Predictors of loss of asthma control induced by corticosteroid withdrawal.

BACKGROUND: Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control. OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: Two patients had a respiratory infection and were withdrawn from the study.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. CONCLUSION: 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.

Smoking, season, and detection of Chlamydia pneumoniae DNA in clinically stable COPD patients.

BACKGROUND: The prevalence and role of Chlamydia pneumoniae in chronic obstructive pulmonary disease (COPD) remain unclear, and molecular methods of detection may help clarify this relationship. METHODS: Consecutive clinically stable patients with smoking-related COPD attending a tertiary care outpatient clinic were enrolled in this cross-sectional study. Peripheral blood mononuclear cells were obtained from 100 patients, and induced sputum was obtained in 62 patients. C. pneumoniae DNA was detected in blood or sputum by nested polymerase chain reaction (PCR). RESULTS: Patients had mean age (standard deviation) of 65.8 (10.7) years, mean forced expiratory volume in one second (SD) of 1.34 (0.61) L, and 61 (61.0%) were male. C. pneumoniae nucleic acids were detected in 27 (27.0%) patients. Among 62 patients with both blood and sputum available, blood specimens were superior to induced sputum for detection of C. pneumoniae DNA (21 versus 7 detected, P=0.003). Current smoking (odds ratio [OR]=2.6, 95 % confidence interval [CI]: 1.1, 6.6, P=0.04), season (November to April) (OR=3.6, 95% CI: 1.4, 9.2, P=0.007), and chronic sputum production (OR=6.4, 95% CI: 1.8, 23.2, P=0.005) were associated with detection of C. pneumoniae DNA. CONCLUSIONS: C. pneumoniae DNA prevalence was higher among current smokers, and during winter/spring months. Prospective molecular studies are needed to examine the role of C. pneumoniae detection in COPD disease symptoms and progression.

Beta2-agonist tolerance and exercise-induced bronchospasm.

The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 microg qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 microg at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.