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Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision

Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into “mainstream” thinking along with traditional concepts which have st...

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Autores principales: Walters, E. Haydn, Shukla, Shakti D., Mahmood, Malik Q., Ward, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488955/
https://www.ncbi.nlm.nih.gov/pubmed/34039673
http://dx.doi.org/10.1183/16000617.0364-2020
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author Walters, E. Haydn
Shukla, Shakti D.
Mahmood, Malik Q.
Ward, Chris
author_facet Walters, E. Haydn
Shukla, Shakti D.
Mahmood, Malik Q.
Ward, Chris
author_sort Walters, E. Haydn
collection PubMed
description Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into “mainstream” thinking along with traditional concepts which have stood the test of time. Such a refining of the accepted disease paradigm is urgently needed as thinking on therapeutic targets is currently under active reconsideration. We feel that generalised airway wall “inflammation” is unduly over-emphasised, and highlight the patchy and variable nature of the pathology (with the core being airway remodelling). In addition, we present evidence for airway wall disease in smokers/COPD as including a hypocellular, hypovascular, destructive, fibrotic pathology, with a likely spectrum of epithelial–mesenchymal transition states as significant drivers of this remodelling. Furthermore, we present data from a number of research modalities and integrate this with the aetiology of lung cancer, the role of chronic airway luminal colonisation/infection by a specific group of “respiratory” bacteria in smokers (which results in luminal inflammation) and the central role for oxidative stress on the epithelium. We suggest translation of these insights into more focus on asymptomatic smokers and early COPD, with the potential for fresh preventive and therapeutic approaches.
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spelling pubmed-94889552022-11-14 Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision Walters, E. Haydn Shukla, Shakti D. Mahmood, Malik Q. Ward, Chris Eur Respir Rev Reviews Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into “mainstream” thinking along with traditional concepts which have stood the test of time. Such a refining of the accepted disease paradigm is urgently needed as thinking on therapeutic targets is currently under active reconsideration. We feel that generalised airway wall “inflammation” is unduly over-emphasised, and highlight the patchy and variable nature of the pathology (with the core being airway remodelling). In addition, we present evidence for airway wall disease in smokers/COPD as including a hypocellular, hypovascular, destructive, fibrotic pathology, with a likely spectrum of epithelial–mesenchymal transition states as significant drivers of this remodelling. Furthermore, we present data from a number of research modalities and integrate this with the aetiology of lung cancer, the role of chronic airway luminal colonisation/infection by a specific group of “respiratory” bacteria in smokers (which results in luminal inflammation) and the central role for oxidative stress on the epithelium. We suggest translation of these insights into more focus on asymptomatic smokers and early COPD, with the potential for fresh preventive and therapeutic approaches. European Respiratory Society 2021-05-26 /pmc/articles/PMC9488955/ /pubmed/34039673 http://dx.doi.org/10.1183/16000617.0364-2020 Text en Copyright ©The authors 2021 https://creativecommons.org/licenses/by-nc/4.0/This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org (mailto:permissions@ersnet.org)
spellingShingle Reviews
Walters, E. Haydn
Shukla, Shakti D.
Mahmood, Malik Q.
Ward, Chris
Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
title Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
title_full Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
title_fullStr Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
title_full_unstemmed Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
title_short Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
title_sort fully integrating pathophysiological insights in copd: an updated working disease model to broaden therapeutic vision
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488955/
https://www.ncbi.nlm.nih.gov/pubmed/34039673
http://dx.doi.org/10.1183/16000617.0364-2020
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