Abstract

BackgroundIt has been suggested that cysteinyl leukotrienes (cysLTs) play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC). The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM) thickening, in endobronchial biopsies in children.Methods29 children, aged 4–15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours.ResultsEBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range) 36.62 (22.60–101.05) versus 249.1 (74.21–526.36) pg/ml, p = 0.004). There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003).ConclusionEBC cysLTs appear to be associated with RBM thickening in asthma.

Highlights

  • It has been suggested that cysteinyl leukotrienes play an important role in airway remodeling

  • Structural changes of remodeling have been found in childhood [13] and recently it has been shown that reticular basement membrane (RBM) thickening, a characteristic feature of remodeling, is present in children with difficult asthma to a similar extent to that seen in adults with asthma [3]

  • There was no significant relationship between the inhaled steroid dose and RBM thickness (r = -0.25, p = 0.21) and there was no difference in RBM thickness whether patients received systemic steroids or not (p = 0.48)

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Summary

Introduction

It has been suggested that cysteinyl leukotrienes (cysLTs) play an important role in airway remodeling. The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM) thickening, in endobronchial biopsies in children. Structural changes of remodeling have been found in childhood [13] and recently it has been shown that reticular basement membrane (RBM) thickening, a characteristic feature of remodeling, is present in children with difficult asthma to a similar extent to that seen in adults with asthma [3]. Measurement of cysteinyl leukotrienes (cysLTs) in EBC could be one such potential non-invasive method of studying airway remodeling. CysLTs have been reported to play an important role in airway remodeling in asthma, with one study indicating that the cysLT1-receptor antagonist montelukast reduces airway smooth muscle cell hyperplasia and subepithelial fibrosis in ovalbumin-sensitised and -challenged mice [4]. CysLTs can be detected in EBC, with elevated levels reported in adults and children with asthma [5,6]

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