{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:05:39Z","timestamp":1789041939325,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["544915"],"award-info":[{"award-number":["544915"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018853","name":"Prince Charles Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018853","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Neutrophil elastase (NE), is an important host defence against lung pathogens. Maintaining a homeostatic balance between proteases such as NE and anti\u2010proteases such as secretory leukocyte protease inhibitor (SLPI), is important to prevent tissue damage. In the cystic fibrosis (CF) lung, elevated protease levels and impaired anti\u2010protease defences contribute to tissue destruction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed lung function and sputum SLPI and NE levels from<jats:italic>Pseudomonas aeruginosa<\/jats:italic>infected and non\u2010infected CF patients (median age 20\u2009years at recruitment) during different phases of clinical disease. Healthy, never smokers served as healthy controls (HC). Sputum total cell counts (TCC) and colony forming units of<jats:italic>P. aeruginosa<\/jats:italic>were also determined in each sputum sample.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to HC, sputum SLPI was significantly reduced and NE increased in all CF subjects whether infected with<jats:italic>P. aeruginosa<\/jats:italic>or not, but the presence of<jats:italic>P. aeruginosa<\/jats:italic>worsened these parameters. Females with chronic<jats:italic>P. aeruginosa<\/jats:italic>infection had significantly lower sputum SLPI levels than males (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Higher sputum SLPI levels were associated with a significantly reduced rate of longitudinal decline in FEV<jats:sub>1<\/jats:sub>% predicted (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Antibiotic treatment in<jats:italic>P. aeruginosa<\/jats:italic>\u2010infected patients significantly decreased sputum TCC and increased SLPI levels, which positively correlated with improved lung function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Airway SLPI is deficient in CF, which appears more marked in<jats:italic>P. aeruginosa<\/jats:italic>\u2010infected female patients. Importantly, a reduced anti\u2010protease to protease ratio is associated with accelerated lung function decline. Treatment of an exacerbation is accompanied by partial recovery of anti\u2010protease defences and significant improvement in lung function, an important clinical outcome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.14450","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:35:21Z","timestamp":1673836521000},"page":"533-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti\u2010protease levels in cystic fibrosis are associated with lung function, recovery from pulmonary exacerbations and may be gender\u2010related"],"prefix":"10.1111","volume":"28","author":[{"given":"Ama\u2010Tawiah","family":"Essilfie","sequence":"first","affiliation":[{"name":"Immunology Department Queensland Institute of Medical Research Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neralee","family":"Houston","sequence":"additional","affiliation":[{"name":"The Menzies Research Institute Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Maniam","sequence":"additional","affiliation":[{"name":"Immunology Department Queensland Institute of Medical Research Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Hartel","sequence":"additional","affiliation":[{"name":"Statistics Department Queensland Institute of Medical Research Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Okano","sequence":"additional","affiliation":[{"name":"Statistics Department Queensland Institute of Medical Research Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-8212","authenticated-orcid":false,"given":"David W.","family":"Reid","sequence":"additional","affiliation":[{"name":"Immunology Department Queensland Institute of Medical Research Brisbane Queensland Australia"},{"name":"University of Queensland St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2004.06.006"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.03.003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.082388"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901716"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000196490"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.11.6.7946401"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81880-2"},{"issue":"5","key":"e_1_2_10_10_1","first-page":"359","article-title":"Regulation of secretory leukocyte proteinase inhibitor (SLPI) production by human bronchial epithelial cells: increase of cell\u2010associated SLPI by neutrophil elastase","volume":"48","author":"Wetering S, van der Linden AC, van Sterkenburg MA, Rabe KF, Scalkwijk J, Hiemstra PS","year":"2000","journal-title":"J Invest Med"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.3.1271-1274.2005"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115994"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021824"},{"key":"e_1_2_10_14_1","first-page":"103","article-title":"Secretory leukocyte protease inhibitor in cystic fibrosis","volume":"42","author":"Stromatt SC","year":"1993","journal-title":"Agents Actions Suppl"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115021"},{"issue":"6","key":"e_1_2_10_16_1","first-page":"1070","article-title":"Inactivation of human bronchial mucosal proteinase inhibitor by Pseudomonas aeruginosa elastase","volume":"126","author":"Johnson DA","year":"1982","journal-title":"Am Rev Respir Dis"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.931"},{"key":"e_1_2_10_18_1","unstructured":"17th Annual Report Australian Cystic Fibrosis Foundation Data Registry CF Australia. 2014: 16\u20137. 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