Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in infants with an extremely low birth weight. Because there is no effective therapy, the mortality of this condition in severely affected patients is high. Therapeutic blocking of the leukotriene system seems to be a logical approach due to the known pathophysiology of BPD. Objectives: The aim of this study was to examine the therapeutic effect of montelukast in preterm children suffering from severe BPD. Methods: We performed an unblinded, prospective trial including infants born between 23 and 27 weeks of gestation suffering from severe BPD. The study drug was montelukast (1 mg/kg of body weight as a single dose daily in the 1st week of therapy, increasing to 1.5 mg/kg of body weight in the 2nd week and finally to 2 mg/kg of body weight in the 3rd week). Treatment was continued until the radiological signs and the clinical symptoms of BPD disappeared or the patient was discharged from the hospital. Each patient included in this study was matched for gestational age, birth weight, and pulmonary severity score to a control. Results: Until March 2014, a total of 22 infants were enrolled into the study. The rates of the primary outcome differed significantly between the montelukast-treated group and the control group. All but 1 of the children in the treatment group survived (91%), whereas 7 of the 11 children in the control group died (survival rate 36%; p = 0.002 using Fisher's exact test). The mean mechanical ventilation time (41.2 ± 25.3 vs. 103.7 ± 90.6 days) was significantly shorter and the mean preterm complication score (3.0 ± 1.7 vs. 5.6 ± 1.4) was significantly lower in treated patients compared to the control group. (p = 0.05 for both items; Wilcoxon's matched-pairs test). Conclusion: Based on the clinical observations, the statistical results, and the relatively low risk of the study drug montelukast, we recommend using this treatment in severe cases of BPD for infants facing a high risk of death.

Interdisciplinary Care of Children with Severe Bronchopulmonary Dysplasia

“…Montelukast may have benefit in its ability to provide bronchodilation and to decrease inflammation, although data in sBPD are limited. 78 …”

Phenotypes of Bronchopulmonary Dysplasia

“…Poor response to standard asthma treatment [16,22] Airway inflammation Bronchodilators [23,24] Systemic or inhaled corticosteroids [22,25] Leukotriene receptor antagonists [26] Distal airspace and vasculature…”

Leukotriene B4mediates macrophage influx and pulmonary hypertension in bleomycin-induced chronic neonatal lung injury

“…Ex-premature infants with severe BPD also had increased urinary LTE 4 (10). Montelukast given as preventive therapy in at-risk preterm infants did not reduce the incidence of moderate-severe BPD (25); however, when employed as rescue therapy for severe late-stage BPD, it conferred a survival advantage (42). Increased cysLTs have also been reported in tracheal aspirates of infants with persistent PHT of the newborn, an acute form of PHT (48).…”