Concentrations of methacholine for bronchial responsiveness according to symptoms, smoking, and immunoglobulin E in a population-based study in Spain

To assess the simultaneous effects of symptoms related to asthma, smoking, and immunoglobulin E (IgE) on the concentrations of methacholine at which different individuals fall below 80% the FEV₁ values obtained with saline, we used parametric survival methods that fit the dose-response nature of bronchial responsiveness (BR). A general population-based sample of 1,615 adults (aged 20 to 44 yr) from five cities in Spain participating in the European Community Respiratory Health Survey was studied. The total number of subjects whose FEV₁ values dropped below 80% was 237 (14.7%). We found that individuals with symptoms related to asthma, whether they were smokers or nonsmokers, responded at lower concentrations of methacholine than individuals without symptoms. The greatest decrease in the concentrations of methacholine at which different percentages of individuals responded was due to symptoms among the nonsmokers (relative percentiles ranging from 0.53 to 0.76, and a 90% confidence band not containing a value one). Among individuals without symptoms, smokers responded at moderately but significantly lower concentrations than nonsmokers, whereas an apparent protective effect of smoking was seen in symptomatic individuals, owing in part to a self-selection bias. The higher the concentration of IgE, the lower were the concentrations of methacholine needed to obtain a given level of BR. Moreover, the magnitude of the decrease in methacholine concentrations leading to a response was constant over all percentages of individuals responding. The analytical methods used in the study permit the incorporation of complexities in the relationships between BR and symptoms, smoking, and IgE, and are generally applicable to situations in which a dose-response relationship occurs.