Maximal Airway Narrowing in a General Population

To characterize airway responses in a population sample, respiratory symptoms, smoking habits, and changes in FEV1 (ΔFEV1) to inhaled methacholine (maximal cumulative dose of 196 µmol or maximal decrease in FEV1 of 50%) were recorded in 201 subjects. From each dose-response curve the plateau (ΔFEV1 ⩽ 5% over two or more dose steps) response, the maximal response (average of responses on the plateau or maximal ΔFEV1 when no plateau was present), slope, and PD20 (dose required to cause ΔFEV1 > 20%) were derived. The pattern of dose-response curves was a continuous change from being flat (maximal ΔFEV1 ⩽ 5%), becoming steeper with a plateau that occurred at a greater change in FEV1 as the curves were shifted more to the left, to being the steepest without a plateau response. Maximal ΔFEV1 was significantly related to the PD20 (r = −0.64, p < 0.001) and the slope (r = 0.63, p < 0.001). A history of doctor-diagnosed asthma or wheeze in the last 12 months was related to the level of the maximal ΔFEV1 and to PD20. Likelihood ratios [LR = sensitlvity/(1 − specificity)] for asthma or wheeze were higher for a maximal ΔFEV1 of 50% plus a PD20 of 4 µmol (LR = 6.5) or 1 µmol (LR = 7) than for either alone. Subjects without reported asthma or wheeze more often had a plateau on the dose-response curve (76%) than those with a positive history (49%, p < 0.001). In subjects with a maximal ΔFEV1 < 50%, those without a plateau more often reported asthma or wheeze and usual cough and were more often current smokers than those with a plateau. These results show that the frequency of asthma symptoms is related to both the degree of maximal airway narrowing and the PD20 and is less in subjects with a plateau response indicating limitation of airway narrowing. The findings support the hypothesis that asthma results from the loss of factors that usually limit maximal airway narrowing.