Association between Plasma Alpha-1-Antitrypsin Concentration and 11-Year Course of Lung Function among Adult Smokers in the SAPALDIA Cohort

O. Senn, E. W. Russi, A. von Eckardstein, M. Imboden, S. Downs, C. Schindler, O. Brändli, M. Gerbase, Ph. Leuenberger, U. Ackermann-Liebrich, N. M. Probst-Hensch, and the SAPALDIA team

Background: COPD is prevalent and a relevant health problem. Tobacco smoking is a well-recognized risk factor, the impact of which on the lung is particularly prominent in individuals with an inherited deficiency of the antiprotease Alpha-1-Antitrypsin (a1-AT). While only between 0.01 and 0.2% of the population of Caucasians are affected by the severe forms of a1-AT deficiency (PiZZ), about 8 to 10% of individuals have genetic variants that lead to a moderate decrease in a1-AT serum concentrations. The impact of moderate a1-AT deficiency on lung function remains controversial, but evidence is accumulating that additional genetic and environmental factors such as air pollutants, occupational exposures, active and passive smoking play a modifying role in this situation. To further investigate the combined impact of moderate a1-AT deficiency, active and passive smoking, and environmental exposures on respiratory health large, well-designed epidemiological studies are needed.

Hypothesis: To investigate the hypothesis that the impact of active smoking on the 11-year decline in lung function, adjusted for lung function at baseline, is stronger among smokers with moderately decreased blood a1-AT concentrations as opposed to smokers with normal a1-AT levels.

Study population: The Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was initiated in 1991 with subjects aged 18-60 years and randomly selected from the general population in eight different regions in Switzerland, representing a broad range of environmental and climatic conditions. 8045 participants were interviewed and examined in detail at baseline and 11 years later to assess the impact of various exogenous factors including air pollution and active as well as passive smoking on respiratory health (Ackermann-Liebrich et al. 1997; Leuenberger et al. 1994; Schindler et al. 2001; Zemp et al. 1999).

Measurements/Outcomes: a1-AT and C-reactive protein (CRP) will be measured in serum samples collected from 1612 active smokers of the SAPALDIA cohort. The effect of a1-AT on the 11-year change in lung function, adjusted for baseline lung function, C-reactive protein (CRP), respiratory tract infections as well as other potential confounders, will be investigated with the help of multiple linear regression models. Blood concentrations of a1-AT, adjusted for CRP and a history of acute respiratory tract infections at blood draw, proved to be a better biomarker of susceptibility in epidemiologic studies than a1-AT genotypes (von Ehrenstein et al. 2002).

Importance of the project: If the results of this study demonstrate an accelerated decrease of lung function among smokers with moderate a1-AT deficiency, this is of practical relevance from a public health and clinical perspective with regard to targeted counselling and screening of susceptible smokers.

Curriculum Vitae of Oliver Senn

Contact 
Dr. Oliver Senn
Universitätsstrasse 27
8006 Zürich
Switzerland
Telephone: 0041-1-255 21 96
Fax: 0041-1-255 45 57
E-mail: oliver.senn@usz.ch