{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:18:03Z","timestamp":1790860683269,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Bronchiectasis is a chronic, heterogeneous airway disease characterised by irreversible bronchial dilatation, recurrent infections, and persistent inflammation, leading to progressive lung damage, frequent exacerbations, and impaired quality of life. Neutrophil-driven inflammation, largely mediated by excessive activity of neutrophil serine proteases such as neutrophil elastase, represents a central pathogenic mechanism and an important therapeutic target. Methods: Brensocatib, a first-in-class, selective, and reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), prevents the activation of neutrophil serine proteases during neutrophil maturation in the bone marrow. By reducing downstream protease activity, brensocatib modulates aberrant neutrophilic inflammation without broadly suppressing immune function. Results: Clinical studies, including the Phase-2 WILLOW trial and the Phase-3 ASPEN trial, have demonstrated that brensocatib significantly reduces exacerbation frequency, prolongs time to first exacerbation, and lowers sputum neutrophil protease activity, with a favourable safety profile. Importantly, these benefits were observed across multiple patient subgroups and in addition to standard-of-care therapies. Conclusions: As the first FDA-approved (12 August 2025) mechanism-based therapy for non\u2013cystic fibrosis bronchiectasis, brensocatib represents a paradigm shift toward targeted, precision treatment of neutrophil-mediated airway disease. Its clinical efficacy, biomarker-driven rationale, and potential to reduce antibiotic dependence highlight brensocatib as a cornerstone therapy in bronchiectasis management and a promising strategy for other neutrophil-driven inflammatory conditions.<\/jats:p>","DOI":"10.3390\/jcm15031257","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T17:20:14Z","timestamp":1770225614000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Brensocatib\u2014Another Therapeutic \u201cWindow of Opportunity\u201d for Patients with Bronchiectasis"],"prefix":"10.3390","volume":"15","author":[{"given":"Florin-Dumitru","family":"Mih\u0103l\u021ban","sequence":"first","affiliation":[{"name":"Department of Cardio-Thoracic Pathology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Institute of Pneumology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra","family":"Ulmeanu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Doctoral School of Biomedical Sciences, University of Oradea, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6742-6334","authenticated-orcid":false,"given":"Ancu\u021ba-Alina","family":"Constantin","sequence":"additional","affiliation":[{"name":"Department of Cardio-Thoracic Pathology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Institute of Pneumology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","unstructured":"(2026, January 22). FDA Approves BRINSUPRITM (brensocatib) as the First and Only Treatment for Non-Cystic Fibrosis Bronchiectasis, a Serious, Chronic Lung Disease. Insmed Incorporated Investor Relations. Available online: https:\/\/investor.insmed.com\/2025-08-12-FDA-Approves-BRINSUPRI-TM-brensocatib-as-the-First-and-Only-Treatment-for-Non-Cystic-Fibrosis-Bronchiectasis,-a-Serious,-Chronic-Lung-Disease."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S2213-2600(18)30053-5","article-title":"Bronchiectasis: New therapies and new perspectives","volume":"6","author":"Chalmers","year":"2018","journal-title":"Lancet. Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jcf.2013.12.009","article-title":"A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis","volume":"13","author":"Konstan","year":"2014","journal-title":"J. Cyst. Fibros."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.jcf.2015.07.009","article-title":"Inhaled alpha1-proteinase inhibitor therapy in patients with cystic fibrosis","volume":"15","author":"Gaggar","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chalmers, J.D., Kettritz, R., and Korkmaz, B. (2023). Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1239151"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5414","DOI":"10.21037\/jtd-2025-180","article-title":"Making real progress in the world of bronchiectasis","volume":"17","author":"Flume","year":"2025","journal-title":"J. Thorac. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1183\/13993003.01033-2015","article-title":"Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: A population-based cohort study","volume":"47","author":"Quint","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.rmed.2013.12.015","article-title":"Mortality in non-cystic fibrosis bronchiectasis: A prospective cohort analysis","volume":"108","author":"Goeminne","year":"2014","journal-title":"Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17534666251390073","DOI":"10.1177\/17534666251390073","article-title":"Prevalence of bronchiectasis: A narrative review","volume":"19","author":"Laska","year":"2025","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1900499","DOI":"10.1183\/13993003.00499-2019","article-title":"Increasing bronchiectasis prevalence in Germany, 2009\u20132017: A population-based cohort study","volume":"54","author":"Ringshausen","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e055672","DOI":"10.1136\/bmjopen-2021-055672","article-title":"Global prevalence of non-tuberculous mycobacteria in adults with non-cystic fibrosis bronchiectasis 2006\u20132021: A systematic review and meta-analysis","volume":"12","author":"Zhou","year":"2022","journal-title":"BMJ Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.17219\/acem\/144200","article-title":"The influence of comorbidities on mortality in bronchiectasis: A prospective, observational study","volume":"30","author":"Stachyra","year":"2021","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"188","DOI":"10.5694\/mja2.52204","article-title":"Bronchiectasis among Indigenous adults in the Top End of the Northern Territory, 2011\u20132020: A retrospective cohort study","volume":"220","author":"Gibbs","year":"2024","journal-title":"Med. J. Aust."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2200611","DOI":"10.1183\/13993003.00611-2022","article-title":"Clinical outcomes of bronchiectasis in India: Data from the EMBARC\/Respiratory Research Network of India registry","volume":"61","author":"Dhar","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/j.jaip.2019.02.026","article-title":"Prevalence and Clinical Implications of Chronic Rhinosinusitis in People with Bronchiectasis: A Systematic Review","volume":"7","author":"Handley","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.resinv.2021.11.004","article-title":"Bronchiectasis in severe asthma and asthmatic components in bronchiectasis","volume":"60","author":"Matsumoto","year":"2022","journal-title":"Respir. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.chest.2023.06.040","article-title":"The Economic Burden of Bronchiectasis: A Systematic Review","volume":"164","author":"Roberts","year":"2023","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.chest.2016.10.055","article-title":"Adult Patients with Bronchiectasis: A First Look at the US Bronchiectasis Research Registry","volume":"151","author":"Aksamit","year":"2017","journal-title":"Chest"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"240096","DOI":"10.1183\/16000617.0096-2024","article-title":"Bronchiectasis in Asia: A review of current status and challenges","volume":"33","author":"Choi","year":"2024","journal-title":"Eur. Respir. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"00060","DOI":"10.1183\/23120541.00060-2022","article-title":"Nontuberculous mycobacteria infection and pulmonary disease in bronchiectasis","volume":"8","author":"Suska","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1701953","DOI":"10.1183\/13993003.01953-2017","article-title":"The independent contribution of Pseudomonas aeruginosa infection to long-term clinical outcomes in bronchiectasis","volume":"51","author":"Shteinberg","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1164\/rccm.201711-2202OC","article-title":"Characterization of the \u201cFrequent Exacerbator Phenotype\u201d in Bronchiectasis","volume":"197","author":"Chalmers","year":"2018","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.21037\/jtd-2024-1945","article-title":"Phenotypes and endotypes in bronchiectasis: A narrative review of progress toward precision medicine","volume":"17","author":"Choi","year":"2025","journal-title":"J. Thorac. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.rmed.2019.07.016","article-title":"Australian adults with bronchiectasis: The first report from the Australian Bronchiectasis Registry","volume":"155","author":"Visser","year":"2019","journal-title":"Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S2213-2600(21)00277-0","article-title":"Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: International consensus recommendations","volume":"10","author":"Aliberti","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1700051","DOI":"10.1183\/13993003.00051-2017","article-title":"Pulmonary exacerbation in adults with bronchiectasis: A consensus definition for clinical research","volume":"49","author":"Hill","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1365-2222.2008.03157.x","article-title":"Acute exacerbations of asthma: Epidemiology, biology and the exacerbation-prone