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Fully integrating pathophysiological insights in copd: An updated working disease model to broaden therapeutic vision

Citation

Walters, EH and Shukla, SD and Mahmood, MQ and Ward, C, Fully integrating pathophysiological insights in copd: An updated working disease model to broaden therapeutic vision, European Respiratory Review, 30, (160) pp. 1-15. ISSN 0905-9180 (2021) [Refereed Article]


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Copyright The authors 2021 This version is distributed under the terms of the Creative Commons Attribution NonCommercial Licence 4.0.

DOI: doi:10.1183/16000617.0364-2020

Abstract

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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Respiratory diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Walters, EH (Professor Haydn Walters)
ID Code:146817
Year Published:2021
Web of Science® Times Cited:1
Deposited By:Medicine
Deposited On:2021-09-28
Last Modified:2021-11-23
Downloads:0

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