{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:25:39Z","timestamp":1791257139708,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) has a genetic component, explaining susceptibility. Tumor necrosis factor (TNF)-\u03b1 polymorphisms have been associated with COPD, but it is unclear if genotype influences clinical phenotype, protein expression, and bioactivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine if a functional polymorphism was important by assessing TNF-\u03b1 expression and activity and its association with clinical severity over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with COPD with rs361525 polymorphism were matched to patients with COPD without rs361525 polymorphism. TNF-\u03b1, its antagonists, and downstream mediators were measured in plasma and sputum. To determine TNF-\u03b1 bioactivity, IL-8 secretion from primary bronchial epithelial cells (PBECs) was measured, and neutrophil migration was assessed using sputum from both subject groups in the presence and absence of TNF-\u03b1 antibody. Subjects were followed annually and compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Patients with polymorphism had more chronic bronchitis, a lower body mass index, and a greater annual decline in FEV1 than patients with COPD without rs361525 polymorphism. TNF-\u03b1 concentrations were 100-fold higher in airway secretions from the patients with the rs361525 polymorphism, with no difference in TNF-\u03b1 antagonists. Their lung secretions contained more IL-8 and myeloperoxidase, consistent with downstream inflammation. Sputum from patients with rs361525 polymorphism induced greater secretion of IL-8 from PBECs and increased neutrophil migration. These effects could be abrogated by TNF-\u03b1 antibody, demonstrating the bioactivity of TNF-\u03b1 in lung secretions from this group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This TNF-\u03b1 polymorphism is associated with clinical features of disease including progression. There is clear evidence of TNF-\u03b1 overexpression and bioactivity with neutrophilic inflammation. The polymorphism is likely to be a factor that influences a COPD disease phenotype and its progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200912-1846oc","type":"journal-article","created":{"date-parts":[[2010,7,16]],"date-time":"2010-07-16T01:43:24Z","timestamp":1279244604000},"page":"192-199","source":"Crossref","is-referenced-by-count":50,"title":["Tumor Necrosis Factor\u2013\u03b1 rs361525 Polymorphism Is Associated with Increased Local Production and Downstream Inflammation in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"182","author":[{"given":"Elizabeth","family":"Sapey","sequence":"first","affiliation":[{"name":"Clinical and Experimental Medicine; University of Birmingham, Edgbaston, Birmingham; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Medicine; University of Birmingham, Edgbaston, Birmingham; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Lung Investigation Unit, University Hospital Birmingham NHS, Foundation Trust, Edgbaston, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Stockley","sequence":"additional","affiliation":[{"name":"Lung Investigation Unit, University Hospital Birmingham NHS, Foundation Trust, Edgbaston, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"key":"2026032101475947000_BIB1","first-page":"1066","volume-title":"Science","year":"1989"},{"key":"2026032101475947000_BIB2","first-page":"195","volume-title":"FEBS Lett","year":"1976"},{"key":"2026032101475947000_BIB3","first-page":"846","volume-title":"Respir 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