pulmicort and Lung-Diseases--Obstructive

Chronic obstructive pulmonary disease (COPD) remains difficult to manage. Patients with COPD present with progressive dyspnea; difficulty in stopping smoking; recurrent exacerbations; and, ultimately, respiratory failure. Because of the lack of proven treatments for COPD and because inhaled corticosteroids can prevent airway inflammation and permanent lung damage in patients with asthma, it has become common practice to prescribe inhaled corticosteroids for patients with COPD despite a lack of data suggesting that these agents have any long-term benefit in these patients. In the past 12 months, three randomized, double-blind, placebo-controlled clinical trials (the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease, the Copenhagen City Lung Study, and the Inhaled Steroids in Obstructive Lung Disease study) designed to assess the long-term effect of inhaled corticosteroids in patients with varying severity of airway obstruction have been presented. The results of these studies have been disappointing; they show little to suggest that any long-term benefit is gained from using inhaled corticosteroids in most patients with COPD, whether they continue to smoke or not.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Budesonide; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Predictive Value of Tests; Quality of Life; Severity of Illness Index

Budesonide, a topically active corticosteroid, has a broad spectrum of clinically significant local anti-inflammatory effects in patients with inflammatory lung diseases including persistent asthma. In infants and young children with persistent asthma, day- and night-time symptom scores, and the number of days in which beta2-agonist bronchodilators were required, were significantly lower during randomised, double-blind treatment with budesonide inhalation suspension 0.5 to 2 mg/day than placebo in 3 multicentre trials. Significantly fewer children discontinued therapy with budesonide inhalation suspension than with placebo because of worsening asthma symptoms in a study that included children who were receiving inhaled corticosteroids at baseline. Recent evidence indicates that budesonide inhalation suspension is significantly more effective than nebulised sodium cromoglycate in improving control of asthma in young children with persistent asthma. At a dosage of 2 mg/day, budesonide inhalation suspension significantly reduced the number of asthma exacerbations and requirements for systemic corticosteroids in preschool children with severe persistent asthma. In children with acute asthma or wheezing, the preparation was as effective as, or more effective than oral prednisolone in improving symptoms. In children with croup, single 2 or 4mg dosages of budesonide inhalation suspension were significantly more effective than placebo and as effective as oral dexamethasone 0.6 mg/kg or nebulised L-epinephrine (adrenaline) 4mg in alleviating croup symptoms and preventing or reducing the duration of hospitalisation. Early initiation of therapy with budesonide inhalation suspension 1 mg/day appears to reduce the need for mechanical ventilation and decrease overall corticosteroid usage in preterm very low birthweight infants at risk for chronic lung disease. In adults with persistent asthma, budesonide inhalation suspension < or =8 mg/day has been compared with inhaled budesonide 1.6 mg/day and fluticasone propionate 2 mg/day administered by metered dose inhaler. Greater improvements in asthma control occurred in patients during treatment with budesonide inhalation suspension than with budesonide via metered dose inhaler, whereas fluticasone propionate produced greater increases in morning peak expiratory flow rates than nebulised budesonide. Several small studies suggest that the preparation has an oral corticosteroid-sparing effect in adults with persistent asthma

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchiolitis; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Croup; Drug Delivery Systems; Female; Humans; Infant; Infant, Newborn; Lung Diseases, Obstructive; Male; Middle Aged

The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: "Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?". A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with "asthmatic features" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.. No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.. This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Patient Dropouts; Randomized Controlled Trials as Topic; Time Factors

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Follow-Up Studies; Forced Expiratory Volume; Forecasting; Glucocorticoids; Humans; Lung Diseases, Obstructive; Peak Expiratory Flow Rate; Pregnenediones; Randomized Controlled Trials as Topic; Smoking; Vital Capacity

Owing to improvements made during the last 15 years in the pathophysiological and pharmacological research, many new corticosteroids have been successfully experimented. They have high activity on the target organ and they are suitable for long term therapies since they have not any systemic and/or local side effects. Nowadays the topical intranasal corticosteroid therapy is indispensable for allergic rhinitis treatment and it is very useful for many nasal and bronchopulmonary diseases (some chronic rhinitis, nasal polyposis, bronchial asthma, chronic obstructive bronchopulmonary diseases). The authors use their personal experience and carefully review the literature to describe the general aspects (pharmacology, pharmacokinetics, toxicology, side effects and contraindications) and to analyze the single drugs currently used in Italy and abroad. Finally, they compare the efficacy of each topical intranasal glucocorticoid among themselves and with other drugs.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Budesonide; Child; Fluocinolone Acetonide; Humans; Hydrocortisone; Lung Diseases, Obstructive; Pregnenediones; Rhinitis

