Methacholine Responsiveness among Working Populations: Relationship to Smoking and Airway Caliber

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Abstract
It has been suggested that the development of bronchial hyperresponsiveness (BHR) in some smokers may be an intermediate event in the progression to chronic obstructive pulmonary disease in this group. If this is true, prevalence data on BHR in a general population should show an independent association between BHR and smoking status. To test this, we analyzed BHR to inhaled methacholine in 654 white men without known asthma, in relation to smoking, skin-test reactivity, type of work (office versus industrial), and indicators of baseline airway caliber (FEV1% predicted and FEV1/FVC). BHR was measured in the traditional way (PC20) and as the slope of FEV1 versus the methacholine concentration (linear scale). A PC20 of < 16 mg/ml was considered "responsive" for analyses of this outcome. We found that although a positive skin test, smoking, and being an industrial worker all appeared to be significant predictors of increased BHR (p < 0.05), once FEV1 (% predicted) and FEV1/FVC% were taken into account, none of these variables alone remained significantly associated with BHR. The strongest predictors of BHR were prechallenge FEV1 and FEV1/FVC (both p < 0.01). The combination of smoking, atopy, and work groups, which identified a small subgroup of atopic smokers who were office workers, also remained significantly associated with increased BHR. We also used a regression model that allowed for comparison of predictors for BHR between the most responsive subset of the population (n = 84) and the remainder of the study population. We found that although smoking was not significantly related to BHR in the majority of the study group, among the more responsive subset, smoking had a significant, negative association with BHR (i.e., smokers were less responsive than nonsmokers at this more responsive end of the population). These results suggest that population studies of BHR must take into account baseline airway caliber population selection factors and the possibility of qualitatively different predictors of BHR at the two ends of the response spectrum.