Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis

Background: Amphiregulin, a member of the epidermal growth factor family, has been shown to promote the growth of fibroblasts, to be associated with the T-helper type 2 cell adaptive immune response, and to up-regulate mucin gene expression. We aimed to determine whether sputum amphiregulin is expre...

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Veröffentlicht in:Chest 2009-09, Vol.136 (3), p.805-810
Hauptverfasser: Kim, Kyung Won, Jee, Hye Mi, Park, Yeo Hoon, Choi, Bong Seok, Sohn, Myung Hyun, Kim, Kyu-Earn
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container_issue 3
container_start_page 805
container_title Chest
container_volume 136
creator Kim, Kyung Won
Jee, Hye Mi
Park, Yeo Hoon
Choi, Bong Seok
Sohn, Myung Hyun
Kim, Kyu-Earn
description Background: Amphiregulin, a member of the epidermal growth factor family, has been shown to promote the growth of fibroblasts, to be associated with the T-helper type 2 cell adaptive immune response, and to up-regulate mucin gene expression. We aimed to determine whether sputum amphiregulin is expressed at elevated levels in patients with asthma or eosinophilic bronchitis (EB), and whether it is associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: A total of 117 children with asthma, 77 with EB, and 84 control subjects were enrolled in this study. Amphiregulin and eosinophil cationic protein (ECP) levels were measured in sputum supernatants. We performed pulmonary function and methacholine challenge tests while measuring total eosinophil count, and serum levels of total IgE and ECP in all children. Results: The children with asthma had significantly higher levels of sputum amphiregulin (mean, 10.80 pg/mL; range, 4.07 to 38.75 pg/mL) than both the children with EB (mean, 5.76 pg/mL; range, 0.61 to 21.65 pg/mL; p = 0.013) and the control subjects (mean, 6.56 pg/mL; range, 0.51 to 17.98 pg/mL; p = 0.003). Sputum amphiregulin levels positively correlated with levels of sputum eosinophils (γ = 0.221; p = 0.007) and sputum ECP (γ = 0.601; p < 0.0001). Negative significant correlations were found between sputum amphiregulin and FEV 1 (γ = −0.181; p = 0.006) or post-bronchodilator therapy FEV 1 (γ = −0.233; p = 0.002). In children with asthma who were not receiving any controller medications, sputum amphiregulin level was negatively correlated with the provocative concentration of methacholine causing a 20% fall in FEV 1 ( r = −0.398; p = 0.008). Conclusions: Our findings suggest that childhood asthma is associated with sputum amphiregulin, whereas EB is not, and that sputum amphiregulin would be a supportive marker of airway inflammation in asthma.
doi_str_mv 10.1378/chest.08-2972
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We aimed to determine whether sputum amphiregulin is expressed at elevated levels in patients with asthma or eosinophilic bronchitis (EB), and whether it is associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: A total of 117 children with asthma, 77 with EB, and 84 control subjects were enrolled in this study. Amphiregulin and eosinophil cationic protein (ECP) levels were measured in sputum supernatants. We performed pulmonary function and methacholine challenge tests while measuring total eosinophil count, and serum levels of total IgE and ECP in all children. Results: The children with asthma had significantly higher levels of sputum amphiregulin (mean, 10.80 pg/mL; range, 4.07 to 38.75 pg/mL) than both the children with EB (mean, 5.76 pg/mL; range, 0.61 to 21.65 pg/mL; p = 0.013) and the control subjects (mean, 6.56 pg/mL; range, 0.51 to 17.98 pg/mL; p = 0.003). Sputum amphiregulin levels positively correlated with levels of sputum eosinophils (γ = 0.221; p = 0.007) and sputum ECP (γ = 0.601; p &lt; 0.0001). Negative significant correlations were found between sputum amphiregulin and FEV 1 (γ = −0.181; p = 0.006) or post-bronchodilator therapy FEV 1 (γ = −0.233; p = 0.002). In children with asthma who were not receiving any controller medications, sputum amphiregulin level was negatively correlated with the provocative concentration of methacholine causing a 20% fall in FEV 1 ( r = −0.398; p = 0.008). Conclusions: Our findings suggest that childhood asthma is associated with sputum amphiregulin, whereas EB is not, and that sputum amphiregulin would be a supportive marker of airway inflammation in asthma.