Distribution of bronchial responsiveness in a general population: Effect of sex, age, smoking, and level of pulmonary function

Bronchial responsiveness (BR) was assessed by the methacholine challenge test in 1,694 subjects from a sample of the general population (aged 8 to 73 yr) enrolled in a prospective epidemiologic study on the natural history of chronic obstructive pulmonary disease (COPD). Information on respiratory symptoms and risk factors for COPD were obtained with a standardized questionnaire. The provocative dose causing a 10%, 15%, and 20% decrease in FEV 1 was reached in 939 (55%), 658 (39%), and 447 (26%) subjects, respectively, after the last cumulative dose of methacholine (i.e., 4.8 mg). The slope of the dose-response curve was also computed in order to attribute a parameter to subjects who did not reach the provocative dose. After natural log transformation, the slope (Ln Slope) of the curve showed a significant association with the degree of airway obstruction, as assessed by FEV 1% predicted, FEV 1/VC%, and FEV 1/FVC%. Therefore, relationships between BR, sex, age, and smoking were evaluated after adjustments for the initial airway caliber (FEV 1, FEV 1 adjusted for height, and FEV 1/VC%). Females showed significantly higher values of Ln Slope than did males after adjustments were made for baseline lung function. In males, higher BR was observed in childhood-adolescence age groups and at older ages, while in females a higher level of BR was observed during childhood. Significantly higher Ln Slope values were found for females who currently smoked than for non- and ex- smokers. No difference was observed in males in relation to smoking habit. A dose-response trend, taking daily cigarette smoking into account, was found in females but not in males. Our data confirm the importance of considering the initial airway caliber in assessing independent effects of age, sex, and smoking on BR. After taking into account initial airway lung function, females show a higher degree of BR than do males for all age groups, with the exception of children <= 12 yr. In addition, in females BR declines after childhood and then remains the same, whereas in males BR declines after childhood, and then rises again in later life. Airways of females appear more susceptible to cigarette smoking than do those of males.