Table 5.

Recent studies on the management of asthma in preschoolers

Study	Design	Aim of study	Subjects	Age	Treatment arms	Main results
Castro-Rodriguez et al. [58] (2018)	Meta-analysis (6 RCTs included)	Compare the efficacy of daily ICS vs. daily oral LTRA	N=3,204	6–54 mo	Any kind of low-dose ICS (FP or BUD) vs. montelukast 4 mg QD, for a minimum of 3 mo	Daily ICS appears more effective than daily oral LTRA for symptom control and for decreasing exacerbations
			Preschoolers with asthma or recurrent wheezing who required controller therapy			Supportive of the recommendation of current guidelines: ICS as the preferred controller, LTRA as alternative
Fitzpatrick et al. [63] (2017)	R, DB, DD, CO	Individualized Therapy for Asthma in Toddlers study	N=300 (enrolled)	12–59 mo	Assess the differential response to daily ICS (FP 44 μg BID) or intermittent ICS (as-needed FP 44 μg BID + albuterol) or daily LTRA (montelukast 4 mg QD) during 16 weeks of each therapy in a randomized order	Asthma control was most likely to be best during daily ICS therapy.
			N=230 (completed)			Daily low-dose ICS should be the first-line therapy in the subjects with aeroallergen sensitization and/or blood eosinophils ≥300/μL
			Preschoolers with mild persistent asthma who required “step-2” asthma therapy			No predictors of best response to LTRA
Yoshihara et al. [60] (2018)	RCT, DB	The first large scale, RCT to assess the efficacy and safety of ICS/LABA in preschoolers	N=300 (enrolled)	8–48 mo	FP/SAL 50/25 μg vs. FP 50 μg during 8-week DB period, after run-in period (FP 100–200 μg/day for ≥2 yr of age, 100 μg/day for <2 yr)	ICS/LABA did not show superior efficacy to ICS alone
			N=268 (completed)			No significant difference in safety was noted with ICS/LABA
			Preschoolers diagnosed with asthma by Japanese guideline and for whom ICS/LABA was considered necessary by their physicians
Kaiser et al. [48] (2016)	Meta-analysis (5 RCTs included)	Assess the efficacy of intermittent highdose ICS for the prevention of asthma exacerbation	N=422	<72 mo	Any kind of high-dose ICS was initiated at the first signs of URTI (nebulized BUD 1mg BID for 7 days or MDI BUD 800 μg/1,600 μg BID for 7 days or nebulized BUD 400 μg QID for 3 days followed by 400 ug BID for 7 days or MDI FP 750 μg BID for 2 days until symptom free)	Reduce the overall risk of subsequent exacerbation requiring systemic corticosteroid by 35%
			Preschoolers with severe intermittent asthma/ EVW (subgroup analysis)			Zeiger et al. [47] revealed no difference between daily low-dose ICS and intermittent high-dose ICS on asthma control and risk of exacerbation.

RCT, randomized controlled trial; ICS, inhaled corticosteroid; LTRA, leukotriene receptor antagonist; FP, fluticasone propionate; BUD, budesonide; QD, quaque die; R, randomized; DB, double blind; DD, double dummy; CO, cross over; BID, bis in die; SAL, salmeterol; LABA, long-acting beta-2 agonist; EVW, episodic viral wheeze; URTI, upper respiratory tract infection; MDI, metered dose inhaler; QID, quarter in die.