Airway TGF-β1 and oxidant stress in children with severe asthma: Association with airflow limitation

Background: TGF-beta 1 is thought to play a role in airway remodeling in asthmatic subjects. TGF-beta 1 expression might be mediated by an excessive burden of reactive oxygen species and oxidant stress. Objective: Given the profound airway oxidant stress we have previously observed in children with severe asthma, we sought to (1) quantify TGF-beta 1 protein and mRNA gene expression in the airways of children with mild-to-moderate and severe atopic asthma and (2) determine the relationship of airway TGF-beta 1 concentrations to oxidant burden (ie, lipid peroxidation), T(H)2-mediated eosinophilic inflammation, and airflow limitation. Methods: Bronchoalveolar lavage fluid was collected from 68 atopic children with asthma (severe asthma, n = 28) and 12 atopic adult control subjects. Airway TGF-beta 1 expression and activation were assessed in relation to airway IL-13, 8-isoprostane, and malondialdehyde concentrations. The relationship of airway TGF-beta 1 expression to airflow limitation in children with asthma was also assessed. Results: Children with severe asthma had higher total airway concentrations of TGF-beta 1 that were associated with increased protein and mRNA expression of TGF-beta 1 in airway macrophages and an increase in concentrations of the lipid peroxidation biomarkers 8-isoprostanes and malondialdehyde. TGF-beta 1 activation was also greater in children with severe asthma and was associated with higher airway 8-isoprostane, malondialdehyde, and IL-13 concentrations. Total airway TGF-beta 1 concentrations were further associated with airflow limitation. Conclusions: Children with severe asthma have increased airway TGF-beta 1 expression and activation associated with an increased airway oxidant burden. Oxidant stress might mediate the effects of TGF-beta 1 and promote airway remodeling in children with severe asthma. (J Allergy Clin Immunol 2012;129:388-96.)