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Background The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162). Methods Embase, MEDLINE and the Cochrane Library were searched for publications relating to bronchiectasis disease burden (December 2017–December 2022). Journal articles and congress abstracts reporting on observational studies, randomised controlled trials and registry studies were included. Editorials, narrative reviews and systematic literature reviews were included to identify primary studies. PRISMA guidelines were followed. Results 1585 unique publications were identified, of which 587 full texts were screened and 149 were included. A further 189 citations were included from reference lists of editorials and reviews, resulting in 338 total publications. Commonly reported symptoms and complications included dyspnoea, cough, wheezing, sputum production, haemoptysis and exacerbations. Disease severity across several indices and increased mortality compared with the general population was reported. Bronchiectasis impacted quality of life across several patient-reported outcomes, with patients experiencing fatigue, anxiety and depression. Healthcare resource utilisation was considerable and substantial medical costs related to hospitalisations, treatments and emergency department and outpatient visits were accrued. Indirect costs included sick pay and lost income. Conclusions Bronchiectasis causes significant clinical and socioeconomic burden. Disease-modifying therapies that reduce symptoms, improve quality of life and reduce both healthcare resource utilisation and overall costs are needed. Further systematic analyses of specific aetiologies and paediatric disease may provide more insight into unmet therapeutic needs.

Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.

Introduction: Pseudomonas aeruginosa is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known. Methods: We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating P. aeruginosa eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for P. aeruginosa at 12 months after eradication treatment. Cystic fibrosis was excluded. Results: Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month P. aeruginosa eradication rate of 40% (95% CI 34–45%; p

Background Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD). Methods A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts. Results During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS. Conclusion This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD.

New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf™; NCT05238675) assessing the efficacy and safety of a novel CatC inhibitor, BI 1291583, in adult patients with bronchiectasis. This multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study has a screening period of at least 6 weeks, a treatment period of 24–48 weeks and a follow-up period of 4 weeks. ∼240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1 mg once daily, 2.5 mg once daily or 5 mg once daily in a 2:1:1:2 ratio, stratified by Pseudomonas aeruginosa infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose–response relationship for the three oral doses of BI 1291583 versus placebo on time to first pulmonary exacerbation up to Week 48 (the primary end-point). Efficacy will be assessed using exacerbations, patient-reported outcomes, measures of symptoms, sputum neutrophil elastase activity and pulmonary function testing. Safety assessment will include adverse event reporting, physical examination, monitoring of vital signs, safety laboratory parameters, 12-lead electrocardiogram, and periodontal and dermatological assessments. If efficacy and safety are demonstrated, results will support further investigation of BI 1291583 in phase 3 trials.

Introduction The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. Methods We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD– [bronchiectasis] BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. Results 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD–BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV1/[forced vital capacity] FVC

Background Airway clearance is a fundamental component of bronchiectasis care. Lung clearance index (LCI) is a measurement of ventilation inhomogeneity. Its responsiveness to long-term airway clearance is unknown. We aimed to compare two methods of daily airway clearance over 4 weeks: autogenic drainage (AD) and oscillating positive airway pressure (oPEP), and to determine effects of airway clearance on LCI and clinical outcomes. Methods Adults with bronchiectasis naive to airway clearance were randomised to daily airway clearance with either AD or oPEP. Difference in LCI as primary outcome, spirometry, sputum volume and purulence, and quality of life were at randomisation and after 4 weeks of airway clearance. Results 51 patients (32 women and 19 men, mean age 66.2±12.8 years) were randomised and 49 completed the study (25 AD and 24 oPEP). The LCI and forced expiratory volume in 1 s did not change between visits between groups (difference between groups 0.02), nor between visits in either group. Sputum quantity decreased in 12 out of 24 (50%) of the oPEP group, and in six out of 25 (24%) of the AD group (p=0.044). The “treatment burden” worsened or was unchanged in 70% of participants randomised to AD and 55% randomised to oPEP (p=0.038). Conclusion Sputum quantity decreased in more participants randomised to oPEP group after 1 month of daily airway clearance, with a better treatment burden. The effects of 4 weeks of airway clearance on LCI were not significant in either treatment group.

Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug–drug interactions, are discussed.

The definition of a disease requires that distinguishing signs and symptoms are present that are common, and that the constellation of signs and symptoms differentiate the condition from other causes. In bronchiectasis, anatomical changes, airways inflammation and airway infection are the distinguishing features that are common to this disease. However, bronchiectasis is a heterogenous disease: signs and symptoms are shared with other airway diseases, there are multiple aetiologies and certain phenotypes of bronchiectasis have distinct clinical and laboratory features that are not common to all people with bronchiectasis. Furthermore, response to therapeutic interventions in clinical trials is not uniform. The concept of bronchiectasis as a treatable trait has been suggested, but this may be too restrictive in view of the heterogeneity of bronchiectasis. It is our opinion that bronchiectasis should be defined as a disease in its own right, but one that shares several pathophysiological features and “treatable traits” with other airway diseases. These traits define the large heterogeneity in the pathogenesis and clinical features and suggest a more targeted approach to therapy.

