A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study
Objective In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD). Methods We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients...
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creator | Jee, Adelle S. Stewart, Iain Youssef, Peter Adelstein, Stephen Lai, Donna Hua, Sheng Stevens, Wendy Proudman, Susanna Ngian, Gene‐Siew Glaspole, Ian N. Moodley, Yuben P. Bleasel, Jane F. Macansh, Sacha Nikpour, Mandana Sahhar, Joanne Corte, Tamera J. Cooley, Helen M. Hansen, Dylan Hill, Catherine Major, Gabor A. C. Moghaddami, Mahin Nash, Peter Roddy, Janet Tymms, Kathleen Walker, Jennifer G. Cooper, Wendy A. Ellis, Samantha J. Goh, Nicole S. L. Grainge, Christopher Hopkins, Peter Keir, Gregory J. Mahar, Annabelle Reynolds, Paul N. Tan, Dino Zappala, Chris J. Nguyen, MaiAnh |
description | Objective
In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD).
Methods
We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified.
Results
A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) (P |
doi_str_mv | 10.1002/art.42491 |
format | Article |
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In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD).
Methods
We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified.
Results
A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) (P < 0.001). The composite index strengthened the performance of individual biomarkers for SSc‐ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was −17.84% and the diffusing capacity for carbon monoxide percent predicted was −20.16%; both P < 0.001).
Conclusion
A composite serum biomarker index, comprising SP‐D, Ca15‐3, and ICAM‐1, may improve the identification and risk stratification of ILD in SSc patients at baseline.</description><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.42491</identifier><identifier>PMID: 36908055</identifier><language>eng</language><publisher>Boston, USA: Wiley Periodicals, Inc</publisher><subject>Australia ; Biomarkers ; Carbon monoxide ; Cell adhesion ; Cohort analysis ; Cohort Studies ; Diagnosis ; Empirical analysis ; Fibrosis ; Humans ; Idiopathic Pulmonary Fibrosis ; Intercellular Adhesion Molecule-1 ; Lung ; Lung diseases ; Lung Diseases, Interstitial - diagnosis ; Lung Diseases, Interstitial - etiology ; Observational studies ; Performance evaluation ; Protein D ; Pulmonary Surfactant-Associated Protein D ; Quality of Life ; Radiography ; Respiratory function ; Scleroderma ; Scleroderma, Systemic ; Surfactant protein D ; Systemic sclerosis</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2023-08, Vol.75 (8), p.1424-1433</ispartof><rights>2023 The Authors. published by Wiley Periodicals LLC on behalf of American College of Rheumatology.</rights><rights>2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3881-5e75cbcfecbb1c75f7a868f072c6b89bd1c529b8ab3109d1f82bd4d23bbcf4373</citedby><cites>FETCH-LOGICAL-c3881-5e75cbcfecbb1c75f7a868f072c6b89bd1c529b8ab3109d1f82bd4d23bbcf4373</cites><orcidid>0000-0002-2844-4370 ; 0000-0002-9010-3999</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.42491$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.42491$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36908055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jee, Adelle S.</creatorcontrib><creatorcontrib>Stewart, Iain</creatorcontrib><creatorcontrib>Youssef, Peter</creatorcontrib><creatorcontrib>Adelstein, Stephen</creatorcontrib><creatorcontrib>Lai, Donna</creatorcontrib><creatorcontrib>Hua, Sheng</creatorcontrib><creatorcontrib>Stevens, Wendy</creatorcontrib><creatorcontrib>Proudman, Susanna</creatorcontrib><creatorcontrib>Ngian, Gene‐Siew</creatorcontrib><creatorcontrib>Glaspole, Ian N.