Faculty Bibliography

BACKGROUND:Bronchiectasis is a chronic respiratory condition involving a cycle of impaired mucociliary clearance, chronic infections, inflammation, and progressive airway destruction, leading to persistent cough with sputum production, dyspnea, and fatigue. Without appropriate management, patients can experience increased exacerbations, reduced quality of life, declining lung function, and increased mortality risk. Variability exists in clinical practice regarding treatment selection, highlighting the need for evidence-based guidance to optimize patient outcomes and standardize care delivery across health care settings. METHODS:An expert panel developed 8 population, intervention, comparator, and outcome (PICO)-based questions addressing treatment of bronchiectasis in adults and conducted a systematic review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the recommendations. RESULTS:Based on 47 studies, the panel developed 13 evidence-based recommendations addressing key management domains, including antibiotic treatment for acute exacerbations, duration and route of antibiotic therapy, long-term suppressive antibiotic and anti-inflammatory therapies, airway clearance strategies, management of hemoptysis and consideration of surgical resection in selected patients. CONCLUSION/CONCLUSIONS:All recommendations are conditional, primarily based on low-certainty evidence. Bronchiectasis research should aim to address many of the uncertainties in management, and priorities are identified within each PICO question. Accurate phenotyping and endotyping may help guide therapeutic decision-making and risk stratification. Treatment interventions must consider potential treatment burdens, including cost, and impact on quality of life. Finally, shared decision-making with patients utilizing a multidisciplinary approach is paramount.

RATIONALE/BACKGROUND:The discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps still remain about the interplay between neutrophilic signatures and microbes in non-tuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world. OBJECTIVES/OBJECTIVE:Evaluate the lower airway microbiota and neutrophilic traits in NTM- and NTM+ bronchiectasis. METHODS:16S rRNA gene sequencing, cell counts, and neutrophil extracellular trap (NET) immunoassays were performed on bronchoscopic lower airway samples in 200 bronchiectasis subjects (108 NTM-, 92 NTM+). A preclinical model of oral commensal micro-aspiration and NTM infection was used to profile the murine lower airways with flow cytometry and a NET assay. MEASUREMENTS AND MAIN RESULTS/RESULTS:Lower airways of NTM+ bronchiectasis patients were enriched with Mycobacterium and oral commensals (e.g., Veillonella, Prevotella and Streptococcus). NET levels were higher in NTM+ BAL. Mycobacterium and oral commensals co-occurred with NET and neutrophils in network studies. Distinct oral commensal taxa were associated with severe disease phenotypes such as cavitary disease and exacerbators. In a murine micro-aspiration model, the combination of oral commensals and Mycobacterium led to a sustained pro-inflammatory immune response marked by an increase in Th17, γδT cells, PD-1+ T lymphocytes as well as higher NET levels. CONCLUSIONS:Our analyses showed that distinct microbiome features beyond the primary pathogen can contribute to neutrophilic inflammation and severe disease phenotypes in bronchiectasis/ NTM-LD.

BACKGROUND AND OBJECTIVE/UNASSIGNED:Treatable traits in bronchiectasis have been classified as pulmonary, etiological, extra-pulmonary and behavioral or lifestyle factors. A range of non-pharmacological interventions may be applied to address these traits, with selected therapies applicable to multiple traits. The aim of this narrative review was to synthesize the evidence for non-pharmacological therapies through the lens of treatable traits for adults with bronchiectasis and highlight the clinical effects of these treatments. METHODS/UNASSIGNED:Electronic searches of PubMed and Medline using specific keywords were conducted. Articles underwent screening for relevance, with potential sources from review articles, systematic and scoping reviews, case series, prospective and retrospective studies, clinical practice guidelines and statements, and editorials in peer-reviewed journals. The data included were limited to English publications from 1980 to 2024. KEY CONTENT AND FINDINGS/UNASSIGNED:Of those traits which fall under the pulmonary and etiology categories, treatment options include airway clearance therapy, adjuncts to airway clearance such as mucoactive agents, smoking cessation programs, non-invasive ventilation and oxygen therapy, including high flow nasal therapy. Extra-pulmonary traits that are amenable to non-pharmacological approaches included psychological symptoms, nutritional concerns, gastroesophageal reflux disease, rhinosinusitis and cardiovascular disease. Treatment options span from cognitive behavioral therapy and counselling, nutritional advice and supplements, lifestyle adjustments and nasal-sinus irrigation. Key behavioral or lifestyle traits are low treatment adherence, smoking and lack of exercise. These are addressed via education and self-management programs, smoking cessation, pulmonary rehabilitation and other forms of exercise or physical activity. CONCLUSIONS/UNASSIGNED:A variety of non-pharmacological therapies may be applied to address treatable traits in those with bronchiectasis and adopting an integrated approach is important to optimize patient outcomes. Further studies could guide the implementation of non-pharmacological interventions for newly identified treatable traits in this population.