Although it has not been evaluated prospectively, the usual treatment for obstructive airway disease after allogeneic hematopoietic stem cell transplantation, which is related to graft versus host disease, consists of intensification of systemic immunosuppressive therapy. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore required. Recently, clinical and functional improvement in patients with obstructive airway disease following allogenic hematopoietic stem cell transplantation treated with inhaled combined Budesonide/Formoterol has been retrospectively reported.. The present prospective multi-centered, randomised double-blind trial is designed to evaluate the efficacy of the combination of budesonide/formoterol (400/12 microg 2 inhalations bid) versus placebo in patients with moderate to severe obstructive airway disease, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic graft versus host disease. The primary outcome will be the improvement of FEV1 at 1 month of treatment. The secondary outcomes will be the clinical and functional pulmonary improvements at 6 months.. The leading hypothesis is that patients treated with inhaled combined Budesonide/Formoterol will show significant improvement of their clinical symptoms and pulmonary functional testing.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Airway Obstruction; Anti-Asthmatic Agents; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dyspnea; Ethanolamines; Follow-Up Studies; Formoterol Fumarate; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases, Obstructive; Placebos; Prospective Studies; Respiratory Function Tests; Statistics, Nonparametric; Time Factors; Transplantation, Homologous; Treatment Outcome

The Novolizer is a breath-actuated multidose dry powder inhaler that was developed as an alternative to the pressurized metered dose inhalers. The efficacy, safety and tolerability of the Novolizer has been compared with those of established inhalational devices for the delivery of salbutamol (Sultanol) in patients with chronic obstructive pulmonary disease and for the administration of budesonide (Pulmicort Turbuhaler) to patients with asthma. In both studies, improvement in forced expiratory volume in 1 s in patients who were randomly assigned to use the Novolizer was comparable with that in patients who used the established devices. Furthermore, no differences in tolerability or safety between the Novolizer and the control devices were observed. Finally, patient acceptance of the Novolizer was high, with the majority of patients who used it stating that they would use the device again.

Topics: Albuterol; Asthma; Bronchodilator Agents; Budesonide; Humans; Lung Diseases, Obstructive; Nebulizers and Vaporizers

We investigated the effect of inhaled glucocorticoid (GC) on bronchial obstruction and on bronchial lability in schoolchildren born preterm. Twenty-one children with bronchial obstruction, increased responsiveness to a beta2-agonist, and/or increased diurnal variation in peak expiratory flow (PEF) were selected for an open longitudinal study of the value of inhaled GC. None of these children had an earlier diagnosis of asthma or current GC treatment. Eighteen children with median (range) birth weight 1025 (640-1600) g and gestational age 28 (24-35) weeks, age at study 10.1 (7.7-13) years, were treated with inhaled budesonide in initially high (0.8 mg m(-2) day(-1) for 1 month) and subsequently lower dose (0.4 mg m(-2) day(-1) for 3 months). Daily symptom scores were recorded. Spirometric values were measured in the clinic at the beginning and end of each treatment period. At home, children used a data storage spirometer. After treatment with budesonide for 4 months, spirometric values in the clinic did not significantly change. The median forced expiratory volume in 1 sec (FEV1) was 74% of predicted both at entry and after budesonide treatment. However, the median number of > or = 20% diurnal change in PEF values at home decreased during treatment. According to the present study, inhaled budesonide for 4 months had no significant effect on basic lung function but may decrease bronchial lability in schoolchildren born preterm.

Topics: Administration, Inhalation; Adolescent; Analysis of Variance; Bronchospirometry; Budesonide; Child; Forced Expiratory Volume; Gestational Age; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Longitudinal Studies; Lung Diseases, Obstructive; Peak Expiratory Flow Rate; Statistics, Nonparametric; Survivors

We compared the effect of inhaled budesonide with placebo on decline in lung function and respiratory symptoms in a three-year study of patients with chronic obstructive pulmonary disease (COPD). We used a parallel-group, randomized, double-blind, placebo-controlled design, nested in an ongoing epidemiological survey. Patients were non-asthmatic subjects with a decreased ratio between forced expiratory volume in one second (FEV1) and vital capacity (VC); i.e., FEV1/VC < or = 0.7. All included patients had an FEV1 which was irreversible to both inhaled terbutaline and prednisolone. Two hundred and ninety patients were randomized to receive either budesonide, 1200 mcg. daily for six months followed by 800 mcg. daily for 30 months, or placebo for 36 months. Patients had a mean age of 59 years and their mean FEV1 was 2.37 liters or 86% of predicted. Crude FEV1 declines were 41.8 ml/year in the placebo group and 45.1 ml/year in the budesonide group. Using a regression model in the intention-to-treat population, patients in the placebo group had an FEV1 decline of 49.1 ml/year in contrast to 46.0 ml/year in the budesonide group; the estimated difference 3.1 ml/year (95% confidence interval--12.8-19.0) was statistically insignificant, p = 0.70. No effect of inhaled budesonide was seen on respiratory symptoms or number of exacerbations. These findings question the role of longterm inhaled corticosteroids in the treatment of mild-moderate COPD.

