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.