The Emerging Role of Alarmin-Targeting Biologics in the Treatment of Patients With COPD

Topic Importance: COPD is a complex, heterogeneous lung disease characterized by persistent airflow limitation secondary to airways and parenchymal abnormalities, and respiratory symptoms, including dyspnea, fatigue, chronic cough, and sputum production. Cigarette smoke exposure is a major contributor to COPD; however, inhalation of toxic particles and other environmental and host factors can contribute to its genesis. Over time, the clinical course is frequently punctuated by exacerbations that further accelerate lung function decline and increase exacerbation risk. Despite current optimal therapy, many patients remain symptomatic, have exacerbations, and have increased morbidity, mortality, and health care costs. This review focuses on current knowledge of COPD pathophysiology, the role of inflammatory mechanisms, and the potential use of biologics to modulate these mechanisms. Review Findings: The inflammatory response in COPD includes both type 1 and type 2 immune cells. Type 2 inflammation is suggested by eosinophilia in a significant proportion of patients with COPD. Studies targeting IL-5 in patients with COPD have failed to demonstrate significant reductions in exacerbations, suggesting that eosinophil modulation alone may be insufficient to treat COPD. Based on a better understanding of the disease and role of alarmins, with a broader role in the inflammatory cascade, it is likely that some biologics may benefit certain COPD endotypes. Ongoing trials will provide information about which groups can benefit from the blocking of specific pathways (eg, IL-5, IL-4/IL-13, IL-33, thymic stromal lymphopoietin). Biologics targeting inflammatory pathways may be effective treatments for specific patients with COPD.