Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease
Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression.CF patients aged 12-38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive d...
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| Veröffentlicht in: | The European respiratory journal 2018-10, Vol.52 (4), p.1801118 |
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| creator | Chandler, Joshua D Margaroli, Camilla Horati, Hamed Kilgore, Matthew B Veltman, Mieke Liu, H Ken Taurone, Alexander J Peng, Limin Guglani, Lokesh Uppal, Karan Go, Young-Mi Tiddens, Harm A W M Scholte, Bob J Tirouvanziam, Rabindra Jones, Dean P Janssens, Hettie M |
| description | Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression.CF patients aged 12-38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO) was quantified by ELISA and activity assays.Increased PRAGMA-%Dis was driven by bronchiectasis and correlated with airway neutrophils. PRAGMA-%Dis correlated with 104 metabolomic features (p |
| doi_str_mv | 10.1183/13993003.01118-2018 |
| format | Article |
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), airway neutrophils (ρ=0.569, p=0.0046) and BALF MPO (ρ=0.803, p=3.9×10
).BALF MetO associates with structural lung damage, airway neutrophils and MPO in early CF. Further studies are needed to establish whether methionine oxidation directly contributes to early CF lung disease and explore potential therapeutic targets indicated by these findings.</description><identifier>ISSN: 0903-1936</identifier><identifier>EISSN: 1399-3003</identifier><identifier>DOI: 10.1183/13993003.01118-2018</identifier><identifier>PMID: 30190273</identifier><language>eng</language><publisher>England</publisher><subject>Bronchiectasis - metabolism ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchoscopy ; Child, Preschool ; Cystic Fibrosis - diagnostic imaging ; Cystic Fibrosis - metabolism ; Disease Progression ; Female ; Humans ; Infant ; Lung - metabolism ; Male ; Methionine - analogs & derivatives ; Methionine - metabolism ; Neutrophils - metabolism ; Oxidants - pharmacology ; Oxidation-Reduction ; Peroxidase - metabolism ; Prospective Studies ; Tomography, X-Ray Computed</subject><ispartof>The European respiratory journal, 2018-10, Vol.52 (4), p.1801118</ispartof><rights>Copyright ©ERS 2018.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-8a47e7a3a0ccd3f04dbff16d8abc261df3432670fd9c5c4828487e14e88df41b3</citedby><cites>FETCH-LOGICAL-c405t-8a47e7a3a0ccd3f04dbff16d8abc261df3432670fd9c5c4828487e14e88df41b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30190273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chandler, Joshua D</creatorcontrib><creatorcontrib>Margaroli, Camilla</creatorcontrib><creatorcontrib>Horati, Hamed</creatorcontrib><creatorcontrib>Kilgore, Matthew B</creatorcontrib><creatorcontrib>Veltman, Mieke</creatorcontrib><creatorcontrib>Liu, H Ken</creatorcontrib><creatorcontrib>Taurone, Alexander J</creatorcontrib><creatorcontrib>Peng, Limin</creatorcontrib><creatorcontrib>Guglani, Lokesh</creatorcontrib><creatorcontrib>Uppal, Karan</creatorcontrib><creatorcontrib>Go, Young-Mi</creatorcontrib><creatorcontrib>Tiddens, Harm A W M</creatorcontrib><creatorcontrib>Scholte, Bob J</creatorcontrib><creatorcontrib>Tirouvanziam, Rabindra</creatorcontrib><creatorcontrib>Jones, Dean P</creatorcontrib><creatorcontrib>Janssens, Hettie M</creatorcontrib><title>Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease</title><title>The European respiratory journal</title><addtitle>Eur Respir J</addtitle><description>Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression.CF patients aged 12-38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO) was