ANNUAL VARIABILITY IN METHACHOLINE RESPONSIVENESS IN NONASTHMATIC WORKING ADULTS

Change in airway responsiveness is used frequently as a clinical as we ll as an epidemiological tool, Changes in airway responsiveness can be superior to other measures of lung function in that they are more sen sitive indicators of an environmental effect, However, normal variatio n in test results must be defined before change can be interpreted, To characterize annual variability in airways responsiveness, we adminis tered a high-dose methacholine challenge at 1 yr intervals for up to 4 yrs to 105 healthy, nonasthmatic working subjects, Using this high-do se protocol, the majority of tests (83%) produced at least a 20% fall in forced expiratory volume in one second (FEV1), allowing standard ca lculation of the provocative dose of methacholine causing a 20% fall i n FEV1 (PD20). An annual change in methacholine responsiveness by one or more doubling doses was seen in at least 30% of subjects each year, The components of variance of airways responsiveness measures were es timated to allow direct comparison of within-subject and between-subje ct variability, The within-subject variability in PD20, was markedly g reater than the comparable within-subject variability in FEV1. respira tory disease epidemiology Level of FEV1 and age were both significant determinants of methacholine responsiveness, Comparison of two methods of expressing methacholine responsiveness (PD20 using the full challe nge up to 250 mg.mL(-1) methacholine, and the dose-response slope usin g data up to 32 mg.mL(-1) methacholine as the maximum dose) had simila r annual variability in censored data and mixed-effects models, We the n developed an approach to statistical analysis of ''right-censored'' methacholine challenge data using a maximum likelihood estimation unde r a censored Gaussian model, These studies of methacholine responsiven ess provide normative data on annual test variability in healthy, nona sthmatic working adults, and show that a shorter low-dose challenge ha s comparable annual variability to a lengthier high-dose challenge.