asthma; Breath Tests; Bronchial Provocation Tests; Bronchodilator Agents; Cross-Sectional Studies; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Linear Models; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Young Adult

To compare the efficacy of theophylline plus salmeterol/fluticasone propionate combination product (SFC) with SFC plus placebo in asthmatic patients.. In this randomized, stratified, parallel-group study, 325 patients were randomized to receive either 200 mg theophylline plus 50/250 μg SFC or placebo tablet plus 50/250 μg SFC twice daily for 24 weeks. Outcome variables included the level of asthma control (assessed by the Asthma Control Test) and the number of patients experiencing ≥1 exacerbations during the 24-week treatment period. Testing of lung function as well as measurement of the levels of inflammatory markers in induced sputum was performed.. There were significantly fewer patients with ≥1 asthma exacerbation in the theophylline plus SFC group (29.6%) when compared with the SFC plus placebo group (46.9%) (p = 0.004). Theophylline plus SFC improved the FEF(25-75%) value, which indicates enhanced small airway function, to a greater extent than SFC plus placebo (66.9 ± 18.8% and 57.4 ± 17.6%, respectively; p < 0.001). A significant decrease in eosinophil count and concentration of eosinophil cationic protein in induced sputum was also seen in the theophylline plus SFC group when compared with the SFC plus placebo group (4.1 ± 2.2% and 6.3 ± 2.7%, 63.6 ± 39.5 μg/L and 89.4 ± 45.6 μg/L, respectively; all p < 0.01).. The combination of theophylline plus SFC may provide greater protection against asthma exacerbations, and its administration is accompanied by significant improvements in small airway function and airway inflammation.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Circadian Rhythm; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Inflammation Mediators; Male; Middle Aged; Peak Expiratory Flow Rate; Respiratory Mechanics; Sputum; Theophylline; Treatment Outcome; Young Adult

The objective of this study was to investigate whether high-dose inhaled fluticasone propionate (FP), alone or in combination with salmeterol (SAL), is as effective as oral prednisolone in reducing airway inflammation and obstruction in cats with experimentally-induced acute asthma. Six cats sensitised to Ascaris suum (AS) were enrolled in a prospective controlled therapeutic trial and underwent four aerosol challenges, at 1-month intervals with AS allergen. The allergen - stimulated animals received four consecutive days treatment with either oral prednisolone at 1mg/kg twice daily, 500 μg of FP inhaled twice daily, or a combination of FP/SAL at 500 μg/50 μg inhaled twice daily, respectively, according to a randomised cross-over design. Treatment-related changes in lung function, airway responsiveness (AR) and bronchoalveolar lavage fluid (BALF) cytology were assessed. Barometric whole-body plethysmography (BWBP) was used for the assessment of respiratory variables and AR. No significant differences in respiratory rate or Penh (an estimate of airflow limitation measured by BWBP) were detected among treatment groups. Allergen-induced airway hyper-responsiveness was significantly inhibited by all three steroid treatments (P<0.05). The mean BALF eosinophil percentage (±SEM) was lower after oral and inhaled corticosteroid treatment and these changes were significant for groups receiving prednisolone and the FP/SAL combination. Findings suggest high-dose FP, particularly in combination with SAL, is effective in ameliorating airway inflammation and hyper-responsiveness in this model of acute feline asthma, and highlight the potential use of these drugs in cats experiencing acute exacerbations of the naturally occurring disease.

Topics: Administration, Inhalation; Administration, Oral; Albuterol; Allergens; Androstadienes; Animals; Anti-Inflammatory Agents; Antigens, Helminth; Ascaris suum; Asthma; Bronchodilator Agents; Cat Diseases; Cats; Cross-Over Studies; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Male; Prednisolone; Prospective Studies

Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.. Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 μg) two puffs bid (plus fluticasone placebo), or active fluticasone (250 μg) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV(1) (PC(20)).. In the patients who did not smoke, there were similar improvements in the methacholine PC(20) with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC(20) difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P < .01. The provocative dose of mannitol required to produce a 15% fall in FEV(1) (PD(15)) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEV(1) and airway resistance.. FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke.. ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov.

Topics: Adult; Albuterol; Androstadienes; Asthma; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Mannitol; Methacholine Chloride; Placebos; Smoking; Spirometry; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome

Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta2-agonist. The present study was designed to evaluate the efficacy of a newly developed fixed combination of ciclesonide and formoterol in comparison to the marketed fixed combination of fluticasone and salmeterol in patients with moderate asthma. This was a phase II, multi-centre, randomized, parallel-group, double-blind, double-dummy study. After a 2-week run-in period, 160 patients with moderate asthma were randomized to a 6-week treatment with ciclesonide/formoterol 320/9 μg bid (CIC/F) or fluticasone propionate/salmeterol 250/50 μg bid (FP/S), both delivered as powder formulations. The primary outcome FEV1 increased during treatment by 0.356 L in the CIC/F group and by 0.288 L in the FP/S group (p < 0.0001). The increases were statistically significant and clinically relevant. The between-treatment analysis demonstrated non-inferiority of CIC/F to FP/S treatment (p < 0.0001). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. No differences were observed between treatments in the frequency of adverse events and overnight urinary cortisol/creatinine ratio. The studied fixed combination of ciclesonide/formoterol is not inferior to the marketed fixed combination of fluticasone/salmeterol in terms of efficacy and tolerability.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Austria; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Germany; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones; Treatment Outcome; Young Adult

The airway contains airway smooth muscle and airway vascular smooth muscle. The acute effects of inhaled long-acting β(2)-adrenergic agonists (LABAs) alone, or in combination with an inhaled glucocorticoid (ICS), on airway smooth muscle tone in asthma are known; however, to the best of our knowledge, their effect on airway vascular smooth muscle tone has not been investigated previously. The objective of this study was to investigate the immediate effects of a LABA and an ICS alone and in combination on airway blood flow (Qaw) as an index of airway vascular smooth muscle tone in patients with stable asthma.. Fourteen subjects with moderate asthma inhaled single doses of salmeterol (50 μg), fluticasone propionate (250 μg), salmeterol/fluticasone propionate (50/250 μg), or placebo; Qaw was measured before and serially for 240 min after drug administration.. Mean Qaw increased after salmeterol and salmeterol/fluticasone propionate, with peaks at 60 min of 34% and 40%, respectively, and returned to baseline by 240 min after inhalation. Fluticasone propionate alone caused a transient decrease in mean Qaw. The maximal changes in Qaw, which occurred at different times, were 60% for salmeterol, 67% for salmeterol/fluticasone propionate, and -19% for fluticasone propionate (P < .05 vs placebo for all).. The LABA salmeterol has an acute vasodilator action on the airway of subjects with stable asthma. The addition of fluticasone propionate, which by itself causes vasoconstriction, does not attenuate the salmeterol-induced vasodilation, suggesting that fluticasone propionate potentiates the vasodilator effect of salmeterol. The vasodilation could be of clinical benefit by promoting the vascular clearance of inflammatory mediators including spasmogens from the airway.. ClinicalTrials.gov; No.: NCT01231230; URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adult; Airway Resistance; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Blood Flow Velocity; Bronchi; Bronchodilator Agents; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Muscle, Smooth; Muscle, Smooth, Vascular; Salmeterol Xinafoate; Vasodilation; Vital Capacity; Young Adult

Inhaled combined therapy improves the pulmonary function in asthmatic patients. The effect on the airway hyperresponsiveness (AHR) and the efficacy of different pharmacological schedules is not well clarified on adolescent asthmatics.. Evaluate the responses to different combined inhaled therapies in adolescent asthmatics and study its impact on exercise induced AHR.. Basal lung function tests (LFT) were performed in 30 adolescents (13 to 16 years old; 19 female) with allergic asthma. They were submitted to exercise challenge test (EC) followed by bronchodilator test (BD). During 4 weeks, 15 adolescents were submitted to inhaled fluticasone/salmeterol (group A) and other 15 to inhaled budesonide/formoterol (group B). After this period, they underwent another functional evaluation as previous.. Before treatment, pulmonary function was similar in both groups. After 4 weeks of treatment, these groups showed an improvement of the basal LFT (p = 0.001 for FEV1 in both), decrease on bronchoconstriction induced by exercise (NS for both) and less recovery on BD response (p = 0.001 and 0.002, for FEV1 respectively groups A and B). Group B showed a better performance, with higher improvement of basal FEF 25/75 (p = 0.001), reduced bronchoconstriction response to EC (p = 0.008 for FEV1) and fewer response to BD test (p < 0.0001 for FEV1 and 0.024 for FEF 25/75) No adverse events were observed.. After 4 weeks of inhaled combined therapy, these patients improved their pulmonary function and bronchomotricity. Those under budesonide/formoterol showed the highest improvement. These medications are a safe measure in controlling the asthma in these patients.

Topics: Adolescent; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Respiratory Function Tests

The combination of an inhaled corticosteroid (ICS), budesonide, and a rapid long-acting β(2)-agonist (LABA), formoterol, in a single inhaler for use as maintenance and reliever therapy (Symbicort Turbuhaler SMART™) effectively achieves a high level of asthma control and reduces exacerbations and asthma-related hospitalizations. The COSMOS study, a multinational, 12-month study (N = 2143), compared budesonide/formoterol maintenance and reliever therapy with salmeterol/fluticasone propionate plus as-needed salbutamol, allowing physicians to modify maintenance doses of both combinations according to routine clinical practice.. The aim of this post hoc sub-group analysis of the COSMOS study is to provide focused data on budesonide/formoterol maintenance and reliever therapy compared with salmeterol/fluticasone propionate plus as-needed salbutamol in patients (aged ≥16 years) enrolled across Asian countries, specifically China, Korea, Taiwan and Thailand.. This sub-analysis of the COSMOS study concerns all 404 randomized patients ≥16 years of age (mean forced expiratory volume in 1 second [FEV(1)] 69.1%) who were recruited from Asian countries. Patients received either budesonide/formoterol (Symbicort Turbuhaler SMART™, n = 198), starting dose 160 mg/4.5 mg two inhalations twice daily (bid) [plus additional as-needed inhalations], or salmeterol/fluticasone propionate (Seretide(®) Diskus(®), n = 206), starting dose 50 mg/250 mg bid (plus salbutamol [Ventolin(®)] as needed). Maintenance doses could be titrated by clinicians after the first 4 weeks (budesonide/formoterol maintenance plus as needed, n = 198; salmeterol/fluticasone propionate plus salbutamol, n = 206). To allow for free adjustment in maintenance doses in both arms, the trial was performed open-label; maintenance doses could be titrated by clinicians after the first 4 weeks. The time to first severe exacerbation (defined as deterioration in asthma resulting in hospitalization/emergency room treatment, oral corticosteroids for ≥3 days or unscheduled visit leading to treatment change) was the primary variable.. The time to first severe exacerbation was prolonged in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate plus salbutamol (log-rank p = 0.024). The risk of a first exacerbation was reduced by 44% (hazard ratio 0.56; 95% confidence interval [CI] 0.32, 0.95; p = 0.033) in patients using the adjusted budesonide/formoterol regimen versus titrated salmeterol/fluticasone propionate. The overall exacerbation rates were 0.16 versus 0.26 events/patient-year, respectively, with a 38% reduction (rate ratio 0.62/patient/year; 95% CI 0.41, 0.94; p = 0.024) in favour of the budesonide/formoterol regimen. Compared with baseline, both regimens provided clinically relevant improvements in asthma control, quality of life and FEV(1); no statistically significant differences between the treatment groups were observed. Mean adjusted (standard deviation) ICS dose (expressed as beclomethasone dose equivalents) during treatment, including as-needed budesonide doses, was 944 (281) and 1034 (394) μg/day, respectively, in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate.. In patients (aged ≥16 years) enrolled from Asian countries as part of the COSMOS study, the budesonide/formoterol maintenance and reliever regimen was associated with a lower future risk of exacerbations versus the physicians' free choice of salmeterol/fluticasone propionate dose plus salbutamol. Single inhaler combination treatment with maintenance plus as-needed budesonide/formoterol was also at least as efficacious as salmeterol/fluticasone propionate dose plus salbutamol in improving current asthma control.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Analysis of Variance; Androstadienes; Asia; Asian People; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Proportional Hazards Models; Time Factors; Treatment Outcome; Young Adult

Treatment guidelines recommend using an inhaled corticosteroid (ICS) plus a long-acting β(2)-agonist (LABA) for childhood asthma when the symptoms are not controlled by ICS alone, but the appropriate use of LABAs in children continues to be debated.. To compare the efficacy of an inhaled salmeterol and fluticasone propionate combination, 50/100 μg twice daily, with fluticasone propionate, 100 μg twice daily, or salmeterol, 50 μg twice daily, in children with multiple-trigger wheeze.. A total of 105 children 4 to 7 years of age with multiple-trigger wheezing based on respiratory symptoms and bronchodilator responsiveness and/or exercise-induced bronchoconstriction without a viral cold were randomized to salmeterol-fluticasone, fluticasone propionate alone, or salmeterol alone via a metered-dose inhaler and a spacer device for 8 weeks. The primary efficacy outcome was exhaled nitric oxide level. Secondary outcomes were lung function measurements via impulse oscillometry, respiratory symptoms, and rescue medication use.. The exhaled nitric oxide levels decreased after all treatments, significantly more so after salmeterol-fluticasone and fluticasone than with salmeterol (adjusted geometric means at 8 weeks: salmeterol-fluticasone, 9.4 ppb; fluticasone, 9.3 ppb; salmeterol, 13.9 ppb; salmeterol-fluticasone vs salmeterol, P = .02; fluticasone vs salmeterol, P = .01). No treatment differences were found with respect to respiratory symptoms or median rescue use. Salmeterol-fluticasone resulted in a small but statistically significant improvement in baseline lung function compared with fluticasone. All treatments were equally well tolerated.. The effects of salmeterol-fluticasone and fluticasone were comparable, although lung function improvement was better with salmeterol-fluticasone than with fluticasone alone. There is no obvious benefit in initiation therapy with salmeterol-fluticasone rather than fluticasone alone in the treatment of steroid-naive children with multiple-trigger wheeze.. Pathway of clinical trial registry of Helsinki University:http://www.hus.fi/?Path=1;28;2530;9899;9900;23618;23903;33578.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Asthma; Breath Tests; Bronchodilator Agents; Child; Child, Preschool; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Nitric Oxide; Precipitating Factors; Respiratory Sounds; Salmeterol Xinafoate; Treatment Outcome

Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy.. This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.. Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.. Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.. clinicaltrials.gov NCT00497237.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Prospective Studies; Young Adult

The SmartTrack (ST) is a new adherence monitoring device for pressurized metered-dose inhalers (pMDI), with remote upload and ringtone reminder capabilities. Our aim was to assess its reliability and patient acceptability.. Baseline Quality Control (QC): Actuation log accuracy and device functionality tests were undertaken. Simulated Patient Use: Salmeterol/fluticasone inhalers with STs were actuated two times twice daily for 48 h. Accuracy of reminders, data logging, and uploads was tested. Patient Field Testing: Devices were quality tested before dispensing. Asthma patients each field-tested one ST for 7 days and recorded actuations in a diary. Uploaded data were compared to pMDI dose counter and patient diaries. Patient-reported ease of use for the ST was recorded.. Baseline QC: 9/10 devices had 100% accuracy; one had an electrical circuit failure. Simulated Patient Use: Accuracy was 99% (2/342 actuations duplicated). Patient Field Testing: One device failed pre-dispensing testing (electrical circuit failure). Eight devices were field-tested by asthma patients (mean age 45, 5 females). Mean actuation log accuracy was 97%. Reminders were 100% accurate. All devices successfully uploaded data. Average patient-rated difficulty of use was 6/100 (1 = extremely easy, 100 = extremely difficult).. The ST has acceptable reliability and utility comparable to other electronic monitoring devices. Its remote data upload capability, reminder functions for missed doses, and graphical display of medication use for patient- and physician-feedback are useful additional features.

Topics: Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Drug Monitoring; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Medication Adherence; Metered Dose Inhalers; Middle Aged; Patient Satisfaction

To observe the difference in the efficacy on the symptoms of bronchial asthma at the chronic persistent stage between acupoint heat-sensitive moxibustion and western medicine with Seretide.. Sixty-four cases were randomly divided into a heat-sensitive moxibustion group (32 cases) and a western medication group (32 cases). In the heat-sensitive moxibustion group, the sensitized points located between Feishu (BL 13) and Geshu (BL 17) or in the region 6-cun lateral from the 1st and the 2nd intercostal spaces of the chest were selected. The heat-sensitive moxibustion was adopted, continuously for 8 days, once per day. In the later 22 days of the 1st month, 12 treatments should be ensured. Two months later, 15 treatments should be guaranteed each month. The time of each treatment was 30 to 90 min. Totally 50 treatments were required. In the western medication group, Seretide inhaler was adopted, one inhalation each time, twice per day, for 3 months totally. The asthmatic symptoms were scored for the patients in two groups and the comparison was made between the two groups.. After 3 months of treatment, the asthmatic symptom scores were all improved for the patients in the heat-sensitive moxibustion group and the western medication group as compared with those before treatment (both P < 0.05). In 6 months of follow-up visit, the asthmatic symptom scores in the heat-sensitive moxibustion group were stable, but those in the western medication group were reduced, there was significant difference between the two groups (P < 0.05).. The acupoint heat-sensitive moxibustion effectively relieves the clinical symptoms for the patients with bronchial asthma at the chronic persistent stage. Its efficacy is similar to that of Seretide inhaler. But the long-term efficacy of the heat-sensitive moxibustion is much better.

Topics: Acupuncture Points; Adolescent; Adult; Albuterol; Androstadienes; Asthma; Chronic Disease; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Moxibustion

The inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting beta(2)-agonist, formoterol fumarate (formoterol), have been combined in a single aerosol inhaler (fluticasone/formoterol). In a randomized, open-label study, fluticasone/formoterol showed similar efficacy to fluticasone/salmeterol after 12 weeks of treatment. This post-hoc analysis compared the onset of bronchodilation with the two treatments.. Adults with mild-to-moderate-severe persistent asthma were randomized to fluticasone/formoterol (100/10 or 250/10 μg twice daily [b.i.d.]) or fluticasone/salmeterol (100/50 or 250/50 μg b.i.d.) for 12 weeks. The onset of bronchodilation (the first post-dose time point at which the forced expiratory volume in 1 second [FEV(1)] was ≥12% greater than the pre-dose value), responder rates (the proportion of patients achieving bronchodilation), and changes in FEV(1) were assessed at days 0 (baseline) and 84.. Fluticasone/formoterol (n = 101) provided more rapid onset of bronchodilation than fluticasone/salmeterol (n = 101) over the first 120 min post-dose on days 0 (hazard ratio [HR] = 1.47 [95% CI 1.05-2.05]) and 84 (HR = 1.77 [95% CI 1.14-2.73]). The odds of a patient achieving bronchodilation within 5 min of dosing were almost four-times higher with fluticasone/formoterol than with fluticasone/salmeterol on day 0 (odds ratio [OR] = 3.97 [95% CI 1.96-8.03]) and almost 10-times higher on day 84 (OR = 9.58 [95% CI 2.14-42.90]); the odds of achieving bronchodilation within 120 min post-dose were approximately twofold higher with fluticasone/formoterol on both days. The overall percentage increase in least-squares (LS) mean FEV1 during the 120-min post-dose period was significantly greater with fluticasone/formoterol than fluticasone/salmeterol on days 0 (LS mean treatment difference: 4.70% [95% CI 1.57-7.83]; P = 0.003) and 84 (2.79% [95% CI 0.65-4.93]; P = 0.011).. These analyses showed that fluticasone/formoterol provided a faster onset of bronchodilation than fluticasone/salmeterol, which was maintained over 12 weeks of treatment. This benefit may facilitate treatment adherence among patients with asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Formoterol Fumarate; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Odds Ratio; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome

In asthma, multidetector row computed tomography (MDCT) detects abnormalities that are related to disease severity, including increased bronchial wall thickness. However, whether these abnormalities could be related to asthma control has not been investigated yet.. Our goal was to determine which changes in airways could be linked to disease control.. Twelve patients with poor asthma control were included and received a salmeterol/fluticasone propionate combination daily for 12 weeks. Patients underwent clinical, functional, and MDCT examinations before and after the treatment period. MDCT examinations were performed using a low-dose protocol at a controlled lung volume (65% TLC). Bronchial lumen (LA) and wall areas (WA) were evaluated at a segmental and subsegmental level using BronCare software. Lung density was measured at the base of the lung. Baseline and end-of-treatment data were compared using the Wilcoxon signed-rank test.. After the 12-week treatment period, asthma control was achieved. Airflow obstruction and air trapping decreased as assessed by the changes in FEV(1) (p < 0.01) and expiratory reserve volume (p < 0.01). Conversely, LA and WA did not vary significantly. However, a median decrease in LA of >10% was observed in half of the patients with a wide intra- and intersubject response heterogeneity. This was concomitant with a decrease in lung density (p < 0.02 in the anteroinferior areas).. MDCT is insensitive for demonstrating any decrease in bronchial wall thickness. This is mainly due to changes in bronchial caliber which may be linked to modifications of the elastic properties of the bronchopulmonary system under treatment.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Bronchi; Bronchography; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Imaging, Three-Dimensional; Male; Pilot Projects; Tomography, X-Ray Computed; Young Adult

