THE EFFECT OF INHALED CORTICOSTEROIDS ON THE MAXIMAL DEGREE OF AIRWAY NARROWING TO METHACHOLINE IN ASTHMATIC SUBJECTS

Airway hyperresponsiveness in asthma is characterized by an increase in sensitivity and in maximal response to airway-narrowing stimuli. Long-term therapy with inhaled corticosteroids is known to reduce airway hypersensitivity in asthmatic patients. To investigate whether these drugs also reduce the maximal degree of airway narrowing we studied the effects of inhaled budesonide on the maximal response plateau of the dose-response curve to inhaled methacholine in mildly asthmatic patients in whom a raised plateau could be measured. Sixteen atopic patients with mild asthma were placed randomly into two parallel treatment groups to receive double-blindly either budesonide (400-mu-g twice daily) or placebo, inhaled via a Turbuhaler(R), for 4 wk. Before treatment, after 2 and 4 wk of treatment, and after 2 and 4 wk of wash-out, complete dose-response curves to methacholine were obtained using a standardized 2-min tidal breathing method. The response was measured by FEV1, expressed in % fall from baseline. A plateau on the log dose-response curve was considered if three or more data points fell within a 5% response range. The maximal response was obtained by averaging the values on the plateau (MFEV1), and the sensitivity was calculated from the provocative concentration of methacholine, causing a 20% fall in FEV1 (PC20). After 4 wk of budesonide treatment, mean MFEV1 decreased from 41.6 to 33.7% fall (p = 0.0004). The changes in MFEV1 were significantly different between placebo and budesonide (p = 0.03). The geometric mean PC20 increased from 3.4 to 6.3 mg/ml (p = 0.02), but the changes in PC20 were not different between the two groups (p = 0.23). We conclude that budesonide limits the increased maximal airway narrowing in asthmatic patients. The results suggest that asthma therapy should include anti-inflammatory drugs such as inhaled corticosteroids in order to limit potentially dangerous degrees of airway narrowing.