{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:53:25Z","timestamp":1791939205988,"version":"4.3.4"},"reference-count":78,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T00:00:00Z","timestamp":1626480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["5R21DC015634\u201002"],"award-info":[{"award-number":["5R21DC015634\u201002"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Cross\u2010sectional study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme\u2010linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1\u2009mg\/ml pepsin at pH\u20095, 6, and 7 for 30\u2009minutes, and cytokine expression was assayed via qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pepsin was observed in the MEF of 77% of patients (range 71\u20132,734\u2009ng\/ml). Pepsin correlated with effusion viscosity, interleukins \u22126 and \u22128, neutrophil elastase, and mucin 5B (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u2009.05). Pepsin\u2010negative MEF was more frequently absent of interleukin 8 or mucin 5B (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u2009.05). Weak acid was generally insufficient to elicit cytokine expression in ME cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      , however, pepsin induced\n                      <jats:italic>IL6<\/jats:italic>\n                      ,\n                      <jats:italic>IL8<\/jats:italic>\n                      , and\n                      <jats:italic>TNF<\/jats:italic>\n                      at pH\u20097 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u2009.05) and weak acid (pH\u20096) facilitated a response at lower pepsin concentration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>\n                      4\n                      <jats:italic>Laryngoscope<\/jats:italic>\n                      , 132:470\u2013477, 2022\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.29749","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T06:35:43Z","timestamp":1626503743000},"page":"470-477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Association of Pepsin With Inflammatory Signaling and Effusion Viscosity in Pediatric Otitis Media"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-357X","authenticated-orcid":false,"given":"Tina L.","family":"Samuels","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin 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