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

Manuel Izquierdo; Chad R Marion; Frank Genese; John D Newell; Wanda K O'Neal; Xingnan Li; Gregory A Hawkins; Igor Barjaktarevic; R Graham Barr; Stephanie Christenson; Christopher B Cooper; David Couper; Jeffrey Curtis; Meilan K Han; Nadia N Hansel; Richard E Kanner; Fernando J Martinez; Robert Paine 3rd; Vickram Tejwani; Prescott G Woodruff; Joe G Zein; Eric A Hoffman; Stephen P Peters; Deborah A Meyers; Eugene R Bleecker; Victor E Ortega; SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) investigators

doi:10.15326/jcopdf.2023.0388

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

Chronic Obstr Pulm Dis. 2023 Jul 26;10(3):199-210. doi: 10.15326/jcopdf.2023.0388.

Authors

Manuel Izquierdo¹, Chad R Marion¹, Frank Genese², John D Newell³, Wanda K O'Neal⁴, Xingnan Li⁵, Gregory A Hawkins⁶, Igor Barjaktarevic⁷, R Graham Barr⁸, Stephanie Christenson⁹, Christopher B Cooper⁷, David Couper¹⁰, Jeffrey Curtis^{11

12}, Meilan K Han¹², Nadia N Hansel¹³, Richard E Kanner¹⁴, Fernando J Martinez¹⁵, Robert Paine 3rd¹⁴, Vickram Tejwani¹⁶, Prescott G Woodruff⁹, Joe G Zein¹⁶, Eric A Hoffman³, Stephen P Peters¹, Deborah A Meyers⁵, Eugene R Bleecker⁵, Victor E Ortega¹⁷; SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) investigators

Affiliations

¹ Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine, Wake Forest, North Carolina, United States.
² Department of Pulmonary Disease, Rochester General Hospital, Rochester, New York, United States.
³ Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States.
⁴ Marisco Lung Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
⁵ Department of Medicine, University of Arizona, Tucson, Arizona, United States.
⁶ Center for Precision Medicine, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States.
⁷ Department of Medicine, David Geffen School of Medicine, Los Angeles, California, United States.
⁸ Columbia University Medical Center, New York City, New York, United States.
⁹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, United States.
¹⁰ Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States.
¹¹ VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States.
¹² Division of Pulmonary and Critical Care Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, United States.
¹³ School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
¹⁴ Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
¹⁵ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College of Cornell University, New York City, New York, United States.
¹⁶ Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.
¹⁷ Department of Internal Medicine, Division of Respiratory Diseases, Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States.

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.

Keywords: COPD; alpha-1 antitrypsin; bronchiectasis; lung function.

Abstract

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