The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β2-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, flutiform ®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol.. Patients aged ≥ 18 years (N = 202) with mild-to-moderate-severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4-10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV1), at week 12.. Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV1 at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV1, change from pre-dose FEV1 at baseline to 2-hour post-dose FEV1 at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol.. The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

A course of combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2) agonist (LABA) for asthma can improve lung function, asthma symptoms and reduce exacerbations. Because both medicinal substance and inhalation devices are associated with clinical efficacy, each ICS/LABA combination may have different features. This study aimed to compare the effects of two widely available formulations, budesonide/formoterol (BUD/FM) delivered by a Turbuhaler(®), and fluticasone/salmeterol (FP/SM) delivered by a Diskus(®), on small airway function and airway inflammation.. Asthmatic patients (n = 40) treated twice daily with FP/SM 250/50 μg with forced expiratory volume in 1 s values controlled above 80% of the predicted normal but with suspected persistent airway inflammation and small airway impairment were enrolled in the study. Patients were randomized into two groups, receiving either twice daily BUD/FM 320/9 μg or FP/SM 250/50 μg, and treatment efficacy was compared after 4 weeks. Outcomes included impulse oscillometry (IOS), fractional exhaled nitric oxide (FeNO), spirometry and Asthma Control Questionnaire (ACQ) scores.. Patients in the BUD/FM group showed significant improvements in their IOS and spirometry parameters of small airway function, FeNO values and ACQ scores, compared with the FP/SM group. There were good correlations between IOS parameters, FeNO and ACQ score changes over the course of the treatment.. BUD/FM twice daily significantly improved small airway impairment and airway inflammation in asthmatic patients, leading to a reduction in asthma symptoms and achievement of good asthma control. In addition, improvement of small airway function may improve airway inflammation and/or lead to better controlled asthma.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Oscillometry; Spirometry

The aim of asthma management is to achieve and maintain clinical control. Control data for children is sparse.. This analysis evaluated factors associated with not achieving well-controlled (WC) asthma using data from a study in 548 children with uncontrolled asthma.. Post hoc analysis of factors affecting the probability of not achieving WC asthma in children receiving salmeterol/fluticasone propionate 50/100 µg bd (SFC) or montelukast 5 mg od (MON), included: reasons for patients failing the asthma control criteria; achievement of overall asthma control; time course of improvement in individual outcomes and composite score; factors associated with not achieving WC asthma.. The proportion of patients failing individual control criteria at baseline was: β2-agonist rescue use: 96%, peak expiratory flow (PEF): 91%, symptoms: 78%, and night-time awakenings: 66%. Most patients failed the composite control score for more than one reason with 482 (99%), 387 (80%), and 249 (52%) failing 2, 3, or 4 control criteria, respectively. Overall asthma control was achieved by 166 (59%) patients in the SFC group and 96 (36%) in the MON group (P < 0.001). Time course of control differed between individual control components with symptoms responding most rapidly and PEF most slowly. Factors significantly influencing the probability of not achieving WC asthma were treatment with MON, country, and night-time awakenings at baseline, treatment being the most important.. Different outcomes improve at different rates. Assessment of one or a few outcomes over-estimates the level of asthma control. An overall composite score in combination with the proportion of patients failing on three or more criteria seemed to most accurately reflect the level of control. Compared with SFC treatment, MON was three times less likely to result in good asthma control.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Peak Expiratory Flow Rate; Treatment Outcome

The mechanisms of airway hyper-responsiveness are only partially understood and the contribution of airway remodelling is unknown. Airway remodelling can be assessed by measuring airway distensibility, which is reduced in asthma, even when lung function is normal. We hypothesised that airway remodelling contributes to airway hyper-responsiveness in asthma, independent of steroid-responsive airway inflammation.. To determine the relationship between airway distensibility and airway responsiveness at baseline and after 12 weeks of inhaled corticosteroid therapy in a group of asthmatics with airway hyper-responsiveness.. Nineteen doctor-diagnosed asthmatics had airway distensibility measured as the slope of the relationship between conductance and lung volume by the forced oscillation technique. Lung function, exhaled nitric oxide and methacholine challenge were also measured. Subjects had inhaled corticosteroid therapy for 12 weeks after which all measurements were repeated.. At baseline, airway distensibility (mean, 95%CI) was 0.19(0.14-0.23) cm H(2)O(-1)s(-1), exhaled nitric oxide was 13.1(10.3-16.6)ppb and airway distensibility correlated with eNO (p=0.04) and disease duration (p=0.02) but not with airway responsiveness (p=0.46), FEV(1) (p=0.09) or age (p=0.23). After treatment, exhaled nitric oxide decreased (p=0.0002), FEV(1) improved (p=0.0001), airway responsiveness improved (p=0.0002), and there was a small improvement in airway distensibility but it did not normalise (p=0.05). Airway distensibility was not correlated with either exhaled nitric oxide (p=0.49) or airway responsiveness (p=0.20).. Uncontrolled airway inflammation causes a small decrease in the distensibility of the airways of asthmatics with airway hyper-responsiveness. The lack of association between airway responsiveness and airway distensibility, both before and after 12 weeks ICS treatment, suggests that airway remodelling does not contribute to airway hyper-responsiveness in asthma.

Topics: Adult; Airway Remodeling; Airway Resistance; Albuterol; Androstadienes; Asthma; Bronchial Hyperreactivity; Drug Combinations; Exhalation; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Surveys and Questionnaires; Total Lung Capacity

Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied.. We sought to determine the clinical consequences of nocturnal asthma symptoms requiring albuterol (NASRAs) in children with mild-to-moderate persistent asthma outside of periods when oral corticosteroids were used for worsening asthma symptoms.. Two hundred eighty-five children aged 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of 3 controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of NASRAs.. NASRAs occurred in 72.2% of participants at least once, and in 24.3% of participants, they occurred 13 or more times. The majority (81.3%) of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use (56.9% of days preceded by nocturnal symptoms vs 18.1% of days not preceded by nocturnal symptoms; relative risk [RR], 2.3; 95% CI, 2.2-2.4), school absence (5.0% vs 0.3%; RR, 10.6; 95% CI, 7.8-14.4), and doctor contact (3.7% vs 0.2%; RR, 8.8; 95% CI, 6.1-12.5). Similar findings were noted during exacerbation periods (RRs of 1.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contacts). Nocturnal symptoms did not predict the onset of exacerbations.. Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences.

Topics: Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Prevalence; Sleep

Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE), whereas sham treatment would not.. Fourteen healthy adults participated in a repeated-measures design in which they received IC and sham treatments in counterbalanced order. PTP and PPE were measured prior to treatments, immediately following treatments, and at 1 and 2 hr following treatments.. IC treatment increased PTP, but sham treatment did not. The increase in PTP was maintained for a 2 hr period following administration. PPE ratings were not significantly correlated with PTP.. IC treatments can have acute, adverse effects on phonation. Detrimental phonatory effects were elicited in participants with no self-reported voice problems. IC treatments are being increasingly prescribed across the lifespan. The current data increase our understanding of the nature of phonatory deterioration associated with IC treatment and lay the groundwork for increased research effort to develop IC treatments that effectively control respiratory disease while minimizing an adverse effect on phonation.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Asthma; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Phonation; Pressure; Time Factors; Voice Disorders; Young Adult

We aimed to evaluate the accuracy of baseline exhaled nitric oxide fraction (F(eNO)) to recognise individuals with difficult-to-treat asthma who have the potential to achieve control with a guideline-based stepwise strategy. 102 consecutive patients with suboptimal asthma control underwent stepwise increase in the treatment with maximal fluticasone/salmeterol combination dose for 1 month. Then, those who remained uncontrolled received oral corticosteroids for an additional month. With this approach, 53 patients (52%) gained control. Those who achieved control were more likely to have positive skin results (60.4% versus 34%; p = 0.01), positive bronchodilator test (57.1% versus 35.8%; p = 0.02) and peak expiratory flow variability > or =20% (71.1% versus 49.1%; p = 0.04). Conversely, depression was more frequent in those who remained uncontrolled (18.4 % versus 43.4 %; p = 0.01). An F(eNO) value > or =30 ppb demonstrated a sensitivity of 87.5% (95% CI 73.9-94.5%) and a specificity of 90.6% (95% CI 79.7-95.9%) for the identification of responsive asthmatics. The current results suggest that F(eNO) can identify patients with difficult-to-treat asthma and the potential to respond to high doses of inhaled corticosteroids or systemic steroids.

Topics: Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anxiety; Asthma; Breath Tests; Bronchodilator Agents; Depression; Drug Combinations; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Nitric Oxide; Peak Expiratory Flow Rate; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Spirometry

Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways.. To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function.. After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed.. Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters.. The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchi; Bronchioles; Chemistry, Pharmaceutical; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Pilot Projects; Respiratory Function Tests

This study investigates the impact of measuring adherence and providing feedback on medication usage by children with unstable asthma. Adherence was measured using an electronic monitoring device. Subjects were randomized to either being told of their adherence during review consultations or for their adherence to remain undisclosed to their parents and treating physician. Subjects were reviewed monthly for 4 months. Twenty-six children aged between 6 and 14 years were recruited. Adherence was significantly higher in the intervention group (79% versus 58%, p <.01). There were significant improvements in clinical measures of disease control compared with baseline in both groups. The change in forced expiratory volume in 1 s (FEV(1)) (% predicted) was greater in those subjects receiving feedback (13.8% versus 9.8%). However, lung function values were lower in the intervention group at baseline and the relative improvement failed to reach statistical significance. Measuring adherence and providing feedback increases the use of preventive medication. A larger study is required to explore implications for disease control.

Topics: Adolescent; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Feedback, Psychological; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Medication Adherence; Patient Education as Topic; Treatment Outcome

Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment. This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler with fixed-dose fluticasone propionate/salmeterol dry powder inhaler regimens on patient-reported outcomes in patients aged > or =18 years with moderate to severe asthma.. In this phase III, randomized, open-label study, 1225 patients were randomized 2:1 to fixed-dose budesonide/formoterol 160/4.5 microg x 2 inhalations (320/9 mug) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 microg twice daily for 1 month. In the subsequent 6 months, patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy, whereas those receiving fixed-dose budesonide/formoterol were randomized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol (adjustable from 320/9 microg twice daily to 320/9 microg once daily or 640/18 microg twice daily).. Mean improvements from baseline to end of treatment in the Asthma Quality of Life Questionnaire (standardized) overall and individual domain scores and the Asthma Control Questionnaire score were clinically important (> or =0.5 points) for all treatments. Patients in both budesonide/formoterol groups reported greater treatment satisfaction on the Asthma Treatment Satisfaction Measure questionnaire than patients in the fluticasone propionate/salmeterol dry powder inhaler group for the attributes of timely relief of symptoms (p < or = .037) and feel medication working (p < or = .020). Onset of Effect Questionnaire scores showed a greater percentage of patients perceiving onset of effect with budesonide/formoterol regimens versus fixed-dose fluticasone propionate/salmeterol (p < or = .002).. Treatment regimens did not differ regarding improvements in asthma-specific quality of life and asthma control. Questions related to perceived rate of onset and feeling medication working in the Asthma Treatment Satisfaction Measure and Onset of Effect Questionnaire generally elicited somewhat more favorable responses with budesonide/formoterol pressurized metered-dose inhaler regimens versus fixed-dose fluticasone propionate/salmeterol dry powder inhaler.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

Asthma guidelines recommend reducing inhaled corticosteroids (ICS) to the minimum effective dose, but the timing of long-acting beta(2)-agonist (LABA) withdrawal is unclear. Recent FDA guidelines recommend LABA withdrawal once asthma is well-controlled. This 13-month double-blind study of patients taking high-dose combination therapy investigated the effect of discontinuation of LABA before ICS down-titration.. Adults using salmeterol/fluticasone combination (SFC) 50/500 microg bd were randomized to SFC 50/500 microg bd or fluticasone propionate (FP) 500 microg bd, with subsequent ICS down-titration 8-weekly using a clinical algorithm. The primary outcome was mean daily FP dose, including ICS for exacerbations.. 82 subjects were randomized. Asthma was well-controlled at baseline, with mean FEV(1) 84.8% predicted and Asthma Control Questionnaire (ACQ) score 0.9. There was no significant difference in mean daily FP dose (SFC: 721 microg, FP:816 microg, p = 0.3), but final dose was lower with SFC (534 microg cf. 724 microg, p = 0.005). ICS dose was reduced by >or=80% in 41% SFC and 15% FP patients. Ambulatory lung function was significantly higher with SFC, but there were no differences between groups in rescue beta(2)-agonist use, clinic spirometry, airway responsiveness, ACQ, sputum eosinophils or FeNO. Baseline airway responsiveness, and pre-reduction blood eosinophils, were significant predictors of mean daily FP dose and dose reduction failure respectively.. Many patients prescribed high-dose combination therapy may be over-treated. Substantial reductions in dose can be achieved with a clinical algorithm, reaching lower FP doses with SFC than FP without losing asthma control or increasing disease activity.. This study was commenced before mandatory registration of clinical trials.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Practice Guidelines as Topic; Respiratory Function Tests; Young Adult

The hypothesis that regular treatment aimed at achieving and maintaining asthma control is accompanied by reduced airway hyper-responsiveness (AHR) was investigated.. Adult patients (PC(20) methacholine <8 mg/ml, FEV(1)% predicted >or=70%) received salmeterol/fluticasone propionate combination 50/250 microg bd (SFC250) for a 12-week run-in; those achieving well-controlled (WC) asthma were randomised to SFC250 (n = 88) or SFC50/500 microg bd (SFC500) (n = 90) for 24 weeks. AHR (PC(20) methacholine), asthma control, lung function, symptoms, exacerbations and safety were assessed.. During the 12 week run-in (SFC250), a greater than 1 doubling dose increase in PC(20) was observed. During randomised treatment, the increase in AHR was similar, and less than 1 doubling dose, for both groups (adjusted geometric mean PC(20) (mg/mL) at 24 weeks: SFC250: 2.796, SFC500: 2.802; p = 0.992). Compared with SFC250, patients receiving SFC500 had a more rapid improvement in AHR (adjusted mean ratio to baseline respectively at week 4: 1.193 vs. 1.386; week 12: 1.395 vs. 1.672; p = non-significant for both) and showed a greater response to treatment in patients with a low baseline PC(20). Patients maintaining WC asthma were 72 (84%) and 64 (74%) in the SFC250 and SFC500 groups respectively. Both doses of SFC were well tolerated; only four exacerbations were reported, all in the SFC500 group.. Regular treatment with SFC resulted in continuous improvement in AHR with maintenance of asthma control in the majority of patients. SFC500 showed a trend for a more rapid improvement in AHR and resulted in greater improvements in patients with a lower baseline PC(20).

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Respiratory Function Tests; Respiratory System; Treatment Outcome; Young Adult

Three fixed maintenance-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) combinations for the treatment of asthma are currently available: salmeterol/fluticasone propionate (Seretide/Advair/Adoair) budesonide/formoterol (Symbicort) and beclometasone/formoterol (Foster). All of these combinations have proven efficacy in terms of controlling symptoms, improving lung function and reducing the rate of exacerbations compared with ICSs and LABAs administered separately. Budesonide/formoterol is also approved for use as maintenance and reliever therapy in a number of countries (Symbicort SMART). Many of the studies supporting the use of budesonide/formoterol combination therapies have included populations of adolescents and adults aged >11 years.. This post hoc analysis compared the efficacy of ICS/LABA fixed maintenance-dose treatment with budesonide/formoterol and salmeterol/fluticasone propionate versus budesonide/formoterol maintenance and reliever therapy in patients with persistent asthma aged > or =16 years.. Following 2-weeks' run-in, 2866 adults aged > or =16 years were randomized to: fixed maintenance-dose budesonide/formoterol 640 microg/18 microg per day, salmeterol/fluticasone propionate 100 microg/500 microg per day plus terbutaline as needed, or budesonide/formoterol 320 microg/9 microg per day plus additional inhalations as needed (budesonide/formoterol maintenance and reliever therapy). Outcome measures included time to first severe asthma exacerbation (primary outcome) and number of severe asthma exacerbations.. Budesonide/formoterol maintenance and reliever therapy prolonged time to first severe exacerbation versus budesonide/formoterol and salmeterol/fluticasone propionate fixed maintenance dose (p = 0.037 and p = 0.0089, respectively). Compared with salmeterol/fluticasone propionate fixed maintenance-dose treatment, fixed maintenance-dose budesonide/formoterol reduced the risk of hospitalizations/emergency-room visits by 28% (relative rate [RR] 0.72; 95% CI 0.53, 0.98; p = 0.034) and budesonide/formoterol maintenance and reliever therapy by 37% (RR 0.63; 95% CI 0.46, 0.87; p = 0.0043). All treatments provided similar improvements in lung function, asthma control days and asthma-related quality of life.. Budesonide/formoterol fixed maintenance dose or maintenance and reliever therapy provides similar improvements in current asthma control and reduces the future risk of hospitalizations/emergency-room treatments versus salmeterol/fluticasone propionate fixed maintenance-dose treatment, providing additional clinical benefit to asthma patients aged > or =16 years.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Emergency Service, Hospital; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Hospitalization; Humans; Kaplan-Meier Estimate; Lung; Male; Middle Aged; Proportional Hazards Models; Quality of Life; Time Factors; Treatment Outcome; Young Adult

Asthma is a major health problem and has significant mortality around the world. Although the symptoms can be controlled by drug treatment in most patients, effective low-risk, non-drug strategies could constitute a significant advance in asthma management. An increasing number of patients with asthma are attracted by acupuncture and moxibustion. Therefore, it is of importance that scientific evidence about the efficacy of this type of therapy is regarded. Our past researches suggested heat-sensitive moxibustion might be effective in treatment of asthma. Our objective is to investigate the effectiveness of heat-sensitive moxibustion compared with conventional drug treatment.. This study is comprised of a multi-centre (12 centers in China), randomized, controlled trial with two parallel arms (A: heat-sensitive moxibustion; B: conventional drug). Group A selects heat- sensitive acupoints from the rectangle region which consist of two outer lateral lines of dorsal Bladder Meridian of Foot-Taiyang, and two horizontal lines of BL13(Fei Shu) and BL17 (Ge Shu);6 inch outer the first and second rib gap of anterior chest. Group B treats with fluticasone/salmeterol (seretide). The outcome measures will be assessed over a 3-month period before each clinic visit at days 15, 30, 60, and 90. Follow-up visit will be at 3, 6 months after the last treatment session. Adverse event information will be collected at each clinic visit.. This trial will utilize high quality trial methodologies in accordance with CONSORT guidelines. It may provide evidence for the effectiveness of heat-sensitive moxibustion as a treatment for chronic moderate persistent asthma. Moreover, the result may propose a new type moxibustion to control asthma.. The trial is registered at Chinese Clinical Trials Registry: ChiCTR-TRC-09000599.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Chronic Disease; Clinical Protocols; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Middle Aged; Moxibustion; Research Design; Sample Size

To probe a better therapy for chronic persistent asthma.. Thirty-six cases of chronic persistent asthma were randomly divided into a beat-sensitive moxibustion group (17 cases) and a western medication group (19 cases). In heat-sensitive moxibustion group, the sensitization points between Feishu (BL 13) and Geshu (BL 17) were selected with heat-sensitive moxibustion; in western medication group, Seretide inhalant was applied. The patients of both groups were continuously treated for 3 months and the therapeutic effects were evaluated by clinical symptom scores and pulmonary ventilation function test.. After treatment, the effective rate of 88.2% (15/17) in heat-sensitive moxibustion group was superior to that of 47.4% (9/19) in western medication group (P < 0.05); the clinical symptom scores and pulmonary ventilation function were obviously improved in the two groups, and the heat-sensitive moxibustion group was superior to the western medication group (all P < 0.05).. For chronic persistent bronchial asthma, heat-sensitive moxibustion can improve the clinical symptoms and the pulmonary ventilation function, and it is better than Seretide inhalant.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Chronic Disease; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Male; Middle Aged; Moxibustion; Pulmonary Ventilation; Treatment Outcome; Young Adult

Some asthma patients remain poorly controlled despite receiving care consistent with treatment guidelines.. This study compared the ability to sleep, work, and participate in leisure activities among subjects with immunoglobulin E-mediated (allergic) asthma initiating omalizumab (omalizumab start group) with subjects receiving moderate-to-high doses of salmeterol/fluticasone combination therapy, who continued on salmeterol/fluticasone combination therapy for at least a year without adding omalizumab (salmeterol/fluticasone combination continuation group).. Subjects completed an Internet-based screener and, if eligible, an Internet-based questionnaire. A propensity score model was utilized in the analysis. Group differences were assessed through logistic and linear regression models. Analyses were adjusted for propensity score quintile, how subjects heard about the study, and responses to retrospective single-item questions.. The analysis population included 86 omalizumab start group subjects and 436 salmeterol/fluticasone combination continuation subjects, recruited from June to November 2006. In the adjusted analyses, the omalizumab start group was more than twice as likely to have controlled asthma as measured by the Asthma Control Test (odds ratio, 2.62; p = 0.005). The omalizumab start group had significantly fewer sleep disturbances as measured by the Jenkins Sleep Evaluation Questionnaire (least-square means difference, -1.65;p = 0.004), less activity impairment as measured by the Work Productivity Activity Impairment-Asthma Scale (least-square means difference, -13.36;p < 0.001), and less difficulty in activities as measured by the Valued Life Activities Questionnaire (least-square means difference, -0.24; p < 0.001).. Asthma subjects who started taking omalizumab reported more improvement in asthma control, fewer sleep problems, less activity impairment, and less difficulty with activities than a similar cohort of subjects who continued taking salmeterol/fluticasone combination therapy.

