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Tammy L Kalber,1,2,* Katherine L Ordidge,1,2,* Paul Southern,3 Michael R Loebinger,1 Panagiotis G Kyrtatos,2,3 Quentin A Pankhurst,3,* Mark F Lythgoe,2,* Sam M Janes1,* 1Lungs for Living Research Centre, UCL Respiratory, University College London, 2UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, 3Healthcare Biomagnetics Laboratory, University College London, London, UK *These authors contributed equally to this work Abstract: Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response. Keywords: mesenchymal stem cells, SPIONs, hyperthermia, MRI, tumor therapy

Background: Serum anti-glycopeptidolipid (GPL) core immunoglobuin A (IgA) antibody test has been proposed as a diagnostic tool for Mycobacterium avium complex pulmonary diseases. Cross-reactivity with other non-tuberculous mycobacteria (NTM), including M. abscessus, indicates that it may have a role as a broader screening test for NTM pulmonary disease (NTM-PD). NTM-PD is believed to be underdiagnosed in patients with bronchiectasis., Research Question: Can the serum anti-GPL core IgA antibody test be used to screen for NTM-PD in bronchiectasis?, Study Design and Methods: Patients from the prospective European Bronchiectasis Registry (EMBARC-BRIDGE; NCT03791086) were enrolled. Patients from the United Kingdom, Italy, Spain, Belgium, the Netherlands, and Germany were included. A control cohort of patients without any underlying lung disease was also recruited. The levels of serum IgA antibodies against the GPL core were measured using an enzyme immunoassay kit, and receiver operating characteristics curve analysis was conducted to evaluate the accuracy of the antibody level in screening for NTM-PD., Results: 282 patients were enrolled (151 [53.6%] female, median age 68 years). Median (quartile 1-3) anti-GPL-core IgA antibody levels were 0.2 (0.1-0.3) U/mL in patients without NTM isolation and NTM-PD (n=238), 0.3 (0.2-0.4) U/mL in NTM isolation that were incompatible with the diagnosis of NTM-PD (n=18) and 1.5 (0.4-6.2) U/mL in NTM-PD (n=26) (P=0.0001). Antibody levels showed excellent accuracy in identifying patients with NTM-PD (area under the curve 0.886, 95% CI 0.800-0.973) in bronchiectasis cohort and also showed excellent discrimination of patients with NTM-PD from those with NTM isolation who did not meet the diagnostic criteria for NTM-PD (0.816, 95% CI 0.687-0.945)., Interpretation: The anti-GPL-core IgA antibody demonstrated excellent efficacy in screening for NTM-PD in a large bronchiectasis cohort., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Aspergillus sp. cause diverse clinical manifestations in bronchiectasis including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS) and raised IgG indicating exposure or infection with Aspergillus., Research Question: What is the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis?, Methods: Bronchiectasis patients enrolled into the EMBARC registry from 2015 to 2022 with laboratory testing for Aspergillus lung disease (total IgE, specific IgE to Aspergillus or Aspergillus skin test, IgG to Aspergillus and blood eosinophil counts) were included for analysis. Modified-ISHAM-ABPA working group criteria (2021) were used to define ABPA., Results: 9953 patients were included. 608 (6.1%) were classified as having ABPA, 570 (5.7%) showed Aspergillus sensitization, 806 (8.1%) had raised Aspergillus-specific IgG without sensitisation, 184 (1.8%) were both sensitised to Aspergillus and had raised Aspergillus-specific IgG and 619 (6.2%) had eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72.0% had negative Aspergillus serology. Patients with ABPA, Aspergillus sensitization, and raised Aspergillus-specific IgG had more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG had higher exacerbation frequency and more severe exacerbations. Aspergillus sensitization associated with increased exacerbations and hospitalisations only in patients not receiving inhaled corticosteroids., Interpretation: Aspergillus lung disease is common in bronchiectasis. Raised IgG to Aspergillus is associated with significantly worse outcomes while ABPA and Aspergillus sensitization are associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use., (Copyright © 2024. Published by Elsevier Inc.)

Background: Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality., Study Design and Methods: European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria., Results: Experts reached a consensus on the symptoms and comorbidities that should and should not prompt testing for nontuberculous mycobacteria. Requirements for testing were scored as high (mean ≥7), medium (mean ≥4-<7) or low (mean <4). Nontuberculous mycobacteria testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3-8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection and haemoptysis should prompt testing for nontuberculous mycobacteria, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms., Conclusions: Assessing patients' risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management., Competing Interests: Conflict of interest: M.R. Loebinger reports consultancy work and/or educational talks for 30 Technology, Armata, AN2 Therapeutics, AstraZeneca, Chiesi, Electromed, Insmed B.V., Parion, Recode, Savara and Zambon. Conflict of interest: S. Aliberti has received honoraria for speaker and consultancy services for GSK, INSMED Inc., Insmed Italy, Insmed Ireland Ltd, Zambon, AstraZeneca, CSL Behring GmbH, Menarini, MSD Italy S.r.l. and Thermofisher Scientific. Conflict of interest: C. Haworth reports consultancy work and/or educational talks for 30 Technology, Aradigm, CSL Behring, Chiesi, Gilead, Grifols, GSK, Insmed B.V., Janssen, LifeArc, Meiji, Mylan, Novartis, Pneumagen, Shionogi, Teva, Vertex and Zambon. Conflict of interest: M. Jankovic Makek has received honoraria for speaker and consultancy services from Insmed B.V., Biomerieux, MSD and Boeringher Ingelheim, and speaker services from Teva, Alkaloid, AstraZeneca and GSK. Conflict of interest: C. Lange has received honoraria for speaking at events supported by Insmed B.V., Gilead and Janssen. He has been a member of a scientific advisory board of Insmed B.V. and received honorarium for this function. Conflict of interest: N. Lorent has received speaker and consultancy services from Insmed B.V., GSK and AstraZeneca. She has been the coordinator of the Belgian NTM faculty meetings and a member of the scientific advisory board, both for Insmed. For these services, fees were paid to her institution (Katholieke Universiteit Leuven/University Hospitals Leuven). Conflict of interest: E. Polverino has received speaker and consultancy services from Insmed B.V., Chiesi, Grifols, GSK, Teva, Electromed, Pfizer, Moderna and Zambon. Conflict of interest: G. Rohde performed speaker and/or consultancy services for Insmed B.V. and Becton Dickinson, and received support for congress attendance from Otsuka. Conflict of interest: N. Veziris performed speaker and/or consultancy services for Insmed B.V. and Becton Dickinson, and is involved in an IMI-AMR project led by Janssen. Conflict of interest: D. Wagner participated in clinical trials supported by Insmed Inc. but otherwise has no conflict of interests to declare. Conflict of interest: J. van Ingen reports honoraria for speaking or advisory boards from Janssen Pharmaceuticals, Insmed B.V, Spero Therapeutics and Paratek., (Copyright ©The authors 2024.)

