Variability of the plateau response to methacholine in subjects without respiratory symptoms

BACKGROUND--Interpretation of measurements of limited maximal airway narrowing, or plateau response, requires knowledge of its variability within subjects and between methods. METHODS--The repeatability of the plateau response to inhaled methacholine with a dosimeter (D) method (maximal dose 210 mumol) and a tidal breathing (T) method (730 mumol), and the agreement of the two methods, were measured in 16 subjects with mild or no asthma. Two tests by each method (D1,D2,T1,T2) were performed in random order over four consecutive days, with a third dosimeter (D3) test one week later. The dose producing a decrease in forced expiratory volume in one second (FEV1) of 10% (PD10) and the plateau were calculated from each dose-response curve. RESULTS--A plateau was reached in all five tests in 12 subjects and in all tests except D3 in 14 subjects. PD10 was inversely related to the plateau (r = -0.95 for D, r = -0.77 for T). The 95% ranges for differences between two determinations of the plateau in a subject were +/- 11.9% (change in FEV1), +/- 19.2%, and +/- 20.3%, estimated from D1-2 and 1-3, and T1-2 tests, respectively. From the same tests the 95% ranges for the difference of a single determination from an individual's true mean value were +/- 8.3%, +/- 13.6%, and +/- 14.3%. The limits of agreement between methods indicated that 95% of the measurements of the plateau by tidal breathing ranged from 15.2% below to 13.3% above those obtained by dosimeter. There was no significant bias between methods. Tachyphylaxis over 24 hours occurred with PD10 but not with the plateau response. CONCLUSIONS--The plateau response is a subject characteristic which is independent of the method of inhalation challenge testing. Repeatability of the plateau is low in this group of subjects with low airway responsiveness.