Progression of Emphysema and Small Airways Disease in Cigarette Smokers

Background Little is known about factors associated with emphysema progression in cigarette smokers. We evaluated factors associated with change in emphysema and FEV1 in subjects with and without chronic obstructive pulmonary disease (COPD). Methods This retrospective study included subjects participating in the COPDGene study and who completed the 5-year follow-up, including inspiratory and expiratory computed tomography (CT) and spirometry. All paired CT scans were analyzed using micro-mapping, which classifies individual voxels as emphysema or functional small airway disease (fSAD). Presence and progression of emphysema and FEV1 were determined based on comparison to nonsmoker values. Logistic regression analyses were used to identify clinical parameters associated with disease progression. Results 3088 subjects were included with a mean ± SD age of 60.7±8.9 years, including 72 nonsmokers. In all GOLD stages, the presence of emphysema at baseline was associated with emphysema progression (Odds ratio (OR): GOLD 0: 4.32; PRISm; 5.73; GOLD 1: 5.16; GOLD 2: 5.69; GOLD 3/4: 5.55; all p≤0.01). If there was no emphysema at baseline, the amount of fSAD at baseline was associated with emphysema progression (OR for 1% increase: GOLD 0: 1.06; PRISm: 1.20; GOLD 1: 1.7; GOLD 3/4: 1.08 all p ≤ 0.03). In 1735 subjects without spirometric COPD, progression in emphysema occurred in 105 (6.1%) subjects and only 21 (1.2%) had progression in both emphysema and FEV1. Conclusions The presence of emphysema is an important predictor of emphysema progression. In patients without emphysema, fSAD is associated with the development of emphysema. In subjects without spirometric COPD, emphysema progression occurred independently of FEV1 decline.