Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.

Abstract

Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including α1-antitrypsin deficiency and its implications for COPD severity are uncharacterized in such individuals. To characterize the impact of bronchiectasis on COPD and explore α1-antitrypsin as a risk factor for bronchiectasis. SPIROMICS participants (N=914; ages 40-80 years; ≥20 pack-years smoking) had HRCT scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization. We performed regression-based models of bronchiectasis with clinical outcomes and quantitative CT measures. We deeply sequenced the gene encoding α1-antritrypsin, SERPINA1, in 835 participants to test for rare variants, focusing on PiZ (Glu366Lys, rs28929474). We identified bronchiectasis in 365 (40%), more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66[SD=8.3] versus 64[SD=9.1] years, p=0.0083), and those with lower lung function (FEV1%predicted=66%[SD=27] versus 77%[SD=25], p<0.0001; FEV1/FVC=0.54[0.17] versus 0.63[SD=0.16], p<0.0001]. Participants with bronchiectasis had greater emphysema (%voxels ≤-950HFU, 11%[SD=12] versus 6.3%[SD=9], p<0.0001) and PRMfSAD (26[SD=15] versus 19[SD=15], p<0.0001). Bronchiectasis was more frequent in the combined PiZZ and PiMZ genotype groups compared to those without PiZ, PiS, or other rare pathogenic variants (N=21 of 40[52%] versus N=283 of 707[40%], OR=1.97; 95%CI=1.002, 3.90, p=0.049), an association attributed to whites (OR=1.98; 95%CI = 0.9956, 3.9; p=0.051). Bronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support α1-antitrypsin guideline recommendations to screen for α1-antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.