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

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Version 2 2024-06-05, 05:38
Version 1 2021-06-10, 19:16
journal contribution
posted on 2024-06-05, 05:38 authored by EH Walters, SD Shukla, Malik Quasir MahmoodMalik Quasir Mahmood, C Ward
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.

History

Journal

European Respiratory Review

Volume

30

Article number

ARTN 200364

Pagination

1 - 15

Location

England

Open access

  • Yes

ISSN

0905-9180

eISSN

1600-0617

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

160

Publisher

EUROPEAN RESPIRATORY SOC JOURNALS LTD