pulmicort and Substance-Withdrawal-Syndrome

Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control.. To identify predictors of loss of control and the kinetics of symptoms, and inflammatory and physiological measurements when inhaled corticosteroids are reduced in patients with stable asthma.. In a single-blind study, the daily dose of inhaled corticosteroid was reduced by one-half at intervals of 20+/-2 days in 17 adults with controlled asthma until loss of asthma control occurred or until the corticosteroid was replaced with placebo for 20 days. The patients recorded symptoms and peak expiratory flow each day, and forced expiratory volume in 1 s (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), exhaled nitric oxide, and eosinophils in sputum and blood were measured every 10 days. A loss of asthma control was defined as a worsening of the symptoms score of at least 20%, and either a decrease in FEV1 of at least 15% or a decrease in PC20 of at least fourfold.. Two patients had a respiratory infection and were withdrawn from the study. In eight patients, asthma became uncontrolled after a mean of 33 days (range 13 to 48 days). This was accurately reflected by a worsening of all parameters. The first parameter to change was the sputum eosinophil percentage (20 days before the loss of asthma control). Significant changes in exhaled nitric oxide, FEV1 and methacholine PC20 were observed only when the symptoms became uncontrolled. A high blood eosinophil count at baseline (risk ratio of 2.5, 95% CI 1.0 to 6.5) and an increase in sputum eosinophil count after the reduction of corticosteroids were predictors of loss of asthma control.. In patients whose asthma is controlled on inhaled corticosteroid, it is prudent not to reduce the dose further if the blood eosinophils are increased or if the sputum eosinophils increase by as little as 1% after the reduction of corticosteroids.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Middle Aged; Peak Expiratory Flow Rate; Single-Blind Method; Sputum; Substance Withdrawal Syndrome

There is uncertainty about the development of airway tolerance to beta-agonists and the phenomenon of rebound bronchoconstriction on beta-agonist withdrawal. We have recently completed a study of the regular terbutaline and budesonide treatment in asthma. We report our observations on the effect of starting and stopping terbutaline treatment on morning and evening peak flows. The study was a randomized four-way, double-dummy, cross-over comparison of regular inhaled terbutaline (500-1000 microg four times daily), budesonide, combined treatment and matching placebo. Each treatment was given for 6 weeks following a 4 week single-blind placebo washout. Ipratropium was used for symptom relief. No other asthma medication was permitted during either the treatment or wash-out periods. Evaluable data were obtained from 52 subjects for both placebo and terbutaline treatment. Changes in mean morning and evening peak flows during terbutaline treatment were compared to the baseline peak flows during the last 2 weeks of the preceding washout. The peak flow changes on stopping terbutaline were also analysed. Mean morning peak flow was not significantly different during terbutaline treatment when compared to either baseline or placebo treatment. Evening peak flows were significantly higher during terbutaline treatment [mean increase 23.1 l min(-1) (95% CI = 18.8, 27.4)]. Analysis of the peak flow changes on a day-by-day basis revealed an initial increase in morning peak flows for the first 2 days of treatment of 19.2 and 13.41 min(-1) [increases of 25.0 and 17.31 min(-1) in comparison with the corresponding values during placebo (P<0.01)] followed by a return to baseline. The increase in evening peak flows was also greater for the first 2 days of treatment than for the remainder of the treatment period (P<0.01). On ceasing terbutaline treatment there was a fall in mean morning peak flow below the baseline on the following morning of 21.6 l min(-1) (P<0.05 compared to placebo). The temporary increase in morning peak flows and greater than expected rise in evening peak flows for the first 2 days of treatment suggest the development of tolerance to the bronchodilator effect of terbutaline. Similarly, the fall in morning peak flows on treatment withdrawal suggests rebound bronchoconstriction. These effects are likely to be mediated by downregulation of the beta-receptor during treatment. The clinical significance of these changes is uncertain in view of the stability of ove

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Substance Withdrawal Syndrome; Terbutaline; Vital Capacity

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

Oral budesonide has been proven effective in short- and long-term treatment of collagenous colitis; however, symptom relapse frequently occurs after drug withdrawal. The aim of this study was to identify the risk factors for symptom relapse in patients with collagenous colitis after withdrawal of short-term budesonide therapy.. One hundred twenty-three patients from 4 randomized controlled studies who achieved clinical remission after short-term treatment with budesonide (9 mg/d) were analyzed, including 40 patients receiving subsequent budesonide maintenance therapy (6 mg/d) for 6 months and 83 patients without active maintenance treatment. Variables available for analysis were age, sex, baseline stool frequency, duration of diarrhea, collagenous band thickness, and lamina propria inflammation. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated by Cox proportional hazard model.. The overall symptom relapse rate was 61%. By multivariate analysis, a baseline stool frequency >5 per day (HR, 3.95; 95% CI, 1.08-14.39), history of diarrhea >12 months (HR, 1.77; 95% CI, 1.04-3.03), and the absence of budesonide maintenance therapy (HR, 2.71; 95% CI, 1.37-5.38) were associated with symptom relapse. The time to relapse was shorter in patients with a baseline stool frequency >5 per day (56 versus 199 d, P = 0.024), as in those with history of diarrhea >12 months (56 versus 220 d, P = 0.009). Budesonide maintenance therapy delayed the time to relapse (56 versus 207 d, P = 0.005).. Our data demonstrate that a high stool frequency at baseline and a long duration of diarrhea are risk factors for symptom relapse in collagenous colitis, whereas budesonide maintenance therapy is a protective factor against symptom relapse.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Diarrhea; Female; Follow-Up Studies; Humans; Inflammation; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Substance Withdrawal Syndrome

Thirty-eight patients with chronic asthma requiring continuous oral corticosteroid treatment took part in a 2-year study. Budesonide, a new inhalation steroid with high topical activity and low systemic effects, was given in stepwise increasing doses from 200 micrograms daily up to 800-1600 micrograms daily and prednisolone doses were decreased gradually on an individual basis. After 2 years, 18 patients had been able to cease oral prednisolone treatment, 11 had decreased the dose by greater than or equal to 50%, three by less than or equal to 50% and two patients had increased their dose. At the end of the study the majority of patients (26) were using 800 micrograms budesonide daily and seven, 1200 micrograms or more daily. There were two dropouts, one due to local side effects and one to a severe pulmonary eosinophilia. Ten patients had local side effects in the form of hoarseness and/or sore throat, and 13 patients had steroid withdrawal symptoms such as arthralgia and myalgia. The asthma condition in all patients was improved, as indicated by the reduced need for hospital admissions. The results indicate that high doses of budesonide should be tried before starting maintenance therapy with oral steroids.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Arthritis; Asthma; Beclomethasone; Budesonide; Female; Humans; Male; Middle Aged; Prednisolone; Pregnenediones; Substance Withdrawal Syndrome