Effect of Supplementary Vitamins on Oxidant Gene Expression in the Lungs of Healthy Smokers

The purpose of this study is to test whether dietary antioxidant supplementation can alter the expression in lung epithelial cells of genes related to oxidant response and whether this response is dependent on factors such as the individual's baseline serum antioxidant status, dietary antioxidant status, and the oxidant/anti-oxidant balance in the lung. The underlying hypothesis is that the intake of vitamins with antioxidant properties (selenomethionine, vitamin E and vitamin C) will boost the antioxidant levels of the airway epithelium sufficient to protect the epithelium from the stress of oxidants in cigarette smoke. Our prior work shows that phenotypic normal smokers (cigarette smokers with normal history, physical exam, lung function tests, and chest x-rays) have marked up and down regulation of > ~200 genes in the airway epithelium. The proposed project will build on past findings by examining whether regulation of gene expression responds to changes in nutritional status. The primary aim will be assessment of gene expression of the airway epithelium (from protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy") obtained before and after taking standard amounts of selenomethionine, vitamin E and vitamin C, or placebo for 30 days. The secondary aims will be to evaluate the ability of vitamin supplementation to raise lung and serum vitamin levels, to reduce the oxidant stress in the lung and systemically (as measured by lung and urinary F2 isoprostane levels, respectively), and to assess the vitamin-induced change in airway epithelial gene expression in genes other than oxidant related genes.

Inclusion criteria

• All study individual should be enrolled in Weill-IRB protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy."
• All study subjects should be able to provide informed consent.
• Males or females ages 18 years and older.
• Current smokers with at least a 15 pack-year history (1 pack year = on average 20 cigarettes per day for 1 year).

Exclusion criteria

• Drug and/or alcohol abuse within the past six months.
• Individuals already on supplemental vitamins.
• Subjects intending to quit smoking in the next 30 days.