How Different Beta-2 Receptor Genotypes Affect an Asthmatic's Response to Regular Salmeterol Treatment

In many patients with asthma, exercise-induced bronchoconstriction is a common and
oftentimes limiting characteristic. Inhaled β2-adrenoreceptor agonists like albuterol are
the most effective treatments available for the relief of acute asthma symptoms. However,
there is evidence that regular use may lead to adverse effects in some patients. Previous
studies have shown that polymorphisms of the β2-adrenergic receptor can influence airway
responses to regular inhaled beta-agonist treatment.

Pharmacogenetics is the study of how genetic differences influence the variability in
patients' responses to therapy, both therapeutic and adverse. Genetic susceptibility and
environmental factors both play major roles in the etiology of asthma. The strong familial
clustering of asthma has lead to a surge of research into the genetic predisposition of
asthma. The aim of the present study is to utilize a double-blinded prospective cohort study
to investigate whether genotype-specific effects occur when assessing the duration of
protection conferred against exercise-induced bronchoconstriction by regular salmeterol
treatment.

Inclusion Criteria:

- Both male and female

- 18 to 50 years of age

- Resting FEV1 ≥ 65% of predicted normal

- Exercise-induced bronchoconstriction defined as a decrease in FEV1 of ≥ 20% following
a standardized exercise challenge when compared to pre-exercise baseline FEV1 value
measured 5 minutes before exercise

- Must be Arg/Arg or Gly/Gly genotype

Exclusion Criteria:

- Long-acting beta agonist use within 12 weeks of the first exercise challenge

- Smoking within past 12 months

- Greater than 10-pack years smoking history

- Unresolved signs and/or symptoms of an upper respiratory tract infection within 4
weeks of first exercise challenge

- Asthma exacerbation within 4 weeks of first exercise challenge requiring change in
type, dose or frequency of medications and/or an unscheduled visit to an health care
provider, including emergency room or hospital

- Subject has exercised or performed strenuous activity within 72 hours of the first
exercise challenge

- Subject has been exposed to cold air sufficient to provoke symptoms of bronchospasm
within 2 hours of exercise challenge

- In addition to asthma, the subject has an active, acute or chronic pulmonary disorder
documented by history, physical examination, or chest x-ray

- Subject has evidence of ischemic, valvular, hypertrophic, familial or other forms of
heart disease that would put the subject at risk during exercise testing or that
would interfere with the ability to achieve protocol-specified heart rates during
exercise testing

- Subject has used systemic corticosteroids within 1 month of first exercise challenge