Primary ciliary dyskinesia (PCD), a disorder of the motile cilia, is now recognised as an underdiagnosed cause of bronchiectasis. Accurate PCD diagnosis comprises clinical assessment, analysis of cilia and the identification of biallelic variants in one of 50 known PCD-related genes, including HYDIN. HYDIN-related PCD is underdiagnosed due to the presence of a pseudogene, HYDIN2, with 98% sequence homology to HYDIN. This presents a significant challenge for Short-Read Next Generation Sequencing (SR-NGS) and analysis, and many diagnostic PCD gene panels do not include HYDIN. We have used a combined approach of SR-NGS with bioinformatic masking of HYDIN2, and state-of-the-art long-read Nanopore sequencing (LR&#95;NGS), together with analysis of respiratory cilia including transmission electron microscopy and immunofluorescence to address the underdiagnosis of HYDIN as a cause of PCD. Bioinformatic masking of HYDIN2 after SR-NGS facilitated the detection of biallelic HYDIN variants in 15 of 437 families, but compromised the detection of copy number variants. Supplementing testing with LR-NGS detected HYDIN deletions in 2 families, where SR-NGS had detected a single heterozygous HYDIN variant. LR-NGS was also able to confirm true homozygosity in 2 families when parental testing was not possible. Utilising a combined genomic diagnostic approach, biallelic HYDIN variants were detected in 17 families from 242 genetically confirmed PCD cases, comprising 7% of our PCD cohort. This represents the largest reported HYDIN cohort to date and highlights previous underdiagnosis of HYDIN-associated PCD. Moreover this provides further evidence for the utility of LR-NGS in diagnostic testing, particularly for regions of high genomic complexity., (© 2024. Crown.)

Background: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes., Methods: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV 1 )) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV 1 ., Results: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV 1 z-score (-1.66). Median FEV 1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV 1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort., Conclusion: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

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 [FEV 1 /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.

Rationale: Chest computed tomography (CT) scans are essential to diagnose and monitor bronchiectasis (BE). To date, few quantitative data are available about the nature and extent of structural lung abnormalities (SLAs) on CT scans of patients with BE. Objectives: To investigate SLAs on CT scans of patients with BE and the relationship of SLAs to clinical features using the EMBARC (European Multicenter Bronchiectasis Audit and Research Collaboration) registry. Methods: CT scans from patients with BE included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). The subscores of this instrument are expressed as percentages of total lung volume. The items scored are atelectasis/consolidation, BE with and without mucus plugging (MP), airway wall thickening, MP, ground-glass opacities, bullae, airways, and parenchyma. Four composite scores were calculated: total BE (i.e., BE with and without MP), total MP (i.e., BE with MP plus MP alone), total inflammatory changes (i.e., atelectasis/consolidation plus total MP plus ground-glass opacities), and total disease (i.e., all items but airways and parenchyma). Measurements and Main Results: CT scans of 524 patients with BE were analyzed. Mean subscores were 4.6 (range, 2.3-7.7) for total BE, 4.2 (1.2-8.1) for total MP, 8.3 (3.5-16.7) for total inflammatory changes, and 14.9 (9.1-25.9) for total disease. BE associated with primary ciliary dyskinesia was associated with more SLAs, whereas chronic obstructive pulmonary disease was associated with fewer SLAs. Lower FEV 1 , longer disease duration, Pseudomonas aeruginosa and nontuberculous mycobacterial infections, and severe exacerbations were all independently associated with worse SLAs. Conclusions: The type and extent of SLAs in patients with BE are highly heterogeneous. Strong relationships between radiological disease and clinical features suggest that CT analysis may be a useful tool for clinical phenotyping.

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., Competing Interests: Conflict of interest: B. Hererro-Cortina reports payment or honoraria for lectures, presentations, manuscript writing or educational events from SEPAR (Spanish Respiratory Society), and has a leadership or fiduciary role in SEPAR. S. Aliberti reports grants from Insmed Incorporated, Chiesi, Fisher and Paykel, and GSK; royalties or licences from McGraw Hill; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Ltd, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MCD Italis Srl, Brahms, Physioassist SAS and GSK SpA; payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK SpA, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon and Fondazione Internazionale Menarini; and participation on a data safety monitoring board or advisory board for Insmed Incorporated, Insmed Italy, AstraZeneca UK Ltd and MSD Italia Srl. P.C. Goeminne reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, GSK and Chiesi; support for attending meetings and/or travel from Chiesi; and participation on a data safety monitoring board or advisory board for Boehringer, GSK and Pfizer. E. Polverino reports grants from Grifols; consulting fees from Insmed, Bayer, Chiesi and Zambon; payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Chiesi, Grifols, GSK, Insmed, Menarini and Zambon; and support for attending meetings and/or travel from Insmed, Pfizer and Moderna. K. Dimakou reports payment or honoraria for lectures, presentations, manuscript writing or educational events 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 board or advisory board for Novartis, GSK and Chiesi. C.S. Haworth reports payment or honoraria for lectures, presentations, manuscript writing or educational events from 30 Technology, CSL Behring, Chisi, Insmed, Janssen, LifeArc, Meiji, Mylan, Pneumagen, Shionogi, Vertex and Zambon. M.R. Loebinger reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2 and Boehringer Ingelheim; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed; and is ERS Infection Group Chair. A. De Soyza reports grants from AstraZeneca, Pfizer, GSK and Novartis; consulting fees from AstraZeneca, Insmed, GSK, Boehringer, 30T and Bayer; and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Pfizer, GSK and Novartis. M. Vendrell reports grants from Chiesi; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed and Publi Creation; support for attending meetings and/or travel from Zambon, Chiesi, Novartis, Behring and Gebro; participation on a data safety monitoring board or advisory board for Insmed; and receipt of equipment, materials, drugs, medical writing, gifts or services from Insmed and Novartis. P.R. Burgel reports grants from GSK and Vertex; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Vertex, Viatris and Zambon; and support for attending meetings and/or travel from AstraZeneca and Chiesi. S. Sutharsan reports grants from Vertex, Galapagos, Insmed, Proteostasis and Corbus; consulting fees from Insmed, Vertex Pharmaceuticals and Boehringer Ingelheim; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals, Boehringer Ingelheim and Insmed. S. Škrgat reports honoraria for educational events, invited lectures and presentations supported by Sanofi, AstraZeneca, Medis, Berlin-Chemie and Chiesi; and participation on a data safety monitoring board or advisory board for AstraZeneca. D. Stolz reports payment or honoraria for lectures, presentations, manuscript writing or educational events from CSL Behring, Berlin-Chemie, Menarini, Novartis, GSK, AstraZeneca, Vifor, Merck, Chiesi