Targeting Type 2 Inflammation and Epithelial Alarmins in Chronic Obstructive Pulmonary Disease: A Biologics Outlook

Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous, progressive inflammatory airway disease associated with significant impact on patients’ lives, including morbidity and mortality, and significant health-care related costs. Current pharmacologic strategies, including first- and second-line therapies such as long-acting β2-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, phosphodiesterase 4 inhibitors, and macrolides, provide relief in patients with COPD. However, many patients remain symptomatic, with persistent symptoms and/or acute exacerbations, and progressive lung function loss. While neutrophilic inflammation is the most common type of inflammation in COPD, 20–40% of patients with COPD exhibit type 2 inflammation, with roles for CD4+ T helper type 2 cells, type 2 innate lymphoid cells, eosinophils, and alternatively activated macrophages. Based on the current limitations of available therapies, significant unmet need exists in COPD management, including the need for targeted therapies to address the underlying pathophysiology leading to disease progression, such as type 2 inflammation, as well as biomarkers to help select patients that would most benefit from the new therapies. Significant progress is being made, with our evolving understanding of the pathobiology of COPD leading to novel therapeutic targets including epithelial alarmins. In this review we describe the current therapeutic landscape in COPD, discuss unmet treatment needs, review the current knowledge of type 2 inflammation and epithelial alarmins in COPD, explore potential biomarkers of type 2 inflammation in COPD, and finally provide a rationale for incorporating therapies targeting type 2 inflammation and epithelial alarmins in COPD.