The 6th World Bronchiectasis and Nontuberculous Mycobacteria Conference Abstract Presentations.

Chronic Obstructive Pulmonary Diseases:Journal of the COPD Foundation® Editor in Chief: Mark T. Dransfield, MD Editors: M. Bradley Drummond, MD, MHS Maria Rosa Faner, PhD Ken Kunisaki, MD, MS Fanny Wai San Ko, MD Barry Make, MD Valerie Press, MD, MPH Nirupama Putcha, MD, MHS Editors: M. Bradley Drummond, MD, MHS Maria Rosa Faner, PhD Ken Kunisaki, MD, MS Fanny Wai San Ko, MD Barry Make, MD Nirupama Putcha, MD, MHS Editors: Peter Barnes, FRCP, FCCP, FMedSci, FRS M. Bradley Drummond, MD, MHS Maria Rosa Faner, PhD Ken Kunisaki, MD, MS Fanny Wai San Ko, MD Barry Make, MD Nirupama Putcha, MD, MHS Menu Current Issue Editorial Board All Issues Latest Issue Articles In Press Plain Language Summary Past Issues Free Subscription Submit a Manuscript Home > Return to Current Issue | RSS Options Conference Abstracts The 6th World Bronchiectasis and Nontuberculous Mycobacteria Conference Abstract Presentations Timothy R. Aksamit, MD1 Elizabeth J. Emery, MPH, PMP2 Ashwin Basavaraj, MD2 Mark L. Metersky, MD3 Anne E. O'Donnell, MD4 Doreen J. Addrizzo-Harris, MD2 Author Affiliations | Correspondence | Abstract | Citation | Keywords | PDF Author Affiliations Mayo Clinic, Rochester, Minnesota, United States New York University Grossman School of Medicine, New York, New York, United States University of Connecticut School of Medicine, Farmington, Connecticut, United States Georgetown University Hospital, Washington, District of Columbia, United States Address correspondence to: Timothy R. Aksamit, MD Pulmonary Disease and Critical Care Medicine Mayo Clinic Rochester, Minnesota Email: aksamit.timothy@mayo.edu Abstract This article does not have an abstract. Citation Citation: Aksamit TR, Emery EJ, Basavaraj A, Metersky ML, O'Donnell AE, Addrizzo-Harris DJ. The 6th World Bronchiectasis and Nontuberculous Mycobacteria Conference abstract presentations. Chronic Obstr Pulm Dis. 2023; 10(4): 450-516. doi: http://doi.org/10.15326/jcopdf.2023.0464 Keywords bronchiectasis, nontuberculous mycobacteria, 6th World Bronchiectasis and NTM Conference PDF Download PDF Version (10412KB) Article References Running Head: 6th World Bronchiectasis and NTM Conference Funding Support: n/a Date of Acceptance: October 4, 2023 │ Published Online Date: October 25, 2023 Abbreviations: NTM=nontuberculous mycobacterial lung disease; WBC2023=6th World Bronchiectasis and Nontuberculous Mycobacteria Conference; WBD=World Bronchiectasis Day Citation: Aksamit TR, Emery EJ, Basavaraj A, Metersky ML, O'Donnell AE, Addrizzo-Harris DJ. The 6th World Bronchiectasis and Nontuberculous Mycobacteria Conference abstract presentations. Chronic Obstr Pulm Dis. 2023; 10(4): 450-516. doi: http://doi.org/10.15326/jcopdf.2023.0464 Introduction The 6th World Bronchiectasis and Nontuberculous Mycobacteria (NTM) Conference (WBC 2023) was held in New York, New York from July 18, 2023 through July 20, 2023. This conference brought together investigators, clinicians, patients, caregivers, and industry representatives involved in the bronchiectasis and NTM space for a far-reaching, engaging, and cutting-edge update from around the world. Attendees included more than 650 participants total with 379 in-person participants and the remainder virtually. Participants included 40 faculty members, almost 90 trainees, 24 exhibitors, and more than 160 patients and caregivers from 30 countries and 6 continents reflecting the authentically global nature of this World Bronchiectasis and NTM conference. In addition to new research advancing the science, presentations by international experts addressed a current, state-of-the-art, comprehensive overview of the pathophysiology, natural disease course, epidemiology, and clinical approach to bronchiectasis and NTM lung disease. Investigators presented 60 posters with their latest research results. Exhibitors included industry representatives underscoring robust collaboration and support across many interests in the bronchiectasis and NTM communities. The World Bronchiectasis and NTM Conference series (Hannover, Germany; Milan, Italy; Washington, D.C.; virtual (2020); Prague, Czech Republic; and New York, New York) celebrates