The natural history of chronic airflow obstruction revisited: An analysis of the Framingham Offspring Cohort

Rationale: Understanding normal lung development and aging in health and disease, both in men and in women, is essential to interpreting any therapeutic intervention. Objectives: We aimed to describe lung function changes in healthy never-smoking males and females, from adolescence to old age, and to determine the effects of smoking and those derived from quitting. Methods: Prospective cohort study within all participants of the Framingham Offspring cohort who had two or more valid spirometry measurements during follow-up (n = 4,391; age range at baseline 13 to 71 yr), with a median follow-up time of 23 years. Measurements and Main Results: To best fit the curves describing FEV₁ changes with age to raw data, we used a generalized additive model with smooth terms and incorporating the subject-specific (longitudinal) random effects. We found that: (1) healthy never-smoker females achieve full lung growth earlier than males, and their rate of decline with age was slightly, but not significantly, lower; (2) smoking increases the rate of lung function decline, both in males and in females; (3) there is a range of susceptibility to the effects of smoking. The presence of respiratory symptoms at baseline and/or a respiratory diagnosis during follow-up appears to identify a group of susceptible smokers; and (4) quitting smoking has a beneficial effect at any age, but it is more pronounced in earlier quitters. Conclusions: Lung function changes from adolescence to old age differ in malesandfemales, smoking has similar deleterious effects in both sexes, and quitting earlier is better.