DISCUSSION
Episodic viral wheezing attacks are common in preschool children and are associated with morbidity. 1, 2, 6 Therefore, it has been the subject of many studies. In this study, the effect of montelukast on the frequency of wheezing in children with mAPI negative EVW was investigated. Daily use of montelukast has been shown to significantly reduce wheezing episodes in patients with EVW who are mAPI negative.
Episodic viral wheezing differs from MTW in that it follows viral URTI and patients are completely free of complaints except for wheezing. Comparing both groups, children with MTW are more likely to develop asthma. 2, 3, 8 When responses to montelukast treatment are added, it will be useful to differentiate and follow-up patients in the clinic in terms of both drug selection and prognosis.
The cysteinyl leukotrienes (CysLTs) are one of the mediators involved in the early stage of allergic reactions, and increase during URTI, which is the main trigger for acute wheezing attacks in children. Also, CysLT-1 antagonists inhibit a mediator involved in the early stage of the allergic inflammatory pathway. 4, 7, 17 There are many studies in the literature evaluating the use of continuous or intermittent LTRA in the treatment of wheezing in children compared to placebo. 12, 18-22 In these studies carried out until present, the effect of montelukast in the treatment of wheezing has been reported as effective in some studies and not effective in others.13-15 Montelukast has been shown to have positive effects on asthma symptoms in the study of Barbara Knorr et al.23 In the study of Bisgaard et al. in year 2005, it was found that maintenance montelukast treatment decreased the rate of exacerbation compared to placebo. It has been shown to be effective in controlling wheezing attacks triggered by viral infections, especially in children aged 2-5 years. 12 In the study of Robertson et al, children aged 2 to 14 years were evaluated and a moderate effect of montelukast on symptoms was reported.21 Bacharier et al. also found that intermittent LTRA reduced severity of symptoms. 18 In the study conducted by Valovirta et al in 2011, more than half of their patients had API positivity, and it was stated that maintenance montelukast did not reduce the attacks but the symptom severity. 22However, it is thought that the children included in the study were truly undiagnosed and MTW and atopic asthmatics were misclassified as EVW. 19 In 2014, Nwokoro et al determined a small but statistically significant reduction in medical care rates in children with the EVW phenotype. 20
The reason for these different results is the complex and heterogeneous structure of different endotypes in children with wheezing.7 Also, there is inconsistency as to whether EVW should be considered a separate entity from MTW, which has an asthma-like phenotype. As a result, the inclusion criteria of patients differ between studies. 14 In some of these studies, the age of the patients was not limited to under 5 years of age, or the API was not differentiated, and it is likely that children with a distinct EVW phenotype were not a homogeneous group in the studies.4 These may inadvertently cause bias in studies, and it should be noted that the rate of unresponsiveness of some patient subgroups to LTRA therapy may vary, as the exact pathophysiology was not determined.
In our study, we classified children under the age of 6 according to mAPI, followed them as EVW and MTW, and evaluated their responses to montelukast use. Studies have shown that most patients improved during follow-up. 3, 12, 18 In our study, we wanted to show that montelukast can be much more effective at mAPI negative EVW. While before montelukast, wheezing followed each URTI complaint, they stated that they recovered only with upper respiratory tract symptoms without wheezing after montelukast. This suggested that montelukast may have limited the viral disease picture. In recent studies conducted with the emergence of Covid infection; montelukast has been shown to inhibit irreversible viral infection by acting on the viral genome.24 In an insilico study, it has been shown that montelukast has anti-viral activity by interfering with the entry of the virus into the host cell. 25 Razi et al. study shows that the immunostimulant given in atopy-negative children is effective. This suggests that EVW under 5 years old may be an immune defect that is insufficient to limit viral infection. 26 In fact, it should not be generalized as asthma under the age of 5, but should be considered as 2 different entities. However, it seems that more studies are needed on this subject. The most important limitation of our study is the small sample size and the lack of long-term results of the patients. It was also a single center study.