Biomarkers in bronchiectasis.

Bronchiectasis is a heterogeneous disease with multiple aetiologies and diverse clinical features. There is a general consensus that optimal treatment requires precision medicine approaches focused on specific treatable disease characteristics, known as treatable traits. Identifying subtypes of conditions with distinct underlying biology (endotypes) depends on the identification of biomarkers that are associated with disease features, prognosis or treatment response and which can be applied in clinical practice. Bronchiectasis is a disease characterised by inflammation, infection, structural lung damage and impaired mucociliary clearance. Increasingly there are available methods to measure each of these components of the disease, revealing heterogeneous inflammatory profiles, microbiota, radiology and mucus and epithelial biology in patients with bronchiectasis. Using emerging biomarkers and omics technologies to guide treatment in bronchiectasis is a promising field of research. Here we review the most recent data on biomarkers in bronchiectasis.

Growing from common ground: nontuberculous mycobacteria and bronchiectasis.

Bronchiectasis and nontuberculous mycobacteria (NTM) are intricately intertwined, with NTM capable of being both a cause and consequence of bronchiectatic disease. This narrative review focuses on the common ground of bronchiectasis and NTM pulmonary disease (NTM-PD) in terms of diagnostic approach, underlying risk factors and treatment strategies. NTM-PD diagnosis relies on a combination of clinical, radiological and microbiological criteria. Although their epidemiology is complicated by detection and reporting biases, the prevalence and pathogenicity of NTM species vary geographically, with Mycobacterium avium complex and Mycobacterium abscessus subspecies most frequently isolated in bronchiectasis-associated NTM-PD. Diagnosis of nodular bronchiectatic NTM-PD should prompt investigation of host factors, including disorders of mucociliary clearance, connective tissue diseases and immunodeficiencies, either genetic or acquired. Treatment of NTM-PD in bronchiectasis involves a multidisciplinary approach and considers the (sub)species involved, disease severity and comorbidities. Current guideline-based antimicrobial treatment of NTM-PD is considered long, cumbersome and unsatisfying in terms of outcomes. Novel treatment regimens and strategies are being explored, including rifampicin-free regimens and inclusion of clofazimine and inhaled antibiotics. Host-directed therapies, such as immunomodulators and cytokine-based therapies, might enhance antimycobacterial immune responses. Optimising supportive care, as well as pathogen- and host-directed strategies, is crucial, highlighting the need for personalised approaches tailored to individual patient needs. Further research is warranted to elucidate the complex interplay between host and mycobacterial factors, informing more effective management strategies.

The impact of smoking on bronchiectasis and its comorbidities.

INTRODUCTION: Bronchiectasis, characterized by irreversible bronchial dilatation, is a growing global health concern with significant morbidity. This review delves into the intricate relationship between smoking and bronchiectasis, examining its epidemiology, pathophysiology, clinical manifestations, and therapeutic approaches. Our comprehensive literature search on PubMed utilized MESH terms including 'smoking,' 'smoking cessation,' 'bronchiectasis,' and 'comorbidities' to gather relevant studies. AREAS COVERED: This review emphasizes the role of smoking in bronchiectasis development and exacerbation by compromising airways and immune function. Interconnected comorbidities, including chronic obstructive pulmonary disease, asthma, and gastroesophageal reflux disease, create a detrimental cycle affecting patient outcomes. Despite limited studies on smoking cessation in bronchiectasis, the review stresses its importance. Advocating for tailored cessation programs, interventions like drainage, bronchodilators, and targeted antibiotics are crucial to disrupting the inflammatory-infection-widening cycle. EXPERT OPINION: The importance of smoking cessation in bronchiectasis management is paramount due to its extensive negative impact on related conditions. Proactive cessation programs utilizing technology and targeted education for high-risk groups aim to reduce smoking's impact on disease progression and related comorbidities. In conclusion, a personalized approach centered on smoking cessation is deemed vital for bronchiectasis, aiming to improve outcomes and enhance patients' quality of life in the face of this complex respiratory condition.

Effects of high-flow nasal cannula oxygen therapy in bronchiectasis and hypercapnia: a retrospective observational study.

