Methacholine dose-response slopes from maximal bronchial challenge tests in asthmatic children: methodological aspects

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholine (dose range: 0.097-30.08 mumol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a delta FEV1 > or = 20%; and (2) a MFEV1 > or = 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % delta FEV1 x mumol-1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student's t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 +/- 2.7 delta FEV1%. mumol-1) was 2.88 times higher than DRR50% (31.6 +/- 3.4 delta FEV1%. mumol-1), and the LSS20% (89.1 +/- 2.8% delta FEV1. mumol-1) was 3.10 times higher than LSS50% (28.8 +/- 1.5% delta FEV1. mumol-1). The goodness of fit of LSS50% was significant in all cases, whereas LSS20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.