(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Chronic-Disease

Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.. To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.. We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021.. We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.. Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.. Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-rel. Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

This is an update of a review published in 2012. A related review "Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates" has been updated as well. Bronchopulmonary dysplasia (BPD) is a serious and common problem among very low birth weight infants, despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent BPD. However, the use of systemic steroids has been associated with serious short- and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract may result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects.. To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator-dependent preterm neonates with birth weight ≤ 1500 g or gestational age ≤ 32 weeks after 7 days of life on the incidence of death or BPD at 36 weeks' postmenstrual age.. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and CINAHL (1982 to 23 February 2017). We also searched clinical trials registers, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.. Randomised or quasi-randomised controlled trials comparing inhaled versus systemic corticosteroid therapy (irrespective of dose and duration) starting after the first week of life in ventilator-dependent very low birth weight infants.. We used standard methodological procedures expected by the Cochrane Collaboration.. We included three trials that involved a total of 431 participants which compared inhaled versus systemic corticosteroids to treat BPD. No new trials were included for the 2017 update.Although one study randomised infants at < 72 hours (N = 292), treatment started when infants were aged > 15 days. In this larger study, deaths were included from the point of randomisation and before treatment started. Two studies (N = 139) randomised and started treatment at 12 to 21 days.Two trials reported non-significant differences between groups for the primary outcome: incidence of death or BPD at 36 weeks' postmenstrual age among all randomised infants. Estimates for the largest trial were Relative risk (RR) 1.04 (95% Confidence interval (CI) 0.86 to 1.26), Risk difference (RD) 0.03 (95% CI -0.09 to 0.15); (moderate-quality evidence). Estimates for the other trial reporting the primary outcome were RR 0.94 (95% CI 0.83 to 1.05), RD -0.06 (95% CI -0.17 to 0.05); (low-quality evidence).Secondary outcomes that included data from all three trials showed no significant differences in the duration of mechanical ventilation or supplemental oxygen, length of hospital stay, or the incidence of hyperglycaemia, hypertension, necrotising enterocolitis, gastrointestinal bleed, retinopathy of prematurity or culture-proven sepsis moderate- to low-quality evidence).In a subset of 75 surviving infants who were enrolled from the United Kingdom and Ireland, there were no significant differences in developmental outcomes at seven years of age between groups (moderate-quality evidence). One study received grant support and the industry provided aerochambers and metered dose inhalers of budesonide and placebo for the same study. No conflict of interest was identified.. We found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator-dependent preterm infants. There was no evidence of difference in effectiveness or adverse event profiles for inhaled versus systemic steroids.A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing adverse events.To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcomes, should be addressed in future studies.

Topics: Administration, Inhalation; Beclomethasone; Bronchopulmonary Dysplasia; Chronic Disease; Dexamethasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory System Agents

Bronchopulmonary dysplasia (BPD) remains an important cause of mortality and morbidity in preterm infants and inflammation plays a significant role in its pathogenesis. The use of inhaled corticosteroids may modulate the inflammatory process without concomitant high systemic steroid concentrations and less risk of adverse effects. This is an update of a review published in 2012 (Shah 2012). We recently updated the related review on "Inhaled versus systemic corticosteroids for treating bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates".. To determine the effect of inhaled versus systemic corticosteroids started within the first 7 days of life on preventing death or BPD in ventilated very low birth weight infants.. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and CINAHL (1982 to 23 February 2017). We searched clinical trials registers, conference proceedings and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.. Randomised or quasi-randomised controlled trials comparing inhaled versus systemic corticosteroid therapy (irrespective of dose and duration) starting in the first seven days of life in very low birth weight preterm infants receiving assisted ventilation.. Clinical outcomes data were extracted and analysed using Review Manager. When appropriate, meta-analysis was performed using typical relative risk (RR), typical risk difference (RD) and weighted mean difference (WMD). Meta-analyses were performed using typical relative risk, typical risk difference (RD), and weighted mean difference with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to benefit or the number needed to harm was calculated. We assessed the quality of evidence was evaluated using GRADE principles.. We included two trials that involved 294 infants. No new studies were included for the 2017 update. The incidence of death or BPD at 36 weeks' postmenstrual age was not statistically significantly different between infants who received inhaled or systemic steroids (RR 1.09, 95% CI 0.88 to 1.35; RD 0.05, 95% CI -0.07 to 0.16; 1 trial, N = 278). The incidence of BPD at 36 weeks' postmenstrual age among survivors was not statistically significant between groups (RR 1.34, 95% CI 0.94 to 1.90; RD 0.11, 95% CI -0.02 to 0.24; 1 trial, N = 206). There was no statistically significant difference in the outcomes of BPD at 28 days, death at 28 days or 36 weeks' postmenstrual age and the combined outcome of death or BPD by 28 days between groups (2 trials, N = 294). The duration of mechanical ventilation was significantly longer in the inhaled steroid group compared with the systemic steroid group (typical MD 4 days, 95% CI 0.2 to 8; 2 trials, N = 294; I² = 0%) as was the duration of supplemental oxygen (typical MD 11 days, 95% CI 2 to 20; 2 trials, N = 294; I² = 33%).The incidence of hyperglycaemia was significantly lower with inhaled steroids (RR 0.52, 95% CI 0.39 to 0.71; RD -0.25, 95% CI -0.37 to -0.14; 1 trial, N = 278; NNTB 4, 95% CI 3 to 7 to avoid 1 infant experiencing hyperglycaemia). The rate of patent ductus arteriosus increased in the group receiving inhaled steroids (RR 1.64, 95% CI 1.23 to 2.17; RD 0.21, 95% CI 0.10 to 0.33; 1 trial, N = 278; NNTH 5, 95% CI 3 to 10). In a subset of surviving infants in the United Kingdom and Ireland there were no significant differences in developmental outcomes at 7 years of age. However, there was a reduced risk of having ever been diagnosed as asthmatic by 7 years of age in the inhaled steroid group compared with the systemic steroid group (N = 48) (RR 0.42, 95% CI 0.19 to 0.94; RD -0.31, 95% CI -0.58 to -0.05; NNTB 3, 95% CI 2 to 20).According to GRADE the quality of the evidence was moderate to low. Evidence was downgraded on the basis of design (risk of bias), consistency (heterogeneity) and precision of the estimates.Both studies received grant support and the industry provided aero chambers and metered dose inhalers of budesonide and placebo for the larger study. No conflict of interest was identified.. We found no evidence that early inhaled steroids confer important advantages over systemic steroids in the management of ventilator-dependent preterm infants. Based on this review inhaled steroids cannot be recommended over systemic steroids as a part of standard practice for ventilated preterm infants. Because they might have fewer adverse effects than systemic steroids, further randomised controlled trials of inhaled steroids are needed that address risk/benefit ratio of different delivery techniques, dosing schedules and long-term effects, with particular attention to neurodevelopmental outcome.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Chronic Disease; Dexamethasone; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory System Agents; Steroids

This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Topical (intranasal) corticosteroids are used with the aim of reducing inflammation in the sinonasal mucosa in order to improve patient symptoms.. To assess the effects of different types of intranasal steroids in people with chronic rhinosinusitis.. The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.. Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing first-generation intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) with second-generation intranasal corticosteroids (e.g. ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, betamethasone sodium phosphate), or sprays versus drops, or low-dose versus high-dose intranasal corticosteroids.. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis (nosebleed). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse event of local irritation. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.. We included nine RCTs (911 participants), including four different comparisons. None of the studies evaluated our first primary outcome measure, disease-specific HRQL. Fluticasone propionate versus beclomethasone dipropionate We identified two small studies (56 participants with polyps) that evaluated disease severity and looked at the primary adverse effect: epistaxis , but no other outcomes. We cannot report any numerical data but the study authors reported no difference between the two steroids. The evidence was of very low quality. Fluticasone propionate versus mometasone furoate We identified only one study (100 participants with polyps) that evaluated disease severity (nasal symptoms scores), which reported no difference (no numerical data available). The evidence was of very low quality. High-dose versus low-dose steroidsWe included five studies (663 participants with nasal polyps), three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children) and two using fluticasone propionate drops (800 µg versus 400 µg). We found low quality evidence relating to disease severity and nasal polyps size, with results from the high-dose and low-dose groups being similar. Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear due to the small size of the improvements.The primary adverse effect, epistaxis , was more common when higher doses were used (risk ratio (RR) 2.06, 95% confidence interval (CI) 1.20 to 3.54, 637 participants, moderate quality evidence). Most of the studies that contributed data to this outcome used a broad definition of epistaxis, which ranged from frank bleeding to bloody nasal discharge to flecks of blood in the mucus. Aqueous nasal spray versus aerosol spray We identified only one poorly reported study (unclear number of participants for comparison of interest, 91 between three treatment arms), in which there were significant baseline differences between the participants in the two groups. We were unable to draw meaningful conclusions from the data.. We found insufficient evidence to suggest that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that the effectiveness of a spray differs from an aerosol. We identified no studies that compared drops with spray.It is unclear if higher doses result in better symptom improvements (low quality evidence), but there was moderate quality evidence of an increased risk of epistaxis as an adverse effect of treatment when higher doses were used. This included all levels of severity of epistaxis and it is likely that the proportion of events that required patients to discontinue usage is low due to the low numbers of withdrawals attributed to it. If epistaxis is limited to streaks of blood in the mucus it may be tolerated by the patient and it may be safe to continue treatment. However, it may be a factor that affects compliance.There is insufficient evidence to suggest that the different types of corticosteroid molecule or spray versus aerosol have different effects. Lower doses have similar effectiveness but fewer side effects.Clearly more research in this area is needed, with specific attention given to trial design, disease-specific health-related quality of life outcomes and evaluation of longer-term outcomes and adverse effects.

Topics: Administration, Intranasal; Adult; Beclomethasone; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Steroids

This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. The use of topical (intranasal) corticosteroids has been widely advocated for the treatment of chronic rhinosinusitis given the belief that inflammation is a major component of this condition.. To assess the effects of intranasal corticosteroids in people with chronic rhinosinusitis.. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.. Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) against placebo or no treatment in patients with chronic rhinosinusitis.. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of local irritation or other systemic adverse events. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.. We included 18 RCTs with a total of 2738 participants. Fourteen studies had participants with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. Intranasal corticosteroids versus placebo or no intervention Only one study (20 adult participants without polyps) measured our primary outcome disease-specific HRQL using the Rhinosinusitis Outcome Measures-31 (RSOM-31). They reported no significant difference (numerical data not available) (very low quality evidence).Our second primary outcome, disease severity , was measured using the Chronic Sinusitis Survey in a second study (134 participants without polyps), which found no important difference (mean difference (MD) 2.84, 95% confidence interval (CI) -5.02 to 10.70; scale 0 to 100). Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group (RR 2.78, 95% CI 1.76 to 4.40; 109 participants). The quality of the evidence was low.Six studies provided data on at least two of the individual symptoms used in the EPOS 2012 criteria to define chronic rhinosinusitis (nasal blockage, rhinorrhoea, loss of sense of smell and facial pain/pressure). When all four symptoms in the EPOS criteria were available on a scale of 0 to 3 (higher = more severe symptoms), the average MD in change from baseline was -0.26 (95% CI -0.37 to -0.15; 243 participants; two studies; low quality evidence). Although there were more studies and participants when only nasal blockage and rhinorrhoea were considered (MD -0.31, 95% CI -0.38 to -0.24; 1702 participants; six studies), the MD was almost identical to when loss of sense of smell was also considered (1345 participants, four studies; moderate quality evidence).When considering the results for the individual symptoms, benefit was shown in the intranasal corticosteroids group. The effect size was larger for nasal blockage (MD -0.40, 95% CI -0.52 to -0.29; 1702 participants; six studies) than for rhinorrhoea (MD -0.25, 95% CI -0.33 to -0.17; 1702 participants; six studies) or loss of sense of smell (MD -0.19, 95% CI -0.28 to -0.11; 1345 participants; four studies). There was heterogeneity in the analysis for facial pain/pressure (MD -0.27, 95% CI -0.56 to 0.02; 243 participants; two studies). The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure.There was an increased risk of. Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life (very low quality evidence). For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of epistaxis is increased (high quality evidence), but these data included all levels of severity; small streaks of blood may not be a major concern for patients. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis; Severity of Illness Index; Sinusitis; Steroids

People with asthma may experience exacerbations or "attacks" during which their symptoms worsen and additional treatment is required. Written action plans may advocate doubling the dose of inhaled steroids in the early stages of an asthma exacerbation to reduce the severity of the attack and to prevent the need for oral steroids or hospital admission.. To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids (ICS) as part of a patient-initiated action plan for home management of exacerbations in children and adults with persistent asthma.. We searched the Cochrane Airways Group Specialised Register, which is derived from searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to March 2016. We handsearched respiratory journals and meeting abstracts.. We included randomised controlled trials (RCTs) that compared increased versus stable doses of ICS for home management of asthma exacerbations. We included studies of children or adults with persistent asthma who were receiving daily maintenance ICS.. Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information.. This review update added three new studies including 419 participants to the review. In total, we identified eight RCTs, most of which were at low risk of bias, involving 1669 participants with mild to moderate asthma. We included three paediatric (n = 422) and five adult (n = 1247) studies; six were parallel-group trials and two had a cross-over design. All but one study followed participants for six months to one year. Allowed maintenance doses of ICS varied in adult and paediatric studies, as did use of concomitant medications and doses of ICS initiated during exacerbations. Investigators gave participants a study inhaler containing additional ICS or placebo to be started as part of an action plan for treatment of exacerbations.The odds of treatment failure, defined as the need for oral corticosteroids, were not significantly reduced among those randomised to increased ICS compared with those taking their usual stable maintenance dose (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.68 to 1.18; participants = 1520; studies = 7). When we analysed only people who actually took their study inhaler for an exacerbation, we found much variation between study results but the evidence did not show a significant benefit of increasing ICS dose (OR 0.84, 95% CI 0.54 to 1.30; participants = 766; studies = 7). The odds of having an unscheduled physician visit (OR 0.96, 95% CI 0.66 to 1.41; participants = 931; studies = 3) or acute visit (Peto OR 0.98, 95% CI 0.24 to 3.98; participants = 450; studies = 3) were not significantly reduced by an increased versus stable dose of ICS, and evidence was insufficient to permit assessment of impact on the duration of exacerbation; our ability to draw conclusions from these outcomes was limited by the number of studies reporting these events and by the number of events included in the analyses. The odds of serious events (OR 1.69, 95% CI 0.77 to 3.71; participants = 394; studies = 2) and non-serious events, such as oral irritation, headaches and changes in appetite (OR 2.15, 95% CI 0.68 to 6.73; participants = 142; studies = 2), were neither increased nor decreased significantly by increased versus stable doses of ICS during an exacerbation. Too few studies are available to allow firm conclusions on the basis of subgroup analyses conducted to investigate the impact of age, time to treatment initiation, doses used, smoking history and the fold increase of ICS on the magnitude of effect; yet, effect size appears similar in c. Current evidence does not support increasing the dose of ICS as part of a self initiated action plan to treat exacerbations in adults and children with mild to moderate asthma. Increased ICS dose is not associated with a statistically significant reduction in the odds of requiring rescue oral corticosteroids for the exacerbation, or of having adverse events, compared with a stable ICS dose. Wide confidence intervals for several outcomes mean we cannot rule out possible benefits of this approach.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Disease Progression; Humans; Randomized Controlled Trials as Topic

Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume and decreased pulmonary resistance have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators might have a role in the prevention and treatment of CLD.. To determine the effect of bronchodilators given as prophylaxis or as treatment for CLD on mortality and other complications of preterm birth in infants at risk for or identified as having CLD.. On 2016 March 7, we used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (from 1966), Embase (from 1980) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982). We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We applied no language restrictions.. Randomised and quasi-randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy for prevention of CLD had to occur within two weeks of birth. Treatment of patients with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation, by metered dose inhaler (with or without a spacer device) or by intravenous or oral administration versus placebo or no intervention. Eligible studies had to include at least one of the following predefined clinical outcomes: mortality, CLD, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, intraventricular haemorrhage (IVH) of any grade, necrotising enterocolitis (NEC), sepsis and adverse effects of bronchodilators.. We used the standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors extracted and assessed all data provided by each study. We reported risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) for continuous data. We assessed the quality of the evidence by using the GRADE approach.. For this update, we identified one new randomised controlled trial investigating effects of bronchodilators in preterm infants. This study, which enrolled 73 infants but reported on 52 infants, examined prevention of CLD with the use of aminophylline. According to GRADE, the quality of the evidence was very low. One previously included study enrolled 173 infants to look at prevention of CLD with the use of salbutamol. According to GRADE, the quality of the evidence was moderate. We found no eligible trial that studied the use of bronchodilator therapy for treatment of individuals with CLD. Prophylaxis with salbutamol led to no statistically significant differences in mortality (RR 1.08, 95% CI 0.50 to 2.31; RD 0.01, 95% CI -0.09 to 0.11) nor in CLD (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17). Results showed no statistically significant differences in other complications associated with CLD nor in preterm birth. Investigators in this study did not comment on side effects due to salbutamol. Prophylaxis with aminophylline led to a significant reduction in CLD at 28 days of life (RR 0.18, 95% CI 0.04 to 0.74; RD -0.35, 95% CI -0.56 to -0.13; NNTB 3, 95% CI 2 to 8) and no significant difference in mortality (RR 3.0, 95% CI 0.33 to 26.99; RD 0.08, 95% CI -0.07 to 0.22), along with a significantly shorter dependency on supplementary oxygen in the aminophylline group compared with the no treatment group (MD -17.75 days, 95% CI -27.56 to -7.94). Tests for heterogeneity were not applicable for any of the analyses, as each meta-analysis included only one study.. Data are insufficient for reliable assessment of the use of salbutamol for prevention of CLD. One trial of poor quality reported a reduction in the incidence of CLD and shorter duration of supplementary oxygen with prophylactic aminophylline, but these results must be interpreted with caution. Additional clinical trials are necessary to assess the role of bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes. We identified no trials that studied the use of bronchodilator therapy for treatment of CLD.

Topics: Albuterol; Aminophylline; Beclomethasone; Bronchodilator Agents; Chronic Disease; Drug Therapy, Combination; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Randomized Controlled Trials as Topic

Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma.. To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration.. We searched the Cochrane Airways Group Asthma Trials Register until January 2015.. We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals.. Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible.. We included in this review a total of 33 trials representing 39 control-intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS.LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies.There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate-quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate-quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate-quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low-quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low-quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD -0.07 puffs/d, 95% CI -0.11 to -0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD -0.08 puffs/d, 95% CI -0.13 to -0.03, three studies, 672 children). No significant group difference was noted in exercise-induced % fall in FEV1, symptom-free days, asthma symptom score, quality of life, use of reliever medication and adverse events.A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials e. In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Disease Progression; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Allergic rhinitis (AR) is a common chronic disorder, affecting 10 -30% of populations. AR has significant morbidity and expense. AR patients treat themselves with over-the-counter medications. However the usual H1 antihistamines are often inadequate. Intranasal corticosteroids effectively diminish AR symptoms. Beclomethasonedipropionate (BDP) was reported to effectively treat adults and children with AR. BDP was a chlorofluorocarbon (CFC) propellant pressurized metered dose inhaler (pMDI). Subsequently BDP appeared in an aqueous format. Some patients preferred the dryer sensation of pMDI to aqueous formulations. The protocol of Montréal, removed CFC devices from medical practice. The remaining intranasal steroids were in aqueous format. Many patients did not like the sensory perceptions using liquids intranasal. They were unlikely to be compliant. BDP hydrofluoroalkanepMDI (BDP HFA) was developed.. The need of active treatment of AR will be reviewed. Chemistry, pharmacokinetics and pharmacodynamics of BDP HFA will be presented. Clinical efficacy studies and safety data which led to the approval of BDP for use in adults and children will be reviewed.. BDP HFA is an option to treat AR, demonstrating a favorable therapeutic index in large double-blind placebo-controlled studies. BDP HFA appeals to select AR patients.

