Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History
Chronic Obstructive Pulmonary Diseases (Miami, Fla.)
Rationale: Bronchiectasis 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.
Objectives: To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.
Methods: SubPopulations 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 results: We identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, p=0.0045), older participants (mean age=66[standard deviation (SD)=8.3] versus 64[SD=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=0.54[0.17] versus 0.63[SD=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 (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%], 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).
Conclusions: Bronchiectasis 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.
Izquierdo, M., Marion, C. R., Genese, F., Newell, J. D., O'Neal, W. K., Li, X., Hawkins, G. A., Barjaktarevic, I., Barr, R. G., Christenson, S., Cooper, C. B., Couper, D., Curtis, J., Han, M. K., Hansel, N. N., Kanner, R. E., Martinez, F. J., Paine, R., Tejwani, V., Woodruff, P. G., Zein, J. G., Hoffman, E. A., Peters, S. P., Meyers, D. A., Bleecker, E. R., & Ortega, V. E. (2023). Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History. Chronic Obstructive Pulmonary Diseases (Miami, Fla.), 10 (3), 199-210. https://doi.org/10.15326/jcopdf.2023.0388