Background Bronchiectasis is a complex disease with geographical variability in its presentation and management. Despite the growing contribution of international registries, real-world data on the Italian bronchiectasis population remain limited. The objective of the present study was to describe the demographic, clinical, microbiological, functional and treatment characteristics of Italian patients with bronchiectasis and to compare them with those of patients from other Southern European countries. Methods This was a secondary analysis of adults from 18 Italian centres included in the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry, with comparisons made to patients in Spain, Greece, Portugal, Turkey, Israel and Malta (Southern European countries). Demographics, comorbidities, exacerbation history, spirometry, microbiology and treatment patterns were evaluated. Results Among 1657 Italian patients, the majority were female (70.5%) with a median age of 65 years, with high rates of idiopathic bronchiectasis (55.4%) and preserved lung function. Compared with other Southern European countries (n=2638), Italian patients had lower disease severity (median Bronchiectasis Severity Index: 6 versus 7; p<0.001), less frequent isolation of Pseudomonas aeruginosa, and lower prevalence of daily sputum production and purulence, despite identical quality of life (median Quality of Life Questionnaire-Bronchiectasis Respiratory Symptom Score: 70.4 in both groups). Treatment patterns differed, with lower use of inhaled antibiotics (1.1% versus 13.1%) and macrolides (6.0% versus 14.3%), but more widespread use of airway clearance (48.4% versus 35.9%) among patients from Italy versus other Southern European countries. Conclusions These findings may reflect earlier referral, diagnostic preferences or structural differences in care delivery in Italy compared with other Southern European countries. This work lays the foundation for tailored national strategies and future longitudinal studies. The largest bronchiectasis cohort ever studied in Italy reveals unique clinical traits and highlights key differences from other Southern European countries, and provides real-world data to shape better care models and guide future research.

RATIONALE:The frequent exacerbator phenotype was previously defined using a threshold of  ≥3 exacerbations per year in bronchiectasis. However, the contribution of each prior exacerbation to future risk as well as the influence of severe exacerbations and different etiologies and regions remain poorly understood. OBJECTIVES:To quantify the risk associated with each prior exacerbation of bronchiectasis in predicting future exacerbations and severe exacerbations, and to determine whether this association varies across different etiologies and geographic regions. METHODS:We analyzed data from the European Bronchiectasis Registry (EMBARC), including 30 countries across Europe and Asia. The association between baseline exacerbation history and future exacerbations was tested using negative binomial regression over up to 5 years of follow-up. Severe exacerbations were defined as those requiring hospitalization. MEASUREMENTS AND MAIN RESULTS:A total of 19 324 patients with bronchiectasis were included. Each prior exacerbation was associated with an increased risk of exacerbations and severe exacerbations. Incidence rate ratio (IRR) for future exacerbations was 1.45 (95% CI 1.34-1.58, P < .001) for 1 exacerbation; 1.84 (95% CI 1.69-1.99, P < .001) for 2 exacerbations; 2.50 (95% CI 2.29-2.73, P < .001) for 3 exacerbations; and 3.56 (95% CI 3.32-3.82, P < .001) for patients with 4 or more prior exacerbations. Additionally, 1 prior severe exacerbation was associated with increased risk of exacerbation (IRR = 1.52, 95% CI 1.45-1.60, P < .001) and strongly associated with future severe exacerbations (IRR = 3.96, 95% CI 3.71-4.22, P < .001). The frequent exacerbator phenotype was consistent across different etiologies and geographic regions. CONCLUSIONS:The frequent exacerbator phenotype is highly consistent across patient subgroups and regions. Each prior exacerbation is associated with a progressively higher risk, with no definitive threshold-defining high risk.