Topics: Activities of Daily Living; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Drug Combinations; Efficiency; Female; Fluticasone-Salmeterol Drug Combination; Humans; Internet; Leisure Activities; Male; Middle Aged; Omalizumab; Patient Satisfaction; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome

Current asthma guidelines emphasize domains of impairment and risk for assessing severity and control, noting the need to consider separately the effects of asthma on asthma quality of life and functional capacity. Proper treatment to control asthma should result in improvements in patient well-being and functional status.. To assess asthma-related quality of life after treatment with combination fluticasone propionate and salmeterol delivered via hydrofluoroalkane 134a metered-dose inhaler compared with the individual components alone.. Asthma-related quality of life was assessed as part of two 12-week, randomized, double-blind, placebo-controlled clinical trials comparing the fluticasone propionate-salmeterol combination administered via a single metered-dose inhaler with salmeterol, fluticasone propionate, and placebo administered via traditional chlorofluorocarbon metered-dose inhaler. The Asthma Quality of Life Questionnaire was completed at baseline and end point. Score changes, overall and for the 4 separate domains, were compared within and among the treatment groups.. A total of 720 of 725 patients completed a baseline Asthma Quality of Life Questionnaire and were included in the analyses. In both studies, all mean scores improved significantly from baseline with the fluticasone propionate-salmeterol combination, with significantly greater improvement in the overall score compared with salmeterol alone, fluticasone propionate alone, and placebo groups. Improvements with the combination were also clinically meaningful compared with changes with salmeterol and placebo in both studies and with fluticasone propionate in study 1.. Treatment with combination fluticasone propionate and salmeterol delivered via hydrofluoroalkane metered-dose inhaler resulted in significantly greater improvements in asthma-related quality of life compared with individual components and placebo administered via traditional chlorofluorocarbon metered-dose inhaler.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires; Treatment Outcome; United States

Salmeterol and fluticasone propionate combination (SFC) provides better asthma control than fluticasone propionate (FP) alone, however, little is known on the effects of differential treatments on airway function and inflammation in patients with mild asthma.. We randomized 27 mild persistent asthma patients treated with the equivalent of 400 microg beclomethasone dipropionate to receive SFC (50/100 microg , 13 patients) or FP (100 microg , 14 patients) twice daily for 8 weeks. We compared the effects of SFC and FP on pulmonary function assessed by spirometry and impulse oscillometry (IOS), eosinophil percentage of induced sputum and serum, and with asthma symptoms and control after each treatment.. We observed that SFC significantly improved forced expiratory volume in one second (p < 0.05), IOS measurements of total resistance R5 (p < 0.01), central resistance R20 (p < 0.05), and distal reactance X5 (p < 0.01) compared with FP. The percentage of eosinophils in sputum, but not in serum, decreased significantly more in the SFC group than in the FP group (p < 0.05). There was also a significant improvement in symptom control in the SFC group (p < 0.05).. These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

Topics: Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Drug Combinations; Eosinophils; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Leukocyte Count; Male; Middle Aged; Oscillometry; Spirometry; Sputum; Treatment Outcome

Uncontrolled asthma is characterized by variability. Current asthma guidelines recommend focussing on the achievement and maintenance of control but few studies have examined in detail, using composite measures of control, the stability and potential duration of control once achieved. In this post-hoc analysis of the results of the Gaining Optimal Asthma controL (GOAL) study, we examine the association between the level of asthma control achieved during the step-up phase of the study and the stability of control experienced during the maintenance phase.. GOAL was a 1-year, randomized, stratified, double-blind study of 3421 patients with uncontrolled asthma, which compared salmeterol/fluticasone propionate combination with fluticasone propionate in achieving two composite, guideline-based measures of control: totally controlled and well-controlled asthma. We analysed the proportion and duration of time spent in control, the effect of treatment on asthma stability, and the impact of asthma control stability on unscheduled use of healthcare resources.. In patients achieving well-controlled or totally controlled asthma, at least well-controlled asthma was maintained for a median of almost 3 and 6 months, and for more than 85% and 95% of weeks of follow-up, respectively. A high level of stability was confirmed in a Markov analysis investigating transitional probability of change in control status. Variability in control was associated with increased probability of an unscheduled healthcare resource use (odds ratio: 1.06, P < 0.001).. Most patients achieving guideline-defined control can maintain at least a similar level of control with regular, stable dosing, with little likelihood of losing control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Logistic Models; Markov Chains; Middle Aged; Odds Ratio; Time Factors

In patients controlled with SFC250 Diskus bd, this double-blind, randomised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd. Six hundred and three patients previously using 1,000 microg BDP (or equivalent) daily +LABA and controlled according to investigator's judgement were recruited. Patients received SFC250 bd during an 8-week open run-in period. Four hundred and seventy six patients (mean age=43 years, mean FEV(1)=2.9+/-1.0) who fulfilled the randomisation criterion ('Well-controlled' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period) entered a 24-week treatment period. The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250. The main criterion was the change from baseline in morning PEF over weeks 1-12 in the per-protocol population. The non-inferiority limit was -15 L/min. At inclusion, the three treatment groups were well balanced. Mean morning PEF was 476, 470 and 465 L/min in the SFC250, SFC100 and FP250 groups, respectively. The adjusted mean change in morning PEF over weeks 1-12 was +1.76+/-2.43 L/min for SFC250, -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250. SFC100 was at least as effective as SFC250 (treatment difference -4.83 [-12.39; 2.72], p=0.151) whereas FP250 was not (treatment difference -18.27 [-26.05; -10.49], p<0.001). Similar results were observed over weeks 13-24 in morning PEF (SFC100-SFC250=-4.54+/-3.84, p=0.238; FP250-SFC250=-20.11+/-3.92, p<0.0001). Secondary endpoints showed a similar pattern. Over weeks 1-12, SFC250 was significantly more effective than FP250 on evening PEF, daily symptoms and bronchodilator use. There was no difference between SFC100 and SFC250. The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups, and 0.21 in FP 250 group (ns, Poisson analysis). All treatments were well tolerated.. In patients achieving asthma control with SFC250, stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250, whereas FP250 was not.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Treatment Outcome; Young Adult

In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or "step down" to either fluticasone propionate (FP) 100 mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, "stepping down" to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS.

Topics: Acetates; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Flow Rates; Humans; Kaplan-Meier Estimate; Male; Patient Satisfaction; Peak Expiratory Flow Rate; Quinolines; Salmeterol Xinafoate; Sulfides; Surveys and Questionnaires

The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI.. We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI.. This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2).. There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated.. Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests

The present study examined the association between guideline-derived asthma control and health-related quality of life, assessed using the Asthma Quality of Life Questionnaire (AQLQ), in patients with uncontrolled asthma whose treatment was directed towards achieving the highest possible level of control. The present randomised, double-blind, parallel-group study compared the efficacy of fluticasone propionate (FP) and salmeterol/fluticasone propionate combination (SFC) in achieving two composite, guideline-derived measures of control: total control (TC) and well-controlled (WC) asthma. Not achieving these levels was classed as not well-controlled (NWC). Doses were augmented until patients achieved TC or reached the maximum dose. This dose was maintained for the remainder of the study. AQLQ was assessed at baseline and at each clinic visit. AQLQ scores improved throughout the study, reaching near-maximal levels in patients achieving TC and WC, and 52-week mean scores in the three control groups were statistically significantly different. Clinically meaningful improvements (mean change from baseline) were: TC group (SFC 1.9, FP 1.8), WC (SFC 1.5, FP 1.5) and NWC (SFC 1.0, FP 0.9). In conclusion, the treatment aimed at controlling asthma improves the health-related quality of life to levels approaching normal. The difference in Asthma Quality of Life Questionnaire scores between total control and well-controlled confirms that patients distinguish even between these high levels of control.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Health Status; Humans; Male; Metered Dose Inhalers; Middle Aged; Quality of Life; Treatment Outcome

This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.. Adult patients with mild persistent asthma (> or = 80% predicted FEV1) receiving 200-500 mug of BDP or equivalent were randomised to receive either FP 100 mug or SFC 50/100 mug twice daily from a Diskus inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.. A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 - 0.89, p < 0.001) at week 2 and 0.81 (0.71 - 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV1 was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 - 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 - 0.34, p = 0.060).. SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV1 values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry. NCT00370591.

Topics: Adult; Albuterol; Androstadienes; Asthma; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Respiratory Function Tests; Respiratory Physiological Phenomena

To identify the asthma patients, on short-acting beta2-agonists alone, who would benefit from initial maintenance therapy (IMT) with salmeterol/fluticasone (SFC) propionate 50/100 microg bd compared with fluticasone propionate (FP) 100 microg bd alone. The results of an integrated analysis of data from four previous trials are presented.. The four original trials were randomised, double-blind, parallel group studies and included patients who had received IMT with SFC 50/100 microg bd or FP 100 microg bd. Patients were >or=12 years with a 6 month history of asthma and >or=15% reversibility in FEV1. Patients had either not received inhaled corticosteroids in the preceding month or were steroid naïve. Patients were assessed to determine whether any GINA-defined asthma characteristics or combination of asthma characteristics could predict those individuals who would achieve well controlled asthma status with IMT with SFC rather than with inhaled steroid alone. Patients with persistent asthma were assessed based on GINA-defined baseline asthma characteristics and well controlled asthma status in response to each treatment was investigated according to combinations of these baseline features. Subsequently, a further range of endpoints, including asthma symptoms, rescue medication use and asthma control, were analysed over weeks 1-12 for the combinations of features where the treatment difference in well controlled asthma status was greatest.. The results of the initial analyses demonstrated that patients exhibiting two or three features of uncontrolled asthma at baseline were more likely to achieve well controlled asthma when treated with SFC than with FP alone, the most significant difference being observed in patients with three baseline features (odds ratio 2.60, 95% CI: 1.87, 3.62, p<0.001). Patients with one baseline feature showed no difference between the FP and SFC groups. Further analyses on data from patients with two or three baseline asthma features, showed that treatment with SFC resulted in significantly greater improvements in mean morning PEF, percentage symptom-free days, nights with no awakenings and rescue-free days compared with FP. In addition, asthma control was achieved earlier in patients in the SFC group. SFC and FP were well tolerated as shown previously in the four individual trials.. Patients on short-acting beta2-agonists alone with two or three features of uncontrolled asthma (moderate to severe airflow limitation/daily symptoms/daily rescue medication use) are most likely to achieve better control, earlier, with SFC 50/100 microg bd initial maintenance treatment compared with FP 100 microg bd alone.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Patient Selection; Peak Expiratory Flow Rate

Many patients with asthma require an inhaled long-acting beta(2)-agonist (LABA) in addition to an inhaled corticosteroid to adequately control their disease.. The purpose of this study was to assess the long-term tolerability of a salmeterol xinafoate/ fluticasone propionate (SFC) hydrofluoroalkane metered-dose inhaler (MDI) at 3 different doses BID.. This 52-week, open-label, stratified, parallel-group study assessed SFC in patients with persistent asthma. Patients, aged > or = 12 years, with a diagnosis of asthma for > or = 6 months, and a percent predicted forced expiratory volume in 1 second (FEV(1)) or peak expiratory flow (PEF) between 40% and 90% were enrolled between January 1999 and June 1999. The last patient completed the 12-month study in June 2000. Patients were allowed to continue their current asthma treatment during run-in, with the exception that short-acting beta(2)-agonists (SABAs), LABAs, and oral bronchodilators were not to be used 6, 12, and 24 hours, respectively, prior to the randomization visit. During the open-label randomized treatment period, patients were instructed to discontinue all other asthma medications with the exception of the albuterol MDI to use on an as-needed basis. Patients were assigned to treatment based on their existing asthma regimen: SABA monotherapy or LABA with or without fluticasone propionate (FP) <250 microg/d or equivalent (group 1); FP 250 to 500 microg/d or equivalent with or without LABA (group 2); and FP >500 to 1000 microg/d or equivalent with or without LABA (group 3). Patients administered 2 inhalations BID of SFC hydrofluoroalkane at doses of 25/50 microg/actuation (group 1), 25/125 microg/actuation (group 2), or 25/250 pg/actuation (group 3). The primary end point was tolerability as assessed by adverse events (AEs). AEs were determined via diary cards and investigator inquiry at visits. Serious AEs were defined as death, any life-threatening event, hospitalization, disability, congenital anomaly in the patient's offspring, or other important medical events judged by the investigator to be serious. Other outcomes included clinical laboratory tests (hematology, chemistry, electrolytes), 24-hour urinary-free cortisol excretion, 12-lead electrocardiograms, oropharyngeal examinations, vital signs, clinic visit lung function tests (FEV(1) and PEF), daily diary card entries of morning PEF, and rescue medication usage.. Of the 372 patients assessed for eligibility, 325 from 22 centers across Canada were enrolled and randomized to treatment. Group 1 consisted of 98 patients (55% women; 86% white; mean age, 37 years; mean [SD] weight, 79 [20] kg). Group 2 consisted of 109 patients (46% women; 94% white; mean age, 44 years; mean [SD] weight, 80 [17] kg). Group 3 consisted of 118 patients (47% women; 90% white; mean age, 45 years; mean [SD] weight, 80 [18] kg). A total of 15 adolescents (aged 12-17 years) comprised 11%, 2%, and 2% of groups 1, 2, and 3, respectively. Treatments were well tolerated, and 274 (84%) of the 325 patients enrolled completed the study. Upper respiratory tract infection was the most common AE reported: 52%, 37%, and 49% of patients in groups 1, 2, and 3, respectively. Twenty (6%) patients withdrew because of an AE, with worsening asthma being the most frequent reason (n = 9). None of the serious AEs (11 [3 %]) were considered drug related by the investigators. Improvements in FEV(1) and PEF and re- duction in symptomatic albuterol use occurred during the first 4 weeks and were maintained in all groups throughout the 52-week study.. BID doses of SFC hydrofluoroalkane 50/100 pg, 50/250 pg, and 50/500 pg administered via MDI for 52 weeks were well tolerated in this population of adolescents and adults with persistent asthma.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Alkanes; Androstadienes; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Drug Combinations; Electrocardiography; Female; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocortisone; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests

Few studies have compared treatment strategies in patients with asthma poorly controlled on low dose inhaled corticosteroids, and little is known about the effects of different treatments on airway inflammation. In this double-blind, placebo-controlled, parallel group study, we compared the effects of salmeterol plus fluticasone propionate (FP) (Seretide; SFC) and FP plus montelukast (FP/M) on sputum inflammatory markers, airway responsiveness, lung function, and symptoms in adult asthmatics.. Sixty-six subjects were randomised to SFC or FP/M for 12 weeks. The primary outcome was changes in neutrophil, eosinophil, macrophage, lymphocyte, and epithelial cell levels in induced sputum. Additional outcomes included the change in other sputum markers of airway inflammation, airway responsiveness, symptom control, and lung function.. Both treatments had no significant effect on induced sputum inflammatory cells, although there was a trend for a reduction in sputum eosinophils. Both treatments significantly improved airway responsiveness, whereas SFC generally led to greater improvements in symptom control and lung function than FP/M. FP/M led to significantly greater reductions in sputum cysteinyl leukotrienes than SFC (treatment ratio 1.80; 95% CI 1.09, 2.94).. Both treatments led to similar control of eosinophilic airway inflammation, although PEF and symptom control were better with SFC. STUDY NUMBER: SAM40030 (SOLTA).

Topics: Acetates; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Cyclopropanes; Cysteine; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Histamine; Humans; Interleukin-8; Leukotriene Antagonists; Leukotrienes; Lung; Male; Quinolines; Spirometry; Sputum; Sulfides; Time Factors; Treatment Outcome; United Kingdom

The effect of ethnicity on the efficacy of salmeterol (S)+fluticasone propionate (FP) has not been examined in Japanese and Caucasian asthmatics. In this study, the efficacy of combination treatment with S and FP from a single inhaler (SFC) was compared with concurrent treatment with S and FP administration from separate inhalers (S+FP) in Japanese and Caucasian asthmatics.. This was a randomised, double-blind, crossover study in male and female Japanese (n=18) and Caucasian (n=17) asthmatics (50-100% predicted FEV(1); >35% reversibility in sGaw). Subjects received SFC (S 50 mcg/FP 250 mcg b.i.d.) and S+FP (S 50 mcg b.i.d.+FP 250 mcg b.i.d.) for 14 days. sGaw and FEV(1) were determined 0-12h after the first and last doses.. Treatment with both SFC and S+FP produced marked bronchodilation, which was maintained 0-12h after the first dose. Baseline sGaw and FEV(1) increased up to 51% and 180 mL, respectively, in Japanese subjects over 2 weeks of treatment, with similar improvements in Caucasian subjects. On Day 14 the 0-12h S+FP:SFC treatment ratios (90% CI) for sGaw AUC and peak were 1.05 (0.98, 1.12) and 1.05 (0.97, 1.14), respectively, in Japanese subjects, and 0.99 (0.92, 1.07) and 0.98 (0.89, 1.07), respectively, in Caucasian subjects, with no difference between the two ethnic groups.. The finding of a similar significant bronchodilator response in Japanese and Caucasian asthmatics following concurrent and combination treatment with salmeterol and FP suggests that the therapeutic response to these agents is comparable and independent of ethnicity in Japanese and Caucasian asthma patients.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Airway Resistance; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asian People; Asthma; Body Height; Cross-Over Studies; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Japan; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests; Salmeterol Xinafoate; Sweden; Treatment Outcome; White People

Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide) plus a short-acting beta(2)-agonist (SABA).. Patients (N=2309) with symptomatic asthma (aged 12 years; forced expiratory volume in 1s 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 microg twice daily plus terbutaline as needed, for 6 months.. Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 microg/day budesonide [1238 microg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 microg/day fluticasone [2000 microg/day BDP equivalent] with salmeterol/fluticasone therapy; P<0.0001). Both treatments were well tolerated.. In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Azides; Budesonide; Child; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Hospitalization; Humans; Lung; Male; Middle Aged; Proportional Hazards Models; Respiratory Function Tests; Serotonin; Treatment Outcome

Asthma is a common chronic disorder of childhood, and it is frequently accompanied by dental and other oral abnormalities. As such, oral and dental effects of asthma medications have been investigated in several studies. However, the effect of combination therapy with a long-acting beta(2)-agonist and a corticosteroid on oral health in children and adolescents has not been reported in the literature.. The aim of this study was to examine whether combination treatment with a long-acting beta(2)-agonist (salmeterol) and a corticosteroid (fluticasone propionate) administered by dry powder inhaler (DPI) affects oral health in children and adolescents with moderate asthma.. This 1-month, single-blind clinical study was conducted at the Department of Periodontology, Ondokuz Mayis University Faculty of Dentistry, Samsun, Turkey. Male and female children and adolescents aged 7 to 17 years with moderate persistent asthma, as classified by the Global Initiative for Asthma guidelines, were studied before and after 1 month of treatment with combination salmeterol 50 microg and fluticasone propionate 100 mug administered by DPI BID. Salivary flow rate and secretory immunoglobulin A (sIgA) level were measured, and periodontal health was assessed by gingival and dental plaque indices for buccal surfaces and periodontal pocket depth.. The study enrolled 15 children and adolescents (8 girls, 7 boys; mean [SD] age, 11 years [45 months]; median age, 13 years; [range, 7-17 years]). At 1 month, mean sIgA, gingival index, buccal surface index, gingival index, dental plaque index, and periodontal pocket depth were not changed significantly from baseline, whereas mean (SD) salivary flow rate was significantly decreased (from 153.21 [39.29] to 113.16 [46.99] microL/5 s; P = 0.015) and dental plaque index on the buccal surface was significantly increased (from 1.43 [0.63] to 1.61 [0.67]; P = 0.01).. In this small study, combination treatment with salmeterol 50 microg and fluticasone propionate 100 microg inhaled twice daily was associated with changes in oral health among these children and adolescents with moderate asthma. Regular follow-up of oral health status may be warranted in children and adolescents during long-term use of a long-acting beta2-agonist and a corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Child; Delayed-Action Preparations; Dental Plaque; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Immunoglobulin A, Secretory; Male; Nebulizers and Vaporizers; Oral Health; Periodontal Index; Powders; Saliva; Single-Blind Method

Asthma control is the goal of treatment, but little data exist to support treatment strategies for stepping down treatment once control has been achieved.. We assessed whether either the long-acting beta2-agonist or corticosteroid could be reduced without loss of asthma control once control had been attained with fluticasone propionate/salmeterol (FSC).. After 12 weeks of open-label treatment with FSC 250/50 microg twice daily, patients whose asthma was well controlled were randomized to FSC 100/50 microg twice daily or fluticasone propionate (FP) 250 microg twice daily. for 12 weeks. The primary endpoint was mean morning peak expiratory flow over the randomized study period. Secondary endpoints included symptom scores, rescue albuterol use, and asthma control.. During open-label treatment, improvements from baseline were seen, and 435 of 641 patients (68%) achieved well controlled status during each of the last 4 weeks of this period. A total of 246 patients received FSC 100/50 microg twice daily and 238 FP 250 microg twice daily. The adjusted mean change in morning peak expiratory flow from the end of open-label treatment was -0.3 L/min for FSC and -13.2 L/min for FP (treatment difference, 12.9 L/min; 95% CI, 8.1-17.6; P<.001). Secondary efficacy endpoints also showed FSC 100/50 microg twice daily to be more effective than FP 250 microg twice daily alone. The majority of patients remained well controlled, but the proportion was higher with FSC.. In patients achieving asthma control with FSC 250/50 microg twice daily, stepping treatment down to a lower dose of FSC 100/50 microg twice daily is more effective than switching to an inhaled corticosteroid alone.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

