Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function
Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers o...
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| Veröffentlicht in: | The European respiratory journal 2018-09, Vol.52 (3), p.1702529 |
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| creator | de Winter-de Groot, Karin M Janssens, Hettie M van Uum, Rick T Dekkers, Johanna F Berkers, Gitte Vonk, Annelotte Kruisselbrink, Evelien Oppelaar, Hugo Vries, Robert Clevers, Hans Houwen, Roderick H J Escher, Johanna C Elias, Sjoerd G de Jonge, Hugo R de Rijke, Yolanda B Tiddens, Harm A W M van der Ent, Cornelis K Beekman, Jeffrey M |
| description | Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers of CFTR function in 34 infants diagnosed with CF. Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p |
| doi_str_mv | 10.1183/13993003.02529-2017 |
| format | Article |
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Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p<0.001), had more abnormalities on chest computed tomography (p=0.049), and had lower z-scores for maximal expiratory flow at functional residual capacity (p=0.033) when compared to children with high FIS values. FIS significantly correlated with sweat chloride concentration (SCC) and intestinal current measurement (ICM) (r= -0.82 and r=0.70, respectively; both p<0.001). Individual assessment of SCC, ICM and FIS suggested that FIS can help to classify individual disease severity.Thus, stratification by FIS identified subgroups that differed in pulmonary and gastrointestinal outcome parameters. FIS of intestinal organoids correlated well with established CFTR-dependent biomarkers such as SCC and ICM, and performed adequately at group and individual level in this proof-of-concept study.</description><identifier>ISSN: 0903-1936</identifier><identifier>EISSN: 1399-3003</identifier><identifier>DOI: 10.1183/13993003.02529-2017</identifier><identifier>PMID: 30166324</identifier><language>eng</language><publisher>England</publisher><subject>Biomarkers - metabolism ; Chlorides - metabolism ; Cystic Fibrosis - complications ; Cystic Fibrosis - diagnosis ; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism ; Exocrine Pancreatic Insufficiency - diagnosis ; Female ; Humans ; Infant ; Ion Transport ; Linear Models ; Male ; Organoids - pathology ; Proof of Concept Study ; Severity of Illness Index</subject><ispartof>The European respiratory journal, 2018-09, Vol.52 (3), p.1702529</ispartof><rights>Copyright ©ERS 2018.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c350t-ff9eff8af9bdbcdeff020578c9718497943c32f3e189e5aaaf4744fc08b584bc3</citedby><cites>FETCH-LOGICAL-c350t-ff9eff8af9bdbcdeff020578c9718497943c32f3e189e5aaaf4744fc08b584bc3</cites><orcidid>0000-0001-9415-4286</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30166324$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Winter-de Groot, Karin M</creatorcontrib><creatorcontrib>Janssens, Hettie M</creatorcontrib><creatorcontrib>van Uum, Rick T</creatorcontrib><creatorcontrib>Dekkers, Johanna F</creatorcontrib><creatorcontrib>Berkers, Gitte</creatorcontrib><creatorcontrib>Vonk, Annelotte</creatorcontrib><creatorcontrib>Kruisselbrink, Evelien</creatorcontrib><creatorcontrib>Oppelaar, Hugo</creatorcontrib><creatorcontrib>Vries, Robert</creatorcontrib><creatorcontrib>Clevers, Hans</creatorcontrib><creatorcontrib>Houwen, Roderick H J</creatorcontrib><creatorcontrib>Escher, Johanna C</creatorcontrib><creatorcontrib>Elias, Sjoerd G</creatorcontrib><creatorcontrib>de Jonge, Hugo R</creatorcontrib><creatorcontrib>de Rijke, Yolanda B</creatorcontrib><creatorcontrib>Tiddens, Harm A W M</creatorcontrib><creatorcontrib>van der Ent, Cornelis K</creatorcontrib><creatorcontrib>Beekman, Jeffrey M</creatorcontrib><title>Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function</title><title>The European respiratory journal</title><addtitle>Eur Respir J</addtitle><description>Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers of CFTR function in 34 infants diagnosed with CF. Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p<0.001), had more abnormalities on chest computed tomography (p=0.049), and had lower z-scores for maximal expiratory flow at functional residual capacity (p=0.033) when compared to children with high FIS values. FIS significantly correlated with sweat chloride concentration (SCC) and intestinal current measurement (ICM) (r= -0.82 and r=0.70, respectively; both p<0.001). Individual assessment of SCC, ICM and FIS suggested that FIS can help to classify individual disease severity.Thus, stratification by FIS identified subgroups that differed in pulmonary and gastrointestinal outcome parameters. FIS of intestinal organoids correlated well with established CFTR-dependent biomarkers such as SCC and ICM, and performed adequately at group and individual level in this proof-of-concept study.</description><subject>Biomarkers - metabolism</subject><subject>Chlorides - metabolism</subject><subject>Cystic Fibrosis - complications</subject><subject>Cystic Fibrosis - diagnosis</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator - metabolism</subject><subject>Exocrine Pancreatic Insufficiency - diagnosis</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Ion Transport</subject><subject>Linear Models</subject><subject>Male</subject><subject>Organoids - pathology</subject><subject>Proof of Concept Study</subject><subject>Severity of Illness Index</subject><issn>0903-1936</issn><issn>1399-3003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEtPAyEUhYnR2Fr9BSaGpZupvObB0jRWTZqYaF0ThoGKtkMFxmZ2_nQZW13dm8s59x4-AC4xmmJc0RtMOacI0SkiOeEZQbg8AuNhmg3jYzBGHNEMc1qMwFkI7wjhglF8CkY0dQUlbAy-X6KX0ZretitoWyPbGODOxjeo-hCtgsbW3gUboHEeNjZoGTQM-kt7G3vYhb0v6iRu5Ro6v5Ktsw0MO71eD48yQAlr6zbSf2gPnYGz-fIZmq5V0br2HJwYuQ764lAn4HV-t5w9ZIun-8fZ7SJTNEcxM4ZrYyppeN3Uqkk9IigvK8VLXDFeckYVJYZqXHGdSykNKxkzClV1XrFa0Qm43u_devfZpbhiY4NKGWWrXRcEQbwqi5ywIknpXqrSz4PXRmy9TfF7gZEY0Is_9OIXvRjQJ9fV4UBXb3Tz7_ljTX8AWLeCAw</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>de Winter-de Groot, Karin M</creator><creator>Janssens, Hettie M</creator><creator>van Uum, Rick T</creator><creator>Dekkers, Johanna F</creator><creator>Berkers, Gitte</creator><creator>Vonk, Annelotte</creator><creator>Kruisselbrink, Evelien</creator><creator>Oppelaar, Hugo</creator><creator>Vries, Robert</creator><creator>Clevers, Hans</creator><creator>Houwen, Roderick H J</creator><creator>Escher, Johanna C</creator><creator>Elias, Sjoerd G</creator><creator>de Jonge, Hugo R</creator><creator>de Rijke, Yolanda B</creator><creator>Tiddens, Harm A W M</creator><creator>van der Ent, Cornelis K</creator><creator>Beekman, Jeffrey M</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9415-4286</orcidid></search><sort><creationdate>20180901</creationdate><title>Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function</title><author>de Winter-de Groot, Karin M ; Janssens, Hettie M ; van Uum, Rick T ; Dekkers, Johanna F ; Berkers, Gitte ; Vonk, Annelotte ; Kruisselbrink, Evelien ; Oppelaar, Hugo ; Vries, Robert ; Clevers, Hans ; Houwen, Roderick H J ; Escher, Johanna C ; Elias, Sjoerd G ; de Jonge, Hugo R ; de Rijke, Yolanda B ; Tiddens, Harm A W M ; van der Ent, Cornelis K ; Beekman, Jeffrey M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c350t-ff9eff8af9bdbcdeff020578c9718497943c32f3e189e5aaaf4744fc08b584bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Biomarkers - metabolism</topic><topic>Chlorides - metabolism</topic><topic>Cystic Fibrosis - complications</topic><topic>Cystic Fibrosis - diagnosis</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator - metabolism</topic><topic>Exocrine Pancreatic Insufficiency - diagnosis</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Ion Transport</topic><topic>Linear Models</topic><topic>Male</topic><topic>Organoids - pathology</topic><topic>Proof of Concept Study</topic><topic>Severity of Illness Index</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Winter-de Groot, Karin