and remains a premier venue for highlighting the international collaboration of a wide range of clinicians, investigators, patients, caregivers, and industry representatives. Other activities raising global awareness in partnership with the World Bronchiectasis and NTM Conference series include World Bronchiectasis Day (WBD) (https://www.bronchiectasisandntminitiative.org/Bronchiectasis/Bronchiectasis-Resources/World-Bronchiectasis-Day). Although a year-long campaign for raising awareness, the WBD initiative involves global activities year-round and is anchored annually on July 1st. The inaugural celebration of World Bronchiectasis Day occurred at the 5th World Bronchiectasis Conference held in Prague, Czech Republic in 2022. Keynote lectures from global experts began the WBC 2023 with comprehensive and organized lectures on bronchiectasis from James Chalmers, MBChB, PhD, from the University of Dundee as well as a lecture on NTM lung disease from Charles L. Daley, MD, from National Jewish Medical Center in Denver, Colorado. The following 2 full days featured bronchiectasis on the first day in a comprehensive fashion including practical hands-on sessions organized by airway clearance experts. Bronchiectasis sessions focused on etiology, pathophysiology, mechanisms of disease, comorbidities, clinical management, and registry updates by leading experts. Poster presentations with lively discussions guided by content experts in the field of bronchiectasis and NTM were held throughout the conference. Awards were presented to top peer-selected rising stars and investigators sharing outstanding work. Early career researchers had an opportunity to meet with established researchers and clinicians during a networking luncheon that was well received and generated new networking, research strategies, and collaborative opportunities. The second full day of the WBC 2023 focused on NTM, with sessions on epidemiology, the role of the environment, research activities, treatment, and novel therapies for bronchiectasis and NTM treatment. Robust interactions between presenters and attendees along with moderators enriched the presentations and information provided, creating a memorable experience for all. The overall upbeat vibe of activities at the conference reflects the exponential growth and explosion of interest in what has been described as the new age of bronchiectasis and NTM lung disease. Great appreciation for tremendous support is extended to many, including but certainly not limited to, patients, caregivers, and industry partners. For those of us fortunate to represent these communities we are all encouraged and passionate regarding progress to date. We are honored to present this collection of abstracts from the WBC 2023 reflecting the high quality and tremendous work of advancing the science and meeting the unmet needs of bronchiectasis and NTM lung disease. NOTE: The following abstracts have NOT been copyedited, but are presented here in their original format, as presented by the authors at the WBC 2023 (July 18-20, 2023) in New York City. The following abstracts are grouped according to their poster section. Case reports presented at the conference are omitted from the publication. Figures are labeled/numbered as they appear, sequentially, within the entire article—not each individual abstract. Therefore, the figure number may not match the abstract number. Rising Star Researcher Awards—Abstract 1 Alpha-1 Antitrypsin and Deoxyribonuclease 1 as Potential Therapies for the Treatment of Bronchiectasis Paul King, MBBS, FRACP, PhD1 Author Affiliations: 1. Monash Medical Centre/Monash University, Melbourne, Victoria, Australia Figure 1 Background: The excessive production of proteases such as neutrophil elastase (NE) drives inflammation and the development of bronchiectasis; the main anti-protease is alpha-1 antitrypsin (AAT). A mechanism of lung protease expression is via neutrophil and macrophage extracellular trap formation (NETs/METs); which are broken down by deoxyribonuclease 1 (DNase 1). The ability of AAT and DNase 1 to reduce inflammation in vitro and in vivo was assessed. Methods: AAT eluted from human serum and recombinant DNase 1 (dornase alfa/Pulmozyme) were