Therapeutic Advances in Bronchiectasis

"Therapeutic Advances in Bronchiectasis: Prof Anne B Chang Queensland University of Technology; Department of Respiratory and Sleep Medicine, Queensland Children’s Hospital, Brisbane; and Menzies School of Health Research, Darwin, Australia Bronchiectasis is coming of age with the realisation of its burden of disease on patients and health systems, combined with increased research and pharmaceutical interest with fresh therapeutics. Early therapeutics focused on using antibiotics. While the first use of inhaled antibacterial solutions for bronchiectasis occurred in 1892[1], specific inhaled antibiotics usage was initially extrapolated from CF data in the 1990s until the first RCT that targeted adults with bronchiectasis.[2] Treatment of bronchiectasis has advanced markedly since the adoption of Cole’s paradigm,[3] which has now evolved into the contemporary vortex model. Using this framework, therapeutic advances include optimised airway clearance strategies, long-term macrolide therapy, inhaled and systemic antibiotics for selected patients, and improved treatment pathways for exacerbations and chronic infection, rehabilitation, muco-active agents (for a subset) as well as specific treatment for different phenotypes.[4] Both neutrophil dominant and eosinophil phenotypes have emerged as a leading therapeutic focus. These have culminated in the development of a therapeutic pipeline of dipeptidyl peptidase 1 (DPP 1) inhibitors including brensocatib, verducatib and HSK31858. Together, these interventions have reduced exacerbation frequency and improved quality of life in appropriately selected patients, and DPP 1 has a disease-modifying effect. In parallel, greater attention is being given to nutrition, vaccination, comorbidities, and adherence to self-management plans, all of which contribute to treatment effectiveness. With respect to antibiotics, several pharmaceutical companies undertook large multicenter RCTs (e.g. AIR-BX, RESPIRE, ORBIT). Despite demonstrating reductions in airway bacterial load, these trials yielded mixed results for their primary clinical endpoints (mostly exacerbations).[5] While possible explanation for the variance include the heterogeneity in microbiome baseline status and geography[5], the latest systematic review (20 RCTs) generally favoured inhaled antibiotics (vs placebo) with reduced exacerbation frequency (RR=0.78, 95%CI 0.68, 0.91) and improved and QoL-Bronchiectasis respiratory symptom score (mean difference=2.51, 95%CI 0.44-4.31).[6] Bronchiectasis management has thus evolved from symptom control toward a more targeted approach. Emerging strategies are increasingly focused on precision medicine, including better risk stratification, biomarker development, and use of imaging and microbiologic data to guide therapy. Overall, therapeutic progress in bronchiectasis reflects a shift toward earlier intervention, prevention of exacerbations, and more personalized care. Despite these advances, important gaps remain in pediatric bronchiectasis, where high-quality evidence is still limited and most treatment decisions are extrapolated from adult data. References 1 Osler W. The principles and practice of medicine: designed for the use of practitioners and students of medicine. New York: D. Appleton and Company, 1892. 2 Barker AF, Couch L, Fiel SB, et al. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 2000; 162: 481-485. 3 Cole PJ. Inflammation: a two edged sword. The model of bronchiectasis. Eur J Respir Dis Suppl 1986; 147: 6-15. 4 Tramontano A, Caporaso M, Macciocchi G, et al. New Perspectives in the Treatment of Bronchiectasis. Arch Bronconeumol 2026; Jan 9:S0300-2896(26)00004-9. 5 Mac Aogain M. Beyond ORBIT: Mapping the Constellation of Pseudomonas Endotypes in Bronchiectasis Clinical Trials. Am J Respir Crit Care Med 2025; 211: 1321-1323. 6 Cordeiro R, Choi H, Haworth CS, et al. The Efficacy and Safety of Inhaled Antibiotics for the Treatment of Bronchiectasis in Adults: Updated Systematic Review and Meta-Analysis. Chest 2024; 166: 61-80. "