TY - JOUR
T1 - A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis–Associated Interstitial Lung Disease
T2 - A Multicenter, Observational Cohort Study
AU - Jee, Adelle S.
AU - Stewart, Iain
AU - Youssef, Peter
AU - Adelstein, Stephen
AU - Lai, Donna
AU - Hua, Sheng
AU - Stevens, Wendy
AU - Proudman, Susanna
AU - Ngian, Gene-Siew
AU - Glaspole, Ian N.
AU - Moodley, Yuben P.
AU - Bleasel, Jane F.
AU - Macansh, Sacha
AU - Nikpour, Mandana
AU - Sahhar, Joanne
AU - Corte, Tamera J.
AU - on behalf of the Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated investigators
N1 - Funding Information:
Supported by Arthritis Australia and Roche Pharmaceuticals. The Australian Scleroderma Interest Group and the Australian Scleroderma Cohort Study are supported by Janssen (Actelion), Scleroderma Australia, Scleroderma Victoria, Arthritis Australia, Musculoskeletal Australia, the Australian Rheumatology Association, St. Vincent's Hospital Melbourne Information Technology Department, the Scleroderma Clinical Trials Consortium, and Bayer. Lung Foundation Australia facilitates the Australian IPF Registry with educational grants from Foundation partners Roche Products, Pty. Limited and Boehringer Ingelheim. Institutional and in‐kind support was provided by the Department of Allergy and Clinical Immunology and Department of Respiratory at the Royal Prince Alfred Hospital, the University of Sydney, and the NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Australia, which is funded by the NHMRC and supported by Foundation partner Boehringer Ingelheim and Program Partners Roche and Galapagos.
Publisher Copyright:
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85159640320&partnerID=8YFLogxK
U2 - 10.1002/art.42491
DO - 10.1002/art.42491
M3 - Article
C2 - 36908055
AN - SCOPUS:85159640320
SN - 2326-5191
VL - 75
SP - 1424
EP - 1433
JO - Arthritis & Rheumatology
JF - Arthritis & Rheumatology
IS - 8
ER -