The dose emitted from dry powder inhalers may be inhalation flow-dependent. Using an ex vivo method, the Electronic Lung, we have measured the aerodynamic characteristics of the emitted dose for both active constituents from Seretide Diskus (salmeterol xinafoate 50 mcg; fluticasone propionate 500 mcg) and Symbicort Turbuhaler (formoterol 6 mcg; budesonide 200 mcg). Electronic inhalation profiles were collected from 20 severe asthmatics (mean PEFR 53% predicted) when they inhaled using a placebo Seretide Diskus and a placebo Symbicort Turbuhaler. These were replayed in the Electronic Lung with the respective active inhaler in situ. Mean(S.D.) peak inhalation flow rates (PIFR) through the Diskus and Turbuhaler were 94.7(32.9) and 76.8(26.2) l min(-1), respectively. From the Electronic Lung the Diskus inhalation profiles provided a mean(S.D.) fine particle dose (FPD) for fluticasone propionate and salmeterol of 20.4(4.8) and 18.4(4.4)% labelled dose. For Turbuhaler inhalation profiles the FPD was 23.1(12.9) and 20.7(11.1)% labelled dose for budesonide and formoterol, respectively. The linear (p < 0.001) relationships between FPD against PIFR for budesonide and formoterol were 3 (p = 0.002) and 2.8 (p = 0.007) times steeper than fluticasone propionate and salmeterol, respectively. The results highlight a more significant effect of inspiratory flow on variable dosage emission when using the Symbicort Turbuhaler compared with the Seretide Diskus.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Severity of Illness Index

The Gaining Optimal Asthma ControL (GOAL) study has shown the superiority of a combination of salmeterol/fluticasone propionate (SFC) compared with fluticasone propionate alone (FP) in terms of improving guideline defined asthma control.. Clinical and economic data were taken from the GOAL study, supplemented with data on health related quality of life, in order to estimate the cost per quality adjusted life year (QALY) results for each of three strata (previously corticosteroid-free, low- and moderate-dose corticosteroid users). A series of statistical models of trial outcomes was used to construct cost effectiveness estimates across the strata of the multinational GOAL study including adjustment to the UK experience. Uncertainty was handled using the non-parametric bootstrap. Cost-effectiveness was compared with other treatments for chronic conditions.. Salmeterol/fluticasone propionate improved the proportion of patients achieving totally and well-controlled weeks resulting in a similar QALY gain across the three strata of GOAL. Additional costs of treatment were greatest in stratum 1 and least in stratum 3, with some of the costs offset by reduced health care resource use. Cost-effectiveness by stratum was 7600 pound (95% CI: 4800-10,700 pound) per QALY gained for stratum 3; 11,000 pound (8600-14,600 pound) per QALY gained for stratum 2; and 13,700 pound (11,000-18,300 pound) per QALY gained for stratum 1.. The GOAL study previously demonstrated the improvement in total control associated with the use of SFC compared with FP alone. This study suggests that this improvement in control is associated with cost-per-QALY figures that compare favourably with other uses of scarce health care resources.

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Models, Statistical; Outcome Assessment, Health Care; Quality of Life; Quality-Adjusted Life Years; Time Factors; Treatment Outcome; United Kingdom

This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids.. The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group.. The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated.. Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Severity of Illness Index; Treatment Outcome

Budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy (SMART) is an effective and well tolerated treatment option for patients with asthma. We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate (Seretide) plus salbutamol (albuterol) as needed (Seretide) Fixed Combination [SFC]).. A cost-effectiveness analysis was performed based on effectiveness and resource-utilisation data collected prospectively in a randomised, 12-month study performed in 2143 patients in 16 countries. Resource utilisation data were pooled and unit costs (euro, year 2003 values) from Italy, France, the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided.. Adolescents and adults with asthma (n = 2143; mean forced expiratory volume in 1 second [FEV(1)] 73% predicted; mean inhaled corticosteroid [ICS] dose 884 microg/day) were randomised to SMART or SFC. The effectiveness measure used was the number of severe exacerbations per patient per year. Direct costs included medication use (budesonide/formoterol 160microg/4.5microg or salmeterol/fluticasone 50microg/100microg, 50microg/250microg or 50microg/500microg plus salbutamol) and nonmedication-related resource use, including days in hospital, emergency room visits, specialist or primary care physician visits and other healthcare provider contacts. Indirect costs, including the number of days when the patient or their carer was unable to attend to their normal daily activities, were also assessed. The study assumed a European societal perspective (i.e. including direct and indirect costs).. Treatment with SMART resulted in significantly fewer severe exacerbations per patient per year compared with SFC (0.24 vs 0.31 events per patient per year; p = 0.0025). Resource use was low in both groups. Medication costs accounted for the majority of the total costs. The increased effectiveness of SMART was achieved at a reduced or similar cost compared with SFC. SMART dominated when German unit costs were applied (i.e. there was a statistically significant reduction in both costs and number of exacerbations). In all other countries, the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided; however, this difference was not statistically significant.. This analysis demonstrates that, compared with SFC, SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy, Germany, France and the UK. SMART provided a reduction in the number of severe exacerbations per patient per year, at no statistically significant increase in cost - or even at a lower cost - compared with SFC plus as-needed reliever salbutamol.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Cost of Illness; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Economics, Pharmaceutical; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged

The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available.. The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose.. Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment.. In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively. Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Receptors, Adrenergic, beta-2

The choice of treatment can have a major impact on the total costs associated with asthma care.. To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus, 100/50 microg, with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone.. Data from a randomized, double-blind, double-dummy, 12-week clinical trial were analyzed. Efficacy end points included (1) symptom-free days (SFDs) during the 12-week period and (2) a 12% or greater increase in forced expiratory volume in 1 second (FEV1) from baseline. The economic analysis was performed from a payer's perspective, and hence only direct costs were included in the analysis. The incremental cost-effectiveness ratio (ICER), which is the mean difference in average costs divided by the mean difference in average effectiveness, was calculated for both effectiveness outcomes (SFDs and FEV1).. For the SFDs end point, the ICER for fluticasone propionate-salmeterol vs montelukast was $2.87 (95% confidence interval, -$1.08 to $6.65), indicating that it costs, on average, an extra $2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast. With regard to FEV1, the ICER was $1.79 (95% confidence interval, -$0.72 to $3.86), indicating that it costs, on average, an extra $1.79 per day to achieve a lung function improvement of 12% or greater from baseline with fluticasone propionate-salmeterol than with montelukast. At a widely acceptable ceiling ratio of $9.95 per day, the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8% for SFDs and was almost 100% for an FEV1 improvement of 12% of greater.. Treating 2 main components of asthma, inflammation and smooth muscle dysfunction, using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone, such as montelukast, as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only.

Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Cyclopropanes; Double-Blind Method; Drug Combinations; Drug Costs; Female; Fluticasone-Salmeterol Drug Combination; Humans; Leukotriene Antagonists; Male; Middle Aged; Prospective Studies; Quinolines; Respiratory Function Tests; Sulfides

There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness.. To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids.. Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment.. Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005).. In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.

Topics: Adenosine Monophosphate; Adolescent; Adult; Aged; Airway Resistance; Albuterol; Androstadienes; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Seasons; Sulfonamides; Treatment Outcome

Inhalers containing corticosteroids and long-acting beta2-agonists are becoming increasingly important in asthma management. A rapid effect is important to patients, particularly during exacerbations. We compared the onset of bronchodilation and patient-perceived relief from dyspnoea following single-inhaler budesonide/formoterol or salmeterol/fluticasone in a model of acute bronchoconstriction. A randomised, double-blind, double-dummy, single-dose, crossover study included 27 outpatients with asthma (mean age 35 years; mean FEV1 90% predicted normal). Immediately following methacholine-induced bronchoconstriction (fall in FEV1 > or = 30%), patients inhaled budesonide/formoterol (160/4.5 microg, 1 or 2 inhalations; Symbicort Turbuhaler), salmeterol/fluticasone (50/250 microg; Seretide Diskus) or placebo on 4 study days. Lung function and Borg score were assessed for 30 min. During methacholine-induced provocation (final mean FEV1 62.5% of baseline), mean Borg score increased 10-fold (from 0.3 to 3.0 units). Hereafter, mean FEV1 at 3 min improved significantly more after budesonide/formoterol 1 and 2 inhalations (37 and 38%, respectively) than after salmeterol/fluticasone (23%; P < 0.001) or placebo (10%; P < 0.001). Median recovery times to 85% of baseline FEV1 were shorter for budesonide/formoterol (1 or 2 inhalations: 3.3 and 2.8 min, respectively) than salmeterol/fluticasone (8.9 min; P < 0.001) and placebo (> 30 min). One min after budesonide/formoterol, dyspnoea was significantly reduced (Borg score -0.86 units, both doses) compared with salmeterol/fluticasone (-0.55 units; P < 0.05) and placebo (-0.23 units; P < 0.001). Budesonide/formoterol provides immediate bronchodilation, faster than salmeterol/fluticasone, which patients can feel during acute methacholine-induced bronchoconstriction.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Nebulizers and Vaporizers

To determine whether initiation of maintenance treatment with the salmeterol (S)/fluticasone propionate (FP) combination (Seretide/Viani/Advair) is more effective than inhaled steroid alone in patients with asthma symptomatic on short-acting bronchodilator alone.. 150 asthma patients with symptoms and prn use of short-acting bronchodilator at least once a week were randomised to 24 weeks' treatment with either S/FP 50/100 microg bd (n = 78) or FP 100 microg bd (n = 72). The primary endpoint was the percentage of symptom-free 'day + night's.. The percentage of symptom-free 'day + night's increased significantly more for S/FP (20 to 64%) compared to FP (24 to 51%). The treatment difference was 15.3%, P = 0.008. In the sub-group of patients with mild asthma the treatment difference was also statistically significant in favour of S/FP (P = 0.0245, n = 74). S/FP was also significantly superior to FP alone for: lung function, salbutamol use prn, day symptom score, symptom-free days, and episode-free 'day + night's. Treatments were equally well tolerated.. Initial maintenance treatment with S/FP is significantly more effective than with inhaled steroid alone for patients symptomatic when treated with short-acting bronchodilator alone. This also apply to patients with mild persistent asthma.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Steroids; Treatment Outcome

The objective of an asthma treatment is to control asthma, particularly to prevent exacerbations.. To study the efficacy, acceptability and safety of the fluticasone/salmeterol (FP/S) combination in preventing asthma exacerbations in comparison with the continuation of previous treatment (TA).. This was a multicentre, randomised, parallel-group study to compare the fixed combination FP/S to TA (treatment with a free combination of an inhaled corticosteroid and a long-acting beta2-agonist) over one year in patients whose asthma was well controlled with their current treatment.. Five hundred and twenty patients were randomized and their data analyzed on an intent-to-treat basis. Seventy-four percent of the patients in the FP/S group and 71% in the TA group had no exacerbation. The 3.12% difference in favor of the FP/S group (90% CI: -3.32% to 9.56%) demonstrated that FP/S was at least as effective TA in preventing asthma exacerbations. Treatment acceptability, evaluated by the patient on visual analog scales (inclusion as part of the daily habits, constraint, simplicity) was better with FP/S (p<0.001) than with TA. Clinical safety was good and comparable in the two groups.. The fixed fluticasone/salmeterol combination provided a protection as good as that obtained with free combinations over a one-year treatment period, with a significant improvement in treatment acceptability and a good clinical safety.

Topics: Adult; Albuterol; Androstadienes; Asthma; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Time Factors

The objective of this study was to compare the efficacy and safety of fluticasone propionate (FP) (44 microg)/salmeterol (21 microg) delivered as two inhalations twice daily via a single hydrofluoroalkane (HFA 134a) metered dose inhaler (MDI) (FSC) with that of placebo HFA 134a (PLA), fluticasone propionate 44 microg chlorofluorocarbon (CFC) alone and salmeterol 21 microg CFC alone (S) in patients (n=360) with persistent asthma previously treated with beta2-agonists (short- or long-acting) or inhaled corticosteroids (ICS). After 12 weeks of treatment, patients treated with FSC had a significantly greater increase (p < or = 0.006) in mean FEV1 AUC(bl) compared with PLA, FP, or S. At end point, mean change from baseline in morning predose FEV1 for FSC (0.58 L) was significantly (p < or = 0.004) greater than PLA (0.14 L), FP (0.36 L), and S (0.25 L). Patients treated with FSC also had a significantly higher probability of remaining in the study without being withdrawn due to worsening asthma (2%) compared with those in the PLA (29%) and S (25%) groups (p < 0.001). Finally, treatment with FSC resulted in significantly (p < or = 0.007) greater improvements in morning and evening peak expiratory flow, need for rescue albuterol, and asthma symptom scores compared with FP, S, and PLA. The safety profile of FSC was also similar to FP or S alone. Initial maintenance treatment of the two main components of asthma, inflammation, and smooth muscle dysfunction (e.g., bronchoconstriction), with FSC results in greater overall improvements in asthma control compared with treatment of either individual component alone.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Child; Chlorofluorocarbons; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests

Asthma guidelines recommend combining inhaled corticosteroids and long-acting inhaled B2-agonists when inhaled corticosteroids alone are insufficient to achieve good control of the disease.. To determine in routine practice whether the fixed-dose fluticasone-salmeterol combination (FP/s) is as least as effective as inhaled corticosteroids combined with long-acting B2-agonists administered separately and to study patient perception.. An open multicentric randomized study was conducted in two matched populations stratified by the prior treatment. Patients insufficiently controlled by moderate-dose inhaled corticosteroids +/- long-acting B2-agonists or high-dose inhaled corticosteroids alone were treated for 3 months using one inhalation of FP/S twice daily or inhaled corticosteroids and long-acting B2-agonists given separately (TC).. Mean improvement in morning PEFR at 3 months was 39.2 +/- 4.1 l/min with FP/S and 30.7 +/- 4.0 l/min with TC. The difference (FP/S-TC: 8.5 l/min, CI95: -0.7 - 17.7 l/min) did not reach significance. There was no difference between the two groups for criteria other than TC. Tolerance was good in both groups.. The fixed-dose fluticasone-salmeterol combination is as least as effective as open combinations of inhaled corticosteroids and long-acting B2-agonists and is appreciated by patients (easier dosing, easier administration).

Topics: Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome

The aim of this study was to compare the efficacy safety and cost of Seretide (salmeterol/fluticasone propionate (Salm/FP), 50/250 microg bd) via Diskus with formoterol (Form; 12 microg bd) and budesonide (Bud; 800 microg bd) given concurrently (Form+Bud) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy. The study used a randomised, double-blind, double-dummy, parallel-group design, consisting of a 2-week run-in period on current corticosteroid therapy (1000-1600 microg/day of BDP or equivalent) and a 12-week treatment period. Symptomatic patients (n = 428) with FEV1 of 50-85% predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP (50/250 microg bd) via a single Diskus inhaleror Form+Bud (12+800 microg bd) via separate Turbuhalers. Clinic, diary card and asthma-related health-care resource utilisation data were collected. Improvement in mean morning peak expiratory flow (PEFam was similar in the Salm/FP and Form+Bud groups. Both PEFam and mean evening PEF (PEFpm) increased by a clinically significant amount (>20 L/min) from baseline in both treatment groups. The mean rate of exacerbations (mild, moderate or severe) was significantly lower in the Salm/FP group (0.472) compared with the Form+Bud group (0.735) (ratio = 0.64; P < 0.001), despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group. Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms, with a higher median percentage of symptom-free nights (P = 0.04), nights with a symptom score <2 (P = 0.03), and nights with no awakenings (P = 0.02). Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group (P<0.05). Both treatments were well tolerated, with a similar low incidence of adverse events. This study showed that in symptomatic patients with moderate-to-severe asthma, Salm/FP (50/250 microg bd), administered in a single convenient device (Diskus), was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud (800 microg bd) given concurrently with Form (12 microg bd) in terms of improvement in PEFam, and superior at reducing exacerbations and nights with symptoms or night-time awakenings. Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Sleep

In recent years, the combination of fluticasone furoate and vilanterol (FF/VI) has emerged as an alternative therapy, since it is administered every 24 h, in contrast to other ICS/LABAs such as fluticasone propionate plus salmeterol (FP/Salm), which requires administration every 12 h. Concerns have arisen over whether the benefit generated by FF/VI justifies the additional costs it involves over FP/Salm. This study aimed at assessing the health and economic consequences of FF/VI in patients with moderate-severe persistent asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with persistent asthma. Total costs and QALYs for FF/VI and FP/Salm were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. We estimated a gain of 16.8 and 10.7 QALYs per patient per year on FF/VI and FP/Salm, respectively. At the same time, we observed a difference of US$216 in total discounted cost per person-year on FF/VI with respect to FP/Salm. The incremental cost-effectiveness ratio (ICER) of FF/VI was USD $70 per QALY with respect to FP/Salm. In the deterministic and probabilistic sensitivity analyses, our base-case results were robust to variations in all assumptions and parameters.. FF/VI is more cost-effective than FP/Salm. The evidence supports using FF/VI therapy in Colombia, and the study should be replicated in other middle-income countries.

Topics: Administration, Inhalation; Androstadienes; Asthma; Benzyl Alcohols; Chlorobenzenes; Cost-Benefit Analysis; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Treatment Outcome

The effectiveness of a fix-dose salmeterol/fluticasone combination therapy in asthma was previously shown for the original product. The study aim was to evaluate the clinical effectiveness and safety of a second entry DPI - dry powder inhaler (Salflumix Easyhaler) in patients with asthma in everyday clinical practice.. This multicenter Investigator-Initiated Study that enrolled 2,037 adult outpatients with asthma treated with Salflumix Easyhaler, was conducted by 220 pulmonologists across Poland. Asthma control was assessed during 3 visits with 6 ± 2 weeks intervals based on the Asthma Control Test (ACT). In addition, patient Satisfaction with Asthma Treatment Questionnaire (SATQ) and adherence and adverse events (AEs) were monitored.. During the observation (86 ± 30 days) the percentage of patients with controlled asthma (ACT 20-25 pts) increased from 35.5% at the first visit to 86.5% at the third visit (. Salflumix Easyhaler is highly effective and well-tolerated by naïve patients with asthma and those switching from another device. In general, patients show good compliance with medical product and are satisfied with the use of this new device, and not reporting difficulties and errors related to its' use. Their physicians' overall perception of Salflumix Easyhaler use is very positive.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Patient Satisfaction; Salmeterol Xinafoate; Treatment Outcome

Bronchial asthma is one of the much known long-term respiratory conditions. Incidence is increasing, in developing countries like Bangladesh. Cross-sectional type of observational study was carried out over one year (July 2017 to June 2018) in the department of Pharmacology with collaboration of the department of Respiratory Medicine and Medicine, Mymensingh Medical College and Hospital, Mymensingh, Bangladesh. A total of 160 patients were selected non-randomly for the study. Inhalation route (52.35%) was the most preferred one over oral route (47.65%). In total 245 drugs, 131 FDC drugs (Salmeterol + Fluticasone) were prescribed with inhalation therapy which is 53.46%, another 9 FDC drugs that is (Ipratropium bromide + Salbutamol) were prescribed with inhalation therapy which is 3.67%, 101 drugs (Salbutamol) were prescribed with inhalation therapy that is 41.23%, 4 drugs (Beclomethasone) were prescribed with inhalation therapy that is 1.64%. Majority of patient were taking inhalation form of anti-asthmatic drugs.

