Predictors of Longitudinal Change in Diffusing Capacity over 8 Years

Abstract

Low single-breath diffusing capacity (D LCO ) values are associated with anatomic emphysema, but the predictors of longitudinal change in D LCO over many years are unknown. Study subjects were adult participants in the longitudinal Tucson Epidemiology Study of Obstructive Lung Disease who had at least one D LCO measurement during either of two surveys 8 yr apart (n 5 543). Smoking status was determined at each examination (current, former, or never smoker). Quitters were defined as those currently smoking at the baseline D LCO examination (1982-1983) and self-reported as no longer smoking at the follow-up exam (1990-1991). The longitudinal D LCO data were analyzed using re- peated measures analysis; because of missing observations this was done using a saturated random effects model. The results showed that males had higher levels of D LCO than females, current smokers had significantly lower levels of D LCO than never smokers, but there was no difference in their mean slopes over time. Smoking history, assessed using pack-years of smoking, was associated with re- duced D LCO levels, independent of whether current or ex-smokers. Males and females demonstrated equivalent rates of decline in D LCO that accelerated with increasing age, and mean D LCO declines were associated with declines in FEV 1 between surveys. Sherrill DL, Enright PL, Kaltenborn WT, Lebo- witz MD. Predictors of longitudinal change in diffusing capacity over 8 years. AM J RESPIR CRIT CARE MED 1999;160:1883-1887. The single-breath diffusing capacity of the lungs for carbon monoxide (D LCO ) is frequently used in the differential diagno- sis of patients with dyspnea in the clinical setting (1), for the characterization of subjects in epidemiological studies of ob- structive and restrictive lung diseases (2), and for surveillance in the occupational setting (3). Among patients who have air- flow limitation owing to cigarette smoking, diffusing capacity is highly correlated with the degree of emphysema on lung computed tomography (CT) scans (4). In recognition of the clinical importance of the D LCO test, the American Thoracic Society has set standards for the performance of D LCO tests (5, 6) and their clinical interpretation. Changes in D LCO over months to years may be important in following the course of chronic obstructive and interstitial re- strictive lung diseases and the efficacy of interventions. Yet most population studies of the correlates of D LCO , including smoking status, have been cross-sectional (7-11). A study of 159 steelworkers in France, with two D LCO tests 5 yr apart, paradoxically found that the exposed workers had a smaller D LCO decline (15%) than did 114 unexposed control workers (20%) (12). Changes in D LCO measured twice 10 yr apart in 122 middle-aged men in London were associated with changes in smoking habit (13). Those who quit smoking had a mean in- crease in D LCO , after correcting for their decrease in CO back pressure (carboxyhemoglobin (COHb) levels). The subjects from these previous longitudinal studies were not from a ran- dom population sample, and factors other than occupational exposures and changes in smoking status were not examined. The objective of this study was to determine predictors of longitudinal change in D LCO during an 8-yr interval of adult participants in the Tucson Epidemiological Study of Obstruc- tive Lung Disease (14). METHODS