The Upper Limit of Normal Rate of Lung Function Decline in Healthy Adults in the Framingham Heart Study

Background: Lung function declines over the course of adulthood; however, a consensus on the normal range of decline in an individual's lung function is lacking.

Research question: What is the normal range and the upper limit of normal (ULN) decline in lung function in adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease?

Study design and methods: A retrospective analysis of healthy individuals who have never smoked (N = 1,305) from the Framingham Heart Study with repeated lung function meeting standards for acceptability and reproducibility was conducted. Longitudinal change was derived using a linear mixed effects model and estimated to a 6-year interval. The ULN decline was defined as the 95th percentile.

Results: The mean follow-up between spirometry examinations was 5.5 years, whereas the mean follow-up between diffusing capacity for carbon monoxide studies was 5.9 years. Decline in FEV₁, FVC, and D accelerated with age, whereas decline in FEV₁/FVC decelerated with age. Decline varied with sex, age, and height. Over a 6-year period, the ULN decline in FEV₁ ranged from 383 to 667 mL, and the ULN decline in Dlco ranged from 3.6 to 9.5 mL/min/mm Hg. Overall, male individuals had faster absolute rates of decline than female individuals, whereas relative (%) rates of decline were similar between sexes.

Interpretation: Lung function decline is nonlinear and accelerates with age. In this cohort, the ULN decline over 6 years often exceeded current guidelines for interpreting significant longitudinal change in lung function.