Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and is a progressive disease characterized by lung injury and inflammation. Unfortunately, smoking cessation has been the only therapeutic intervention proven to slow disease progress and decrease mortality;however some people continue to have rapid loss of lung function and airway inflammation despite abstinence from smoking. These observations suggest that there may be continued exposures in the environment which act to perpetuate the inflammatory state. Endotoxin is a pro-inflammatory agent, present in cigarette smoke and ubiquitous in the environment. Chronic exposure to endotoxin in animal studies has caused physiologic changes consistent with pulmonary emphysema and human inhalational studies have shown that endotoxin causes inflammatory changes similar to those seen in the airways of individuals with COPD. Exposure to endotoxin has known adverse pulmonary consequences in workers in certain occupational settings, including obstructive abnormalities in lung function and accelerated lung function decline. Though domestic endotoxin levels are lower than those seen in occupational settings, the biological relevance of chronic exposure to these lower levels has been demonstrated by our studies as well as other epidemiological studies which link domestic endotoxin exposure with adverse health outcomes in other chronic lung diseases, including asthma. Therefore, it is a compelling hypothesis that exposure to domestic endotoxin promotes inflammation and worsening of respiratory symptoms and lung function in COPD patients;however no epidemiological studies have evaluated the effect of domestic endotoxin exposure on COPD morbidity. The proposed study will examine the effect of domestic endotoxin exposure on health status and pulmonary and systemic inflammation in former smokers with COPD. Specifically, we propose a longitudinal study to measure settled dust and airborne endotoxin levels, at baseline, 3 months and 6 months, in homes of 75 former smokers with COPD. We will measure both settled dust and airborne endotoxin concentrations in order to determine which exposure is associated with a greater risk of respiratory disease. Additionally, we propose to collect extensive phenotypic data, including respiratory symptoms, quality of life, lung function and pulmonary and systemic markers of inflammation (exhaled nitric oxide, induced sputum and serum markers). We hypothesis that higher levels of indoor endotoxin concentrations lead to lower lung function, worse quality of life, greater symptoms and increased airway and systemic inflammation in former smokers with COPD. Additionally, repeated measures of endotoxin will allow us to assess potential sources and temporal variability of indoor endotoxin concentrations. Completion of the proposed work will 1) expand the relatively small body of evidence on the perpetuation of airway inflammation and disease in COPD patients who stop smoking, 2) contribute greatly to the understanding of novel risk factors fueling the epidemic of COPD.
With chronic obstructive pulmonary disease (COPD) being the fourth leading cause of death in the US, with limited treatment options, understanding environmental factors which perpetuate the disease is an important public health priority. The work proposed herein will further our understanding of the effect of the domestic environment, specifically domestic endotoxin exposure, on the perpetuation of airway inflammation and progression of COPD, providing essential information in an area in which limited epidemiological investigations have been conducted to date. Our results will provide the necessary clinical and scientific foundation to develop future gene-environment interaction and intervention studies aimed at reducing endotoxin exposure in order to decrease COPD morbidity and mortality.
