Effect of Montelukast on Experimentally-Induced RV16 Infection in Asthma

Viral infections are important causes of wheezing illnesses throughout childhood and in
adults with asthma. There has been progress in identifying mechanisms and risk factors for
severe respiratory symptoms, and in particular, wheezing. Given this close relationship, it
would be attractive to apply antiviral strategies to the prevention and treatment of asthma,
and both RV and RSV are obvious targets. Unfortunately, attempts at developing an RSV vaccine
have so far been unsuccessful, and vaccination to prevent RV infection does not seem to be
feasible due to the large number of serotypes. Antiviral medications have been tested in
clinical trials, however one problem with this approach is that once the clinical signs and
symptoms appear, viral replication is well underway.

The other potential therapeutic approach for respiratory viral infections would be to
selectively inhibit pro-inflammatory immune responses induced by the virus. The beneficial
effects of systemic glucocorticoids indicate that this approach is valid; the challenge will
be to develop treatments with greater efficacy and a reduced potential for adverse effects.
The large body of information linking cysteinyl leukotrienes to viral infections, allergic
inflammation, and asthma exacerbations, strongly supports the hypothesis that virus-induced
leukotrienes contribute to the severity of respiratory infections and in susceptible
individuals, lead to lower airway obstruction and exacerbations of asthma. We propose to use
montelukast in an experimental viral challenge model to explore this hypothesis.

Inclusion Criteria:

A subject with mild persistent asthma is eligible for participation in the study if all of
the following inclusion criteria apply:

- Male or female with no health concerns that might affect the outcome of the study

- Age 18-65 range

- diagnosis of mild persistent asthma based on clinical findings such as cough, wheeze
and shortness of breath

- a history of asthma for at least six months prior to screening

- FEV1> 80% of predicted

- presence of allergy based on at least one positive prick skin test when tested with a
standard panel of common allergens

- ability to produce sputum when induced during the baseline assessments

- asthma medications consisting of only inhaled short acting B-agonist taken as needed

- reversible airways disease as indicated by > 12% reversibility post B-agonist or

- methacholine hyperresponsiveness (PC20 < 8 mg/ml)

- ability to give valid informed consent to participate by signing and dating a written
consent form

Exclusion Criteria:

A subject is not eligible to participate in this study if any of the following exclusion
criteria apply:

- History of severe episodes of asthma with respiratory infections

- Screening serum RV16 antibody titer > 1

- Current smoker or has a smoking history exceeding 5 pack years

- Currently receiving immunotherapy

- Currently participating in another clinical trial or has participated in an
investigational drug trial within one month of screening

- Unable, in the judgment of the investigator, to comply with directions and/or tolerate
the procedures required for participation in this trial

- Pregnant or breast-feeding or has a planned pregnancy during the course of the study

- Regular use of an asthma controller such as montelukast or an inhaled corticosteroid.