Elevating COPD Management: Enhancing Treatment and Improving Patient Outcomes - Episode 7
The Role of Type 2 Inflammation of COPD
Panelists discuss the emerging recognition of type 2 inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD) , highlighting differences from asthma in eosinophil thresholds and therapeutic responses, the roles of key cytokines IL-4, IL-13, and IL-5 in driving airway inflammation and remodeling, and the promise and challenges of targeting these pathways with biologics to improve outcomes while emphasizing the need for further research to understand the distinct inflammatory mechanisms in COPD.
Type 2 inflammation, traditionally associated with asthma, is now recognized as playing a role in a subset of patients with COPD. While it was once thought to have little relevance to COPD, emerging evidence shows that elevated eosinophil levels serve as a biomarker for type 2 inflammation in these patients. However, the nature of type 2 inflammation in COPD may not be identical to that in asthma. For example, eosinophil thresholds used to define this inflammation are generally higher in COPD, and the clinical response to therapies targeting type 2 pathways can differ. Moreover, blood eosinophil levels may not fully reflect airway inflammation, highlighting the need to consider the overall clinical context and track eosinophil trends over time.
The cytokines IL-4, IL-13, and IL-5 play central roles in type 2 inflammation. IL-4 and IL-13 are involved in several processes such as promoting immunoglobulin E production, mucus secretion, airway remodeling, and eosinophil recruitment, contributing to fibrosis and goblet cell hyperplasia that impair lung function. IL-5 primarily regulates eosinophil growth, survival, and activation in the airway but may also have effects on tissue remodeling. These cytokines act downstream in the inflammatory cascade and orchestrate the immune response typical of type 2 inflammation. Blocking these pathways with targeted biologics offers a promising therapeutic approach. Currently, therapies like dupilumab target the shared receptor for IL-4 and IL-13, while drugs such as mepolizumab and benralizumab focus on IL-5 or its receptor, with ongoing studies exploring their efficacy in COPD.
Unlike asthma, where allergens are the main trigger of type 2 inflammation, COPD involves a more complex interplay of factors. In addition to adaptive immune responses, innate immune cells such as type 2 innate lymphoid cells contribute to inflammation in COPD, potentially triggered by viruses, pollutants, and cigarette smoke. Most patients with COPD have neutrophilic inflammation characteristic of type 1 and type 3 pathways, but a significant subset displays type 2 signatures. While blocking these cytokines may reduce eosinophilic inflammation and improve outcomes, further research is needed to clarify how type 2 inflammation in COPD differs functionally from asthma and to optimize treatment strategies accordingly.