</creatorcontrib><creatorcontrib>Moodley, Yuben P.</creatorcontrib><creatorcontrib>Bleasel, Jane F.</creatorcontrib><creatorcontrib>Macansh, Sacha</creatorcontrib><creatorcontrib>Nikpour, Mandana</creatorcontrib><creatorcontrib>Sahhar, Joanne</creatorcontrib><creatorcontrib>Corte, Tamera J.</creatorcontrib><creatorcontrib>Cooley, Helen M.</creatorcontrib><creatorcontrib>Hansen, Dylan</creatorcontrib><creatorcontrib>Hill, Catherine</creatorcontrib><creatorcontrib>Major, Gabor A. C.</creatorcontrib><creatorcontrib>Moghaddami, Mahin</creatorcontrib><creatorcontrib>Nash, Peter</creatorcontrib><creatorcontrib>Roddy, Janet</creatorcontrib><creatorcontrib>Tymms, Kathleen</creatorcontrib><creatorcontrib>Walker, Jennifer G.</creatorcontrib><creatorcontrib>Cooper, Wendy A.</creatorcontrib><creatorcontrib>Ellis, Samantha J.</creatorcontrib><creatorcontrib>Goh, Nicole S. L.</creatorcontrib><creatorcontrib>Grainge, Christopher</creatorcontrib><creatorcontrib>Hopkins, Peter</creatorcontrib><creatorcontrib>Keir, Gregory J.</creatorcontrib><creatorcontrib>Mahar, Annabelle</creatorcontrib><creatorcontrib>Reynolds, Paul N.</creatorcontrib><creatorcontrib>Tan, Dino</creatorcontrib><creatorcontrib>Zappala, Chris J.</creatorcontrib><creatorcontrib>Nguyen, MaiAnh</creatorcontrib><creatorcontrib>Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</creatorcontrib><creatorcontrib>the Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</creatorcontrib><title>A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheumatol</addtitle><description>Objective
In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD).
Methods
We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified.
Results
A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) (P < 0.001). The composite index strengthened the performance of individual biomarkers for SSc‐ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was −17.84% and the diffusing capacity for carbon monoxide percent predicted was −20.16%; both P < 0.001).
Conclusion
A composite serum biomarker index, comprising SP‐D, Ca15‐3, and ICAM‐1, may improve the identification and risk stratification of ILD in SSc patients at baseline.</description><subject>Australia</subject><subject>Biomarkers</subject><subject>Carbon monoxide</subject><subject>Cell adhesion</subject><subject>Cohort analysis</subject><subject>Cohort Studies</subject><subject>Diagnosis</subject><subject>Empirical analysis</subject><subject>Fibrosis</subject><subject>Humans</subject><subject>Idiopathic Pulmonary Fibrosis</subject><subject>Intercellular Adhesion Molecule-1</subject><subject>Lung</subject><subject>Lung diseases</subject><subject>Lung Diseases, Interstitial - diagnosis</subject><subject>Lung Diseases, Interstitial - etiology</subject><subject>Observational studies</subject><subject>Performance evaluation</subject><subject>Protein D</subject><subject>Pulmonary Surfactant-Associated Protein D</subject><subject>Quality of Life</subject><subject>Radiography</subject><subject>Respiratory function</subject><subject>Scleroderma</subject><subject>Scleroderma, Systemic</subject><subject>Surfactant protein D</subject><subject>Systemic