used. In vitro experiments were performed using blood and bronchoalveolar lavage (BAL) samples from human subjects that were infected with influenza A virus (IAV) or nontypeable Haemophilus influenzae (NTHi) to upregulate NET/MET and NE expression; AAT and DNase 1 were added. In vivo experiments were performed in mice infected with IAV/NTHi and administered inhalational AAT and DNase 1 for 3 days. Results: Samples were obtained from 22 adults (mean age of 51 ± 16 years). Infection induced prominent NET (Fig. 1A) and MET expression in vitro, which was reduced by the addition of DNase 1 (p<0.0001). AAT reduced NE expression in vitro (Fig. 1B), (p<0.0001). AAT reduced inflammation in infected mice as assessed by lung weight and BAL white cell count (n=8 mice, p<0.05) (Fig. 1C), this effect was enhanced by the addition of DNase 1. Conclusions: Alpha-1 antitrypsin reduces lung inflammation and this effect is enhanced by the addition of DNase 1. Rising Star Researcher Awards—Abstract 2 Prevalence and Factors Associated with the Isolation of Fungi in the Sputum of Bronchiectasis Patients Pamela J. McShane, MD1 Amanda E. Brunton, MPH2 Radmilla Choate, MPH, PhD3 David Fraulino, MD4 Christopher Richards, MD5 Kevin Winthrop, MD, MPH2 Kevin Tsui, MD6 Restrepo I. Marcos, MD, MSc, PhD7 Diego J. Maselli Cacer, MD8 Mark L. Metersky, MD4 Author Affiliations: 1. University of Texas Health Science Center at Tyler, Tyler, Texas, United States 2. Oregon Health and Science University, Portland, Oregon, United States 3. University of Kentucky, Lexington, Kentucky, United States 4. University of Connecticut School of Medicine, Farmington, Connecticut, United States 5. Mass General, Boston, Massachusetts, United States 6. University of Chicago, Chicago, Illinois, United States 7. University of Texas Health at San Antonio, San Antonio, Texas, United States 8. UT Health San Antonio, San Antonio, Texas, United States Figure 2 Background: The presence of fungi in the sputum of bronchiectasis patients is common but the clinical significance is not fully understood. Methods: We analyzed data from patients enrolled in the U.S. Bronchiectasis Research Registry as of December 2022 with documented fungal culture results. Fungi included Aspergillus, Scedosporum, and other. Patients with ABPA were excluded. Descriptive statistics were computed for baseline demographics and clinical characteristics for the overall sample, stratified by presence positive or negative fungal culture. Values were compared using the chi-square test for categorical variables and t-tests for continuous variables. Results: 2,230 patients with bronchiectasis and at least one fungal culture result were included in the study. 42.6% (949/2230) were positive and 57.4% (1281/2230) had no growth on fungal culture. Table 1 shows demographics and clinical characteristics. FEV1 percent predicted was lower in patients with > 1 positive fungal culture than no growth (mean 71.8 +21.8 vs 75.3 +22.1, p=0.0006). Eosinophilia (>150 cells/uL) was more common in patients with positive fungal cultures than in patients with no growth (52.4% [98/193] vs 40.1% [95/193], p=0.011), but prevalence of asthma did not differ according to fungal culture result. Growth of bacteria was more often accompanied by a positive fungal culture than no growth on fungal cultures (62.0% [588/949] vs 46.3% [589/1272], p=<0.0001). Users of corticosteroids (oral or inhaled) were more likely to have a positive fungal culture than a negative result (10.4% [53/509] vs 6.5% [35/539], p=0.022). NTM infection status, exacerbation frequency, and bronchiectasis severity as measured by BSI did not differ between patients with positive or negative fungal culture (p=0.615; p=0.303; p=0.232, respectively). Conclusions: In the U.S., the presence of fungus in the sputum of bronchiectasis patients was associated with worse lung function, but does not appear to impact other important clinical outcomes such as exacerbations and severity of disease. Acknowledgements The authors would like to acknowledge the COPD Foundation, a 501(c)(3) nonprofit organization, who manages the Bronchiectasis and NTM Research Registry. The Registry is funded by the Richard H. Scarborough Bronchiectasis Research