®. Foundation, DO Manuel Izquierdo, DO PhD Chad R. Marion, DO Frank Genese, MD John D. Newell, PhD Wanda K. O’Neal, PhD Xingnan Li, PhD Gregory A. Hawkins, MD PhD Igor Barjaktarevic, MD PhD R. Graham Barr, MD Stephanie Christenson, MD Christopher B. Cooper, PhD David Couper, MD Jeffrey Curtis, M. M. Meilan K. Han, M. M. Nadia N. Hansel, MD Richard E. Kanner, MD Fernando J. Martinez, Iii Robert Paine, MD Vickram Tejwani, M. M. Prescott G. Woodruff, MD PhD Joe G. Zein, PhD Eric A. Hoffman, MD PhD Stephen P. Peters, PhD Deborah A. Meyers, MD Eugene R. Bleecker, MD Victor E. Ortega
{"title":"Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.","authors":"®. Foundation, DO Manuel Izquierdo, DO PhD Chad R. Marion, DO Frank Genese, MD John D. Newell, PhD Wanda K. O’Neal, PhD Xingnan Li, PhD Gregory A. Hawkins, MD PhD Igor Barjaktarevic, MD PhD R. Graham Barr, MD Stephanie Christenson, MD Christopher B. Cooper, PhD David Couper, MD Jeffrey Curtis, M. M. Meilan K. Han, M. M. Nadia N. Hansel, MD Richard E. Kanner, MD Fernando J. Martinez, Iii Robert Paine, MD Vickram Tejwani, M. M. Prescott G. Woodruff, MD PhD Joe G. Zein, PhD Eric A. Hoffman, MD PhD Stephen P. Peters, PhD Deborah A. Meyers, MD Eugene R. Bleecker, MD Victor E. Ortega","doi":"10.15326/jcopdf.2022.0388","DOIUrl":null,"url":null,"abstract":"Rationale\nBronchiectasis 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.\n\n\nObjectives\nTo characterize the impact of bronchiectasis on COPD and explore α1-antitrypsin as a risk factor for bronchiectasis.\n\n\nMethods\nSPIROMICS 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).\n\n\nMeasurements and Main Results\nWe 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).\n\n\nConclusions\nBronchiectasis 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.","PeriodicalId":10249,"journal":{"name":"Chronic obstructive pulmonary diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chronic obstructive pulmonary diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15326/jcopdf.2022.0388","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale
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.
Objectives
To characterize the impact of bronchiectasis on COPD and explore α1-antitrypsin as a risk factor for bronchiectasis.
Methods
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).
Measurements and Main Results
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).
Conclusions
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.
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