RationaleBronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including alpha-1 antitrypsin deficiency, and its implications for COPD severity are uncharacterized in such individuals.ObjectivesTo characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.MethodsSubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) participants (N=914; ages 40-80 years; ≥20-pack-year smoking) had high-resolution computed tomography (CT) 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 -alpha-1 antitrypsin, SERPINA1, in 835 participants to test for rare variants, focusing on the PiZ genotype (Glu366Lys, rs28929474).Measurements and Main ResultsWe identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66standard deviation (SD)=8.3 versus 64SD=9.1 years, p=0.0083), and those with lower lung function (forced expiratory volume in 1 second FEV1 percentage predicted=66%SD=27 versus 77%SD=25, p<0.0001; FEV1 to forced vital capacity FVC ratio=0.540.17 versus 0.63SD=0.16, p<0.0001). Participants with bronchiectasis had greater emphysema (%voxels ≤-950 Hounsfield units, 11%SD=12 versus 6.3%SD=9, p<0.0001) and parametric response mapping functional small airways disease (26SD=15 versus 19SD=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 70740%, odds ratio OR=1.97; 95% confidence interval CI=1.002, 3.90, p=0.049), an association attributed to White individuals (OR=1.98; 95%CI = 0.9956, 3.9; p=0.051).ConclusionsBronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support alpha-1antitrypsin guideline recommendations to screen for alpha-1 antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.