Background: Primary ciliary dyskinesia is an inherited cause of bronchiectasis. Little is known about disease course and outcomes in adults compared to other bronchiectasis aetiologies. Methods: Data were analysed from four prospective international bronchiectasis registries (EMBARC- Europe, BRR -USA, CanBE-NTM -Canada and ABR -Australia). Comparisons of disease severity and outcomes were made between people with PCD and bronchiectasis of other causes. Follow up data for exacerbations and severe exacerbations were assessed using negative binomial regression adjusted for confounders. Cox proportional hazards regression was used to investigate the association between PCD diagnosis and new infection with Pseudomonas aeruginosa and mortality. A nested biomarker study was conducted in European patients (EMBARC-BRIDGE). Results: 836/24601 (3.3%) adults with bronchiectasis had a diagnosis of PCD. Compared to other aetiologies, patients with PCD were significantly younger at baseline (median age (IQR) 41 (29-58) vs 68 (59-75), with lower FEV1% predicted (67.8 (IQR 47.2-85.4) vs 76.7 (IQR 57.4-94.4)) and were more frequently infected with P. aeruginosa (40.7% vs 18.2%), Haemophilus influenzae (23.3 vs 14.6) and other pathogens. In the nested mechanistic study Adults with PCD had significantly higher levels of airway neutrophilic inflammation (NE, PR3, AZU1, OLFM4). Bronchiectasis was bilateral and predominantly in the middle and lower lobes.In long-term follow-up, Adults with PCD were at higher risk of exacerbations and severe exacerbations even after adjustment for confounders (age, sex, lung function, COPD, asthma, NTM diagnosis, P. aeruginosa infection, MRC dyspnoea score, medications, country/region) Incidence Rate Ratio (IRR) 1.32 (95% CI 1.13-1.53) and IRR 1.66(1.35-2.06) respectively. Patients with PCD were at markedly increased risk of new P.aeruginosa infection. Mortality risk was not increased. Conclusion: Adults with Adults with PCD are a very high risk endotype of bronchiectasis with an increased risk of exacerbations, severe exacerbations and new P. aeruginosa infection. Funding: EMBARC is supported by the European Respiratory Society through the Clinical Research Collaboration programme. EMBARC4 is supported by project partners Astrazeneca, Alarmin Therapeutics, Boehringer Ingelheim, Centauri therapeutics, Chiesi, CSL Behring, Glaxosmithkline, Grifols, Insmed, Lifearc, Roche, UCB Therapeutics, Verona Pharma, Zambon. BEAT-PCD is supported by the European Respiratory Society. JDC and AS are supported by GSK/Asthma and Lung UK Chair of Respiratory Research. Declaration of Interest: A Shoemark reports support for the present manuscript from the European Respiratory Society through the EMBARC3 consortium, which is supported by project partners Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Grifols, Insmed, Janssen, Lifearc, Novartis, and Zambon; grants or contracts from AstraZeneca and Lifearc; consulting fees from Spirovant, Translate Bio, and ReCode Therapeutics; payment or honoraria from Translate Bio, Ethris, and Insmed; and unpaid involvement in European Respiratory Society Clinical Research Collaborations (EMBARC, BEATPCD, and AMR Lung). F C Ringshausen reports grants or contracts to institution from the German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU/EFPIA), iABC Consortium (including Alaxia, Basilea, Novartis, and Polyphor), Mukoviszidose Institute, Novartis, and Insmed Germany; consulting fees from Parion Sciences, Boehringer Ingelheim, Insmed, and Chiesi; payment or honoraria from I!DE Werbeagentur GmbH, Insmed, Grifols, University Hospital Hamburg, AstraZeneca, Clinigo GmbH, and Sanofi; participation on Data Safety Monitoring or Advisory Boards for Insmed, Boehringer Ingelheim, Parion Sciences, and Chiesi; roles as co-chair of the German Bronchiectasis Registry PROGNOSIS, member of the Steering Committee of the European Bronchiectasis Registry EMBARC, and PI of the German Center for Lung Research; and fees