Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis

• Published in: Sarcoidosis, vasculitis, and diffuse lung diseases Vol. 32; no. 3; pp. 228 - 236
• Main Authors: Kennedy, Barry, Branagan, Peter, Moloney, Fiachra, Haroon, Muhammad, O'Connell, Oisin J, O'Connor, Terence M, O'Regan, Kevin, Harney, Sinead, Henry, Michael T
• Format: Journal Article
• Language: English
• Published: Italy 14-09-2015
• Subjects: Aged; Aged, 80 and over; Biomarkers - blood; Case-Control Studies; Diagnosis, Differential; Female; Humans; Idiopathic Pulmonary Fibrosis - blood; Idiopathic Pulmonary Fibrosis - diagnosis; Idiopathic Pulmonary Fibrosis - physiopathology; Lung - diagnostic imaging; Lung - physiopathology; Lung Diseases, Interstitial - blood; Lung Diseases, Interstitial - diagnosis; Lung Diseases, Interstitial - physiopathology; Male; Matrix Metalloproteinase 7 - blood; Middle Aged; Mucin-1 - blood; Predictive Value of Tests; Prognosis; Prospective Studies; Respiratory Function Tests; Scleroderma, Systemic - blood; Scleroderma, Systemic - diagnosis; Scleroderma, Systemic - physiopathology; Time Factors; Tomography, X-Ray Computed
• ISSN: 1124-0490; 2532-179X

SSc-ILD and IPF demonstrate significant morbidity and mortality. Predicting disease progression is challenging in both diseases.
We sought a serum biomarker that could identify patients with SSc-ILD or IPF and prospectively predict short-term decline in lung function in these patients.
10 healthy controls, 5 SSc w/o ILD, 6 SSc-ILD and 13 IPF patients underwent venesection. An array of cytokines including KL-6, SP-D and MMP7 were measured. PFTs were obtained at baseline and six months. Cytokine measurements were correlated with PFTs.
KL-6 in IPF patients (633 ng/ml, IQR 492-1675) was significantly elevated compared to controls (198 ng/ml, IQR 52-360, p<0.01) and SSc w/o ILD patients (192 ng/ml, IQR 0-524, p<0.05); KL-6 in SSc-ILD patients (836 ng/ml, IQR 431-1303) was significantly higher than in controls (p<0.05). SP-D was significantly higher in IPF patients (542 ng/ml, IQR 305-577) compared to controls (137 ng/ml, IQR 97-284, p<0.01) or to SSc w/o ILD patients (169 ng/ml, IQR 137-219, p<0.05). In comparison with controls (0.0 ng/ml, IQR 0.0-0.6), MMP7 was significantly higher in both IPF patients (2.85 ng/ml, IQR 1.5-3.6, p<0.05) and SSc-ILD patients (5.41 ng/ml, IQR 2.6-7.2, p<0.001). Using a cut-off level of 459ng/ml for KL-6 and of 1.28 ng/ml for MMP7, 18 out of 19 patients with ILD had a serum value of either KL-6 or MMP7 above these thresholds. For all ILD patients, baseline serum SP-D correlated with ΔFVC %pred over six months (r=-0.63, p=0.005, 95% CI -0.85 to -0.24).
Combining KL-6 with MMP7 may be a useful screening tool for patients at risk of ILD. SP-D may predict short-term decline in lung function.