{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:03:16Z","timestamp":1791421396105,"version":"4.3.3"},"reference-count":30,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020483","name":"insmed","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["JDR Clinical &amp; Translational Research"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1 (cathepsin C), in development to treat chronic non\u2013cystic fibrosis bronchiectasis. The phase 2, randomized, placebo-controlled WILLOW trial (NCT03218917) was conducted to examine whether brensocatib reduced the incidence of pulmonary exacerbations. Brensocatib prolonged the time to the first exacerbation and led to fewer exacerbations than placebo. Because brensocatib potentially affects oral tissues due to its action on neutrophil-mediated inflammation, we analyzed periodontal outcomes in the trial participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>Patients with bronchiectasis were randomized 1:1:1 to receive once-daily oral brensocatib 10 or 25 mg or placebo. Periodontal status was monitored throughout the 24-week trial in a prespecified safety analysis. Periodontal pocket depth (PPD) at screening, week 8, and week 24 was evaluated. Gingival inflammation was evaluated by a combination of assessing bleeding upon probing and monitoring the L\u00f6e-Silness Gingival Index on 3 facial surfaces and the mid-lingual surface.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>At week 24, mean \u00b1 SE PPD reductions were similar across treatment groups: \u22120.07 \u00b1 0.007, \u22120.06 \u00b1 0.007, and \u22120.15 \u00b1 0.007 mm with brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. The distribution of changes in PPD and the number of patients with multiple increased PPD sites were similar across treatment groups at weeks 8 and 24. The frequencies of gingival index values were generally similar across treatment groups at each assessment. An increase in index values 0\u20131 and a decrease in index values 2\u20133 over time and at the end of the study were observed in all groups, indicating improved oral health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In patients with non\u2013cystic fibrosis bronchiectasis, brensocatib 10 or 25 mg had an acceptable safety profile after 6 months\u2019 treatment, with no changes in periodontal status noted. Improvement in oral health at end of the study may be due to regular dental care during the trial and independent of brensocatib treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Knowledge Transfer Statement:<\/jats:title>\n                    <jats:p>The results of this study suggest that 24 weeks of treatment with brensocatib does not affect periodontal disease progression. This information can be used by clinicians when considering treatment approaches for bronchiectasis and suggests that the use of brensocatib will not be limited by periodontal disease risks. Nevertheless, routine dental\/periodontal care should be provided to patients irrespective of brensocatib treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23800844231196884","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T04:55:33Z","timestamp":1695617733000},"page":"277-285","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Periodontal Effects of the Reversible Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Bronchiectasis"],"prefix":"10.1177","volume":"9","author":[{"given":"J.C.","family":"Gunsolley","sequence":"first","affiliation":[{"name":"Department of Periodontics, Virginia Commonwealth University School of Dentistry, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.D.","family":"Chalmers","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, Dundee, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Sibila","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Respiratory Institute, Hospital Cl\u00ednic\u2013Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias, and University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Insmed Incorporated, Bridgewater, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.A.","family":"Scannapieco","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, University at Buffalo School of Dental Medicine, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"bibr1-23800844231196884","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1990.tb01106.x"},{"key":"bibr2-23800844231196884","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021713"},{"key":"bibr3-23800844231196884","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2012.09.011"},{"key":"bibr4-23800844231196884","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0380OC"},{"key":"bibr5-23800844231196884","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1996.67.6.617"},{"key":"bibr6-23800844231196884","doi-asserted-by":"crossref","unstructured":"Gomes-Filho IS, Cruz SSD, Trindade SC, Passos-Soares JS, Carvalho-Filho PC, Figueiredo ACMG, Lyrio AO, Hintz AM, Pereira MG, Scannapieco F. 2020. Periodontitis and respiratory diseases: a systematic review with meta-analysis. 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