Topics: Administration, Inhalation; Administration, Intranasal; Beclomethasone; Chronic Disease; Glucocorticoids; Humans; Metered Dose Inhalers; Patient Compliance; Rhinitis, Allergic

Chronic lung disease (CLD) remains a serious and common problem among very low birth weight (VLBW) infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent CLD. However, the use of systemic steroids has been associated with serious short and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects.. To determine the effect of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight < 1500 g or gestational age < 32 weeks after two weeks of life for the treatment of evolving CLD.. Randomised and quasi-randomised trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 to June 2007), EMBASE (1980 to June 2007), CINAHL (1982 to June 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web site (1990 to April 2007). This search was updated in June 2011 and included additional searches of Clinicaltrials.gov, Controlled-trials.com and Web of Science.. Randomised or quasi-randomised trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent VLBW infants.. Data were extracted regarding clinical outcomes and were analysed using Review Manager. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to benefit (NNTB) or the number needed to harm (NNTH) was calculated.. Five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non-ventilator dependent patients and three trials qualified for inclusion in this review. No new trials were identified in the 2011 update.Halliday et al (Halliday 2001) randomised infants at < 72 hours (n = 292), while Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) randomised at 12 to 21 days. The data from the two trials of Rozycki et al and Suchmoski et al are combined using meta-analytic techniques. The data from the trial by Halliday et al are reported separately, as outcomes were measured over different time periods from the age at randomisation.In none of the trials was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks PMA among all randomised infants. The estimates for the trial by Halliday et al (Halliday 2001) were RR 1.10 (95% CI 0.82 to 1.47), RD 0.03 (95% CI -0.08 to 0.15).For the trials by Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) the typical RR was 1.02 (95% CI 0.83 to 1.25) and the typical RD 0.01 (95% CI -0.11 to 0.14); (number of infants = 139 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days of age, death by 28 days or 36 weeks PMA, the combined outcome of death by or CLD at 28 days or 36 weeks PMA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long-term neurodevelopmental outcomes was not available.. This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.

Topics: Administration, Inhalation; Beclomethasone; Chronic Disease; Dexamethasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung Diseases; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory System Agents

Chronic lung disease (CLD) remains an important cause of mortality and morbidity in preterm infants and inflammation plays an important role in its pathogenesis. The use of inhaled corticosteroids may modulate the inflammatory process without concomitant high systemic steroid concentrations and less risk of adverse effects.. To determine the effect of inhaled versus systemic corticosteroids started within the first two weeks of life on preventing CLD in ventilated very low birth weight (VLBW) infants.. Randomised and quasi-randomised trials were identified by searching The Cochrane Library, MEDLINE , EMBASE , CINAHL, reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web site in June 2007.This search was updated in June 2011 and included additional searches of Clinicaltrials.gov, Controlled-trials.com and Web of Science.. Randomised or quasi-randomised clinical trials comparing inhaled versus systemic corticosteroid therapy (regardless of the dose and duration of therapy) started in the first two weeks of life in VLBW infants receiving assisted ventilation.. Outcomes including CLD at 28 days or 36 weeks postmenstrual age (PMA), mortality, the combined outcome of death or CLD at 28 days or 36 weeks PMA, other pulmonary outcomes and adverse effects were evaluated. All data were analysed using RevMan 5.1. Meta-analyses were performed using relative risk (RR), risk difference (RD), and mean difference (MD) with their 95% confidence intervals (CI). If RD was significant, the numbers needed to benefit (NNTB) or to harm (NNTH) were calculated.. No new trials were identified in this update. Two trials qualified for inclusion in this review. The incidence of CLD at 36 weeks PMA was increased (of borderline statistical significance) in the inhaled steroid group [RR 1.45 (95% CI 0.99 to 2.11); RD 0.11 (95% CI 0.00 to 0.21), p = 0.05, one trial, n = 278]. The incidence of CLD at 36 weeks PMA among all survivors [RR 1.34 (95% CI 0.94 to 1.90); RD 0.11 (95% CI -0.02 to 0.24), one trial, n = 206], oxygen dependency at 28 days (two trials, n = 294), death by 28 days (two trials, n = 294) or 36 weeks PMA (two trials, n = 294) and the combined outcome of death or CLD by 28 days (two trials, n = 294) or 36 weeks PMA (one trial, n = 278) did not differ significantly between the groups. The duration of mechanical ventilation was significantly longer in the inhaled steroid group as compared to the systemic steroid group [typical MD 4 days (95% CI 0.2 to 8); two trials, n = 294] as was the duration of supplemental oxygen [typical MD 11 days (95% CI 2 to 20); two trials, n = 294]. The incidence of hyperglycaemia was significantly lower in the group receiving inhaled steroids [RR 0.52 (95% CI 0.39 to 0.71); RD -0.25 (95% CI -0.37 to -0.14); one trial, n = 278; NNTB 4 (95% CI 3 to 7) to avoid one infant experiencing hyperglycaemia]. The rate of patent ductus arteriosus was increased in the group receiving inhaled steroids [RR 1.64 (95% CI 1.23 to 2.17); RD 0.21 (95% CI 0.10 to 0.33); one trial, n = 278; NNTH 5 (95% CI 3 to 10)]. No information was available on long-term neurodevelopmental outcomes.. This review found no evidence that early inhaled steroids confer important advantages over systemic steroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as a part of standard practice for ventilated preterm infants. Because they might have fewer adverse effects than systemic steroids, further randomised controlled trials of inhaled steroids are needed that address risk/benefit ratio of different delivery techniques, dosing schedules and long-term effects, with particular attention to neurodevelopmental outcome.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Chronic Disease; Dexamethasone; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung Diseases; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory System Agents; Steroids

Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increase in compliance and tidal volume and decrease in pulmonary resistance have been documented with use of bronchodilators in studies of pulmonary mechanics in infants with CLD. Therefore, it is possible that bronchodilators might have a role in the prevention and treatment of CLD.. To determine the effect of bronchodilators given either prophylactically or as treatment for CLD on mortality and other complications of prematurity in preterm infants at risk for or having CLD.. For this update of the review, searches of The Cochrane Library, Issue 3, 2012; MEDLINE 1966; EMBASE; CINAHL; personal files and reference lists of identified trials were performed in March 2012. In addition Web of Science and abstracts from the Annual meetings of the Pediatric Academic Societies were searched electronically from 2000 to 2012 on PAS Abstracts2view(TM.) No language restrictions were applied.. Randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy had to occur within two weeks of birth for prevention of CLD. For treatment of CLD, treatment had to be initiated before discharge from the neonatal unit. The intervention had to include the administration of a bronchodilator either by nebulisation, metered dose inhaler (with or without a spacer device), intravenously or orally versus placebo or no intervention. Eligible studies had to include at least one of the predefined clinical outcomes (mortality, CLD, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, any grade of intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), sepsis and adverse effects of bronchodilators. Adverse effects of bronchodilators included hypokalaemia, tachycardia, cardiac arrhythmias, tremor, hypertension and hyperglycaemia).. We used the standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two investigators extracted and assessed all data for each study. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes and weighted mean difference (WMD) for continuous data.. In this update we identified four randomised controlled trials investigating the effects of bronchodilators in preterm infants. None of these studies fulfilled our inclusion criterion that clinical outcomes should be reported. One eligible study was previously found dealing with prevention of CLD; this study used salbutamol and enrolled 173 infants. No eligible studies were found dealing with treatment of CLD. Prophylaxis with salbutamol did not show a statistically significant difference in mortality (RR 1.08; 95% CI 0.50 to 2.31; RD 0.01; 95% CI -0.09 to 0.11) or CLD (RR 1.03; 95% CI 0.78 to 1.37; RD 0.02; 95% CI -0.13 to 0.17). No statistically significant differences were seen in other complications associated with CLD or preterm birth. No side effects due to salbutamol were commented on in this study.. There are insufficient data to reliably assess the use of salbutamol for the prevention of CLD. Further clinical trials are necessary to assess the role of salbutamol or other bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.

Topics: Albuterol; Beclomethasone; Bronchodilator Agents; Chronic Disease; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Randomized Controlled Trials as Topic

Long-acting inhaled ss(2)-adrenergic agonists (LABAs) are recommended as 'add-on' medication to inhaled corticosteroids (ICS) in the maintenance therapy of asthmatic adults and children aged two years and above.. To quantify in asthmatic patients the safety and efficacy of the addition of LABAs to ICS in patients insufficiently controlled on ICS alone.. We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until May 2008.. We included RCTs if they compared the addition of inhaled LABAs versus placebo to the same dose of ICS in children aged two years and above and in adults.. Two review authors independently assessed studies for methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the relative risk (RR) of asthma exacerbations requiring rescue oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), rescue beta2-agonist use, symptoms, withdrawals and adverse events.. Seventy-seven studies met the entry criteria and randomised 21,248 participants (4625 children and 16,623 adults). Participants were generally symptomatic at baseline with moderate airway obstruction despite their current ICS regimen. Formoterol or salmeterol were most frequently added to low-dose ICS (200 to 400 microg/day of beclomethasone (BDP) or equivalent) in 49% of the studies. The addition of a daily LABA to ICS reduced the risk of exacerbations requiring oral steroids by 23% from 15% to 11% (RR 0.77, 95% CI 0.68 to 0.87, 28 studies, 6808 participants). The number needed to treat with the addition of LABA to prevent one use of rescue oral corticosteroids is 41 (29, 72), although the event rates in the ICS groups varied between 0% and 38%. Studies recruiting adults dominated the analysis (6203 adult participants versus 605 children). The subgroup estimate for paediatric studies was not statistically significant (RR 0.89, 95% CI 0.58 to 1.39) and includes the possibility of the superiority of ICS alone in children.Higher than usual dose of LABA was associated with significantly less benefit. The difference in the relative risk of serious adverse events with LABA was not statistically significant from that of ICS alone (RR 1.06, 95% CI 0.87 to 1.30). The addition of LABA led to a significantly greater improvement in FEV(1) (0.11 litres, 95% 0.09 to 0.13) and in the proportion of symptom-free days (11.88%, 95% CI 8.25 to 15.50) compared to ICS monotherapy. It was also associated with a reduction in the use of rescue short-acting ss(2)-agonists (-0.58 puffs/day, 95% CI -0.80 to -0.35), fewer withdrawals due to poor asthma control (RR 0.50, 95% CI 0.41 to 0.61), and fewer withdrawals due to any reason (RR 0.80, 95% CI 0.75 to 0.87). There was no statistically significant group difference in the risk of overall adverse effects (RR 1.00, 95% 0.97 to 1.04), withdrawals due to adverse health events (RR 1.04, 95% CI 0.86 to 1.26) or any of the specific adverse health events.. In adults who are symptomatic on low to high doses of ICS monotherapy, the addition of a LABA at licensed doses reduces the rate of exacerbations requiring oral steroids, improves lung function and symptoms and modestly decreases use of rescue short-acting ss(2)-agonists. In children, the effects of this treatment option are much more uncertain. The absence of group difference in serious adverse health events and withdrawal rates in both groups provides some indirect evidence of the safety of LABAs at usual doses as add-on therapy to ICS in adults, although the width of the confidence interval precludes total reassurance.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Chronic Disease; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Written action plans providing guidance in the early treatment of asthma exacerbations have traditionally advocated doubling of inhaled corticosteroids (ICS) as one of the first steps in treatment.. To compare the clinical effectiveness of increasing the dose of ICS versus keeping the usual maintenance dose as part of a patient-initiated action plan at the onset of asthma exacerbations.. We searched the Cochrane Airways Group Specialised Register (last search October 2009) which is derived from searches of CENTRAL, MEDLINE, EMBASE and CINAHL, as well as handsearched respiratory journals and meeting abstracts.. Randomised controlled trials (RCTs) that compared the strategy of increasing the daily dose of ICS to continuing the same ICS dose in the home management of asthma exacerbations in children or adults with persistent asthma on daily maintenance ICS.. Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information.. Five RCTs (four parallel-group and one cross-over) involving a total of 1250 patients (28 children and 1222 adults) with mild to moderate asthma were included. The mean daily baseline ICS dose was 555 mcg (range 200 mcg to 795 mcg) and the mean daily ICS dose achieved following increase was 1520 mcg (range 1000 mcg to 2075 mcg), in CFC beclomethasone dipropionate equivalents. Three parallel-group studies in adults (two doubling and one quadrupling; mean achieved daily dose of 1695 mcg with a range of 1420 to 2075 mcg), involving 1080 patients contributed data to the primary outcome. There was no significant reduction in the need for rescue oral corticosteroids when patients were randomised to the increased ICS compared to stable maintenance dose groups (OR 0.85, 95% CI 0.58 to 1.26). There was no significant difference in the overall risk of non-serious adverse events associated with the increased ICS dose strategy, but the wide confidence interval prevents a firm conclusion. No serious adverse events were reported.. There is very little evidence from trials in children. In adults with asthma on daily maintenance ICS, a self-initiated ICS increase to 1000 to 2000 mcg/day at the onset of an exacerbation is not associated with a statistically significant reduction in the risk of exacerbations requiring rescue oral corticosteroids. More research is needed to assess the effectiveness of increased ICS doses at the onset of asthma exacerbations (particularly in children).

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Disease Progression; Humans; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects.. To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma.. We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007.. Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01).. The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent CLD. However, the use of systemic steroids has been associated with serious short and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects.. To determine the effect of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight < 1500 g or gestational age < 32 weeks after two weeks of life for the treatment of evolving CLD.. Randomized and quasi-randomized trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - June 2007), EMBASE (1980 - June 2007), CINAHL (1982 - June 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies website (1990 - April 2007).. Randomized or quasi-randomized trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent very low birth weight preterm infants.. Data were extracted regarding clinical outcomes including CLD at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age or 36 weeks PMA, other pulmonary outcomes and adverse effects. All data were analyzed using RevMan 4.2.10. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to treat (NNT) was calculated.. Data from one additional trial were available for inclusion in this update. Thus, five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non-ventilator dependent patients and three trials qualified for inclusion in this review. Halliday et al (Halliday 2001) randomized infants at < 72 hours, while Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) randomized at 12 - 21 days. The data from the two trials of Rozycki et al and Suchmoski et al are combined using meta-analytic techniques. The data from the trial by Halliday et al are reported separately, as outcomes were measured over different time periods from the age at randomization. In none of the trials was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks PMA among all randomized infants. The estimates for the trial by Halliday et al (Halliday 2001) were RR 1.10 (95% CI 0.82, 1.47), RD 0.03 (95% CI -0.08, 0.15); number of infants (n = 292). For the trials by Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) the typical RR was 1.02 (95% CI 0.83, 1.25) and the typical RD 0.01 (95% CI -0.11, 0.14); (number of infants = 139 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days of age, death by 28 days or 36 weeks PMA, the combined outcome of death by or CLD at 28 days or 36 weeks PMA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long-term neurodevelopmental outcomes was not available.. This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.

Topics: Administration, Inhalation; Beclomethasone; Chronic Disease; Dexamethasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung Diseases; Randomized Controlled Trials as Topic; Respiration, Artificial

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2007) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2006).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma.. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. Seventy-one studies (14,602 participants) representing 74 randomised comparisons met the inclusion criteria. Methodological quality was fair. Dose ratio 1:2: FP produced a significantly greater end of treatment FEV1 (0.04 litres (95% CI 0 to 0.07 litres), end of treatment and change in morning PEF, but not change in FEV1 or evening PEF. This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. FP led to fewer symptoms and less rescue medication use. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in morning PEF, evening PEF, and FEV1 over BDP or BUD. The effects on exacerbations were mixed. There were no significant differences incidence of hoarseness, pharyngitis, candidiasis, or cough.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing sore throat and when given at the same daily dose leads to increased hoarseness. There are concerns about adrenal suppression with Fluticasone given to children at doses greater than 400 mcg/day, but the randomised trials included in this review did not provide sufficient data to address this issue.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.. To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.. The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of January 2006.. Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.. Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.. Eight studies (1260 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.. There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Fluticasone; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma.. We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer.. Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P < 0.05) but no significant difference in plasma cortisol response.. There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low power. These demonstrate CIC has similar effectiveness and efficacy to FP and BUD (though equivalence is not certain) and findings regarding oral deposition and HPA suppression are inconclusive. There is no direct comparative evidence that CIC causes fewer side effects since none of the studies reported patient-based outcomes.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Chronic Disease; Diagnosis, Differential; Drug Administration Schedule; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Nurse Practitioners; Nurse's Role; Patient Satisfaction; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Triamcinolone

Inhaled beclomethasone dipropionate (BDP) has been, together with inhaled budesonide, the mainstay of anti-inflammatory therapy for asthma for many years. A range of new prophylactic therapies for asthma is becoming available and BDP has been reformulated using a hydrofluoroalkane-134a (HFA) propellant which is free from chlorofluorocarbon (CFC).. The objectives of this review were to: (1) Compare the efficacy of BDP with placebo with both CFC and HFA propellants in the treatment of chronic asthma. (2) Explore the possibility that a dose response relationship exists for BDP in the treatment of chronic asthma. (3) To provide the best estimate of the efficacy of BDP as a benchmark for evaluation of newer asthma therapies.. Electronic searches were current as of January 2003.. Randomised parallel group design trials for a minimum period of four weeks, in children and adults comparing CFC-BDP or HFA-BDP with placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. We analysed data with RevMan Analyses 1.0.2.. 60 studies recruiting 6542 participants met the inclusion criteria. CFC-BDP (57 studies): In non-oral steroid treated patients, at doses of 400 mcg/day or less CFC-BDP produced significant improvements from baseline in a number of efficacy measures compared with placebo, including forced expiratory volume in one second (FEV1) 360 ml (95% CI 260 to 460); FEV1 (% predicted) WMD 12.41% (95% CI 8.18 to 16.64) and morning peak expiratory flow rate (am PEF) WMD 35.95 L/min (95% CI 27.85 to 44.04). BDP also led to reductions in rescue beta-2 agonist use compared with placebo of -2.32 puffs/d (95% CI -2.55 to -2.09) and reduced the relative risk (RR) of trial withdrawal due to an asthma exacerbation 0.25 (95% CI 0.12 to 0.51). Subgroup analyses based on treatment duration provide support to the proposal that a treatment period of greater than four weeks is required to realise a fuller treatment effect. In oral steroid treated patients BDP led to significantly greater reductions in oral prednisolone use WMD -4.91 mg/d (95% CI -5.88 to -3.94 mg/d) and greater likelihood of withdrawing oral steroid treatment RR 8.02 (95% CI 3.23 to 19.92). HFA-BDP (3 studies): In non-oral steroid-treated patients, HFA-BDP was significantly more effective than placebo in improving FEV1, morning and evening PEF, FEF25 to 75%, reduced asthma symptoms and beta2-agonists daily consumption. Significant effects for such outcomes were apparent after six weeks of treatment. In oral steroid treated patients, HFA-BDP improved significantly FEV1 and am PEF. The summary estimates for these outcomes suggested a high level of heterogeneity, and divergent aims of the studies may contribute to the variation we observed. Limited data on adverse events were reported.. This review has quantified the efficacy of CFC-BDP and HFA-BDP in the treatment of chronic asthma and strongly supports its use. Current asthma guidelines recommend titration of dose to individual patient response, but the published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma. There are insufficient data to draw any conclusions concerning dose-response in people with severe asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2004) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma.. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. Fifty six studies (12, 119 participants) met the inclusion criteria. Methodological quality was variable. Dose ratio 1:2: FP produced a significantly greater FEV1 (0.14 litres, 95% Confidence Interval (CI) 0.06 to 0.22), morning PEF (11.10 L/min, 95%CI 3.12 to 19.09 L/min) and evening PEF (9.31 L/min, 95%CI 5.12 to 13.5 L/min). This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in am PEF (9.58 L/min (95% CI 5.20 to 13.97)), pm PEF (7.41 L/min (95% CI 2.61 to 12.22)), and FEV1 (0.09 L (0.02 to 0.17)). The effects on exacerbations were mixed. There was an increase in the incidence of hoarseness, but no significant difference in pharyngitis, candidiasis, or cough.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing hoarseness when given at the same daily dose. Future studies should attempt to establish the relative efficacy of inhaled steroids delivered with CFC-free propellants.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic

