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

Abstract

BackgroundLung 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 QuestionWhat is the normal range and the upper limit of normal (ULN) decline in lung function of adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease? Study Design and MethodsA retrospective analysis of healthy, never-smokers (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. ResultsThe mean follow-up between spirometry examinations was 5.5 years, while the mean follow-up between diffusing capacity for carbon monoxide (DLCO) studies was 5.9 years. Decline in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and DLCO accelerated with age, while 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 mL to 667 mL, and the ULN decline in DLCO ranged from 3.6 ml/min/mmHg to 9.5 ml/min/mmHg. Overall, men had faster absolute rates of decline than women, while relative (%) rates of decline were similar between sexes. InterpretationLung function decline is non-linear 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.