Introduction: Pseudomonas aeruginosa is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known. Methods: We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating P. aeruginosa eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for P. aeruginosa at 12 months after eradication treatment. Cystic fibrosis was excluded. Results: Six observational studies including 289 patients were included in the meta-analysis. Our metaanalysis found a 12-month P. aeruginosa eradication rate of 40% (95% CI 34–45%; p<0.00001), with no significant heterogeneity (I² =0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41–55%) than systemic antibiotics alone (27%, 13–45%). Conclusion: Eradication treatment in bronchiectasis results in eradication of P. aeruginosa from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone. [ABSTRACT FROM AUTHOR]

Introduction People with bronchiectasis frequently request specialist advice to prepare for travelling, but there are few publications providing advice on safe travel with bronchiectasis. There is a need for recommendations on adapting everyday treatment to the requirements during travelling. Methods A panel of 13 patient volunteers formulated questions regarding different aspects of travelling, including safety of travel, maintaining regular treatment during travel, and dealing with deterioration while away. Patient input was used to derive a questionnaire and circulated among a panel of bronchiectasis experts. Where 80% or more experts agreed on a response, a recommendation was made. Results A total of 26 bronchiectasis experts answered the questionnaire. Recommendations were made on safety of travel, choice of destinations and activities, choice of travel insurance, carrying medications and devices, maintaining regular treatments in transport, documentation to be provided and oxygen requirements. Some statements did not reach an 80% agreement; in many cases these statements may be valid for some, but not all bronchiectasis patients. Conclusions The general agreement was that it is considered safe for most people with bronchiectasis to travel. Careful planning and preparation with robust communication between patients and their healthcare provider prior to travel for different scenarios is fundamental to a successful journey.

The association of bronchiectasis with chronic rhinosinusitis (CRS) has been reported. However, apart from primary ciliary dyskinesia (PCD) and cystic fibrosis (CF), predisposing conditions have not been established. We aimed to define clinical and laboratory features that differentiate patients with bronchiectasis with upper airway symptoms (UASs) and without PCD from patients without UASs. We reviewed charts of adults with bronchiectasis, excluding CF and PCD. UASs were defined as nasal discharge most days of the year, sinusitis or nasal polyps. Laboratory data included IgG, total IgE, blood eosinophils, sputum bacteriology and lung function. A radiologist blinded to UAS presence scored bronchiectasis (Reiff score) and sino-nasal pathology (Lund–Mackay score). Of 197 patients, for the 70 (35%) with UASs, symptoms started earlier (34±25 versus 46±24 years; p=0.001), disease duration was longer (median 24 versus 12 years; p=0.027), exacerbations were more frequent (median 3 versus 2 per year; p=0.14), and peripheral blood eosinophil (median 230 versus 200 μL−1; p=0.015) and total IgE (median 100 versus 42 IU·mL−1; p=0.085) levels were higher. The sinus computed tomography score was independently associated with exacerbations, with 1 point on the Lund–Mackay score associated with a 1.03-fold increase in the number of exacerbations per year (95% CI 1.0–1.05; p=0.004). These findings may implicate a higher disease burden in patients with UASs. We hypothesise that UASs precede and may in some cases lead to the development of bronchiectasis.

Expression of p.Arg117His cystic fibrosis (CF) transmembrane conductance regulator is influenced by a polythymidine (poly-T) tract and a thymidine–guanine (TG) repeat on intron 9, which vary in length and affect exon 10 skipping. We compared clinical characteristics and the rate of progression of lung disease of CF patients carrying the p.Arg117His mutation with different intron 9 varying sequences (poly-T) and mutation classes in trans. Data were collected from patients in Northern Ireland, UK, including diagnostic features, sweat chloride, nutritional status, sputum microbiology, CF-related complications and lung function. Poly-T and TG repeats were determined by PCR. Forced expiratory volume in 1 s (FEV1) decline was determined from linear regression of FEV1 measurements of patients over time. We identified 62 patients with p.Arg117His, 55 with a class I/II mutation in trans and six with p.Arg117His/p.Gly551Asp. 42 patients had 5T and 13 had 7T. All patients had 12 TG repeats. Patients with p.Arg117His-5T had greater lung function decline, sweat chloride concentrations, pancreatic insufficiency and prevalence of Pseudomonas aeruginosa infection compared with patients with p.Arg117His-7T. Lung function decline and disease severity in p.Arg117His is determined by the poly-T tract length and identity of the mutation in trans. Patients with p.Arg117His-5T and a second class I/II mutation have a severity similar to p.Phe508del homozygous patients, although lung function decline is delayed to an older age. There may be linkage disequilibrium between p.Arg117His and 12 TG repeats.

Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age