Topics: Administration, Inhalation; Adult; Aged; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Time Factors; Vital Capacity

A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.. Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.. Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.. Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-Agonists; Aged; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Prednisone; Treatment Outcome

Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD.. We used a parallel-group, randomised, double-blind, placebo-controlled design in a singlecentre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital capacity of 0.7 or less; FEV1 which showed no response (<15% change) to 1 mg inhaled terbutaline or prednisolone 37.5 mg orally once daily for 10 days. 290 patients were randomly assigned budesonide, 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months, or placebo for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat.. The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year, budesonide group 45.1 mL per year). The estimated rates of decline from the regression model did not differ significantly (49.1 mL vs 46.0 mL per year; difference 3.1 mL per year [95% CI -12.8 to 19.0]; p=0.7). Before the study, the minimum relevant difference was defined as 20 mL per year; this difference was outside the 95% CI. No effect of inhaled budesonide was seen on respiratory symptoms. 316 exacerbations occurred during the study period, 155 in the budesonide group and 161 in the placebo group. Treatment was well tolerated.. Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD.

Topics: Administration, Inhalation; Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Time Factors; Treatment Outcome

Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years.. Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups.. In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.

Topics: Administration, Inhalation; Adult; Aged; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Smoking

Withdrawal of inhaled corticosteroids is known to worsen disease control in bronchial asthma but similar data are lacking in chronic obstructive pulmonary disease (COPD). We hypothesized that clinical exacerbations requiring treatment would occur more often in patients whose inhaled corticosteroids were stopped than in other patients not treated with these agents. We studied 272 patients in mean age 65 (SD 0.8) years, mean FEV1 42.8 (SD 12.6)% predicted, entering the run-in phase of the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. All had been clinically stable for at least 6 weeks and there were no differences in the degree of bronchodilator reversibility, baseline lung function or pack-years of smoking between the 160 patients receiving inhaled corticosteroids and those not so treated. Inhaled corticosteroids were withdrawn in the first week of the study and during the remaining 7 weeks of the study 38% of those previously treated with these drugs had an exacerbation compared to 6% of the chronically untreated group. Patients receiving inhaled corticosteroids reported a longer duration of symptoms but neither this or any other recorded variable predicted the risk of exacerbation. These data suggest that abrupt withdrawal of inhaled corticosteroids should be monitored carefully even in patients with apparently irreversible COPD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Substance Withdrawal Syndrome; Vital Capacity

The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease (COPD). Forty patients with stable COPD entered the study, and received prednisolone (37.5 mg o.d.) for 2 weeks. They were subsequently divided into steroid-irreversible and steroid-irreversible, using 15% of baseline as a dividing point. In each group patients were randomized to receive budesonide 400 micrograms b.i.d. or placebo for 6 months. During treatment with prednisolone, three patients dropped out because of side effects. Of the remaining 37, only two patients (5%) were reversible with prednisolone forced expiratory volume in 1s [(FEV1) > 15% of baseline], and among the steroid-irreversible, 26 patients were evaluated after 6 months treatment with either placebo or budesonide. No significant differences in spirometry values, symptoms, or number of exacerbations were found between these two groups. Reversibility with prednisolone is rarely seen in COPD. In outpatients with stable COPD and no signs of asthma or atopy, 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Lung Diseases, Obstructive; Middle Aged; Nebulizers and Vaporizers; Patient Selection; Predictive Value of Tests; Prednisolone; Treatment Outcome

The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 microg budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC20AMP, PC20MCh, or FEV1 after placebo pretreatment. Budesonide increased PC20MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p = 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p < 0.001). We conclude that AMP did not elicit greater sensitivity than MCh in assessing short-term effects of budesonide on AHR in smokers with COPD. We suggest that long-term treatment with inhaled corticosteroids might be beneficial, by reducing neutrophil load in the airways and improving the action of anticholinergic drugs.

Topics: Adenosine Monophosphate; Administration, Inhalation; Anti-Inflammatory Agents; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cholinergic Antagonists; Female; Forced Expiratory Volume; Glucocorticoids; Histamine; Histamine H1 Antagonists; Humans; Interleukin-8; Ipratropium; Leukocyte Count; Longitudinal Studies; Lung Diseases, Obstructive; Male; Methacholine Chloride; Middle Aged; Neutrophils; Placebos; Smoking; Terfenadine; Time Factors

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bone Density; Budesonide; Female; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Pilot Projects

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

Topics: Administration, Inhalation; Administration, Topical; Adult; Advertising; Aged; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Europe; Forced Expiratory Volume; Glucocorticoids; Hospital Records; Humans; Lung Diseases, Obstructive; Mass Media; Middle Aged; Patient Selection; Smoking; Vital Capacity

Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.. In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.. Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.. Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.