sclerosis</subject><issn>2326-5191</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp10ctu1DAUBmALgWhVuuAFkCU2IDGtL3HisAvDrdKgSkxZR7Zz0rok8dR2gNnxDix5O56EM0zLAglvbFnf-WX5J-QxZyecMXFqYj4pRFHze-RQSFEulGDq_t2Z1_yAHKd0zXDVFSuZekgOZFkzzZQ6JD8bugzjJiSfga4hziN95cNo4meI9Gzq4BvtQ6T5Cuhrby4nhImGnq63KcPoHV27AeLu9tf3H01KwXmTocPRDDFln70Z6GqeLnE8gUnwkjb0wzxk72BHXtBzmyB-MdmHCekyXIWY6TrP3fYRedCbIcHx7X5EPr19c7F8v1idvztbNquFk1rzhYJKOet6cNZyV6m-MrrUPauEK62ubcedErXVxkrO6o73Wtiu6IS0OFTISh6RZ_vcTQw3M6Tcjj45GAYzQZhTKypdKhwtFdKn_9DrMEd8OCpdCI1ISlTP98rhz6QIfbuJHv9023LW7kprsbT2T2lon9wmznaE7q-8qwjB6R589QNs_5_UNh8v9pG_AWtro_k</recordid><startdate>202308</startdate><enddate>202308</enddate><creator>Jee, Adelle S.</creator><creator>Stewart, Iain</creator><creator>Youssef, Peter</creator><creator>Adelstein, Stephen</creator><creator>Lai, Donna</creator><creator>Hua, Sheng</creator><creator>Stevens, Wendy</creator><creator>Proudman, Susanna</creator><creator>Ngian, Gene‐Siew</creator><creator>Glaspole, Ian N.</creator><creator>Moodley, Yuben P.</creator><creator>Bleasel, Jane F.</creator><creator>Macansh, Sacha</creator><creator>Nikpour, Mandana</creator><creator>Sahhar, Joanne</creator><creator>Corte, Tamera J.</creator><creator>Cooley, Helen M.</creator><creator>Hansen, Dylan</creator><creator>Hill, Catherine</creator><creator>Major, Gabor A. C.</creator><creator>Moghaddami, Mahin</creator><creator>Nash, Peter</creator><creator>Roddy, Janet</creator><creator>Tymms, Kathleen</creator><creator>Walker, Jennifer G.</creator><creator>Cooper, Wendy A.</creator><creator>Ellis, Samantha J.</creator><creator>Goh, Nicole S. L.</creator><creator>Grainge, Christopher</creator><creator>Hopkins, Peter</creator><creator>Keir, Gregory J.</creator><creator>Mahar, Annabelle</creator><creator>Reynolds, Paul N.</creator><creator>Tan, Dino</creator><creator>Zappala, Chris J.</creator><creator>Nguyen, MaiAnh</creator><general>Wiley Periodicals, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</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>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2844-4370</orcidid><orcidid>https://orcid.org/0000-0002-9010-3999</orcidid></search><sort><creationdate>202308</creationdate><title>A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study</title><author>Jee, Adelle S. ; Stewart, Iain ; Youssef, Peter ; Adelstein, Stephen ; Lai, Donna ; Hua, Sheng ; Stevens, Wendy ; Proudman, Susanna ; Ngian, Gene‐Siew ; Glaspole, Ian N. ; Moodley, Yuben P. ; Bleasel, Jane F. ; Macansh, Sacha ; Nikpour, Mandana ; Sahhar, Joanne ; Corte, Tamera J. ; Cooley, Helen M. ; Hansen, Dylan ; Hill, Catherine ; Major, Gabor A. C. ; Moghaddami, Mahin ; Nash, Peter ; Roddy, Janet ; Tymms, Kathleen ; Walker, Jennifer G. ; Cooper, Wendy A. ; Ellis, Samantha J. ; Goh, Nicole S. L. ; Grainge, Christopher ; Hopkins, Peter ; Keir, Gregory J. ; Mahar, Annabelle ; Reynolds, Paul N. ; Tan, Dino ; Zappala, Chris J. ; Nguyen, MaiAnh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3881-5e75cbcfecbb1c75f7a868f072c6b89bd1c529b8ab3109d1f82bd4d23bbcf4373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Australia</topic><topic>Biomarkers</topic><topic>Carbon monoxide</topic><topic>Cell adhesion</topic><topic>Cohort analysis</topic><topic>Cohort Studies</topic><topic>Diagnosis</topic><topic>Empirical analysis</topic><topic>Fibrosis</topic><topic>Humans</topic><topic>Idiopathic Pulmonary Fibrosis</topic><topic>Intercellular Adhesion Molecule-1</topic><topic>Lung</topic><topic>Lung diseases</topic><topic>Lung Diseases, Interstitial - diagnosis</topic><topic>Lung Diseases, Interstitial - etiology</topic><topic>Observational studies</topic><topic>Performance evaluation</topic><topic>Protein D</topic><topic>Pulmonary Surfactant-Associated Protein D</topic><topic>Quality of Life</topic><topic>Radiography</topic><topic>Respiratory function</topic><topic>Scleroderma</topic><topic>Scleroderma, Systemic</topic><topic>Surfactant protein D</topic><topic>Systemic sclerosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jee, Adelle S.