{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:20:28Z","timestamp":1774113628893,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T00:00:00Z","timestamp":1387756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["569246"],"award-info":[{"award-number":["569246"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Abstract<\/jats:title>Background and objective<\/jats:title>The non\u2010eosinophilic phenotype of asthma (NEA<\/jats:styled-content>) is associated with chronic airway inflammation and airway neutrophilia. An accumulation of apoptotic airway epithelial cells, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, with the potential for inflammation of surrounding tissues. Apoptosis may occur via the T<\/jats:styled-content> cell granzyme B<\/jats:styled-content> pathway. The role of granzyme B<\/jats:styled-content> in NEA<\/jats:styled-content> is not known. The aim of this study was to investigate production of granzyme B<\/jats:styled-content> and its inhibitor proteinase inhibitor (PI<\/jats:styled-content>)\u20109 by T<\/jats:styled-content> cells from induced sputum and compare expression between eosinophilic, NEA<\/jats:styled-content> and healthy controls.<\/jats:p><\/jats:sec>Methods<\/jats:title>We investigated T<\/jats:styled-content> cell intracellular granzyme B<\/jats:styled-content> and its inhibitor, PI<\/jats:styled-content>\u20109, in sputum from healthy control subjects (n<\/jats:italic>\u2009=\u200910), and patients with NEA<\/jats:styled-content> (n<\/jats:italic>\u2009=\u200922) or eosinophilic asthma (EA<\/jats:styled-content>) (n<\/jats:italic>\u2009=\u200915) using flow cytometry.<\/jats:p><\/jats:sec>Results<\/jats:title>Granzyme B<\/jats:styled-content> expression and the ratio of granzyme B<\/jats:styled-content> to PI<\/jats:styled-content>\u20109 positive cells were highest in those with NEA<\/jats:styled-content> for both CD3<\/jats:styled-content>+ and CD4<\/jats:styled-content>+ T<\/jats:styled-content> cells. The expression of granzyme B<\/jats:styled-content> was not statistically different between patients with NEA<\/jats:styled-content> and EA<\/jats:styled-content>; however, the ratio of granzyme B<\/jats:styled-content> to PI<\/jats:styled-content>\u20109 positive cells for CD3<\/jats:styled-content>+ T<\/jats:styled-content> cells was significantly higher in those with NEA<\/jats:styled-content> compared with EA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Induced sputum provides a non\u2010invasive tool for investigating T<\/jats:styled-content> cell cytotoxic mediators in the various asthma subtypes. Granzyme B<\/jats:styled-content> expression is increased in NEA<\/jats:styled-content> and the contribution of granzyme B<\/jats:styled-content> to chronic inflammation requires further study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.12213","type":"journal-article","created":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T09:04:49Z","timestamp":1387789489000},"page":"280-287","source":"Crossref","is-referenced-by-count":8,"title":["Altered sputum granzyme B<\/scp> and granzyme B<\/scp>\/proteinase inhibitor\u20109 in patients with non\u2010eosinophilic asthma"],"prefix":"10.1111","volume":"19","author":[{"given":"Jodie L","family":"Simpson","sequence":"first","affiliation":[{"name":"Centre for Asthma and Respiratory Disease The University of Newcastle Newcastle New South Wales Australia"},{"name":"Department of Respiratory and Sleep Medicine John Hunter Hospital Hunter Medical Research Institute Newcastle New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter G","family":"Gibson","sequence":"additional","affiliation":[{"name":"Centre for Asthma and Respiratory Disease The University of Newcastle Newcastle New South Wales Australia"},{"name":"Department of Respiratory and Sleep Medicine John Hunter Hospital Hunter Medical Research Institute Newcastle New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine The University of Queensland Brisbane Queensland Australia"},{"name":"The Prince Charles Hospital Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Upham","sequence":"additional","affiliation":[{"name":"School of Medicine The University of Queensland Brisbane Queensland Australia"},{"name":"Princess Alexandra Hospital Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"James","sequence":"additional","affiliation":[{"name":"Sir Charles Gairdner Hospital Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul N","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"},{"name":"Lung Research Laboratory, Hanson Institute Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Hodge","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"},{"name":"Lung Research Laboratory, Hanson Institute Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"AMAZES Study Research Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,12,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2006.00784.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1640OC"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.073429"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.3.9812110"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/148.3.713"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)01813-9"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00137704"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00077604"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2009.03244.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000088436"},{"key":"e_1_2_7_12_1","first-page":"419","article-title":"Epithelial cell apoptosis and lung remodeling","volume":"4","author":"Kuwano K","year":"2007","journal-title":"Cell. 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