Occupational dust, fume, and gas exposures have been associated with the development of chronic obstructive pulmonary disease (COPD). Genetic and familial factors also contribute to the risk of COPD. Individuals with alpha1-antitrypsin deficiency (alpha11ATD) comprise one of these genetically susceptible populations. The major environmental risk factor for COPD and for alpha1AT deficient individuals who are homozygous (PI*Z) is personal tobacco use. However, preliminary studies suggest that occupational respiratory exposures may also contribute to the severity of this disease. We hypothesize that exposure to occupational and environmental respiratory irritants (dust, fumes, smoke, and gas) increases the risk of both chronic respiratory symptoms and airflow obstruction in genetically susceptible individuals with PI* Z alpha1AT deficiency. This hypothesis will be tested through the following specific aims: 1) To evaluate the association between specific types of occupational and environmental respiratory exposures and the presence and severity of specific pulmonary symptoms and airflow obstruction. 2) To assess the potential interaction or confounding effects between different types of respiratory irritant exposures and/or personal and environmental tobacco smoke in predicting risk of respiratory symptoms. 3) To assess the potential interaction between personal or environmental tobacco smoke and respiratory infections in predicting risk of respiratory symptoms and airflow limitation. 4) To validate the model developed as a predictive model by repeated re-sampling of the original data set, i.e. bootstrapping, that could help health professionals counsel and educate PI*Z patients concerning their risks from environmental and occupational exposures. A cross-sectional design will be used in an expanded cohort of >300 patients with alpha1At deficiency PI*Z. The goal of this proposal is to better understand the burden of obstructive lung disease due to occupational exposures in PI*Z individuals. Such research offers an opportunity to investigate environmental and genetic interactions in which the gene trait that confers susceptibility is known but in which the environmental triggers are not.
| Mayer, Annyce S; Stoller, James K; Vedal, Sverre et al. (2006) Risk factors for symptom onset in PI*Z alpha-1 antitrypsin deficiency. Int J Chron Obstruct Pulmon Dis 1:485-92 |
