Montelukast reverses airway remodeling in actively sensitized young mice

Pediatric Pulmonology
Stephane DebelleixMichael Fayon

Abstract

Asthma is characterized by airway hyperresponsiveness (AHR) and inflammation leading to airway remodeling (AR). In children, AR may occur very early prior to the age of 6 years. Treatments to prevent or reverse AR are unknown. We sought to determine (i) whether short allergenic sensitization at a young age in a mouse model may induce enhanced AR and inflammation compared to adults; (ii) the effect of Montelukast on such AR. Immature and adult Balb/c mice were sensitized and challenged with ovalbumin. AHR and AR were measured using cultured precision-cut lung slices and inflammation by bronchoalveolar lavage. Experiments were repeated after administration of Montelukast. OVA-challenged mice developed AHR to methacholine regardless of age of first exposure to OVA. Young mice developed greater thickened basement membrane, increased smooth muscle mass, and increased area of bronchovascular fibrosis compared with adult mice. Cellular infiltrates in BAL differed depending upon animal age at first exposure with higher eosinophilia measured in younger animals. Montelukast decreased ASM mass, BAL cellularity. We provide thus evidence for a greater degree of AR after allergenic sensitization and challenge in younger mice versus adults. T...Continue Reading

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Citations

Sep 24, 2019·Expert Review of Respiratory Medicine·Hoang Kim Tu TrinhHae-Sim Park
Jul 13, 2019·American Journal of Respiratory Cell and Molecular Biology·Jennifer L Ingram
Jun 11, 2020·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Zhenxing XuWei Guo
Oct 6, 2020·Frontiers in Pharmacology·Jean BarréCédric Annweiler

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