The GRC-BLSA Program in Pulmonary Aging focused upon: a. Accelerated Decline in Pulmonary Function Predicts Coronary Heart Disease Death In BLSA men, an elevated risk for cardiac death follows an accelerated decline in FEV1, independent of the effects of the initial FE1% predicted, cigarette smoking and other common CHD risk factors. There were 79 CHD deaths and 804 survivors over the 1 to 28.5 year follow- up period. After adjusting for common CHD risk factors in a time-dependent Cox proportional hazards analysis, the highest relative risks for cardiac mortality were associated with quintile of subsequent FEV1 decline, even among never-smokers. The elevated risk associated with decline in FEV1 was specific to coronary death. Thus, rate of pulmonary function decline appears to be a new risk factor for CHD death. b. Age-Associated Changes in FEV1 in Healthy, Non- Smoking Men and Women Longitudinal analyses of changes in FEV1 were conducted among 91 men and 82 women who had no history of respiratory problems and had never smoked cigarettes. The FEV1 data were modeled using a mixed-effects regression model and longitudinal percentile distributions of FEV1 level were constructed. The findings showed 1) the average longitudinal rate of decline in FEV1 was approximately 240-340 ml/decade in men and women, 2) none of the participants exhibited a sustained improvement in FEV1, and 3) between-subjects variability is greater in men than women and increases with age in men, but decreases with age in women. c. Development of a Mathematical Model of Pulmonary Aging A new model of normal pulmonary aging is being developed based upon the change in physiologic emptying of the lungs. Digitized spirometry from BLSA healthy, nonsmokers, without evidence of heart disease, is converted into distributions of emptying times by moments analysis. Those healthy nonsmokers with minimal lung function decline will define the standard of optimal pulmonary aging. Aging of the lung will be defined as a significant increase beyond optimal in the proportion of ventilatory emptying described by long time constants. The age-related decline of individual pulmonary function may be described over longitudinal follow-up by a mixed- effects model which includes parameters for Intercept, Time Interval, (Time Interval)2, Age and Mean Emptying Time.
