{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:46:12Z","timestamp":1791899172022,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To explore the relationship between recurrent otitis media (ROM), chronic media otitis with effusion (COM), and laryngopharyngeal reflux disease (LPRD) in pediatric populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>PubMed, Scopus, and Cochrane databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Review Methods<\/jats:title>\n                    <jats:p>\n                      Two investigators independently screened papers with PRISMA guidelines considering the following primary outcomes: LPRD prevalence in pediatric ROM and COM, diagnostic methods used, and detection rates of gastroduodenal markers in middle ear effusions. Two random\u2010effects meta\u2010analyses were performed to estimate the pooled prevalence of pepsin\/pepsinogen detection in middle ear effusions and to compare pepsin concentrations between COM\/ROM patients and controls using standardized mean differences (Hedges'\n                      <jats:italic>g<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010eight studies were included (2070 pediatric patients). The cumulated gastroesophageal reflux disease prevalence in COM children was estimated to 50.7%, while 27.6% of children reported pharyngeal reflux events. Fifteen studies measured pepsin in effusions, reporting a pooled detection prevalence of 72.5% (95% CI: 53.7%\u201088.0%), rising to 85.6% with ELISA\u2010based methods versus 17.9% with enzymatic assays. The pooled standardized mean difference in pepsin concentration between OME patients and controls was large and significant (Hedges'\n                      <jats:italic>g\u2009<\/jats:italic>\n                      =\u20091.92, 95% CI: 0.58\u20103.25,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.005). Alkaline\u2010activated gastroduodenal mediators were assessed in 3 studies, with detection rates ranging from 39.6% to 100% for trypsin and from 32% to 42% for bile salts. Substantial heterogeneity was found for COM\/ROM and reflux disease diagnostic criteria, gastroduodenal biomarker measurements, and outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gastroduodenal biomarkers are present in middle ear effusions of children with COM and ROM. Future prospective transversal studies exploring alkaline\u2010activated enzymes and bile salts in effusion of children with documented pharyngeal reflux events are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ohn.70488","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:52:31Z","timestamp":1791895951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pediatric Laryngopharyngeal Reflux Disease and Otitis Media With Effusion: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-0845","authenticated-orcid":false,"given":"J\u00e9r\u00f4me R.","family":"Lechien","sequence":"first","affiliation":[{"name":"Department of Surgery UMONS Research Institute for Health Sciences and Technology, University of Mons Mons Belgium"},{"name":"Department of Otolaryngology and Head and Neck Surgery Foch Hospital, Paris Saclay University Paris France"},{"name":"Department of Otolaryngology and Head and Neck Surgery CHU Saint\u2010Pierre Brussels Belgium"},{"name":"Department of Otolaryngology and Head and Neck Surgery Elsan Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Briganti","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry and Computational Medicine UMONS Research Institute for Health Sciences and Technology, University of Mons Mons Belgium"},{"name":"Department of Psychiatry CHU Helora Mons Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"4","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/lary.31134","article-title":"The Dubai definition and diagnostic criteria of laryngopharyngeal reflux: the IFOS consensus","volume":"134","author":"Lechien JR","year":"2024","journal-title":"Laryngoscope"},{"issue":"3","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.otc.2025.01.006","article-title":"Pepsin, mucosal injury, and pathophysiology of non\u2010acid reflux","volume":"58","author":"Samuels TL","year":"2025","journal-title":"Otolaryngol Clin North Am"},{"issue":"5","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.otohns.2009.08.022","article-title":"Pepsin as a causal agent of inflammation during nonacidic reflux","volume":"141","author":"Samuels TL","year":"2009","journal-title":"Otolaryngol Head Neck Surg"},{"issue":"4","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/coa.14047","article-title":"Association between laryngopharyngeal reflux, gastroesophageal reflux and recalcitrant chronic rhinosinusitis: a systematic review","volume":"48","author":"Lechien JR","year":"2023","journal-title":"Clin Otolaryngol"},{"issue":"2","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/ohn.529","article-title":"Laryngopharyngeal reflux and benign vocal fold lesions: a systematic review and meta\u2010analysis","volume":"170","author":"Ren QW","year":"2024","journal-title":"Otolaryngol Head Neck Surg"},{"issue":"8","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.15537\/smj.2025.46.8.20250129","article-title":"Prevalence and clinical features of laryngopharyngeal reflux in adults with chronic tonsillitis","volume":"46","author":"Fageeh YA","year":"2025","journal-title":"Saudi Med J"},{"key":"e_1_2_9_8_1","first-page":"443","article-title":"Evaluation of Gastro\u2010Esophageal Reflux Disease (GERD), as a possible cause of Eustachian tube dysfunction in adults","volume":"94","author":"Sivero L","year":"2023","journal-title":"Ann Ital Chir"},{"issue":"3","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/0194599811430809","article-title":"Association between otitis media and gastroesophageal reflux: a systematic review","volume":"146","author":"Miura MS","year":"2012","journal-title":"Otolaryngol Head Neck Surg"},{"issue":"7","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"e801","DOI":"10.1097\/MAO.0000000000003123","article-title":"Association between laryngopharyngeal reflux and media otitis: a systematic review","volume":"42","author":"Lechien JR","year":"2021","journal-title":"Otol Neurotol"},{"issue":"4","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1001\/jama.2017.19163","article-title":"Preferred reporting items for a systematic review and meta\u2010analysis of diagnostic test accuracy studies: the PRISMA\u2010DTA statement","volume":"319","author":"McInnes MDF","year":"2018","journal-title":"JAMA"},{"key":"e_1_2_9_12_1","unstructured":"ThompsonM TiwariA FuR et al. 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