Fund, the Anna-Maria and Stephen Kellen Foundation, a Research Grant from Insmed Incorporated, and the Bronchiectasis and NTM Industry Advisory Committee. Also, this work would not be possible without comprehensive chart reviews and data recording by the dedicated research coordinators and PIs at each participating Registry site. Rising Star Researcher Awards—Abstract 3 A Single Centre Analysis of Non-Tuberculous Mycobacteria from Johannesburg, South Africa Lamla Nqwata, MBCHB1 Jotam Pasipanodya2 Marianne Black3 Charles Feldman4 Author Affiliations: 1. Health Department, Johannesburg, Gauteng, South Africa 2. Stanford Health Centre, California, California, United States 3. National Health Laboratory Services, Johannesburg, Gauteng, South Africa 4. Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, Gauteng, South Africa Figure 3 Background: In Sub-Sahara African setting, paucity of data regarding the distribution of individual Mycobacterial species and related comorbidities results in underappreciation of nontuberculous mycobacteria (NTM) diseases, allocation of fewer resources with potential adverse outcomes for patients. We hypothesized concomitant infections would be the most significant risk factors that influence patients’ trajectories and outcomes in our South African settings. Methods: A retrospective review of all clinical isolates that were positive for NTM between 1 January 2010 and 30 June 2017 and the corresponding medical records of the patients at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), South Africa were extracted, reviewed, and analysed for long-term survival. Cox regression and log rank tests were used to compare survival between patients stratified by NTM species, whether ATS criteria were met, HIV status and CD4 counts. Results: Mycobacterium avium complex (Mac) was found in 90 (70%), M. fortuitum 6 (5%) and M. gordonae 5 (4%) out of the 123 patients followed up for median (interquartile range [IQR]) of 1(0.5 – 4.5) years (Figure A&B). HIV 96 (78%) and previous PTB episode 38(30%) were the common comorbid illnesses, while 60 (49%) were observed without antibiotics given. Median age of patients was 39 (IQR 31-51) with male predominance 71(58%), cavitary lesion chest X-ray in 12 (10%) and initial bacterial load of 1.64 (IQR1.25 – 2.39) log10 colony forming units. Overall, 27(22%) were successfully treated and 28 (23%) died (Figure 1). The adjusted hazard rate for low CD4 counts ≤50 cells/mm3 was 2.79 (95% Confidence Intervals [CI], 1.20 - 6.50), while that for those with unknown CD4 counts was 4.01 (95% CI, 1.17 – 13.77) compared to CD4 counts >50 cells/mm3 (Figure D). Conclusions: Among patients with pulmonary NTM in our environment, MAC is the most common isolate. HIV infection is significant risk factor for early death regardless of gender. Rising Star Researcher Awards—Abstract 4 Distinct Features of the Lower Airway Microbiome in NTM Bronchiectasis Shivani Singh, MD, PhD1 Fares Darawshy1 Kirby Erlandson1 Destiny Collazo1 Kelsey Krolikowski1 Isabella Atandi1 Clea Barnett, MD1 Yonghua Li1 Imran Sulaiman, MD, PhD1 Miao Chang1 Rosemary Schluger, RN1 Ibrahim Kocak1 Rajbir Singh1 Colin McCormick1 Yaa Kyeremateng1 James Tsay, MD1 Ashwin Basavaraj, MD2 David Kamelhar, MD1 Doreen J. Addrizzo-Harris, MD1 Leopoldo Segal, MD1 Benjamin Wu, MD1 Author Affiliations: 1. NYU Langone Health, New York, New York, United States 2. NYU Grossman School of Medicine, New York, New York, United States Figure 4 Background: The lower airway microbiome of patients with non-tuberculous mycobacterial lung disease (NTM-LD)/bronchiectasis holds a complex set of microbes, but the influence of the non-pathogen fraction of the microbiome on the disease process is unknown. The significance of the interaction between the microbiome and a dominant or a non-dominant pathogen is also unknown. Here, we investigated whether distinct lower airway microbial communities indicate different patterns of pathogen colonization in bronchiectasis. Methods: Patients with bronchiectasis underwent clinically indicated bronchoscopies. Samples (upper/ lower airways and backgrounds) underwent 16S rRNA gene sequencing and were analyzed with QIIME2, PhyloSeq and EdgeR. Results: In a cohort of 