TY - JOUR T1 - <em>In vitro</em>, <em>in silico</em> and <em>in vivo</em> study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01680-2017 SP - 1701680 AU - Igor L. Chernyavsky AU - Richard J. Russell AU - Ruth M. Saunders AU - Gavin E. Morris AU - Rachid Berair AU - Amisha Singapuri AU - Latifa Chachi AU - Adel H. Mansur AU - Peter H. Howarth AU - Paddy Dennison AU - Rekha Chaudhuri AU - Stephen Bicknell AU - Felicity R.A.J. Rose AU - Salman Siddiqui AU - Bindi S. Brook AU - Christopher E. Brightling Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/04/12/13993003.01680-2017.abstract N2 - Bronchial thermoplasty is a treatment for asthma. Whether during thermoplasty the airway wall fraction exposed to temperatures necessary to affect cells is sufficient to explain its histopathological impact is unclear.Airway smooth muscle and bronchial epithelial cells were exposed to media (37–70°C) for 10 seconds to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution following thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 severe asthmatics.In vitro airway smooth muscle and epithelial cell number decreased significantly following addition of media heated to ≥65°C. In silico simulations showed heterogeneous heat distribution; amplified in larger airways, with &lt;10% of the airway wall heated &gt;60°C for airways with an inner radius ∼4 mm. In vivo 6 weeks post-thermoplasty asthma control (ACQ6) improved (mean difference: 0.7 [95%-CI 0.1–1.3]; p=0.03), airway smooth muscle mass decreased (absolute median reduction: 5 [IQR 0–10]%; p=0.03) and epithelial integrity increased (14 [6–29]%; p=0.007); neither of which were related to improved asthma control.Integrated in vitro and in silico modelling suggested that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating; nor did this reduction confer a greater improvement in asthma control.This study shows unexpected possible mechanisms of action in bronchial thermoplasty treatment for asthmaFootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: L. ChernyavskyConflict of interest: Dr. Russell has nothing to disclose.Conflict of interest: Dr. Saunders reports grants from 7th EU Framework, grants from Wellcome Trust, grants from NIHR, during the conduct of the study.Conflict of interest: Dr. Morris has nothing to disclose.Conflict of interest: Dr. Berair has nothing to disclose.Conflict of interest: Miss Singapuri has nothing to disclose.Conflict of interest: Dr. Chachi has nothing to disclose.Conflict of interest: Dr. Mansur reports grants from Astrazeneca pharmaceuticals, personal fees from Novartis, GSK, AZ, NAPP, BI others, outside the submitted work; .Conflict of interest: Dr. Howarth reports grants from European Union, during the conduct of the study; .Conflict of interest: Paddy DennisonConflict of interest: Dr. Chaudhuri reports being an Advisory Board member for GSK, AstraZeneca, Teva and Novartis and receiving educational grants for her institute from Novartis; receiving fees for speaking at meetings organised by GSK, AstraZeneca, Chiesi and attending international conferences sponsored by Novartis, Teva, AstraZeneca, Boehringer-Ingelheim.Conflict of interest: Dr. Bicknell has nothing to disclose.Conflict of interest: Dr. Rose has nothing to disclose.Conflict of interest: Professor. Siddiqui reports personal fees from Astra Zeneca, personal fees from Boehringer Ingelheim, personal fees from Owlstone Nanotech Ltd, personal fees from Novartis, grants from NAPP pharmaceuticals, personal fees from Mundipharma, from the European Respiratory Society, outside the submitted work.Conflict of interest: Dr. Brook has nothing to disclose.Conflict of interest: CEB has received paid to his Institution grants and Consultancy from GSK, Novartis, Chiesi, MedImmune/AZ, BI, MSD, Prep, Vectura, TEVA, Sanofi, Regeneron, Roche/Genentech ER -