for clinical trial participation paid to institution from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Parion Sciences, Recode, Ruhr University-Bochum, University of Dundee, UMC Utrecht, and Vertex. M R Loebinger reports consulting fees from 30 Technology, AstraZeneca, Insmed, Chiesi, ReCode, Boehringer Ingelheim, Ethris, Mannkind, AN2 Therapeutics, MucPharm, and Galapagos; payment or honoraria from Insmed; support for attending the BTS winter meeting from Insmed; and participation on a Data Safety Monitoring or Advisory Board for Sanofi. M Crisafulli reports sponsorship of the Australian Bronchiectasis Registry (ABR) paid to Lung Foundation Australia from Insmed Incorporated, Boehringer Ingelheim, GSK, Zambon, and AstraZeneca. A E Brunton reports a role as an employee of the Bronchiectasis and NTM Association, which sponsors the BRR. E Polverino reports consulting fees from Insmed, Grifols, Pari, and CSL Behring; payment or honoraria from Insmed, Pari, Grifols, and CSL Behring; and participation on a Data Safety Monitoring or Advisory Board for Insmed. R Ewen reports payment or honoraria from Boehringer Ingelheim Pharma GmbH & Co. KG and support for attending meetings and/or travel from Boehringer Ingelheim Pharma GmbH & Co. KG and Chiesi GmbH. A De Soyza reports grants and contracts to institution from GSK, 30 Technology, and Sanofi; consulting fees from 30 Technology, Insmed, AstraZeneca, and Sanofi; and payment or honoraria from AstraZeneca, Bayer, GSK, Insmed, Zambon, Sanofi, Fisher & Paykel, and Inogen. M Vendrell reports payment or honoraria to institution from Insmed and Teva; support for attending meetings and/or travel from Pari, Grifols, Chiesi, Insmed, and Gebro; participation on a Data Safety Monitoring or Advisory Board for Insmed; and a role as President of the Catalan Respiratory Society SOCAP involving Chiesi, Astra, Bial, Sanofi, Vivisol, Pfizer, Pari, Resmed, Boehringuer, Faes, and Menarini. P R Burgel reports grants or contracts to institution from Vaincre la Mucoviscidose; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Insmed, MSD, Vertex, and Viatris; and support for attending meetings and/or travel paid to institution from AstraZeneca, Chiesi, and Zambon. C S Haworth reports grants or contracts to institution from AstraZeneca; consulting fees from 30 Technology, AstraZeneca, BiomX, Boehringer Ingelheim, Chiesi, Clarametyx, Infex, Insmed, LifeArc, Pneumagen, Revagenix, Sanofi, Vertex, and Zambon; payment or honoraria from Chiesi, Insmed, Vertex, and Zambon; payment for expert testimony from Zambon; and a role as an ECFS Board member. K Dimakou reports payment or honoraria to institution from Novartis, Boehringer Ingelheim, GSK, Norma Hellas, Chiesi, AstraZeneca, and Zambon; support for attending meetings and/or travel from Novartis, Boehringer Ingelheim, GSK, Norma Hellas, Chiesi, AstraZeneca, and Menarini; and participation on a Data Safety Monitoring or Advisory Board for Novartis, GSK, and Chiesi. F Blasi reports grants from AstraZeneca, Chiesi, and Insmed; consulting fees from Menarini; and personal fees for lectures and advisory boards from AstraZeneca, Chiesi, Boehringer Ingelheim, GSK, Grifols, Insmed, Menarini, MSD, OM Pharma, Pfizer, Sanofi, Vertex, and Zambon. J Altenburg reports consulting fees from Insmed; payment or honoraria from Takeda Nederland, Insmed, and Chiesi; and participation on a Data Safety Monitoring or Advisory Board for Insmed. M Shteinberg reports grants or contracts from the Tel Aviv League for Lung Disease and G. Baum Foundation; consulting fees from AstraZeneca, Boehringer Ingelheim, Dexcel, Insmed, Kamada, Synchrony Medical, Trumed, and Zambon; payment or honoraria from AstraZeneca, Boehringer Ingelheim, CSL Behring, GSK, Kamada, Sanofi, and Insmed; support for attending meetings and/or travel from Boehringer Ingelheim Israel, AstraZeneca Israel, Kamada, Rafa, and GSK Israel; participation on a Data Safety Monitoring or Advisory Board for Bonus Biotherapeutics, Boehringer