200 patients, a large proportion (n=94, 47%) met the diagnostic criteria for NTM-LD. In the NTM–group, Pseudomonas was frequently recovered in culture (15.7%). Within this group, there was a sub-cohort of patients showing high dominance, or low alpha diversity, and a distinct microbial composition that presented with frequent exacerbations. In the NTM+ group, a high proportion (44%) exhibited a secondary pathogen in culture. In both NTM+ and NTM- subjects, patients who grew a secondary pathogen in cultures had lower alpha diversity than those who did not (p<0.05, Fig. A. B). Compositionally, based on alpha diversity analyses, isolation of a secondary pathogen was also associated with distinct taxonomic differences (Fig. C.D). In particular, differential enrichment analyses (EdgeR) showed that within the NTM+ group, positivity for a secondary pathogen was associated with enrichment with Stenotrophomonas and Pseudomonas (Fig. E), whereas in the NTM- group, there was enrichment with Enterobacteriaceae and Moraxella (Fig. F). DESeq2 showed that in the NTM- group, positive respiratory culture was associated with enrichment with Moraxella. Conclusions: This study illustrates that heterogeneity and structure of the lung microbiome in bronchiectasis is in part dependent on the main pathogen isolated and the presence of a secondary pathogen. Bronchiectasis and Genetics—Abstract 5 Validation of a Commercial Human ELISA Kit to Measure Alpha-1 Antitrypsin (AAT) in Sputum Ianire Gallego Amaro1 Letizia Traversi, MD1 Almudena Felipe, MD1 Antonio Álvarez, MD, PhD1 David Clofent, MD1 Mario Culebras, MD, PhD1 ML De Souza Galvão, MD1 Karina Loor, MD1 Eva Polverino, MD, PhD1 Author Affiliations: 1. Department of Respiratory Medicine, Vall d’Hebron University Hospital, Barcelona, Spain Figure 5 Background: Bronchiectasis (BE) is a chronic disease characterized by persistent lung inflammation. AAT participates as one of the main lung proteins with anti-proteinase capacity, mainly targeting neutrophil elastase. Quantification of AAT in blood samples is widely used in both clinical practice and research, but little attention has been paid to clinical methods for evaluating AAT concentrations in sputum (AATs). The aim of this study was to validate an ELISA to measure AATs in samples collected from BE patients compared with healthy subjects. Methods: Spontaneous sputum samples were collected from 34 clinically stable BE patients, while induced sputum was obtained from a control group of 9 age-matched (±10yrs), healthy, non-smoking volunteers. Sputum samples were processed and the supernatant were frozen at -80°C. Quantification of AATs was measured by a sensitive sandwich ELISA (Hycult Biotech). All samples were diluted 5x with supplied dilution buffer according to the manufacturer’s recommendations. Statistical analysis of the data was carried out with GraphPad 9.0.1. Results: Standard curve was generated for concentrations between 0,00016 and 0,01 mg/dL. The sample dilution was appropriate, and samples showed concentrations within this range. The results obtained from the preliminary analysis of AATs concentration showed a significant difference between BE patients and controls (0.086 mg/dL vs 0.126 mg/dL; p = 0.005). Conclusions: These preliminary data of AAT quantification with ELISA technique in sputum can represent a base for future studies. Moreover, the lower AATs in BE, compared to controls, suggests that AAT could represent a useful biomarker and provide compelling information about pathophysiology of BE. Bronchiectasis and Genetics—Abstract 6 Lung Function Differences in Primary Ciliary Dyskinesia: Radial Spoke (RSPH) vs DNAH5 Mutations Kunal Jakharia, MD1 Maimoona Zariwala, PhD1 Kelli M. Sullivan, MPH1 Nicole Capps, DNP1 Lin Feng-Chang, PhD1 Lang Li, BA1 Margaret Leigh, MD1 Kenneth N. Olivier, MD, MPH1 Michael Knowles, MD1 Author Affiliations: 1. University of North Carolina, Chapel Hill, North Carolina, United States Figure 6 Background: In Primary Ciliary Dyskinesia (PCD), a genetically heterogenous disorder, 2 loss of function (LOF) mutations could conceptually cause greater loss of ciliary and pulmonary function compared to those who do NOT have 2 LOF mutations. Mutations in RSPH1 