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

Sarcoidosis Vasc Diffuse Lung Dis. 2015 Sep 14;32(3):228-36.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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