Role of pepsin and pepsinogen: Linking laryngopharyngeal reflux with otitis media with effusion in children

Objectives/Hypothesis To analyze the relationship between laryngopharyngeal reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis media with effusion (OME). Study Design Prospective case‐control study. Methods Children with OME who required adenoidectomy and tympanostomy/tymp...

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Veröffentlicht in:The Laryngoscope 2014-07, Vol.124 (7), p.E294-E300
Hauptverfasser: Luo, Hua-Nan, Yang, Qi-Mei, Sheng, Ying, Wang, Zheng-Hui, Zhang, Qing, Yan, Jing, Hou, Jin, Zhu, Kang, Cheng, Ying, Wang, Bo-Tao, Xu, Ying-Long, Zhang, Xiang-Hong, Ren, Xiao-Yong, Xu, Min
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container_end_page E300
container_issue 7
container_start_page E294
container_title The Laryngoscope
container_volume 124
creator Luo, Hua-Nan
Yang, Qi-Mei
Sheng, Ying
Wang, Zheng-Hui
Zhang, Qing
Yan, Jing
Hou, Jin
Zhu, Kang
Cheng, Ying
Wang, Bo-Tao
Xu, Ying-Long
Zhang, Xiang-Hong
Ren, Xiao-Yong
Xu, Min
description Objectives/Hypothesis To analyze the relationship between laryngopharyngeal reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis media with effusion (OME). Study Design Prospective case‐control study. Methods Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes placement were enrolled in OME group, whereas children with adenoid hypertrophy (AH) who required adenoidectomy and individuals who required cochlear implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen mRNA and protein levels were assessed by real‐time fluorescence‐based quantitative polymerase chain reaction and immunohistochemistry in adenoid specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were evaluated by enzyme‐linked immunosorbent assay in middle ear fluid and plasma from the OME and CI groups. Results The levels of pepsinogen protein expressed in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid specimens from the OME group were significantly higher than those in the AH group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group were 51.93 ± 11.58 ng/mL and 728 ± 342.6 ng/mL, respectively, which were significantly higher than those in the CI group (P 
doi_str_mv 10.1002/lary.24538
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Study Design Prospective case‐control study. Methods Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes placement were enrolled in OME group, whereas children with adenoid hypertrophy (AH) who required adenoidectomy and individuals who required cochlear implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen mRNA and protein levels were assessed by real‐time fluorescence‐based quantitative polymerase chain reaction and immunohistochemistry in adenoid specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were evaluated by enzyme‐linked immunosorbent assay in middle ear fluid and plasma from the OME and CI groups. Results The levels of pepsinogen protein expressed in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid specimens from the OME group were significantly higher than those in the AH group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group were 51.93 ± 11.58 ng/mL and 728 ± 342.6 ng/mL, respectively, which were significantly higher than those in the CI group (P &lt; .001). In addition, the concentrations of pepsin in dry ears were significantly lower than those in serous and mucus ears in the OME group (F = 22.77, P &lt; .001).Finally, the concentration of pepsinogen in middle ear effusion was positively correlated with the expression intensity of pepsinogen protein in cytoplasm of epithelial cells(r = 0.73, P &lt; .05) in the OME group. Conclusions Pepsin and pepsinogen in middle ear effusion are probably caused by LPR and may be involved in the pathogenesis of OME. Level of Evidence 3b Laryngoscope, 124:E294–E300, 2014</description><identifier>ISSN: 0023-852X</identifier><identifier>EISSN: 1531-4995</identifier><identifier>DOI: 10.1002/lary.24538</identifier><identifier>PMID: 24284944</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adenoids - chemistry ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Esophageal pH Monitoring ; Female ; Follow-Up Studies ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; laryngopharyngeal reflux ; Laryngopharyngeal Reflux - complications ; Laryngopharyngeal Reflux - genetics ; Laryngopharyngeal Reflux - metabolism ; Male ; Otitis media with effusion ; Otitis Media with Effusion - etiology ; Otitis Media with Effusion - genetics ; Otitis Media with Effusion - metabolism ; pepsin ; Pepsin A - biosynthesis ; Pepsin A - genetics ; pepsinogen ; Pepsinogen A - biosynthesis ; Pepsinogen A - genetics ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - analysis ; RNA, Messenger - genetics</subject><ispartof>The Laryngoscope, 2014-07, Vol.124 (7), p.E294-E300</ispartof><rights>2013 The American Laryngological, Rhinological and Otological Society, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4658-2016bc423173b3577780cc68f9ceecd0d1c0d0103c04e427c14af292cc18ba7b3</citedby><cites>FETCH-LOGICAL-c4658-2016bc423173b3577780cc68f9ceecd0d1c0d0103c04e427c14af292cc18ba7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Flary.24538$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Flary.24538$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24284944$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Hua-Nan</creatorcontrib><creatorcontrib>Yang, Qi-Mei</creatorcontrib><creatorcontrib>Sheng, Ying</creatorcontrib><creatorcontrib>Wang, Zheng-Hui</creatorcontrib><creatorcontrib>Zhang, Qing</creatorcontrib><creatorcontrib>Yan, Jing</creatorcontrib><creatorcontrib>Hou, Jin</creatorcontrib><creatorcontrib>Zhu, Kang</creatorcontrib><creatorcontrib>Cheng, Ying</creatorcontrib><creatorcontrib>Wang, Bo-Tao</creatorcontrib><creatorcontrib>Xu, Ying-Long</creatorcontrib><creatorcontrib>Zhang, Xiang-Hong</creatorcontrib><creatorcontrib>Ren, Xiao-Yong</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><title>Role of pepsin and pepsinogen: Linking laryngopharyngeal reflux with otitis media with effusion in children</title><title>The Laryngoscope</title><addtitle>The Laryngoscope</addtitle><description>Objectives/Hypothesis To analyze the relationship between laryngopharyngeal reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis media with effusion (OME). Study Design Prospective case‐control study. Methods Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes placement were enrolled in OME group, whereas children with adenoid hypertrophy (AH) who required adenoidectomy and individuals who required cochlear implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen mRNA and protein levels were assessed by real‐time fluorescence‐based quantitative polymerase chain reaction and immunohistochemistry in adenoid specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were evaluated by enzyme‐linked immunosorbent assay in middle ear fluid and plasma from the OME and CI groups. Results The levels of pepsinogen protein expressed in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid specimens from the OME group were significantly higher than those in the AH group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group were 51.93 ± 11.58 ng/mL and 728 ± 342.6 ng/mL, respectively, which were significantly higher than those in the CI group (P &lt; .001). In addition, the concentrations of pepsin in dry ears were significantly lower than those in serous and mucus ears in the OME group (F = 22.77, P &lt; .001).Finally, the concentration of pepsinogen in middle ear effusion was positively correlated with the expression intensity of pepsinogen protein in cytoplasm of epithelial cells(r = 0.73, P &lt; .05) in the OME group. Conclusions Pepsin and pepsinogen in middle ear effusion are probably caused by LPR and may be involved in the pathogenesis of OME. 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Yang, Qi-Mei ; Sheng, Ying ; Wang, Zheng-Hui ; Zhang, Qing ; Yan, Jing ; Hou, Jin ; Zhu, Kang ; Cheng, Ying ; Wang, Bo-Tao ; Xu, Ying-Long ; Zhang, Xiang-Hong ; Ren, Xiao-Yong ; Xu, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4658-2016bc423173b3577780cc68f9ceecd0d1c0d0103c04e427c14af292cc18ba7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenoids - chemistry</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Esophageal pH Monitoring</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>laryngopharyngeal reflux</topic><topic>Laryngopharyngeal Reflux - complications</topic><topic>Laryngopharyngeal Reflux - genetics</topic><topic>Laryngopharyngeal Reflux - metabolism</topic><topic>Male</topic><topic>Otitis media with effusion</topic><topic>Otitis Media with Effusion - etiology</topic><topic>Otitis Media with Effusion - genetics</topic><topic>Otitis Media with Effusion - metabolism</topic><topic>pepsin</topic><topic>Pepsin