EFFECT OF CESSATION OF SHORT-TERM THERAPY WITH IPRATROPIUM BROMIDE ONLUNG FUNCTION AND AIRWAY RESPONSIVENESS

Regular exposure to antimuscarinic drugs would be expected to upregula te airway muscarinic receptors and could cause a transient increase in airways obstruction if treatment was stopped or omitted. We have exam ined peak expiratory flow rate (PEFR) during treatment and forced expi ratory flow in one second (FEV1) and airway responsiveness to three co nstrictor agonists (as the provocative dose of agonist causing a 20% f all in FEV1, (PD20)) following cessation of regular inhaled ipratropiu m bromide, in 13 subjects with mild stable asthma. Subjects inhaled pl acebo and ipratropium bromide, 80 mu g q.i.d. for 14 days in a cross-o ver fashion with a 1 week run-in/wash-out period before and after each treatment period. Subjects recorded symptom scores and PEFR throughou t the study, and FEV1 and PD20 to histamine, methacholine and metabisu lphite were measured before and after cessation of treatment. When com pared to baseline, FEV1 was lower after cessation of ipratropium than after placebo, with a significant difference 30 h after the last dose (difference 190 mL; 95% confidence interval (95% CI) 310-70 mL; p<0.02 ), FEV1 measured 6-10 days later, did not differ significantly. PEFR w as significantly lower after cessation of ipratropium than after place bo on Day 15 (19-37 h after the last dose) (mean difference 4.6%; 95% CI 1.6-7.5%; p<0.01) but not on Day 16. There were no significant chan ges in PD20 histamine, methacholine and metabisulphite, symptom scores or rescue bronchodilator use after cessation of treatment. Thus, tran sient bronchoconstriction was found around 30 h after cessation of reg ular therapy with inhaled ipratropium for 2 weeks, The mechanism is un clear, as no evidence of muscarinic receptor upregulation was found. A lthough the changes were small and unlikely to be important for most p atients, the results of this study indicate that the timing of lung fu nction measurements relative to the last dose of ipratropium is import ant when interpreting the course of lung function in long-term studies .