have been reported to be associated with milder lung disease than other gene mutations (Knowles, M et al, AJRCCM 2014). We compared lung function in subjects with RSPH1 and non-RSPH1 (“other-RSPH”) radial spoke mutations to mutations in DNAH5 (most common PCD gene). Methods: Cross-sectional analysis was performed on demographic, spirometric, and genetic data from prospective studies by the Genetic Disorders of Mucociliary Clearance Consortium (GDMCC). Participants with pathogenic/likely pathogenic variants in RSPH1, other-RSPH and DNAH5 were subdivided by variant functionality: 2 LOF (both variants - LOF) and not2LOF (one or two variants - not LOF) subgroups and sex. FEV1 percent predicted (FEV1pp) and Z-scores (GLI reference) were compared between the groups and subgroups using statistical regression analysis, adjusting for age, sex and LOF. Results (Table): 18 other-RSPH subjects had RSPH4A and one each had RSPH9 and RSPH3 mutations. There was no difference in FEV1 and Z-score between RSPH1 and DNAH5 group; other-RSPH group had significantly worse FEV1 and Z-score compared to DNAH5. 2LOF males and not2LOF females of other-RSPH group had lower FEV1 and Z-score compared to their DNAH5 counterparts. Within DNAH5, 2LOF females had worse FEV1 compared to not2LOF females and 2LOF males. Conclusions: Our data suggest that RSPH1 variants are not associated with milder lung disease than DNAH5. Subjects with non-RSPH1 mutation, mostly RSPH4A, had worse lung disease compared to those with DNAH5 mutation. We postulate, this may be due to factors that need further exploration including healthcare disparities among RSHP4A subjects. Along with the specific gene involved, sex and LOF status of the mutation also impacts lung function. Bronchiectasis I—Abstract 7 The Clinical and Socioeconomic Burden of Bronchiectasis: Preliminary Results of A Systematic Literature Review James D. Chalmers, MD, PhD1 Marcus Mall2 Pamela J. McShane, MD3 Kim G. Nielsen4 Michal Shteinberg, MD, PhD5 Sean D. Sullivan6 Sanjay H. Chotirmall, MD, PhD7 Author Affiliations: 1. Division of Molecular and Clinical Medicine, Ninewells Hospital, University of Dundee, Dundee, Scotland, United Kingdom 2. Charité – Universitätsmedizin Berlin, Berlin, Brandenburg, Germany 3. University of Texas Health Science Center at Tyler, Tyler, Texas, United States 4. Copenhagen University Hospital, Rigshospitalet, Copenhagen, Byen København, Denmark 5. Lady Davis Carmel Medical Center, Haifa, Israel 6. University of Washington, Seattle, Washington, United States 7. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore Background: The overall burden of bronchiectasis (BE) continues to lack clarification even after the introduction of clinical care recommendations. A better understanding of the overall burden could support development of new therapies. We present preliminary findings of a systematic literature review (SLR) of the overall clinical and socioeconomic burden of BE across aetiologies and its associated diseases. Methods: Following PRISMA guidelines, Embase, MEDLINE and Cochrane Library were searched for publications relating to BE disease burden (December 2017–2022). Journal articles and congress abstracts reporting on observational studies, randomised controlled trials and registry studies were included, as well as editorials, narrative reviews and existing SLRs for the purpose of identifying primary studies. A reviewer screened all titles and abstracts to identify publications for full-text review, which were then screened for potential inclusion. A second reviewer verified both screening steps. Results: In total, 1624 publications were identified, of which 636 full texts were screened and 95 were included in this preliminary analysis. Of these, the majority (n=77) reported on non-cystic fibrosis BE, although few (n=18) reported on individual aetiologies and associated diseases. Commonly reported symptoms and complications included reduced lung function, exacerbations, cough, sputum, dyspnoea, haemoptysis and respiratory infections, with disease severity reported across several indices and mortality reported in several studies. BE impacted health-related quality of life across several patient-reported outcome measures