Topics: Administration, Inhalation; Administration, Oral; Aged; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Prednisolone; Single-Blind Method; Treatment Failure

Airways hyperresponsiveness (AHR) is an important feature of patients with chronic obstructive pulmonary disease (COPD). Little is known about factors that modulate AHR in COPD.. To study these factors, we performed a long-term, double-blind, parallel intervention study in 58 male, non-allergic patients with COPD.. During a period of 2 years, patients were treated with inhaled budesonide (1600 microg/day), inhaled budesonide (1600 microg/day) plus oral prednisolone (5 mg/day), or placebo. PC20 histamine was measured at 4-monthly intervals. The influence of treatment, smoking, age, level of lung function, initial serum IgE level and peripheral blood eosinophils on level and longitudinal change of PC20 histamine was analysed.. During follow-up, PC20 decreased in our group, and this decrease was not influenced by treatment. PC20 tended to decrease faster in current smokers than in ex-smokers. PC20 was significantly associated with pre-challenge FEV1 at each time point. Level nor decline of PC20 were significantly related to age. A higher initial serum IgE level was independently associated with a lower PC20. Moreover, a higher initial serum IgE level was associated with a slower annual decline of PC20, regardless of treatment, pre-challenge FEV1, and other modulating factors. No significant associations were found between initial blood eosinophils and level or decline of PC20.. We conclude that AHR increases over time in non-allergic patients with COPD. Treatment with an inhaled corticosteroid alone or in combination with oral prednisolone does not change this increase. Our study suggests an important role for IgE in the course of the disease, since a higher initial serum IgE level predicts a more favourable course with regard to annual decline of PC20 histamine.

Topics: Aged; Anti-Inflammatory Agents; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Double-Blind Method; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Immunoglobulin E; Longitudinal Studies; Lung Diseases, Obstructive; Male; Middle Aged; Prednisolone

The role of glucocorticoids in the treatment of chronic obstructive pulmonary disease (COPD) is controversial. We have previously described high numbers of neutrophils and high concentrations of the inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and of the cell activation markers eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO), and human neutrophil lipocalin (HNL) in COPD patients as compared with controls, and have postulated that the cytokines TNF-alpha and IL-8 play a role in propagating the inflammatory response in COPD. We have now studied the effects of inhaled and oral glucocorticoids on these inflammatory indices in induced sputum. Initially, we studied the effect of a 2-wk course of inhaled budesonide (800 mg twice daily for 2 wk) in 13 patients with severe COPD (mean FDV1: 35% predicted). There was no clinical benefit in either lung function or symptom scores, and no significant change in the inflammatory indices as measured by total and differential cell counts and concentrations of TNF-alpha eosinophil activation markers ECP and EPO, and neutrophil activation markers MPO and HNL. Because the lack of anti-inflammatory effect might have been due to poor drug delivery as a result of severe airflow limitation, we undertook a study examining the antiinflammatory effect of oral prednisolone (30 mg daily for 2 wk) in patients with COPD and undertook the same measurements in 10 patients with atopic asthma. Sputum eosinophil numbers, ECP, and EPO were significantly reduced in the asthmatic patients but were not modified in COPD. This confirms the clinical impression that inhaled steroids have little antiinflammatory effect, at least in the short term in this group of patients, and suggests that the inflammatory process in COPD is resistant to the antiinflammatory effect of glucocorticoids.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Cytokines; Female; Glucocorticoids; Humans; Inflammation; Lung Diseases, Obstructive; Male; Middle Aged; Prednisolone; Pregnenediones; Respiratory Function Tests; Sputum

A significant, large minority of patients with chronic obstructive pulmonary disease (COPD) respond favorably to corticosteroid treatment; but the benefit may be outweighed by its side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to an inhaled B2-agonist would individualize steroid responders. In 44 patients with stable COPD in a double- blind crossover trial, we compared a 6-week course of inhalations of 800 micrograms/d budesonide with a placebo, separated by a 4-week interval when no medication was taken. In 33 out of 42 responders to the B2-agonist who remained in the study, there was a significant improvement in FEV1 of greater than 20% following budesonide inhalation, as compared to placebo. There was also a significant difference between the 2 periods of treatment as to the mean number of B2-agonist inhalations. We conclude that about 1/4 of patients with stable COPD respond to bronchodilators, and treatment with inhaled steroids improves spirometry data and inhaled B2-agonist consumption in about 3/4.

