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

Abstract

BACKGROUND:

SSc-ILD and IPF demonstrate significant morbidity and mortality. Predicting disease progression is challenging in both diseases.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: Barry Kennedy, Peter Branagan, Fiachra Moloney, Muhammad Haroon, Oisin J O'Connell, Terence M O'Connor, Kevin O'Regan, Sinead Harney, Michael T Henry
• Journal: Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG (Sarcoidosis Vasc Diffuse Lung Dis) Vol. 32 Issue 3 Pg. 228-36 (Sep 14 2015) ISSN: 2532-179X [Electronic] Italy
• PMID: 26422568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• MUC1 protein, human
• Mucin-1
• MMP7 protein, human
• Matrix Metalloproteinase 7

Topics

• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Case-Control Studies
• Diagnosis, Differential
• Female
• Humans
• Idiopathic Pulmonary Fibrosis (blood, diagnosis, physiopathology)
• Lung (diagnostic imaging, physiopathology)
• Lung Diseases, Interstitial (blood, diagnosis, physiopathology)
• Male
• Matrix Metalloproteinase 7 (blood)
• Middle Aged
• Mucin-1 (blood)
• Predictive Value of Tests
• Prognosis
• Prospective Studies
• Respiratory Function Tests
• Scleroderma, Systemic (blood, diagnosis, physiopathology)
• Time Factors
• Tomography, X-Ray Computed