Multiple experimental systems examining the effect of mechanical forces on the respiratory epithelium in vitro are of interest; however, relevance in human disease is debatable without in vivo evidence. We have shown that the responses found in vitro are indeed mimicked by human airway responses. To investigate the effects of bronchoconstriction on airway responses, volunteers with mild allergic asthma who were only taking, as required, short-acting β-agonists as bronchodilator therapy were recruited and exposed to one of four repeated inhaled challenges: allergen (inducing both bronchoconstriction and eosinophilic inflammation), methacholine (inducing bronchoconstriction but no increase in eosinophilic inflammation), and two control conditions (saline inhalation and methacholine challenge preceded by inhaled albuterol to control for any direct chemical effect of methacholine). The allergen and methacholine groups were matched for an initial drop in FEV1.34 Bronchial biopsy specimens were obtained before and after the repeated challenges and the respiratory epithelium examined by immunohistochemistry.1 There was a similar degree of epithelial activation (increased TGF-β immunoexpression in the epithelium), airway metaplasia to a more mucus-producing phenotype (increased epithelial mucus staining, possibly as a result of EGFR activation), and airway remodeling (subepithelial collagen deposition) in the methacholine and allergen groups, with no increases in the saline and albuterol/methacholine groups. This finding suggests that bronchoconstriction induced both epithelial activation and airway remodeling. Other researchers have found similar results, where blocking bronchoconstriction with long-acting β-agonists (LABAs) prevents remodeling as measured by myofibroblast numbers following allergen challenge.35 Consequently, these findings suggest that (better adherence to) bronchodilator drugs may improve patient outcomes and help to prevent clinical manifestations related to remodeling, such as persistent airway narrowing, lung function decline, and corticosteroid resistance.