Association between functional small airways disease and 3-year change in emphysema in the SPIROMICS cohort

Background: Radiologic small airways disease is associated with subsequent emphysema increase. Aim: Determine if this association is: a) seen as early as 3 years of follow-up; b) present in milder disease; c) modified by age. Methods: We included SPIROMICS ever-smokers (88 normal spirometry; 139 GOLD 1-2 COPD; 43 GOLD 3-4 COPD) with thoracic CTs at enrollment and Year 3. Parametric Response Mapping was applied to co-registered inspiratory and expiratory CT images to measure the extent of functional small airways disease (PRMfSAD) and emphysema (PRMEmph) as % of total lung volume. We examined the association between baseline PRMfSAD (by 10% increments) and 3-year change in PRMEmph using linear regression models adjusted for age, sex, BMI, smoking status and baseline PRMEmph, and tested for interaction between baseline PRMfSAD and age. Results: Mean age was 65.1±8.6 years (range 41-80), mean FEV1 was 77.3±23.3 % predicted, and 52.2% of participants were women. Medians (interquartile intervals) were 16.1% (5.7%-26.7%) for baseline PRMfSAD; 3.0% (1.0%-7.7%) for baseline PRMEmph; and 0.5% (0.03%-1.9%) for 3-year PRMEmph change. Baseline PRMfSAD was associated with 3-year increase in PRMEmph in all 270 participants (β=0.40; 95%CI 0.24-0.57; p<0.001) and the subgroup of 227 participants with normal or GOLD 1-2 spirometry (β=0.31; 95%CI 0.13-0.49; p<0.001). There was a significant interaction between PRMfSAD and age (β=-0.017; 95%CI -0.032 to -0.002; p=0.02) such that the association between PRMfSAD and increase in PRMEmph was stronger in younger individuals. Conclusion: Early detection of radiologic small airways disease can help identify smokers at risk for emphysema progression.