alpha1-Antitrypsin deficiency and lung disease: risk modification by occupational and environmental inhalants.
Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable disease associated with high morbidity and mortality. Severe and intermediate alpha1-antitrypsin (AAT) deficiency (serum levels <11 and 11-20 micromol.L(-1), respectively) increase the risk of COPD in active smokers. However, little is known about the interaction of severe and intermediate AAT deficiency with modifiable COPD risk factors other than active smoking. In this study, a MEDLINE search was carried out for studies investigating the combined effect of environmental inhalants (occupation and passive smoking) and AAT deficiency in the lung. A total of 18 studies using established methods for the assessment of AAT deficiency were included in this review. Occupational exposures and passive smoking affected lung function decline or prevalence of respiratory symptoms in four out of five studies investigating subjects with severe AAT deficiency, and in eight out of 13 studies with a focus on intermediate AAT deficiency. While study designs mostly prohibited formal assessment of effect modification, an interaction between intermediate AAT deficiency and passive smoking was identified in two studies with children. Additional study limitations included small sample size, poor adjustment for confounding and misclassification of environmental exposure as well as AAT activity. In conclusion, population-based epidemiological studies with associated biobanks are needed to identify gene-environment interactions and population subgroups susceptible to alpha1-antitrypsin deficiency.
Senn
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Dept of Molecular Epidemiology/Cancer Registry, University of Zurich, Vogelsangstrasse 10, 8091 Zurich, Switzerland.
Russi
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Imboden
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Probst-Hensch
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NM
D000393:Air Pollutants / Q000032:analysis*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015897:Comorbidity; D006801:Humans; D008171:Lung Diseases / Q000453:epidemiology*; D009784:Occupational Diseases / Q000453:epidemiology*; D016273:Occupational Exposure / Q000032:analysis*; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000706:statistics & numerical data*; D019896:alpha 1-Antitrypsin Deficiency / Q000453:epidemiology*
D000393:Air Pollutants; D014028:Tobacco Smoke Pollution