The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.. To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.. The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of March 2005.. Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.. Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.. Seven studies (1230 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.. There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2003) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. 48 studies (11,479 participants) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01 to 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5 to 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1 to 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.76, 95%CI 0.53 to 1.09). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.43 to 3.24) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although there was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Corticosteroids have been widely used to treat or prevent CLD due to their anti-inflammatory properties. However, the use of systemic steroids has been associated with serious short and long term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects.. To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight

Topics: Administration, Inhalation; Beclomethasone; Chronic Disease; Dexamethasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung Diseases; Respiration, Artificial

Topics: Anti-Bacterial Agents; Beclomethasone; Chronic Disease; Dexamethasone; Drug Therapy, Combination; Evidence-Based Medicine; Glucocorticoids; Humans; Otitis Media with Effusion; Practice Guidelines as Topic

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.. 42 studies (>10,000 patients) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01, 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5, 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1, 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.77, 95%CI 0.54, 1.10). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.42, 3.28) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Beclomethasone dipropionate (BDP) and budesonide (BUD) are used widely in the treatment of chronic asthma. The two drugs have different in vitro pharmacokinetic characteristics. It is unclear whether this translates into clinically significant differences in efficacy or safety when treating children and adults with chronic asthma.. To assess clinical outcomes in studies which have compared inhaled BDP and BUD in the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Prospective, randomised trials comparing BDP to BUD in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.. 24 studies met the criteria for inclusion (1174 subjects). Methodological quality was variable. A meta-analysis of crossover studies did not demonstrate a significant difference between BDP and BUD for FEV1, morning PEF, evening PEF, asthma symptoms or rescue beta2 agonist use, over a dose range of 400 to 1000 mcg/d. The majority of crossover trials had significant design flaws related to a lack of washout and/or failure to exclude carryover effects so the results must be viewed with caution. A single crossover study with adequate washout showed that BUD 400 mcg/d delivered via Turbohaler dry powder inhaler (DPI) may be more effective than BDP 400 mcg/d delivered via Rotahaler DPI in reducing histamine bronchial hyper-responsiveness: Weighted Mean Difference (WMD) 0.43 log10 PC20 FEV1 (95% Confidence Intervals (CI) 0.05, 0.81 log10 PC20 FEV1). A meta-analysis of two parallel group, dose down-titration studies (231 patients) showed that less BUD delivered via a Turbohaler DPI was required to maintain control in adults asthmatics compared to BDP delivered via metered dose inhaler with or without a spacer: WMD 444 mcg/d (95% CI 332, 556 mcg/d).. There is limited high quality randomised controlled trial data comparing the relative efficacy of BDP and BUD. Current guidelines (BTS 1997, GINA 1995, NHLBI 1997) assume BDP and BUD to have equal efficacy, such that for each defined level of asthma severity, the recommended doses BDP and BUD are the same. Although there is some data to suggest that BUD via Turbohaler is more effective than BDP via either Rotahaler or MDI (with and without spacer), these comparisons are confounded by use of different delivery devices, and are not sufficient to warrant a change in guideline recommendations.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic

Substantial advances have been achieved during the last decade in our understanding of the biological bases of the sense of smell, as well as in the clinical identification, diagnosis, and management of dysosmia. Nasal obstruction can result from inflammatory, neoplastic, traumatic, and developmental alterations within the nasal cavity. All these processes, if they result in bilateral restriction of airflow to the olfactory neuroepithelium, presumably alter the ability to smell. Rhinitis, nasal polyposis, and rhinosinusitis are accompanied by decreased ability to smell. Benign and malignant neoplasms can obstruct the nasal chamber and thereby alter airflow to the olfactory receptors without damaging the olfactory neuroepithelium. The purpose of this synthesis is to provide an advanced review of the literature in order to describe the basis of smell alterations in nasal polyposis and chronic rhinosinusitis.

Topics: Anti-Inflammatory Agents; Beclomethasone; Chronic Disease; Humans; Nasal Polyps; Olfaction Disorders; Otorhinolaryngologic Surgical Procedures; Paranasal Sinus Diseases; Prednisolone; Therapeutic Irrigation

Asthma has been recognized as a chronic inflammatory disorder of the airway. The early use of antiinflammatory agents, one of which is inhaled corticosteroids, is advocated in the treatment of chronic asthma. Beclomethasone dipropionate (BDP) is effective in childhood asthma. CD4 T-cell activation correlate with the values of the coefficient variation (CV) of peak expiratory flow (PEF) in asthmatic patients, suggesting that CV of PEF is a good marker for assessing not only the variability of airway obstruction but also the degree of airway inflammation. PEF monitoring is useful for better controlling asthma, because some patients treated with inhaled corticosteroid may still remain undertreated.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; CD4-Positive T-Lymphocytes; Child; Chronic Disease; Cromolyn Sodium; Humans; Lymphocyte Activation; Monitoring, Physiologic; Peak Expiratory Flow Rate

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Chronic Disease; Drug Therapy, Combination; Glucocorticoids; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Randomized Controlled Trials as Topic; Sulfonamides; Tosyl Compounds

Inhaled beclomethasone diproprionate (BDP) has been, together with inhaled budesonide, the mainstay of anti-inflammatory therapy for asthma for many years. A range of new prophylactic therapies for asthma is becoming available and BDP is now frequently used as the reference treatment against which these newer agents are being compared.. The objectives of this review were to: a) Compare the efficacy of BDP with placebo in the treatment of chronic asthma. b) Explore the possibility that a dose response relationship exists for BDP in the treatment of chronic asthma. c) To provide the best estimate of the efficacy of BDP as a benchmark for evaluation of newer asthma therapies.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and Glaxo Wellcome for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing BDP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager (Revman) 4.0.3 with Metaview 3.1.. 52 studies were selected for inclusion (3459 subjects). The studies were generally of high methodological quality. In non-oral steroid treated patients, BDP produced significant improvements in a number of efficacy measures compared to placebo including FEV1 weighted mean difference (WMD) 340ml (95% CI 190-500ml); FEV1 (% predicted) WMD 6% (95% CI 0.4 to 11.5%) and morning PEFR WMD 50 L/min (95% CI 8 to 92 L/min). BDP also led to reductions in rescue beta2 agonist use compared to placebo WMD 1.75 puffs/d (95% CI 1.4 to 2.4 puffs/d) and reduced the likelihood of trial withdrawal due to asthma exacerbation relative risk (RR) 0.26 (95% CI 0.15 to 0.43). In oral steroid treated patients BDP led to significantly greater reductions in oral prednisolone use WMD 5 mg/d (95% CI 4 to 6 mg/d) and a higher likelihood of discontinuing oral prednisolone RR 0.54 (95% CI 0.43 to 0.67). There was little evidence for a clincially worthwhile dose response effect, but few studies recruited patients with more severe asthma.. This review has quantified the efficacy of BDP in the treatment of chronic asthma and strongly supports its use. Current asthma guidelines recommend titration of dose to individual patient response, but the published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma. There are insufficient data to draw any conclusions concerning dose-response in patients with severe disease.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic

Nasal allergy is statistically related to inflammatory chronic sinusitis as a risk factor. But one question still remains unanswered: are the reactions and modifications observed in the sinuses after natural exposure to a nasal allergen or after nasal allergen challenge linked to an IgE mediated mechanism? Similarities in symptoms, eosinophils and mediators of inflammation in the mucosa have been found between allergic rhinitis and sinusitis. The same applies for the deposition of Major Basic Protein (MBP) and treatment results, especially when topical steroids are found. An original prospective study was held among 106 patients (24 patients allergic to perennial allergens, 82 non allergic patients) suffering from bilateral chronic inflammatory (no polyposis) ethmoidal sinusitis. The allergic group was submitted to a 3 months antiallergic treatment (Cetirizine 10 mg once a day, Beclomethasone dipropionate 50 micrograms three times a day) before being referred for bilateral endonasal ethmoidectomy under endoscopic control. Scores for rhinorrhea, nasal obstruction and global comfort (global assessment) were compared before and after ethmoidectomy. Both groups were significantly improved by surgery. Comparing both groups, no significant difference was found before and after surgery regarding the three above mentioned parameters. This suggests that 1) symptoms are common to both perennial nasal allergy and chronic ethmoidal sinusitis, 2) medical treatment failure in allergy must require a CT scan of the sinuses to assess a possible accompanying chronic sinusitis, 3) chronic ethmoidal sinusitis is probably the leading factor responsible for nasal symptoms such as rhinorrhea and nasal obstruction when associated with perennial allergy.

Topics: Allergens; Anti-Allergic Agents; Anti-Inflammatory Agents; Beclomethasone; Blood Proteins; Cetirizine; Chronic Disease; Endoscopy; Eosinophil Granule Proteins; Eosinophils; Ethmoid Sinus; Ethmoid Sinusitis; Humans; Immunoglobulin E; Inflammation Mediators; Mucous Membrane; Nasal Mucosa; Nasal Obstruction; Prospective Studies; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial; Ribonucleases; Risk Factors; Sinusitis; Tomography, X-Ray Computed

Bronchial asthma is no longer considered a condition with isolated, acute episodes of bronchoconstriction. Rather, asthma is now understood to be a chronic inflammatory disorder of the airways. Therefore anti-inflammatory agents and, more specifically, inhaled corticosteroids are at present the most effective controllers in long-term treatment and prevention of asthma. Asthma is highly variable, so precise classification of severity is needed for management. Asthma therapy recommended in guidelines follows a stepwise approach in which the level of therapy is increased (step up) as the severity of asthma increased and therapy decreased (step down) once control is achieved and sustained. In this stepwise approach, inhaled corticosteroid is a key drug and establishment of the dosage of inhaled corticosteroid is most important.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Japan; Practice Guidelines as Topic; Severity of Illness Index; Societies, Medical; World Health Organization

Our data indicate that 1800 micrograms of per day is more effective than 1400 micrograms/day at the beginning of long-term management of severe asthma in adults whose symptoms are not controlled with the combination of 800 approximately 900 micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600 micrograms/day) of inhaled steroid is more useful and should be promptly began to treat severe asthma. Oral steroid therapy for long-term management should be introduced to mostly severe case after high dose inhaled BDP therapy reveals to be failure.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate

Sarcoidosis is a chronic multisystem granulomatous disease that has a predilection for pulmonary and upper respiratory tract involvement. Because the initial signs and symptoms of sarcoidosis may be identical to those of other forms of chronic sinonasal inflammatory disease, these patients will often first seek treatment from an otolaryngologist. We present a series of 28 patients whose primary symptoms was involvement of a sinonasal tract. A new staging system is proposed to categorize the severity and sites of involvement and to guide the aggressiveness of therapy. Sarcoidosis should be considered in the differential diagnosis of inflammatory sinonasal disease.

Topics: Adult; Beclomethasone; Chronic Disease; Constriction, Pathologic; Diagnosis, Differential; Edema; Epistaxis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Obstruction; Nose Deformities, Acquired; Nose Diseases; Paranasal Sinus Diseases; Prednisone; Sarcoidosis; Tissue Adhesions; Triamcinolone Acetonide

Over an 18-month period 31 patients (27 female and 4 male) were referred to the ENT department of our clinic for a 1-month to 14-year history of isolated non-productive cough. As ENT examination, including posterior rhinoscopy, was normal, these patients were sent to the pneumology department. Physical examination and X-ray films of the chest were negative, and the patients did not take an angiotensin converting enzyme inhibitor that could have induced this cough. Inhalation of acetylcholine lowered vital capacity by 32 +/- 14% and forced expiratory volume by 34 +/- 16%, a test which is the hallmark of bronchial hyperreactivity. Three patients were atopic. We believe that this cough can be the only manifestation of bronchial asthma. In these patients, cough was suppressed or strongly attenuated by the inhalation, 5 times a day, of salbutamol 200 mg puffs and beclomethasone dipropionate 250 mcg. In addition, the atopic patients were prescribed 10 puffs of sodium cromoglycate per day. Complaints of isolated non-productive cough must always suggest that possibility of bronchial asthma, and a bronchial provocation test must be performed to confirm this diagnosis.

Topics: Adolescent; Adult; Aged; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Chronic Disease; Cough; Cromolyn Sodium; Female; Humans; Hypersensitivity, Immediate; Male; Middle Aged

Topics: Allergens; Animals; Asthma; Beclomethasone; Bronchodilator Agents; Chronic Disease; Histamine Antagonists; Humans

The effects of high-dose inhaled beclomethasone dipropionate were studied retrospectively in 123 asthma patients who were inadequately controlled on standard doses of beclomethasone dipropionate, or who required oral corticosteroids to control their asthma. High-dose beclomethasone dipropionate was administered by aerosol which delivered 250 micrograms beclomethasone dipropionate per metered dose. Thirty-one percent of the steroid-dependent patients (n = 65) were able to stop maintenance oral steroid after the introduction of beclomethasone dipropionate 250 and a further 48% were able to reduce their daily dosage. The mean reduction in daily maintenance prednisone was 5.2 mg. Comparing a six month period before and during treatment with beclomethasone dipropionate 250, asthma control was improved in 69% of all patients. This was accompanied by a 53% reduction in the number of acute attacks requiring supplementary courses of oral corticosteroid and a 70% reduction in admissions to hospital. Prior to beclomethasone dipropionate 250, 21% of the steroid-dependent patients were maintained on alternate day prednisone whereas after the introduction of beclomethasone dipropionate 250, 44% of those 45 still requiring continuous prednisone were maintained on an alternate-day regimen.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Drug Evaluation; Female; Humans; Male; Middle Aged; Prednisone; Retrospective Studies; Substance-Related Disorders

In a first chapter the author reviews the mechanisms of action of corticoids in respiratory diseases. Moreover the causes and the prevalence of unwanted side-effects are discussed. The advantages of synthetic glucocorticoids with short half-life time in pneumology are stressed. In the following chapters, the rationale of long-term corticoid treatments of asthma, in non allergic obstructive chronic lung diseases, in sarcoidosis and in the thoracic localisations of some collagen diseases is presented in detail. Regarding the treatment of asthma the author discusses the advantages of the alternate-day therapy, the use of corticoids in aerosols and the ratioale of ACTH. The usefulness of alternate-day therapy in sarcoidosis is also advocated.

Topics: Adrenocorticotropic Hormone; Aerosols; Asthma; Beclomethasone; Bronchitis; Chemical Phenomena; Chemistry; Chronic Disease; Collagen Diseases; Glucocorticoids; Humans; Lung Diseases, Obstructive; Respiratory Tract Diseases; Sarcoidosis; Time Factors

At doses similar to those used in the treatment of chronic bronchial asthma, intranasal beclomethasone dipropionate is effective in alleviating nasal symptoms of seasonal allergic and perennial rhinitis in about three-quarters of patients. Eye symptoms are not relieved. The carry-over effect of the evening dose is useful in preventing early morning attacks of sneezing. Intranasal beclomethasone dipropionate is useful in controlling symptoms persisting after polypectomy and may possibly delay or eliminate the need for the surgical removal of nasal polyps, which may shrink after several weeks or months of treatment.

Topics: Administration, Intranasal; Adrenal Glands; Adult; Beclomethasone; Child; Chronic Disease; Clinical Trials as Topic; Cromolyn Sodium; Drug Evaluation; Humans; Hydrocortisone; Methylprednisolone; Nasal Polyps; Placebos; Rhinitis, Allergic, Seasonal; Seasons

Asthma guidelines suggest that normal or near normal lung function should be one of the goals for good asthma control. Therefore, children with chronic persistent asthma and reduced peripheral airway function were assessed after the replacement of conventional inhaled corticosteroids (ICS) with an extrafine aerosol formulation, hydrofluoroalkane-134a beclomethoasone diproprionate (HFA-BDP).. Lung function and clinical details were studied in children with moderate persistent asthma who regularly attended the pediatric pulmonary outpatient clinic at Kosair Children's Hospital, Louisville, Kentucky, USA.. A total of 20 children, 7 girls and 13 boys, with stable asthma but reduced forced expiratory flows between 25% and 75% of vital capacity (FEF(25-75) ) were included in the study.. After the initial assessment, each subject was switched from conventional ICS to HFA-BDP. All other medications remained the same. Reassessment of lung function and clinical status was performed at least 3 weeks after the intervention.. FEF(25-75) increased from a mean of 50.75% to 68.85% predicted (P < 0.001). Forced expiratory volume in 1 sec (FEV(1)) also increased significantly from 84.6% to 93.8% predicted (P = 0.001). No changes asthma symptoms were observed.. Compared to conventional ICS, the use of HFA-BDP in asthmatic children significantly improves airflow in both the large and the peripheral airways without loss of asthma control.

Topics: Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Chronic Disease; Female; Humans; Hydrocarbons, Fluorinated; Lung; Male; Respiratory Function Tests; Retrospective Studies

Loratadine added to montelukast has been suggested to improve endpoints of asthma.. This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods. Patients (N = 406) were 15 to 65 years of age with a forced expiratory volume in 1 second (FEV(1))-predicted of 50% to 85%, FEV(1) reversibility > or = 15%, and a minimal level of daytime symptoms and beta -agonist use. This three-part 2X2 crossover-study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral montelukast 10 mg, loratadine 10 mg, montelukast 10 mg + loratadine 10 mg, or twice daily inhaled beclomethasone 200 mu g. A subsequent 48-week extension study compared montelukast + loratadine with beclomethasone. The primary endpoint was the percentage change from baseline in FEV(1).. Over 6 weeks of double-blind treatment, significant improvements (p < 0.05) in the primary endpoint of FEV(1) were seen for montelukast + loratadine versus loratadine (least-square mean percentage-point difference of 5.8%), beclomethasone versus montelukast + loratadine (2.35%), montelukast versus loratadine (5.94%), and beclomethasone versus montelukast (4.65%); a numerical improvement (p = 0.054) was seen for montelukast + loratadine versus montelukast (1.60%). Significant improvements for montelukast + loratadine versus montelukast were seen in some secondary endpoints (evening peak expiratory flow, nocturnal asthma symptom score, nocturnal awakenings, and asthma-specific quality of life) but not others. Significant improvements in most endpoints except daytime asthma symptoms score were seen for montelukast + loratadine versus loratadine. In the extension study, both montelukast + loratadine and beclomethasone improved several endpoints. All treatments were generally comparable in the percentage of patients with clinical and laboratory adverse experiences.. In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV(1) and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast + loratadine versus beclomethasone was seen in any endpoint.

