PMID- 29700102 OWN - NLM STAT- MEDLINE DCOM- 20190521 LR - 20220517 IS - 1399-3003 (Electronic) IS - 0903-1936 (Print) IS - 0903-1936 (Linking) VI - 51 IP - 5 DP - 2018 May TI - In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss. LID - 10.1183/13993003.01680-2017 [doi] LID - 1701680 AB - Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival.Airway smooth muscle and bronchial epithelial cells were exposed to media (37-70 degrees C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma.In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to >/=65 degrees C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60 degrees C in airways with an inner radius of approximately 4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1-1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0-10; p=0.03) and epithelial integrity increased (14%, IQR 6-29; p=0.007). Neither of the latter two outcomes was related to improved asthma control.Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control. CI - Copyright (c)ERS 2018. FAU - Chernyavsky, Igor L AU - Chernyavsky IL AUID- ORCID: 0000-0003-0284-9318 AD - School of Mathematics, University of Manchester, Manchester, UK. AD - These authors contributed equally to the study. FAU - Russell, Richard J AU - Russell RJ AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. AD - These authors contributed equally to the study. FAU - Saunders, Ruth M AU - Saunders RM AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. AD - These authors contributed equally to the study. FAU - Morris, Gavin E AU - Morris GE AD - Dept of Cardiovascular Sciences, University of Leicester, Leicester, UK. FAU - Berair, Rachid AU - Berair R AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. FAU - Singapuri, Amisha AU - Singapuri A AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. FAU - Chachi, Latifa AU - Chachi L AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. FAU - Mansur, Adel H AU - Mansur AH AD - Heart of England NHS Trust, Birmingham, UK. FAU - Howarth, Peter H AU - Howarth PH AD - Clinical and Experimental Sciences, University of Southampton, Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Trust, Southampton, UK. FAU - Dennison, Patrick AU - Dennison P AD - Clinical and Experimental Sciences, University of Southampton, Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Trust, Southampton, UK. FAU - Chaudhuri, Rekha AU - Chaudhuri R AD - Gartnavel General Hospital, Glasgow, UK. AD - Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. FAU - Bicknell, Stephen AU - Bicknell S AD - Gartnavel General Hospital, Glasgow, UK. FAU - Rose, Felicity R A J AU - Rose FRAJ AD - Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK. FAU - Siddiqui, Salman AU - Siddiqui S AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. FAU - Brook, Bindi S AU - Brook BS AD - School of Mathematical Sciences, University of Nottingham, Nottingham, UK. AD - Co-senior authors. FAU - Brightling, Christopher E AU - Brightling CE AD - Dept of Infection, Immunity and Inflammation, Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. AD - Co-senior authors. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - MR/M004643/1/MRC_/Medical Research Council/United Kingdom GR - MR/N011538/1/MRC_/Medical Research Council/United Kingdom GR - WT082265/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180524 PL - England TA - Eur Respir J JT - The European respiratory journal JID - 8803460 SB - IM MH - Adult MH - Aged MH - Airway Remodeling MH - Apoptosis MH - Asthma/*therapy MH - Bronchial Thermoplasty/adverse effects/*methods MH - Bronchoscopy MH - Computer Simulation MH - Epithelial Cells/*metabolism MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Models, Biological MH - Muscle, Smooth/*pathology PMC - PMC6003767 COIS- Conflict of interest: R.M. Saunders reports grants from 7th EU Framework, Wellcome Trust and National Institute for Health Research, during the conduct of the study. Conflict of interest: A.H. Mansur has received an educational grant for service support from AstraZeneca Pharmaceuticals, and received fees for talks and advisory group contribution and conference attendance from Novartis, GlaxoSmithKline, AstraZeneca, Napp Pharmaceuticals, Boehringer Ingelheim and others, outside the submitted work. Conflict of interest: P.H. Howarth reports grants from the European Union (AirPROM collaborative grant), during the conduct of the study. Conflict of interest: R. Chaudhuri reports being an advisory board member for GlaxoSmithKline, AstraZeneca, Teva Pharmaceutical Industries and Novartis and receiving educational grants for her institute from Novartis; receiving fees for speaking at meetings organised by GlaxoSmithKline, AstraZeneca, Chiesi and for attending international conferences sponsored by Novartis, Teva Pharmaceutical Industries, AstraZeneca and Boehringer Ingelheim. Conflict of interest: S. Siddiqui reports personal fees for advisory board participation from AstraZeneca and Boehringer Ingelheim, personal fees for advisory/consulting from Owlstone Nanotech and Mundipharma, speaker fees from Novartis, grants for imaging research in asthma from Napp Pharmaceuticals, and speaker fees from the European Respiratory Society, outside the submitted work. Conflict of interest: C.E. Brightling has received, paid to his institution, grants and consultancy fees from GlaxoSmithKline, Novartis, Chiesi, MedImmune/AstraZeneca, Boehringer Ingelheim, MSD Pharmaceuticals, PrEP Biopharm, Vectura, Teva Pharmaceutical Industries, Sanofi, Regeneron and Roche/Genentech. Conflict of interest: I.L. Chernyavsky reports research fellowship support from the European Commission (FP7 AirPROM) and a grant from Medical Research Council UK (New Investigator Research Grant), during the conduct of the study. EDAT- 2018/04/28 06:00 MHDA- 2019/05/22 06:00 PMCR- 2018/06/15 CRDT- 2018/04/28 06:00 PHST- 2017/08/17 00:00 [received] PHST- 2018/03/29 00:00 [accepted] PHST- 2018/04/28 06:00 [pubmed] PHST- 2019/05/22 06:00 [medline] PHST- 2018/04/28 06:00 [entrez] PHST- 2018/06/15 00:00 [pmc-release] AID - 13993003.01680-2017 [pii] AID - ERJ-01680-2017 [pii] AID - 10.1183/13993003.01680-2017 [doi] PST - epublish SO - Eur Respir J. 2018 May 24;51(5):1701680. doi: 10.1183/13993003.01680-2017. Print 2018 May.