BACKGROUND: The effectiveness of high-flow nasal cannula (HFNC) therapy in patients with bronchiectasis experiencing hypercapnia remains unclear. Our aim was to retrospectively analyze the short-term outcomes of HFNC therapy in such patients, and to further explore the predictors of HFNC treatment failure in this particular patient population. METHODS: A retrospective review was conducted on patients with bronchiectasis who received HFNC (n = 70) for hypercapnia (arterial partial pressure of carbon dioxide, PaCO2 ≥ 45 mmHg) between September 2019 and September 2023. RESULTS: In the study population, 30% of patients presented with acidemia (arterial pH < 7.35) at baseline. Within 24 h of HFNC treatment, there was a significant reduction in PaCO2 levels by a mean of 4.0 ± 12.7 mmHg (95% CI -7.0 to -1.0 mmHg). Concurrently, arterial pH showed a statistically significant increase with a mean change of 0.03 ± 0.06 (95% CI 0.01 to 0.04). The overall hospital mortality rate in our study was 17.5%. The median length of hospital stay was 11.0 days (interquartile range [IQR] 8.0 to 16.0 days). Sub-analysis revealed no statistically significant differences in hospital mortality (19.0% vs. 20.4%, p = 0.896), length of hospital stay (median 14.0 days [IQR 9.0 to 18.0 days] vs. 10.0 days [IQR 7.0 to 16.0 days], p = 0.117) and duration of HFNC application (median 5.0 days [IQR 2.0 to 8.5 days] vs. 6.0 days [IQR 4.9 to 9.5 days], p = 0.076) between the acidemia group and the non-acidemia group (arterial pH ≥ 7.35). However, more patients in the non-acidemia group had do-not-intubate orders. The overall treatment failure rate for HFNC was 28.6%. Logistic regression analysis identified the APACHE II score (OR 1.24 per point) as the independent predictor of HFNC failure. CONCLUSIONS: In patients with bronchiectasis and hypercapnia, HFNC as an initial respiratory support can effectively reduce PaCO2 level within 24 h of treatment. A high APACHE II score has emerged as a prognostic indicator for HFNC treatment failure. These observations highlight randomized controlled trials to meticulously evaluate the efficacy of HFNC in this specific population.

Targeting respiratory microbiomes in COPD and bronchiectasis.

INTRODUCTION: This review summarizes our current understanding of the respiratory microbiome in COPD and Bronchiectasis. We explore the interplay between microbial communities, host immune responses, disease pathology, and treatment outcomes. AREAS COVERED: We detail the dynamics of the airway microbiome, its influence on chronic respiratory diseases, and analytical challenges. Relevant articles from PubMed and Medline (January 2010-March 2024) were retrieved and summarized. We examine clinical correlations of the microbiome in COPD and bronchiectasis, assessing how current therapies impact upon it. The potential of emerging immunotherapies, antiinflammatories and antimicrobial strategies is discussed, with focus on the pivotal role of commensal taxa in maintaining respiratory health and the promising avenue of microbiome remodeling for disease management. EXPERT OPINION: Given the heterogeneity in microbiome composition and its pivotal role in disease development and progression, a shift toward microbiome-directed therapeutics is appealing. This transition, from traditional 'pathogencentric' diagnostic and treatment modalities to those acknowledging the microbiome, can be enabled by evolving crossdisciplinary platforms which have the potential to accelerate microbiome-based interventions into routine clinical practice. Bridging the gap between comprehensive microbiome analysis and clinical application, however, remains challenging, necessitating continued innovation in research, diagnostics, trials, and therapeutic development pipelines.

Bronchiectasis management in adults: state of the art and future directions.

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials (RCTs) have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent RCTs.

Embosphere microspheres size for bronchial artery embolization in patients with hemoptysis caused by bronchiectasis: a retrospective comparative analysis of 500-750 versus 700-900 µm microspheres.

BACKGROUND: Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. METHODS: A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500-750 µm microspheres, and group B patients were treated with 700-900 µm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. RESULTS: Median follow-up was 30.2 months (range, 20.3-56.5 months). The final analysis included a total of 112 patients (49-77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500-750 µm Embosphere microspheres, and group B (N = 44), which received 700-900 µm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12-2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10-2.72; P = 0.028) were independent risk factors for recurrent bleeding. CONCLUSIONS: For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500-750 µm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700-900 µm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700-900 µm) Embosphere microspheres is associated with the reduced cost of an embolic agent.

Pathophysiology of non-cystic fibrosis bronchiectasis in children and adolescents with asthma: A protocol for systematic review and meta-analysis.

