# Pediatric Asthma: Where Has Montelukast Gone?
## 4 Montelukast in Pediatric Asthma  
### Montelukast's First Steps in Asthma Treatment  
The first evidence in support of montelukast's usefulness in asthma management was provided by well-designed trials in adult subjects demonstrating its efficacy in improving asthma control and in providing protection against exercise-induced bronchoconstriction [31,32]. This soon led toward the evaluation of montelukast applicability in the pediatric population, also due to some of its main features, which made it particularly attractive. First, oral administration in one or two daily doses represented a substantial advantage for children, virtually neutralizing the relevant issues related to poor compliance or inadequate technique with ICSs, which are still the cornerstone of maintenance therapy for pediatric asthma. Furthermore, the concerns associated with the adverse effects on growth, bone mineralization, and adrenal axis, associated with long-term steroid therapy [33], were not raised by montelukast, which is a non-steroidal anti-inflammatory agent.  
Montelukast's efficacy in school-aged [34] and preschool children [35,36] was first reported in studies published between the end of the 1990s and the early 2000s. In addition to its efficacy, montelukast was soon found to be superior to other drugs such as mast-cell stabilizers. School-aged children with mild-to-moderate asthma showed a significant improvement in their nocturnal symptoms and in the use of beta-agonists after a 4-week treatment with montelukast compared to inhaled nedocromil [37]. Similarly, when compared to inhaled cromolyn, montelukast led to a greater reduction in alloteroul use, to higher adherence, and the satisfaction of both the parents and patients [38]. Data from these trials contributed to the progressive reduction in the use of chromosomes until their exclusion from pediatric asthma guidelines, and further strengthened the evidence regarding montelukast's efficacy. Therefore, since its first mention as a possible therapeutic option in the 2002 Global Initiative for Asthma (GINA) Report [39], further studies have progressively improved the definition of the role of montelukast in the therapeutic management of children with asthma. Given the clinical benefit observed in asthmatic children older than 5 years, which is generally lower than that derived from low-dose ICSs [40], montelukast has soon found its application as an add-on treatment in children with poor asthma control despite low-dose ICSs. Such an indication was also confirmed in 2012 by the GINA Report [41]. Nevertheless, combination therapy (montelukast + ICS) proved less effective in controlling symptoms in school-aged children with moderate-persistent asthma than increasing from low to moderate doses of ICSs [42], and montelukast was demonstrated to be an ineffective ICS sparing alternative in these subjects [43].  
With regard to preschool children, also in 2012, GINA recommended the use of leukotriene modifiers to reduce viral induced asthma exacerbations in children with a history of intermittent asthma [44]. Nevertheless, more detailed indications were provided by the 2008 European Respiratory Society (ERS) Task Force, proposing a new classification of preschool wheeze, with the definition of the two phenotypes \"episodic viral wheeze\" and \"multiple-trigger wheeze\" [45]. Such definitions not only had diagnostic and prognostic implications, but more importantly, entailed a different therapeutic approach. Indeed, ICSs were recommended as the first-choice maintenance treatment for multiple-trigger  
Figure 1: Not-asthma conditions with potential clinical applications of montelukast [17,18,24,26,28].  
wheeze [46], and montelukast, to be started at the first symptoms of a viral cold, was recommended for episodic wheeze [47].