phenotype","volume":"39","author":"Dougherty","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1378\/chest.07-0490","article-title":"Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis","volume":"132","author":"Soriano","year":"2007","journal-title":"Chest"},{"key":"ref_29","first-page":"81","article-title":"Prognostic Value of Frequent Exacerbations in Bronchiectasis: The Relationship With Disease Severity","volume":"55","author":"Athanazio","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1056\/NEJMra2202819","article-title":"Bronchiectasis\u2014A Clinical Review","volume":"387","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S2213-2600(25)00160-2","article-title":"Symptoms, risk of future exacerbations, and response to long-term macrolide treatment in bronchiectasis: An observational study","volume":"13","author":"Sibila","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.arbres.2022.09.004","article-title":"Pathophysiology of Chronic Bronchial Infection in Bronchiectasis","volume":"59","author":"Solarat","year":"2023","journal-title":"Arch. Bronconeumol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1164\/rccm.202108-1889OC","article-title":"Characterization of Eosinophilic Bronchiectasis: A European Multicohort Study","volume":"205","author":"Shoemark","year":"2022","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1164\/rccm.202303-0499OC","article-title":"Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study","volume":"208","author":"Choi","year":"2023","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Papaioannou, A.I., Fouka, E., Ntontsi, P., Stratakos, G., and Papiris, S. (2022). Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050850"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.rmed.2011.01.015","article-title":"Elevated peripheral airway nitric oxide in bronchiectasis reflects disease severity","volume":"105","author":"Shoemark","year":"2011","journal-title":"Respir. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"240085","DOI":"10.1183\/16000617.0085-2024","article-title":"Exacerbations of bronchiectasis","volume":"33","author":"Johnson","year":"2024","journal-title":"Eur. Respir. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gozzi-Silva, S.C., Teixeira, F.M.E., Duarte, A.J.d.S., Sato, M.N., and de Mendon\u00e7a Oliveira, L. (2021). Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve?. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.674258"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lee, H., Kim, S.H., Lee, S.-K., Choi, H., Chung, S.J., Park, D.W., Park, T.S., Moon, J.-Y., Kim, T.-H., and Kim, S.-H. (2023). Impact of air pollution on healthcare utilization in patients with bronchiectasis. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1233516"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1164\/rccm.202310-1729OC","article-title":"Endotypes of Exacerbation in Bronchiectasis: An Observational Cohort Study","volume":"210","author":"Gao","year":"2024","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1164\/rccm.201605-1027OC","article-title":"Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis","volume":"195","author":"Chalmers","year":"2017","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1900303","DOI":"10.1183\/13993003.00303-2019","article-title":"A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation","volume":"53","author":"Shoemark","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.21037\/jtd-2025-289","article-title":"Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: A narrative review","volume":"17","author":"Tang","year":"2025","journal-title":"J. Thorac. Dis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.molimm.2012.09.011","article-title":"Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis","volume":"55","author":"Chalmers","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2101840","DOI":"10.1183\/13993003.01840-2021","article-title":"SPLUNC1 is a novel marker of disease severity and airway infection in bronchiectasis","volume":"58","author":"Keir","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2003157","DOI":"10.1183\/13993003.03157-2020","article-title":"Neutrophil dysfunction in bronchiectasis: An emerging role for immunometabolism","volume":"58","author":"Giam","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1702590","DOI":"10.1183\/13993003.02590-2017","article-title":"Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS","volume":"52","author":"Uhel","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.12703\/r\/9-25","article-title":"Phagocytosis and neutrophil extracellular traps","volume":"9","author":"DeLeo","year":"2020","journal-title":"Fac. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2401050","DOI":"10.1183\/13993003.01050-2024","article-title":"Targeting neutrophil serine proteases in bronchiectasis","volume":"65","author":"Chalmers","year":"2025","journal-title":"Eur. Respir. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1172\/JCI0213462","article-title":"Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis","volume":"109","author":"Adkison","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"280528","DOI":"10.1155\/2012\/280528","article-title":"The immune response and its therapeutic modulation in bronchiectasis","volume":"2012","author":"Daheshia","year":"2012","journal-title":"Pulm. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S175","DOI":"10.1080\/13693780802163370","article-title":"Regulation of immunity in bronchiectasis","volume":"47","author":"Boyton","year":"2009","journal-title":"Med. Mycol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"00683","DOI":"10.1183\/23120541.00683-2024","article-title":"Natural killer cells in the lung: Novel insight and future challenge in the airway diseases","volume":"11","author":"Pianigiani","year":"2025","journal-title":"ERJ Open Res."},{"key":"ref_54","first-page":"123","article-title":"The role of neutrophils in asthma","volume":"50","author":"Chen","year":"2021","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1055\/s-0041-1730891","article-title":"Pathophysiology of Bronchiectasis","volume":"42","author":"Keir","year":"2021","journal-title":"Semin. Respir. Crit. Care. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Voynow, J.A., Zheng, S., and Kummarapurugu, A.B. (2020). Glycosaminoglycans as Multifunctional Anti-Elastase and Anti-Inflammatory Drugs in Cystic Fibrosis Lung Disease. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01011"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1164\/rccm.201712-2423OC","article-title":"Blood Neutrophils Are Reprogrammed in Bronchiectasis","volume":"198","author":"Bedi","year":"2018","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/omi.12252","article-title":"The roles of NADPH oxidase in modulating neutrophil effector responses","volume":"34","author":"Zeng","year":"2019","journal-title":"Mol. Oral. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e180132","DOI":"10.1172\/jci.insight.180132","article-title":"Treg and neutrophil extracellular trap interaction contributes to the development of immunosuppression in sepsis","volume":"9","author":"Shi","year":"2024","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12931-023-02444-z","article-title":"Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: Results from the WILLOW trial","volume":"24","author":"Cipolla","year":"2023","journal-title":"Respir. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"211","DOI":"10.33696\/immunology.6.208","article-title":"Evaluation of Neutrophil Elastase Inhibitors as Potential Therapies for ELANE Associated Neutropenia","volume":"6","author":"Makaryan","year":"2024","journal-title":"J. Cell Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1056\/NEJMoa2021713","article-title":"Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis","volume":"383","author":"Chalmers","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1164\/rccm.202408-1545OC","article-title":"Broad Immunomodulatory Effects of the Dipeptidyl Peptidase-1 Inhibitor Brensocatib in Bronchiectasis: Data from the Phase 2, Double-Blind, Placebo-controlled WILLOW Trial","volume":"211","author":"Johnson","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.1601831113","article-title":"Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation","volume":"113","author":"Brook","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1002\/bcp.70027","article-title":"Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase-1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study","volume":"91","author":"Wang","year":"2025","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/cpt.1053","article-title":"Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects","volume":"104","author":"Jauhiainen","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9457","DOI":"10.1021\/acs.jmedchem.6b01127","article-title":"Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986)","volume":"59","author":"Doyle","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Sutton, V.R., Watt, S.V., Akhlaghi, H., Cipolla, D.C., Chen, K.-J., LaSala, D., McDonald, P.P., Beavis, P.A., Munoz, I., and Hodel, A.W. (2024). Pharmacologic inhibition of dipeptidyl peptidase 1 (cathepsin C) does not block in vitro granzyme-mediated target cell killing by CD8 T or NK cells. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1396710"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4046\/trd.2023.0010","article-title":"Exacerbation Prevention and Management of Bronchiectasis","volume":"86","author":"Choi","year":"2023","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1056\/NEJMoa2411664","article-title":"Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis","volume":"392","author":"Chalmers","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"00151","DOI":"10.1183\/23120541.00151-2024","article-title":"Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics","volume":"10","author":"Chalmers","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/cpdd.1094","article-title":"Safety, Tolerability, and Pharmacokinetic Evaluation of Single and Multiple Doses of the Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Healthy Japanese and White Adults","volume":"11","author":"Usansky","year":"2022","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_73","first-page":"29768675241300808","article-title":"Bronchiectasis-COPD Overlap Syndrome: A Comprehensive Review of its Pathophysiology and Potential Cardiovascular Implications","volume":"19","author":"Alam","year":"2024","journal-title":"Ther. Adv. Pulm. Crit. Care. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s00408-025-00844-0","article-title":"Emerging Therapeutics in COPD: Mapping Innovation to Treatable Traits","volume":"203","author":"Cazzola","year":"2025","journal-title":"Lung"},{"key":"ref_75","unstructured":"Wasfy, J., Kim, K., Tuochette, D., McKenna, A., Richardson, M., Herce-Hagiwara, B., Kim, S., Phillips, M., and Ollendorf, D. (2025, December 03). Brensocatib for Non-Cystic Fibrosis Bronchiectasis: Effectiveness and Value. Available online: https:\/\/icer.org\/wp-content\/uploads\/2025\/10\/ICER_NCFB-Final-Report_For-Publication_103025.pdf."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1164\/rccm.202501-0032ED","article-title":"Dancing with DPP-1: The Inflammatory Tango of Bronchiectasis","volume":"211","author":"Waterer","year":"2025","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1007\/s00011-023-01774-4","article-title":"BI 1291583: A novel selective inhibitor of cathepsin C with superior in vivo profile for the treatment of bronchiectasis","volume":"72","author":"Kreideweiss","year":"2023","journal-title":"Inflamm. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1097\/MS9.0000000000004101","article-title":"FDA approval of brensocatib: A new therapeutic breakthrough in non-cystic fibrosis bronchiectasis","volume":"87","author":"Fatima","year":"2025","journal-title":"Ann. Med. Surg."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Fan, L.-C., Lu, H.-W., Wei, P., Ji, X.-B., Liang, S., and Xu, J.-F. (2015). Effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: A meta-analysis of randomized controlled trials. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-0872-5"},{"key":"ref_80","unstructured":"Editor, A.G. (2026, January 22). Brensocatib Becomes First Approved Treatment for Non-Cystic Fibrosis Bronchiectasis in Adults, Adolescents | Pharmacy Times. Available online: https:\/\/www.pharmacytimes.com\/view\/brensocatib-becomes-first-approved-treatment-for-non-cystic-fibrosis-bronchiectasis-in-adults-adolescents."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/bcp.16344","article-title":"The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration","volume":"91","author":"Yeung","year":"2025","journal-title":"Br. J. Clin. Pharmacol"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"A3495","DOI":"10.1164\/ajrccm.2025.211.Abstracts.A3495","article-title":"Efficacy of Brensocatib in Patients With Non-Cystic Fibrosis Bronchiectasis With vs Without Maintenance Use of Macrolides: An Analysis of the ASPEN Trial","volume":"211","author":"Haworth","year":"2025","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2584413","DOI":"10.1080\/07853890.2025.2584413","article-title":"The role of neutrophils in bronchiectasis","volume":"57","author":"Liang","year":"2025","journal-title":"Ann. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1186\/s12931-025-03407-2","article-title":"Efficacy and safety of DPP-1 inhibitors in bronchiectasis: A GRADE-assessed meta-analysis of randomized controlled trials","volume":"26","author":"Emara","year":"2025","journal-title":"Respir. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s40262-025-01550-z","article-title":"A Phase IIa, Single-Blind, Placebo-Controlled, Parallel-Group Study to Assess Safety, Tolerability, and Pharmacokinetics\/Pharmacodynamics of Brensocatib in Adults with Cystic Fibrosis","volume":"64","author":"Konstan","year":"2025","journal-title":"Clin. Pharmacokinet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1656316","DOI":"10.3389\/fphar.2025.1656316","article-title":"Dipeptidyl peptidase 1 inhibitors for inflammatory respiratory diseases: Mechanisms, clinical trials, and therapeutic prospects","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Pharmacol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T17:38:28Z","timestamp":1770226708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":86,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15031257"],"URL":"https:\/\/doi.org\/10.3390\/jcm15031257","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]}}}