and Sanofi; and participation on a data safety monitoring board or advisory board for GSK and CSL Behring. P. Kauppi reports support for attending meetings and/or travel from Nordic Respiratory Academy; participation on a data safety monitoring board or advisory board for Swedish Orphan Biovitrium; a leadership or fiduciary role for the Finnish Respiratory Society and Finnish Tuberculosis Foundation Grant Committee; and receipt of equipment, materials, drugs, medical writing, gifts or services from Theravance. A. Bossios reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi; and is Secretary of Assembly 5 (Airway diseases, asthma, COPD and chronic cough) of the ERS, Vice-chair of the Nordic Severe Asthma Network (NSAN)-NORDSTAR and a member of the Steering Committee of the ERS CRC for severe asthma (SHARP). I. Clifton reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and GSK; and participation on a data safety monitoring board or advisory board for AstraZeneca, GSK and Infex Therapeutics. M.L. Crichton reports consulting fees from Boxer Capital LLC. P. Walker is Chair of the British Thoracic Society. D. Obradovic is President of the Serbian Society of Intensive Care Medicine. A. Amorim reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Zambon Group, and support for attending meetings and or/travel from Zambon Group, Boehringer Ingelheim and Novartis Farma. F. Blasi reports grants from AstraZeneca, Chiesi and Insmed; consulting fees from Menarini; and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi, GSK, Guidotti, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Viatris, Vertex and Zambon. M. Jankovic Makek reports consulting fees from Insmed, Biomerieux and MSD; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, MSD, Pfizer and Teva; and support for attending meetings and/or travel from MSD, Pfizer and Berlin-Chemie. M. Shteinberg reports consulting fees from GSK, Boehringer Ingelheim, Kamada and Zambon; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada and Sanofi; support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GSK and Rafa; participation on a data safety monitoring board or advisory board for Bonus Therapeutics, Israel; leadership or fiduciary roles for EMBARC Management, Israel Pulmonology Society Board and the Israel Society for TB and Mycobacterial Diseases; receipt of equipment, materials, drugs, medical writing, gifts or services from Trudell Medical Int.; and is and Associate Editor of the American Journal of Respiratory and Critical Care Medicine. J.D. Chalmers reports grants from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GSK, Grifols, Insmed, LifeArc and Novartis; and consulting fees from AstraZeneca, Chiesi, GSK, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. F.C. Ringshausen reports grants from German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU/EFPIA) and iABC Consortium (including Alaxia, Basilea, Novartis and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer and InfectoPharm; consulting fees from Parion, Grifols, Zambon, Insmed and Helmholtz-Zentrum für Infektionsforschung; payment or honoraria for lectures, presentations, manuscript writing or educational events from I!DE Werbeagentur GmbH, Interkongress GmbH, AstraZeneca, Insmed, Grifols and Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne; support for attending meetings and/or travel from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group Mukoviszidose e.V.; participation on a data safety monitoring board or advisory board for Insmed, Grifols and Shionogi; leadership or fiduciary roles as Coordinator of the ERN-LUNG Bronchiectasis Core Network, Chair of the German Bronchiectasis Registry PROGNOSIS, Member of the Steering Committee of the European Bronchiectasis Registry EMBARC, Member of the Steering Committee of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM, Co-Speaker of the Medical Advisory Board of the German Kartagener Syndrome and PCD Patient Advocacy Group, Speaker of the Respiratory Infections and TB group of the German Respiratory Society, Speaker of the Cystic Fibrosis group of German Respiratory Society (DGP), principal investigator of the German Center for Lung Research, Member of the Protocol Review Committee of the PCD-CTN and Member of Physician Association of the German Cystic Fibrosis Patient Advocacy Group; and other financial or non-financial interests in AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: Asthma is commonly reported in patients with a diagnosis of bronchiectasis., Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma., Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography-confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression., Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs., Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes., Methods: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up., Results: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV 1 ), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence., Conclusion: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis., Competing Interests: Conflict of interest: S. Aliberti reports grants or contracts from Insmed Incorporated, Chiesi, Fisher & Paykel and GlaxoSmithKline, royalties or licences from McGraw Hill, consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon SpA, AstraZeneca UK Ltd, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MCD Italia Srl, Brahms, PhysioAssist SAS and GlaxoSmithKline SpA, payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline SpA, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon and Fondazione Internazionale Menarini, and participation on a data safety monitoring board or advisory board for Insmed Incorporated, Insmed Italy, AstraZeneca UK Ltd and MSD Italia Srl. F.C. Ringshausen reports grants or contracts 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, Insmed Germany, Grifols, Bayer and InfectoPharm, consulting fees from Parion, Grifols, Zambon, Insmed and Helmholtz-Zentrum für Infektionsforschung, payment or honoraria for lectures, presentations, manuscript writing or educational events from I!DE Werbeagentur GmbH, Interkongress GmbH, AstraZeneca, Insmed, Grifols and Universitätsklinikum Frankfurt am Main, payment for expert testimony from Social Court Cologne, support for attending meetings and/or travel from the German Kartagener Syndrome and Primary Ciliary Dyskinesia (PCD) Patient Advocacy Group Mukoviszidose eV, participation on a data safety monitoring board or advisory board for Insmed, Grifols and Shionogi, and leadership or fiduciary roles as Coordinator of the ERN-LUNG Bronchiectasis Core Network, Chair of the German Bronchiectasis Registry PROGNOSIS, Member of the SteerCo of the European Bronchiectasis Registry EMBARC, Member of the SteerCo of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM, Co-Speaker of the Medical Advisory Board of the German Kartagener Syndrome and PCD Patient Advocacy Group, Speaker of the Respiratory Infections and TB group of the German Respiratory Society (DGP), Speaker of the Cystic Fibrosis group of German Respiratory Society (DGP), PI of the German Center for Lung Research (DZL), Member of the Protocol Review Committee of the PCD-CTN, and Member of the Physician Association of the German Cystic Fibrosis Patient Advocacy Group; F.C. Ringshausen has other financial or non-financial interests with AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon. R. Dhar reports payment or honoraria for lectures, presentations, manuscript writing or educational events from LUPIN, CIPLA and Glenmark. C.S. Haworth reports payment or honoraria for lectures, presentations, manuscript writing or educational events from 30 Technology, CSL Behring, Chisi, Insmed, Janssen, LifeArc, Meiji, Mylan, Pneumagen, Shionogi, Vertex and Zambon. M.R. Loebinger reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2 and Boehringer Ingelheim, payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, and a leadership or fiduciary role as ERS Infection Group Chair. K. Dimakou reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Novartis, Boehringer Ingelheim, GlaxoSmithKline, Norma Hellas, Chiesi, AstraZeneca and Zambon, support for attending meetings and/or travel from Novartis, Boehringer Ingelheim, GlaxoSmithKline, Norma Hellas, Chiesi, AstraZeneca and Menarini, and participation on a data safety monitoring board or advisory board for Novartis, GlaxoSmithKline and Chiesi. M.L. Crichton reports consulting fees from Boxer Capital LLC. A. De Soyza reports grants or contracts from AstraZeneca, Pfizer, GlaxoSmithKline and Novartis, consulting fees from AstraZeneca, Insmed, GlaxoSmithKline, Boehringer, 30T and Bayer, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Pfizer, GlaxoSmithKline and Novartis. M. Vendrell reports grants or contracts from Chiesi, payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed and Publi Creation, support for attending meetings and/or travel from Zambon, Chiesi, Novartis, Behring and Gebro, participation on a data safety monitoring board or advisory board for Insmed, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Insmed and Novartis. P-R. Burgel reports grants or contracts from GlaxoSmithKline and Vertex, consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, MSD, Vertex, Viatris and Zambon, and support for attending meetings and/or travel from AstraZeneca and Chiesi. S. Skrgat reports honoraria for educational events, invited lectures and presentations supported by Sanofi, AstraZeneca, Medis, Berlin-Chemie and Chiesi, and participation on a data safety monitoring board or advisory board for AstraZeneca. A. de Roux reports consulting fees from Adboard Insmed, payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, AstraZeneca, GlaxoSmithKline, Berlin-Chemie and Boehringer Ingelheim, support for attending meetings and/or travel from AstraZeneca, and advisory board participation with Insmed. A. Bossios reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, and leadership or fiduciary roles as Secretary of ERS Assembly 5 (Airway diseases, asthma, COPD and chronic cough), Vice-chair of the Nordic Severe Asthma Network (NSAN)-NORDSTAR and on the Steering Committee of ERS CRC Severe Asthma (SHARP). P. Kauppi reports support for attending meetings and/or travel from the Nordic Respiratory Academy, participation on a data safety monitoring board or advisory board for the Swedish Orphan Biovitrium, leadership or fiduciary roles for the Finnish Respiratory Society and Finnish Tuberculosis Foundation Grant Committee, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Theravance. M. Murris reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Pfizer, payment for expert testimony from Vertex, support for attending meetings and/or travel from Zambon, and participation on a data safety monitoring board or advisory board for Zambon and Viatris. D. Obradovic reports a leadership or fiduciary role as president of the Serbian Society of Intensive Care Medicine. A. Amorim reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Zambon Group, and support for attending meetings and or/travel from Zambon Group, Boehringer Ingelheim and Novartis Farma. E. Van Braeckel reports grants or contracts from Insmed, Boehringer Ingelheim and Zambon. A. Shoemark reports consulting fees from Spirovant and Translate Bio, payment or honoraria for lectures, presentations, manuscript writing or educational events from Translate Bio, Ethris and Insmed, leadership or fiduciary roles in ERS CRCs (EMBARC, BEATPCD, AMR). M. Shteinberg reports consulting fees from GlaxoSmithKline, Boehringer Ingelheim, Kamada and Zambon, payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Teva, Novartis, Kamada and Sanofi, support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GlaxoSmithKline and Rafa, participation on a data safety monitoring board or advisory board for Bonus Therapeutics, Israel, leadership or fiduciary roles in EMBARC, Israel Pulmonology Society, and Israel Society for TB and Mycobacterial Diseases, receipt of equipment, materials, drugs, medical writing, gifts or other services from Trudell Medical International, and is Associate Editor of the American Journal of Respiratory and Critical Care Medicine. P.C. Goeminne reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, GlaxoSmithKline and Chiesi, support for attending meetings and/or travel from Chiesi, and participation on a data safety monitoring board or advisory board for Boehringer, GlaxoSmithKline and Pfizer. T. Welte reports grants from the German Ministry of Research and Education (BMBF), consulting fees and lecture honoraria from AstraZeneca, Chiesi, Grifols, GlaxoSmithKline, Insmed, MSD, Novartis, Pfizer and Sanofi, leadership roles for the German Center for Lung Research (DZL) – Board of Directors, Novartis Foundation – Board of Directors, Chairman of the Board of Trustees for CAPNETZ Foundation, German Lung Foundation, German Sepsis Foundation, and is Past President of the ERS, German Society of Pneumology and German Sepsis Society. F. Blasi reports grants or contracts from AstraZeneca, Chiesi, GlaxoSmithKline and Insmed, consulting fees from Menarini, GlaxoSmithKline and Om Pharma, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi, GlaxoSmithKline, Guidotti, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Viatris, Vertex and Zambon. E. Polverino reports grants or contracts from Grifols, consulting fees from Insmed, Bayer, Chiesi and Zambon, payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Chiesi, Grifols, GlaxoSmithKline, Insmed, Menarini and Zambon, and support for attending meetings and/or travel from Insmed, Pfizer and Moderna. J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, LifeArc and Novartis, and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon, and is Chief Editor of the European Respiratory Journal. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Rationale: Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection. Objectives: This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection ( Mycobacterium avium complex [MAC] and M. abscessus [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability. Methods: Thirty-two adult patients with refractory NTM infection (MAC, n  = 24; MABS, n  = 8) were recruited into two cohorts: those with ( n  = 16) and without ( n  = 16) ongoing GBT. Nebulized molgramostim 300 μg/d was administered over 48 weeks. Sputum cultures and smears and clinical assessments (6-min-walk distance, symptom scores, Quality of Life-Bronchiectasis Questionnaire score, and body weight) were collected every 4 weeks during treatment and 12 weeks after the end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive monthly negative cultures during the treatment period. Results: Eight patients (25%) achieved culture conversion on treatment (seven [29.2%] patients with MAC infection, one [12.5%] patient with MABS infection); in four patients, this was durable after the end of treatment. Of the 24 patients with MAC infection, an additional 4 patients had a partial response, converting from smear positive at baseline to smear negative at the end of treatment, and time to positivity in liquid culture media increased. Two of these patients sustained negative cultures from the end of treatment. Other clinical endpoints were unchanged. Serious adverse events were mainly pulmonary exacerbations or worsening NTM infection. Three deaths, not treatment related, were reported. Conclusions: In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. Less benefit was seen for MABS infection. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.Clinical trial registered with www.clinicaltrials.gov (NCT03421743).