Ingelheim, AstraZeneca, Insmed, and GSK; and roles as Associate Editor for AJRCCM, Treasurer for the Israeli Society for Tuberculosis and Mycobacterial Diseases, management board member for EMBARC, editorial board member for ERJ, and ERS taskforce member for bronchiectasis guidelines and transitioning in bronchiectasis. P C Goeminne reports consulting fees from AstraZeneca and Boehringer Ingelheim; payment or honoraria from AstraZeneca, Insmed, and RMEI; support for attending meetings and/or travel from AstraZeneca and Chiesi; participation on a Data Safety Monitoring or Advisory Board for Boehringer Ingelheim; and an unpaid board member role for the Belgian Respiratory Society. R Dhar reports payment or honoraria from Cipla, GSK, Glenmark, AstraZeneca, Zuventus, Sanofi, and Lupin; and participation on a Data Safety Monitoring or Advisory Board for Glenmark, Lupin, Sun Pharma, and Cipla. S Aliberti reports grants or contracts to institution from GSK; consulting fees from Insmed Incorporated, Insmed Netherlands BV, Insmed Germany GmbH, Physioassist SAS, Boehringer Ingelheim Italia SpA, Boehringer Ingelheim International GmbH, Thermo Fisher Scientific, Zambon Italia Srl, Sanofi Srl, Providens DOO, Pfizer Srl, Limare LLC, GSK SpA, Chiesi Farmaceutici SpA, and Vertex Pharmaceuticals (Europe) Limited; and participation on a Data Safety Monitoring or Advisory Board for GSK SpA, Boehringer Ingelheim Italia SpA, Moderna Italy Srl, Zambon SpA, Chiesi Farmaceutici SpA, Insmed Incorporated, Insmed Netherlands BV, AN2 Therapeutics Inc, Modernatx, and Boehringer Ingelheim International GmbH. C S Thornton reports grants or contracts from CIHR, Alberta Innovates Health Solutions, NFRF, CHEST Foundation, CFI JELF, Cystic Fibrosis Canada, and the Cystic Fibrosis Foundation; consulting fees from Boehringer Ingelheim and Clarametyx; support for attending meetings and/or travel from the Cystic Fibrosis Foundation; and participation on a Data Safety Monitoring or Advisory Board for the AirNET Trial (investigator-initiated trial). L Morgan reports consulting fees from GSK, Boehringer Ingelheim, Insmed, Chiesi, and AstraZeneca; payment or honoraria from Boehringer Ingelheim, Insmed, Sanofi, GSK, and AstraZeneca; participation on a Data Safety Monitoring or Advisory Board for AstraZeneca, Chiesi, GSK, and Boehringer Ingelheim; honorary roles as CI of the Australian Bronchiectasis Registry and Chair of Lung Foundation Australia; and fees for clinical trial participation paid to institution from AstraZeneca, Boehringer Ingelheim, Insmed, Parion, and Mannkind. M L Metersky reports grants or contracts from Insmed, Armata, and Sanofi; payment or honoraria from Insmed, Boehringer Ingelheim, and UCB; participation on a Data Safety Monitoring or Advisory Board for Verona, Renovion, and AN2; and a leadership or fiduciary role for the Bronchiectasis & NTM Association. J D Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, Gilead, Grifols, Insmed, and Trudell; and consulting fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Insmed, Janssen, Novartis, Pfizer, and Zambon. P J McShane, M B Long, R C Hull, M Frohlich, E D Johnson, E Cant, M Smith, J Jarand, and L Burr have no conflicts of interest to report.

BACKGROUND:Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis. This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis. METHODS:This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479). FINDINGS:2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019). INTERPRETATION:Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis. FUNDING:European Respiratory Society, Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols, Insmed, Janssen, Lifearc, Roche, Verona Pharma, Zambon, National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, Program of the Shanghai Shenkang Development Center, EU/European Federation of Pharmaceutical Industries and Associations, Innovative Medicines Initiative, and Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium.

