Viruses in bronchiectasis.

Bronchiectasis is a chronic respiratory condition characterised by irreversible dilation of the bronchi, leading to recurrent respiratory infections and chronic inflammation. Bacterial infections have been well-recognised as contributors to disease progression as well as potent inducers of exacerbations for decades. However, recent studies have indicated that viruses are present in up to 50% of exacerbations, raising questions over the role viruses may play in bronchiectasis.

Symptoms, risk of future exacerbations, and response to long-term macrolide treatment in bronchiectasis: an observational study.

Background: Previous studies have suggested that daily symptoms are a marker of bronchiectasis disease activity and could therefore identify patients at increased risk of exacerbation. However, international bronchiectasis guidelines recommend long-term macrolide treatment only in patients with three or more exacerbations per year. We aimed to investigate if symptoms independently predict future exacerbations and therefore identify additional responders to long-term macrolide treatment.

Inflammatory and mucociliary dysfunction based endotypes across the spectrum of chronic airway diseases.

Background: There is substantial overlap between features of COPD, asthma, bronchiectasis(BE) and cystic fibrosis(CF). Each is characterised by inflammation and mucociliary dysfunction.

Research Question: Is there a relationship between inflammation and mucociliary clearance in chronic respiratory conditions and can biology rather than disease labels stratify patients into therapeutically relevant subtypes?

Study Design And Methods: Patients were categorized by primary disease and clinical characteristics, spontaneous sputum was collected, inflammatory markers (neutrophil elastase(NE) and 19 cytokines), sputum properties (DNA content, mucins, rheology, dry weight) and microbiome (long read 16S sequencing) were measured.

The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe chronic obstructive pulmonary disease: A randomized trial (MUSIC).

Introduction: The microbiome is associated with exacerbation risk, quality of life and mortality in COPD. Inhaled corticosteroid (ICS) treatment has been reported to alter the microbiome through modulating host defence. How ICS alters the microbiome and whether effects are equal between different ICS preparations is debated.

Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review.

Background And Objective: Bronchiectasis is a chronic respiratory disease characterized by predominantly neutrophilic inflammation, recurrent infection and pathological dilatation of the airways. Current therapeutic strategies primarily target infections and improving mucus clearance. However, no current treatment can directly ameliorate neutrophilic inflammation.

Investigating the impact of dipeptidyl peptidase-1 inhibition in humans using multi-omics.

Background: Dipeptidyl peptidase-1 (DPP-1/Cathepsin C) processes and activates neutrophil serine proteases. Brensocatib (an oral, reversible, competitive DPP-1 inhibitor) is a novel therapy for bronchiectasis previously shown to reduce sputum protease activity and prevent exacerbations. Broader effects of DPP-1 inhibition on the immune response have not been investigated.

Diagnosis and Management of Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline.

Background: Understanding of the diagnosis and treatment of adults with community-acquired pneumonia (CAP) has evolved thanks to new evidence, experience, and emerging technologies. This document updates evidence-based clinical practice guidelines on four key questions for the diagnosis and management of adult patients with CAP.

Methods: A multidisciplinary panel integrated systematic reviews of comparative evidence with other relevant research and clinical experience, then applied Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to produce recommendations using the Evidence to Decision Framework.

Endotypes of Infection in Bronchiectasis Are Associated with Inhaled Antibiotic Response: Results from Two Randomized, Double-Blind, Placebo-controlled Phase III Trials (ORBIT 3 and ORBIT 4).

Replicate phase III trials of inhaled antibiotics in patients with bronchiectasis have produced inconsistent results. This study investigated if different microbial and inflammatory endotypes are linked to antibiotic response in patients with chronic infection. ORBIT-3 and ORBIT-4 were phase III trials of inhaled liposomal ciprofloxacin compared with placebo in patients with bronchiectasis with chronic infections.

Neutrophil-derived biomarkers in bronchiectasis: identifying a common therapeutic target.

Bronchiectasis is a chronic respiratory disease that can lead to a substantial decline in lung function, ultimately leading to a significantly increased risk of morbidity and mortality. Despite the increasing global impact of bronchiectasis, no specific (or licensed) treatment for the disease currently exists, with most available therapies, though beneficial, focusing on symptom management and infection control. In part, the lack of specific treatments for bronchiectasis may be due to a lack of established biomarkers for the disease.

Greater disease severity in adults with paediatric-onset adult-onset bronchiectasis: a multicenter EMBARC registry study.

Background: Young adults with paediatric- onset bronchiectasis (POBE) represent a minority of bronchiectasis patients and are poorly characterized. We aimed to compare the characteristics and severity of adults with POBE to adult-onset bronchiectasis (AOBE).

