# Pediatric Asthma: Where Has Montelukast Gone?
## 4 Montelukast in Pediatric Asthma
### School-Age Asthma
In these patients, respiratory symptoms [105; 106], lung function [105; 106; 107], and serum inflammatory markers [105] have been shown to improve more significantly with the association of montelukast and budesonide in comparison to budesonide alone. On the other hand, a recent systematic review and meta-analysis from China stated that in the stepwise approach of pediatric asthma therapy, better symptom control (mean difference in asthma control test score: 2.30; 95% CI 1.39-3.21, \(p<0.001\)) and lung function improvement (mean difference in peak expiratory flow% predicted: 5.45; 95% CI 1.57-9.34, \(p=0.006\)) were achieved by adding salmeterol rather than montelukast to inhaled fluticasone [108]. Such conclusions are only apparently in contrast to those achieved by [PERSON] and coworkers. The combination of these findings supports the role of montelukast as a valuable add-on option in children with suboptimal asthma control with daily ICSs, even though evidence is still insufficient to make it the first choice when compared to salmeterol. As a surrogate outcome of the therapeutic effects of montelukast, some authors have recently analyzed the consequences of its withdrawal in children with asthma. The assessment of lung function, fraction of exhaled nitric oxide (FeNO), and the asthma control test did not significantly differ between the placebo and montelukast groups within 2 weeks after withdrawal [109]. A systematic review confirmed and extended these findings, concluding that only limited and short-term effects of deprescribing montelukast have been reported in the literature [110]. Despite the experience of large variability in clinical response when administered to asthmatic children, there is growing evidence of beneficial effects determined by montelukast on several biomarkers. Particularly, montelukast has been shown to regulate the T helper 1 (Th1)/Th2 balance, to increase the expression of CD4+CD25+ regulatory T cells, and to decrease the airway inflammation typical of asthma [111]. In addition, the observation that treatment with montelukast is associated with the reduction in the eosinophil count and of markers of airway remodeling in induced sputum supports its possible role in the modulation of asthma-related airway modifications and in the reduction in eosinophil inflammation [11; 112]. A possible explanation of these discrepancies is not difficult to hypothesize and is perceived, even if not proven, by many clinicians: montelukast may be of help in some individuals, but completely useless in others. Unfortunately, we do not know how to differentiate them prospectively [113]. Evidence in support of this statement is starting to emerge as, for instance, montelukast has been shown to be a better controller medication in obese rather than in lean patients with early-onset atopic asthma [114]. Indeed, in obese patients with asthma, relative corticosteroid resistance has been reported [115], and body mass index seems to correlate with leukotriene synthesis [116], thus making anti-leukotrienes the potentially ideal medication for this category of subjects. A further step in delineating which patients are more likely to benefit from montelukast therapy has been proposed by a Polish study [117]. To identify potential risk factors for respiratory exacerbations, the authors analyzed inflammatory markers in children with mild asthma during the 12 months following the change from ICS to montelukast therapy. Their findings showed that in 75% of patients, asthma control was adequately maintained, and that high induced sputum eosinophils (>2.5%) and raised levels of FeNO (>20 ppb) represented the most important predictors of exacerbations after switching from ICSs to montelukast [117]. More interestingly, a recent study demonstrated that genetic variation in LTA4H, a gene involved in the leukotriene pathway, may contribute to variability in montelukast response.