How to identify MAC-PD patients with limited treatment options: an expert consensus https://bit.ly/3QwLQ8T., Competing Interests: Conflict of interest: A. Fløe reports participation on an advisory board for Insmed Inc., outside the submitted work. Conflict of interest: P.R. Burgel reports grants or contracts from GSK and Vertex, outside the submitted work; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Pfizer, Vertex, Viatris and Zambon, outside the submitted work. Conflict of interest: A. Calcagno reports receiving support for the present manuscript from Insmed; consulting fees from Insmed, outside the submitted work; and speakers’ honoraria from Insmed, outside the submitted work. Conflict of interest: E. Polverino reports support for the present manuscript from Lena Group; grants or contracts from Grifols, outside the submitted; consulting fees from Insmed, Chiesi, Zambon and Electromed, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, Chiesi, Zambon, Teva, Boehringer, Glaxo and Electromed, outside the submitted work; payment for expert testimony from Chiesi, outside the submitted work; support for attending meetings and/or travel from Insmed, Teva, Glaxo and Chiesi, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Insmed, Electromed, and Chiesi, outside the submitted work. Conflict of interest: G. Rohde reports personal fees from AstraZeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis and Pfizer for consultancy during advisory board meetings, outside the submitted work; and personal fees from AstraZeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures including service on speakers' bureaus, outside the submitted work. Conflict of interest: H.J.F. Salzer reports receiving support for the present manuscript from Insmed; and honoraria for lectures from Insmed, GSK, Gilead and Chiesi, outside the submitted work. Conflict of interest: A. Sánchez-Montalvá reports receiving support for the present manuscript from Insmed; and consulting fees from Insmed, outside the submitted work. Conflict of interest: M. Shteinberg reports receiving support for the present manuscript from Insmed. A. Sánchez-Montalvá reports grants or contracts from GSK, Trumed and Novartis, outside the submitted work; consulting fees from GSK, Boehringer Ingelheim, Kamada and Zambon, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada and Sanofi, outside the submitted work; support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GSK and Rafa, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Boards for Bonus Therapeutics, Israel, outside the submitted work; a leadership or fiduciary role in an other board, society, committee or advocacy group for EMBARC management, Israel Pulmonology Society board, and Israel society for TB and mycobacterial diseases, outside the submitted work; receipt of equipment, materials, drugs, medical writing, gifts or other services from Trudell Medical Intnl; receipt of supply to clinical trial, outside the submitted work; other financial or non-financial interests. A. Sánchez-Montalvá is Associate Editor, American Journal of Respiratory and Critical Care Medicine, with a direct stipend, outside the submitted work. Conflict of interest: E. Van Braeckel reports support for the present manuscript from Publi Creations SAM – Lenagroup; grants or contracts from Insmed, outside the submitted work; consulting fees from Insmed, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work. E. Van Braeckel is Chair of the Belgian Respiratory Society working group on respiratory infections, unpaid, outside the submitted work. Conflict of interest: J. van Ingen reports grants or contracts from MannKind and AN2, outside the submitted work; patents planned, issued or pending: Inhaled tigecycline for M. abscessus treatment, outside the submitted work. Conflict of interest: N. Veziris reports receiving support for the present manuscript from Insmed; grants or contracts from Bioversys, outside the submitted work; consulting fees from Insmed and Becton Dickinson, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work; payment for expert testimony from Insmed, outside the submitted work; support for attending meetings and/or travel from Insmed, outside the submitted work; and was involved in the Respiri-NTM consortium with Janssen, outside the submitted work. Conflict of interest: D. Wagner reports support for the present manuscript from Publi Creations SAM via an unrestricted grant by Insmed Inc.; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Biomerieux, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, outside the submitted work; and participation in clinical trials for Insmed, outside the submitted work. Conflict of interest: S. Aliberti reports grants or contracts from Insmed Incorporated, Chiesi, Fisher & Paykel and GSK, outside the submitted work; royalties or licences from McGraw Hill, outside the submitted work; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Limited, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MSD Italia S.r.l., Brahms, Physioassist SAS and GlaxoSmithKline Spa, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, Insmed Italy, Insmed Ireland Ltd, Zambon, and Fondazione Internazionale Menarini, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for INSMED Incorporated, INSMED Italy, AstraZeneca UK Limited, and MSD Italia S.r.l, outside the submitted work. Conflict of interest: F. Blasi reports grants or contracts from AstraZeneca, Chiesi, GlaxoSmithKline and Insmed, outside the submitted work; consulting fees from GlaxoSmithKline, Menarini and OM Pharma, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Chiesi, GlaxoSmithKline, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Vertex, Viatris and Zambon, outside the submitted work. Conflict of interest: A. Papavasileiou reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work. Conflict of interest: M.R. Loebinger reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, Savara, Boehringer Ingelheim and Mannkind, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work; and is chair of the ERS Respiratory Infection group, outside the submitted work. Conflict of interest: D. Grogono reports consulting fees from Insmed, outside the submitted work; and support received from Insmed for attending a consensus meeting. Conflict of interest: C. Prados has nothing to disclose., (Copyright ©The authors 2024.)