Topics: Acetates; Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Beclomethasone; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Loratadine; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Young Adult

The most common approach for the treatment of chronic graft-versus-host disease (cGVHD) has been the long-term use of systemic steroids. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with relatively low absorption from the gastrointestinal mucosa. It has been successfully used to treat acute GVHD (aGVHD), but its use in the cGVHD setting is far more limited. In the current study, BDP was administered to 33 patients who underwent allogeneic transplantation and had biopsy-proven gastrointestinal cGVHD (GI cGVHD). Twenty-six patients with GI cGVHD received BDP as first-line and 7 as either second- or third-line treatment. All patients received BDP together with a calcineurin inhibitor, except for 1 patient who was also receiving mycophenolate mofetil (MMF). BDP was administered for a minimum of 16 weeks and was tapered during 4 additional weeks. Of those patients receiving BDP as the first line of treatment, 22 (84.6%) achieved complete remission (CR) of GI cGVHD, 2 (7.7%) achieved a partial response (PR) and 2 (7.7%) did not respond or progressed. Median time to response was 28 days. Nevertheless, only 7 (27%) patients had maintained the response at last follow-up, whereas 19 (73%) finally relapsed or progressed. Median time to relapse was 147 days after the end of BDP. In the case of the patients who received BDP as a second- or third-line treatment, 3 (42.9%) achieved CR and 2 (28.6%) PR. For the whole series of patients, 13 patients (39.4%) were not receiving immunosuppressive treatment at final follow-up. Only 4 patients developed cytomegalovirus (CMV) reactivation, which was successfully treated with antiviral drugs. No fungal infection was observed during the treatment period. In conclusion, the current study shows that BDP, in the absence of systemic steroids, is a highly effective initial therapeutic approach for GI cGVHD, which helps to avoid complications related to systemic steroids.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Beclomethasone; Biopsy; Chronic Disease; Female; Follow-Up Studies; Gastrointestinal Diseases; Graft vs Host Disease; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Transplantation, Homologous

It is important to determine whether chronic cough is associated with asthma and can be helped by treatment with inhaled corticosteroids.. To compare the effects of beclomethasone and placebo in patients with chronic cough for at least 8 weeks after excluding those with cough due to postnasal drip and gastroesophageal reflux disease.. A prospective, randomized, double-blind, placebo-controlled study comprising 64 patients was performed for 2 weeks. The active group received metered-dose inhaler chlorofluorocarbon-beclomethasone (1,500 microg/d), and the placebo group received identical-appearing placebo inhalers. All the participants completed a respiratory questionnaire and underwent bronchoprovocation testing (BPT) with methacholine and allergy skin testing. The primary outcome measure was a decrease in daily cough scores (symptom diary and visual analog scale) during the 2-week treatment period.. The active group comprised 44 patients and the placebo group 20 patients. Cough duration averaged 20 weeks. At the end of treatment 82% of the active group and 15% of the placebo group had complete resolution of cough. In the active group 22 patients (50%) had positive BPT results, and in the placebo group 10 patients (50%) had positive results. There was no correlation between treatment response and responses on the respiratory questionnaire, allergy skin testing, or BPT.. Therapy with high-dose inhaled beclomethasone provided an excellent response in a subgroup of patients with chronic cough that did not correlate with atopy or airway hyperresponsiveness.

Topics: Adult; Aged; Allergens; Anti-Inflammatory Agents; Beclomethasone; Bronchial Provocation Tests; Chronic Disease; Cough; Double-Blind Method; Female; Humans; Male; Methacholine Chloride; Middle Aged; Patient Compliance; Prospective Studies; Skin Tests; Spirometry; Treatment Outcome

There is considerable evidence from the literature that children with chronic lung disease of infancy (CLD) have abnormal pulmonary function in childhood and this could have an impact on their life quality and overall health. There are similarities between CLD and asthma, and corticosteroids are the mainstay treatment for asthma. Many physicians use inhaled corticosteroids in children with CLD with no evidence. Therefore we wish to conduct a randomized double-blinded placebo controlled trial to test for the role of inhaled corticosteroids in children aged from 3 to 9 years with a history of CLD. Our primary hypothesis will be that inhaled corticosteroids are beneficial in children with CLD.. Our primary hypothesis is that using inhaled steroids; Beclomethasone Dipropionate (QVAR) 100 mcg 2 puffs 2 times a day for 6 weeks will improve the respiratory system resistance and the quality of life in children with CLD.. We propose that Beclomethasone Dipropionate (QVAR) will affect the pulmonary function after 6 weeks of treatment. In summary we think that our study will highlight knowledge on whether the use of inhaled steroids is clinically effective for CLD.

Topics: Anti-Asthmatic Agents; Beclomethasone; Child; Child, Preschool; Chronic Disease; Double-Blind Method; Female; Humans; Lung Diseases; Male; Placebos; Quality of Life; Respiratory Function Tests; Treatment Outcome

Chronic lung disease (CLD) is one of the most severely disabling conditions of extremely low-birth-weight infants. Systemic corticosteroids are effective but cause many adverse effects. Targeted therapy with inhaled corticosteroids may be an effective and less toxic alternative.. To evaluate the additive effect of inhaled corticosteroids on markers of lung inflammation in infants receiving a 7-day course of systemic steroids.. Preterm neonates weighing 1 kg or less and aged 12 to 28 days who were prescribed a 7-day course of systemic corticosteroids for evolving CLD were studied prospectively and randomized to receive either a tapering 4-week course of beclomethasone metered-dose inhaler (MDI) (n = 5) or placebo MDI (n = 6). Primary outcome variables were the levels of pro- and anti-inflammatory cytokines, IL-8, TNF-alpha, IL-1alpha, and sIL-2R.. This study was terminated early following literature reports of the adverse neurodevelopmental effects of dexamethasone. Measurements of respiratory and serum IL-8, IL-1alpha and TNF-alpha were similar between the study group taking inhaled and systemic corticosteroids and the study group taking systemic steroids alone. No differences were found between the two groups in relation to dynamic compliance or resistance.. The addition of inhaled corticosteroids to a 7-day systemic course of corticosteroids did not alter cytokine response or improve pulmonary function.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Biomarkers; Chronic Disease; Cytokines; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung; Lung Diseases; Pneumonia

The use of nebulization for the administration of inhaled steroids plays an important role in asthma patients who are unable to use pressurized aerosol or dry-powder inhalers effectively. Moreover, the type of nebulizer used may affect how much drug is delivered to the lungs. The objective of this multinational, multicentre, randomized, active-controlled, parallel-group study was to compare the efficacy and safety of nebulized corticosteroids in adult patients with chronic asthma. Following a 1-week placebo run-in period, 205 patients, aged 18-65 years, with moderate persistent asthma were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 2,400 microg day(-1) b.i.d. (n = 103), or fluticasone propionate (FP) suspension for nebulization 2,000 microg day(-1) b.i.d. (n = 102), both administered by a jet nebulizer Comparable efficacy in controlling asthma was demonstrated by the two treatments at study end, as evident when evaluating various efficacy parameters (pulmonary function tests, asthma exacerbations and symptoms, and the use of rescue salbutamol). The primary efficacy endpoint was the variation in the pulmonary expiratory flow (PEF) at treatment end over the baseline visit. For the intent-to-treat population, in the BDP group mean PEF values increased statistically significantly from 5.2 +/- 1.31 s(-1) to 5.7 +/- 1.61 s(-1), while in the FP group the increase was from 5.2 +/- 1.21 s(-1) to 5.8 +/- 1.81 s(-1). Mean PEF values as per cent of predicted also increased in a statistically significant way, from 71% to 77.1 % in the BDP group, and from 70.1% to 76.9% in the FP group. The two treatments were equally well tolerated.A total of 23 and 32 patients in the BDP and FP groups, respectively, reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP 2,400 microg day(-1) and FP 2,000 microg day(-1), both suspensions for nebulization administered via a jet nebulizer, are equally effective, with an acceptable safety and tolerability profile, when used in adult patients with moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Vital Capacity

Our objective was to determine the safety and efficacy of aerosol beclomethasone vs. systemic dexamethasone for extubation in premature infants at high risk for chronic lung disease (CLD). Intubated preterm infants who were identified as being at high risk for moderate-severe CLD on day 14 of life were randomized to one of four groups. The control group received systemic dexamethasone and aerosol placebo, while the other three groups received either high (2.40-3.69 microg/kg/day delivered to lungs), medium (1.0-1.85 microg/kg/day), or low (0.48-0.74 microg/kg/day) dose aerosol beclomethasone and systemic placebo. Those receiving aerosol steroids who remained ventilator-dependent after 7 days were switched to standard 42-day tapering doses of systemic dexamethasone. The primary outcome was extubation within 1 week of starting steroids, using predefined criteria. Secondary variables included changes in lung function, rates of side effects, and tracheal aspirate white blood cell counts. Sixty-one infants with birth weights of 761 +/- 18 g (mean +/- SEM) and gestational ages of 25.7 +/- 0.2 weeks were randomized to one of the four groups. Seven of 15 infants in the control systemic dexamethasone group were successfully extubated compared with 3/16 in the high-dose beclomethasone group, 1/15 in the medium-dose group, and 2/15 in the low-dose group (P < 0.01). Only dexamethasone subjects demonstrated improvements in lung function over the study period. These infants also had significant increases in blood pressure and blood glucose levels, as well as a decline in their tracheal aspirate white blood cell count. In conclusion, aerosol beclomethasone at the very low doses used in this study did not facilitate extubation in intubated premature infants at high risk for moderate-severe CLD.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Chronic Disease; Device Removal; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Lung Diseases; Male; Outcome Assessment, Health Care; Respiration, Artificial; Respiratory Function Tests; Ventilator Weaning

To determine whether the dose of inhaled corticosteroids can be stepped down in patients with chronic stable asthma while maintaining control.. One year, randomised controlled, double blind, parallel group trial.. General practices throughout western and central Scotland.. 259 adult patients with asthma receiving regular treatment with inhaled corticosteroids at high dose (mean dose 1430 microg beclomethasone dipropionate).. Participants were allocated to receive either no alteration to their dose of inhaled corticosteroid (control) or a 50% reduction in their dose if they met criteria for stable asthma (stepdown).. Comparison of asthma exacerbation rates, asthma related visits to general practice and hospital, health status measures, and corticosteroid dosage between the two groups.. The proportions of subjects with asthma exacerbations were not significantly different (stepdown 31%, control 26%, P=0.354). Similarly, the numbers of visits to general practice or hospital and the disease specific and generic measures of health status over the one year period were not significantly different. On average the stepdown group received 348 microg (95% confidence interval 202 microg to 494 microg) of beclomethasone dipropionate less per day than the controls (a difference of 25%), with no difference in the annual dose of oral corticosteroids between the two treatment regimens.. By adopting a stepdown approach to the use of inhaled steroids at high doses in asthma a reduction in the dose can be achieved without compromising asthma control.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Double-Blind Method; Health Status; Humans; Middle Aged; Treatment Outcome

Symptoms often deteriorate in well-controlled asthmatics after a step down in inhaled beclomethasone dipropionate (iBDP) therapy if the serum concentration of eosinophil cationic protein (sECP) is high. This deterioration is significantly abrogated by pranlukast, a leukotriene receptor antagonist, or by seratrodast, a thromboxane A2 receptor antagonist. However, these results were based on short-term (less than 6 months) observations.. We studied 35 well-controlled adult asthmatics. We assigned the patients into different groups according to their sECP levels before the step down: (i) group A, sECP < 25 microg/L; (ii) group B, sECP > or = 25 microg/L; and (iii) group C, sECP > or = 25 microg/L but patients treated with pranlukast or seratrodast. We began the study with a step down in iBDP therapy (initial step down), then followed the clinical course of the asthma for 2 years. During the study period, we decreased, increased or maintained the iBDP dose on the basis of the stepwise approach described in the National Institutes of Health guidelines. We monitored the time and frequency of exacerbation and evaluated the iBDP dose required to control the asthma symptoms.. The rates of exacerbation after the step down were high in groups A and B. In group A, the conditions were again qualified for the step down in all patients, but this was not the case for most group B patients. From 15 to 21 months after the initial step down, the average dose of iBDP required to control symptoms was significantly higher in group B than in group A patients (P = 0.0127-0.0373). The exacerbation rate in group C after 12 months tended to be lower than in the other two patient groups (P = 0.0743). In group C, the average dose of iBDP from 9 to 24 months after the initial step down was significantly lower than before the step down (P < 0.0001) and was not significantly different from the mean dose of iBDP in groups A or B.. High sECP in well-controlled asthma may indicate the necessity for a higher iBDP dose over a long period than when the sECP concentration is not high. Even if sECP is high, pranlukast or seratrodast help to prevent exacerbation of asthma and enable successful step down in iBDP therapy for at least 2 years thereafter.

Topics: Adult; Aged; Analysis of Variance; Asthma; Beclomethasone; Benzoquinones; Blood Proteins; Chromones; Chronic Disease; Drug Therapy, Combination; Eosinophil Granule Proteins; Female; Glucocorticoids; Heptanoic Acids; Humans; Leukotriene Antagonists; Male; Middle Aged; Prognosis; Prospective Studies; Prostaglandin Antagonists; Respiratory Mechanics; Ribonucleases; Statistics, Nonparametric

To compare the cost effectiveness of hydrofluoroalkane 134a-beclomethasone dipropionate (HFA-BDP; Qvar) [corrected] with chlorofluorocarbon-beclomethasone dipropionate (CFC-BDP) in patients with chronic stable asthma previously receiving CFC-BDP, from the perspective of a healthcare provider.. Cost-effectiveness analysis based on a 12-month pragmatic, randomised, parallel group, open-label clinical trial assessing safety and efficacy of HFA-BDP at approximately half the dose of CFC-BDP in patients with stable asthma.. International, multicentre study at 57 study sites in the US, UK, The Netherlands, and Belgium. Healthcare costs were calculated for UK-based healthcare [in 1999 as pounds (pounds sterling)].. Patients (n = 473) > or =12 years of age with currently stable asthma that had been stable (i.e. no exacerbations requiring oral corticosteroid use in the last 4 weeks) for at least the preceding month.. Average and incremental cost-effectiveness ratios based upon symptom-free days, improvement in health-related quality of life, and total and drug-only direct healthcare costs.. Patients in the HFA-BDP group experienced a significantly higher percentage of symptom-free days than patients in the CFC-BDP group by the end of the study period (42.4 vs 20.0%; p = 0.006). A greater percentage of patients in the HFA-BDP group had a clinically significant improvement in health-related quality of life than in the CFC-BDP group [35.3 (n = 116/329) vs 16.1% (n = 18/112)]. Total per patient healthcare costs were similar between the two groups. The average cost per symptom-free day per patient was 1.36 pounds sterling for HFA-BDP and 1.81 pounds sterling for CFC-BDP based on total healthcare costs. The incremental cost per symptom-free day for using HFA-BDP instead of CFC-BDP was negative, indicating that HFA-BDP is a dominant strategy and may be a cost-saving intervention compared with CFC-BDP. A sensitivity analysis varying both cost and outcome parameters further supported this finding for most scenarios tested. The cost to achieve a clinically significant improvement in health-related quality of life over the study period was 13.24 pounds sterling per improved patient per week for HFA-BDP and 29.38 pounds sterling per patient per week for CFC-BDP.. These findings indicate that HFA-BDP is a cost-effective intervention when compared with CFC-BDP in this group of patients with stable asthma. In the majority of scenarios HFA-BDP provides more effective asthma control at a similar cost to CFC-BDP.

Topics: Asthma; Beclomethasone; Chlorofluorocarbons; Chronic Disease; Cost-Benefit Analysis; Humans; Hydrocarbons, Fluorinated; Prospective Studies; Quality of Life; Treatment Outcome

A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.. The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.. A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.. Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).. Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Prospective Studies; Treatment Outcome

Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported.. To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma.. Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively.. Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period.. Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Leukocyte Count; Leukotriene Antagonists; Male; Middle Aged; Predictive Value of Tests; Quinolines; Sulfides; Time

High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.. Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.. It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.. It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Biomarkers; Budesonide; Chronic Disease; Contusions; Creatinine; Female; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Quality of Life

The use of short-acting beta2-agonists is associated with oral mucosa injuries that are probably provoked by decreased saliva flow and decreased concentrations of immunoglobulin (Ig)A in saliva.. To explore the effect of salmeterol, alone or combined with beclomethasone, on the health of oral mucosa, as well as its effect on saliva flow and IgA concentration in saliva.. Patients ranging in age from 6 to 15 years with moderate-persistent chronic asthma were enrolled. Patients received two 6-week treatments, one with salmeterol plus beclomethasone and the other with only salmeterol, with a 1-week washout period between treatments. Patients had oral cavity examinations and assessments of saliva flow, IgA in saliva, and total protein in saliva before the beginning and at the end of each treatment. The results of the baseline oral examinations were normal in all patients. The postsalmetrol (PS) examinations detected 13 patients with gingivitis and the postbeclomethasone-salmeterol (PBS) examinations disclosed 10 patients with gingivitis and 1 with lower-lip ulceration. Baseline saliva flow was 16.25 +/- 7.04 mm/minute (confidence interval [CI] 95% 13.67; 18.89), PS was 13.53 +/- 5.93 mm/minute (CI 95% 11.33; 15.73), and PBS was 16.57 +/- 5.54 mm/minute (CI 95% 14.51; 18.62). No statistical differences between the different assessments were found. Mean saliva IgA at baseline was 4.99 +/- 1.96 mg/dL (CI 95% 4.26; 5.71), PS IgA was 6.53 +/- 3.02 mg/dL (CI 95% 5.41; 7.65), and PBS IgA was 4.82 +/- 1.98 mg/dL (CI 95% 4.08; 5.56). PS IgA was significantly higher than the other two determinations (P < 0.05 by Bonferroni and Tukey tests). Baseline saliva IgA-to-protein ratio was 0.72 +/- 0.24 (95% CI 0.64; 0.80), PS IgA:protein ratio was 1.02 +/- 0.38 (95% CI 0.88; 1.16), and PBS IgA:protein ratio was 0.72 +/- 0.25 (95% CI 0.62; 0.82). PS IgA:protein ratio was significantly higher than the other two determinations (P < 0.05 by Bonferroni and Tukey tests).. In the present study it was demonstrated that salmeterol alone or in combination with beclomethasone induced injuries in the oral mucosa, but only salmeterol alone induced increases in the total and protein-adjusted IgA in saliva.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Child; Chronic Disease; Cross-Over Studies; Drug Interactions; Female; Humans; Immunoglobulin A; Longitudinal Studies; Male; Mouth Diseases; Saliva; Salivary Glands; Salivary Proteins and Peptides; Salivation; Salmeterol Xinafoate; Single-Blind Method

Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.. In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 microgram beclomethasone dipropionate (BDP) daily and inhaled beta(2) agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 microgram BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 microgram BDP) over a six month period was examined.. One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.. There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

Topics: Adolescent; Adult; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Chronic Disease; Double-Blind Method; Family Practice; Female; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Theophylline; Treatment Outcome

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Chronic Disease; Clodronic Acid; Fluticasone; Humans; Infusion Pumps; Male; Middle Aged; Osteoporosis

The purpose of this study was to compare the effects of daily inhaled beclomethasone (3 x 500 microg) started on day 3 of life, with that of systemic dexamethasone (0.5 mg/kg/day) started between days 11-13 on clinical variables, lung inflammation, and pulmonary microvascular permeability in preterm infants at risk for chronic lung disease (CLD). Following administration of surfactant, preterm neonates with RDS and a birth weight of less than 1,200 g were included in this comparative observational pilot study when still mechanically ventilated and with an oxygen requirement on the third day of life. The patients (gestational age 26.1+/-0.9 weeks, birth weight 826+/-140 g, mean+/-SD) were alternately allocated to prophylactic treatment with inhaled beclomethasone (n = 7), or to early systemic dexamethasone therapy after day 10 of life, if clinically indicated (n = 9). Pulmonary inflammation and lung permeability were assessed by analyzing the levels of interleukin-8, elastase alpha1 proteinase inhibitor, free elastase activity, and albumin in tracheal aspirates on days 10 and 14 of life. The secretory component of IgA served as reference protein. We observed no significant differences in the concentrations of interleukin-8, elastase alpha1 proteinase inhibitor, and albumin between the two groups on day 10 of life. On day 14, 3 (median; range, 1-3) days following initiation of dexamethasone treatment, concentrations of the inflammatory mediators and of albumin were significantly lower in the group on systemic steroid therapy than in the group treated with inhaled steroids (P < 0.01). Additionally, there was a significant difference in oxygen requirements between both groups on day 14. In the group treated with inhaled steroids, concentrations of the inflammatory mediators, albumin, and oxygen requirements did not show a difference between day 10 and 14. We conclude that, in contrast to systemic dexamethasone treatment, a 12-day course of inhaled beclomethasone does not affect lung inflammation and pulmonary microvascular permeability in preterm infants at risk for CLD within the first 2 weeks of life.

