Nitric Oxide, LPS and the Pathogenesis of Asthma Phase 1

The purpose of the study is to determine the role of nitric oxide (NO) in asthma. We
determine the effect of promoter polymorphisms in the gene for the NO producing enzyme,
nitric oxide synthase (NOS2), on exhaled NO in healthy African Americans and Caucasians. We
compare exhaled NO levels between African Americans and Caucasians. Information on race or
ethnicity, serum samples, blood pressure, exhaled breath condensate and health
questionnaires will be collected.

Three single nucleotide polymorphisms (SNPs) have been identified in Africans that are
associated with increases in systemic NO production. These studies determine whether the
NOS2 promoter SNPs are associated with differences in basal exhaled NO levels. The study of
exhaled NO levels in individuals with asthma is confounded by the presence of cell types
besides bronchial epithelium that produce NO, by differences in the severity of asthma and
by the use of medications such as corticosteroids which alter exhaled NO levels.

Therefore, in this study exhaled NO levels in asymptomatic healthy African Americans and
Caucasians are measured. The initial analysis of exhaled NO levels indicate that a subset
of African American samples contained lower levels of NO than previous measurements of
exhaled NO levels in Caucasians. Because differences in exhaled NO levels may influence
bronchodilation and other airway responses, as part of this study, the exhaled NO levels of
the African American subjects are compared to the results of sample collections from
Caucasian samples.

In addition to measures of exhaled NO levels, information on race or ethnicity and DNA
samples are collected to characterize samples collected from African American and Caucasian
subjects. Serum samples, measures of blood pressure and exhaled breath condensate samples
are collected from African Americans and Caucasians to control for confounding variables.
Repeated measures of exhaled NO levels are collected to control for fluctuations in exhaled
NO levels related to upper respiratory infections.

Inclusion Criteria:

- Willing/able to give informed consent

- self declared non-atopic, non-asthmatic

- never cigarette smoker,

- no significant occupational exposure to respiratory irritants or toxins,

- no chronic illness

- no chronic use of medications (excluding contraceptive medication),

- no historical unstable cardiac or severe lung disease,

- within study age parameters of 18 - 40

Exclusion Criteria:

- occupational exposure to hay or grain

- smoked 20 or more packs of cigarettes in a lifetime.

- prior allergen immunotherapy

- Allergy and or asthma

- Students or employees under direct supervision by protocol investigators are
ineligible

- Nursing mothers

- pregnancy

- Other investigational medication within the last 30 days

- Other medical or psychological conditions which, in the opinion of the investigator,
might create undue risk to the subject or interfere with the subject's ability to
comply with the protocol requirements