Respiratory specialists have made the case for considering COPD as an immune-mediated inflammatory disease,  a theory that they say potentially opens the door to targeting specific disease pathways.

According to the expert group, which included UK-based respiratory consultants Dr Richard Russel and Professor Mona Bafadhel, while current COPD treatment strategies focus on improving symptoms with bronchodilators and inhaled corticosteroids, there is an opportunity to improve outcomes by targeting disease pathogenesis.

“Given the shared immunopathogenesis of COPD with immune-mediated inflammatory diseases, there is an opportunity now to stratify patients with COPD on the basis of immunophenotypes in addition to airflow limitation”.

This, they said, could help to identify specific patient immune clusters for biological therapies in ways that have been successful for the conventional immune-mediated inflammatory diseases.

“Similar approaches in severe asthma, by focusing on eosinophils, have resulted in anti-IL-5, antiIL-5 receptor, and dual anti-IL-4 and IL-13 (also used in atopic dermatitis) therapies,” they noted, in an article published in The Lancet Respiratory Medicine.

While the pathogenesis of COPD is not yet fully understood, inhalation of noxious inhaled particles that chronically activate epithelial cells and macrophages has been suggested as a potential disease trigger. And although the role of eosinophils in the immunopathogenesis of COPD remains unclear, “there is a strong association between eosinophils, exacerbation risk, and treatment response”, thy wrote.

Deviant adaptive immune responses also play a role in COPD progression, the authors said. “For example, an expansion of CD8 T cells is observed and proposed to be important in tissue remodelling processes. In addition, both the total number of circulating B cells and the proportion of small airways containing B cell-rich lymphoid follicles are increased with disease severity.

“This immune signature reflects persistent adaptive immune responses, a finding that is also associated with emphysema and a hallmark of multiple conventional immune-mediated inflammatory diseases.

“Together, this chronic inflammatory environment mediates a persistent release of proteases, contributing to airway destruction and the release of growth factors that contribute to mucus hypersecretion, underpinning COPD pathology”.

The authors also noted that studies on immune-mediated inflammatory diseases have shown the importance of accumulation of myeloid cells and raised cytokine concentrations – which are also observed in COPD – in triggering activation of various immune cell lineages.

Also, pulmonary manifestations of inflammatory disease have been reported for rheumatoid arthritis, spondyloarthritis, and inflammatory bowel disease, “demonstrating that similar dysregulated immune processes are capable of secondary or comorbid conditions”.

“These shared immune processes suggest that, based on immunopathological grounds alone, COPD should be added to the growing list of immune-mediated inflammatory diseases”, they argued.

As such, the authors propose that inflammation is an “essential component driving disease progression” across the five COPD types recently suggested by the 2022 Lancet Commission on COPD (genetic, early-life events, infection, smoking, and environment exposure), and “consequently should be considered in all disease stratification”.