Topics: Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Cross-Sectional Studies; Drug Prescriptions; Fluticasone-Salmeterol Drug Combination; Hospitals; Humans; Pharmaceutical Preparations

We reviewed recent clinical studies evaluating the safety and efficacy of LABA/LAMA/ICS fixed dose combinations by searching the PubMed database. Molecular mechanisms and clinical data support the use of a once-daily, single-inhaler fixed dose combination of the LABA/LAMA/ICS indacaterol/glycopyrronium/mometasone (IND/GLY/MF), the first therapy combining three agents in a fixed dose approved in Europe for the treatment of uncontrolled asthma.. IND/GLY/MF was superior to both IND/MF and salmeterol/fluticasone, a well-established LABA/ICS combination improving the lung function in uncontrolled asthma. Moreover, IND/GLY/MF, delivered through the Breezhaler inhaler in a single inhalation, is the first inhaled therapy prescribed alongside a digital companion, a sensor and the Propeller app, allowing for improved treatment adherence, reduced rescue inhaler usage and hospitalizations, increased patient satisfaction and asthma control.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Muscarinic Antagonists; Quinolones

Apart from the individual diseases, some patients also show overlapping manifestations of asthma and COPD. Nevertheless, the diagnosis of COPD is often delayed due to inaccessibility to spirometry; the prevalence of the asthma COPD overlap phenotype is rather high given the exposure to biomass smoke. Furthermore, the rates of exacerbations are twice as high compared to the patients with either of the diseases. A treatment strategy that would reduce the risk of exacerbations would contribute immensely to the management of such patients. Evidence of eosinophilia (marker of inflammation) in patients with asthma, asthma COPD overlap phenotype or COPD alone should prompt treatment with a combination of inhaled corticosteroids (ICS)/ long-acting β-agonists (LABA); several studies have shown improvement in the airflow limitation and reduction in the rate of exacerbations with salmeterol-fluticasone combination (SFC). Considering the association of COPD and cardiovascular diseases (CVD), it is critical to determine the cardiovascular safety of the LABA in such patients. Salmeterol is a highly selective partial b-2 agonist; the TORCH study and the studies comparing formoterol and salmeterol infer that there is no increased risk of new cardiovascular adverse events either with Salmeterol or SFC. Furthermore, the combination may provide certain degree of cardio-protection. Since COPD per se increases the risk of CVD, the cardio-safety of salmeterol outweighs its onset of action. SFC has well substantiated benefits in patients with asthma, COPD and high-risk patients such as those with an overlap of COPD and asthma symptoms, patients with elevated eosinophils and pre-existing CVD. An advisory board was hence conducted, which discussed the role of combination of salmeterol and fluticasone (SFC) not only in asthma and COPD but also in asthma COPD overlap phenotype. Based on the panel's clinical experience and the expertise derived thereof, the propositions regarding the place of SFC therapy in patients with stable and uncontrolled asthma, asthma COPD overlap phenotype and COPD has been put forth.

Topics: Asthma; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

To evaluate the budgetary impact of using budesonide + formoterol (Symbicort Turbuhaler) as maintenance therapy in real clinical practice compared with standard therapy for asthma of varying severity: for mild asthma with on-demand salbutamol; for moderate and severe asthma with the drug salmeterol + fluticasone and salbutamol on demand.. A static mathematical model was built to assess the impact on the budget when introducing the drug budesonide + formoterol (Symbicort Turbuhaler) in the treatment of asthma into clinical practice from the point of view of the state. Demographic data was taken from the official data of the Federal State Statistics Service. Direct medical costs included the cost of medicines, the cost of hospitalization of patients associated with the development of asthma exacerbations, and the cost of scheduled outpatient visits. Indirect costs considered the loss of GDP due to hospitalization of patients against the background of asthma exacerbations. A one-way sensitivity analysis was performed to confirm the robustness of the study results.. Assessment of direct costs in the treatment of mild, moderate and severe asthma showed that a gradual increase in the proportion of patients receiving the drug budesonide + formoterol (Symbicort Turbuhaler) over the years to 5.5, 7.7 and 9.7% accordingly, led to an increase in the cost of pharmacotherapy over 3 years by 1.7 billion rubles, while direct non-drug costs associated with the treatment of complications that developed during the treatment of asthma decreased by 8.3 billion rubles. Thus, the reduction in total direct costs amounted to RUB 6.7 billion. At the same time, indirect costs decreased by 6.0 billion rubles. The total reduction in all costs (direct and indirect) when switching patients to budesonide + formoterol (Symbicort Turbuhaler) amounted to 12.5 billion rubles. In addition, the use of the drug budesonide + formoterol (Symbicort Turbuhaler) resulted in a decrease in the number of exacerbations: in the first year by 3137, in the second by 4393 and in the third by 5534 cases. A total of 13 064 asthma exacerbations were prevented over 3 years.. Increasing the proportion of patients with asthma of varying severity receiving therapy with budesonide + formoterol (Symbicort Turbuhaler) will reduce the financial burden on both the healthcare system and the budgetary system.. Цель. Оценить влияние препарата будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) на бюджет при его применении в качестве поддерживающей терапии в реальной клинической практике в сравнении со стандартной терапией при бронхиальной астме (БА) различной степени тяжести: для БА легкого течения с сальбутамолом по требованию, для БА среднетяжелого и тяжелого течения с препаратом салметерол + флутиказон и сальбутамолом по требованию. Материалы и методы. Построена статическая математическая модель для оценки влияния лекарственного препарата будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) в лечении БА на бюджет при внедрении его в клиническую практику с точки зрения государства. Демографические данные взяты из официальных данных Федеральной службы государственной статистики. Прямые медицинские затраты включали расходы на лекарственные средства, затраты на госпитализацию пациентов, сопряженную с развитием обострений БА, и затраты на плановые амбулаторные визиты. Косвенные затраты учитывали потерю ВВП в связи с госпитализацией пациентов на фоне обострений БА. Односторонний анализ чувствительности провели для подтверждения надежности результатов исследования. Результаты. Оценка прямых затрат при лечении БА легкого, среднетяжелого и тяжелого течения показала, что постепенное увеличение доли пациентов, получающих препарат будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза), в 1, 2, 3-й год приема до 5,5, 7,7 и 9,7% соответственно, привело к возрастанию затрат на фармакотерапию за это время на 1,7 млрд руб., при том что прямые нелекарственные затраты, связанные с лечением осложнений, развившихся на фоне лечения БА, уменьшились на 8,3 млрд руб. Таким образом, снижение суммарных прямых затрат составило 6,7 млрд руб. Косвенные затраты при этом сократились на 6,0 млрд руб. Общее снижение всех затрат (прямых и косвенных) при переключении пациентов на будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) составило 12,5 млрд руб. Кроме того, препарат будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) помог снизить число обострений: в 1-й год на 3137, во 2-й на 4393 и в 3-й на 5534 случая. Суммарно за 3 года было предотвращено 13 064 обострения БА. Заключение. Увеличение доли пациентов с БА различной степени тяжести, получающих терапию с препаратом будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза), позволит снизить финансовую нагрузку как на систему здравоохранения, так и на бюджетную систему государства в

Topics: Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Delivery of Health Care; Drug Combinations; Economics, Pharmaceutical; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans

Fluticasone propionate/salmeterol multidose, dry powder inhaler (MDPI) was the first and only authorized generic inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combination inhaler at the time of this study. This offers the potential for significant prescription cost-savings for both patients and accountable care organizations. The objective of the study was to demonstrate patients' clinical response to generic fluticasone propionate/salmeterol MDPI when switched from one of its brand name competitors.. The study was approved by the Institutional Review Board at MCPHS University. This was a prospective chart review of a large, multi-center ambulatory care organization in the Greater Boston area. Patients 12 years of age or older who were switched from a brand-name ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI were included in the study. The primary endpoint was worsened asthma control requiring a change in therapy, oral corticosteroid therapy, or hospitalization at or before 12 weeks after the inhaler was switched.. In total, 203 patients met inclusion criteria. Of those 203 patients, 35 had a change in therapy due to worsened asthma control (17.2% of patients, 95% CI 12.0% to 22.4%) within 12 weeks. Total projected yearly prescription cost-savings for patients who were switched and remained on the generic inhaler was $581,628.. Eighty-three percent of patients maintained appropriate asthma control after switching from a brand ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI for 12 weeks. Switching to the generic inhaler resulted in significant prescription cost-savings for the accountable care organization.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Ambulatory Care; Asthma; Bronchodilator Agents; Drug Combinations; Drugs, Generic; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Nebulizers and Vaporizers; Powders; Propionates; Prospective Studies; Salmeterol Xinafoate

Nonadherence in difficult-to-control asthma can be identified using 7-day FeNO suppression testing where patients take additional fluticasone via Diskus with an Inhaler Compliance Assessment (INCA) acoustic monitoring device attached, and self-measure FeNO at home. However, this is inconvenient for patients attending a tertiary center and limited by FeNO meter availability. It is not known if this approach alters clinical outcomes.. A service evaluation of FeNO suppression testing was undertaken in clinical practice.. Twenty-one of 23 subjects offered replacement of their usual ICS/LABA with fluticasone/salmeterol+INCA as the initial intervention accepted and completed 28 days of monitoring. Fourteen (66.6%) patients reduced their FeNO by >42% (FeNO suppressors), accompanied by improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire, and blood eosinophils, similar to the 7-day test (n = 74). Twenty-two of 62 (35.5%) FeNO suppressors progressed to biological therapy, compared with 24 of 33 (72.7%) nonsuppressors (P = .0006). FeNO suppressors taking maintenance prednisolone (n = 13) who did not receive biological therapy reduced the median baseline dose from 10 to 3 mg, with further reductions limited by adrenal suppression.. Replacing existing inhaled therapy with fluticasone/salmeterol+INCA for 28 days is acceptable to the majority of people with difficult-to-control asthma and identifies prior medication nonadherence. INCA monitoring coupled with clinical support potentially improves patient adherence and asthma control, preventing unnecessary progression to biological therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Asthma; Drug Combinations; Electronics; Fluticasone-Salmeterol Drug Combination; Humans; Medication Adherence

Previous studies have found suboptimal control of symptom burden to be widespread among patients with asthma and chronic obstructive pulmonary disease (COPD). The Phase IV SPRINT study was conducted in 10 countries in Europe to assess asthma disease control and COPD symptom burden in patients treated with a fixed-dose combination (FDC) of inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs). SPRINT included 1101 patients with asthma and 560 with COPD; all were receiving treatment with an FDC of ICS/LABA, delivered via various inhalers. Data were obtained over a 3-month period, during a single routine physician's office visit. Asthma control was defined as Asthma Control Test (ACT) score >19. COPD symptom burden was assessed by COPD Assessment Test (CAT), with a CAT score <10 defining low COPD symptom burden. Among patients using any ICS/LABA FDC, 62% of patients with asthma had achieved disease control (ACT score >19) and 16% of patients with COPD had low symptom burden (CAT score <10).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dry Powder Inhalers; Europe; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Treatment Outcome

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Drug Administration Schedule; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Indans; Mometasone Furoate; Quinolones

Összefoglaló. Az allergiás betegségekben szenvedő emberek száma világszerte, köztük Magyarországon is növekszik. Az egészségügyi ellátórendszerek azon dolgoznak, hogy minél hatékonyabban tudják felhasználni a rendelkezésre álló forrásokat. Az Allergic Rhinitis and its Impact on Asthma (ARIA) szervezet célja az allergiás náthában szenvedő betegek ellátásának javítása, szakmai ajánlások készítése, aktualizálása. Ennek egyik módja integrált betegellátási utak kidolgozása. Célunk ezek hazai elérhetővé tétele, az ajánlások széles körű elterjesztése az Európai Unió (EU) többi tagállamához hasonlóan Magyarországon is. Az ARIA más nemzetközi innovatív szervezetek bevonásával olyan integrált betegellátási utakat fejlesztett ki, amelyek allergiás nátha, esetleg társbetegsége, az asztma esetén támogatják a kezelést. Ezeket újgenerációs irányelvek kidolgozása útján alkották, amelyekhez felhasználták a mobiltechnológiából és pollenkamra-vizsgálatokból származó valós evidenciákat is. A gyógyszeres terápia optimalizálásához a vizuális analóg skálán alapuló, úgynevezett Mobil Légúti Figyelő Hálózat algoritmusát digitalizálták, és valós evidenciák felhasználásával tovább finomították. Allergén immunterápiára az ARIA a világon elsőként dolgozott ki integrált betegellátási utakat 2019-ben. A kezelési irányelvekhez való adherenciaszint alacsony, a betegek a tüneteik erőssége alapján módosítják a kezelést. A flutikazon-propionát-azelasztin kombináció hatása erősebb az intranasalis kortikoszteroidokénál, míg az utóbbi hatásosabb az oralis H1-antihisztaminoknál. A mobiltelefonokban tárolt elektronikus napló vagy más 'mobile health' (mHealth) eszközök használata segíti a betegek kiválasztását allergén immunterápiára. Az ARIA által javasolt algoritmus megfelelőnek mutatkozott az allergiás rhinitis kezelésére, ezért ezek az irányelvek bekerülnek integrált betegellátási utakba, és részét fogják képezni az EU Egészségügyi és Élelmiszer-biztonsági Főigazgatósága digitalizált, személyközpontú gondozási anyagainak. Az allergén immunterápia hatékony az inhalatív allergének által okozott allergiás betegségekben, alkalmazását azonban korlátozni kell gondosan válogatott betegekre. Orv Hetil. 2020; 161(49): 2059-2071. Summary. The number of allergic patients is increasing all over the world, also in Hungary. Delivering effective and cost-effective health care is essential for all health care systems. ARIA (Allergic Rhinitis and its Impact on Asthma) aims to improve the care of patients who

Topics: Asthma; Change Management; Fluticasone-Salmeterol Drug Combination; Humans; Hungary; Immunotherapy; Integrative Medicine; Practice Guidelines as Topic; Rhinitis, Allergic; Telemedicine; Treatment Outcome

Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta. The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age.. A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records.. Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.

Topics: Asthma; Bronchodilator Agents; Child, Preschool; Female; Fluticasone-Salmeterol Drug Combination; Humans; Infant; Male; Retrospective Studies; Treatment Outcome

Topics: Acetates; Anti-Asthmatic Agents; Antipsychotic Agents; Asthma; Autism Spectrum Disorder; Bronchodilator Agents; Child; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Quinolines; Rhinitis, Allergic; Risperidone; Sulfides; Treatment Outcome

Data on inhaler technique and its effects on maternal and fetal outcomes during pregnancy are seldom reported. The primary objective of this study was to evaluate inhaler technique and identify errors in inhaler use among pregnant women with asthma. Secondary objectives were to identify factors associated with poor inhaler technique and study the association between inhaler technique and maternal and fetal outcomes. This was a cross-sectional, face-to-face, prospective study of 80 pregnant women with physician-diagnosed asthma. Seventy-three and 41 asthmatic pregnant women reported using pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), respectively. Overall, wrong inhaler technique was observed in 47 (64.4%) subjects. Among pMDI users, correct inhaler use was observed in only 26/73 (35.6%) of the patients, with lack of coordination between inhalation and generation of the aerosol and failure to breathe out gently before using the inhaler, being the most common errors. Among DPI users, 21 (51.2%) demonstrated correct inhaler use, with failure to perform a breath-hold for 10 seconds after inhaling the powder and to exhale gently before using the inhaler being the most common errors. Significant associations between inhaler technique and patient's understanding of asthma medications and the kind of follow-up clinic (respiratory versus nonrespiratory clinic) were found. No significant associations between inhaler technique and various maternal and fetal outcomes or asthma control were found. In conclusion, improper inhalation technique is significantly prevalent in pregnant asthmatic women, particularly among those being followed in nonspecialized respiratory clinics. The lack of significant association between the inhaler technique and asthma control (and hence maternal and fetal outcomes) may simply reflect the high prevalence of uncontrolled asthma and significant contribution of other barriers to poor asthma control in the current patient's cohort. Multidisciplinary management of asthma during pregnancy with particular emphasis on patient's education is imperative.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cesarean Section; Congenital Abnormalities; Cross-Sectional Studies; Disease Progression; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Humans; Infant, Low Birth Weight; Infant, Newborn; Metered Dose Inhalers; Patient Medication Knowledge; Pregnancy; Pregnancy Complications; Prospective Studies; Qatar; Respiratory Distress Syndrome, Newborn

Asthma has a substantial impact on quality of life and health care resources. The identification of a more cost-effective, yet equally efficacious, treatment could positively influence the economic burden of this disease. Fluticasone propionate/Formoterol (FP/FOR) may be as effective as Fluticasone Salmeterol (FP/SAL). We evaluated non-inferiority of asthma control in terms of the proportion of patients free from exacerbations, and conducted a cost impact analysis.. This historical, matched cohort database study evaluated two treatment groups in the Optimum Patient Care Research Database in the UK: 1) an FP/FOR cohort of patients initiating treatment with FP/FOR or changing from FP/SAL to FP/FOR and; 2) an FP/SAL cohort comprising patients initiating, or remaining on FP/SAL pMDI combination therapy. The main outcome evaluated non-inferiority of effectiveness (defined as prevention of severe exacerbations, lower limit of the 95% confidence interval (CI) of the mean difference between groups in patient proportions with no exacerbations is -3.5% or higher) in patients treated with FP/FOR versus FP/SAL.. After matching 1:3, we studied a total of 2472 patients: 618 in the FP/FOR cohort (174 patients initiated on FP/FOR and 444 patients changed to FP/FOR) and 1854 in the FP/SAL cohort (522 patients initiated FP/SAL and 1332 continued FP/SAL). The percentage of patients prescribed FP/FOR met non-inferiority as the adjusted mean difference in proportion of no severe exacerbations (95%CI) was 0.008 (-0.032, 0.047) between the two cohorts. No other significant differences were observed except acute respiratory event rates, which were lower for patients prescribed FP/FOR (rate ratio [RR] 0.82, 95% CI 0.71, 0.94).. Changing to, or initiating FP/FOR combination therapy, is associated with a non-inferior proportion of patients who are severe exacerbation-free at a lower average annual cost compared with continuing or initiating treatment with FP/SAL.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Cohort Studies; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Quality of Life; Treatment Outcome; United Kingdom

Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management.. Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days' wages it would cost the least paid public servant were analysed.. The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days' wages for inhaled salbutamol to 17.1 days' wages for formoterol/budesonide inhalers and 27.8 days' wages for spirometry.. Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Diagnostic Techniques, Respiratory System; Drug Combinations; Drug Costs; Fluticasone-Salmeterol Drug Combination; Health Services Accessibility; Humans; Leukotriene Antagonists; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry; Uganda

Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is a refractory disease closely associated with bronchial asthma. We recently reported on the efficacy of ultra-fine particle inhaled corticosteroids (ICS) (hydrofluoroalkane-134a-beclomethasone dipropionate: HFA-BDP) exhalation through the nose (ETN) treatment for mild-to-moderate asthmatics with ECRS. However, the effect of HFA-BDP ETN was found to be transient in some cases with severe ECRS and asthma, requiring treatment with higher-dose ICS and long-acting β2-agonists (LABA). Here, we present a case of refractory ECRS with severe asthma treated with a combination of high-dose ICS and LABA ETN, and we discuss the mechanisms for its effectiveness.. A 57-year-old man was treated with the combined regimen of HFA-BDP ETN and salmeterol/fluticasone combination (SFC) dry powder inhaler (DPI) for his refractory ECRS with severe asthma. For better control, we replaced SFC-DPI with SFC metered-dose inhaler (MDI) ETN and evaluated the clinical effect and corticosteroid sensitivity. We also examined the flow and deposition of fine particles released by SFC-MDI ETN.. After switching to SFC-MDI ETN, the patient's conditions markedly resolved with the restoration of corticosteroid sensitivity and PP2A activity. The fine particles released by SFC-MDI ETN at least partially flowed out through the external nares and seemed to be deposited on the ethmoid sinus.. Fine particle ICS/LABA ETN might be an additional therapeutic option for refractory ECRS with severe asthma and corticosteroid insensitivity.
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Topics: Asthma; Chronic Disease; Dry Powder Inhalers; Eosinophilia; Fluticasone-Salmeterol Drug Combination; Humans; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Rhinitis; Severity of Illness Index; Sinusitis; Treatment Outcome

Topics: Adult; Asthma; Drugs, Generic; Fluticasone-Salmeterol Drug Combination; Humans; Therapeutic Equivalency

INTRODUCTION    Asthma is a highly prevalent disease that often requires maintenance therapy. Combined inhaled corticosteroid (ICS) and long‑acting β2‑agonist (LABA) inhalers are one of the available maintenance treatment options. OBJECTIVES    This prospective observational study aimed to assess asthma control in patients treated with ICS/LABA inhalers and to identify factors related to optimal asthma control. PATIENTS AND METHODS    The study included 5789 asthmatic patients from Poland, treated with one of the following ICS/LABA inhalers at clinically appropriate doses: beclomethasone/formoterol, fluticasone/ salmeterol, or budesonide/formoterol. The follow‑up lasted 6 months (4 visits in total). The outcomes were physician-reported and patient‑reported asthma control and occurrence of adverse drug reactions. A retrospective logistic regression analysis was performed to identify a potential association between age, obesity, and smoking and the level of disease control. RESULTS    A total of 4469 patients completed the study. Throughout the study period, the rate of patient‑reported control of asthma increased from 24.8% to 67.7%, while physician‑reported control increased from 22.6% to 66.4%. The incidence of exacerbations decreased from 23.4% to 1.9%. Less than 0.1% of the patients reported adverse drug reactions. Age, obesity (body mass index ≥30 kg/m2), and smoking were confirmed as factors negatively affecting disease control, with combined ICS/LABA inhalers potentially reducing their effect. CONCLUSION    Our results confirm the efficacy and safety of combined ICS/LABA inhalers in a real‑life clinical setting. They also corroborate the finding that obesity, older age, and smoking are risk factors for poor asthma control.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Delayed-Action Preparations; Dose-Response Relationship, Drug; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Nebulizers and Vaporizers; Treatment Outcome

The potential consequences of confounding due to drug formulary restrictions in pharmacoepidemiologic research remain incompletely understood. Our objective was to illustrate this potential bias using the example of fluticasone/salmeterol combination therapy, an oral inhaler used to treat asthma and chronic obstructive pulmonary disease, whose use is restricted in the province of Quebec, Canada.. We identified all new users of fluticasone/salmeterol in Quebec's administrative databases and classified those who received their initial dispensing of fluticasone/salmeterol between 1 September 1999 and 30 September 2003 as users from the liberal period and those who received it between 1 January 2004 and 31 October 2006 as users from the restricted period. The primary outcome was time to first hospitalization for respiratory causes within 12 months of cohort entry.. Our cohort included 72 154 new users from the liberal period and 5058 from the restricted period. Compared with use during the liberal period, use during the restricted period was associated with an increased rate of hospitalization for respiratory causes (crude hazard ratio [HR] = 1.41, 95% confidence interval [CI] = 1.32, 1.51). Subsequent adjustment for age, sex, and hospitalization for respiratory causes in the previous year attenuated the association (HR = 1.05, 95%CI = 0.98, 1.12). Further adjustment for other potential confounders resulted in a lower rate during the restricted period (HR = 0.78, 95%CI = 0.73, 0.83).. Formulary restrictions can result in substantial and unexpected confounding and should be considered during the design and analysis of pharmacoepidemiologic studies.

