Maximal response plateau to methacholine as a reliable index for reducing inhaled budesonide in moderate asthma

Although some studies suggest that asthma deteriorates after reducing inhal ed steroids, results of long-term studies indicate that this might not be t rue for all patients. The aim of this study was to determine the utility of the detection of a plateau on the concentration-response curves to inhaled methacholine as a marker for safely reducing the dose of inhaled budesonid e in asthmatic patients who are well-controlled with a moderately high dose of this inhaled steroid. A total of 46 patients with moderate asthma, well-controlled for at least 6 months by treatment with 800 mu g budesonide daily, were included in the s tudy, Subjects were treated for a 2-week run-in period with their usual dos e of budesonide. At the end of the run-in, all subjects were challenged wit h methacholine (0.095-200 mg.mL(-1)). Plateau responses, median effective c oncentration values, slopes and provocative concentration of methacholine c ausing a 20% fall in forced expiratory volume in one second (FEV1) values w ere measured. For the subsequent 12 weeks, patients were treated in an open design with budesonide at a reduced dose (200 mu g once daily), and were a sked to record their peak expiratory flow (PEF) in the morning and in the e vening. In addition, asthma symptoms and use of rescue terbutaline were rec orded in diaries. Plateaus were present in 24 patients, whereas 22 subjects showed concentrat ion-response curves without evidence of a plateau, Ten patients in the nonp lateau group deteriorated after reducing inhaled budesonide, compared to on e patient in the plateau group (p=0.002). In the nonplateau group, FEV1 dec reased from a baseline value of 3.28+/-0.19 L to 2.94+/-0.20 L at week 12 ( p<0.0001). Like wise, morning PEF decreased fi om 419+/-19 L.min(-1) at bas eline to 394+/-19 L.min(-1) at week 12 (p=0.02). By contrast, these variabl es remained unchanged in the plateau group. In conclusion, in asthmatic patients, well-controlled with a moderately hig h dose of budesonide, the detection of a plateau on the concentration-respo nse curve to inhaled methacholine may be used as a marker for safely reduci ng the colticosteroid dose.