BACKGROUND: The pathophysiological mechanisms by which asthma and bronchiectasis are associated are still unclear. The association of these two diseases can result in more severe symptoms and a greater number of exacerbations. OBJECTIVE: The aim of this systematic review is to collect evidence of the pathophysiology of non-cystic fibrosis bronchiectasis with associated asthma in children and adolescents, aged 6-18 years old. METHODS: A systematic and comprehensive search will be performed using eight main databases, PubMed, PubMed PMC, BVS/BIREME, Scopus, EMBASE, Cochrane Library, Scielo and Web of Science. Articles will be searched from the earliest available time to July 2023. The studied population will be composed of children and adolescents with asthma and non-cystic fibrosis bronchiectasis. From the data obtained, all articles found will be transferred to the Rayyan platform. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols Checklist (PRISMA P-2015). In addition, if sufficient data are available, a meta-analysis will be conducted. Two independent reviewers will conduct the studies selection, data extraction, and risk of bias assessment. The outcome measures will be to analyze if non-cystic fibrosis bronchiectasis is related to a specific inflammatory profile. DISCUSSION: A systematic review will provide better knowledge about the etiopathogenesis and causes of the association between asthma and bronchiectasis and its role in the severity and control of asthma. Identifying, selecting and critically evaluating studies on asthma and bronchiectasis, would be possible to illuminate the characteristics of children and adolescents with associated diagnoses and provide information to help individualized treatments in order to control and prevent complications. The findings of this study will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in July 2023 (registration number CRD42023440355).

Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Improving the Diagnosis and Treatment of Paediatric Bronchiectasis Through Research and Translation.

Bronchiectasis, particularly in children, is an increasingly recognised yet neglected chronic lung disorder affecting individuals in both low-to-middle and high-income countries. It has a high disease burden and there is substantial inequity within and between settings. Furthermore, compared with other chronic lung diseases, considerably fewer resources are available for children with bronchiectasis. The need to prevent bronchiectasis and to reduce its burden also synchronously aligns with its high prevalence and economic costs to health services and society. Like many chronic lung diseases, bronchiectasis often originates early in childhood, highlighting the importance of reducing the disease burden in children. Concerted efforts are therefore needed to improve disease detection, clinical management and equity of care. Modifiable factors in the causal pathways of bronchiectasis, such as preventing severe and recurrent lower respiratory infections should be addressed, whilst also acknowledging the role played by social determinants of health. Here, we highlight the importance of early recognition/detection and optimal management of bronchiectasis in children, and outline our research, which is attempting to address important clinical knowledge gaps discussed in a recent workshop. The research is grouped under three themes focussing upon primary prevention, improving diagnosis and disease characterisation, and providing better management. Our hope is that others in multiple settings will undertake additional studies in this neglected field to further improve the lives of people with bronchiectasis. We also provide a resource list with links to help inform consumers and healthcare professionals about bronchiectasis and its recognition and management.

[Annual review of bronchiectasis research in 2023].

This review focuses on the latest advances in bronchiectasis from October 1st, 2022 to September 30th, 2023, including the etiology, diagnosis, treatment, comorbidities, and management of bronchiectasis in order to provide a reference in clinical diagnosis and treatment, and future research of bronchiectasis for domestic peers.

Severity of bronchiectasis predicts use of and adherence to high frequency chest wall oscillation therapy - Analysis from the United States Bronchiectasis and NTM research registry.

BACKGROUND: High frequency chest wall oscillation (HFCWO) is a form of airway clearance therapy that has been available since the mid-1990s and is routinely used by patients suffering from retained pulmonary secretions. Patients with cystic fibrosis (CF), neuromuscular disease (NMD), and other disorders, including bronchiectasis (BE) and COPD (without BE), are commonly prescribed this therapy. Limited evidence exists describing HFCWO use in the BE population, its impact on long-term management of disease, and the specific patient populations most likely to benefit from this therapy. This study sought to characterize the clinical characteristics of patients with BE who have documented use of HFCWO at baseline and 1-year follow-up. METHODS: An analysis from a large national database registry of patients with BE was performed. Demographic and clinical characteristics of all patients receiving HFCWO therapy at baseline are reported. Patients were stratified into two groups based on continued or discontinued use of HFCWO therapy at 1-year follow-up. RESULTS: Over half (54.8 %) of patients who reported using HFCWO therapy had a Modified Bronchiectasis Severity Index (m-BSI) classified as severe, and the majority (81.4 %) experienced an exacerbation in the prior two years. Of patients with 1-year follow-up data, 73 % reported continued use of HFCWO. Compared to patients who discontinued therapy, these patients were more severe at baseline and at follow-up suggesting that patients with more severe disease are more likely to continue HFCWO therapy. CONCLUSIONS: Patients who have more severe disease and continue to experience exacerbations and hospitalizations are more likely to continue HFCWO therapy. CLINICAL TRIAL REGISTRATION: NA.