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., Competing Interests: Conflict of interest: S. Aliberti has received fees outside of this work from Insmed, Zambon, AstraZeneca, CSL Behring GmbH, Grifols, Fondazione Internazionale MENARINI, MSD Italia S.r.l., Brahms, Physioassist SAS and GlaxoSmithKline. S.D. Dell has received grants outside of this work from Boehringer Ingelheim, Vertex and Sanofi, and she owns the copyright to the PCD-QOL Questionnaires. T.W. Ferkol has received consulting fees from Translate Bio and Arrowhead Pharmaceuticals. R.A. Athanazio has received personal fees outside of this work from Astrazeneca, Chiesi, GSK, Omron, Sanofi, Vertex and Zambon. K.G. Nielsen is part of the European Reference Network on respiratory diseases (ERN-LUNG) and director of PCD CTN. F.C. Ringshauen has received fees outside of this work from AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon. M. Shteinberg has received consulting fees from AstraZeneca, Boehringer Ingelheim, Dexcel, Kamada, Synchrony Medical, Trumed and Zambon. J.D. Chalmers has received grants outside of this work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Gilead Sciences, Grifols, Insmed, Janssen, Novartis, Pfizer and Zambon; and is an associate editor of this journal. The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: Mucociliary clearance is dysfunctional in people with primary ciliary dyskinesia, resulting in the accumulation of dehydrated mucus in the airways that is difficult to clear. We undertook a study to assess the benefit on lung function of treatment with a nebulised epithelial sodium channel (ENaC) blocker, idrevloride, with or without hypertonic saline, in people with primary ciliary dyskinesia., Methods: The CLEAN-PCD trial was a phase 2, randomised, double-blind, placebo-controlled crossover trial conducted at 32 tertiary adult and paediatric care centres and university hospitals in Canada, Denmark, Germany, Italy, the Netherlands, Poland, the UK, and the USA. People with a confirmed diagnosis of primary ciliary dyskinesia, aged 12 years or older, with a percentage of predicted FEV 1 (ppFEV 1 ) in the range of 40% to <90%, were randomly assigned in a 2:2:1:1 ratio (block size=6), stratified by ppFEV 1 at screening, to one of four sequences: (1) idrevloride in hypertonic saline in treatment period 1 then hypertonic saline in treatment period 2; (2) hypertonic saline in treatment period 1 then idrevloride in hypertonic saline in treatment period 2; (3) idrevloride in treatment period 1 then placebo in treatment period 2; and (4) placebo in treatment period 1 then idrevloride in treatment period 2. The idrevloride dose was 85 μg and hypertonic saline was 4·2% NaCl. 3 mL of each study treatment was nebulised twice daily for 28 days in treatment periods 1 and 2; the two 28-day treatment periods were separated by a 28-day washout period. The primary endpoint was absolute change from baseline in ppFEV 1 after 28 days. Safety assessments and reports of adverse events were made at clinic visits during each treatment period and by a follow-up telephone call 28 days after the last dose of study drug. Additionally, adverse events could be reported at a follow-up telephone call 3 days after the start of dosing and as they arose. Participants who received at least one dose of study drug were included in the safety analyses (safety set), and those who also had spirometry data were included in the efficacy analyses (full analysis set). The completed study is registered (EudraCT 2015-004917-26; ClinicalTrials.govNCT02871778)., Findings: Between Sep 14, 2016, and May 31, 2018, 216 patients were screened and 123 were randomly assigned to one of four crossover sequences. Across the two treatment periods, treatment with idrevloride in hypertonic saline was initiated in 80 patients and completed in 78 patients (all 78 had data available and were included in the analysis); hypertonic saline initiated in 81 patients and completed in 76 patients (75 had data available and were included in the analysis); idrevloride initiated in 37 patients and completed in 35 patients (34 had data available and were included in the analysis); and placebo initiated in 36 patients and completed in 34 patients (all 34 had data available and were included in the analysis). Greater absolute increases in ppFEV 1 from baseline to 28 days of treatment were seen with idrevloride in hypertonic saline (least-squares mean absolute change from baseline 1·0 percentage points, 95% CI -0·4 to 2·4) than with hypertonic saline alone (least-squares mean absolute change from baseline of -0·5 percentage points, -2·0 to 0·9; difference 1·5 percentage points, 95% CI <0·1 to 3·0; p=0·044). There was no significant difference in ppFEV 1 for the parallel comparison of idrevloride in hypertonic saline compared with placebo or the crossover comparison of idrevloride with placebo. Adverse events were similar across treatments (57 to 65% of patients). Cough occurred in a greater proportion of participants during treatments that contained idrevloride or hypertonic saline compared with placebo, and oropharyngeal pain occurred in a greater proportion of participants during idrevloride treatments than during treatment with hypertonic saline alone or placebo, whereas chest discomfort was more common during treatments that included hypertonic saline., Interpretation: In this phase 2 crossover study, idrevloride in hypertonic saline was safe and associated with improved lung function over a 28-day period in people with primary ciliary dyskinesia compared with hypertonic saline alone. Larger, longer clinical studies are warranted to explore the potential benefits of idrevloride in combination with hypertonic saline in people with primary ciliary dyskinesia., Funding: Parion Sciences, under agreement with Vertex Pharmaceuticals., Competing Interests: Declaration of interests FCR has contracts or grants from the German Center for Lung Research, German Center for Infection Research, Innovative Medicines Initiative (European Union and European Federation of Pharmaceutical Industries and Associations) funded project “Inhaled antibiotics in bronchiectasis and cystic fibrosis” (including Alaxia, Basilea, Novartis, and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer, and InfectoPharm; consulting fees from Parion Sciences, Grifols, Zambon, Insmed, and Helmholtz-Zentrum für Infektionsforschung; payment or honoraria from I!DE Werbeagentur, Interkongress, AstraZeneca, Insmed, Grifols, and Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne; support for meetings attended from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advisory Group, and Mukoviszidose; participated in an advisory board for Insmed, Grifols, and Shionogi; has leadership roles in the following organisations: European Reference Network-Lung Bronchiectasis Core Network, German Bronchiectasis Registry PROGNOSIS, Steering Committee of the European Bronchiectasis Registry EMBARC, Steering Committee of the European Non-Tuberculous Mycobacteria Registry EMBARC-NTM, Medical Advisory Board of the German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group, Respiratory Infections and Tuberculosis group of the German Respiratory Society (Deutsche Gesellschaft für Pneumologie), Cystic Fibrosis group of German Respiratory Society (Deutsche Gesellschaft für Pneumologie), German Center for Lung Research, Protocol Review Committee of the Primary Ciliary Dyskinesia - Clinical Trial Network, and Physician Association of the German Cystic Fibrosis Patient Advocacy Group; and has received fees for clinical trial participation from AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex, and Zambon. AJS has received grants or contracts from The National Institutes of Health, The Office of Rare Disease Research, The National Center for Advancing Translational Sciences, The National Heart, Lung, and Blood Institute grant (U54HL096458), The Chest Foundation, and Fondation Pierre Lavoie; has received consulting fees from Parion Sciences; has received meeting support from The Chest Foundation; and participated on an advisory board for