Journal article
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, Vol.10(3), pp.199-210
07/26/2023
DOI: 10.15326/jcopdf.2023.0388
PMCID: PMC10484491
PMID: 37199731
Abstract
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.
To characterize the impact of bronchiectasis on COPD and explore α1-antitrypsin as a risk factor for bronchiectasis.
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,
, in 835 participants to test for rare variants, focusing on PiZ (Glu
Lys, rs28929474).
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 (FEV
%predicted=66%[SD=27] versus 77%[SD=25], p<0.0001; FEV
/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 PRM
(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).
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.
Details
- Title: Subtitle
- Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History
- Creators
- Manuel Izquierdo - Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine Medical Center, Wake Forest, North Carolina, United StatesChad R Marion - Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine Medical Center, Wake Forest, North Carolina, United StatesFrank Genese - Rochester General HospitalJohn D Newell - University of IowaWanda K O'Neal - University of North Carolina at Chapel HillXingnan Li - University of ArizonaGregory A Hawkins - Center for Precision Medicine, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United StatesIgor Barjaktarevic - Department of Medicine, David Geffen School of Medicine, Los Angeles, California, United StatesR Graham Barr - Columbia University Irving Medical CenterStephanie Christenson - University of California, San FranciscoChristopher B Cooper - Department of Medicine, David Geffen School of Medicine, Los Angeles, California, United StatesDavid Couper - Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United StatesJeffrey Curtis - University of Michigan–Ann ArborMeilan K Han - University of Michigan–Ann ArborNadia N Hansel - Johns Hopkins UniversityRichard E Kanner - University of UtahFernando J Martinez - Cornell UniversityRobert Paine III - University of UtahVickram Tejwani - Cleveland ClinicPrescott G Woodruff - University of California, San FranciscoJoe G Zein - Cleveland ClinicEric A Hoffman - University of IowaStephen P Peters - Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine Medical Center, Wake Forest, North Carolina, United StatesDeborah A Meyers - University of ArizonaEugene R Bleecker - University of ArizonaVictor E Ortega - Mayo Clinic in ArizonaNational Heart, Lung and Blood Institute’s SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) investigators
- Resource Type
- Journal article
- Publication Details
- Chronic obstructive pulmonary diseases, Vol.10(3), pp.199-210
- DOI
- 10.15326/jcopdf.2023.0388
- PMID
- 37199731
- PMCID
- PMC10484491
- ISSN
- 2372-952X
- eISSN
- 2372-952X
- Grant note
- HHSN268200900017C / NHLBI NIH HHS R01 HL111527 / NHLBI NIH HHS HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS U24 HL141762 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS HHSN268200900013C / NHLBI NIH HHS HHSN268201100037C / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS HHSN268200900018C / NHLBI NIH HHS HHSN268200900014C / NHLBI NIH HHS R01 HL142992 / NHLBI NIH HHS
- Language
- English
- Electronic publication date
- 05/16/2023
- Date published
- 07/26/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984410801602771
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