Topics: Administration, Inhalation; Aerosols; Budesonide; Cross-Over Studies; Double-Blind Method; Glucocorticoids; Humans; Lung Diseases, Obstructive; Pregnenediones

Bone mass and biochemical bone markers were prospectively studied in 33 patients with chronic obstructive pulmonary disease treated for 1 year with inhaled beclomethasone 200 micrograms/q.i.d. (group A, 8 men and 4 women), inhaled budesonide 200 micrograms/q.i.d. (group B, 6 men and 5 women), or not requiring steroids (group C, 6 men and 4 women). Both inhaled corticosteroids decreased serum concentrations of the osteoblastic markers, osteocalcin and carboxy-terminal propeptide of type I collagen (PICP). The osteoclastic marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) increased significantly more in patients on beclomethasone than in those on budesonide. The decrease in bone mineral density was more pronounced in patients treated with beclomethasone (1.1% in the spine 1.7% in the hip P < 0.05) compared to those treated with budesonide (0.6% in both spine and hip) or in the control group. Inhaled corticosteroids affect biochemical bone markers and bone mineral density, but there is a different effect for the two corticosteroids evaluated in the present study.

Topics: Administration, Inhalation; Adult; Aged; Alkaline Phosphatase; Beclomethasone; Biomarkers; Bone Density; Budesonide; Calcium; Collagen; Collagen Type I; Female; Glucocorticoids; Homeostasis; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Osteocalcin; Osteoporosis; Peptide Fragments; Peptides; Pregnenediones; Procollagen; Prospective Studies

To determine the effectiveness of treatment with corticosteroids in patients with COPD.. In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.. Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.. Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.

Topics: Administration, Inhalation; Administration, Oral; Budesonide; Double-Blind Method; Drug Therapy, Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Prednisolone; Pregnenediones

Nebulized corticosteroids in acute bronchospasm may offer topical anti-inflammatory activity while minimizing undesirable systemic effects. We compared the side-effect profile of nebulized budesonide (2 mg twice daily) with that of oral prednisolone (30 mg once daily) in a randomized parallel-group study of 19 adults with severe acute airway obstruction. Over the 5 days of the study, baseline forced expiratory volume in 1 second (FEV1) increased from 1.8 (95% confidence interval [CI], 0.7) to 2.1 (95% CI, 0.7) L in the group that received oral corticosteroids compared with 1.9 (95% CI, 0.7) to 2.0 (95% CI, 0.7) L in the group that received nebulized corticosteroid. All biochemical variables were similar at day 1. Comparison of budesonide treatment with prednisolone on day 5 showed that urinary corticosteroid metabolites were significantly higher (2012 [95% CI, 812] compared with 1079 [95% CI, 346] mg/24 hr [p < 0.05]), urinary androgen metabolites were not different, serum osteocalcin was elevated (2.3 [95% CI, 1.4] compared with 0.6 [95% CI, 0.6] ng/ml [p < 0.05]), and 24-hour urinary calcium to creatinine ratios were lower (0.28 [95% CI, 0.1] compared with 0.53 [95% CI, 0.2]), whereas urinary hydroxyproline to creatinine ratios were similar. The biochemical markers associated with corticosteroid side effects improve in patients treated with nebulized corticosteroids compared with patients who receive conventional treatment.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adult; Aerosols; Androgens; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Calcium; Creatinine; Forced Expiratory Volume; Glucocorticoids; Humans; Hydroxyproline; Lung Diseases, Obstructive; Osteocalcin; Prednisolone; Pregnenediones; Treatment Outcome

A significant minority of patients with COPD have favorable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to inhaled beta 2-agonist will serve to individualize steroid responders. We compared a 6-week course of 800 micrograms/d inhaled budesonide with placebo, separated by 4 weeks when no medication was taken, in a double-blind crossover trial, in 8 patients responding to inhaled beta 2-agonist, and in 22 nonresponders with stable COPD. In six of eight "responders to beta 2-agonist," there was a significant improvement in the FEV1 (defined as > or = 20%) following inhaled budesonide, as compared with placebo. In the 22 "nonresponders to beta 2-agonist," there was no significant improvement in the mean FEV1 (1.41 +/- 0.1 L before, and 1.61 +/- 0.1 L after treatment) with inhaled budesonide or placebo. Over the 6-week course of treatment by either budesonide or placebo, the nonresponders reported similar beta 2-agonist consumption (4.8 +/- 0.2 and 5.0 +/- 0.1 puffs per patient per day, respectively). However, there was a significant difference between the two periods of treatment in the responders as for the mean daily number of beta 2-agonist inhalations (2.4 +/- 0.1 in the budesonide period as compared with 5.3 +/- 0.1 in the placebo period; p < 0.005). We conclude that treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about 25% of patients with stable COPD, and this rate is increased to about 75% in patients who respond to beta 2-agonist inhalation.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pregnenediones; Spirometry

The aim of the study was to carry out assessment of the respiratory function of patients with COPD undergoing a three month (600 microgram) treatment with an inhaled steroid--Budesonide. This was a double blind study carried out on 57 patients. During treatment with Budesonide a clinical improvement was seen. Respiratory function parameters did not alter throughout the 3 month treatment period, although bronchial reactivity diminished. Side effects were seen only in 3 patients--in all it was dysphonia. It seems that Budesonide can be added to other treatment protocols in patients with exacerbations of chronic bronchitis.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pregnenediones; Respiratory Mechanics; Voice Disorders

Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain.. Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment.. In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids.. No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bone and Bones; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Osteocalcin; Peptide Fragments; Pregnenediones; Procollagen

Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide.. Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed.. At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67.9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4.8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0.67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant.. In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.

