Clinical and immunological factors in emphysema progression: Five-year prospective longitudinal exacerbation study of chronic obstructive pulmonary disease (LES-COPD)

Rationale: Cross-sectional studies of T-cell responses to selfantigens correlate with baseline emphysema severity. Objectives: Weinvestigated whether clinical and/or immunological factors could predict disease progression, such as emphysema, FEV1, and 6-minute-walk distance (6MWD), in former and active smokers in a 5-year prospective study. Methods: We recruited 224 ever smokers over 40 years of age and with greater than a 15 pack-year smoking history. Measurements and Main Results: Repeated spirometry, 6MWD, and peripheral blood T-cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest computed tomography (CT) scans (34 to 65 mo apart) were used to quantify emphysema progression. Of the 141 ever-smokers with baseline and repeat CT scans, the mean (SD) annual rate of change in percent emphysema was 10.46 (0.92), ranging from 21.8 to 14.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (10.15 per 5-unit decrease in BMI; 95% confidence interval, 10.03 to 10.29). In active smokers, increased IFN-γ and IL-6 T-cell responses had a positive association with the annual rate of emphysema progression. Male sex and IL-6 T-cell responses to elastin fragments were significantly associated with annual 6MWD decline, whereas IL-13 was associated with an increase in annual 6MWD. Conclusions: The rate of emphysema progression quantified by CT scans among ever-smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells and low BMI may temporize progression of emphysema.