Topics: Asthma; Bronchodilator Agents; Cohort Studies; Confounding Factors, Epidemiologic; Databases, Factual; Drug Utilization Review; Fluticasone-Salmeterol Drug Combination; Formularies as Topic; Hospitalization; Humans; Mortality; Outcome Assessment, Health Care; Pharmacoepidemiology; Pulmonary Disease, Chronic Obstructive; Quebec; Retrospective Studies

A 9-y-old, colony-bred, female vervet monkey (Chlorocebus sabaeus) presented with a 6-y history of open-mouth breathing, tachypnea, and sibilant wheezing. These symptoms did not significantly affect her activity or quality of life. Thoracic radiographs and results of bronchoalveolar lavage supported the diagnosis of asthma. Treatment comprising intramuscular prednisolone (tapered over 2 mo from twice daily to every other day), inhaled salmeterol-fluticasone (25 μg-250 μg per actuation twice daily) by mask, and a metered dose inhaler was successful in restoring a normal respiratory pattern. Despite the availability of several primate models of human asthma, this case represents the first report of spontaneous asthma in a NHP.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Age Factors; Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage; Bronchodilator Agents; Chlorocebus aethiops; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Injections, Intramuscular; Lung; Monkey Diseases; Prednisolone; Radiography, Thoracic; Respiratory Function Tests; Treatment Outcome

Topics: Asthma; Bronchodilator Agents; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Disease Progression; Drug Therapy, Combination; Fluticasone-Salmeterol Drug Combination; Humans; Randomized Controlled Trials as Topic; Risk Factors

Chronic obstructive pulmonary disease (COPD) affects approximately 15 million people in the United States and accounts for approximately $36 billion in economic burden, primarily due to medical costs. To address the increasing clinical and economic burden, the Global Initiative for Chronic Obstructive Lung Disease emphasizes the use of therapies that help prevent COPD exacerbations, including inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA).. To evaluate health care costs and utilization among COPD patients newly initiating ICS/LABA combination therapy with budesonide/formoterol (BFC) or fluticasone/salmeterol (FSC) in a managed care system.. COPD patients aged 40 years and older who initiated BFC (160/4.5 μg) or FSC (250/50 μg) treatment between March 1, 2009, and March 31, 2012, were identified using claims data from major U.S. health plans. BFC and FSC patients were propensity score matched (1:1) on age, sex, prior asthma diagnosis, prior COPD-related health care utilization, and respiratory medication use. COPD-related, pneumonia-related, and all-cause costs and utilization were analyzed during the 12-month follow-up period. Post-index costs were assessed with generalized linear models (GLMs) with gamma distribution. Health care utilization data were analyzed via logistic regression (any event vs. none) and GLMs with negative binomial distribution (number of visits) and were adjusted for the analogous pre-index variable as well as pre-index characteristics that remained imbalanced after matching.. After matching, each cohort had 3,697 patients balanced on age (mean 64 years), sex (female 52% BFC and 54% FSC), asthma and other comorbid conditions, prior COPD-related health care utilization, and respiratory medication use. During the 12-month follow-up, COPD-related costs averaged $316 less for BFC versus FSC patients ($4,326 vs. $4,846; P = 0.003), reflecting lower inpatient ($966 vs. $1,202; P < 0.001), pharmacy ($1,482 vs. $1,609; P = 0.002), and outpatient/office ($1,378 vs. $1,436; P = 0.048) costs, but higher emergency department ($257 vs. $252; P = 0.033) costs. Pneumonia-related health care costs were also lower on average for BFC patients ($2,855 vs. $3,605; P < 0.001). Similarly, initiating BFC was associated with lower all-use health care costs versus initiating FSC ($21,580 vs. $24,483; P < 0.001, respectively). No differences in health care utilization were found between the 2 groups.. In this study, although no difference was observed in rates of health care utilization, COPD patients initiating BFC treatment incurred lower average COPD-related, pneumonia-related, and all-cause costs versus FSC initiators, which was driven by cumulative differences in inpatient, outpatient, and pharmacy costs.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; United States

Pressurized metered-dose inhalers (pMDI) such as fluticasone propionate and salmeterol (FP/SAL) are commonly used for the treatment of asthma in the UK. Previously, a budget impact analysis demonstrated that use of FP and formoterol fumarate (FP/FORM) pMDI as an alternative to FP/SAL pMDI, would be a cost-saving option for the UK National Health Service (NHS). This budget impact analysis aimed to update the existing analysis with prescription volume data and real-world evidence since the introduction of FP/FORM to the UK market.. Patient Data (IMS Information Solutions UK Ltd) moving annual total (MAT) August 2015 were used to ascertain the number of units of pMDI prescribed. Annual costs to the NHS in terms of drug, administration, monitoring and adverse event costs, were used to estimate the potential budget impact for FP/FORM and FP/SAL. Costs were calculated for current prescription volumes (12% FP/FORM, 88% FP/SAL), and for different prescription volume scenarios (FP/FORM at 0%, 25%, 50% and 100%). Real-world evidence and budget impact at a clinical commissioning group (CCG) level were also considered.. Total annual costs per person year were less with FP/FORM (£625) than with FP/SAL (£734). Annual costs to the NHS based on the current prescription volumes and clinical trial data were estimated at £210.0M, however, based on real-world evidence, costs were estimated at £179.8M. For all scenarios with increased FP/FORM prescription volumes, the annual total costs to the NHS decreased. This was reflected at a CCG level.. The use of FP/FORM as an alternative to FP/SAL can result in cost savings for the NHS when assessing drug, administration, monitoring and adverse events costs. The inclusion of data released since the launch of FP/FORM within the budget impact analysis demonstrates that the potential cost savings to the NHS that were previously published are being translated to clinical practice.. Mundipharma, UK.

Topics: Asthma; Cost Savings; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Impact Assessment; Humans; Metered Dose Inhalers; Models, Economic; State Medicine; United Kingdom

Topics: Adult; Anti-Asthmatic Agents; Asthma; Diet; Eosinophilic Esophagitis; Female; Fluticasone-Salmeterol Drug Combination; Food Hypersensitivity; Humans; Immunoglobulin E

Dry powder inhaler (DPI) users frequently exhale into their inhaler mouthpiece before the inhalation step. This error in technique compromises the integrity of the drug and results in poor bronchodilation. This study investigated the effect of four exhalation factors (exhalation flow rate, distance from mouth to inhaler, exhalation duration, and relative air humidity) on dry powder dose delivery. Given that acoustic energy can be related to the factors associated with exhalation sounds, we then aimed to develop a method of identifying and quantifying this critical inhaler technique error using acoustic based methods.. An in vitro test rig was developed to simulate this critical error. The effect of the four factors on subsequent drug delivery were investigated using multivariate regression models. In a further study we then used an acoustic monitoring device to unobtrusively record the sounds 22 asthmatic patients made whilst using a Diskus(™) DPI. Acoustic energy was employed to automatically detect and analyze exhalation events in the audio files.. All exhalation factors had a statistically significant effect on drug delivery (p<0.05); distance from the inhaler mouthpiece had the largest effect size. Humid air exhalations were found to reduce the fine particle fraction (FPF) compared to dry air. In a dataset of 110 audio files from 22 asthmatic patients, the acoustic method detected exhalations with an accuracy of 89.1%. We were able to classify exhalations occurring 5 cm or less in the direction of the inhaler mouthpiece or recording device with a sensitivity of 72.2% and specificity of 85.7%.. Exhaling into a DPI has a significant detrimental effect. Acoustic based methods can be employed to objectively detect and analyze exhalations during inhaler use, thus providing a method of remotely monitoring inhaler technique and providing personalized inhaler technique feedback.

Topics: Acoustics; Administration, Inhalation; Aerosols; Air; Algorithms; Asthma; Bronchodilator Agents; Case-Control Studies; Drug Delivery Systems; Dry Powder Inhalers; Equipment Design; Exhalation; Fluticasone-Salmeterol Drug Combination; Humans; Humidity; Inhalation; Lung; Multivariate Analysis; Powders; Regression Analysis; Respiratory Sounds; Signal Processing, Computer-Assisted; Sound Spectrography; Time Factors

After the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany.. Patients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses.. Highest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of "concomitant LABA and ICS users" increased from 52.0 to 57.6% within the study period, whereas for "LABA users without ICS" a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present.. Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Beclomethasone; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Drug Combinations; Drug Therapy, Combination; Drug Utilization Review; Female; Fluticasone-Salmeterol Drug Combination; Germany; Glucocorticoids; Guideline Adherence; Humans; Male; Middle Aged; Mometasone Furoate; Practice Guidelines as Topic; Practice Patterns, Physicians'; Salmeterol Xinafoate; Young Adult

To assess, using a standard observational tool, the ability of patients to demonstrate and maintain proper inhaled medication administration techniques following pharmacist education.. Six-month observational study.. Patients' homes or adult day health center.. Patients in a Program for All-inclusive Care for the Elderly (PACE) prescribed one or more inhaled medications used at least once daily.. Instruction by on-site clinical pharmacist.. Hickey's Pharmacies Inhaler Technique assessment (score range: 0-20, higher better).. Forty-two patients were evaluated at baseline, taught proper techniques for using inhaled medications, assessed immediately following the education, and re-assessed 4-6 weeks later. The mean pre-assessment score was 14 (SD 4.5, range 0-20), the initial post-assessment score increased to 18 (SD 3, range 10-20). The second post-assessment (4-6 weeks later) score mean was 17.7 (SD 3, range 10-20). Both follow-up scores were significantly improved from baseline (p < 0.05). Multivariable analysis indicated the strongest predictors of second post-training score were: score after initial pharmacist training and being subscribed to auto-refill. These characteristics predicted ∼70% of the variance in the second score (p < 0.001).. These results indicate that education by a pharmacist combined with an auto-refill program can improve and sustain appropriate inhaler use by community-dwelling elders in a PACE program. The improved score was maintained 4-6 weeks later indicating a sustained benefit of medication administration education. Optimal inhaler use ensures optimal dosing and supports appropriate inhaler treatment in lieu of oral agents.

Topics: Administration, Inhalation; Adult Day Care Centers; Age Factors; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Drug Delivery Systems; Female; Fluticasone-Salmeterol Drug Combination; Humans; Independent Living; Male; Middle Aged; Nebulizers and Vaporizers; Outcome Assessment, Health Care; Patient Education as Topic; Pharmacists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Inhaled corticosteroid/long-acting β2-agonist combinations and/or long-acting muscarinic antagonists are recommended first-line therapies for preventing chronic obstructive pulmonary disease (COPD) exacerbation. Comparative effectiveness of budesonide/formoterol combination (BFC, an inhaled corticosteroid/long-acting β2-agonist combination) vs tiotropium (long-acting muscarinic antagonist) in the US has not yet been studied.. Using US claims data from the HealthCore Integrated Research Environment, COPD patients (with or without comorbid asthma) ≥40 years old initiating BFC or tiotropium between March 1, 2009 and February 28, 2012 and at risk for exacerbation were identified and followed for 12 months. Patients were propensity score matched on demographics and COPD disease severity indicators. The primary outcome was time to first COPD exacerbation. Secondary outcomes included COPD exacerbation rate, health care resource utilization, and costs.. The Cox proportional hazards model for time to first exacerbation yielded a hazard ratio (HR) of 0.78 (95% CI =[0.70, 0.87], P<0.001), indicating a 22% reduction in risk of COPD exacerbation associated with initiation of BFC versus tiotropium. A post hoc sensitivity analysis found similar effects in those who had a prior asthma diagnosis (HR =0.72 [0.61, 0.86]) and those who did not (HR =0.83 [0.72, 0.96]). BFC initiation was associated with lower COPD-related health care resource utilization and costs ($4,084 per patient-year compared with $5,656 for tiotropium patients, P<0.001).. In COPD patients new to controller therapies, initiating treatment with BFC was associated with improvements in health and economic outcomes compared with tiotropium.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Asthma; Bronchodilator Agents; Budesonide; Comorbidity; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Hospitalization; Humans; Insurance Claim Reporting; Male; Middle Aged; Muscarinic Antagonists; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

The clinical usefulness of fixed-dose maintenance therapy with salmeterol/fluticasone (SFC) and budesonide/formoterol combination inhaler (BUD/FM) has been established, though evidence of the long-term anti-inflammatory effects of these 2 inhalers are limited.. Patients with moderate persistent adult asthma who had received SFC 50/250μg bid with well-control status were recruited. After switching to 8-week therapy with fixed-dose BUD/FM 4 puffs (640/18μg) (phase-1), patients chose either SFC or BUD/FM. FeNO and ACT score were evaluated every 8 weeks until the end of the 52-week treatment period for both treatment groups (phase-2).. In total, 103 patients were examined: BUD/FM was chosen by 34 patients (BUD/FM group), while SFC was chosen by 23 (SFC group). Thirty-six received SFC consistently from the beginning of the study (control). Patients in the BUD/FM and SFC groups showed significant improvements in ACT scores and FeNO levels in phase-1; these beneficial effects persisted for 52 weeks in the BUD/FM group. On the other hand, in the SFC group, although the FeNO level decreased from 54.3 ± 26.4 ppb to 41.9 ± 18.3 ppb in phase-1, it increased to 54.5 ± 26.2 ppb, a level similar to the baseline prior to the beginning of BUD/FM therapy, at 8 weeks in phase-2, and remained at 50-odd ppb thereafter.. These results suggest that maintenance therapy with fixed-dose BUD/FM is a useful treatment option exerting an airway anti-inflammatory effect for a period as long as 1 year, even for asthmatics who could not accomplish total control with SFC.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Budesonide; Case-Control Studies; Drug Combinations; Ethanolamines; Exhalation; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Medication Adherence; Middle Aged; Nebulizers and Vaporizers; Nitric Oxide; Young Adult

Low adherence with asthma treatment may be associated with suboptimal outcomes and hence create a treatment gap in the real-life setting. The objective of this study was to assess the long-term association between adherence to treatment with fixed-dose fluticasone propionate/salmeterol (FSC) and the risk of exacerbations and health care utilization in patients with asthma.. Observational single cohort study utilizing the Quebec Health Insurance databases. All patients (age >12 years) with a diagnosis of asthma (ICD9-CM 493.xx) between 2001 and 2010 were entered into the study cohort at the time of their first prescription for FSC at any dose. Follow-up continued to the last known claim or death. Adherence to treatment was ascertained as compliance (medication possession ratio ≥80%) and persistence (absence of treatment gap ≥30 days).. Outcomes assessed were exacerbations defined as one of the following: use of oral corticosteroid (OCS), emergency room (ER) visit for asthma or hospitalization for asthma. Asthma related health care resource utilizations ascertained were number of prescription claims for rescue medications, ER visits, hospitalizations, intensive care unit (ICU) stay, intubations, and general practitioner (GP) and respirologist visits.. A total of 19,126 patients were included in the study. The proportion of compliant and persistent patients were 42.7% and 29.3% respectively. Multivariate logistic regression analyses showed a significantly reduced adjusted odds of exacerbations for compliant (OR = 0.48; 95% CI: 0.44-0.54) and persistent patients (OR = 0.42; 95% CI: 0.38-0.48). Similarly, significantly lower rates of health care utilization were observed for compliant and persistent patients.. The results of this large population-based study have shown that increased adherence to treatment with FSC is associated with lower risk for exacerbations, lower rescue medication use and lower health care utilization in asthma patients. Despite the typical limitations of an administrative database study including validity of the diagnosis, the fact that compliance and persistence are calculated based on filled claims which does not guarantee that the patients actually took their medications, and the absence of clinical and laboratory data, the findings have implications for physician and patient awareness of the importance of adherence in the management of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Disease Progression; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Glucocorticoids; Health Services; Humans; Male; Medication Adherence; Middle Aged; Quebec; Retrospective Studies; Treatment Outcome

To observe changes in the lung function of asthmatic children with different symptoms during treatment, and to investigate the clinical significance of bronchial reversibility test in the treatment of asthma in children.. A total of 417 asthmatic children were treated by salmeterol/fluticasone inhalation for more than 3 months. These patients were divided into asymptomatic, single cough, paroxysmal cough and wheeze (cough+wheeze or wheeze alone) groups based on the symptoms when they revisited the clinic. Thirty-four healthy children were used as a control group. All children underwent bronchial reversibility test using nebulized salbutamol. Lung function testing was performed before and after the test.. After nebulization of salbutamol, each asthma group showed significantly decreased rate of abnormal lung function and significantly increased forced expiratory volume in one second percent (FEV1%) predicted (P<0.05). Before salbutamol nebulization, the single cough, paroxysmal cough and wheeze groups had significantly higher rates of abnormal lung function and significantly lower FEV1% predicted than the control group (P<0.05). There were significant differences in the rate of abnormal lung function and FEV1% predicted among the asthma groups (P<0.05). After salbutamol nebulization, the paroxysmal cough and wheeze groups had significantly higher rates of abnormal lung function than the control group (P<0.05), but there were no significant differences between other asthma and control groups; the wheeze group had significantly lower FEV1% predicted than the control group, but no significant differences were found between other asthma and the control groups. The positive rate of bronchial reversibility test in each asthma group was significantly higher than in the control group (P<0.05). There were significant differences in the positive rate of the test between the asthma groups except between the asymptomatic and single cough groups (P<0.05).. Asthmatic children with different symptoms demonstrate different lung functions during treatment. Bronchial reversibility test combined with lung function test is useful in assessing asthma control and guiding treatment.

Topics: Administration, Inhalation; Adolescent; Albuterol; Androstadienes; Asthma; Bronchi; Child; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male

Physicians are not always aware that locally administered glucocorticoids can cause systemic toxicity. This risk is greatly enhanced in the case of pharmacological interactions. We present two cases of HIV-infected patients who developed Cushing-like symptoms as a result of a pharmacological interaction. Their antiretroviral treatment regimen consisted of atazanavir, ritonavir, tenofovir and emtricitabine. One patient received salmeterol/fluticasone inhalations for asthmatic bronchitis. The other was treated with intra-articular triamcinolonacetonide injections for ongoing shoulder complaints. Ritonavir exhibits strong inhibition of hepatic enzyme CYP 3A4, which is part of the major metabolic pathway of most glucocorticoids. As a result of this interaction even locally administered glucocorticoids can cause symptoms of overdose, e.g. Cushing-like symptoms. Beclomethasone is a safe alternative for inhaled glucocorticoids as it is not metabolized by CYP 3A4. There is no substitute for intra-articular administration of triamcinolonacetonide. Depending on necessity of the administration of the drug, changing ritonavir-containing antiretroviral therapy to a non-interacting compound, e.g., an integrase inhibitor, is an option.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Combinations; Drug Interactions; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; Humans; Male; Ritonavir

The purpose of this study was to assess drug utilization patterns of fluticasone propionate (FP)/salmeterol (SAL) combination (FSC) and SAL over the 7-year period of 2005-2011 in patients with asthma as part of the Risk Evaluation and Mitigation Strategies (REMS).. A descriptive, retrospective observational study utilizing national pharmacy data and employer-based claims data to characterize drug utilization patterns.. For patients with asthma, the total number of FSC and SAL dispensings and users of FSC and SAL has declined between 2005 and 2011. During this period, FSC and SAL dispensing for asthma decreased 24% and 76%, respectively, with a more pronounced decline between 2010 and 2011 relative to other years. The total number of patients with asthma who were dispensed FSC has decreased by 10% among adults and by 40% in children and adolescents. While SAL-containing medications decreased, dispensing of FP monotherapy increased 39% during the same 7-year period. The number of patients dispensed FP for asthma has increased 47% in children 4-11 years of age, 72% in adolescents 12-17 years of age, and 6% in adults. SAL use without a controller was infrequent and decreasing, reported by 1.7% and 0.5% of patients with asthma in 2005 and 2011, respectively.. In patients with asthma, use of FSC and SAL decreased between 2005 and 2011, while the use of FP increased. Use of SAL monotherapy was infrequent and declined during the study period. The data suggest that the substantial communication activities have encouraged appropriate prescribing of long-acting β2-adrenergic agonist (LABA).