A - biosynthesis</topic><topic>Pepsin A - genetics</topic><topic>pepsinogen</topic><topic>Pepsinogen A - biosynthesis</topic><topic>Pepsinogen A - genetics</topic><topic>Prospective Studies</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Hua-Nan</creatorcontrib><creatorcontrib>Yang, Qi-Mei</creatorcontrib><creatorcontrib>Sheng, Ying</creatorcontrib><creatorcontrib>Wang, Zheng-Hui</creatorcontrib><creatorcontrib>Zhang, Qing</creatorcontrib><creatorcontrib>Yan, Jing</creatorcontrib><creatorcontrib>Hou, Jin</creatorcontrib><creatorcontrib>Zhu, Kang</creatorcontrib><creatorcontrib>Cheng, Ying</creatorcontrib><creatorcontrib>Wang, Bo-Tao</creatorcontrib><creatorcontrib>Xu, Ying-Long</creatorcontrib><creatorcontrib>Zhang, Xiang-Hong</creatorcontrib><creatorcontrib>Ren, Xiao-Yong</creatorcontrib><creatorcontrib>Xu, Min</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>The Laryngoscope</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Hua-Nan</au><au>Yang, Qi-Mei</au><au>Sheng, Ying</au><au>Wang, Zheng-Hui</au><au>Zhang, Qing</au><au>Yan, Jing</au><au>Hou, Jin</au><au>Zhu, Kang</au><au>Cheng, Ying</au><au>Wang, Bo-Tao</au><au>Xu, Ying-Long</au><au>Zhang, Xiang-Hong</au><au>Ren, Xiao-Yong</au><au>Xu, Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of pepsin and pepsinogen: Linking laryngopharyngeal reflux with otitis media with effusion in children</atitle><jtitle>The Laryngoscope</jtitle><addtitle>The Laryngoscope</addtitle><date>2014-07</date><risdate>2014</risdate><volume>124</volume><issue>7</issue><spage>E294</spage><epage>E300</epage><pages>E294-E300</pages><issn>0023-852X</issn><eissn>1531-4995</eissn><abstract>Objectives/Hypothesis To analyze the relationship between laryngopharyngeal reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis media with effusion (OME). Study Design Prospective case‐control study. Methods Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes placement were enrolled in OME group, whereas children with adenoid hypertrophy (AH) who required adenoidectomy and individuals who required cochlear implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen mRNA and protein levels were assessed by real‐time fluorescence‐based quantitative polymerase chain reaction and immunohistochemistry in adenoid specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were evaluated by enzyme‐linked immunosorbent assay in middle ear fluid and plasma from the OME and CI groups. Results The levels of pepsinogen protein expressed in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid specimens from the OME group were significantly higher than those in the AH group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group were 51.93 ± 11.58 ng/mL and 728 ± 342.6 ng/mL, respectively, which were significantly higher than those in the CI group (P &lt; .001). In addition, the concentrations of pepsin in dry ears were significantly lower than those in serous and mucus ears in the OME group (F = 22.77, P &lt; .001).Finally, the concentration of pepsinogen in middle ear effusion was positively correlated with the expression intensity of pepsinogen protein in cytoplasm of epithelial cells(r = 0.73, P &lt; .05) in the OME group. Conclusions Pepsin and pepsinogen in middle ear effusion are probably caused by LPR and may be involved in the pathogenesis of OME. Level of Evidence 3b Laryngoscope, 124:E294–E300, 2014</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24284944</pmid><doi>10.1002/lary.24538</doi><tpages>7</tpages></addata></record>
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subjects Adenoids - chemistry
Child
Child, Preschool
Enzyme-Linked Immunosorbent Assay
Esophageal pH Monitoring
Female
Follow-Up Studies
Gene Expression Regulation
Humans
Immunohistochemistry
laryngopharyngeal reflux
Laryngopharyngeal Reflux - complications
Laryngopharyngeal Reflux - genetics
Laryngopharyngeal Reflux - metabolism
Male
Otitis media with effusion
Otitis Media with Effusion - etiology
Otitis Media with Effusion - genetics
Otitis Media with Effusion - metabolism
pepsin
Pepsin A - biosynthesis
Pepsin A - genetics
pepsinogen
Pepsinogen A - biosynthesis
Pepsinogen A - genetics
Prospective Studies
Real-Time Polymerase Chain Reaction
RNA, Messenger - analysis
RNA, Messenger - genetics
title Role of pepsin and pepsinogen: Linking laryngopharyngeal reflux with otitis media with effusion in children
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