Topics: Administration, Inhalation; Aged; Albuterol; Budesonide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Ipratropium; Lung; Lung Diseases, Obstructive; Male; Middle Aged; Prednisone; Pregnenediones

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Double-Blind Method; Europe; Female; Glucocorticoids; Humans; Inflammation; Lung Diseases, Obstructive; Male; Middle Aged; Pregnenediones; Research Design; Smoking

We have compared the effects of three-month periods of treatment with an inhaled corticosteroid, budesonide 600 micrograms twice daily and with placebo on bronchial responses to inhaled histamine and to bronchodilators in a double-blind crossover trial in 14 middle-aged male smokers (mean age, 59.6 years) with mild airways obstruction (mean FEV1 2.42 L, 80 percent predicted [range, 48 to 110 percent]). Responsiveness to inhaled histamine was assessed monthly by the provocative concentration (mg/ml) reducing FEV1 by 20 percent (PC20). Bronchodilator response to a combination of inhaled salbutamol (5 mg) and ipratropium (0.5 mg) was assessed before and after three months' treatment. Compliance with treatment was checked by weighing aerosol canisters, and by measuring plasma budesonide and metabolites. There was no significant change in FEV1 (budesonide mean 2.38 L [SEM 0.17] vs placebo 2.40 L [0.17]), vital capacity (budesonide mean 3.69 L [0.17] vs placebo 3.81 L [0.17]) or in bronchodilator responsiveness (mean increase over baseline FEV1, budesonide 11.6 [2.7] percent vs placebo 10.5 [3.2] percent). There was a small overall reduction in bronchoconstrictor responsiveness over the period of the trial, but there was no effect of 12 weeks of budesonide treatment compared with 12 weeks of placebo treatment (mean log PC20 during budesonide 0.595 [SEM 0.063], placebo 0.591 [SEM 0.055]). Following the three-month crossover trial, six men continued for nine more months to receive budesonide in a single-blind trial and the results were compared with those in six men who took no active treatment for the subsequent nine months. No improvements in baseline spirometry, home peak flow measurements, bronchoconstrictor or bronchodilator responsiveness were observed after 12 months of budesonide treatment. Thus, a regimen of budesonide treatment that consistently attenuates bronchial responsiveness in asthmatic subjects had no effect in these men; larger and longer trials will be required to establish whether a subgroup of smokers shows a favorable response.

Topics: Administration, Inhalation; Aged; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Double-Blind Method; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Patient Compliance; Pregnenediones; Pulmonary Ventilation; Single-Blind Method; Smoking

Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma. The aim of the present randomised, double blind study was to assess the effect of eight weeks' treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease. Twenty four subjects (23 male) entered the study. Their ages ranged from 40 to 70 (mean 57) years, with a mean of 35 (range 9-80) pack years of smoking; the mean FEV1 was 53% (range 32-74%) predicted and geometric mean PC20 (histamine concentration causing a 20% fall in FEV1) 0.96 (range 0.07-7.82) mg/ml. After a two week washout, single blind, placebo period, 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks. The only additional drug to be taken was ipratropium bromide "if needed." Twenty one patients completed the study, 10 in the budesonide group and 11 in the placebo group. The standard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step. There was a significant reduction in dyspnoea in the budesonide group, but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups. No significant differences in spirometric values, peak expiratory flow, PC20 histamine, or citric acid cough threshold were found between the groups. Although differences were not significant, some of the changes showed a trend in favour of budesonide. Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined.

Topics: Administration, Inhalation; Adult; Aged; Bronchodilator Agents; Budesonide; Cough; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pregnenediones; Smoking; Spirometry

