# Pediatric Asthma: Where Has Montelukast Gone?
## 4 Montelukast in Pediatric Asthma
### Preschool Wheezing  
In 2014, six years after its publication, the ERS classification of preschool wheeze in episodic viral and multiple-trigger phenotypes [45] was partially reconsidered by its own authors, who acknowledged some limits of such categories in real-life clinical practice. Namely, the frequent overlap of wheeze patterns and their variation over time or with treatment made the wheeze category unclear in many patients. Furthermore, in terms of treatment indications, ICSs were confirmed as the preferred therapeutic approach for multiple-trigger wheeze, but were also indicated as a reasonable choice in episodic viral wheeze, particularly with frequent or severe episodes [75]. These considerations, representing a partial resizing of the role of montelukast in early-life wheezing, are supported by several studies. Indeed, [PERSON] and coworkers showed that children 2 to 4 years with mild persistent asthma achieved similar symptom control with ICSs and montelukast, even though a significantly greater benefit in terms of a lower rate of exacerbations requiring oral steroids or additional asthma medications was observed for patients receiving inhaled budesonide [76]. Similarly, a study from Pakistan comparing montelukast and ICSs in asthmatic preschoolers reported a more frequent need for step-up therapy in patients receiving LTRAs [77]. Furthermore, a cost-effective analysis of a double low-dose inhaled budesonide versus the association of low-dose ICS and montelukast in preschoolers with persistent asthma suggested that the first therapeutic strategy was associated with fewer exacerbations and lower costs [78]. Even when compared to the placebo, montelukast, administered intermittently to preschool children with >2 wheezing episodes, did not significantly reduce the number of unscheduled medical attendances for acute respiratory symptoms [79]. The mentioned findings were further strengthened by several metanalyses and reviews that analyzed the available literature on the topic. A large systematic review involving more than 3000 preschool children with asthma or recurrent wheezing concluded that ICSs represented a better option than LTRAs to control daily symptoms [80]. Interestingly, one of the most feared drawbacks of ICS therapy, the linear growth impairment, did not result in being more relevant in children receiving daily or as-needed ICSs than in those treated with montelukast [81]. In addition, two meta-analyses showed that compared to the placebo, montelukast was not more effective in reducing exacerbations in preschoolers with wheezing disorders (mean difference, 0.07, 95% confidence interval [CI], \(-\)0.14-0.29, \(p\) = 0.5), [82] nor in those with episodic viral wheeze (odds ratio 0.77, 95% CI 0.48-1.25) [83]. On the other hand, findings in contrast to the conclusions achieved by the mentioned meta-analyses have been reported. A Japanese study enrolling 93 patients aged 1-5 years with wheezing symptoms more than once a month but less than once a week showed less exacerbations and less need for step-up treatment in children receiving montelukast than in those under no controller therapy [84]. Moreover, [PERSON] and coworkers found no significant differences between preschoolers with a history of one to three wheezing episodes randomized to receive montelukast, fluticasone, or no treatment for 12 weeks [85]. With a similar study design, but larger population, a Chinese study randomized 239 preschool children with recurrent wheeze to receive fluticasone propionate, oral montelukast, or budesonide suspension for 12 weeks. After comparing the number of wheezing episodes, the emergency visits, and the treatment costs between groups, the authors concluded that the three preventive treatments were equally effective, with the fluticasone propionate being the less expensive drug [86].