The dose-response slope: a useful method for expressing the results of methacholine provocation tests in healthy subjects?

In order to study the reproducibility of different indices of airway responsiveness, two bronchial provocations with increasing methacholine concentrations up to 256 mg ml-1 were performed within 2 weeks on 30 healthy volunteers. The dose-response slope [DRS = maximal fall (%) in pulmonary function/maximal non-cumulative methacholine dose (mumol)] was calculated from forced expiratory volume in 1 s (FEV1) and from area under the expiratory flow-volume curve (AEFV). DRS reproducibility within 2 weeks in responsive (decline in FEV1 greater than 20%) and non-responsive subjects (decline in FEV1 less than 20%) was assessed. After log-transformation of the data the reproducibility was assessed with intraclass correlations (ICC) [with 95% confidence intervals (CIicc)], mean difference with limits of agreement (delta +/- SD), 95% confidence intervals for a single measurement (CIsm), and the absolute difference of the observations of the two days from each other (zero = ideal reproducibility). Provocative doses (PD20FEV1) could be calculated for 14 subjects on both occasions. In this responsive group the reproducibility of all the parameters used (PD20FEV1, DRSFEV1 and DRSAEFV) was high. In the non-responsive group, DRSFEV1 demonstrated a slightly, but not clearly, lower ICC than DRSAEFV. However, DRSFEV1 had clearly wider limits of agreement and CIsm than DRSAEFV. Also, with DRSFEV1 the observations of the two days differed significantly more from each other than with DRSAEFV (P less than 0.05).