Inhaled antiasthmatic steroids have been assumed and yet never proved to exert their antiasthmatic effect by topical action in the airways. We tested the hypothesis that the efficacy of inhaled budesonide (BUD) might be due instead to its systemic activity after absorption. We compared inhaled and oral BUD with doses selected to ensure higher peak plasma levels and a greater area under the plasma concentration curve with the oral treatment. After pretreatment with beclomethasone to maximize asthma control, 47 adults with asthma were randomized to receive 0.4 mg of inhaled BUD per day (n = 16) or 1.4 mg of oral BUD per day (n = 15), or placebo (n = 16) in double-blind fashion and then followed weekly until asthma relapsed or for 8 weeks if no relapse occurred. "Relapse" was defined as a drop in the mean peak expiratory flow rate greater than 2 SEM below the mean during the baseline week before switching to the test drugs. The time to relapse was the primary outcome variable. Time to relapse was longer with inhaled than with oral BUD (medians, 22 versus 7.9 days; p = 0.003) or placebo (medians, 22 versus 9 days; p = 0.004). Oral BUD and placebo did not differ (p = 0.41). The morning serum cortisol levels remained normal during all three treatments. Thus, at conventional dosage the antiasthmatic effect of inhaled BUD may be fully explained by a local intrapulmonary action.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Patient Compliance; Peak Expiratory Flow Rate; Pregnenediones

Inhaled corticosteroid (ICS) use is associated with an increased risk of pneumonia. This study was performed to determine if ICS use is associated with an increased risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) or tuberculosis (TB).We conducted a population-based nested case-control study using linked laboratory and health administrative databases in Ontario, Canada, including adults aged ≥66 years with treated obstructive lung disease (

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Budesonide; Case-Control Studies; Female; Fluticasone; Humans; Logistic Models; Lung Diseases, Obstructive; Male; Mycobacterium Infections, Nontuberculous; Ontario; Risk Factors; Tuberculosis

Serum periostin is a potential biomarker of response to therapies that target type 2 inflammation in asthma. The objectives of this study were to describe: 1) the distribution of serum periostin levels in adults with symptomatic airflow obstruction; 2) its relationship with other variables, including type 2 biomarkers; and 3) the effect of inhaled corticosteroids on periostin levels.Serum periostin levels were measured in a cross-sectional study exploring phenotypes and biomarkers in 386 patients aged 18-75 years who reported wheeze and breathlessness in the past 12 months. In 49 ICS-naïve patients, periostin levels were measured again after 12 weeks of budesonide (800 μg·day(-1)).The distribution of serum periostin levels was right skewed (mean±sd 57.3±18.6 ng·mL(-1), median (interquartile range) 54.0 (45.1-65.6) ng·mL(-1), range 15.0-164.7 ng·mL(-1)). Periostin was positively associated with exhaled nitric oxide (Spearman's rho=0.22, p<0.001), blood eosinophil count (Spearman's rho=0.21, p<0.001), and total IgE (Spearman's rho=0.14, p=0.007). The Hodges-Lehmann estimator (95% CI) of change in periostin level after ICS therapy was -4.8 (-6.7- -3.2) ng·mL(-1) (p<0.001).These findings provide data on the distribution of serum periostin in adults with symptomatic airflow obstruction, the weak associations between periostin and other type 2 markers, and the reduction in periostin with inhaled corticosteroid therapy.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Budesonide; Cell Adhesion Molecules; Cross-Sectional Studies; Eosinophils; Exhalation; Female; Humans; Inflammation; Lung Diseases, Obstructive; Male; Middle Aged; New Zealand; Nitric Oxide; Respiratory Function Tests; Respiratory Sounds; Risk Factors; Surveys and Questionnaires; Young Adult

Forced expiratory volumes are reduced in chronic obstructive pulmonary disease (COPD), mainly as a result of inflammatory and morphological changes in the small airways (with a diameter < 2 mm) and in the alveoli. However, it is difficult to detect minor changes in small airways by spirometry measurements. To study the effects on small airways of inhaled corticosteroids (ICS), 19 stable COPD patients were investigated; 15 were evaluated by ventilation-perfusion (V(A)/Q) relationships, assessed by the multiple inert gas elimination technique, and by diffusing capacity for carbon monoxide (DL(CO)), assessed by the single breath technique. Measurements were repeated after 2 months of budesonide inhalations (800 microg) twice daily. Before ICS treatment: mean forced expiratory volume in 1 sec (FEV1) as a percentage of predicted (% P) was 40.1 (+/- 16.0)%, DL(CO)% P was 45.7 (+/- 25.0)% and 6.0 (+/- 6.4)% of the ventilation was directed at high V(A)/Q areas. The mean of the V(A)/Q ratio for ventilation (V-mean) was 2.7 times higher than normal. After 2 months of ICS: the mean of DL(CO)% P increased by 8.6 (+/- 19.4)%, and FEV1/vital capacity decreased by 6.9 (+/- 11.3)%. Basal morning and ACTH-stimulated S-cortisol levels were significantly reduced. All the V(A)/Q relationships remained unchanged. In conclusion, a significant increase in diffusion capacity for carbon monoxide levels after treatment with corticosteroid inhalations for 2 months was shown, but no significant improvements were found in forced expiratory airflow, lung volumes, or V(A)/Q relationships.