Topics: Administration, Inhalation; Beclomethasone; Capillary Permeability; Chronic Disease; Dexamethasone; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation Mediators; Interleukin-8; Lung; Lung Diseases; Pancreatic Elastase; Pilot Projects; Protease Inhibitors; Respiration, Artificial

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides

Following otitis media, 10% to 50% of children develop residual middle ear effusion with concurrent hearing loss and potential cognitive, behavioral, and language impairment. Prophylactic antibiotics and tympanostomy tubes are currently recommended treatments for chronic middle ear effusion.. In a double-blind, placebo-controlled, randomized study of chronic middle ear effusion, we assessed the effectiveness of topical intranasal beclomethasone as an adjunct to prophylactic antibiotic therapy.. Sixty-one children, aged 3 to 11 years with persistent middle ear effusion greater than 3 months, were randomized into three treatment groups: (1) prophylactic antibiotics; (2) prophylactic antibiotics plus intranasal beclomethasone (336 micrograms/day); and (3) prophylactic antibiotics plus intranasal placebo. Patients were evaluated with aeroallergen skin tests at entry; and tympanogram, otoscopic examination, and symptom questionnaire at 0, 4, 8, and 12 weeks.. While middle ear pressures, otoscopic examinations, and symptom scores were improved for each treatment group over 12 weeks of therapy, the beclomethasone plus antibiotics group improved all three measures more rapidly than the antibiotics-alone and placebo nasal spray plus antibiotics groups over the first 8 weeks. Only the beclomethasone group significantly improved left (P = .004) and right (P = .01) middle ear pressures over 12 weeks. Resolution of chronic middle ear effusions was more frequent in the beclomethasone group (P < or = .05 at 4 and 8 weeks). No difference in response to nasal steroids was observed between atopic and nonatopic subjects.. We conclude that intranasal beclomethasone may be a useful adjunct to prophylactic antibiotic treatment of chronic middle ear effusion.

Topics: Acoustic Impedance Tests; Acute Disease; Administration, Intranasal; Anti-Bacterial Agents; Anti-Inflammatory Agents; Beclomethasone; Child; Child, Preschool; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Otitis Media; Otitis Media with Effusion; Otoscopes; Patient Compliance; Severity of Illness Index; Sinusitis; Treatment Outcome

Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 microg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441-5435 pg/ml), TNF-alpha 37.3 pg/ml (3.75-524 pg/ml) and ECP 33 ng/ml (1.5-250 ng/ml) versus age-matched healthy controls: IL-8 median 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) and ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-4556 pg/ml; TNF-alpha 13.9 pg/ml, 4.1-291.6 pg/ml; ECP 32.3 ng/ml, 3.7-58.4 ng/ml). Our results demonstrate that conventional management of sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.

Topics: Acetylcysteine; Administration, Intranasal; Adolescent; Adult; Agammaglobulinemia; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Ataxia Telangiectasia; Azithromycin; Beclomethasone; Blood Proteins; Child; Child, Preschool; Chronic Disease; Common Variable Immunodeficiency; Eosinophil Granule Proteins; Ethmoid Sinusitis; Female; Frontal Sinusitis; Glucocorticoids; Humans; Immunization, Passive; Interleukin-8; Lymphoproliferative Disorders; Magnetic Resonance Imaging; Male; Nasal Lavage Fluid; Paranasal Sinuses; Radiography; Ribonucleases; Sinusitis; Tumor Necrosis Factor-alpha

We studied the usefulness of 18 weeks of therapy with two high doses of inhaled beclomethasone dipropionate (BDP) in the management of severe asthma in adults. The patients had asthma symptoms that had not been controlled by combination therapy with BDP (800 micrograms/day) and bronchodilators. They were divided into two groups. Patients in group A (n = 16) were treated with 1800 micrograms/day of BDP and bronchodilators. Patients in group B (n = 10) were treated with 1400 micrograms/day of BDP and bronchodilators. BDP was inhaled via a large spacer (Volumatic). Eleven patients in group A and 6 patients in group B had been given an oral steroid regularly before the study. Asthma symptom scores, peak expiratory flow (PEF), pulmonary function, bronchial reactivity to methacholine, the total amount of oral steroid, and adrenocortical function were recorded. Results. 1) Clinical characteristics before the start of the study did not differ between groups. 2) Asthma symptom scores decreased to a greater extent in patients who received the higher dose of BDP than in those who received the lower dose. 3) Only the higher dose of BDP significantly increased evening and morning % PEF, as measured 6 weeks and 8 weeks after the start of the treatment. 4) Only the higher dose of BDP significantly increased the FEV1 and the PC20 for methacholine. FVC did not increase. 5) Only the higher dose of BDP significantly decreased the total amount of oral steroid needed to control asthma. 6) Results of the rapid ACTH test indicated that neither dose of BDP suppressed adrenocoritical function. Furthermore, the serum cortisol level measured early in the morning increased to within the normal range in the three patients in whom oral steroid therapy could be reduced or stopped after treatment. These data indicate that 1800 micrograms of BDP per day is more effective than 1400 micrograms/day at the beginning of long-term management of severe chronic asthma in adults whose symptoms are not controlled with the combination of 800 micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600 micrograms/day) of an inhaled steroid is more useful and should be promptly begun to treat severe asthma.

Topics: Administration, Inhalation; Adult; Age of Onset; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged

Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease.. Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology.. Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology.. Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.

Topics: Anti-Inflammatory Agents; Bacterial Infections; Beclomethasone; Child; Child, Preschool; Chronic Disease; Double-Blind Method; Female; Humans; Male; Native Hawaiian or Other Pacific Islander; New South Wales; Otitis Media with Effusion; Rhinitis; Seasons

To study the effects of an inhaled steroid on airway hyperresponsiveness (AHR) in chronic stable asthma, AHR was measured every month for 1 year in seven patients after their asthma had stabilized, i.e., when they had no wheezing or dyspnea, and their peak expiratory flow rates (PEFR) were at least 80 percent of the highest value. During the study period, no patient wheezed or had dyspnea, and daily variation in PEFR was less than 20 percent. In six patients, FEV1 was stable, and PEFR was always at least 80 percent of the highest value. AHR became less severe, by a factor of at least 2, in five of these six patients, but one patient's condition did not improve. The one patient whose PEFR fell below 80 percent of the highest value had more than a 4-fold increase in the severity of AHR. In conclusion, the severity of AHR can be reduced, even in patients with chronic stable asthma, if daily PEFR can be maintained in an optimal range by long-term use of inhaled corticosteroids.

Topics: Administration, Inhalation; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chronic Disease; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

We studied the usefulness of 24 weeks of therapy with inhaled beclomethasone dipropionate (BDP) in the management of mild and moderately severe asthma in adults. To determine the optimal dose and treatment duration, the patients were divided into three groups. Patients in group I (n = 10) were treated with bronchodilators but no BDP. Patients in group II (n = 12) received bronchodilators and 450 micrograms/day of BDP. Patients in group III (n = 17) received bronchodilators and 900 micrograms/day of BDP. BDP was inhaled via a large spacer (Volumatic). Asthma scores were measured before treatment began, and again every 2 weeks for the duration of the study (26 weeks). Peak expiratory flows (PEF) were measured before treatment began, 2 weeks after treatment had begun, and again every four weeks until the end of the study. Vital capacity, FEV1, and bronchial reactivity to methacholine were measured before treatment began, and again 12 weeks and 24 weeks after it had begun. Adrenocortical function in patients in group III was measured with a rapid ACTH test, at the same time as the pulmonary functions were measured. The results were: 1) Asthma scores decreased more in patients who received the higher dose of BDP than in those who received the lower dose, especially during the second 12 weeks. 2) After two weeks of treatment, %PEF had increased significantly in both groups that received BDP, but after six weeks of treatment there was no further improvement. %PEF did not improve in the group given bronchodilators only. 3) In the patients whose baseline %PEF was less than 80%, only the higher dose of BDP significantly increased %PEF. 4) Only the higher dose of BDP increased the %VC, the FEV1%, and the PD20 for methacholine. 5) Asthma type and severity were not related to the usefulness of BDP therapy. 6) Results of the rapid ACTH test indicated that the higher dose of BDP did not suppress adrenocortical function. These data indicate that 900 micrograms of BDP per day is more effective than 450 micrograms/day as initial therapy for long-term management of mild or moderate asthma in adults, and that the dose of BDP should be reviewed after 3 months of treatment. Patients in whom asthma is well-controlled may tolerate a reduction in dose, and those in whom asthma is not well-controlled may require a higher dose.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged; Time Factors

Clinical experiences have suggested distinct differences in responses to anti-asthmatic drugs between patients suffering early morning asthmatic attacks and those experiencing nocturnal ones. However, there has been no report on any difference in the improvement of asthmatic flow dipping after inhaled and/or oral steroid treatment. In this retrospective study, the peak expiratory flow rates (PEF), which had been monitored four times a day, were reviewed in 40 chronic asthmatics. The group consisted of 19 patients with very low PEF (geometrical mean PEF/week [mPEF] < 60% of the personal best PEF), 15 patients with moderately low PEF (mPEF 60% to 70% of personal best PEF), 2 patients with mildly low PEF (mPEF 70% to 80% of personal best PEF) and 4 patients with occasionally low PEF (mPEF > 80% of personal best PEF). Of 40 chronic asthmatics, 22 patients had morning dipping alone and 10 patients had both morning dipping and nocturnal dipping. After inhaled and/or oral steroid treatment at sufficient level, mPEF was improved in all patients. All the dipping disappeared except for morning dipping in five cases. We concluded that there was a difference in responses to inhaled and/or oral steroids during early morning dipping and during nocturnal dipping in chronic asthmatics. There should be further investigation to discriminate between pathophysiological events that may be related to morning dipping and to nocturnal dipping.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Asthma; Beclomethasone; Chronic Disease; Circadian Rhythm; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisolone; Retrospective Studies

The physiopathology of chronic cough remains obscure. We evaluated the possibility that chronic cough in nonasthmatic subjects is associated with airway inflammation, and if this is so, what the relationship between this inflammation and the possible etiology of cough might be, as well as its response to inhaled steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The evaluation included a respiratory questionnaire, a physical examination, allergy skin-prick tests, chest and sinus radiographs, esophageal pH monitoring, measurements of expiratory flows, methacholine and citric acid challenges, and flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies. Fourteen subjects further accepted participation in a randomized, double-blind crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a placebo for 1 mo each. Four groups of subjects were identified according to the presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an increased number of inflammatory cells in their bronchoalveolar lavage fluid (BALF), but there was no significant difference between the four subgroups of coughers. As compared with control subjects, the bronchial biopsies of subjects with chronic cough showed increased epithelial desquamation (p = 0.004) and inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia. These findings were not significantly different between the different etiologic groups. In subjects with chronic cough, basement-membrane thickness was normal and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Asthma; Beclomethasone; Bronchi; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Cough; Double-Blind Method; Female; Humans; Male

The prevalence of posterior subcapsular cataracts in young patients receiving inhaled glucocorticoids for treatment of chronic asthma is unknown. In a cross-sectional study, slit-lamp examinations were done on 95 consecutive young patients who were taking inhaled beclomethasone or budesonide. No posterior subcapsular cataracts were found. The median age of the patients was 13.8 (range 5.8-24.8). The median dose of inhaled beclomethasone or budesonide was 750 micrograms/day (range 300-2000), or 12.9 micrograms/kg per day (range 7.5-34.2). The median duration of treatment was 5 years (range 1-15). 77% of the patients had not used oral glucocorticoids in the year preceding the examination. This study suggests that routine screening for posterior subcapsular cataracts in this patient population is not warranted.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cataract; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Female; Humans; Male; Manitoba; Patient Compliance; Pregnenediones

With mucosal inflammation contributing to the pathogenesis of asthma, it is increasingly accepted that long term steroid inhalers may induce remission in chronic long standing asthmatics. The present study involved 44 stable asthmatics who were randomly given either beclomethasone dipropionate inhaler (50 ug) 2 puffs qds or salbutamol inhaler (100 mcg) 2 puffs tds in addition to their oral bronchodilators. Pulmonary function testing, bronchoalveolar lavage and complete blood count were done at basal and weekly intervals and at the end of the study. The absolute eosinophil count showed a significant drop in the beclomethasone group as compared to the salbutamol group. Serial lung functions showed a significant improvement in the pre-bronchodilator PEFR and the pre-bronchodilator FVC in the beclomethasone group as compared to the salbutamol group. There was no significant change in the lavage eosinophil count pre and post-bronchodilator in both groups. Steroid inhalers are thus useful in long term management of bronchial asthma especially with respect to reducing bronchodilator requirement.

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Vital Capacity

To compare the benefits and adverse reactions of theophylline and beclomethasone (BDP) in the long-term control of mild to moderate chronic asthma in children.. Multicentered, double-blind, double-placebo, randomized, controlled trial.. One hundred ninety-five children between the ages of 6 and 16 years with mild to moderate asthma.. Treatment with either BDP, 84 micrograms four times a day, or sustained-release theophylline administered twice daily in doses adjusted for optimum control of symptoms.. Daily diary record of symptoms, peak flow rates, supplemental bronchodilator and glucocorticoid treatment, doctor and hospital visits, absence from work and school, and side effects.. Aerosol BDP and sustained-release theophylline were effective primary treatments for mild to moderate chronic asthma. Beclomethasone resulted in comparable symptom control with less bronchodilator use and fewer courses of systemic steroids than did theophylline. Side effects were observed significantly more frequently with theophylline than with BDP. Growth velocity suppression was noted with BDP and was more pronounced in boys. Suppression was not associated with alterations in cortisol measurements either at baseline or following stimulation.. Both theophylline and BDP are effective therapy for mild to moderate asthma. Caution must be used with the administration of BDP in children because of possible growth velocity suppression.

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Child; Chronic Disease; Double-Blind Method; Female; Forced Expiratory Volume; Growth; Humans; Male; Peak Expiratory Flow Rate; Theophylline; Treatment Outcome

Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a "bronchial sample." The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adult; Aerosols; Airway Obstruction; Albumins; Beclomethasone; Blood Gas Analysis; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chronic Disease; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Inflammation; Lactoferrin; Male; Middle Aged; Muramidase; Smoking; Transferrin; Vital Capacity

Three combination regimens, (1) inhaled albuterol (ALB) with oral theophylline (THEO), (2) inhaled ALB with inhaled beclomethasone dipropionate (BDP), or (3) inhaled ALB, inhaled BDP, and oral THEO, were evaluated and compared as optimal pharmacotherapy for chronic asthma in 111 children. In this double-blind, parallel-group, multicenter study, children, aged 6 to 16 years with moderately severe asthma (unstable despite daily medications), were treated with one of the combinations for 12 weeks. Patients were evaluated every 4 weeks by spirometry and serum THEO measurement. Patients kept daily symptom diaries, measured peak flow rates twice daily, and recorded adverse events. Treatment groups did not differ in disease or demographic characteristics at study entry. All three combination treatments provided and maintained significant improvement in FVC, FEV1, and FEF25%-75% volume points, and compared with that of pretreatment, with no significant differences between treatments. Throughout the 12-week treatment period, however, patients receiving BDP had lower symptom scores, fewer had more than one asthma attack, fewer required "bursts" of prednisone (p = 0.001), and fewer required rescue medication (p = 0.009). Significantly more patients receiving BDP said that they felt better than they did at the beginning of the study compared with the number of patients not receiving BDP (p = 0.002). Adverse events were similar among treatment groups.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Albuterol; Asthma; Beclomethasone; Chi-Square Distribution; Child; Chronic Disease; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Humans; Theophylline

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisone; Vital Capacity

Thirty-one patients with a dry cough for at least 1 h duration in more than half of the last 30 days and with no recent respiratory infection participated in a clinical trial to evaluate the effect of inhaled beclomethasone dipropionate (BDP). Lung function was normal and reversibility was excluded by spirometry before and after bronchodilator and by no diurnal variation in home peak flow monitoring. Only one had significant eosinophilia and only three were mildly hyperreactive by bronchial provocation with histamine. After a 1-week run-in period the patients were randomly allocated to receive either BDP 4 puffs of 50 micrograms b.i.d., or placebo. After 2 weeks the patients were crossed over and received the alternative treatment for another 2-week period. The degree of cough, disturbance of night sleep and peak expiratory flow morning and evening were recorded daily in a diary. Spirometry was performed at each control visit. A significant period effect from run-in to period 1 and/or from period 1 to period 2 was demonstrated for cough and disturbance at night but not for peak flow or spirometry. However, no significant treatment effect was found for any of the measured variables.

Topics: Administration, Inhalation; Adolescent; Adult; Beclomethasone; Bronchial Provocation Tests; Chronic Disease; Clinical Trials as Topic; Cough; Double-Blind Method; Female; Humans; Male; Middle Aged; Random Allocation

Twice-daily and four-times daily treatment with beclomethasone dipropionate aerosol were compared in a double dummy crossover study in patients with severe chronic bronchial asthma. The trial consisted of two two-month treatment periods preceded by a two-week baseline period. No significant difference was found in the morning or evening PEF, in symptom scores for wheeze, cough, sputum, sleep disturbance, limitation of daily activity, rhinitis, daily usage of bronchodilator aerosol or requirement for additional oral corticosteroids. The study has confirmed that in management of severe bronchial asthma, a twice-daily regimen of beclomethasone dipropionate aerosol is as effective as four-times daily treatment, if the total daily dose of beclomethasone dipropionate is kept unchanged.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged; Random Allocation; Time Factors

In a short-term, open cross-over clinical efficacy study, inhalation of budesonide 800 micrograms once daily was compared to inhalation of budesonide 400 micrograms twice daily and beclomethasone dipropionate 200 micrograms four times daily in 20 patients with stable steroid-dependent chronic asthma. Budesonide was inhaled through a spacer tube. The drugs were given in 3-week periods. Clinical symptoms, consumption of beta 2-agonists and peak flow were measured. In all but one patient, the reduced frequency of budesonide inhalations to only once daily has not given significantly different results compared with more frequent inhalations.

Topics: Administration, Intranasal; Asthma; Beclomethasone; Budesonide; Chronic Disease; Clinical Trials as Topic; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones; Random Allocation

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Budesonide; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones

A randomised double-blind crossover study was undertaken in 25 patients with variable airflow obstruction to assess the benefit of separating the inhalation of beta-agonist aerosols and corticosteroid aerosols by a timed interval of more than five minutes. Twenty-two patients (11 men and 11 women) completed 12 weeks of study; they inhaled 200 micrograms salbutamol followed either immediately or after a timed interval by 100 micrograms beclomethasone dipropionate two to four times daily. Morning and evening peak expiratory flow rates, symptom scores, additional beta-agonist inhaler usage, and subjective responses on a visual-analogue scale were recorded throughout. Results from the two last four-week periods, with and without the interval between drugs, were analysed. No differences were found. It is concluded that the theoretical benefit of delaying corticosteroid inhalation until optimum bronchodilatation has been achieved with a beta-agonist is not demonstrable in outpatient practice.

Topics: Adolescent; Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Random Allocation; Time Factors

Some patients with chronic asthma treated with beclomethasone aerosol (BA) derive significant symptom benefit, yet have persisting adrenal suppression due in part to their BA therapy. The daily dose of BA required is higher in patients with atopy. We therefore assessed the usefulness of ancillary treatment with cromolyn sodium (CS), a drug known to inhibit atopic asthma, to try to improve the balance of risk vs benefit in such patients. Thirty asthmatics, well controlled on high-dose BA (mean, 1,040 micrograms +/- 97 SE) but with morning cortisol levels averaging approximately 10 micrograms/dl, were allocated randomly to placebo or CS inhalant, used in addition to their regular BA and other asthma medications. After 4 wk, their BA dose was halved. Both groups were monitored for greater than 6 mo by daily symptom diaries and peak flows, and by spirograms and morning serum cortisol tests every 4 wk. Mean cortisol levels rose 27% after BA dose reduction (p less than 0.05) but asthma worsened. Risk-benefit assessments 20 wk after reducing the BA showed a general tendency for higher cortisol values to be coupled with worsening of the asthma symptoms and FEF25%-75%. The distributions of good, fair, and poor risk-benefit responses were the same in both CS and placebo-treated groups (p = 0.20). In other asthmatics who may have less associated bronchitis or small airways obstruction than these patients, CS might prove useful, but in these adult chronic asthmatics with this particular therapeutic problem, there was no discernible BA-sparing effect or other clinical advantage from adding CS to their established BA regimen.