</description><identifier>ISSN: 0012-3692</identifier><identifier>EISSN: 1931-3543</identifier><identifier>DOI: 10.1378/chest.08-2972</identifier><identifier>PMID: 19447920</identifier><identifier>CODEN: CHETBF</identifier><language>eng</language><publisher>Northbrook, IL: American College of Chest Physicians</publisher><subject>Amphiregulin ; Analysis of Variance ; Asthma - metabolism ; Biological and medical sciences ; Bronchial Hyperreactivity - metabolism ; Bronchial Provocation Tests ; Bronchitis - metabolism ; Cardiology. Vascular system ; Case-Control Studies ; Child ; Chronic obstructive pulmonary disease, asthma ; EGF Family of Proteins ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Female ; Glycoproteins - metabolism ; Humans ; Immunoglobulin E - blood ; Inflammation - metabolism ; Intercellular Signaling Peptides and Proteins - metabolism ; Leukocyte Count ; Male ; Medical sciences ; Methacholine Chloride ; Mucins - genetics ; Mucins - metabolism ; Pneumology ; Prospective Studies ; Sputum - chemistry ; Statistics, Nonparametric ; Up-Regulation</subject><ispartof>Chest, 2009-09, Vol.136 (3), p.805-810</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-263cec8500e4549985641da8c902249cbcb25fa071df2e97ba9e3fcb63f727173</citedby><cites>FETCH-LOGICAL-c361t-263cec8500e4549985641da8c902249cbcb25fa071df2e97ba9e3fcb63f727173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21911356$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19447920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Kyung Won</creatorcontrib><creatorcontrib>Jee, Hye Mi</creatorcontrib><creatorcontrib>Park, Yeo Hoon</creatorcontrib><creatorcontrib>Choi, Bong Seok</creatorcontrib><creatorcontrib>Sohn, Myung Hyun</creatorcontrib><creatorcontrib>Kim, Kyu-Earn</creatorcontrib><title>Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis</title><title>Chest</title><addtitle>Chest</addtitle><description>Background: Amphiregulin, a member of the epidermal growth factor family, has been shown to promote the growth of fibroblasts, to be associated with the T-helper type 2 cell adaptive immune response, and to up-regulate mucin gene expression. We aimed to determine whether sputum amphiregulin is expressed at elevated levels in patients with asthma or eosinophilic bronchitis (EB), and whether it is associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: A total of 117 children with asthma, 77 with EB, and 84 control subjects were enrolled in this study. Amphiregulin and eosinophil cationic protein (ECP) levels were measured in sputum supernatants. We performed pulmonary function and methacholine challenge tests while measuring total eosinophil count, and serum levels of total IgE and ECP in all children. Results: The children with asthma had significantly higher levels of sputum amphiregulin (mean, 10.80 pg/mL; range, 4.07 to 38.75 pg/mL) than both the children with EB (mean, 5.76 pg/mL; range, 0.61 to 21.65 pg/mL; p = 0.013) and the control subjects (mean, 6.56 pg/mL; range, 0.51 to 17.98 pg/mL; p = 0.003). Sputum amphiregulin levels positively correlated with levels of sputum eosinophils (γ = 0.221; p = 0.007) and sputum ECP (γ = 0.601; p &lt; 0.0001). Negative significant correlations were found between sputum amphiregulin and FEV 1 (γ = −0.181; p = 0.006) or post-bronchodilator therapy FEV 1 (γ = −0.233; p = 0.002). In children with asthma who were not receiving any controller medications, sputum amphiregulin level was negatively correlated with the provocative concentration of methacholine causing a 20% fall in FEV 1 ( r = −0.398; p = 0.008). Conclusions: Our findings suggest that childhood asthma is associated with sputum amphiregulin, whereas EB is not, and that sputum amphiregulin would be a supportive marker of airway inflammation in asthma.</description><subject>Amphiregulin</subject><subject>Analysis of Variance</subject><subject>Asthma - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bronchial Hyperreactivity - metabolism</subject><subject>Bronchial Provocation Tests</subject><subject>Bronchitis - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>EGF Family of Proteins</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Eosinophils</subject><subject>Female</subject><subject>Glycoproteins - metabolism</subject><subject>Humans</subject><subject>Immunoglobulin E - blood</subject><subject>Inflammation - metabolism</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Leukocyte Count</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methacholine Chloride</subject><subject>Mucins - genetics</subject><subject>Mucins - metabolism</subject><subject>Pneumology</subject><subject>Prospective Studies</subject><subject>Sputum - chemistry</subject><subject>Statistics, Nonparametric</subject><subject>Up-Regulation</subject><issn>0012-3692</issn><issn>1931-3543</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLxDAURoMoOj6WbqUb3VXzaJNmOQ6-QBBEcRnSNDWRJB2TlmH-vXFm0NXlcs_3XTgAnCN4jQhrbpTRabyGTYk5w3tghjhBJakrsg9mECJcEsrxEThO6QvmHXF6CI4QryrGMZwB_6qdHO0QkrHL4laPK61DMfdLY6P-nJwNhQxdMbdxJdfFU-id9H4TKPJpYazrYg582NEU8zQaLzf83ZBsGHKJs6q4jUNQxo42nYKDXrqkz3bzBLzf370tHsvnl4enxfy5VISiscSUKK2aGkJd1RXnTU0r1MlGcYhxxVWrWlz3EjLU9Vhz1kquSa9aSnqGGWLkBFxte5dx-J6yIOFtUto5GfQwJUEZrXCOZ7DcgioOKUXdi2W0Xsa1QFD8-hUbvwI24tdv5i92xVPrdfdP74Rm4HIHyKSk66MMyqY_DiOOEKlp5m62nLGfZpVdi-Slc7mWbF9-DVMM0iFCBRENrMkPnwWWJQ</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Kim, Kyung Won</creator><creator>Jee, Hye Mi</creator><creator>Park, Yeo Hoon</creator><creator>Choi, Bong Seok</creator><creator>Sohn, Myung Hyun</creator><creator>Kim, Kyu-Earn</creator><general>American College of Chest