Appendices

Appendix 1

Appendix 2

Appendix 1

Summary of evidence for the efficacy of montelukast in children with each clinical pattern of asthma

	Author	Design	Key findings
Persistent asthma
Randomised placebo-controlled trials	Knorr et al., 2001¹³	Montelukast 4 mg once daily at bedtime for 12 weeks in pre-school children with mild-to-moderate persistent asthma (n=689)	Montelukast superior to placebo on: percentage asthma-free days, daytime asthma symptoms, night-time asthma symptoms, days with asthma symptoms, need for SABA or oral corticosteroids, physician's global evaluation No significant difference vs placebo in exacerbations rate, caregiver's global evaluation, quality of life Benefits observed from first day No difference vs placebo in adverse event rate
	Knorr et al., 1998¹⁴ Becker et al., 2004¹⁷	Montelukast 5 mg once daily at bedtime for 8 weeks in school children with persistent asthma (n=336) Included children with moderately severe (FEV150-85% predicted) asthma One-third taking ICS	Montelukast superior to placebo on: FEV1improvement, SABA use, days with asthma exacerbations (21% vs 26%), quality of life No significant difference vs placebo on: absenteeism from school, nocturnal awakening, daytime asthma symptom score. Onset of action rapid and sustained No difference vs placebo in adverse event rate In subgroup with milder asthma (FEV1> 75% predicted), montelukast superior to placebo on: FEV1improvement, PEF, night-time wakening, quality of life
	Phipatanakul et al., 2002⁴²	School children with asthma triggered by exposure to cat allergens (n=18)	Montelukast superior on: FEV1response to allergen exposure, duration of challenge tolerated No significant difference vs placebo for upper respiratory response
	Phipatanakul et al., 2003⁴³	24-week trial of montelukast during planned ICS tapering in children with stable persistent asthma taking low-to-moderate ICS doses (n=36)	Montelukast superior to placebo on: number of rescue-free days, ICS dose reduction achieved ICS requirement increased in placebo control group
Randomised comparative trials	Garcia Garcia et al., 2005¹⁶	Montelukast 5 mg once daily vs fluticasone 100 mcg twice daily in school children with mild persistent asthma for 12 months (n=994) Designed to demonstrate non-inferiority for primary outcome: change from baseline in % days free of rescue medications (e.g. SABA, systemic corticosteroids)	Montelukast not inferior to ICS on primary outcome Fluticasone superior on: FEV1, days without SABA, quality of life, systemic corticosteroid requirement, acute asthma episodes Both montelukast and fluticasone well tolerated
	Luskin et al., 2003¹⁹	Montelukast vs fluticasone in school children with mild persistent asthma (n=104) 12-month prospective open-label observational study	Montelukast and fluticasone equally effective on: emergency visits, hospitalisation, symptoms at study completion, SABA use, oral prednisolone use. Montelukast superior on adherence
	Sorkness et al., 2007²⁰	Montelukast once daily vs fluticasone 100 mcg twice daily for 48 weeks in school children with mild-to-moderate persistent asthma	Fluticasone superior on: symptom-free days, SABA use, improvement in number of asthma control days, improvement in episode-free days, FEV1, morning and evening PEF No difference for growth over 48 weeks
	Zeiger et al., 2006²¹	Montelukast vs fluticasone for 16 weeks in school children with mild-to- moderate persistent asthma	Fluticasone superior to montelukast on: number of asthma control days, Asthma Control Questionnaire, SABA use, FEV₁, peak expiratory flow
	Ostrom et al., 2005²²	Montelukast 5 mg once daily vs fluticasone 50 mcg twice daily for 12 weeks in school children (n=342) with moderate-to-severe persistent asthma (baseline FEV160-85% predicted)	Fluticasone superior to montelukast on: FEV1, morning and evening PEF, percentage rescue-free days, night-time symptom score, mean total symptom score, SABA use
	Jat et al., 2006²³	Combination montelukast 5 mg once + budesonide 200 mcg daily vs budesonide 400 mcg/day alone in children with moderate persistent asthma	Similar efficacy on: FEV1, asthma symptom scores Budesonide 400 mcg/day markedly superior to montelukast plus low-dose budesonide on exacerbation rate (33.3% vs 9.1%; P < 0.01)
	Peroni et al., 2005⁴⁴	Montelukast vs budesonide in children with mild asthma exposed to known allergen trigger (house dust mite)	Both budesonide and montelukast protected against fall in FEV1on allergen challenge Budesonide, but not montelukast, protected against increase in bronchial hyperresponsiveness after allergen challenge
Intermittent asthma
Randomised placebo-controlled trials	Bisgaard et al., 2003²⁵	Long-term (12 months) montelukast in pre-school children with intermittent asthma and a history of recurrent viral-induced exacerbations taking ICS (n=549)	Montelukast superior to placebo on: exacerbation rate, ICS requirement Number of positive viral tests too low to permit correlation of reduction exacerbations with prevention of viral-induced episodes
	Robertson et al., 2007³	12-month study of parent-initiated montelukast course commenced at onset of viral infection or asthma symptoms in school children with intermittent asthma	Montelukast superior to placebo on: reduction in symptoms, days off school, need for doctor visits Non-significant trend favouring montelukast for: specialist attendances and hospitalisations, duration of episode, SABA use, prednisolone use
	Bisgaard et al., 2003⁴⁵	28-day course montelukast in infants (3-36 months) hospitalised with acute RSV bronchiolitis	Montelukast superior to placebo on: proportion of symptom-free days and nights, cough rate, delayed acute respiratory episodes
Exercise-induced asthma
Randomised placebo- controlled trials	Melo et al., 2003³⁰	Montelukast taken for 1 week in atopic school children with exercise- induced bronchoconstriction	Montelukast superior to placebo on: reduction in immediate-phase and late-phase bronchoconstriction following exercise challenge Montelukast abolished late-phase bronchoconstriction
	Kemp et al., 1998³¹	Montelukast 5 mg once daily in school children	Montelukast superior to placebo on protection against exercise-induced bronchoconstriction Protective effect seen after 2 days' treatment
	Kim et al., 2005³²	Montelukast taken for 8 weeks in children with exercise-induced asthma (n=64)	Montelukast superior to placebo on protection against exercise-induced bronchoconstriction Bronchoprotective effect sustained for 8 weeks after cessation of treatment

Appendix 2

Search Strategy

A. Medline 1996 to Present with Daily Update (Ovid) Search strategy:

1 montelukast.mp. [mp=title, original title, abstract, name of substance word, subject heading word] (843)

2 leukotriene receptor antagonist$.mp. [mp=title, original title, abstract, name of substance word, subject heading word] (784)

3 1 or 2 (1373)

4 limit 3 to (humans and English language and (clinical trial, all or guideline or meta analysis or practice guideline or randomized controlled trial or “review”)) (590)

B. Medline 1996 to Present with Daily Update (Ovid)

Search strategy:

1 Asthma, Exercise-Induced/ (1313)

2 montelukast.mp. [mp=title, original title, abstract, name of substance word, subject heading word] (846)

3 1 and 2 (32)

C. Pubmed clinical queries

1 montelukast + therapy + narrow (specific) (249)

2 Limit 1 to: (human + English + [meta-analysis or RTC] + age 0–18 years) (141)