Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma

Abstract

Purpose: Several markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma.

Methods: Young children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during the run-in period; and 2) having a serum EDN (sEDN) level ≥ 53 ng/mL, with positive specific immunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups: the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONT group received montelukast 4 mg once daily. Ineligible patients were invited to receive montelukast 4 mg once daily (OBS group). Treatment period was 12 weeks.

Results: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000) over the 12-week study period. There was no significant change in sEDN in the BIS group but there was a significant decrease in the MONT group (P < 0.000). Patients in the OBS group with high EDN levels (< 53 ng/mL) showed a significant decrease due to MONT treatment (P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups (P < 0.000).

Conclusions: EDN is a useful relatively non-invasive biomarker for predicting responses to montelukast and budesonide treatment of preschool children with beta2-agonist responsive recurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry, UMIN000008335).

Keywords: Biomarkers; asthma; children; eosinophil-derived neurotoxin.

Fig. 1. Study protocol.

At visit 1, patients who met inclusion criteria were tested for sEDN and HDM-IgE, then entered to run-in period. After 2 weeks of run-in period, the results of sEDN and HDM-IgE were reported to the study physician and the patients who met randomization criteria were randomized to receive budesonide or Montelukast for 12 weeks. Those who did not meet randomization criteria, yet had symptoms during run-in period were invited to receive montelukast. Clinical assessment was made at each visit and with asthma symptom diary recorded by the caregivers. At visit 5, sEDN was measured. sEDN, serum eosinophil-derived neurotoxin; HDM-IgE, house dust mite-immunoglobulin E; R, randomization.

Fig. 2. Patient flow.

R, randomization; BIS, budesonide inhalation suspension; MONT, eligible and receiving montelukast; OBS, not eligible and receiving montelukast; EDN, eosinophil-derived neurotoxin; HDM, house dust mite.

Fig. 3. Changes in ACD per week.

ACD, asthma control days; BIS, budesonide inhalation suspension; MONT, eligible and receiving montelukast.

Fig. 4. Change in sEDN with treatment. BIS group showed no significant change in sEDN level over 12-week treatment period (A). MONT group showed significant change in sEDN level over 12-week treatment period (B) (P < 0.000).

OBS group with low sEDN (< 53 ng/mL) showed no significant change in sEDN over 12-week treatment period with montelukast (C). OBS group with elevated sEDN (< 53 ng/mL) showed significant decrease (P = 0.023) in sEDN over 12-week treatment period with montelukast (D). ^*P < 0.01, paired t-test. sEDN, serum eosinophil-derived neurotoxin; Pre, sEDN level taken at −2 weeks but used at 0 weeks to determine eligibility of study subject; Post, sEDN level at 12 weeks; BIS, budesonide inhalation suspension; MONT, eligible and receiving montelukast; OBS, not eligible and receiving montelukast; EDN, eosinophil-derived neurotoxin.