and domains, with patients experiencing fatigue, anxiety and depression. Healthcare resource utilisation (HCRU; hospitalisations/readmissions/length of stay/annual hospital days) was considerable. Patients, health insurance companies and healthcare systems accrued substantial medical costs related to hospitalisations, treatments, and emergency department and outpatient visits. Indirect costs included sick pay and lost income. Conclusions: These preliminary results suggest that BE causes significant overall clinical and socioeconomic burden. Disease-modifying therapies that reduce symptoms, improve quality of life and reduce HCRU and costs are needed. Bronchiectasis I—Abstract 8 Efficacy and Safety of Dipeptidyl Peptidase-1 (DPP-1) Inhibition in Long-Term Macrolide Users with Bronchiectasis: A Post-Hoc Analysis of the WILLOW Trial Charles S. Haworth, MD1 Pamela J. McShane, MD2 Carlos Fernandez, MD, MPH, MBA3 Sebastian Fucile, PhD3 Melanie Lauterio, PhD3 Andrea Maes, PhD3 Ariel Teper, MD3 James D. Chalmers, MD, PhD4 Author Affiliations: 1. Royal Papworth Hospital and University of Cambridge, Cambridge, United Kingdom 2. University of Texas Health Science Center at Tyler, Tyler, Texas, United States 3. Insmed Incorporated, Bridgewater, New Jersey, United States 4. Division of Molecular and Clinical Medicine, Ninewells Hospital, University of Dundee, Dundee, Scotland, United Kingdom Figure 7 Background: Neutrophil serine proteases, such as neutrophil elastase (NE), are activated by DPP-1 in the bone marrow. Brensocatib, a reversible DPP-1 inhibitor, prolonged time to first exacerbation vs placebo in non–cystic fibrosis bronchiectasis (NCFBE) patients in the phase 2 WILLOW trial (NCT03218917). Long-term macrolides are widely used and have been shown to reduce neutrophilic inflammation. The present post-hoc analysis compares patient characteristics and outcomes in WILLOW subgroups based on long-term macrolide use. Methods: Adult bronchiectasis patients received once-daily brensocatib (10 or 25 mg) or placebo. Patients on stable long-term macrolide therapy could be included in the trial. Endpoints included time to first exacerbation, annualized rate of pulmonary exacerbations, sputum NE changes, and treatment-emergent adverse events (TEAEs). Pooled results from brensocatib arms are presented. Results: Patients on long-term macrolide treatment (n=44) were more likely to have P. aeruginosa cultured from sputum, a higher background exacerbation rate, lower baseline FEV1, higher baseline levels of sputum NE, higher Bronchiectasis Severity Index (BSI) scores, a medical history of asthma, and inhaled steroid use than patients without long-term macrolide treatment (n=212) (Table). Brensocatib prolonged time to first exacerbation (hazard ratio 0.60 [95% CI: 0.25–1.45] in the macrolide subgroup; 0.60 [0.38–0.94] for the subgroup without macrolides) and reduced exacerbation rates in patients with and without long-term macrolide treatment (Table). Brensocatib led to greater median reductions of sputum NE levels vs placebo at Week 24 (Table). Similar TEAE rates were observed across all subgroups. The most common TEAEs across the pooled brensocatib arms were increased sputum, cough, and dyspnea. Conclusions: Consistent with overall WILLOW results, brensocatib prolonged time to first exacerbation and reduced exacerbation rates and sputum NE levels vs placebo regardless of long-term macrolide use, and was generally well tolerated with consistent safety signals. A confirmatory phase 3 trial (ASPEN; NCT04594369) is ongoing. Bronchiectasis I—Abstract 9 The Efficacy and Safety of Colistimethate Sodium Delivered via the I-neb in Patients with Bronchiectasis and Pseudomonas Aeruginosa Infection: The PROMIS-I and PROMIS-II Randomised Controlled Trials Charles S. Haworth, MD1 Michal Shteinberg, MD, PhD2 Kevin Winthrop, MD, MPH3 Alan Barker, MD3 Francesco Blasi, MD4 Aikaterini Dimakou, MD, PhD5 Lucy Morgan, BMed, PhD6 Anne E. O'Donnell, MD7 Felix C. Ringshausen8 Oriol Sibila9 Rachel Thomson, MBBS, PhD10 James D. Chalmers, MD, PhD11 Author Affiliations: 1. Royal Papworth Hospital and University of Cambridge, Cambridge, United Kingdom 2. Lady Davis Carmel Medical Center, Haifa, Israel 3. Oregon Health