Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision. (26th May 2021)

• Record Type: Journal Article
• Authors: Walters, E. Haydn; Shukla, Shakti D.; Mahmood, Malik Q.; Ward, Chris
• Is Part Of: European respiratory review. Volume 30:Number 160(2021)
• Publication Date: 2021-05-26
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases; Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Electronic journals; Periodical; Periodicals; Periodicals; 616.2
• DOI: 10.1183/16000617.0364-2020
• Languages: English
• ISSNs: 0905-9180

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. We discuss the pathogenesis and pathophysiology of COPD, emphasising their need to be reassessed as a whole and integrated with traditional concepts to refine the disease paradigm. This is urgently needed to open-up thinking about therapeutic targets. https://bit.ly/3pTyrsi