Biological Therapies in Chronic Obstructive Pulmonary Disease: New Directions in Personalised Respiratory Medicine.

Abstract

Chronic obstructive pulmonary disease (COPD), a leading cause of global morbidity and mortality, is a complex and heterogeneous respiratory condition characterised by incompletely reversible airflow obstruction on spirometry. The aetiologies and pathological patterns of COPD are varied, which has long been viewed as a hindrance to targeted treatment. Yet inflammation is central to the diverse mechanisms of COPD pathogenesis, and type 2 inflammation has emerged as a measurable, modifiable and clinically meaningful therapeutic target in those patients in whom it is identified. The approval of first biological therapy against type 2 inflammation in COPD builds on our understanding of immunological mechanisms in airways diseases, is informed by a decade of randomised trials and makes possible a fundamental shift in our approach to this common condition. This review will (1) assess aspects of pathological inflammation in COPD, namely type 1, 2 and 3 inflammation, and the role of epithelial alarmins; (2) examine data from randomised trials on the efficacy and safety of monoclonal antibodies against inflammatory mediators in COPD; and (3) discuss future directions for biological therapies in COPD, including new patient populations, new agents and new approaches that focus on high-risk disease and open the door to prevention.