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Wiley, Pediatric Pulmonology, 6(53), p. 701-709

DOI: 10.1002/ppul.23980

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Montelukast reverses airway remodeling in actively sensitized young mice

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

AbstractAsthma 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.AimWe 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.MethodsImmature 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.ResultsOVA‐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.ConclusionWe provide thus evidence for a greater degree of AR after allergenic sensitization and challenge in younger mice versus adults. This study provides proof of concept that airway remodeling can be prevented and reversed in this case by anti‐asthmatic drug Montelukast in this model.