Anne Chang

"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. "

"Bronchiectasis exacerbations remain a significant cause of morbidity in children, associated with increased symptom burden, reduced quality of life, and recurrent health care utilisation and future lung function deterioration. Growing evidence indicates that exacerbation risk is shaped by a combination of clinical, microbiological, and radiological factors rather than by a single determinant. Previous exacerbation frequency, prior hospitalisation, younger age at presentation, chronic bacterial infection, and more extensive structural lung disease have all been associated with a higher likelihood of subsequent events. Although prediction is still imprecise at the individual level, these features may help define a higher-risk phenotype that can support closer surveillance and earlier intervention. Our recent work showed that the ‘daily wet-cough dominant’ and ‘Wheeze Dyspnoea’ phenotypes were associated with increased risk of hospitalisations post-recruitment. We have also identified six neutrophil-associated genes were associated with a future exacerbation, suggesting that peripheral blood gene expression may help identify children at risk of exacerbations. Prevention strategies are more established and include regular airway clearance, prompt treatment of wet cough episodes, vaccination, nutritional support, and individualized action plans. In selected children, long-term macrolide therapy may reduce exacerbation frequency, while careful follow-up and early intervention can limit progression. Overall, the current evidence supports a risk-stratified approach that combines clinical assessment with proactive management. We need future research that use validated paediatric prediction tools that integrate clinical, microbiologic, and imaging data to better guide prevention and treatment. "

"Long Term prognosis of Chronic Suppurative Lung Disease Prof Dr Anna Marie Nathan Non-CF Bronchiectasis (NCFBE) and CSLD are the leading causes of BE in Asia. Recent interest has moved NCFBE out of the “orphan” disease category. Paediatric bronchiectasis is reversible with timely diagnosis and effective treatment (1). However, data on the ideal management of NCFBE remain limited, with a limited armamentarium of treatment options, especially in children, where randomised trials are severely lacking 1. We have published data on children with CSLD/BE 2. Seventy-eight per cent of children who performed spirometry had values <80% of the normal predicted value. Anthropometric measurements in children with NCFBE were static despite treatment. PC-QOL scores were low 2. A study from Thailand found that pulmonary exacerbation occurred in 80% of children, with a higher rate in non-infectious bronchiectasis than postinfectious bronchiectasis (90.9% vs 61.5%, p = 0.036). Hospitalisation was required for 77.1% of children, with a higher rate of non-infectious bronchiectasis than postinfectious bronchiectasis (86.3% vs 53.8%, p = 0.033) 3. Seventy-seven per cent of interviewed parents had abnormal DASS21 scores, with 54% being stressed and 51% being depressed. Parents of children diagnosed with CF had significantly lower DASS21 scores, hence indicating better mental health scores compared to non-CF CSLD 2. The presence of Pseudomonas aeruginosa (Pa) in the airways of patients with non-CF bronchiectasis has been associated with accelerated lung function decline and increased morbidity and mortality. Guidelines suggest inhaled antibiotics to promote eradication 1(1). We have found that eradication is associated with improved quality-of-life outcomes, with significant improvements in PC-QoL scores and cough scores after 3 months of treatment observed in patients who received both systemic and inhaled antibiotics (P = 0.002 and P = 0.003, respectively), but not in patients who received inhaled antibiotics alone (P = 0.09 and P = 0.89, respectively 4. In a study examining long-term outcomes of childhood bronchiectasis, young adults with bronchiectasis rarely attended adult respiratory clinics despite being symptomatic and having multiple emergency doctor visits5. This reflects inefficient transition programmes for our patients, which will translate to very poor adult outcomes. References 1.Chang, A. B., Fortescue, R., Grimwood, K., Alexopoulou, E., Bell, L., Boyd, J., Bush, A., Chalmers, J. D., Hill, A. T., Karadag, B., Midulla, F., McCallum, G. B., Powell, Z., Snijders, D., Song, W. J., Tonia, T., Wilson, C., Zacharasiewicz, A., & Kantar, A. (2021). European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis. The European respiratory journal, 58(2), 2002990. https://doi.org/10.1183/13993003.02990-2020 2. Nathan, A. M., Muthusamy, A., Thavagnanam, S., Hashim, A., & de Bruyne, J. (2014). Chronic suppurative lung disease in a developing country: impact on child and parent. Pediatric pulmonology, 49(5), 435–440. https://doi.org/10.1002/ppul.23001 3.Sitthikarnkha P, Anekvorakul A, Niamsanit S, Techasatian L, Saengnipanthkul S, Uppala R. Clinical characteristics and outcome of non-cystic fibrosis bronchiectasis in children: A tertiary care perspective. SAGE Open Med. 2025 Feb 19;13:20503121251320849. doi: 10.1177/20503121251320849. PMID: 39980590; PMCID: PMC11840848 4. Goh WT, Hng SY, Azanan MS, Eg KP, Adam Q, Lee QY, et al. Utility of inhaled antibiotics in children with exacerbations of non-cystic fibrosis bronchiectasis: A pilot study. Pediatr Respirol Crit Care Med 2026;XX:XX-XX. 5. Sibanda D, Singleton R, Clark J, Desnoyers C, Hodges E, Day G, et al. Adult outcomes of childhood bronchiectasis. Int J Circumpolar Health 2020;79:1731059 "

Protracted bacterial bronchitis (PBB) is a common cause of chronic wet cough in children and an important contributor to respiratory morbidity. Increasing evidence suggests that PBB and bronchiectasis are not distinct disease entities but instead represent different stages along a spectrum. PBB and bronchiectasis share many clinical, microbiological and immunological features. Furthermore, persistent bacterial infection, neutrophilic airway inflammation and immune responses provide mechanistic links between PBB and bronchiectasis. Longitudinal follow-up studies have also demonstrated that recurrent PBB and persistent lower airway infection are associated with an increased risk of developing bronchiectasis, highlighting the importance of early recognition and effective management. Integrating advances in basic, translational, and clinical research, will improve the understanding of the PBB-bronchiectasis continuum. Identifying children at risk of developing bronchiectasis will allow targeted, implementable interventions to prevent irreversible lung disease and improve respiratory outcomes.