title: 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.
  
  
  OBJECTIVE
  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.affiliation: Department of Respiratory Medicine, Mercy University Hospital, Cork, Ireland.. barrykennedy2009@gmail.com.
authors.forename: Barry
authors.initials: B
authors.lastname: Kennedy
authors.forename: Peter
authors.initials: P
authors.lastname: Branagan
authors.forename: Fiachra
authors.initials: F
authors.lastname: Moloney
authors.forename: Muhammad
authors.initials: M
authors.lastname: Haroon
authors.forename: Oisin J
authors.initials: OJ
authors.lastname: O'Connell
authors.forename: Terence M
authors.initials: TM
authors.lastname: O'Connor
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Regan
authors.forename: Sinead
authors.initials: S
authors.lastname: Harney
authors.forename: Michael T
authors.initials: MT
authors.lastname: Henry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7