Smoking damages the airway epithelium. The major mechanism by which this is done is by
molecules called free radicals. Our body attempts to deal with these damaging molecules in
two ways. One mechanism is via the presence of protective anti-oxidant vitamins and the
other is via proteins that are produced by the body to convert free radicals to safer, less
reactive molecules. Vitamins in our diet play a significant role in antioxidant defenses by
directly neutralizing the damaging free-radicals and by providing co-factors to cellular
proteins that neutralize the free radicals. This project is designed to look at the effects
of giving individuals supplemental vitamins to see if it improves their defenses against
oxidant insults. The investigators plan to look at the effects of these supplements over a
30 day period and monitor the effects by measuring vitamin levels in the blood and in the
lung, and by measuring the response of cells in the lung through the increase or decrease in
expression of genes responsive to oxidants.
To participate in this protocol, the research subject should first 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", fulfilling the inclusion/exclusion criteria of that protocol.
They will be invited to participate in this Vitamin protocol only if they meet the
additional inclusion/exclusion criteria of this protocol.
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.
- 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
- 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).
- 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.