Journal club

Neutrophilic inflammation is a key driver of bronchiectasis progression and exacerbations. Brensocatib, an oral inhibitor of dipeptidyl peptidase 1 (DPP1), prevents activation of neutrophil serine proteases. The phase III randomised double-blind ASPEN trial (N Engl J Med 2025;392:1569–1581) evaluated the efficacy and safety of once-daily brensocatib at 10 mg or 25 mg compared with placebo over 52 weeks in 1721 patients with non-cystic fibrosis bronchiectasis across 35 countries. The annualised rate of adjudicated pulmonary exacerbations was significantly reduced with brensocatib. Patients receiving 10 mg and 25 mg experienced 1.02 and 1.04 exacerbations per year respectively, compared with 1.29 in the placebo group. This corresponded to rate ratios of 0.79 (95% CI, 0.68 to 0.92; p=0.004) and 0.81 (95%CI, 0.69 to 0.94; p=0.005). Time to first exacerbation was delayed with both doses, and nearly half of brensocatib-treated patients remained exacerbation-free at 1 year compared with 40.3% in the placebo group. Lung function decline was smallest in the 25 mg group, with an average decline of 24 milliliters compared with 62 milliliters with placebo (p=0.04). Quality of life, as measured by the Respiratory Symptoms domain of the Quality of Life–Bronchiectasis questionnaire, improved more with brensocatib, especially at the higher dose. The incidence of adverse events was …