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In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss.

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posted on 01.06.2018, 09:06 by Igor L. Chernyavsky, Richard J. Russell, Ruth M. Saunders, Gavin E. Morris, Rachid Berair, Amisha Singapuri, Latifa Chachi, Adel H. Mansur, Peter H. Howarth, Patrick Dennison, Rekha Chaudhuri, Stephen Bicknell, Felicity R. A. J. Rose, Salman Siddiqui, Bindi S. Brook, Christopher E. Brightling
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°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°C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60°C in airways with an inner radius of ∼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.

Funding

The work was part supported by AirPROM 7th EU Framework grant 270194 (all authors), Medical Research Council (MRC) grant MR/N011538/1 (I.L. Chernyavsky), MRC grant MR/M004643/1 (B.S. Brook), Wellcome Trust Senior Fellowship WT082265 (C.E. Brightling) and by National Institute for Health (NIHR) Leicester Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Funding information for this article has been deposited with the Crossref Funder Registry.

History

Citation

European Respiratory Journal, 2018, 51:1701680

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

AM (Accepted Manuscript)

Published in

European Respiratory Journal

Publisher

European Respiratory Society: ERJ

issn

0903-1936

eissn

1399-3003

Acceptance date

29/03/2018

Copyright date

2018

Publisher version

http://erj.ersjournals.com/content/51/5/1701680

Notes

The file associated with this record is under embargo until 18 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.;This article has supplementary material available from erj.ersjournals.com.

Language

en

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