</creatorcontrib><creatorcontrib>Stewart, Iain</creatorcontrib><creatorcontrib>Youssef, Peter</creatorcontrib><creatorcontrib>Adelstein, Stephen</creatorcontrib><creatorcontrib>Lai, Donna</creatorcontrib><creatorcontrib>Hua, Sheng</creatorcontrib><creatorcontrib>Stevens, Wendy</creatorcontrib><creatorcontrib>Proudman, Susanna</creatorcontrib><creatorcontrib>Ngian, Gene‐Siew</creatorcontrib><creatorcontrib>Glaspole, Ian N.</creatorcontrib><creatorcontrib>Moodley, Yuben P.</creatorcontrib><creatorcontrib>Bleasel, Jane F.</creatorcontrib><creatorcontrib>Macansh, Sacha</creatorcontrib><creatorcontrib>Nikpour, Mandana</creatorcontrib><creatorcontrib>Sahhar, Joanne</creatorcontrib><creatorcontrib>Corte, Tamera J.</creatorcontrib><creatorcontrib>Cooley, Helen M.</creatorcontrib><creatorcontrib>Hansen, Dylan</creatorcontrib><creatorcontrib>Hill, Catherine</creatorcontrib><creatorcontrib>Major, Gabor A. C.</creatorcontrib><creatorcontrib>Moghaddami, Mahin</creatorcontrib><creatorcontrib>Nash, Peter</creatorcontrib><creatorcontrib>Roddy, Janet</creatorcontrib><creatorcontrib>Tymms, Kathleen</creatorcontrib><creatorcontrib>Walker, Jennifer G.</creatorcontrib><creatorcontrib>Cooper, Wendy A.</creatorcontrib><creatorcontrib>Ellis, Samantha J.</creatorcontrib><creatorcontrib>Goh, Nicole S. L.</creatorcontrib><creatorcontrib>Grainge, Christopher</creatorcontrib><creatorcontrib>Hopkins, Peter</creatorcontrib><creatorcontrib>Keir, Gregory J.</creatorcontrib><creatorcontrib>Mahar, Annabelle</creatorcontrib><creatorcontrib>Reynolds, Paul N.</creatorcontrib><creatorcontrib>Tan, Dino</creatorcontrib><creatorcontrib>Zappala, Chris J.</creatorcontrib><creatorcontrib>Nguyen, MaiAnh</creatorcontrib><creatorcontrib>Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</creatorcontrib><creatorcontrib>the Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jee, Adelle S.</au><au>Stewart, Iain</au><au>Youssef, Peter</au><au>Adelstein, Stephen</au><au>Lai, Donna</au><au>Hua, Sheng</au><au>Stevens, Wendy</au><au>Proudman, Susanna</au><au>Ngian, Gene‐Siew</au><au>Glaspole, Ian N.</au><au>Moodley, Yuben P.</au><au>Bleasel, Jane F.</au><au>Macansh, Sacha</au><au>Nikpour, Mandana</au><au>Sahhar, Joanne</au><au>Corte, Tamera J.</au><au>Cooley, Helen M.</au><au>Hansen, Dylan</au><au>Hill, Catherine</au><au>Major, Gabor A. C.</au><au>Moghaddami, Mahin</au><au>Nash, Peter</au><au>Roddy, Janet</au><au>Tymms, Kathleen</au><au>Walker, Jennifer G.</au><au>Cooper, Wendy A.</au><au>Ellis, Samantha J.</au><au>Goh, Nicole S. L.</au><au>Grainge, Christopher</au><au>Hopkins, Peter</au><au>Keir, Gregory J.</au><au>Mahar, Annabelle</au><au>Reynolds, Paul N.</au><au>Tan, Dino</au><au>Zappala, Chris J.</au><au>Nguyen, MaiAnh</au><aucorp>Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</aucorp><aucorp>the Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheumatol</addtitle><date>2023-08</date><risdate>2023</risdate><volume>75</volume><issue>8</issue><spage>1424</spage><epage>1433</epage><pages>1424-1433</pages><issn>2326-5191</issn><eissn>2326-5205</eissn><abstract>Objective
In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc–associated interstitial lung disease (SSc‐ILD).