M</creatorcontrib><creatorcontrib>Janssens, Hettie M</creatorcontrib><creatorcontrib>van Uum, Rick T</creatorcontrib><creatorcontrib>Dekkers, Johanna F</creatorcontrib><creatorcontrib>Berkers, Gitte</creatorcontrib><creatorcontrib>Vonk, Annelotte</creatorcontrib><creatorcontrib>Kruisselbrink, Evelien</creatorcontrib><creatorcontrib>Oppelaar, Hugo</creatorcontrib><creatorcontrib>Vries, Robert</creatorcontrib><creatorcontrib>Clevers, Hans</creatorcontrib><creatorcontrib>Houwen, Roderick H J</creatorcontrib><creatorcontrib>Escher, Johanna C</creatorcontrib><creatorcontrib>Elias, Sjoerd G</creatorcontrib><creatorcontrib>de Jonge, Hugo R</creatorcontrib><creatorcontrib>de Rijke, Yolanda B</creatorcontrib><creatorcontrib>Tiddens, Harm A W M</creatorcontrib><creatorcontrib>van der Ent, Cornelis K</creatorcontrib><creatorcontrib>Beekman, Jeffrey M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The European respiratory journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Winter-de Groot, Karin M</au><au>Janssens, Hettie M</au><au>van Uum, Rick T</au><au>Dekkers, Johanna F</au><au>Berkers, Gitte</au><au>Vonk, Annelotte</au><au>Kruisselbrink, Evelien</au><au>Oppelaar, Hugo</au><au>Vries, Robert</au><au>Clevers, Hans</au><au>Houwen, Roderick H J</au><au>Escher, Johanna C</au><au>Elias, Sjoerd G</au><au>de Jonge, Hugo R</au><au>de Rijke, Yolanda B</au><au>Tiddens, Harm A W M</au><au>van der Ent, Cornelis K</au><au>Beekman, Jeffrey M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function</atitle><jtitle>The European respiratory journal</jtitle><addtitle>Eur Respir J</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>52</volume><issue>3</issue><spage>1702529</spage><pages>1702529-</pages><issn>0903-1936</issn><eissn>1399-3003</eissn><abstract>Forskolin-induced swelling (FIS) of intestinal organoids from individuals with cystic fibrosis (CF) measures function of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein mutated in CF.We investigated whether FIS corresponds with clinical outcome parameters and biomarkers of CFTR function in 34 infants diagnosed with CF. Relationships with FIS were studied for indicators of pulmonary and gastrointestinal disease.Children with low FIS had higher levels of immunoreactive trypsinogen (p=0.030) and pancreatitis-associated protein (p=0.039), more often had pancreatic insufficiency (p<0.001), had more abnormalities on chest computed tomography (p=0.049), and had lower z-scores for maximal expiratory flow at functional residual capacity (p=0.033) when compared to children with high FIS values. FIS significantly correlated with sweat chloride concentration (SCC) and intestinal current measurement (ICM) (r= -0.82 and r=0.70, respectively; both p<0.001). Individual assessment of SCC, ICM and FIS suggested that FIS can help to classify individual disease severity.Thus, stratification by FIS identified subgroups that differed in pulmonary and gastrointestinal outcome parameters. FIS of intestinal organoids correlated well with established CFTR-dependent biomarkers such as SCC and ICM, and performed adequately at group and individual level in this proof-of-concept study.</abstract><cop>England</cop><pmid>30166324</pmid><doi>10.1183/13993003.02529-2017</doi><orcidid>https://orcid.org/0000-0001-9415-4286</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The European respiratory journal, 2018-09, Vol.52 (3), p.1702529 |
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| source | MEDLINE; Free E-Journal (出版社公開部分のみ） |
| subjects | Biomarkers - metabolism Chlorides - metabolism Cystic Fibrosis - complications Cystic Fibrosis - diagnosis Cystic Fibrosis Transmembrane Conductance Regulator - metabolism Exocrine Pancreatic Insufficiency - diagnosis Female Humans Infant Ion Transport Linear Models Male Organoids - pathology Proof of Concept Study Severity of Illness Index |
| title | Stratifying infants with cystic fibrosis for disease severity using intestinal organoid swelling as a biomarker of CFTR function |
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