The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma

Abstract

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma.In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined.No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean¡SD FEV0.5 (189.0¡37.8 and 214.4¡44.9 mL before and after treatment, respectively), FeNO (29.8¡10.0 and 19.0¡8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast.In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

“…Exhaled nitric oxide and other assessments of airways inflammation Elevated exhaled nitric oxide fractions (FeNO) have been found in wheezing infants, especially when they are atopic [70,71], and these normalise during treatment with ICSs [72] and montelukast [73,74]. FeNO in infants are affected by environmental exposures and genetic predisposition to atopy [75].…”

Montelukast exerts no acute direct effect on NO synthases

“…Taken together these assays clearly gave no evidence of any direct inhibitory effect of montelukast on NOS isoenzymes within the concentration range from 10 -7 to 10 -4 M, far exceeding that achieved during drug therapy (39). Therefore, alternative explanantions for the decreased NO levels measured in expired air from asthmatic subjects after treatment with montelukast should be considered (18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

“…Since no acute inhibitory effect on NO synthesis, neither directly on the three NOS isoenzymes, nor a suppression of the expression of iNOS was found, alternative explanantions for the decreased NO levels measured in expired air from asthmatic subjects after treatment with montelukast must be considered (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). They may be explained by changes in quantities or sites of NO generation, binding or more distal processes.…”

“…A number of studies in asthmatic subjects treated with montelukast have shown that such LTD 4 receptor blockade is associated with lower levels of exhaled NO (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). In a murine allergic asthma model in which inflammation was induced by injection of ovalbumin, no evidence for a change in inducible NOS (iNOS) mRNA levels following montelukast treatment was observed (28).…”

Biomarkers in asthma and allergic rhinitis

“…ICS and other anti-inflammatory therapies for asthma, including leukotriene receptor antagonists (LTRA) and omalizumab (anti-IgE), have been shown to reduce eNO both in children and adults [127][128][129][130].…”