Introduction:Chronic rhinosinusitis (CRS) is a common comorbidity in bronchiectasis. Previous studies suggested that bronchiectasis with CRS is associated with elevated type 2 biomarkers, representing an "eosinophilic bronchiectasis" phenotype. However, whether the association with type 2 inflammation exists in rare aetiologies of bronchiectasis such as primary ciliary dyskinesia (PCD) or immune deficiency is unknown. Our aim was to explore the prevalence of CRS with and without nasal polyposis (CRSwNP and CRSnNP), their impact on bronchiectasis outcomes, and their association with type 2 inflammatory biomarkers in patients with bronchiectasis of various aetiologies. Methods:Using data from the EMBARC bronchiectasis registry, we classified patients with bronchiectasis as having no CRS, CRSnNP or CRSwNP. Regression models were used to test the effect of CRS on symptom scores and long-term outcomes. Multivariate models were created for elevated "type 2 biomarkers", defined as elevated blood eosinophil count or total IgE. Results:Among 16 640 people with bronchiectasis, 2703 (20.9%) had CRSnNP and 1223 (7.3%) had CRSwNP. CRSwNP and CRSnNP were associated with worse symptoms and more frequent exacerbations, but lower hospitalisations and mortality. Type 2 biomarkers were elevated in people with comorbid CRSwNP in idiopathic bronchiectasis, but not in bronchiectasis secondary to PCD or immune deficiency. In multivariable analysis, CRSwNP was independently associated with elevated type 2 biomarkers. Conclusions:CRS and nasal polyposis are common comorbidities in bronchiectasis, associated with worse symptoms and exacerbations. Elevated type 2 biomarkers are associated with CRS, but this finding is dependent on the aetiology of bronchiectasis.

Rationale: Pseudomonas aeruginosa airway infection is associated with increased exacerbations and poor outcomes in bronchiectasis. Our prior study (GREAT-1) showed that gremubamab—a bivalent, bispecific mAb targeting Psl exopolysaccharide and PcrV T3SS component—enhanced neutrophil clearance of P. aeruginosa and reduced virulence ex-vivo. Here we report the efficacy and safety of gremubamab in a proof-of-concept trial in bronchiectasis patients with P. aeruginosa infection. Methods: In a multi-centre, multinational (UK and Spain), randomized, double-blind, placebo-controlled trial, people with CT-confirmed bronchiectasis and sputum positive for P. aeruginosa were randomised 1:1:1 to 1500mg or 500mg gremubamab intravenous infusion, or placebo, once every four weeks for 12 weeks. Serum and sputum samples were obtained on days 1, 7, 14, 28, 56, 84 (end-of-treatment;EoT), and 168 (12-week follow-up). The primary outcome was change from baseline in quantitative sputum cultures at day 84. Key secondary outcomes included change from baseline in the St. George's Respiratory Questionnaire (SGRQ) and the quality of life bronchiectasis questionnaire (QoL-B), time to first exacerbation, FEV1 and safety. As a proof-of-concept study, statistical significance was pre-specified at the 1-sided p<0.1 level. Results: 37 participants were randomised, n=12 in the gremubamab 1500mg group (age 65.7±13.8 [mean±SD], 66.7% female), n=13 in the 500mg group (age 60.3±16.7, 84.6% female), n=12 in the placebo group (age 65.9±14.4, 66.7% female). Gremubamab treatment resulted in a significant reduction in bacterial load at EoT (day 84) with the 500mg dose compared with placebo treatment ([estimate[80%CI]]; -1.25 log-CFU (-2.33 to -0.16); 1-sided p=0.071; ANCOVA), meeting the trial primary endpoint. A non-significant directional trend was observed for the 1500mg dose (-0.66(-1.71 to 0.39); p=0.2). The SGRQ was significantly improved versus placebo at EoT (500mg: -10.8(-4.93 to -16.7), p=0.02; 1500mg: -12.1(-6.5 to -17.7), p=0.008). The proportion of patients achieving a clinically significant SGRQ improvement was higher for both gremubamab 500mg (38.5%) and 1500mg (41.7%) versus placebo (8.3%). Clinically significant benefit in favour of gremubamab treatment at EoT was observed for multiple QoL-B domains. Time to first exacerbation was significantly prolonged at the 1500mg dose versus placebo (p=0.046; restricted mean survival time method). There was no effect on FEV1. Adverse events (AEs) were reported in 91.7%, 84.6% and 89.2% of the 1500mg, 500mg and placebo groups, respectively, and severe AEs in 0%, 15.4% and 16.7%. Conclusion: Gremubamab treatment significantly reduced P. aeruginosa airway bacterial load and improved patient-reported quality of life in patients with bronchiectasis, providing proof-of-concept for specific anti-microbial monoclonal antibody therapy.

