{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:18:26Z","timestamp":1790054306944,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,10,12]],"date-time":"2014-10-12T00:00:00Z","timestamp":1413072000000},"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":["569246"],"award-info":[{"award-number":["569246"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Abstract<\/jats:title>Background and objective<\/jats:title>Corticosteroid resistance in chronic obstructive pulmonary disease (COPD<\/jats:styled-content>) is a major challenge. We have reported increased bronchial epithelial cell apoptosis and increased airway CD8 T<\/jats:styled-content>\u2010cell numbers in COPD<\/jats:styled-content>. Apoptosis can be induced via the serine protease, granzyme B<\/jats:styled-content>. However, glucocorticosteroids fail to adequately suppress granzyme B<\/jats:styled-content> production by CD8 T<\/jats:styled-content> cells. We previously showed that low\u2010dose azithromycin reduced airways inflammation in COPD<\/jats:styled-content> subjects and we hypothesized that it would also reduce granzyme B<\/jats:styled-content> production by CD8 T<\/jats:styled-content> cells.<\/jats:p><\/jats:sec>Methods<\/jats:title>We administered 250\u2009mg azithromycin daily for 5 days then twice weekly (total 12 weeks) to 11 COPD<\/jats:styled-content> subjects (five current smokers; six ex\u2010smokers) and assessed granzyme B<\/jats:styled-content> in the airway (bronchoalveolar lavage), intra\u2010epithelial compartment and peripheral blood, collected before and following administration of azithromycin. To then dissect the effects of on CD4<\/jats:styled-content> and CD8 T<\/jats:styled-content>\u2010cell subsets, we applied an in vitro<\/jats:italic> assay and physiologically relevant concentrations of azithromycin (and, for comparison, n\u2010acetyl cysteine) and stimulation of peripheral blood mononuclear cells from five healthy subjects with CD3<\/jats:styled-content>\/CD28 T<\/jats:styled-content>\u2010cell expander.<\/jats:p><\/jats:sec>Results<\/jats:title>T<\/jats:styled-content>\u2010cell granzyme B<\/jats:styled-content> production in both airway and intra\u2010epithelial compartments was reduced in COPD<\/jats:styled-content> patients following 12 weeks of azithromycin treatment, with no significant effect in blood. Both azithromycin and n\u2010acetyl cysteine suppressed CD4 T<\/jats:styled-content>\u2010cell granzyme B<\/jats:styled-content> production, but only azithromycin was effective at reducing CD8+ T<\/jats:styled-content>\u2010cell granzyme B<\/jats:styled-content> production in vitro<\/jats:italic>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>We provide further evidence for the application of low\u2010dose azithromycin as an attractive adjunct treatment option for controlling epithelial cell apoptosis, abnormal airway repair and chronic inflammation in COPD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.12415","type":"journal-article","created":{"date-parts":[[2014,10,13]],"date-time":"2014-10-13T00:29:23Z","timestamp":1413160163000},"page":"95-100","source":"Crossref","is-referenced-by-count":19,"title":["Increased CD8 T<\/scp>\u2010cell granzyme B<\/scp> in COPD<\/scp> is suppressed by treatment with low\u2010dose azithromycin"],"prefix":"10.1111","volume":"20","author":[{"given":"Sandra","family":"Hodge","sequence":"first","affiliation":[{"name":"Lung Research Laboratory Hanson Institute Adelaide South Australia Australia"},{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Hodge","sequence":"additional","affiliation":[{"name":"Lung Research Laboratory Hanson Institute Adelaide South Australia Australia"},{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Holmes","sequence":"additional","affiliation":[{"name":"Lung Research Laboratory Hanson Institute Adelaide South Australia Australia"},{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertus","family":"Jersmann","sequence":"additional","affiliation":[{"name":"Lung Research Laboratory Hanson Institute Adelaide South Australia Australia"},{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Lung Research Laboratory Hanson Institute Adelaide South Australia Australia"},{"name":"Department of Thoracic Medicine Royal Adelaide Hospital Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,12]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Australian Lung Foundation Access Economics.Economic impact of COPD and cost effective solutions report. 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