Methods
We analyzed 28 biomarkers in 640 participants: 259 patients with SSc‐ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF‐controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc‐ILD, and its association with lung function, disease extent on radiography, and patient health–related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc‐ILD from IPF‐controls were identified.
Results
A composite biomarker index, comprising surfactant protein D (SP‐D), Ca15‐3, and intercellular adhesion molecule 1 (ICAM‐1), was strongly associated with SSc‐ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59–35.21) (P < 0.001). The composite index strengthened the performance of individual biomarkers for SSc‐ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was −17.84% and the diffusing capacity for carbon monoxide percent predicted was −20.16%; both P < 0.001).
Conclusion
A composite serum biomarker index, comprising SP‐D, Ca15‐3, and ICAM‐1, may improve the identification and risk stratification of ILD in SSc patients at baseline.</abstract><cop>Boston, USA</cop><pub>Wiley Periodicals, Inc</pub><pmid>36908055</pmid><doi>10.1002/art.42491</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2844-4370</orcidid><orcidid>https://orcid.org/0000-0002-9010-3999</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2326-5191 |
ispartof | Arthritis & rheumatology (Hoboken, N.J.), 2023-08, Vol.75 (8), p.1424-1433 |
issn | 2326-5191 2326-5205 |
language | eng |
recordid | cdi_proquest_miscellaneous_2786510965 |
source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
subjects | Australia Biomarkers Carbon monoxide Cell adhesion Cohort analysis Cohort Studies Diagnosis Empirical analysis Fibrosis Humans Idiopathic Pulmonary Fibrosis Intercellular Adhesion Molecule-1 Lung Lung diseases Lung Diseases, Interstitial - diagnosis Lung Diseases, Interstitial - etiology Observational studies Performance evaluation Protein D Pulmonary Surfactant-Associated Protein D Quality of Life Radiography Respiratory function Scleroderma Scleroderma, Systemic Surfactant protein D Systemic sclerosis |
title | A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T20%3A36%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Composite%20Serum%20Biomarker%20Index%20for%20the%20Diagnosis%20of%20Systemic%20Sclerosis%E2%80%93Associated%20Interstitial%20Lung%20Disease:%20A%20Multicenter,%20Observational%20Cohort%20Study&rft.jtitle=Arthritis%20&%20rheumatology%20(Hoboken,%20N.J.)&rft.au=Jee,%20Adelle%20S.&rft.aucorp=Australian%20Scleroderma%20Cohort%20Study,%20Australian%20Scleroderma%20Interest%20Group,%20Australian%20Idiopathic%20Pulmonary%20Fibrosis%20Registry,%20and%20associated%20investigators&rft.date=2023-08&rft.volume=75&rft.issue=8&rft.spage=1424&rft.epage=1433&rft.pages=1424-1433&rft.issn=2326-5191&rft.eissn=2326-5205&rft_id=info:doi/10.1002/art.42491&rft_dat=%3Cproquest_cross%3E2842809633%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2842809633&rft_id=info:pmid/36908055&rfr_iscdi=true |