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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Veröffentlicht in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2023-08, Vol.75 (8), p.1424-1433
Hauptverfasser: 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
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container_issue 8
container_start_page 1424
container_title Arthritis & rheumatology (Hoboken, N.J.)
container_volume 75
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
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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</creator><creatorcontrib>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 ; Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators ; the Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators</creatorcontrib><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 &lt; 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 &lt; 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 &amp; 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 &amp; 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”). 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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 &amp; 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 &lt; 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 &lt; 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. 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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. 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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 &amp; 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 &lt; 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 &lt; 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>
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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
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