Abstract: Background: Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolled asthma in which the airway smooth muscle is eliminated using radio-ablation. While this emerging therapy shows promising outcomes, little is known about its effects on airway inflammation. We examined the concentration of pro-inflammatory airway cytokines and factors, and of smooth muscle actin abundance, in patients before and in the weeks after bronchial thermoplasty. Methods: Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthma were collected from the right lower lobe prior to, and 3 and 6 weeks post, initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage, and for the presence of alpha-smooth muscle actin in endobronchial biopsies. Results: Smooth muscle actin expression was decreased in endobronchial biopsies of 7 of 11 subjects by week 6. In bronchoalveolar lavage fluid, both TGFβ1 and RANTES/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty. Conclusion: Clinical improvement and reduction in smooth muscle actin after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway, and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.