We investigated determinants of change in bronchial reactivity in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), a population-based cohort with wide age range (29-72 yrs at follow-up). The role of sex, age, atopic status, smoking and body mass index (BMI) on percentage change in bronchial reactivity slope from the baseline value was analysed in 3,005 participants with methacholine tests in 1991 and 2002, and complete covariate data. Slope was defined as percentage decline in forced expiratory volume in 1 s from its maximal value per micromole of methacholine. Bronchial hyperreactivity prevalence fell from 14.3 to 12.5% during follow-up. Baseline age was nonlinearly associated with change in reactivity slope: participants aged <50 yrs experienced a decline and those above an increase during follow-up. Atopy was not associated with change, but accentuated the age pattern (p-value for interaction = 0.038). Smoking significantly increased slope by 21.2%, as did weight gain (2.7% increase per BMI unit). Compared with persistent smokers, those who ceased smoking before baseline or during follow-up experienced a significant decrease in slope (-27.7 and -23.9%, respectively). Differing, but not statistically different, age relationships and effect sizes for smoking and BMI between sexes were found. Mean bronchial reactivity increases after 50 yrs of age, possibly due to airway remodelling or ventilation-perfusion disturbances related to cumulative lifetime exposures.