Montelukast for Early Life Wheezing

BACKGROUND:

Asthma has a large impact on the children of our society. It is among the most common
chronic diseases of childhood and is the leading cause of absenteeism from school. It is
unknown as to why more children are having recurrent episodes of wheezing and why some
children have asthma while others do not. There is increasing evidence that differences in
innate immune responses among children can determine which child will have recurrent
wheezing and asthma. While many studies have focused on the factors that initiate innate
immune responses, there are relatively few studies of the downstream factors that cause
abnormal airway responses. There is evidence that eicosanoid mediators are part of the
innate immune response and can function as its effector arm for allergic responses. The
ability of leukotrienes and prostaglandins to produce central features of the asthma
phenotype is well described and there is emerging evidence that lipoxins facilitate
restoration of allergic changes in the airways. This study will test the hypothesis that the
balance of airway eicosanoid expression during early-life wheezing illness and the
genetically determined capacity to respond will predict recurrent wheezing. Moreover, an
intervention to restore a more normal tissue response to this imbalance will reduce symptoms
of early-life wheezing and subsequent recurrent episodes.

DESIGN NARRATIVE:

This will be a prospective, double-blind, randomized, placebo-controlled, parallel-group
study of the effects of montelukast on the duration of wheezing in children 12 months to 3
years of age who are under the care of a physician for a wheezing illness. Study treatment
will be given for 56 days. Participants who are 2 to 3 years old will receive either 5-mg
montelukast tablets or matching placebo. Participants who are 12 months to 2 years old will
receive 4-mg montelukast granules or matching placebo. The primary outcome parameter of this
study will be the number of days that the infant is observed to be free of wheezing by the
primary caregiver. The secondary outcome parameters will be the number of wheezing episodes
during the treatment period and the rate of recurrent wheezing during the follow-up period.
The study, which is a consortium arrangement between the Brigham and Women's Hospital and
the Hacettepe University Medical Center in Turkey, will recruit children only from the
Ankara area of Hacettepe University Medical Center in Turkey.

This study will be one of three, which include: 1) measuring the airway eicosanoid profiles
of pediatric "wheezing" patients 3 months to 3 years old; 2) determining if genetic variants
in eicosanoid metabolic and response pathways are associated with recurrent wheezing; and 3)
determining how intervention with montelukast (singulair) affects symptoms and the rate of
recurrent wheezing.

Inclusion Criteria:

- Physician-diagnosed wheezing illness

Exclusion Criteria:

- Asthma

- Prematurity

- Known intolerance to montelukast