quantified by ELISA and activity assays.Increased PRAGMA-%Dis was driven by bronchiectasis and correlated with airway neutrophils. PRAGMA-%Dis correlated with 104 metabolomic features (p<0.05, q<0.25). The most significant annotated feature was methionine sulfoxide (MetO), a product of methionine oxidation by MPO-derived oxidants. We confirmed the identity of MetO in BALF and used reference calibration to confirm correlation with PRAGMA-%Dis (Spearman's ρ=0.582, p=0.0029), extending to bronchiectasis (PRAGMA-%Bx; ρ=0.698, p=1.5×10
), airway neutrophils (ρ=0.569, p=0.0046) and BALF MPO (ρ=0.803, p=3.9×10
).BALF MetO associates with structural lung damage, airway neutrophils and MPO in early CF. Further studies are needed to establish whether methionine oxidation directly contributes to early CF lung disease and explore potential therapeutic targets indicated by these findings.</description><subject>Bronchiectasis - metabolism</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Bronchoscopy</subject><subject>Child, Preschool</subject><subject>Cystic Fibrosis - diagnostic imaging</subject><subject>Cystic Fibrosis - metabolism</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Lung - metabolism</subject><subject>Male</subject><subject>Methionine - analogs & derivatives</subject><subject>Methionine - metabolism</subject><subject>Neutrophils - metabolism</subject><subject>Oxidants - pharmacology</subject><subject>Oxidation-Reduction</subject><subject>Peroxidase - metabolism</subject><subject>Prospective Studies</subject><subject>Tomography, X-Ray Computed</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>eNpVkU1v1DAQhi1ERZfCL0BCPnJJmcl4E_uChCraIrXqpb1wsRx73DXKxkucLd1_32y_BKf5fmdGjxCfEI4RNX1FMoYA6BhwjqsaUL8Ri3222qffigUYoAoNNYfifSm_AbBRhO_EIQEaqFtaiF-XO-7zhsd8n4IrLB_tlPIgc5RrnlazmwaWrpTsk5u4yL9pWkl2Y7-Tflem5GVM3ZhLKrLfDrcypMKz1AdxEF1f-OOzPRI3pz-uT86ri6uznyffLyqvYDlV2qmWW0cOvA8UQYUuRmyCdp2vGwyRFNVNCzEYv_RK11rpllGx1iEq7OhIfHvS3Wy7NQfPwzS63m7GtHbjzmaX7P-VIa3sbb6zLZAyS5wFvjwLjPnPlstk16l47ns3cN4WWyNg3RijaW6lp1Y__1tGjq9rEOyein2hYh-p2D2Veerzvxe-zrxgoAeBV4sK</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Chandler, Joshua D</creator><creator>Margaroli, Camilla</creator><creator>Horati, Hamed</creator><creator>Kilgore, Matthew B</creator><creator>Veltman, Mieke</creator><creator>Liu, H Ken</creator><creator>Taurone, Alexander J</creator><creator>Peng, Limin</creator><creator>Guglani, Lokesh</creator><creator>Uppal, Karan</creator><creator>Go, Young-Mi</creator><creator>Tiddens, Harm A W M</creator><creator>Scholte, Bob J</creator><creator>Tirouvanziam, Rabindra</creator><creator>Jones, Dean P</creator><creator>Janssens, Hettie 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><scope>5PM</scope></search><sort><creationdate>201810</creationdate><title>Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease</title><author>Chandler, Joshua D ; Margaroli, Camilla ; Horati, Hamed ; Kilgore, Matthew B ; Veltman, Mieke ; Liu, H Ken ; Taurone, Alexander J ; Peng, Limin ; Guglani, Lokesh ; Uppal, Karan ; Go, Young-Mi ; Tiddens, Harm A W M ; Scholte, Bob J ; Tirouvanziam, Rabindra ; Jones, Dean P ; Janssens, Hettie M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-8a47e7a3a0ccd3f04dbff16d8abc261df3432670fd9c5c4828487e14e88df41b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Bronchiectasis - metabolism</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Bronchoscopy</topic><topic>Child, Preschool</topic><topic>Cystic Fibrosis - diagnostic imaging</topic><topic>Cystic Fibrosis - metabolism</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Lung - metabolism</topic><topic>Male</topic><topic>Methionine - analogs & derivatives</topic><topic>Methionine - metabolism</topic><topic>Neutrophils - metabolism</topic><topic>Oxidants - pharmacology</topic><topic>Oxidation-Reduction</topic><topic>Peroxidase - metabolism</topic><topic>Prospective Studies</topic><topic>Tomography, X-Ray Computed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chandler, Joshua D</creatorcontrib><creatorcontrib>Margaroli, Camilla</creatorcontrib><creatorcontrib>Horati, Hamed</creatorcontrib><creatorcontrib>Kilgore, Matthew B</creatorcontrib><creatorcontrib>Veltman, Mieke</creatorcontrib><creatorcontrib>Liu, H Ken</creatorcontrib><creatorcontrib>Taurone, Alexander J</creatorcontrib><creatorcontrib>Peng, Limin</creatorcontrib><creatorcontrib>Guglani, Lokesh</creatorcontrib><creatorcontrib>Uppal, Karan</creatorcontrib><creatorcontrib>Go, Young-Mi</creatorcontrib><creatorcontrib>Tiddens, Harm A W M</creatorcontrib><creatorcontrib>Scholte, Bob J</creatorcontrib><creatorcontrib>Tirouvanziam, Rabindra</creatorcontrib><creatorcontrib>Jones, Dean P</creatorcontrib><creatorcontrib>Janssens, Hettie 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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The European respiratory journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chandler, Joshua D</au><au>Margaroli, Camilla</au><au>Horati, Hamed</au><au>Kilgore, Matthew B</au><au>Veltman, Mieke</au><au>Liu, H Ken</au><au>Taurone, Alexander J</au><au>Peng, Limin</au><au>Guglani, Lokesh</au><au>Uppal, Karan</au><au>Go, Young-Mi</au><au>Tiddens, Harm A W M</au><au>Scholte, Bob J</au><au>Tirouvanziam, Rabindra</au><au>Jones, Dean P</au><au>Janssens, Hettie M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease</atitle><jtitle>The European respiratory journal</jtitle><addtitle>Eur Respir J</addtitle><date>2018-10</date><risdate>2018</risdate><volume>52</volume><issue>4</issue><spage>1801118</spage><pages>1801118-</pages><issn>0903-1936</issn><eissn>1399-3003</eissn><abstract>Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression.CF patients aged 12-38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO) was quantified by ELISA and activity assays.Increased PRAGMA-%Dis was driven by bronchiectasis and correlated with airway neutrophils. PRAGMA-%Dis correlated with 104 metabolomic features (p<0.05, q<0.25). The most significant annotated feature was methionine sulfoxide (MetO), a product of methionine oxidation by MPO-derived oxidants. We confirmed the identity of MetO in BALF and used reference calibration to confirm correlation with PRAGMA-%Dis (Spearman's ρ=0.582, p=0.0029), extending to bronchiectasis (PRAGMA-%Bx; ρ=0.698, p=1.5×10
), airway neutrophils (ρ=0.569, p=0.0046) and BALF MPO (ρ=0.803, p=3.9×10
).BALF MetO associates with structural lung damage, airway neutrophils and MPO in early CF. Further studies are needed to establish whether methionine oxidation directly contributes to early CF lung disease and explore potential therapeutic targets indicated by these findings.</abstract><cop>England</cop><pmid>30190273</pmid><doi>10.1183/13993003.01118-2018</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Bronchiectasis - metabolism Bronchoalveolar Lavage Fluid - chemistry Bronchoscopy Child, Preschool Cystic Fibrosis - diagnostic imaging Cystic Fibrosis - metabolism Disease Progression Female Humans Infant Lung - metabolism Male Methionine - analogs & derivatives Methionine - metabolism Neutrophils - metabolism Oxidants - pharmacology Oxidation-Reduction Peroxidase - metabolism Prospective Studies Tomography, X-Ray Computed |
| title | Myeloperoxidase oxidation of methionine associates with early cystic fibrosis lung disease |
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