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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Respiratory Society
2021
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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. |
format | Online Article Text |
id | pubmed-9488955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | European Respiratory Society |
record_format | MEDLINE/PubMed |
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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