Topics: Administration, Inhalation; Aged; Anti-Inflammatory Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Lung; Lung Diseases, Obstructive; Male; Middle Aged; Pilot Projects; Pulmonary Diffusing Capacity; Ventilation-Perfusion Ratio; Vital Capacity

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Eosinophils; Glucocorticoids; Humans; Inflammation; Lung Diseases, Obstructive; Sputum

Topics: Administration, Inhalation; Atrophy; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Humans; Long-Term Care; Lung Diseases, Obstructive; Middle Aged; Skin

Topics: Administration, Inhalation; Bronchodilator Agents; Budesonide; Humans; Lung Diseases, Obstructive; Smoking

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Chronotherapy; Glucocorticoids; Humans; Lung Diseases, Obstructive; Treatment Outcome

Glucocorticoids (gcs) are known to be effective in the treatment of asthma. In chronic obstructive pulmonary disease (COPD), however, no beneficial effects are demonstrated in most patients. Hypothetically, this may be explained by an overexpressed beta-glucocorticoid receptor (GR) compared to the alpha-GR. The aim of this study was to investigate alpha- and beta-GR mRNA levels and ratios in patients with COPD with or without glucocorticoid treatment. GR and, as a control, metallothionein (MT) 2 mRNA levels were compared between patients with COPD receiving glucocorticoids (COPD + gcs), glucocorticoid naive COPD-patients (COPD - gcs) and non-COPD control patients not using gcs. Bronchoscopy was performed and bronchial epithelial cells were sampled with brushing. Smoking did not influence alpha- and beta-GR levels and ratios, nor the MT2 mRNA expression level. The alpha-GR mRNA expression was lower in the COPD - gcs group than in controls. Both GR forms were higher in the COPD + gcs patients than in the COPD - gcs patients, but not different from the levels measured in the controls. alpha 1/beta-GR mRNA ratios did not differ between the groups and averaged 1.7, suggesting no inhibitory effect of the beta-GR on the alpha 1 form. MT2 levels were upregulated in the COPD + gcs patients as compared to the COPD - gcs group, indicating a pharmacological glucocorticoid effect. In the present study it is demonstrated that basal GR mRNA levels are lower in patients with COPD. Although this needs to be investigated further, this might explain, in part, the non-responsiveness of patients with COPD to gcs.

Topics: Adult; Aged; Beclomethasone; Blotting, Northern; Bronchi; Budesonide; Chi-Square Distribution; Cross-Sectional Studies; Epithelial Cells; Female; Gene Expression; Glucocorticoids; Humans; Isomerism; Lung Diseases, Obstructive; Male; Middle Aged; Receptors, Glucocorticoid; RNA, Messenger; Statistics, Nonparametric

To determine the extent of inhaled corticosteroid use among patients with chronic obstructive pulmonary disease (COPD).. Review of medical records.. Tertiary-care university teaching hospital.. Seventy-two consecutive patients prescribed an inhaled corticosteroid during hospitalization.. None.. Patient demographics, inhaled corticosteroid regimen, respiratory diagnosis, and inhaled corticosteroid use before and during hospitalization.. The majority of patients (85%) were receiving their prescribed corticosteroid inhaler prior to admission. Beclomethasone dipropionate 250 micrograms/puff was the most commonly prescribed inhaled corticosteroid formulation accounting for 43% of the total corticosteroid inhaler orders. COPD was the most common respiratory diagnosis (43%) associated with inhaled corticosteroid use, followed by asthma (37%), COPD/asthma (13%), and no diagnosis (7%). During the study period, the proportion of all hospitalized patients with COPD who also received inhaled corticosteroid prescriptions (35%) was not significantly different from all hospitalized patients with asthma who received inhaled corticosteroid prescriptions (33%).. The rate of inhaled corticosteroid use far exceeds the rate expected among the general population of patients with COPD. Educational intervention is needed to encourage compliance with published guidelines for the management of COPD.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Chi-Square Distribution; Drug Utilization; Female; Hospitalization; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Practice Patterns, Physicians'; Pregnenediones

Topics: Aged; Aspergillosis; Budesonide; Female; Glucocorticoids; Humans; Lung Diseases, Fungal; Lung Diseases, Obstructive; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Opportunistic Infections

Topics: Aerosols; Airway Resistance; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Humans; Lung Diseases, Obstructive; Nebulizers and Vaporizers; Pilot Projects; Pregnenediones; Radiography

Topics: Absorption; Administration, Topical; Aerosols; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Eye; Female; Glaucoma; Glucocorticoids; Humans; Ipratropium; Lung Diseases, Obstructive; Nebulizers and Vaporizers; Pregnenediones

Topics: Administration, Inhalation; Administration, Topical; Adult; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Humans; Lung Diseases, Obstructive; Pregnenediones

Topics: Adrenal Glands; Adult; Aged; Budesonide; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Lung Diseases, Obstructive; Middle Aged; Prednisone; Pregnenediones