Methods: Data from four EMBARC (European Bronchiectasis Registry) centers were analyzed.

Analysis of airway inflammation demonstrates a mechanism for T2-biologic failure in asthma.

Background: Targeted type 2 (T2) biologics have transformed asthma care, but the clinical response to biologic therapy varies between patients.

Objective: We sought to assess airways inflammation in T2-high asthmatic patients treated with anti-IL-5 biologics to investigate whether differential mechanism of airway inflammation explains varied response to biologics.

Methods: Proteomic analysis (Olink, 1463 protein panel) and high-sensitivity cytokine analysis (ELISAs) were performed on induced sputum from T2-high severe asthmatic patients in the UK multicenter Mepolizumab EXacerbation study.

Dipeptidyl peptidase-1 inhibitors in bronchiectasis.

Dipeptidyl peptidase (DPP)-1 (also known as cathepsin C) inhibitors are the first disease-specific therapy shown to be effective in bronchiectasis. The mechanism of action of DPP-1 inhibitors is suppression of activity of neutrophil serine proteases (NSPs) by preventing them from being activated during neutrophil maturation in the bone marrow. NSPs exert multiple directly damaging effects and contribute to ongoing dysregulated airway inflammation.

Short-term stability of the sputum microbiota in bronchiectasis and cystic fibrosis.

https://bit.ly/3URkv42.

Seroprevalence of in patients with COPD in a UK cohort.

https://bit.ly/4gQCDnM.

Dual Bronchodilators in Bronchiectasis Study: a randomised controlled trial.

https://bit.ly/4fuuHHX.

Anxiety, depression, physical disease parameters and health-related quality of life in the BronchUK national bronchiectasis cohort.

Background: Bronchiectasis is associated with psychological comorbidity and poor quality of life (QoL), yet guidelines lack focus on psychological morbidity. Using data obtained from the BronchUK database (1341 patients), we examined the link between anxiety/depression and physical disease severity, QoL and long-term outcomes in bronchiectasis.

Methods: Computed tomography-confirmed bronchiectasis patients enrolled in the BronchUK study with Hospital Anxiety and Depression Scale (HADS-A/D) data were studied.

Sputum metagenomics in bronchiectasis reveals pan-European variation: an EMBARC-BRIDGE study.

Background: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry shows considerable variation in culturable microbes in sputum between different European countries. The additive role of next-generation metagenomic sequencing remains unexplored and the association with antimicrobial resistomes unknown.

Methods: We used next-generation shotgun metagenomic sequencing to prospectively assess sputum from 349 individuals recruited into the EMBARC Bronchiectasis Research Involving Databases, Genomics and Endotyping (BRIDGE) study from three European regions: Northern and Western Europe, Southern Europe and the UK.

Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.

Background: In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation.

Methods: In a phase 3, double-blind trial, we randomly assigned patients with bronchiectasis (in a 1:1:1 ratio for adults and a 2:2:1 ratio for adolescents) to receive brensocatib (10 mg or 25 mg once per day) or placebo.

Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal (UNIVERSAL) study: a prospective observational cohort study protocol.

Background: Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies.

Trial Conduct, Baseline Characteristics, and Symptom Burden of Patients in the ARISE Study.

Introduction: ARISE was a global clinical trial designed to generate evidence demonstrating the utility of the patient-reported outcome instruments Quality of Life-Bronchiectasis (QOL-B) [Respiratory Domain (RD) only] and Patient-Reported Outcomes Measurement Information System Short Form v1.0-Fatigue 7a (PROMIS F SF-7a) in patients with newly diagnosed or recurrent Mycobacterium avium complex lung disease (MACLD). Here, we describe trial conduct, patient characteristics, and patient-reported symptoms at baseline among patients enrolled in ARISE.

Neutrophilic inflammation in bronchiectasis.

Noncystic fibrosis bronchiectasis, hereafter referred to as bronchiectasis, is a chronic, progressive lung disease that can affect people of all ages. Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life. The pathophysiology of bronchiectasis has been described as a vicious vortex of chronic inflammation, recurring airway infection, impaired mucociliary clearance and progressive lung damage that promotes the development and progression of the disease.

Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial.

Background: Airway neutrophil inflammation with excessive neutrophil serine proteases is implicated in frequent exacerbations of bronchiectasis. HSK31858 is a novel reversible inhibitor of DPP-1. We aimed to assess the efficacy and safety of HSK31858 in decreasing the frequency of bronchiectasis exacerbations among adults with bronchiectasis.