This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Tobacco smoke is the number one preventable cause of heart and lung disease in the United States. In the lung, tobacco smoke most commonly causes lung cancer and chronic obstructive pulmonary disease (COPD). COPD is a spectrum of diseases such as chronic bronchitis (smokers cough) and emphysema (destruction of lung tissue). COPD can cause smokers to be severely short of breath with minimal activity such as bathing or walking. It is the number one reason why people have to breathe supplemental oxygen and a leading cause of death in smokers. COPD affects 8 per 1,000 people and is expected to be the 5th leading cause of disability worldwide by 2020.For many years we have known that tobacco smoke is the number one cause of COPD, yet very little is known about why tobacco smoke causes COPD. For instance, although the 80-90% of patients with COPD are smokers, only 10-20% of smokers develop COPD. Why only 10-20% of smokers develop COPD is the subject of this study. Since exposure to tobacco smoke is primarily through the lung, we have elected to examine the differences in the lungs of smokers with and without COPD. Tobacco smoke injures the lung in many ways, but a major mechanism is through the thousands of toxin substances in the gas and tar (particulate) components of tobacco smoke. Some of these substances cause DNA mutations (leading to cancer) and other substances cause tissue injury and death leading to loss of lung function. Some of the injury can be prevented by antioxidants (e.g. Vitamin C and E), but cause of most of injury remains unknown and needs to be studied at the molecular level to better understand why tobacco smoke causes lung injury.The lung tissue is composed of cells and the cells are composed of molecules such as proteins (brick and mortar of cells), lipids (protective envelope of cells), and DNA (the genetic information of cells). We obtain these samples by inserting a flexible fiber optic tube (bronchoscope) into the lungs of smokers and withdrawing some of the fluid that lines the inside of the lungs. Using very new techniques in protein identification (proteomics), we will identify which proteins are present or absent in lining fluid in smokers with COPD compared to those without COPD. We will also identify how these proteins are damaged by tobacco smoke. These studies will help us understand how tobacco smoke injures the lung and may lead to the development of novel tests to identify and treat the 10-20% of smokers who will develop COPD.
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