The clinical aim of this trial is to assess whether intermittent montelukast is an effective
treatment strategy in preschool wheeze. The mechanisms aim of the trial is to determine
whether there is a genetically highly-responsive subgroup of children. In designing this
trial the investigators have incorporated several novel aspects. First, parents will be able
to adjust the use of oral montelukast to their child's symptoms. This allows the
investigators to recruit both "episodic" and "multi trigger" patterns of preschool wheeze -
and control for any change in wheeze pattern during the trial. Second, before the
investigators issue the trial medication, the investigators will assess children's
leukotriene genes, focusing primarily on a gene called ALOX5. This ALOX5 "stratification"
step will ensure that an equal number of potentially "treatment-responsive" children receive
the active drug (montelukast) and the dummy medicine - and the equal numbers will help the
investigators to assess the role of ALOX5. For the trial, the investigators will first
recruit 1,300 children with a history of preschool wheeze, then divide them into the group
with "responsive" and "less responsive" genes by their ALOX5 status. The investigators will
then issue parents with the trial medication; 50% will be given montelukast and 50% will be
given dummy medication. Parents will start the trial medication whenever their child develops
a cold, and stop the medication when wheeze resolve. Parents will also be able to give the
trial medication for wheeze between colds. Over the 12 month trial period, the investigators
will assess the number of unscheduled attendances to a medical practitioner for wheeze for
each child. At the end of the trial, the investigators will determine whether montelukast is
effective then whether there is a difference in response to montelukast between the 2 ALOX5
gene groups.
At the same time, the investigators will measure many other genes that may influence response
to montelukast, as well as the amount of leukotrienes that are excreted in the urine before
and during attacks. Using these results, the investigators will be able to both inform
national treatment policy, and develop new concepts on the mechanism of preschool wheeze that
will inform the development of new therapies. Since children will continue to receive
"normal" inhaled therapy, there are no ethical issues in giving a dummy medicine to half of
the 1300 children to be recruited. The study will be the largest trial in wheezy preschool
children to date, and may open up genetic testing in preschool wheeze.