Chest
Original ResearchCOPDα;1-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts
Section snippets
Study Populations
The case-control study was performed at Haukeland University Hospital (Bergen, Norway). Case and control subjects were whites aged ≥ 40 years and current or ex-smokers of ≥ 2.5 pack-years. Case subjects had COPD with a post-bronchodilator (BD) FEV1/FVC ratio < 0.7 and FEV1 < 80% predicted.7 Control subjects had normal spirometry (post-BD FEV1/FVC, ≥ 0.7; FEV1, ≥ 80% predicted).
The family-based International COPD Genetics Network (ICGN) study included participants from 10 study centers in Europe
Characteristics of Study Subjects
The characteristics of study subjects in the Norway case-control study are shown in Table 1. A total of 834 cases subjects and 835 control subjects with either PI MM or PI MZ were included. Forty-four (5.3%) case subjects and 34 (4.1%) control subjects were PI MZ (P = .244). Quantitative emphysema data were available for 408 case subjects and 422 control subjects, and data on airway wall thickness were available for 387 cases and 393 control subjects. PI MZ control subjects had smoked more than
Discussion
We examined the associations between AAT PI MZ heterozygosity and COPD-related phenotypes in two large populations: a case-control study from Norway and a multicenter family study from Europe and North America. To our knowledge, this study is the first to examine quantitative CT phenotypes in PI MZ carriers. In both populations, PI MZ was associated with lower FEV1/(F)VC ratio compared with PI MM. In the case-control study, PI MZ also was associated with more-severe emphysema on chest CT scan.
Acknowledgments
Author contributions: Dr Sørheim: contributed to the data analysis and the writing and review of the manuscript.
Dr Bakke: contributed to the data collection and the writing and review of the manuscript.
Dr Gulsvik: contributed to the data collection and the writing and review of the manuscript.
Dr Pillai: contributed to the writing and review of the manuscript.
Dr Johannessen: contributed to the data analysis, statistical support, and the writing and review of the manuscript.
Dr Gaarder:
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Funding/Support: This work was supported by the National Institutes of Health [Grants HL075478, P01 083069, R01 HL084323 (to Dr Silverman) and HL080242 (to Dr Hersh)] and a grant from the α;-1 Foundation (to Dr Hersh). Both studies discussed in this article were supported by GlaxoSmithKline.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).
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Dr Pillai is currently at Roche Pharmaceuticals (Nutley, NJ)