Introduction Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe. Methods Patients with bronchiectasis were enrolled into the European Bronchiectasis Registry from 2015 to 2022. Patients were grouped into ICS users and non-users at baseline and clinical characteristics associated with ICS use were investigated. Patients were followed up for clinical outcomes of exacerbation, hospitalisation and mortality for up to 5 years. We evaluated if elevated blood eosinophil counts (above the laboratory upper limit of normal) modified the effect of ICS on exacerbations. Results 19 324 patients were included for analysis and 10 109 (52.3%) were recorded as being prescribed ICS at baseline. After exclusion of patients with a history of asthma, COPD and/or ABPA, 3174/9715 (32.7%) patients with bronchiectasis were prescribed ICS. Frequency of ICS use varied across countries, ranging from 17% to 85% of included patients. ICS users had more severe disease, with significantly worse lung function, higher Bronchiectasis Severity Index scores and more frequent exacerbations at baseline (p<0.0001). Overall, ICS users did not have a reduced risk of exacerbation or hospitalisation during follow-up, but a significant reduction in exacerbation frequency was observed in the subgroup of ICS users with elevated blood eosinophil counts (relative risk 0.70, 95% CI 0.59 to 0.84, p<0.001). Conclusion ICS use is common in bronchiectasis, including in those not currently recommended ICS according to bronchiectasis guidelines. ICS use may be associated with reduced exacerbation frequency in patients with elevated blood eosinophils.

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. METHODS:We used data from the EMBARC registry, a multicentre international bronchiectasis database. Baseline symptoms were evaluated with the quality-of-life bronchiectasis questionnaire respiratory symptoms score (QoL-B-RSS), followed-up for at least 1 year, and were related to the future risk of exacerbations. We subsequently conducted a post-hoc pooled analysis of three randomised controlled trials of macrolides (ie, BLESS, BAT, and EMBRACE) in 341 participants with bronchiectasis to determine if baseline symptoms were associated with response to long-term macrolide treatment, using a negative binomial regression model. FINDINGS:9466 patients from the 19 324 patients included in the EMBARC registry had available QoL-B-RSS assessment at baseline and 1-year follow-up. The median age was 68 years (IQR 58-74), 5763 (60·9%) were female, and 3703 (39·1%) were male. The median Bronchiectasis Severity Index score was 7 (4-10) and Pseudomonas aeruginosa was present in the sputum of 2041 (21·6%) patients within 12-months of baseline. Previous exacerbations (rate ratio (RR) for every additional exacerbation 1·11, 95% CI 1·10-1·12; p<0·0001) and symptoms (RR for every 10 points lower QoL-B-RSS 1·10, 1·09-1·11; p<0·0001) were identified as independent risk factors for future exacerbations. The number of exacerbations during 1-year of follow-up was similar between patients with three or more exacerbations at baseline and average symptom scores (QoL-B-RSS 60-70; RR 1·58, 95% CI 1·48-1·69) and the group with no previous exacerbations but high symptom scores (RR 1·55, 1·41-1·70). The same pattern was observed in the post-hoc analysis of randomised controlled trials, both in the macrolide and placebo groups. The number-needed-to-treat to prevent exacerbations with long-term macrolide therapy was similar for patients selected based on frequent exacerbations (1·45, 95% CI 1·08-2·24) and in those with few previous exacerbations, but high symptom scores 1·43 (1·06-2·18). INTERPRETATION:Our results suggest that symptoms are an independent risk factor for future exacerbations in bronchiectasis. Patients who are highly symptomatic derive a similar benefit from macrolide treatment as patients with a high baseline exacerbation frequency. FUNDING:EU, European Federation of Pharmaceutical Industries and the Associations Innovative Medicines Initiative Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society.