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Androstadienes; Asthma; Child; Child, Preschool; Drug Combinations; Drug Utilization; Fluticasone-Salmeterol Drug Combination; Humans; Retrospective Studies; Salmeterol Xinafoate; United States; Young Adult

In practice it is logical that inhalers are prescribed only after patients have received training and demonstrated their ability to use the device. However, many patients are unable to use their pressurised metered-dose inhaler devices (pMDIs) correctly. We assessed the relationship between asthma control and patients' ability to use their prescribed pMDIs.. Evaluation of 3,981 (46% male) primary care asthma patient reviews, which included inhaler technique and asthma control, by specialist nurses in primary care in 2009. The paper focuses on people currently prescribed pMDI devices.. Accurate data on reliever and preventer inhaler prescriptions were available for 3,686 and 2,887 patients, respectively. In patients prescribed reliever inhalers, 2,375 (64%) and 525 (14%) were on pMDI alone or pMDI plus spacer, respectively. For those prescribed preventers, 1,976 (68%) and 171 (6%) were using a pMDI without and with a spacer, respectively. Asthma was controlled in 50% of patients reviewed. The majority of patients (60% of 3,686) were using reliever pMDIs, 13% with spacers. Incorrect pMDI use was associated with poor asthma control (p<0.0001) and more short burst systemic steroid prescriptions in the last year (p=0.038). Of patients using beclometasone (the most frequently prescribed preventer drug in our sample), significantly more of those using a breath-actuated pMDI device (p<0.0001) and a spacer (p<0.0001) were controlled compared with those on pMDIs alone.. Patients who are able to use pMDIs correctly have better asthma control as defined by the GINA strategy document. Beclometasone via a spacer or breath-actuated device resulted in better asthma control than via a pMDI alone. Patients prescribed pMDIs should be carefully instructed in technique and have their ability to use these devices tested; those unable to use the device should be prescribed a spacer or an alternative device such as one that is breath-actuated.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Patient Education as Topic; Pregnadienediols; Retrospective Studies; Self Administration; Treatment Outcome; Young Adult

Efficacy trials suggest that extra-fine particle beclometasone dipropionate-formoterol (efBDP-FOR) is comparable to fluticasone propionate-salmeterol (FP-SAL) in preventing asthma exacerbations at a clinically equivalent dosage. However, switching from FP-SAL to efBDP-FOR has not been evaluated in real-world asthma patients.. The REACH (Real-world Effectiveness in Asthma therapy of Combination inHalers) study investigated the clinical and cost effectiveness of switching typical asthma patients from FP-SAL to efBDP-FOR.. A retrospective matched (1:3) observational study of 1,528 asthma patients aged 18-80 years from clinical practice databases was performed. Patients remaining on FP-SAL (n=1,146) were compared with those switched to efBDP-FOR at an equivalent or lower inhaled corticosteroid (ICS) dosage (n=382). Clinical and economic outcomes were compared between groups for the year before and after the switch. Non-inferiority (at least equivalence) of efBDP-FOR was tested against FP-SAL by comparing exacerbation rates during the outcome year.. efBDP-FOR was non-inferior to FP-SAL (adjusted exacerbation rate ratio 1.01 (95% CI 0.74 to 1.37)). Switching to efBDP-FOR resulted in significantly better (p<0.05) odds of achieving overall asthma control (no asthma-related hospitalisations, bronchial infections, or acute oral steroids; salbutamol ≤200μg/day) and lower daily short-acting β2-agonist usage at a lower daily ICS dosage (mean -130μg/day FP equivalents; p<0.001). It also reduced mean asthma-related healthcare costs by £93.63/patient/year (p<0.001).. Asthma patients may be switched from FP-SAL to efBDP-FOR at an equivalent or lower ICS dosage with no reduction in clinical effectiveness but a significant reduction in cost.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Drug Substitution; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Health Services; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

National asthma treatment guidelines recommend low/medium-dose inhaled corticosteroids (ICSs) as initial therapy in mild asthma patients. However, low doses of a fixed-dose combination of ICS and long-acting β-agonists are sometimes used. This study compares asthma-related outcomes and health care utilization and costs in clinical practice in patients starting fluticasone propionate 100 μg and salmeterol 50 μg via Diskus (FSC) or mometasone furoate (MF).. A retrospective cohort study was conducted to compare asthma-related outcomes in asthma patients who received FSC or MF, using a large health insurance claims dataset spanning January 2004-December 2008. Patients with ≥1 claim with an asthma ICD-9-CM diagnosis code and ≥2 FSC or MF prescriptions were included, stratified into FSC or MF groups by study drug received first and matched using propensity score.. A total of 18,283 patients met inclusion criteria (14,044 FSC and 4239 MF); 3799 matched pairs were identified (mean follow-up: FSC 548 days, MF 537 days). FSC patients had lower risk of asthma-related exacerbation (Hazard ratio = 0.88, 95% CI 0.81-0.95, p = .002), defined as either asthma-related emergency department (ED) visits/hospitalizations or receipt of systemic corticosteroids (SCSs); fewer SCS claims (mean 0.28 vs. 0.33, p = .021); and fewer asthma-related physician office (PO) and hospital outpatient (HO) visits (mean 1.17 vs. 1.63, p < .001). However, asthma-related ED visits were higher with FSC (p = .004), and FSC patients had higher total costs of asthma-related health care ($953 vs. $862, p = .002).. In asthma patients initiating ICS therapy, MF had lower asthma-related ED visits. However, FSC may reduce the use of SCS and asthma-related PO/HO visits.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Cohort Studies; Delivery of Health Care; Drug Combinations; Emergency Service, Hospital; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Medication Adherence; Middle Aged; Mometasone Furoate; Pregnadienediols; Proportional Hazards Models; Retrospective Studies; United States; Young Adult

Topics: Albuterol; Androstadienes; Asthma; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Smoking

Asthma is a chronic disease characterized by acute symptomatic episodes with variable severity and duration. Pharmacological asthma management aims to achieve and maintain control without side effects, thus improving quality of life and reducing the economic impact. Recently, a clinical trial showed the non-inferiority of beclomethasone/formoterol (BDP/F) versus fluticasone propionate/salmeterol (FP/S) in adults with moderate to severe persistent asthma. However, this study did not provide evidence on costs and did not quantify quality-of-life parameters.. The objective of the present study was to assess the cost effectiveness and cost utility of BDP/F versus FP/S in patients with moderate to severe asthma from the perspective of the Italian National Health Service (NHS).. A Markov model (MM) was used, with five health states for the different levels of asthma control: successful control, sub-optimal control, outpatient-managed exacerbation, inpatient-managed exacerbation, and death. Model data were derived from the ICAT SE study and from expert panels. Three outcomes were considered: time spent in successful control state, costs and quality-adjusted life-years (QALYs).. The model shows that BDP/F treatment led to a slight increase of weeks in successful control compared with FP/S, with a lower cost. The probabilistic sensitivity analysis highlights that in 64% and 68% of the Monte Carlo simulations, BDP/F outperformed FP/S in terms of weeks in successful control and QALYs. Considering the expected cost of the two strategies, in 90% of simulations BDP/F was the least expensive choice. In particular, BDP/F was cost saving as compared with FP/S in about 63% and 59% of simulations as shown by the cost-utility and cost-effectiveness analysis, respectively.. Overall, from the Italian NHS perspective, BDP/F treatment is associated with a reduction in cost and offers a slight increase of effectiveness in terms of weeks spent in successful control and QALYs.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Computer Simulation; Cost-Benefit Analysis; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Italy; Markov Chains; Models, Economic; Quality-Adjusted Life Years; Severity of Illness Index

Fixed combination fluticasone-salmeterol is the most used anti-inflammatory asthma treatment in North America, yet no studies report the actual respiratory tract dose or the distribution of drug within the lungs. Inflammation due to asthma affects all airways of the lungs, both large and small. Inhaled steroid delivery to airways results from a range of drug particle sizes, with emphasis on smaller drug particles capable of reaching the peripheral airways. Previous studies suggested that smaller drug particles increase pulmonary deposition and decrease oropharyngeal deposition.. To characterize the dose of fluticasone-salmeterol hydrofluoroalkane-134a (HFA) (particle size, 2.7 μm) delivered to asthmatic patients and examine the drug distribution within the lungs. The results were compared with the inhalation delivery of HFA beclomethasone (particle size, 0.7 μm).. A crossover study was conducted in asthmatic patients with commercial formulations of fluticasone-salmeterol and HFA beclomethasone radiolabeled with technetium Tc 99m. Deposition was measured using single-photon emission computed tomography/computed tomography gamma scintigraphy.. Two-dimensional planar image analysis indicated that 58% of the HFA beclomethasone and 16% of the fluticasone-salmeterol HFA were deposited in the patient's lungs. The oropharyngeal cavity and gut analyses indicated that 77% of the fluticasone-salmeterol HFA was deposited in the oropharynx compared with 35% of the HFA beclomethasone.. The decreased peripheral airway deposition and increased oropharyngeal deposition of fluticasone-salmeterol HFA was a result of its larger particle size. The smaller particle size of HFA beclomethasone allowed a greater proportion of lung deposition with a concomitant decrease in oropharyngeal deposition.

Topics: Administration, Inhalation; Aerosol Propellants; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Lung; Particle Size; Radionuclide Imaging

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Albuterol; Androstadienes; Asthma; Child; Child, Preschool; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Growth; Humans; Hydrocortisone; Male

Topics: Airway Resistance; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchi; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Muscle, Smooth; Muscle, Smooth, Vascular; Salmeterol Xinafoate; Vasodilation

Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary.. Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients.. 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs.. Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our conclusions.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cost Control; Costs and Cost Analysis; Dose-Response Relationship, Drug; Drug Combinations; Drug Substitution; Ethanolamines; Fees, Pharmaceutical; Female; Fluticasone-Salmeterol Drug Combination; Humans; Hungary; Linear Models; Male; Middle Aged; Patient Compliance; Reference Standards; Retrospective Studies; World Health Organization; Young Adult

Whether small airways dysfunction persists in patients with asthma receiving standard community treatment is unknown. Impulse oscillometry (IOS) is a sensitive measure of small airways function.. To assess the degree of small airways dysfunction in a cross-section of patients with community-managed asthma.. We analyzed primary care referral data from patients with persistent asthma (n = 378) receiving standard community therapy, screened using spirometry and IOS. We compared patients by British Thoracic Society asthma treatment step (2-4).. Step 2 patients were not different from step 3 patients receiving long-acting beta-agonist (LABA). Step 4 patients differed from step 2 by: higher inhaled corticosteroid (ICS) dose (P < .0001); lower forced expiratory volume in 1 second (FEV(1)%; P = .02) and forced mid-expiratory flow (FEF(25-75%); P = .001); higher frequency of resonance (F(res); P = .02) and peripheral airway resistance (R5-R20; P = .006); whereas for steps 3 vs 4 there were differences in F(res) (P < .05) and R5-R20 (P = .006). There were high proportions of abnormality for R5-R20 (>0.03 kPa/L/s) at steps 2, 3, and 4, respectively: 64.6%, 63.5%, and 69.9%. Step 2 patients receiving extra-fine particle ICS demonstrated lower total airway resistance at 5Hz (R5) vs patients receiving standard ICS (124.1% vs 138.3%, P < .05), with no difference in FEV(1). At step 4, R5 remained elevated at 141.3% despite concomitant LABA, with only 2.4% using extra-fine ICS.. Persistent small airways dysfunction occurs despite treatment at steps 2 through 4 of current asthma guidelines. Extra-fine ICS may reduce airway resistance at step 2. Prospective studies with extra-fine ICS ± LABA at steps 2 through 4 are required to discern whether improving small airways function might result in long-term improved control.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Airway Resistance; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Oscillometry; Respiratory Function Tests; Respiratory System; Spirometry

National asthma treatment guidelines recommend either the use of inhaled corticosteroids (ICS) or ICS in combination with a long-acting bronchodilator for the treatment of moderate to severe asthma. Even though asthma is common among older adults, few studies have assessed the differences in effectiveness between these two recommended therapies in patients over 65 years of age.. The aim of this study was to assess the association of the fluticasone-salmeterol combination (FSC) or ICS initiation on asthma-related events in Medicare-eligible asthma patients.. This was a retrospective observational study using a large health claims database (July 1, 2001 to June 30, 2008). Subjects 65 to 79 years of age with 12-month preindex and 3- to 12-month postindex eligibility, an asthma diagnosis (ICD-493.xx), and with 1 or more FSC or ICS claims at index were included. Subjects with an FSC or ICS claim in the preindex and any claim for chronic obstructive pulmonary disease were excluded. Subjects were observed until they had an event (emergency department [ED] inpatient hospitalization [IP], combined IP/ED or oral corticosteroid [OCS] use) or were no longer eligible in the database, whichever came first. Cox proportional hazards regression was used to assess risk of an asthma-related event (IP, ED, or IP/ED). Baseline characteristics (age, sex, region, index season, comorbidities, preindex use of short-acting β-agonists, OCS, other asthma controllers, and asthma-related ED/IP visits) were independent covariates in the model.. A total of 10,837 met the criteria (4843 ICS and 5994 FSC). Age (70.4 and 70.5 years, respectively) and the percentage of female subjects (65.5% and 64.8%, respectively) were similar. Asthma-related events were also similar at baseline. Postindex unadjusted rates occurring after >30 days were ED (1.8% vs 1.5%, P = 0.18), IP (2.7% vs 1.7%, P < 0.001), and ED/IP (4.1% vs 2.8%, P < 0.001) for ICS and FSC, respectively. Subjects who received FSC were associated with a 32% (adjusted HR = 0.68; 95% CI, 0.51-0.91) lower risk of experiencing an IP visit and a 22% (HR = 0.78; 95% CI, 0.62-0.98) lower risk of experiencing an ED/IP visit. No differences were observed for ED visits (HR = 0.94; 95% CI, 0.68-1.29).. In Medicare-eligible asthma patients, FSC use was associated with lower rates of asthma-related serious exacerbations compared with ICS.

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Databases, Factual; Drug Combinations; Emergency Service, Hospital; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Hospitalization; Humans; Male; Medicare; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; United States

Asthma is one of the most common chronic diseases in children. It is attributable to complicated coactions between various genetic factors and environmental allergens.. We attempt to unfold the mechanism of asthmatic disorder and research the molecular mechanism of Seretide on asthmatic disease.. Using the GSE31773 microarray datasets downloaded from Gene Expression Omnibus database, we first screened the differentially expressed genes between healthy control and asthmatic samples cells based on classical t-test and false discovery rate < 0.05 as significant threshold. The underlying molecular mechanisms were investigated by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, the crosstalk network of pathways was also constructed.. A total of 2011 differentially expressed genes were obtained by comparing asthmatic sample treated with Seretide and healthy controls. A total of 403 differentially expressed genes were collected between asthma samples untreated by Seretide and healthy sample controls. The enriched pathway of differentially expressed genes included signal transduction disorder (such as TGF-beta signaling pathway) and metabolism disorder (such as Phenylalanine metabolism). There were 27 pathway crosstalk pairs among 13 pathways.. Our findings will help to clarify the molecular mechanism of Seretide and offer advices for asthma pathogenesis, Seretide therapy and follow-up treatment.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Case-Control Studies; Databases, Genetic; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Gene Expression; Gene Expression Profiling; Humans; Models, Genetic; Molecular Targeted Therapy; Signal Transduction

Selection of inhaler device type appears to influence real-world effectiveness of inhaled corticosteroids (ICS), but data are lacking on the role of inhaler device in ICS and long-acting β2-agonist (LABA) combination therapy for asthma.. This retrospective matched cohort study compared 1-year asthma outcomes for UK patients initiating fixed-dose combination (FDC) fluticasone-salmeterol delivered by pressurised metered-dose inhaler (pMDI) versus dry powder inhaler (DPI). Patients with asthma aged 4-80 years receiving a first prescription for FDC fluticasone-salmeterol by pMDI or DPI were matched on baseline demographic and asthma severity measures. Co-primary outcomes were asthma control (a composite measure comprising no recorded hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory infection) and exacerbation rate.. Compared with the DPI cohort (n = 1567), patients in the pMDI cohort (n = 1567) had significantly greater odds of achieving asthma control during the outcome year (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.01 to 1.40). Exacerbation rate was lower but not significantly in the pMDI cohort (adjusted rate ratio for pMDI cohort, 0.82; 95% CI 0.66 to 1.00). The odds of treatment success (defined as no exacerbations and no change in asthma therapy) was significantly greater in the pMDI cohort (OR 1.23; 95% CI, 1.07 to 1.42).. For UK primary care patients, pMDIs appear to achieve better asthma control outcomes than DPIs for delivery of FDC fluticasone-salmeterol. Pragmatic trials are needed to further investigate real-world outcomes with different inhaler devices for combination therapy.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Child; Child, Preschool; Disease Progression; Drug Combinations; Drug Therapy, Combination; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Middle Aged; Research Design; Retrospective Studies; Treatment Outcome; United Kingdom; Young Adult

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Cushing Syndrome; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Young Adult

The relationship between airway structural changes (remodeling) and airways hyperresponsiveness (AHR) is unclear. Asthma guidelines suggest treating persistent asthma with inhaled corticosteroids and long acting beta-agonists (LABA). We examined the link between physiological function and structural changes following treatment fluticasone and salmeterol separately or in combination in a mouse model of allergic asthma.. BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by six daily inhalation exposures. Treatments included 9 daily nebulized administrations of fluticasone alone (6 mg/ml), salmeterol (3 mg/ml), or the combination fluticasone and salmeterol. Lung impedance was measured following methacholine inhalation challenge. Airway inflammation, epithelial injury, mucus containing cells, and collagen content were assessed 48 hours after OVA challenge. Lungs were imaged using micro-CT.. Treatment of allergic airways disease with fluticasone alone or in combination with salmeterol reduced AHR to approximately naüve levels while salmeterol alone increased elastance by 39% compared to control. Fluticasone alone and fluticasone in combination with salmeterol both reduced inflammation to near naive levels. Mucin containing cells were also reduced with fluticasone and fluticasone in combination with salmeterol.. Fluticasone alone and in combination with salmeterol reduces airway inflammation and remodeling, but salmeterol alone worsens AHR: and these functional changes are consistent with the concomitant changes in mucus metaplasia.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Animals; Asthma; Disease Models, Animal; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Lung; Mice; Mice, Inbred BALB C

We commenced to estimate the economic impact of salmeterol/fluticasone combination (SFC) therapy compared to fluticasone propionate (FP) therapy for asthma control in Japanese patients. A Markov model with five health states, developed by Price in 2002, was used. 1-week transition probabilities among status of asthma management were obtained from literature and epidemiological data from public data base. Direct cost for treatment was estimated from Japan medical fee schedule. Cost and effectiveness were not discounted due to 12-week simulation by the model. Univariate sensitivity analyses were undertaken to examine the main variables affecting cost-effectiveness. Probabilistic analysis was also undertaken to discuss statistical argument and to provide information for decision-making. In this analysis, the model was run over a 12-week period of time using transition probabilities. The results showed that treatment with SFC resulted in a higher proportion of totally controlled weeks per patient than treatment with FP (65.0 vs. 49.5%; incremental effectiveness by 15.5%), and lower mean direct asthma management costs ( yen168 702 vs. yen227 820). Probabilistic sensitivity analysis, conducted to assess robustness of the above base case result, showed that in the 95% of cases SFC was dominant (more effective and less costly) to FP. It suggested that SFC will be the most cost-effective therapy for asthma control. It would, however, be required to further evaluate cost-effectiveness of SFC in long-term observation.

