Essential need for rethink of COPD airway pathology: implications for new drug approaches for prevention of lung cancer as well as small airway fibrosis
Sukhwinder Singh Sohal, Eugene Haydn Walters
School of Health Sciences, University of Tasmania, Launceston, TAS, Australia
We read with interest the recent comprehensive review by Sowmya P Lakshmi et al on potential new therapies for COPD in the International Journal of Chronic Obstructive Pulmonary Disease.1 The review says that only by understanding the core pathological processes, new therapeutics emerge, and it encourages that leading respiratory journals are recognizing this. However, we would suggest that, in this review, the overall view of the pathology of COPD airway disease does not reflect the current literature. In particular, the airway wall in at least mild to moderate COPD is hypo-cellular and hypo-vascular, with markedly active epithelial–mesenchymal transition (EMT)2 as part of epithelial activation and reprogramming.3 This process is closely related to small airway fibrosis and airflow obstruction. Inhaled corticosteroids (ICSs) affect these key epithelial cellular activation and vascular aspects of COPD,2 and more research on alternatives to corticosteroid on these aspects is urgently needed. It is of interest that the peroxisome proliferator-activated receptor system that the reviewers mention has implication for EMT induction,1 as has the TGF/Activin family and the Wnt system; these pathways are replete with potential drug targets.
Sowmya P Lakshmi,1,2 Aravind T Reddy,1,2 Raju C Reddy1,2
1Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, 2Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA
We thank Drs Sohal and Walters for their interest in our review entitled “Emerging pharmaceutical therapies for COPD”.1 In their Letter to the Editor, they called attention to the role of epithelial–mesenchymal transition (EMT) in COPD. Although our article covered the most recent literature regarding various aspects of COPD pathophysiology, it was by no means intended to be a comprehensive overview but instead focused on current and impending therapeutic advances.
View the original paper by Lakshimi and colleagues.
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Published Date: 4 December 2017
A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial–mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study
Sohal SS, Soltani A, Reid D, Ward C, Wills KE, Muller HK, Walters EH
Published Date: 27 May 2014