{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:19:47Z","timestamp":1788239987032,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01HL136499"],"award-info":[{"award-number":["NIH R01HL136499"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dysregulated protease activity contributes to airway inflammation and tissue remodeling in cystic fibrosis (CF); however, the role of the lysosomal cysteine protease Cathepsin B (CTSB) remains incompletely defined. This cross\u2010sectional study investigates relationships between pro\u2010CTSB and mature CTSB activity with CF\u2010specific pathogens and airway inflammation in children with and without CF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Bronchoalveolar lavage fluid (BALF) was collected from clinically indicated bronchoscopies in children (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200952 CF,\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009161 non\u2010CF). CTSB was interrogated using ELISA, fluorogenic activity assay, and Western blot analysis to distinguish pro\u2010 and mature CTSB. Total bacterial and total fungal load (TFL) were quantified by quantitative polymerase chain reaction, and community composition was determined by 16S bacterial and 18S fungal sequencing. Concentrations of proinflammatory cytokines and neutrophil elastase (NE) were measured via Luminex multiplatform and a spectrophotometric assay, respectively. Analyses included Spearman's rank correlations and Wilcoxon rank\u2010based tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pro\u2010CTSB and CTSB activity were significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) elevated in CF BALF and in samples with a positive\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      airway culture. Pro\u2010CTSB concentrations correlated with staphylococcal relative abundance (RA,  =\u20090.25,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.02) and reduced bacterial diversity (\u2009=\u2009\u22120.41,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Mature CTSB activity correlated with TFL (\u2009=\u20090.50,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp. RA (\u2009=\u20090.36,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.04). Western blot analysis confirmed pro\u2010CTSB expression and mature CTSB in BALF with measurable activity. Both CTSB measures correlated strongly with NE and proinflammatory cytokines (\u2009\u2265\u20090.47,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Pro\u2010CTSB concentrations negatively correlated with FEV1\/FVC measurements in CF (\u2009=\u2009\u22120.32,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BALF CTSB concentration may serve as a CF\u2010specific biomarker of infection\u2010related inflammation and obstructive lung disease driven by specific pathogen interactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71793","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:40:31Z","timestamp":1786704031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cathepsin B, Airway Pathogens, and Inflammation in the Lower Airways of Children With Cystic Fibrosis"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9587-6681","authenticated-orcid":false,"given":"Matthew K.","family":"Fought","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Sleep Medicine University of Washington and Seattle Children's Hospital Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2745-0103","authenticated-orcid":false,"given":"Brandie D.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Colorado School of Public Health University of Colorado Denver Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Sleep Medicine University of Washington and Seattle Children's Hospital Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kirk Harris","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Laguna","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Sleep Medicine University of Washington and Seattle Children's Hospital Seattle Washington 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