BACKGROUND:Aspergillus species cause diverse clinical manifestations in bronchiectasis including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS), and raised IgG indicating exposure to, or infection with, Aspergillus. RESEARCH QUESTION:What are the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis? STUDY DESIGN AND METHODS:Patients with bronchiectasis enrolled into the European Bronchiectasis Registry from 2015 through 2022 with laboratory testing for Aspergillus lung disease (total IgE, IgE specific to Aspergillus or Aspergillus skin test, or IgG specific to Aspergillus and blood eosinophil counts) were included for analysis. Modified International Society for Human and Anima Mycology ABPA working group criteria (2024) were used to define ABPA. RESULTS:Nine thousand nine hundred fifty-three patients were included. Six hundred eight patients (6.1%) were classified as having ABPA, 570 patients (5.7%) showed AS, 806 patients (8.1%) showed raised Aspergillus-specific IgG without AS, 184 patients (1.8%) showed both AS and had raised Aspergillus-specific IgG levels, and 619 patients (6.2%) demonstrated eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72% showed negative Aspergillus serologic findings. Patients with ABPA, AS, or raised Aspergillus-specific IgG demonstrated more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG experienced higher exacerbation frequency and more severe exacerbations. AS was associated with increased exacerbations and hospitalizations only in patients not receiving inhaled corticosteroids. INTERPRETATION:Aspergillus lung disease is common in bronchiectasis. Raised IgG levels to Aspergillus were associated with significantly worse outcomes, whereas ABPA and AS were associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use.

Rationale: COPD and bronchiectasis are commonly reported together. Studies report varying impacts of co-diagnosis on outcomes, which may be related to different definitions of disease used across studies. Objectives: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) associated with bronchiectasis and its relationship with clinical outcomes. We further investigated the impact of implementing the standardized ROSE criteria (radiological bronchiectasis [R], obstruction [FEV1/FVC ratio <0.7; O], symptoms [S], and exposure [>= 10 pack-years of smoking; E]), an objective definition of the association of bronchiectasis with COPD. Methods: Analysis of the EMBARC (European Bronchiectasis Registry), a prospective observational study of patients with computed tomography-confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively define the association of bronchiectasis with COPD. Key outcomes during a maximum of 5 years of follow-up were exacerbations, hospitalization, and mortality. Measurements and Main Results: A total of 16,730 patients with bronchiectasis were included; 4,336 had a clinician-assigned codiagnosis of COPD, and these patients had more exacerbations, worse quality of life, and higher severity scores. We observed marked overdiagnosis of COPD: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of >= 10 pack-years of smoking. Therefore, 2,157 patients (55.4%) met the ROSE criteria for COPD. Compared with patients without COPD, patients who met the ROSE criteria had increased risks of exacerbations and exacerbations resulting in hospitalization during follow-up (incidence rate ratio, 1.25; 95% confidence interval, 1.15-1.35; vs. incidence rate ratio, 1.69; 95% confidence interval, 1.51-1.90, respectively). Conclusions: The label of COPD is often applied to patients with bronchiectasis who do not have objective evidence of airflow obstruction or a smoking history. Patients with a clinical label of COPD have worse clinical outcomes.