COPD: the role of neutrophils in inflammation, pathophysiology, and as drug targets

Neutrophils are innate immune effector cells that play a vital role in host defense against infection. They exert antimicrobial activities through degranulation, phagocytosis, intracellular killing, production of reactive oxygen species, and neutrophil extracellular traps. Dysregulation of neutrophil abundance, phenotype, and immune activity is a commonly observed inflammatory feature of chronic obstructive pulmonary disease (COPD), a chronic inflammatory disorder of the lungs with no effective cure. Here, we review the clinical association and involvement of neutrophils in COPD pathogenesis, progression, and exacerbation. The association between neutrophilia, airway microbial imbalance (dysbiosis), and clinical manifestations of COPD is described. We summarize the impact (or lack of) of current treatments, including inhaled corticosteroids, macrolide antibiotics, and phosphodiesterase inhibitors, on neutrophilic inflammation or neutrophilia-associated features. Finally, we review potential future therapeutic options to address neutrophilic inflammation in COPD currently in clinical development, including anti-alarmins and inhibitors of neutrophil mediators.