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Cromolyn Sodium; Drug Combinations; Humans

Flunisolide, a derivative of fluocinolone acetonide, is advocated for intranasal inhalation for the treatment of perennial and seasonal allergic rhinitis. It is rapidly absorbed by all routes of administration, but it quickly undergoes extensive first-pass metabolism to a 6 beta-hydroxylated metabolite, which possesses only weak corticosteroid effects. Intranasal flunisolide relieves nasal symptoms (but not eye symptoms) in both perennial and seasonal allergic rhinitis, being most effective in patients who have an allergic component to their rhinitis; and like other corticosteroids it may reduce the need for systemic antihistamines in such patients, expecially during peak pollen periods. A few well designed comparative studies have shown flunisolide to be as effective as intranasal beclomethasone, and (in a single study) more effective than intranasal sodium cromoglycate solution. Only transient side effects have occurred, including nasal stinging and throat irritation. No Candida infections have been clinically apparent in short or longer term trials. Resting morning plasma cortisol levels have not been suppressed by usual therapeutic doses of intranasal flunisolide, but the drug's effects on hypothalamo-pituitary-adrenal (HPA) axis integrity during conditions of stress have not been evaluated.

Topics: Beclomethasone; Chronic Disease; Clinical Trials as Topic; Cromolyn Sodium; Fluocinolone Acetonide; Glucocorticoids; Histamine Antagonists; Humans; Kinetics; Rhinitis; Rhinitis, Allergic, Seasonal

A double-blind cross-over trial was carried out to compare the effect of identical placebo with that of salbutamol inhalers used 30 min before inhalation of 100 microgram of beclomethasone dipropionate (B.D.P.) in 18 chronic asthmatics over two consecutive 4-week periods. The salbutamol and B.D.P. combination resulted in a significant improvement in the peak expiratory flow-rate and F.E.V.1, significantly less use of the rescue inhaler, and better control.

Topics: Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Bronchi; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Placebos

Topics: Administration, Intranasal; Adolescent; Adult; Bacteria; Beclomethasone; Candida albicans; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Placebos; Rhinitis, Allergic, Seasonal

The effects of beclomethasone, dipropionate aerosol (DBA) (400 microgram/day) on clinical course, pulmonary function, and pituitary-adrenal function was studied in 34 steroid-dependent asthmatic children. Asthma severity was assessed by daily symptom and medication scores, peak flow measured three times a day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal cortisol levels, cortisol responses to intravenous (IV) corticotropin (ACTH), and steroid responses to IV metyrapone. After 12 weeks of BDA therapy, 30 of 34 patients no longer required prednisone. Mean weekly symptom and medication scores and the number of attacks decreased significantly (P less than .01)). A significant improvement was demonstrated in the patients' peak flow (P less than .01), forced expiratory volume in one second, and maximum midexpiratory flow rates (P less than .01). Thirty of the 34 patients initially had abnormal metyrapone responses, 28 had abnormal diurnal cortisol levels, whereas only 14 had abnormal IV ACTH response tests. Although significant improvement was noted in the mean metyrapone and diurnal cortisol tests, only partial recovery of pituitary-adrenal function was observed in 20 patients, complete recovery in 5, and no change in 9. BDA was found to be therapeutically superior to oral steroids in the group of steroid-dependent asthmatic children and produced no serious adverse effects.

Topics: Administration, Oral; Adolescent; Adrenal Glands; Adult; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Lung; Male; Pituitary Gland; Pituitary-Adrenal Function Tests; Prednisone

In a double-blind study beclomethasone dipropionate inhaled as a dry powder in doses of 100 microgram four times daily and 150 microgram four times daily was compared with the conventional aerosol dose of 100 microgram four times daily in 20 outpatients with chronic asthma. Each of the three treatments was given for four weeks. The dry powder in a dose of 150 microgram four times daily had advantages over the other two treatments in terms of FEV1 and the number of exacerbations of asthma during the study. There were no adverse reactions to inhaling dry-powder beclomethasone. It was concluded that this new way of administering the drug was effective in chronic asthma, and should allow most patients with chronic asthma who cannot use conventional pressurised aerosols efficiently to benefit from inhaled corticosteroid treatment.

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Powders; Respiratory Function Tests; Respiratory Therapy

Twenty-two children suffering from severe perennial rhinitis were treated with intranasal beclomethasone dipropionate (300 microgram/day) and an identical placebo aerosol in a double-blind cross-over trial. The results confirmed the value of beclomethasone dipropionate in improving nasal symptoms and signs due to perennial rhinitis, and allergic eye symptoms caused by associated conjunctivitis.

Topics: Administration, Intranasal; Adolescent; Aerosols; Beclomethasone; Child; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Placebos; Rhinitis, Allergic, Seasonal

In a 26-wk double-blind controlled study of 34 patients whose asthma had been poorly controlled despite oral steroids, valuable clinical and pulmonary function improvement was derived by adding beclomethasone aerosol to the prednisone regimen. The amount of improvement correlated linearly with beclomethasone dosage over the range 200 to 1,600 microng/day. These patients required relatively high dosage. Success in achieving asymptomatic status was only 26% with the conventional 400 microng/day and 60% at 1,600 microng/day. Oropharyngeal candidiasis was also dose-related but did not prohibit the use of high-dosage beclomethasone. Respiratory infections, physical signs, blood glucose, and electrolytes were unaffected by the drug. A dose-related suppression of cortisol secretion was demonstrated, but about 1/4 of the group had normal plasma cortisol even at 1,600 microng/day plus the oral prednisone. An individualized risk-benefit assessment seems a better basis for choosing an optimal beclomethasone regimen for each patient than adherence to a conventionalized fixed dosage of 400 microng/day. This requires definition of: (1) a specific goal of treatment in the individual patient and the beclomethasone dosage required to achieve it; (2) the adrenocortical functional response of that particular patient to the desired dose of beclomethasone; and (3) the presence and degree of any dose-limiting constraints such as preexisting complications of steroid use.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Candidiasis, Oral; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eosinophils; Female; Humans; Hydrocortisone; Leukocyte Count; Male; Middle Aged; Prednisone

Topics: Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Cough; Humans; Spasm

Topics: Adult; Aerosols; Atrophy; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Common Cold; Hemorrhage; Humans; Infections; Nasal Polyps; Nose; Rhinitis; Rhinitis, Allergic, Seasonal

Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued.

Topics: Administration, Oral; Adrenal Glands; Aerosols; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Humans; Hydrocortisone; Hypothalamus; Pituitary Gland; Prednisone; Substance Withdrawal Syndrome

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aerosols; Aged; Aspergillosis; Asthma; Beclomethasone; Candidiasis; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Pregnancy; Seasons; Substance-Related Disorders; Time Factors

1. Five years' experience in the use of beclomethasone dipropionate aerosol (BDA) in the treatment of 315 patients with upper respiratory tract allergy is reviewed. 2. A total of 223 patients with perennial rhinitis was treated. In 23, where the nasal allergy had recurred after oral corticosteroid therapy for asthma was withdrawn, BDA was effective in 69% of cases. A similar success rate (68%) was recorded in 169 patients suffering from perennial allergic rhinitis alone, but a satisfactory response was observed in only 45% of 31 patients with nasal polypi. 3. In 92 patients with seasonal allergic rhinitis freedom from symptoms was achieved in 80%. 4. A total of approximately 534 patient-years of treatment has been recorded without any evidence of side-effects either clinically or on nasal biopsy.

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Humans; Rhinitis; Seasons

In a double-blind, randomized study, 93 corticosteroid-independent patients with chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 mug per day of its vehicle for 4 wk to determine and compare the effectiveness and safety of the preparations. Evaluations made before, at weekly intervals during, and 1 wk after treatment indicated that beclomethasone dipropionate aerosol was superior to its vehicle is improving FVC, FEV1, FEF25%--75%, and clinical signs and symptoms, and in the overall evaluations by both the investigators and the patients. Plasma cortisol levels measured at the end of the second and fourth weeks were not substantially different from those before treatment in either group. No significant side effects or abnormalities in laboratory results were noted.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Methylprednisolone; Middle Aged; Respiratory Function Tests

Topics: Adult; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Female; Forced Expiratory Volume; Humans; Male; Methylprednisolone; Middle Aged; Peak Expiratory Flow Rate; Vital Capacity

At doses similar to those used in the treatment of chronic bronchial asthma, intranasal beclomethasone dipropionate is effective in alleviating nasal symptoms of seasonal allergic and perennial rhinitis in about three-quarters of patients. Eye symptoms are not relieved. The carry-over effect of the evening dose is useful in preventing early morning attacks of sneezing. Intranasal beclomethasone dipropionate is useful in controlling symptoms persisting after polypectomy and may possibly delay or eliminate the need for the surgical removal of nasal polyps, which may shrink after several weeks or months of treatment.

Topics: Administration, Intranasal; Adrenal Glands; Adult; Beclomethasone; Child; Chronic Disease; Clinical Trials as Topic; Cromolyn Sodium; Drug Evaluation; Humans; Hydrocortisone; Methylprednisolone; Nasal Polyps; Placebos; Rhinitis, Allergic, Seasonal; Seasons

Beclomethasone dipropionate aerosol therapy can replace or diminish systemic corticosteroid therapy in the majority of asthmatics. In a clinical trial of 41 patients with perennial asthma, the 10 who had not required long-term corticosteroid therapy improved symptomatically and in pulmonary function. Of the 31 who had required prolonged systemic corticosteroid therapy 12 were able to discontinue oral prednisone therapy, 15 were able to decrease the maintenance dose of prednisone and only 4 were unable to decrease the dose; all maintained satisfactory lung function and some showed improvement. Discontinuation of systemic corticosteroid therapy was accomplished more readily in patients whose daily maintenance dose was less than 15 mg and who had been taking the drug for less than 3 years. Side effects consisted of a "dry throat" in seven patients, two of whom had throat infections with Candida albicans. Recurrence of rhinitis after discontinuation or reduction of systemic corticosteroid therapy was noted in 11 patients.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Clinical Trials as Topic; Cough; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Prednisone; Respiratory Function Tests; Sputum

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Spirometry

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Cough; Female; Humans; Male; Methylprednisolone; Middle Aged; Rhinitis; Rhinitis, Allergic, Seasonal

Topics: Aerosols; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Humans; Methylprednisolone; Middle Aged; Prednisone

Topics: Administration, Oral; Administration, Topical; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Candidiasis; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Methylprednisolone; Mouth Diseases; Mouth Mucosa; Nystatin; Pharyngeal Diseases; Placebos; Prednisone; Propionates

Topics: Administration, Topical; Adolescent; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Epistaxis; Female; Glucocorticoids; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Mucosa; Placebos; Respiratory Therapy; Rhinitis, Allergic, Seasonal; Sneezing; Time Factors

Topics: Aerosols; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Glucocorticoids; Methylprednisolone; Placebos; Prednisolone; Respiratory Insufficiency; Respiratory Therapy

Topics: Administration, Topical; Adult; Aerosols; Aged; Airway Obstruction; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Placebos; Spirometry; Time Factors

Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.

Topics: Acute Disease; Adult; Beclomethasone; Chronic Disease; Cidofovir; Cytomegalovirus Infections; Etanercept; Female; Foscarnet; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infliximab; Japan; Male; Middle Aged; Mycophenolic Acid; Off-Label Use; Postoperative Complications; Registries; Transplantation, Homologous; Virus Diseases

Chronic respiratory diseases (CRDs) affect hundreds of millions of people. The United Nations 2011 meeting on non-communicable diseases (NCDs) marked a turning point in addressing this burden. The targets established following this meeting incorporated specific measures to address the availability and affordability of essential medicines. These are aligned with the sustainable development goals (SDGs) and the push for universal health coverage. However, essential medicines for CRDs remain unaffordable and unavailable to many. For asthma, the availability of medicines was respectively 30.1% and 43.1% in the public and private sectors. The maximum annual costs of treatment were US$102.10 for beclometasone, US$82.99 for salbutamol and US$1501.79 for budesonide, representing respectively 40%, 15% and 209% of per capita income in Malawi, Burkina Faso and Guinea. Multiple factors contribute to poor availability and affordability. Experience from human immunodeficiency virus/acquired immune-deficiency syndrome shows that medicines and care can be delivered in low-income countries and among the NCDs. A unique example of an effective mechanism for providing access to affordable essential CRD medicines is the Asthma Drug Facility. Working on the six health system building blocks proposed by the World Health Organization can help countries address not only problems regarding access to medicines, but also those hampering adequate care. Improving medicine supply systems, training, national guidelines, financing, research, data utilisation and models of care at the primary health care level will help. A CRD target (e.g., 50% reduction in asthma hospitalisations) as well as the use of asthma as a measure for health system effectiveness and CRDs as a tracer for SDGs would help focus global, national and local leadership.

Topics: Albuterol; Anti-Asthmatic Agents; Beclomethasone; Burkina Faso; Chronic Disease; Developing Countries; Drugs, Essential; Guidelines as Topic; Guinea; Health Services Accessibility; Humans; Malawi; Noncommunicable Diseases; Private Sector; Public Sector; Respiration Disorders; United Nations; World Health Organization

The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice.. Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done.. Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation.. Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.

Topics: Airway Remodeling; Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoalveolar Lavage Fluid; Chronic Disease; Collagen; Disease Models, Animal; Drug Evaluation, Preclinical; Interleukin-13; Leukocyte Count; Lung; Male; Mice; Nitric Oxide; ortho-Aminobenzoates; Transforming Growth Factor beta1

Pouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory.. To evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis.. Ten consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10 mg⁄day for 8 weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ).. Eight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8-14) and 3 (range 2-9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77-175) to 175 (range 85-220) (p<0.001).. Eight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Beclomethasone; Chronic Disease; Female; Humans; Male; Pouchitis; Quality of Life; Remission Induction; Severity of Illness Index

Topics: Anti-Inflammatory Agents; Beclomethasone; Chronic Disease; Colectomy; Comorbidity; Enteral Nutrition; Eosinophilia; Follow-Up Studies; Humans; Infant; Intestinal Pseudo-Obstruction; Male; Myenteric Plexus; Neuritis; Prednisone; Treatment Outcome

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Drug Administration Schedule; Drug Therapy, Combination; Humans; Long-Term Care; Secondary Prevention; Treatment Outcome

We identify an autosomal mutation in the CSF3R gene in a family with a chronic neutrophilia. This T617N mutation energetically favors dimerization of the granulocyte colony-stimulating factor (G-CSF) receptor transmembrane domain, and thus, strongly promotes constitutive activation of the receptor and hypersensitivity to G-CSF for proliferation and differentiation, which ultimately leads to chronic neutrophilia. Mutant hematopoietic stem cells yield a myeloproliferative-like disorder in xenotransplantation and syngenic mouse bone marrow engraftment assays. The survey of 12 affected individuals during three generations indicates that only one patient had a myelodysplastic syndrome. Our data thus indicate that mutations in the CSF3R gene can be responsible for hereditary neutrophilia mimicking a myeloproliferative disorder.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Animals; Beclomethasone; Child; Chronic Disease; Dimerization; Female; Genes, Dominant; Germ-Line Mutation; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukocytosis; Male; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Middle Aged; Models, Molecular; Molecular Sequence Data; Myeloproliferative Disorders; Neutrophils; Point Mutation; Protein Structure, Tertiary; Receptors, Colony-Stimulating Factor; Recombinant Proteins; Transplantation, Heterologous; Transplantation, Isogeneic; Young Adult

(1) Asthma is influenced by a variety of factors and its natural history varies over time. Clinically, asthma ranges from fleeting respiratory discomfort to incapacitating dyspnoea due to frequent and severe attacks. (2) This article examines the general principles of long-term drug therapy for asthma patients, taking into account the results of the clinical drug evaluation described in part I of this review (French edition). (3) The four most recent clinical practice guidelines did not take into account the latest data on the potentially severe adverse effects of long-acting beta-2 agonists. At least two of these guidelines received financial support from drug companies. (4) There is a general consensus that intermittent asthma does not require continuous therapy. For these patients, drug treatment is based on short-acting beta-2 agonists taken solely when symptoms arise. (5) Long-term treatment of persistent asthma is based on inhaled steroids at doses adapted to severity. However, given the adverse effects of inhaled steroids, the minimal effective dose should be identified and treatment should be reduced in a stepwise manner once asthma is under control. (6) When severe asthma persists or does not improve with high-dose inhaled steroid therapy, the treatment with the best risk-benefit balance is oral steroid therapy. (7) The use of long-acting beta-2 agonists is limited to the control of nocturnal symptoms when inhaled steroid therapy is inadequate. (8) Standard drugs used for asthma have no proven foetotoxicity, whereas poorly controlled asthma carries a risk of complications for both the mother and her unborn child.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-Agonists; Asthma; Beclomethasone; Bronchodilator Agents; Canada; Chronic Disease; Disease Management; Female; France; Humans; Long-Term Care; Male; Practice Guidelines as Topic; Prednisolone; Pregnancy; Pregnancy Complications; Steroids; Theophylline; United Kingdom; United States

Growth impairment and adrenal suppression secondary to inhaled corticosteroids (ICS) is a well-recognised phenomenon. We report a 13-year-old boy, treated long-term for asthma, who presented with short stature while on low-dose inhaled corticosteroid (beclomethasone 200 microg/d). Investigations revealed evidence of severe adrenal suppression. Weaning off the steroid treatment resulted in recovery of adrenal activity and rapid growth. While low-dose ICS are normally considered to have few side effects, this case illustrates the extreme variability of individual sensitivity and the need for careful surveillance of all children treated with long-term steroids.

Topics: Adolescent; Adrenal Insufficiency; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Child; Child Development; Chronic Disease; Developmental Disabilities; Growth Hormone; Humans; Male; Time Factors

To determine the value of inhaled corticosteroids in the management of chronic inflammatory airway disease in dogs.. Medical records of dogs that were presented for the investigation of respiratory disease were reviewed retrospectively. Criteria for inclusion were knowledge of previous medical treatment including side effects, diagnosis of the underlying disease, use of inhaled corticosteroids and at least two-months follow-up data.. Thirteen dogs that fulfilled the criteria were identified. Ten dogs were diagnosed with chronic bronchitis and three with eosinophilic bronchopneumopathy. Four dogs had not previously received corticosteroid treatment for their respiratory disease, and all these showed a reduction or a resolution of clinical signs without obvious side effects after inhaled corticosteroid therapy. Nine dogs had previously received oral or parenteral corticosteroids for treatment of their respiratory disease, and all had exhibited side effects. Five of these dogs were treated with inhaled corticosteroids alone, and all exhibited an improvement in clinical signs without observable side effects. The remaining four dogs were treated with a combination of inhaled and oral corticosteroids, and all showed improvement in clinical signs and reduction in side effects. Inhaled medication was well tolerated in all dogs.. Inhaled corticosteroids were used for the management of chronic bronchitis and eosinophilic bronchopneumopathy in 13 dogs, and these may have the advantage of reducing side effects associated with oral corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchitis; Bronchopneumonia; Chronic Disease; Dog Diseases; Dogs; Female; Fluticasone; Male; Pulmonary Eosinophilia; Respiratory Tract Diseases; Retrospective Studies; Treatment Outcome

The aims of the present study were to examine the prevalence and clinical features of cough variant asthma (CVA) among patients with chronic and persistent cough at an outpatient clinic in Japan, and the efficacy of treatment with an inhaled corticosteroid.. This prospective study was conducted at a general internal medicine outpatient clinic in Japan over a 12-month period. CVA was diagnosed as chronic cough without wheezing or any apparent cause, that had persisted for more than 8 weeks, with a normal CXR and spirometry but with bronchial hyperresponsiveness to methacholine, and relief of cough after bronchodilator treatment. We also examined the effects of inhaled beclomethasone propionate on symptoms and differences in PEF between early morning and evening.. Of 55 patients suffering from chronic cough, 23 satisfied the criteria for CVA. Their cough occurred more frequently at night and early in the morning. Early morning PEF was significantly lower than evening PEF with a mean variability of 11.5 +/- 4.1%. Treatment with beclomethasone propionate improved coughing and significantly increased early morning PEF, reducing variability to less than 10%.. These findings suggest that CVA is most common among patients with chronic cough not due to any apparent cause. The efficacy of inhaled corticosteroid suggests that early intervention is effective in the treatment of CVA.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Chronic Disease; Circadian Rhythm; Cough; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Hospitals, General; Humans; Japan; Male; Middle Aged; Outpatient Clinics, Hospital; Prevalence; Prospective Studies; Treatment Outcome

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Double-Blind Method; Fluticasone; Humans; Randomized Controlled Trials as Topic

We analyzed the rate of decline of pulmonary function annually over 2 years in 49 patients with chronic asthma, who were being treated with inhaled corticosteroid (beclomethasone). The coefficient of linear regression of pulmonary function based on dose of inhaled corticosteroid may be used to track the exact rate of the decline of pulmonary function. The declining rate of pulmonary function is faster in the early stages of the disease, in spite of the treatment with inhaled beclomethasone. In chronic asthmatics, the distal airway units appear to deteriorate, and the extent of deterioration probably changes with the progression of the disease.

