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Change in LungFunction andMorbidity fromChronic ObstructivePulmonary Disease inα1-Antitrypsin MZHeterozygotes Morten DahlAnne Tybjærg‐HansenPeter Lange2002 год

Change in Lung Function and Morbidity from Chronic Obstructive Pulmonary Disease in α1-Antitrypsin MZ Heterozygotes: A Longitudinal Study of the General Population
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Аннотация: Background: A deteriorating effect of severe α1-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain. Objective: To test the hypothesis that MZ intermediate α1-antitrypsin deficiency affects pulmonary function and disease. Design: Population-based cohort study with 21-year follow-up. Setting: Copenhagen, Denmark. Participants: 9187 adults randomly selected from the Danish general population. Measurements: Plasma α1-antitrypsin levels, annual decrease in FEV1, airway obstruction, and hospitalization and mortality from chronic obstructive pulmonary disease (COPD). Results: 451 participants (4.9%) carried the MZ genotype. Plasma α1-antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype (Student t-test, P < 0.001). Annual decrease in FEV1 was 25 mL in MZ heterozygotes and 21 mL in persons with the MM genotype (t-test, P = 0.048). Airway obstruction was found in 19% of MZ heterozygotes compared with 15% of MM carriers (chi-square test, P = 0.023); in a logistic regression analysis adjusted for age, sex, and tobacco consumption, the corresponding odds ratio was 1.3 (CI, 1.0 to 1.7). The incidence of hospitalization and mortality from COPD was 32 cases per 10 000 person-years in persons with the MZ genotype and 22 cases per 10 000 person-years in those with the MM genotype (log-rank test, P = 0.063). In a Cox regression model adjusted for age, sex, tobacco use, and FEV1 at study entry, relative risk for COPD outcomes in persons with the MZ genotype versus persons with the MM genotype was 1.5 (CI, 1.0 to 2.3). All these results were independent of the S and E alleles in this gene and were not affected by cystic fibrosis ΔF508 heterozygosity. Conclusions: MZ heterozygotes had a slightly greater rate of decrease in FEV1 and were modestly over-represented among persons with airway obstruction and COPD. In the population at large, MZ heterozygosity may account for a fraction of COPD cases—on the order of 2%, similar to the percentage of persons with COPD who have the severe but rare ZZ genotype.
Год издания: 2002
Авторы: Morten Dahl, Anne Tybjærg‐Hansen, Peter Lange, Jørgen Vestbo, Børge G. Nordestgaard
Издательство: American College of Physicians
Источник: Annals of Internal Medicine
Ключевые слова: Protease and Inhibitor Mechanisms, Pulmonary Hypertension Research and Treatments, Parasites and Host Interactions
Другие ссылки: Annals of Internal Medicine (HTML)
PubMed (HTML)