Parion Sciences, ReCode Therapeutics, and The Primary Ciliary Dyskinesia Foundation. KGN received grants or contracts from the Children's Lung Foundation; consulting fees from Boehringer Ingelheim, Parion Sciences, AstraZeneca, ReCode, and ETHRIS; participated on an advisory board for Boehringer Ingelheim, Parion Sciences, AstraZeneca, ReCode, and ETHRIS; received fees for clinical trial participation from Insmed, Vertex, and ALK-Abelló; and is a Director of the Primary Ciliary Dyskinesia - Clinical Trial Network. HM received honoraria for lectures from Vertex. MRL received consulting fees from Armata, 30T, Astra Zeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, Savara, and Boehringer Ingelheim; payment or honoraria for presentations from Insmed; and is the Infection group chair for the European Respiratory Society. MAZ received funding from Parion Sciences for the current work. KHD is an employee and owns stocks or stock options for Parion Sciences. MWL received funding from Parion Sciences for the current work; received grants or contracts from National Institutes of Health and Primary Ciliary Dyskinesia Foundation; support for attending meetings from American Thoracic Society; and is a member of the Primary Ciliary Dyskinesia Foundation Board. MRK owns stocks or stock options in Parion Sciences. TWF received grants or contracts from National Institutes of Health (AI146999, HL125241, and HL096458), Parion Sciences, and ReCode Therapeutics; consulting fees from Translate Bio and Arrowhead Pharmaceuticals; and participated in an advisory board for ReCode Therapeutics. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management., Competing Interests: Declaration of competing interest All authors are members of NTM Network UK, which is a network of healthcare professionals, researchers and patients from across the UK who have an interest in infections caused by non-tuberculous mycobacteria. TGDC has received non-financial support from Napp and GSK for attendance at ERS conference; TGDC's employer has received payment for his participation in advisory boards or for providing teaching sessions from AstraZeneca, Chiesi, GSK, Novartis, Boehringer Ingelheim, and Insmed, outside the submitted work. CC received non-financial support from GSK for attendance at ERS; CC's employer has received financial support from AstraZeneca through her grant application; CC received payment for her participation in advisory boards or providing teaching from AstraZeneca, Chiesi, GSK and Insmed, outside the submitted work. RH has received consultancy fees from Insmed, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression., Research Question: What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis?, Study Design and Methods: Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis., Results: Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26)., Interpretation: The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with identification of patient populations at risk for NTM-PD to drive prompt testing and appropriate initiation of therapy., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. R. L. reports receiving honorarium from Insmed, AstraZeneca, Chiesi, Grifols, Savara, Armata; J. K. Q. has received grants from The Health Foundation, Medical Research Council, GlaxoSmithKline, Bayer, Boehringer Ingelheim, Asthma UK-British Lung Foundation, HDR UK, Chiesi, and AstraZeneca and personal fees for advisory board participation or speaking fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Chiesi, Insmed, and Bayer; J. v. I. reports honorarium for speaking or advisory boards from Janssen Pharmaceuticals, Insmed, Spero Therapeutics, and Paratek; R. v. d. L. is an employee of Insmed B.V.; M. O. is an employee of Insmed Germany GmbH; R. C. and A. K. are employees of Accuscript Consultancy., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Non-tuberculous mycobacteria (NTM) and Aspergillus are ubiquitous organisms that have the potential to cause significant pulmonary disease in certain clinical contexts. An association is known to exist between NTM and Aspergillus lung infections. However, it is unclear if NTM infection predisposes to Aspergillus infection or vice versa. It is also unclear whether treatment for one results in a favourable ecological niche that facilitates the growth of the other and promotes subsequent clinical disease. An improved understanding of the link between these two pulmonary pathogens is critical to guide improvements in clinical practice, and ultimately, enhance outcomes among patients who are at risk of experiencing these infections, either concomitantly or sequentially. Here, we discuss the association between pulmonary NTM and Aspergillus infections. We address the frequency with which coinfection or sequential infections are reported to occur, predisposing risk factors that have been identified and the impact on clinical outcomes. Current data on the mechanistic links between NTM and Aspergillus lung infections are also considered. The potential implications for routine clinical practice are explored.

Objectives: Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages., Methods: Antibiotic susceptibility testing was performed using CLSI breakpoints (n = 95), and plaque assays were used for phage susceptibility testing (subset of n = 88, 35 rough and 53 smooth morphology). WGS was completed using the Illumina platform and analysed using Snippy/snp-dists and Discovery and Extraction of Phages Tool (DEPhT)., Results: Amikacin and Tigecycline were the most active drugs (with 2 strains resistant to amikacin, and one strain with Tigecycline MIC of 4 μg/mL). Most strains were resistant to all other drugs tested, with Linezolid and Imipenem showing the least resistance, at 38% (36/95) and 55% (52/95), respectively. Rough colony morphotype strains were more phage-susceptible than smooth strains (77%-27/35 versus 48%-25/53 in the plaque assays, but smooth strains are not killed efficiently by those phages in liquid infection assay). We have also identified 100 resident prophages, some of which were propagated lytically. DCC1 (20%-18/90) and DCC4 (22%-20/90) were observed to be the major clones and WGS identified 6 events of possible patient-to-patient transmission., Discussion: Many strains of M. abscessus complex are intrinsically resistant to available antibiotics and bacteriophages represent an alternative therapeutic option, but only for strains with rough morphology. Further studies are needed to elucidate the role of hospital-borne M. abscessus transmission., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bronchiectasis is a heterogeneous, neglected disease with few multicentre studies exploring the causes, severity, microbiology, and treatment of the disease across Europe. This aim of this study was to describe the clinical characteristics of bronchiectasis and compare between different European countries., Methods: EMBARC is an international clinical research network for bronchiectasis. We report on a multicentre, prospective, observational, non-interventional, cohort study (the EMBARC registry) conducted across 27 European countries and Israel. Comprehensive clinical data were collected from adult patients (aged ≥18 years) at baseline and annual follow-up visits using electronic case report form. Data from individual countries were grouped into four regions (the UK, northern and western Europe, southern Europe, and central and eastern Europe according to modified EU EuroVoc classification). Follow-up data were used to explore differences in exacerbation frequency between regions using a negative binomial regression model., Findings: Between Jan 12, 2015, and April 12, 2022, 16 963 individuals were enrolled. Median age was 67 years (IQR 57-74), 10 335 (60·9%) participants were female and 6628 (39·1%) were male. The most common cause of bronchiectasis in all 16 963 participants was post-infective disease in 3600 (21·2%); 6466 individuals (38·1%) were classified as idiopathic. Individuals with bronchiectasis experienced a median of two exacerbations (IQR 1-4) per year and 4483 (26·4%) patients