Topics: Administration, Inhalation; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Respiratory Function Tests

Damage to the airway epithelium is one prominent feature of chronic asthma. Corticosteroids induce apoptosis in inflammatory cells, which in part explains their ability to suppress airway inflammation. However, corticosteroid therapy does not necessarily reverse epithelial damage. We hypothesized that corticosteroids may induce airway epithelial cell apoptosis as one potential explanation for persistent damage. We tested this hypothesis in cultured primary central airway epithelial cells and in the cell line 1HAEo(-). Treatment with dexamethasone, beclomethasone, budesonide, or triamcinolone each elicited a time-dependent and concentration-dependent cell death. This cell death was associated with cleavage of nuclear chromatin, mitochondrial depolarization, cytochrome c extrusion, activation of caspase-9, and expression of phosphatidylserine on the outer cell membrane. Inhibitors of caspase activity blocked apoptotic cell death, as did overexpression of the apoptosis regulators Bcl-2 or Bcl-x(L). We demonstrated that CD95 ligation is not essential for the corticosteroid-induced apoptosis in airway epithelial cells. These data demonstrate that corticosteroids induce apoptotic cell death of airway epithelium. This raises the possibility that at least one of the major components of chronic airway damage in asthma, epithelial shedding and denudation, may in part result from a major therapy for the disease.

Topics: Anti-Asthmatic Agents; Anti-Inflammatory Agents; Apoptosis; Asthma; bcl-X Protein; Beclomethasone; Bronchodilator Agents; Budesonide; Caspase 9; Caspases; Cells, Cultured; Chronic Disease; Cytochrome c Group; Dexamethasone; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; fas Receptor; Genes, bcl-2; Humans; Inflammation; Proto-Oncogene Proteins c-bcl-2; Receptors, Interleukin-2; Respiratory Mucosa; Time Factors; Triamcinolone

A 54-year-old woman complained of dyspnea, cough, and productive sputum. Auscultation detected a wheeze in the left and right lung fields. Chest x-ray and computed tomographic films showed non-segmental infiltration in the left upper lung field. Laboratory data revealed eosinophilia in peripheral blood and sputum, elevated levels of serum interleukin-5 (IL-5), airflow limitation, hypoxemia, and heightened airway sensitivity to methacholine (D min : 0.42 units). Bronchoalveolar lavage disclosed an increase in the total number of cells, a 32% increase in eosinophils, and a decreased CD 4/CD 8 ratio of 0.7. Transbronchial lung biopsy specimens revealed infiltrations of eosinophils in the alveolar and interstitial compartments. The histologic features of bronchial biopsy specimens included increased eosinophils in the submucosa and squamous metaplasia. In addition, blood glucose and HbA 1 c levels were elevated. Chronic eosinophilic pneumonia complicated by bronchial asthma and diabetes mellitus was diagnosed. Because the patient was diabetic, she was given suplatast tosilate to reduce the production of IL-5, and high-dose inhaled corticosteroid (beclometasone dipropionate, 1,600 mcg/day) instead of oral corticosteroid therapy. Her symptoms were relieved, peak expiratory flow rates increased, serum IL-5 levels became undetectable, airway sensitivity to methacholine decreased (D min : 4.64 units), and the radiographic abnormalities disappeared. Furthermore, treatment with beclomethasone dipropionate was progressively reduced to 1,200 mcg/day over the subsequent year without relapse. It was concluded that suplatast tosilate and high-dose inhaled corticosteroid therapy may be an effective alternative therapeutic approach to chronic eosinophilic pneumonia in some cases.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Arylsulfonates; Asthma; Beclomethasone; Chronic Disease; Diabetes Complications; Diabetes Mellitus; Female; Humans; Interleukin-5; Middle Aged; Pulmonary Eosinophilia; Sulfonium Compounds

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Cyclopropanes; Double-Blind Method; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Middle Aged; Quinolines; Randomized Controlled Trials as Topic; Reproducibility of Results; Sulfides; Treatment Outcome

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Double-Blind Method; Female; Fluticasone; Humans; Male; Randomized Controlled Trials as Topic; Reproducibility of Results; Respiratory Function Tests

Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p<0.05) and the trabecular bone density (p<0.01). Among patients > or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p<0.05), total bone mineral density (p<0.01) and cortical bone mineral density (p<0.01). Bone mineral density in the distal radius measured by pQCT and the vertebral bodies by axis QCT were correlated, regardless of whether systemic glucocorticoids were administered. Glucocorticoid administration not only decreases trabecular but also cortical bone mineral density. Since cortical bone provides strength and stiffness, it appears that the loss of cortical bone is responsible for the increased incidence of fracture seen in patients receiving systemic glucocorticoid therapy.

Topics: Aged; Asthma; Beclomethasone; Bone Density; Bone Resorption; Chronic Disease; Female; Glucocorticoids; Humans; Lumbar Vertebrae; Male; Outpatients; Predictive Value of Tests; Radius; Spinal Fractures; Tomography, X-Ray Computed

Endogenously released nitric oxide (NO) has been detected in the exhaled air of humans. Exhaled NO (NOexh) levels have been significantly increased in patients with inflammatory airways disorders such as asthma, and NOexh has been suggested to be a usable marker of airway inflammation. In the present study, NOexh levels were measured both in steroid-treated and untreated subjects with mild asthma, and were correlated with the degree of airway hyperresponsiveness (AHR), measured as the dose of histamine that produced a 20% decrease in FEV1 (PC20histamine). NOexh levels, which were significantly increased in steroid-naive patients (Group A1: NOexh = 21 +/- 11 ppb; n = 56) in comparison with levels in control subjects (Group B: NOexh = 10 +/- 2 ppb; n = 20; p < 0.001), correlated significantly with the PC20histamine (r = -0.65; p < 0.0001). The NOexh level was significantly lower in patients with chronic cough of other causes than bronchial asthma (Group A2: NOexh = 11 +/- 3 ppb; n = 18) when compared with the level in subjects with mild asthma (Group A1: p < 0.001). Therefore, the noninvasive measurement of NOexh allowed us to discriminate, among patients with respiratory complaints, between those with and without AHR. In asthmatic subjects treated with inhaled steroids, the NOexh levels were significantly lower (Group A3: NOexh = 13 +/- 5 ppb; n = 25) than in untreated subjects (Group A1; p < 0.01), and there was no relationship with the PC20histamine (r = -0.18, p = NS). These findings confirm that NOexh reflects AHR in patients with mild asthma who have not already been treated with inhaled steroids. Patients treated with inhaled steroids had an NOexh level comparable to levels in control subjects, although AHR could still be demonstrated.

Topics: Adrenergic beta-Agonists; Adult; Airway Obstruction; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Bronchial Hyperreactivity; Bronchial Provocation Tests; Chronic Disease; Cough; Dyspnea; Female; Forced Expiratory Volume; Glucocorticoids; Histamine; Humans; Male; Nitric Oxide; Respiration; Respiratory Sounds

Neuropeptides act on most of the components of the bronchial environment. They influence bronchomotor tone and bronchial vascular caliber and permeability. To investigate the nonadrenergic, noncholinergic system within the airways in asthma and chronic bronchitis, we performed endobronchial biopsies in 16 normal human volunteers, 49 patients with asthma of varying severity, including 16 patients treated with oral corticosteroids, and 13 patients with chronic bronchitis. Frozen sections of biopsies stained with specific antibodies against the neural marker PGP 9.5, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were analyzed for the presence of nerves through indirect immunofluorescence. Nerves were present in most of the biopsies and were found within and below the epithelium and adjacent to smooth muscle, glands, and blood vessels. By comparison with those in normal subjects, the numbers of VIP-immunoreactive nerves were not significantly decreased in patients with asthma and chronic bronchitis, but NPY-immunoreactive nerves were significantly decreased in the smooth muscle of these latter two groups of patients (p < 0.005). There was no correlation between disease severity and the number of nerves found in the biopsies. This study does not confirm previous findings in autopsy material of some defects in sensory and VIP-containing nerves in severe asthma.

Topics: Administration, Oral; Adolescent; Adult; Aged; Asthma; Beclomethasone; Biomarkers; Biopsy; Bronchi; Bronchitis; Bronchoconstriction; Calcitonin Gene-Related Peptide; Capillary Permeability; Chronic Disease; Epithelium; Female; Fluorescent Antibody Technique, Direct; Glucocorticoids; Humans; Male; Middle Aged; Mucous Membrane; Muscle, Smooth; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Prednisone; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide; Vasomotor System

In a cross-sectional study, we evaluated success in the control of asthma as defined by criteria for symptoms, for FEV1/FVC, and for peak flow rates. One hundred and three patients with chronic asthma who had been treated with inhaled steroids were studied. Chest tightness, dyspnea, wheezing, sputum production, and coughing were each scored from 1 (worst) to 5 (best). Symptoms were said to have been controlled if the symptoms scores for the preceding 4 weeks were greater than or equal to 20; FEV1/FVC was said to be under control if it was greater than or equal to 70% when measured in the clinic; peak flow was said to have been controlled if the lowest peak flow in the preceding 4 weeks was greater than or equal to 80% of the highest measured value. Symptoms were controlled in 72% of the patients, FEV/FVC was under control in 83%, and peak flow was controlled in 66%. The patients were grouped by severity of disease into four classes, and these percentages did not differ significantly among the classes. In 22 out of 74 (30%) patients in whom symptoms were controlled, peak flow was not controlled. Furthermore, in 18 out of 64 (28%) patients in whom symptoms and FEV/FVC were controlled, peak flow was not controlled. We concluded that in treating asthma, not should symptoms be controlled, but peak flow should also be measured each day to avoid undertreatment.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Monitoring, Physiologic; Peak Expiratory Flow Rate; Vital Capacity

Effects of reducing or stopping inhaled beclomethasone dipropionate (BDP) on airway hyperresponsiveness (AHR) were evaluated in stable chronic asthma. In 16 patients, after the best control (no symptoms, peak expiratory flow rate [PEF] > 80% best) was achieved for at least 3 months, the dose of BDP was reduced to 2/3 to 1/2. No differences were observed in the mean FEV1, PEF and AHR between before and 3 months after the reduction of BDP. In 7 patients, after the almost normal level of AHR was achieved, the dose of BDP was gradually reduced and then discontinued. Three out of the 7 patients had maintained the adequate level of AHR over 14 months, but in the other 4 patients AHR deteriorated below normal level and re-administration of BDP was needed due to worsening of symptoms and PEF. In conclusion, a gradual reduction of the dose of BDP is possible, if the best control is achieved for at least 3 months. The possibility of discontinuation of BDP may exist in some patients after achieving adequate AHR.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chronic Disease; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

In 1990 we reported an initial prospective study of 100 patients using a four-stage system for classification of chronic rhinosinusitis. Between January 1988 and July 1992, we used this system in staging an additional 1814 patients, on whom 2980 intranasal sphenoethmoidectomies were performed. In this staging system a protocol trial of medication was given for 2 weeks, followed by axial and coronal computed tomography. Medication consisted of a second-generation cephalosporin antibiotic, usually cefuroxime; a 4-day burst of intraoral steroids, usually prednisone; and an antihistamine decongestant if not contraindicated. The stages of chronic hyperplastic rhinosinusitis included the stages described in the 1990 report (i.e., stage I, single-focus disease; stage II, discontiguous disease throughout the ethmoid labyrinth; stage III, diffuse disease responsive to medication; and stage IV, diffuse disease unresponsive to or poorly responsive to medication). The results of this study have shown that the computed tomography staging system based on computed tomography extent of disease after medical therapy is a simple, easily remembered, and very effective modality for the classification of chronic sinusitis. This system provides a rationale for discussing and planning surgery with patients and physicians and is a convenient reference for the reporting of end results. More importantly, a linear relationship between disease stage and outcomes is demonstrated. This statistically highly significant feature of the staging system provides a firm basis for the production of outcomes after various treatment strategies, particularly ethmoidectomy and the treatment of sinusitis.

Topics: Beclomethasone; Cefuroxime; Chronic Disease; Clinical Protocols; Combined Modality Therapy; Ethmoid Sinus; Ethmoid Sinusitis; Follow-Up Studies; Guaifenesin; Histamine H1 Antagonists; Humans; Hyperplasia; Nasal Decongestants; Patient Care Planning; Prednisone; Prospective Studies; Recurrence; Rhinitis; Sinusitis; Sphenoid Sinus; Tomography, X-Ray Computed; Treatment Outcome

The transcription factor Fos is involved in cell proliferation and differentiation. Its expression in normal and pathological adult human tissues and cells has rarely been studied. We therefore studied bronchial biopsies obtained from 14 normal subjects (NS), 18 non-steroid-treated asthmatics, 10 corticosteroid-treated asthmatics and 10 patients with chronic bronchitis (CB), in addition to 34 patients with lung cancer (LC), by immunofluorescence for Fos immunoreactivity, using a highly specific polyclonal antibody. Bronchial tissue of 0/10 NS, 11/18 non-steroid-treated asthmatics, 1/10 steroid-treated asthmatics, 0/10 CB and 1/34 LC expressed Fos. In asthmatic patients, the expression was heterogeneous, localized to epithelial cells and correlated with the epithelium shedding (tau = 0.45, P = 0.0001). Corticosteroid-treated patients rarely expressed Fos, suggesting a role for this proto-oncogene in asthmatic bronchial inflammation. Fos was rarely expressed in the normal and pathological (CB, LC) proliferative compartment of the human bronchi, suggesting its low role in cell proliferation of the large airways.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Beclomethasone; Bronchi; Bronchitis; Budesonide; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chronic Disease; Female; Fluorescent Antibody Technique; Humans; Lung Neoplasms; Male; Middle Aged; Pregnenediones; Proto-Oncogene Mas; Proto-Oncogene Proteins c-fos

Systemic administration of corticosteroids was attempted in the treatment of olfactory loss resistant to topical corticosteroid treatment in patients with nasal and paranasal disease and post-upper respiratory infection. Significant efficacy was achieved with a short course of high-dose oral corticosteroids in patients with non-allergic sinus disease. On the other hand, anosmia induced by upper respiratory infection failed to respond to systemic corticosteroid treatment, suggesting permanent damage to the olfactory receptor cell. The underlying mechanism of effectiveness observed in patients with sinus disease may be explained by improvement of the mucosal thickening of the olfactory fissure, leading to the access of an odorant to the olfactory neuroepithelium.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Beclomethasone; Chronic Disease; Female; Glucocorticoids; Humans; Male; Middle Aged; Nose Diseases; Olfaction Disorders; Prednisolone; Respiratory Tract Infections; Sinusitis; Treatment Failure

Topics: Administration, Inhalation; Beclomethasone; Chronic Disease; Female; Humans; Middle Aged; Prednisolone; Pulmonary Eosinophilia

As an initial investigation to determine whether or not inhaled corticosteroids can be discontinued, we evaluated the results of discontinuation in patients who had been well controlled with inhaled corticosteroids for more than one year prior to this study. The average dose of BDP which the patients had been inhaling at the start of this study was 365 micrograms/day. To determine the effect of discontinuing inhaled corticosteroids, we compared the patients' peak expiratory flow rates and the frequency of beta-agonist use between the 4-week observation period and follow-up periods of varying duration. Only three out of twenty patients enrolled were able to maintain their discontinuation of BDP, while the remaining seventeen patients restarted after a mean period of 30.8 days. Mean peak flow values began to fall during the first week after discontinuation, and decreased morning peak flow values became significant in the 2nd, 3rd and 4th weeks. The mean peak flow value during the observation period was 85.2% of each patient's personal best, but had dropped to 68.8% of this level just before restarting inhaled corticosteroid. The frequency of beta-agonist use during the study period (2.99 +/- 3.39 times a day) was significantly higher than during the observation period (1.94 +/- 2.95 times a day). This finding strongly suggests that the patients' asthmatic conditions had become unstable during the study period. These results suggest that any decision to discontinue the use of inhaled corticosteroid, even in well controlled patients with chronic asthma, should be taken with great care.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged

Topics: Administration, Inhalation; Asthma; Beclomethasone; Chronic Disease; Female; Glaucoma, Open-Angle; Humans; Middle Aged

The main goal of asthma treatment has usually been to maintain normal air potency with bronchodilators. A prompt improvement in physiologic measures of expiratory flow can be observed after administration beta-2-agonists or steroids. The present study aimed to assay the influence of fenoterol or beclomethasone therapy on the pulmonary ventilation (VC, FEV1, FEV1%), the heart action (heart rate, QT interval, 24 hours ECG) and the potassium balance in examined group. 20 patients with chronic asthmatic bronchitis were divided on two group (A and B). Group A consisted 10 subjects and patients were treated with fenoterol, the second group (Group B) consisted 10 subjects too, and patients were treated with beclomethasone. After five days treatment in all subjects an increase VC, FEV1 and FEV1% were observed. In group A (inhalation of fenoterol) we observed: 1--the significant increase of heart rate, QT interval, and frequency of cardiac arrhythmias and 2--significant decrease plasma potassium levels. In group B we didn't observed a significant changes in heart function and potassium levels. We concluded that nebulization of fenoterol, even in low doses, required control of the plasma potassium concentration and the evaluation of the heart action.

Topics: Asthma; Beclomethasone; Bronchitis; Chronic Disease; Female; Fenoterol; Forced Expiratory Volume; Heart; Humans; Male; Middle Aged; Potassium; Respiratory Function Tests

We investigated whether or not the inhalation method of beclomethasone dipropionate (BDP) influences patient compliance and the clinical effects of therapy in chronic bronchial asthma, together with a basic study on the lung deposition of BDP using a twin Impinger when various numbers of puffs were discharged into three different spacers (Volumatic, InspirEase, Aerochamber). It was clearly shown that only the spacer, Volumatic maintained a high deposition rate of BDP in the lung model with a dose of 4-puffs/inhalation. Eighteen chronic asthmatic patients were studied. The patients inhaled BDP (800-1600 micrograms/day) by 1-puff/inhalation using a large spacer, Volumatic, for 12 weeks, and they then inhaled the same dose of BDP as given in the previous period by 4-puffs/inhalation using the spacer for 16 weeks. We compared the compliance of BDP, attack score, %PEFR and frequency of beta-agonist inhalation between these two periods. The compliance of BDP was markedly improved after changing from 1-puff/inhalation (92.8%) to 4-puffs/inhalation (99.8%). In the 4-puffs/inhalation period, attack score and %PEFR were significantly improved as compared to the 1-puff/inhalation period. The frequency of beta-agonist inhalation use in the 4-puffs/inhalation period was significantly lower than that in the 1-puff/inhalation period. These results indicate that when high dose steroid inhalation is given with a large spacer in chronic asthmatic patients, we should advice them of the appropriate inhalation method in order to obtain good compliance and clinical effects.

