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, Vickram Tejwani, Prescott G Woodruff, Joe G Zein, Eric A Hoffman, Stephen P Peters, Deborah A Meyers, Eugene R Bleecker, Victor E Ortega
{"title":"支气管扩张症对慢性阻塞性肺病严重程度的影响以及阿尔法-1 抗胰蛋白酶缺乏症是有大量吸烟史者的一个风险因素。","authors":"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, Vickram Tejwani, Prescott G Woodruff, Joe G Zein, Eric A Hoffman, Stephen P Peters, Deborah A Meyers, Eugene R Bleecker, Victor E Ortega","doi":"10.15326/jcopdf.2023.0388","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>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.</p><p><strong>Objectives: </strong>To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.</p><p><strong>Methods: </strong>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, <i>SERPINA1</i>, in 835 participants to test for rare variants, focusing on the PiZ genotype (Glu<sup>366</sup>Lys, rs28929474).</p><p><strong>Measurements and main results: </strong>We identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, <i>p</i>=0.0045), older participants (mean age=66[standard deviation (SD)=8.3] versus 64[SD=9.1] years, <i>p</i>=0.0083), and those with lower lung function (forced expiratory volume in 1 second [FEV<sub>1</sub> ] percentage predicted=66%[SD=27] versus 77%[SD=25], <i>p</i><0.0001; FEV<sub>1</sub> to forced vital capacity [FVC] ratio=0.54[0.17] versus 0.63[SD=0.16], <i>p</i><0.0001). Participants with bronchiectasis had greater emphysema (%voxels ≤-950 Hounsfield units, 11%[SD=12] versus 6.3%[SD=9], <i>p</i><0.0001) and parametric response mapping functional small airways disease (26[SD=15] versus 19[SD=15], <i>p</i><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, <i>p</i>=0.049), an association attributed to White individuals (OR=1.98; 95%CI = 0.9956, 3.9; <i>p</i>=0.051).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484491/pdf/JCOPDF-10-199.pdf","citationCount":"0","resultStr":"{\"title\":\"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, 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, Vickram Tejwani, Prescott G Woodruff, Joe G Zein, Eric A Hoffman, Stephen P Peters, Deborah A Meyers, Eugene R Bleecker, Victor E Ortega\",\"doi\":\"10.15326/jcopdf.2023.0388\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>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.</p><p><strong>Objectives: </strong>To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.</p><p><strong>Methods: </strong>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, <i>SERPINA1</i>, in 835 participants to test for rare variants, focusing on the PiZ genotype (Glu<sup>366</sup>Lys, rs28929474).</p><p><strong>Measurements and main results: </strong>We identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, <i>p</i>=0.0045), older participants (mean age=66[standard deviation (SD)=8.3] versus 64[SD=9.1] years, <i>p</i>=0.0083), and those with lower lung function (forced expiratory volume in 1 second [FEV<sub>1</sub> ] percentage predicted=66%[SD=27] versus 77%[SD=25], <i>p</i><0.0001; FEV<sub>1</sub> to forced vital capacity [FVC] ratio=0.54[0.17] versus 0.63[SD=0.16], <i>p</i><0.0001). Participants with bronchiectasis had greater emphysema (%voxels ≤-950 Hounsfield units, 11%[SD=12] versus 6.3%[SD=9], <i>p</i><0.0001) and parametric response mapping functional small airways disease (26[SD=15] versus 19[SD=15], <i>p</i><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, <i>p</i>=0.049), an association attributed to White individuals (OR=1.98; 95%CI = 0.9956, 3.9; <i>p</i>=0.051).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-07-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484491/pdf/JCOPDF-10-199.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.15326/jcopdf.2023.0388\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.15326/jcopdf.2023.0388","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.
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.
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