had a hospitalisation for exacerbation in the previous year. When examining the percentage of all isolated bacteria, marked differences in microbiology were seen between countries, with a higher frequency of Pseudomonas aeruginosa and lower Haemophilus influenzae frequency in southern Europe, compared with higher H influenzae in the UK and northern and western Europe. Compared with other regions, patients in central and eastern Europe had more severe bronchiectasis measured by the Bronchiectasis Severity Index (51·3% vs 35·1% in the overall cohort) and more exacerbations leading to hospitalisations (57·9% vs 26·4% in the overall cohort). Overall, patients in central and eastern Europe had an increased frequency of exacerbations (adjusted rate ratio [RR] 1·12, 95% CI 1·01-1·25) and a higher frequency of exacerbations leading to hospitalisations (adjusted RR 1·71, 1·44-2·02) compared with patients in other regions. Treatment of bronchiectasis was highly heterogeneous between regions., Interpretation: Bronchiectasis shows important geographical variation in causes, microbiology, severity, and outcomes across Europe., Funding: European Union-European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative., Translations: For the Arabic, French, German, Greek, Hebrew, Irish, Russian and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JC reports grants or contracts from Grifols; consulting fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, Glaxosmithkline, Grifols, Insmed, Janssen, Novartis, Pfizer, and Zambon; and leadership or fiduciary roles as Chair of European Respiratory Society (ERS) Bronchiectasis Guideline Task Force, Chief Editor of European Respiratory Journal, and Chair of EMBARC Clinical Research Collaboration. EP reports grants or contracts from Grifols; consulting fees from Bayer, Zambon, Pfizer, Chiesi, Shire, Shionogi, Insmed, Moderna, and Pfizer; payment for expert testimony from Chiesi; leadership or fiduciary roles as ERS Task Force for Bronchiectasis Guidelines, co-chair of EMBARC; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Zambon. FR reports grants or contracts from German Center for Lung Research (DZL), German Center for Infection Research (EU and European Federation of Pharmaceutical Industries and Associations [EFPIA]) and iABC Consortium (including Alaxia, Basilea, Novartis, and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer, and InfectoPharm, to the institution; consulting fees from Parion, Grifols, Zambon, Insmed, Helmholtz-Zentrum für Infektionsforschung; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from I!DE Werbeagentur, Interkongress, AstraZeneca, Insmed, Grifols, and Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne, to the institution; support for attending meetings or travel from German Kartagener Syndrome and PCD PAG, and Mukoviszidose; participation on a Data Safety Monitoring Board or Advisory Board for Insmed, Grifols, and Shionogi; leadership or fiduciary role in other board, society, committee, or advocacy groups as Coordinator of the ERN-LUNG Bronchiectasis Core Network; Chair of the German Bronchiectasis Registry PROGNOSIS; Member of the SteerCo of the European Bronchiectasis Registry EMBARC; Member of the SteerCo of the European Non-tuberculous Mycobacterial registry EMBARC-NTM; Co-Speaker of the Medical Advisory Board of the German Kartagener Syndrome and PCD PAG; Speaker of the Respiratory Infections and tuberculosis group of the German Respiratory Society (DGP; Speaker of the Cystic Fibrosis group of DGP; Prinicipal Investigator for DZL; Member of the Protocol Review Committee of the PCD-CTN; Member of Physician Association of the German Cystic Fibrosis PAG; and fees for clinical trial participation paid to the institution from AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex, and Zambon. ADS reports grants or contracts from Bayer, Gilead, Pfizer, Astrazeneca, and Novartis, outside of the submitted work; consulting fees from Boehringer, Bayer, Gilead, Pfizer, GSK, and Astrazeneca, outside of the submitted work; support for attending meetings or travel from AstraZeneca, Chiesi, and GSK; and participation on a Data Safety Monitoring Board or Advisory Board for Bayer. MV reports participation in EMBARC registry; grants or contracts from Chiesi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed and Publi creation; support for attending meetings or travel from Zambon, Chiesi, Novartis, Behring; participation on a Data Safety Monitoring Board or Advisory Board for Insmed; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Insmed and Novartis. PRB reports grants or contracts from GSK and Vertex, to the institution; consulting fees from Insmed, Vertex, Viatris, and Zambon; and participation on a Data Safety Monitoring Board or Advisory Board for Insmed. CH reports grants or contracts from the National Institute for Health and Care Research (NIHR 2020, NIHR133876 Seven versus Fourteen Days Antibiotics for Patients with Bronchiectasis Requiring Intravenous Antibiotics to the institution and NIHR [2020–2023] Bronchodilators and corticosteroids in bronchiectasis) to the institution; consulting fees from 30 Technology, CSL Behring, Chiesi, Insmed, Janssen, LifeArc, Meiji, Mylan, Novartis, Pneumagen, Shionogi, and Zambon; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Zambon, Insmed, Chiesi, and 30 Technology. ML reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, and Savara; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed; and the ERS Infection Group chair role. KD reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Novartis, AstraZeneca, Boehringer Ingelheim, Chiesi, and Norma Hellas; and upport for attending meetings or travel from Novartis, AstraZeneca, Boehringer Ingelheim, Chiesi, Pfizer, Norma Hellas, and Menarini. MM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer; payment for expert testimony from Vertex; support for attending meetings or travel from Zambon; and participation on a Data Safety Monitoring Board or Advisory Board from Zambon, and Viatris. TW reports grants or contracts from German Ministry of Research and Education and consulting fees from AstraZeneca, GSK, and Insmed. FB reports grants or contracts from AstraZeneca, Chiesi, GSK, Insmed; consulting fees from GSK, Menarini, OM Pharma; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Chiesi, GSK, Grifols, Insmed, Menarini, Novartis, Ompharma, Pfizer, Sanofi, Vertex, Viatris, and Zambon. MS reports grants or contracts from GSK and Trudell pharma; consulting fees from AstraZeneca, Boehringer Ingelheim, Dexcel, Kamada, Synchrony Medical, Trumed, and Zambon; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, and Kamada; support for attending meetings or travel from Boehringer Ingelheim, AstraZeneca, and Kamada; participation on a Data Safety Monitoring Board or Advisory Board for Bonus Biotherapeutics, Boehringer Ingelheim, and AstraZeneca; leadership or fiduciary role in other board, society, committee, or advocacy group with Israeli Pulmonology Society, Israeli Society for Tuberculosis and Mycobacterial Diseases, and EMBARC as unpaid management board member and ERJ, Chest as unpaid Editorial board member; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Trudell Medical International. JSE reports grants or contracts from EU FP7 with Novartis and Polyphor; and consulting fees from Vertex. PG reports payment or honoraria for a lecture on bronchiectasis from GSK. SA reports grants or contracts from Insmed, Chiesi, Fisher & Paykel, to the institution; royalties or licenses with McGraw Hill; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland, Zambon, AstraZeneca UK, AstraZeneca Pharmaceutical, CSL Behring, Grifols, Fondazione Charta, Boehringer Ingelheim, Chiesi Farmaceutici Spa, Zcube, MENARINI, MSD Italia, Physioassist SAS, and GlaxoSmithKline Spa; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon, and Fondazione Internazionale Menarini; and participation on a Data Safety Monitoring Board or Advisory Board for Insmed Incorporated, Insmed Italy, AstraZeneca UK, and MSD Italia. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)