Topics: Adult; Asthma; Beclomethasone; Chronic Disease; Evaluation Studies as Topic; Female; Humans; Lung; Male; Middle Aged; Respiratory Therapy

Seventy-eight pediatric patients with moderate to severe chronic asthma, aged 6 to 16 years, who failed to respond well to inhaled DSCG and theophylline RTC, were treated with beclomethasone dipropionate inhaler (BDI) for 0.5 to 10 years (mean: 4.2 +/- 2.4 years). The efficacy rate gradually increased with time: 61.1% at one year after the start of the treatment and 89.5% at three years. Long-term BDI therapy over five years did not cause suppression of height growth or adrenocortical functions (early morning cortisol level and rapid ACTH test). However, the safety of long-term BDI therapy in children still needs to be studied more thoroughly and established. Further investigation will be necessary since some cases did not respond to BDI therapy while others died of exacerbated asthmatic symptoms soon after the start of BDI therapy.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex; Adrenal Cortex Function Tests; Asthma; Beclomethasone; Body Height; Child; Chronic Disease; Female; Humans; Hydrocortisone; Male

Topics: Adolescent; Adrenal Cortex Hormones; Asthma; Beclomethasone; Child; Chronic Disease; Drug Therapy, Combination; Humans

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Beclomethasone; Chronic Disease; Cromolyn Sodium; Humans; Nebulizers and Vaporizers; Parasympatholytics

Fifteen bronchial asthma patients were followed-up for 6 months. They were administered beclomet-250 in a daily dose 1000 micrograms. The patients' clinical status was characterized by positive changes, ventilation function of the lungs improved. The drug was discovered to produce no suppressive action on adrenal function. Besides, the patients did not develop oropharyngeal candidiasis.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Chronic Disease; Drug Evaluation; Female; Humans; Hydrocortisone; Male; Middle Aged; Respiration; Time Factors

We investigated compliance and inhaler technique in 50 patients with airway obstruction (26 asthma, 24 chronic bronchitis) being treated with inhaled steroid (beclomethasone dipropionate, BDP) via a dry powder inhaler (Rotahaler omega). Patients had already participated for one year in a 2-year trial of BDP in general practice. They were treated daily with two dry powder inhalations of 400 micrograms BDP in combination with a bronchodilator. Compliance with BDP was measured by counting capsules (single-blind) at the end of a 4-month period and through a questionnaire. Counting capsules revealed non-compliance in 46% of the patients. Compliance was not related to age, sex, diagnosis or side-effects of BDP. In chronic bronchitis, but not in asthma, compliance was related to the outcome parameters of steroid treatment (pulmonary symptoms, change in lung function and non-specific bronchial responsiveness). The inhaler technique was judged insufficient in 27% of the patients. This study stresses the importance of regular instruction in inhaler technique and proper information about prophylactic steroid treatment by the general practitioner during the treatment of asthma and chronic bronchitis.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Treatment Outcome

Conventional doses of aerosolized beclomethasone dipropionate (BDP) of up to 400 micrograms/day by inhalation has often failed to normalize the pulmonary function of chronic adult patients. Therefore it may be necessary to administer the individual maximum dose of BDP to reduce bronchial inflammation. In 13 patients (2 males and 11 females, mean age 49.2 +/- 3.7 years old) with chronic asthma whose minimum %PEFRs were lower than 80% under treatment with conventional doses of BDP, the clinical benefit of high dose inhalation therapy with BDP was studied for four consecutive weeks by comparing % peak expiratory flow rate (%PEFR) measured four times a day both before and 10 minutes after inhaled procaterol (PCR) in a cross-over fashion. Mean morning %PEFRs before inhaled PCR during the first two weeks with a lower dose of BDP (419 +/- 24 micrograms/day) and during the following two weeks with a higher dose of BDP (904 +/- 55 micrograms/day) were 60.6 +/- 3.1% and 77.5 +/- 4.1%, respectively (p less than 0.01). Average increases in %PEFR during the higher dose period before and after inhaled PCR were 12.1% and 12.4%, respectively, which was observed by the end of the first week after the start of higher dose of BDP in 12 out of 13 patients. Since there were no adverse reactions such as hoarseness, oral thrush and candidiasis during the period with higher doses of BDP, it was concluded that we should promptly employ higher doses of BDP in patients who did not respond satisfactorily to conventional doses of BDP.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Beclomethasone; Chronic Disease; Drug Administration Schedule; Female; Humans; Male; Middle Aged

Topics: Administration, Inhalation; Beclomethasone; Chronic Disease; Female; Humans; Middle Aged; Prednisolone; Pulmonary Eosinophilia

Height and weight were measured every six months in a long term prospective study of 66 children with chronic perennial asthma for a mean 13.1 years. There was no evidence of growth retardation on entry into the study. Growth developed along normal lines in all 66 children until about 10 years, and in 35 of these children growth continued along normal lines throughout the whole period of follow up. Thirty children showed the physiological decelerating growth velocity pattern seen in children with delay in the onset of puberty, and one child had an early menarche. The tendency for delay in the onset of puberty was significant for both boys and girls and was noted to be independent of severity of asthma. Once puberty finally began in these children, complete catch up growth resulted in the attainment of the predicted adult height. Long term prophylactic inhalation of beclomethasone dipropionate in 26 children in a dosage up to 600 mcg/day before puberty and 400 mcg/day during puberty was shown not to affect growth. It is concluded that asthma had no direct influence on growth in height but was associated with delay in the onset of puberty. The pre-adolescent physiological deceleration of growth velocity that occurs in these children gives the impression of growth retardation.

Topics: Asthma; Beclomethasone; Body Height; Body Weight; Child; Chronic Disease; Cromolyn Sodium; Female; Growth; Humans; Male; Prednisolone; Prospective Studies; Puberty, Delayed; Time Factors

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Child; Chronic Disease; Female; Humans; Hydrocortisone; Male

Forty patients suffering from chronic bronchitis with basal forced expiratory volume in one second (FEV1) values at least 20% below ECSC (European Community Steel and Coal) predicted values were treated with a combination of salbutamol plus beclomethasone dipropionate or with theophylline for a period of 4 weeks. Methacholine bronchial inhalation challenges were performed before and after treatment. Both treatments produced significant increases in FEV1, forced vital capacity (FVC) and FEV1 100/FVC, while only the salbutamol plus beclomethasone dipropionate combination significantly reduced the decrease in FEV1 values after bronchial inhalation challenge.

Topics: Adult; Albuterol; Beclomethasone; Bronchial Provocation Tests; Bronchial Spasm; Bronchitis; Chronic Disease; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Methacholine Compounds; Middle Aged; Theophylline

The authors provide comparative data derived during study of the time-course of changes in IgM, IgG and IgA and cellular eosinophilic and basophilic allergic reactions during application of pentoxyl and becotide alone and combined in multiple modality treatment of 161 patients with chronic obstructive bronchitis. Application of pentoxyl was accompanied mainly by quantitative increment of immunoglobulins, particularly IgA and IgG, and moderately pronounced desensitization effect that manifested by attenuation of the eosinophilic reaction and spontaneous degranulation of basophils. Application of becotide in multiple modality treatment led primarily to attenuation of the cellular allergic reactions under study and less marked increment of immunoglobulins. The combined use of the drugs for bronchitis exacerbation produced maximally pronounced desensitization (according to the eosinophilic reaction and basophil degranulation data) as compared to the effect of these drugs used alone on the patients' allergic status. It is recommended that patients with chronic bronchitis exacerbation should receive pentoxyl (during immunoglobulin deficiency and proneness to allergy), becotide inhalations to obtain primarily desensitization effect, and combined pentoxyl and becotide (in patients with high risk of sensitization).

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Basophils; Beclomethasone; Bronchitis; Chronic Disease; Drug Therapy, Combination; Eosinophils; Female; Histamine; Humans; Immunity; Immunoglobulins; Male; Middle Aged; Pentoxyl; Time Factors; Uracil

Topics: Adolescent; Adult; Beclomethasone; Bronchitis; Chronic Disease; Combined Modality Therapy; Female; Humans; Male; Middle Aged

Topics: Adult; Atropine Derivatives; Beclomethasone; Bronchi; Bronchial Provocation Tests; Bronchial Spasm; Bronchitis; Chronic Disease; Ethanolamines; Fenoterol; Histamine; Histamine Antagonists; Humans; Ipratropium; Male; Middle Aged

Asthma can be conceptualized as a disease system ranging from the molecular to the social level. It is important to monitor both subjective and objective indices appropriate to different parts of the system. Objective indices alone are not enough. It is also important to distinguish disability from symptom severity or frequency and pulmonary impairment. The personality of the patient or the duration of follow-up can profoundly affect the perceived outcome of a particular treatment. It is important in controlled trials, and also in clinical practice, to take these factors into account.

Topics: Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Humans; Patient Compliance; Pulmonary Ventilation

Corticosteroid inhalants, beclomethasone dipropionate (BDP) and budesonide, were compared with each other and with oral prednisolone in patients with steroid dependent chronic bronchial asthma. In a first study in 23 patients the PEF values during 2 weeks' therapy with a supplementary dose of 200 or 800 micrograms of budesonide or 400 micrograms of BDP were found to be better than those noted during a preceding week with a supplementary dose of 30 mg prednisolone. In a following open study 31 patients on an initial maintenance therapy consisting of a standard dose of BDP and a mean daily dose of 9 mg prednisolone were treated with increasing (when necessary) doses of budesonide instead of BDP and decreasing (if possible) dose of prednisolone. After one year's treatment 21 patients were well controlled without oral prednisolone, and the mean prednisolone dose for the entire group was 2.5 mg a day. During the study lung function significantly improved in the subgroup of patients who were initially on the highest dose of oral prednisolone. In a third study in 17 patients the effects on lung function and on symptom scores were compared after a supplementary therapy with 10 or 20 mg oral prednisolone, or 400 or 800 micrograms budesonide. During such treatment the effect of 400 micrograms budesonide on PEF was the same as that of 10 mg prednisolone, and 800 micrograms budesonide and 20 mg prednisolone seemed to be equipotent. For corticosteroid dependent patients with severe asthma the introduction of budesonide seems to offer an improvement, allowing substantial reduction or withdrawal of oral prednisolone. This had not been possible earlier in such patients without deterioration of lung function and their clinical state. During treatment with budesonide lung function remained unchanged or improved.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aerosols; Aged; Asthma; Beclomethasone; Budesonide; Chronic Disease; Female; Humans; Male; Middle Aged; Prednisolone; Pregnenediones

Topics: Adrenal Cortex Hormones; Asthma; Beclomethasone; Child; Chronic Disease; Female; Hospitalization; Humans; Male

Topics: Adolescent; Asthma; Beclomethasone; Child; Chronic Disease; Dermatitis, Atopic; Eye Diseases; Female; Humans; Male

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Chronic Disease; Female; Humans; Male; Middle Aged; Ultrasonics

Topics: Adolescent; Adult; Beclomethasone; Child; Chronic Disease; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Nose Diseases; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Aerosols; Asthma; Beclomethasone; Child; Chronic Disease; Depression, Chemical; Dose-Response Relationship, Drug; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Prednisone

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Humans

Topics: Aerosols; Albuterol; Asthma; Beclomethasone; Chronic Disease; Drug Therapy, Combination; Humans

Topics: Albuterol; Asthma; Beclomethasone; Chronic Disease; Drug Therapy, Combination; Humans

Irritative effects of three steroidal anti-inflammatory drugs on the gastrointestinal tract of rats and dogs were determined. With either single or repeated subcutaneous administration these drugs dose dependently irritated the gastric mucosa of both species. The intestinal mucosa was less affected. Concomitant oral administration of aspirin or subcutaneous administration of indomethacin revealed an aggravation of aspirin-induced gastric ulcers by betamethasone valerate and inhibition of indomethacin-induced intestinal ulcers by beta-methasone dipropionate. These two steroidal drugs had no noxious effect on healing of chronic gastric ulcers induced in rats and dogs. Betamethasone valerate, however, delayed the healing of gastric ulcer in rats. Indomethacin, a non-steroidal anti-inflammatory drug, also induced serious damage to the gastric and intestinal mucosa both of rats and dogs. Indomethacin ingestion delayed the healing of chronic gastric ulcer in rats but not in dogs. Since both steroidal and non-steroidal drugs induce damage to the gastrointestinal tract, a careful monitoring of the patients' complaints should be carried out when these compounds are used as a systemic treatment. Steroidal drugs used in this study, however, appear to be highly safe from the point of dose inasmuch as they are used as a topical treatment.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Beclomethasone; Betamethasone; Betamethasone Valerate; Chronic Disease; Digestive System; Dogs; Indomethacin; Irritants; Male; Rats; Stomach Ulcer

Topics: Acute Disease; Adolescent; Asthma; Beclomethasone; Bronchodilator Agents; Child; Child, Preschool; Chronic Disease; Cromolyn Sodium; Female; Hospitalization; Humans; Male; Psychotherapy; Respiratory Hypersensitivity

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Humans

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged; Organization and Administration; Prednisolone; Thailand

The clinical and pathological features of five children who died of asthma over a recent 12-month period are reported. All had severe, chronic asthma requiring maintenance corticosteroid therapy. Three had been receiving beclomethasone dipropionate by inhalation and these had acute inflammation of the tracheobronchial tree at necropsy. Adrenal atrophy was found in all four cases examined histologically, despite normal short tetracosactrin tests in three of these shortly before they died. The need for high-dose corticosteroid by mouth for exacerbations of asthma in those weaned from oral steroids is emphasized by these deaths. The introduction of beclomethasone dipropionate by inhalation has led to an increase in the number of children in this high-risk group.

Topics: Adolescent; Adrenal Cortex Hormones; Aerosols; Asthma; Australia; Beclomethasone; Child; Chronic Disease; Female; Humans; Male

Topics: Beclomethasone; Chronic Disease; Drug Tolerance; Humans; Laryngitis; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Pharyngitis; Rhinitis, Allergic, Seasonal

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Humans

Topics: Aerosols; Beclomethasone; Bronchitis; Child; Chronic Disease; Female; Humans; Pulmonary Eosinophilia

15 adult chronic asthmatic patients who were on daily maintenance dose of oral steroid for at least 6 months were studied. Following an investigation period of 2 weeks, the patients were started on BDA, 100 microgram four times daily. The daily oral steroid dose, which averaged 12 mg of prednisone or its equivalent, was gradually reduced by about 1 mg per day. The trial lasted 8 weeks, at the end of which, ten patients were as good or better on BDA than on oral steroids. Two patients had to return to oral corticosteroid therapy before the trial ended and three patients were unable to discontinue their oral steroid treatment. The lack of systemic effects of BDA was demonstrated by the appearance of symptoms which were apparently previously suppressed by the oral steroids and the excretion of normal amounts of 17-OHCS in the urine in some to the patients who had evidence of adrenal suppression while on oral steroids.

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Chronic Disease; Humans; Respiratory Function Tests; Substance-Related Disorders

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Child; Chronic Disease; Female; Humans; Male; Prednisolone

The clinical effectiveness of beclomethasone dipropionate (BDP) aerosol and adrenal function after withdrawal of oral corticosteroid therapy were evaluated in 32 severely steroid-dependent asthmatic patients. Twenty-four of 28 patients were able to discontinue oral glucocorticosteroid therapy, while four failed to do so. Ventilatory studies showed no substantial changes at the end of six months' BDP treatment. In 24 patients, adrenal insufficiency was present before BDP therapy was started. In 20 of those patients, the response of cosyntropin returned to normal two months after discontinuation of systemic steroid treatment and administration of BDP.

Topics: Administration, Oral; Adrenal Glands; Adrenal Insufficiency; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Drug Evaluation; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Middle Aged; Respiratory Function Tests

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Middle Aged

Topics: Aerosols; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Female; Humans; Male; Methylprednisolone

A study of the growth patterns of 19 children with chronic asthma, whose growth had become retarded while they were receiving regular treatment with prednisolone, showed that this trend was reversed after the substitution of corticotrophin.

Topics: Adolescent; Adrenocorticotropic Hormone; Asthma; Beclomethasone; Body Height; Child; Child, Preschool; Chronic Disease; Female; Growth; Growth Disorders; Humans; Male; Prednisolone; Time Factors

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aminophylline; Asthma; Beclomethasone; Betamethasone; Bronchodilator Agents; Chronic Disease; Cromolyn Sodium; Humans; Hydrocortisone; Lung Diseases, Obstructive; Prednisone

Topics: Adolescent; Adult; Aged; Asthma; Beclomethasone; Bronchitis; Child; Chronic Disease; Drug Evaluation; Female; Humans; Long-Term Care; Male; Methylprednisolone; Middle Aged

Topics: Aerosols; Beclomethasone; Blood Gas Analysis; Bronchitis; Chronic Disease; Humans; Hydrocortisone; Lung Diseases, Obstructive; Methylprednisolone; Pulmonary Emphysema; Respiratory Function Tests

Topics: Adolescent; Adult; Aerosols; Age Factors; Aged; Asthma; Beclomethasone; Child, Preschool; Chronic Disease; Female; Humans; Immunoglobulin E; Male; Methylprednisolone; Middle Aged; Prednisone; Skin Tests; Spirometry

Topics: Adrenal Cortex Function Tests; Adult; Aerosols; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Prednisone; Propionates; Time Factors

Fifty-two steroid-dependent adults with chronic perennial asthma were transferred to beclomethasone dipropionate aerosol. The tests demonstrated a significant improvement with beclomethasone in terms of the diary score, bronchodilator use, and PEF and FEV1.0 measurements, as compared with the previous period of prednisolone treatment. Before the transfer, 26 of the patients displayed one or more diseases or symptoms which were probably due to systemic steroid medication. Morning cortisol levels, along with the response to tetracosactrin had in all cases returned to normal when tests were carried out 41 days after transfer to beclomethasone dipropionate. In a group of 12 patients with the lowest 11-OHCS basal values, the mean of their 11-OHCS values during prednisolone treatment was as low as 0.14 plus or minus 0.06 mumol/l, but tetracosactrin challenge induced an elevation to a normal level, 0.33 plus or minus 0.13 mumol/l. After 41 days of beclomethasone treatment, the corresponding values were 0.56 plus or minus 0.90 plus or minus 0.28 mumol/l. Thirty-seven patients experienced one or more disturbing symptoms after transfer to beclomethasone. In many cases, the symptoms of allergic rhinitis were troublesome and persistent leading to a sixfold increase in the use of antihistaminic tablets. When the patients had learned to exhale through the nose following beclomethasone inhalation, the use of antihistaminic tablets again diminished to some extent. Moreover, two cases of ulcerative colitis were encountered during the beclomethasone treatment. During a follow-up period of one year, 14 patients were again receiving prednisolone; most often, this was due to worsening of the asthma because of respiratory infections. During the beclomethasone treatment, a continuous significant improvement in PEF was noted after isoprenaline inhalation, suggesting that further benefit may be obtained by the employment of bronchodilator aerosols as an essential part of the treatment.

Topics: 11-Hydroxycorticosteroids; Adult; Aerosols; Asthma; Beclomethasone; Chronic Disease; Cosyntropin; Drug Therapy, Combination; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Peak Expiratory Flow Rate; Prednisolone; Respiratory Therapy

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Humans; Methylprednisolone

Topics: Administration, Topical; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Candidiasis, Oral; Chronic Disease; Glucocorticoids; Humans; Prednisone

Topics: Aerosols; Asthma; Beclomethasone; Child, Preschool; Chronic Disease; Humans; Methylprednisolone; Respiratory Therapy