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

Authors

• Manuel Izquierdo, Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine, Wake Forest, North Carolina, United States.
• Chad R. Marion, Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine, Wake Forest, North Carolina, United States.
• Frank Genese, Rochester Regional HealthFollow
• John D. Newell, Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States.
• Wanda K. O'Neal, Marisco Lung Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
• Xingnan Li, Department of Medicine, University of Arizona, Tucson, Arizona, United States.
• Gregory A. Hawkins, Center for Precision Medicine, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States.
• Igor Barjaktarevic, Department of Medicine, David Geffen School of Medicine, Los Angeles, California, United States.
• R Graham Barr, Columbia University Medical Center, New York City, New York, United States.
• Stephanie Christenson, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, United States.
• Christopher B. Cooper, Department of Medicine, David Geffen School of Medicine, Los Angeles, California, United States.
• David Couper, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States.
• Jeffrey Curtis, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States.
• Meilan K. Han, Division of Pulmonary and Critical Care Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, United States.
• Nadia N. Hansel, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
• Richard E. Kanner, Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
• Fernando J. Martinez, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College of Cornell University, New York City, New York, United States.
• Robert Paine, Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
• Vickram Tejwani, Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.
• Prescott G. Woodruff, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, United States.
• Joe G. Zein, Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.
• Eric A. Hoffman, Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States.
• Stephen P. Peters, Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine, Wake Forest, North Carolina, United States.
• Deborah A. Meyers, Department of Medicine, University of Arizona, Tucson, Arizona, United States.
• Eugene R. Bleecker, Department of Medicine, University of Arizona, Tucson, Arizona, United States.
• Victor E. Ortega, Department of Internal Medicine, Division of Respiratory Diseases, Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States.

Department

Pulmonary Medicine

Document Type

Article

Publication Title

Chronic Obstructive Pulmonary Diseases (Miami, Fla.)

Abstract

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.

First Page

199

Last Page

210

DOI

10.15326/jcopdf.2023.0388

Volume

10

Issue

3

Publication Date

7-26-2023

PubMed ID

37199731

Recommended Citation

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