Topics: Albuterol; Androstadienes; Asian People; Asthma; Cost-Benefit Analysis; Drug Combinations; Evidence-Based Medicine; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Markov Chains; Models, Statistical

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Nebulizers and Vaporizers; Therapeutic Equivalency

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Drug Interactions; Fluticasone-Salmeterol Drug Combination; Humans

When an adequate standard of asthma control is not achieved with maintenance treatment of inhaled corticosteroids, the addition of a long-acting beta(2)-adrenergic receptor agonist (LABA) bronchodilator is recommended. Using a combination product, salmeterol/fluticasone propionate (Seretide or Advair) or budesonide/formoterol (Symbicort) is preferred for convenience and avoids any risk that LABA might be used as monotherapy. As formoterol has a rapid onset of bronchodilator effect, the budesonide/formoterol combination can be used for both the maintenance and reliever components of asthma treatment (Symbicort SMART) and this is endorsed as an effective treatment by the Global Initiative for Asthma. The efficacy of this approach has been evaluated in a series of well conducted, controlled studies. Current control of asthma symptoms is improved or achieved with reduced total dose administration with Symbicort SMART compared with any reasonable alternate option. In every study, the risk of severe exacerbations was lower with Symbicort SMART than comparator treatment. Patients who benefit to the greatest extent are those with evidence of more severe asthma and greater exacerbation risk. When initiated in suitable patients in conjunction with appropriate education, Symbicort SMART is dominant in pharmacoeconomic terms. Symbicort SMART delivers improved asthma outcomes with lower treatment and social costs than any alternative.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Controlled Clinical Trials as Topic; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Humans

The use of dry-powder inhalers (DPIs) to administer respiratory medicines is increasing, and new DPIs are likely to be developed because of expiring patents. However, there is considerable debate concerning the extent to which DPIs are interchangeable without altering disease control or the safety profile of the treatment.. This study was designed to compare the pharmacokinetic (PK), pharmacodynamic (PD), efficacy, and safety data for 2 DPIs delivering a combination of salmeterol 50 microg plus fluticasone propionate (FP) 250 microg (SFC 50/250) to investigate assumptions of bioequivalence.. Three studies compared SFC 50/250 delivery using a reservoir powder inhalation device (RPID) and a Diskus multiple-dose inhaler: an in vitro assessment of fine-particle-mass (FPM) profiles of the emitted doses; a PK/PD study of SFC 50/250 administered in two 14-day crossover treatment periods to 22 adults with moderate, persistent asthma to determine the equivalence of the RPID and Diskus inhaler in terms of drug delivery and systemic exposure; and a 12-week clinical efficacy and safety study of SFC 50/250 in 270 patients > or =12 years of age with moderate, persistent asthma to assess the equivalence of the RPID and Diskus inhaler based on peak expiratory flow (PEF) rates. FPM was summed from the quantity of active pharmaceutical ingredient deposited on stages 1 to 5 of a cascade impactor, representing an aerodynamic particle size range of 0.8 to 6.2 microm. Systemic exposure to SFC 50/250 was declared no greater with RPID than with the Diskus inhaler if the upper limit of the 90% CI for the ratio of FP AUC for the 2 devices was below the upper limit of the equivalence range (ie, <1.25). Adverse events, clinical laboratory test results, and vital signs were recorded throughout the 2 clinical studies.. In vitro, mean FPM values for the RPID and Diskus inhaler, respectively, were 13.1 and 12.8 microg/dose for salmeterol (P = NS) and 66.8 and 66.2 microg/dose for FP (P = NS). The only notable differences were mean FP for particle sizes 2.3 to 3.2 microm (21.4 microg/dose for RPID, 25.6 microg/dose for Diskus) and for sizes 4.0 to 6.2 microm (17.3 microg/dose for RPID, 11.7 microg/dose for Diskus). In the PK/PD study, there were 22 patients (16 men and 6 women), most (86%) of whom were white. Mean (SD) age was 26.0 (5.0) years (range, 19-35 years), and mean (SD) weight was 67.3 (8.9) kg. The 2 inhalers did not meet the criteria for declaring bioequivalence: estimated ratios (RPID:Diskus) were 2.00 (90% CI, 1.56 to 2.55) for FP AUC up to the time point of next dosing and 1.92 (90% CI, 1.64 to 2.25) for salmeterol maximum observed plasma concentration at the end of the dosing interval (at steady state). Urine cortisol (0-24 hours) was significantly lower for the RPID than for the Diskus inhaler (ratio, 0.74 [95% CI, 0.57 to 0.96]; P = 0.026); no significant difference in plasma cortisol was noted between the 2 inhalers (ratio, 0.85 [95% CI, 0.7 to 1.04]). A small but statistically significant increase in maximum heart rate (5 beats/min) was noted in the RPID group (ratio, 1.05 [95% CI, 1.01 to 1.10]; P = 0.029). No notable differences in other PD end points were observed. Drug-related adverse events occurred in both groups (2 [dysphagia and tremor] in the RPID group and 3 [2 cases of dysphonia, 1 case of mucous-membrane irritation] in the Diskus group). There were 270 patients (136 females, 134 males) in the clinical efficacy and safety study, most (94%) of whom were white; mean (SD) age was 37.2 (17.0) years (range, 11-77 years) in the RPID group and 35.4 (17.2) years (range, 12-77 years) in the Diskus group. The RPID and the Diskus inhaler met the predefined equivalence criteria (+/-15 L/min) in terms of mean change in morning PEF from baseline: 3.9 L/min (95% CI, -3.1 to 11.0). The 2 SFC 50/250 inhalers were well tolerated; the most frequently reported adverse event was bronchitis, reported by 12% of the patients in the RPID group and 9% of those in the Diskus group. The only serious adverse event, which occurred in the RPID group and was related to bronchial infection, was considered unrelated to treatment.. In vitro particle size distribution data were potentially superimposable for the RPID and the Diskus inhaler. The 2 devices were considered to be clinically equivalent in terms of mean morning PEF but were not considered equivalent in terms of PK systemic exposure. The 2 SFC 50/250 inhalers were well tolerated and had comparable safety profiles; no serious adverse events were attributed to the study product.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Area Under Curve; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Therapeutic Equivalency; Young Adult

Although current National Asthma Education and Prevention Program (NAEPP) guidelines indicate low-dose inhaled corticosteroid (ICS) monotherapy as the preferred treatment for patients with mild persistent asthma, many patients receive ICS and long-acting beta(2)-agonist (LABA) combinations. The objective of the current study was to evaluate asthma-related charges in patients with mild asthma who began treatment with mometasone furoate (MF) versus those who began treatment with a fluticasone propionate/salmeterol (FPS) combination.. This retrospective administrative claims database analysis collected data from the 365-day periods before (preindex period) and after (postindex period) the study index date from patients with mild asthma aged 12 to 65 years who began treatment with MF or FPS. Asthma-related inpatient, outpatient, pharmaceutical, and total charges; exacerbations; short-acting beta(2)-agonist (SABA) canister claims; and adherence to therapy were assessed. Matched cohorts of MF and FPS patients were compared using multivariate generalized linear regression models.. Among matched MF (n = 4094) and FPS (n = 4094) cohorts, MF patients had significantly lower postindex asthma-related total charges ($2136 vs $2315, respectively; P = 0.0003), lower pharmaceutical charges ($727 vs $925, respectively; P < 0.0001), fewer exacerbations (0.14 vs 0.16, respectively; P = 0.0306), fewer SABA canister claims (0.9 vs 1.0, respectively; P < 0.0001), and greater adherence measured by prescription fills (3.0 vs 2.8, respectively; P < 0.0001). Asthma-related inpatient charges, outpatient charges, and adherence measured by percent of days covered were not significantly different between treatment cohorts. Limitations included a lack of additional ICS and ICS/LABA therapies, a lack of pediatric patients, and the general limitations associated with retrospective database analyses (e.g., no patient records).. These data suggest that MF may be more cost-effective than FPS for the treatment of mild asthma. To effectively and efficiently manage asthma, it is important for clinicians to follow current NAEPP guidelines, which indicate ICS monotherapy as preferred treatment for mild persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Case-Control Studies; Child; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Health Resources; Humans; Male; Middle Aged; Mometasone Furoate; Multivariate Analysis; Pregnadienediols; Retrospective Studies; Young Adult

An association between salmeterol use and serious asthma episodes or asthma-related mortality has been noted in 2 clinical trials; however, a causal relationship has not been established. To date, observational studies have not replicated this finding.. To examine the relationship between number of prescriptions dispensed of salmeterol-containing products and inhaled corticosteroid (ICS)-containing products and the rates of asthma-related hospitalizations and mortality in the United States.. In this ecologic study, annual age-adjusted rates of asthma-related hospitalization and asthma-related mortality from US population-based sources were graphed alongside annual number of prescriptions dispensed of salmeterol- and ICS-containing products by year from 1991 to 2004. We computed the Spearman rank correlations between number of prescriptions dispensed and serious events (asthma-related hospitalization rate, number of hospitalizations, asthma-related mortality rate, and number of asthma deaths).. During more than 14 years, while number of prescriptions dispensed of salmeterol-containing and ICS-containing products increased, age-adjusted asthma-related mortality rates declined and asthma-related hospitalization rates remained relatively stable. The number of asthma-related deaths has decreased steadily since the mid-1990s.. This study provides population-level evidence that asthma-related death rates declined and asthma-related hospitalization rates remained relatively constant for more than 14 years during a period of improvements in asthma management per treatment guidelines, including increased use of maintenance medications, such as ICSs and salmeterol.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Centers for Disease Control and Prevention, U.S.; Drug Combinations; Drug Utilization; Fluticasone-Salmeterol Drug Combination; Health Care Surveys; Hospitalization; Humans; National Center for Health Statistics, U.S.; Salmeterol Xinafoate; Survival Rate; United States; Vital Statistics

To identify the relationship between resource utilization and treatment of asthma in subjects who were first time users of controller therapies, either fluticasone propionate (FP) and salmeterol delivered in a single Diskus device (FSC) or FP monotherapy.. A retrospective, observational cohort analysis evaluated pharmacy and medical claims from subjects from a commercial managed-care database, which is similar in makeup to the US privately insured population, with a diagnosis of asthma and ≥1 prescription for FSC or FP dispensed from 1/1/2001 to 4/30/2005. Outcomes of interest were asthma-related emergency department (ED) visits, inpatient (IP) visits, and a combined outcome (IP or ED visits). Predicted rates of asthma-related and all-cause intubations were also reported for each cohort. Multivariate analysis of events was conducted using logistic regression and Cox proportional hazard regression. All outcomes were adjusted for differences in baseline characteristics.. There were 58 270 subjects identified (FSC, n = 42 466; FP, n = 15 804). Mean age was 37.65 years and 35.75% was female. The use of FSC was associated with lower risk of having an asthma-related ED visit (adjusted OR 0.79; 95% CI, 0.72-0.87) and an asthma-related ED/IP visit (OR 0.80; 95% CI, 0.73-0.88). Asthma-related ED and ED/IP rates were also significantly lower for FSC than for FP. There were no differences observed in post-index asthma-related intubations rates.. In this observational study using a large managed-care database, subjects treated with FSC were at significantly less risk for developing serious asthma exacerbations and had lower resource utilization than a cohort of subjects treated with FP. This is clinically meaningful despite the inherent limitations of these types of observational studies.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Asthma; Cohort Studies; Disease Progression; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Observation; Retrospective Studies; Treatment Outcome; Young Adult

Asthma management guidelines state that a low-dose inhaled corticosteroid (ICS) is the preferred treatment for mild persistent asthma and that coadministration of a long-acting beta(2)-agonist (LABA) should be reserved for patients whose asthma is uncontrolled by single-entity ICS. However, it appears that many patients in the United States with mild persistent asthma are initially treated with combinations of fluticasone propionate/salmeterol (FPS).. The aim of this study was to examine whether use of FPS was consistent with asthma management guidelines.. A commercial insurance database was analyzed retrospectively to identify patients aged 12 to 62 years who had >or=1 pharmacy claim for FPS between October 1, 2004, and September 30, 2006. An index date corresponding to the date of the first FPS pharmacy claim was assigned to each patient. Medical and pharmacy claims data were analyzed for the 365-day period before the index date (preindex period). The severity of patients' asthma was inferred from their history of claims. Patients were identified as having more severe asthma if, during the preindex period, they either received >365 doses of short-acting beta(2)-agonists (SABAs), an oral corticosteroid (OCS), or an emergency department (ED) asthma visit with an OCS prescription, or were hospitalized for their asthma.. Among 87,459 patients with new FPS claims, 60.8% were female, and the mean age was 37.3 years. Of these patients, 60,453 (69.1%) had no preindex ICS pharmacy claim or claims that would indicate moderate or severe asthma. In the preindex period, only 6.3% had received an ICS, 7.4% had >365 SABA doses, 22.7% had used an OCS, 1.1% had an ED visit with an OCS prescription, and 1.5% had been hospitalized.. More than two thirds of the patients who initiated FPS treatment had neither received an ICS prescription before their first FPS pharmacy claim nor had evidence of asthma severity that would appear to warrant the use of an ICS/LABA combination.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Drug Utilization; Female; Fluticasone-Salmeterol Drug Combination; Humans; Insurance Claim Review; Insurance Coverage; Insurance, Pharmaceutical Services; Male; Middle Aged; Retrospective Studies; Severity of Illness Index

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Smoking

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Treatment Outcome

Monitoring was required for the introduction of non-chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) to ensure that there were no unexpected adverse events due to the new products. A postmarketing surveillance study has been conducted to evaluate the introduction of the MDI Seretide Evohaler (hydrofluoroalkane-134a inhaler containing salmeterol and fluticasone propionate).. To summarise the modified prescription-event monitoring (PEM) study conducted to evaluate the introduction of Seretide Evohaler and discuss the relevance of this type of study towards pharmacovigilance risk-management planning.. Modified PEM methodology was used to examine the introduction of Seretide Evohaler into general practice in England. Patients were identified from the first National Health Service prescriptions dispensed in England for Seretide Evohaler. One postal questionnaire was sent to the prescribing doctor, requesting demographic information, severity of the indication, concomitant medication for this condition, smoking history, event data 3 months prior to and 3 months after the first prescription for Seretide Evohaler and also reason for stopping if it had been stopped. Pregnancies, deaths and selected events were followed up. Incidence density ratios were calculated to compare event rates 3 months prior to and 3 months after the introduction of Seretide Evohaler. A matched cohort analysis examined oral corticosteroid use and hospital admissions between the pre- and post-exposure periods.. The cohort comprised 13,464 patients prescribed Seretide Evohaler, with a response rate of 62%. There was no significant difference in the length of courses of oral corticosteroid use when the pre- and post-exposure periods were compared. A matched cohort analysis showed there was no increase in the use of oral corticosteroids (relative risk [RR] 0.95; 95% CI 0.90, 0.99) or hospital admissions in the post-exposure period (RR 0.87; 95% CI 0.73, 1.04). When the number of patients with events were compared for the periods 3 months before and 3 months after exposure, fewer events were reported in the post-exposure period. There were 64 patients who experienced adverse events within an hour of using Seretide Evohaler, including one report of paradoxical bronchospasm and one of myocardial infarction with fatal outcome that were both assessed as possibly related to treatment.. The results of the study suggest that the introduction of Seretide Evohaler was generally well tolerated. The modified methodology has allowed a comparison of the event rates before and after the introduction of this CFC-free inhaler into general practice.

Topics: Adult; Aerosol Propellants; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; England; Female; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Pregnancy; Product Surveillance, Postmarketing; Pulmonary Disease, Chronic Obstructive

Topics: Acetates; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Cyclopropanes; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Respiratory Function Tests; Sulfides

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation.. Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined.. The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal.. Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

Topics: Albuterol; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Asthma; Bronchoalveolar Lavage; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Respiratory Syncytial Virus Infections; Salmeterol Xinafoate

To explore asthma symptom perception and the relationship between asthma symptom perception and adherence to asthma treatment.. Adult patients (N=120) of asthma/allergy specialty clinics, taking Advair as a controller medication, were enrolled in this cross-sectional descriptive study.. Ninety-seven participants completed 4 weeks of daily diaries to assess subjective symptom perception and measured peak expiratory flow rates (PEFR), both done twice daily. Individual perceptual accuracy scores (PAS) were determined by correlating the subjective symptom perception scores with the PEFRs. Measures included demographic variables, illness identity (personal control and treatment control, consequences, and timeline-cyclical subscales of the IPQ-R), asthma severity (FEV1 percentage) and a single-item indicator of perceived asthma severity. Adherence was measured by the Medication Adherence Report Scale (MARS) and by an Advair dose count (percentage of doses taken as prescribed).. Independent t tests comparing adherence rates of good versus poor perceivers were not significant, using either the percentage Advair dose count or the MARS. Multiple regression analyses showed that years with asthma, illness identity, and peak flow variability were all significant explanatory variables for perceptual accuracy.. Peak flow variability adds complexity to the relationship between perceptual accuracy and adherence that warrants further investigation.

Topics: Adaptation, Psychological; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Awareness; Cross-Sectional Studies; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Health Knowledge, Attitudes, Practice; Humans; Internal-External Control; Male; Middle Aged; Models, Psychological; Nursing Methodology Research; Patient Compliance; Patient Education as Topic; Peak Expiratory Flow Rate; Regression Analysis; Self Care; Self Concept; Severity of Illness Index; Sick Role; Surveys and Questionnaires

Due to common features of asthma and allergic rhinitis, a single therapeutic approach to treating both of these conditions has been proposed.. To compare and contrast the use of rhinitis medications in a group of children initiating various controller therapies for asthma.. A retrospective, observational study using an integrated managed care database of children aged 4-17 years with an initial medical claim for asthma and an initial pharmacy claim for fluticasone propionate (FP) and salmeterol in a single inhaler (FSC), FP alone, montelukast (MON), or combination FP + MON. Outcomes included the percentage of children initiating controller asthma therapy with prescriptions for non-sedating antihistamine (NSA) and intranasal corticosteroids (INCS) and the mean number of prescriptions for NSA and INCS.. A total of 5247 children were included. The percentage of children who filled prescriptions for NSA or INCS and the mean number of prescriptions dispensed was similar among children treated with FSC, FP, MON, and FP + MON. There were no significant differences in the relative risk of dispensing either a NSA or INCS across cohorts. Observational studies are limited by their use of administrative data and lack of access to patient records.. Children started on common asthma controller therapy are frequent users of rhinitis medications. The quantity and frequency of these medications is not different between dispensed asthma regimens.

Topics: Acetates; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cyclopropanes; Drug Combinations; Drug Prescriptions; Fluticasone; Fluticasone-Salmeterol Drug Combination; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Leukotriene Antagonists; Quinolines; Retrospective Studies; Rhinitis; Sulfides

Asthma, owing to its chronic nature, is associated with a substantial economic burden. Healthcare providers need to compare the cost effectiveness of alternative asthma treatment options to ensure that they obtain the best value for money from the resources they control. The objective of the current study was to compare the cost effectiveness of salmeterol/fluticasone propionate in combination with fluticasone propionate plus montelukast in patients with symptomatic asthma uncontrolled with inhaled corticosteroid (ICS) monotherapy.. Direct healthcare resource data were prospectively collected during a double-blind, randomized, 12-week clinical study of inhaled salmeterol/fluticasone propionate 50/100 microg twice daily (n = 356) and inhaled fluticasone propionate 100 microg twice daily plus oral montelukast 10mg daily (n = 369). Resources were costed in Dutch guilders (NLG) from the perspective of The Netherlands healthcare system using 1999/2000 prices, but have been presented in US dollars and euros. The primary effectiveness measure was the proportion of successfully treated weeks (based on mean morning PEF values). Secondary measures were episode-free days, symptom-free days, and symptom-free nights.. Salmeterol/fluticasone propionate was more effective than fluticasone propionate plus montelukast as measured by the proportion of successfully treated weeks mean 63.3% vs 39.0%; median difference 25%; p < 0.001). Salmeterol/fluticasone propionate was also more effective than fluticasone propionate plus montelukast according to the secondary effectiveness measures. The mean total direct daily healthcare costs per patient were 16% higher with fluticasone propionate plus montelukast than with salmeterol/fluticasone propionate mainly due to higher drug costs in the former group (2.25 US dollars vs 1.94; 1.92 euro vs 1.66, respectively; the NLG was fixed against the euro at a rate of 1 euro = NLG2.2 on 31 December 1998; 1 US dollars = NLG1.883, June 2003; 1 US dollars= 0.848 euro, June 2003). Incremental cost-effectiveness analyses showed that salmeterol/fluticasone propionate was dominant over fluticasone propionate plus montelukast and sensitivity analyses showed these results to be robust.. Salmeterol/fluticasone propionate is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with symptomatic asthma uncontrolled by ICS.

Topics: Acetates; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Middle Aged; Multicenter Studies as Topic; Netherlands; Quinolines; Randomized Controlled Trials as Topic; Sulfides

The utility of a new therapy, in this instance fluticasone and salmeterol combination (FSC), is determined by multiple uncontrollable factors in individual patients and can be measured by continued use and efficacy over time. Over one year from April 2001, 186 patients with persistent asthma were switched from controller pharmacotherapy to FSC at equidose to prior inhaled corticosteroid. Follow-up data on 171 (92%) indicated 129 (75%) had continued FSC for one year. Compared to the 42 who discontinued FSC, those who continued had significant reduction of asthmatic exacerbations, improved spirometry, and reduced usage of inhaled reliever and systemic corticosteroid.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Middle Aged; Spirometry; Treatment Outcome

Topics: Administration, Inhalation; Albuterol; Anaphylaxis; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Drug Contamination; Fluticasone-Salmeterol Drug Combination; Humans; Lactose; Male; Milk Hypersensitivity; Milk Proteins; Powders

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Meta-Analysis as Topic; Odds Ratio; Salmeterol Xinafoate

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Interprofessional Relations; Pharmacists; Practice Patterns, Physicians'

According to national asthma guidelines, asthma severity can be classified as intermittent, mild, moderate, or severe on the basis of lung function, symptoms, nighttime awakenings, and exacerbations. Although it is widely believed that patients might not remain consistently in any given severity category over time, few studies have examined this directly.. We sought to assess the variability in disease severity-control among patients with persistent asthma who have not yet received an asthma maintenance treatment.. We performed an analysis of asthma severity-control over time in placebo-treated patients (n = 85) from 2 randomized, double-blind, 12-week clinical trials in patients with asthma previously receiving beta(2)-agonists alone. Asthma severity-control was assessed on the basis of morning percent predicted peak expiratory flow, albuterol use, and symptoms.. At baseline, all patients met the criteria for moderate or severe persistent asthma (mean FEV(1) of 64% of predicted value or albuterol use and symptoms on 4.7 and 6.0 days per week, respectively). The mean percentage of treatment weeks that patients met all criteria for intermittent, mild, moderate, and severe asthma were 9%, 14%, 71%, and 6%, respectively. On the basis of morning peak expiratory flow, patients were classified as having intermittent-mild, moderate, or severe disease on 52%, 41%, and 7% of days, respectively. With regard to days per week with albuterol use or asthma symptoms, patients spent 59% and 45% of weeks, respectively, in the intermittent and mild categories.. Asthma control cannot be adequately assessed in many patients by using discrete point-in-time assessments of lung function, short-acting beta-agonist use, or asthma symptoms. This might lead to underestimation of disease severity and contribute to inadequate therapy and, ultimately, asthma morbidity.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Child; Disease Management; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Severity of Illness Index

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Inflammation

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Drug Combinations; Drug Therapy, Combination; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans

Topics: Albuterol; Androstadienes; Asthma; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Global Health; Humans; Multicenter Studies as Topic; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index; Treatment Outcome