Physicians</general><scope>IQODW</scope><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></search><sort><creationdate>20090901</creationdate><title>Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis</title><author>Kim, Kyung Won ; Jee, Hye Mi ; Park, Yeo Hoon ; Choi, Bong Seok ; Sohn, Myung Hyun ; Kim, Kyu-Earn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-263cec8500e4549985641da8c902249cbcb25fa071df2e97ba9e3fcb63f727173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Amphiregulin</topic><topic>Analysis of Variance</topic><topic>Asthma - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bronchial Hyperreactivity - metabolism</topic><topic>Bronchial Provocation Tests</topic><topic>Bronchitis - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>EGF Family of Proteins</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Eosinophils</topic><topic>Female</topic><topic>Glycoproteins - metabolism</topic><topic>Humans</topic><topic>Immunoglobulin E - blood</topic><topic>Inflammation - metabolism</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Leukocyte Count</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methacholine Chloride</topic><topic>Mucins - genetics</topic><topic>Mucins - metabolism</topic><topic>Pneumology</topic><topic>Prospective Studies</topic><topic>Sputum - chemistry</topic><topic>Statistics, Nonparametric</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Kyung Won</creatorcontrib><creatorcontrib>Jee, Hye Mi</creatorcontrib><creatorcontrib>Park, Yeo Hoon</creatorcontrib><creatorcontrib>Choi, Bong Seok</creatorcontrib><creatorcontrib>Sohn, Myung Hyun</creatorcontrib><creatorcontrib>Kim, Kyu-Earn</creatorcontrib><collection>Pascal-Francis</collection><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>Chest</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Kyung Won</au><au>Jee, Hye Mi</au><au>Park, Yeo Hoon</au><au>Choi, Bong Seok</au><au>Sohn, Myung Hyun</au><au>Kim, Kyu-Earn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis</atitle><jtitle>Chest</jtitle><addtitle>Chest</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>136</volume><issue>3</issue><spage>805</spage><epage>810</epage><pages>805-810</pages><issn>0012-3692</issn><eissn>1931-3543</eissn><coden>CHETBF</coden><abstract>Background: Amphiregulin, a member of the epidermal growth factor family, has been shown to promote the growth of fibroblasts, to be associated with the T-helper type 2 cell adaptive immune response, and to up-regulate mucin gene expression. We aimed to determine whether sputum amphiregulin is expressed at elevated levels in patients with asthma or eosinophilic bronchitis (EB), and whether it is associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children. Methods: A total of 117 children with asthma, 77 with EB, and 84 control subjects were enrolled in this study. Amphiregulin and eosinophil cationic protein (ECP) levels were measured in sputum supernatants. We performed pulmonary function and methacholine challenge tests while measuring total eosinophil count, and serum levels of total IgE and ECP in all children. Results: The children with asthma had significantly higher levels of sputum amphiregulin (mean, 10.80 pg/mL; range, 4.07 to 38.75 pg/mL) than both the children with EB (mean, 5.76 pg/mL; range, 0.61 to 21.65 pg/mL; p = 0.013) and the control subjects (mean, 6.56 pg/mL; range, 0.51 to 17.98 pg/mL; p = 0.003). Sputum amphiregulin levels positively correlated with levels of sputum eosinophils (γ = 0.221; p = 0.007) and sputum ECP (γ = 0.601; p &lt; 0.0001). Negative significant correlations were found between sputum amphiregulin and FEV 1 (γ = −0.181; p = 0.006) or post-bronchodilator therapy FEV 1 (γ = −0.233; p = 0.002). In children with asthma who were not receiving any controller medications, sputum amphiregulin level was negatively correlated with the provocative concentration of methacholine causing a 20% fall in FEV 1 ( r = −0.398; p = 0.008). Conclusions: Our findings suggest that childhood asthma is associated with sputum amphiregulin, whereas EB is not, and that sputum amphiregulin would be a supportive marker of airway inflammation in asthma.</abstract><cop>Northbrook, IL</cop><pub>American College of Chest Physicians</pub><pmid>19447920</pmid><doi>10.1378/chest.08-2972</doi><tpages>6</tpages></addata></record>
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subjects Amphiregulin
Analysis of Variance
Asthma - metabolism
Biological and medical sciences
Bronchial Hyperreactivity - metabolism
Bronchial Provocation Tests
Bronchitis - metabolism
Cardiology. Vascular system
Case-Control Studies
Child
Chronic obstructive pulmonary disease, asthma
EGF Family of Proteins
Enzyme-Linked Immunosorbent Assay
Eosinophils
Female
Glycoproteins - metabolism
Humans
Immunoglobulin E - blood
Inflammation - metabolism
Intercellular Signaling Peptides and Proteins - metabolism
Leukocyte Count
Male
Medical sciences
Methacholine Chloride
Mucins - genetics
Mucins - metabolism
Pneumology
Prospective Studies
Sputum - chemistry
Statistics, Nonparametric
Up-Regulation
title Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis
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