A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis-Associated Interstitial Lung Disease: A
Adelle S Jee1, Iain Stewart2, Peter Youssef3
1Department of Respiratory Medicine, Royal Prince Alfred Hospital, School of Medicine, University of Sydney Faculty of Medicine and Health, and Australia National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Sydney, New South Wales, Australia.
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.
