Targeting neutrophilic inflammation in COPD: rethinking, refining and reprogramming

Extract Despite recent advances in type 2 (T2)-targeted biologics, which have been shown to reduce exacerbations and improve lung function in COPD patients with evidence of T2 inflammation, the majority of COPD patients exhibit a neutrophil predominant pattern of airway inflammation. Neutrophilic inflammation is associated with more frequent exacerbations [1], more rapid lung function decline [2] and alveolar destruction. Consequently, there remains a large unmet need for effective treatments targeting non-T2 inflammation in COPD. Myeloperoxidase (MPO), an abundant neutrophil granule protein, plays an essential role in the destruction of pathogens following engulfment by neutrophils, synergising with additional killing mechanisms, including proteolytic enzymes contained within neutrophil granules. However, release of MPO during neutrophil degranulation, neutrophil extracellular trap (NET)-osis or cell death leads to lung tissue damage. Consequently, MPO has emerged as a promising candidate target for this neutrophilic phenotype, supported by encouraging pre-clinical data [3].