Table 4.
Investigator | Patients Controls | Biomarker / Summary | ROC curve analysis Cut-off values | Specificity – Sensitivity Diagnostic accuracy | Limitations |
Ohnishi et al. 51 | 33 82 |
Comparative study of KL-6, SP-A, SP-D, MCP-1 as serum markers for ILDs | Yes KL-6: 465 U/ml Sp-A: 48.2 ng/ml Sp-D: 116 ng/ml MCP-1: 1.080 ng/ml |
KL-6: 94 - 96- 96% Sp-A: 86 -82 - 85% Sp-D: 95- 70- 88% MCP-1: 93- 52- 81% |
Small number of patients / Non ILD-specific markers / Potential influence by malignancies |
Takahashi et al. 55 | 42 108 |
Serum levels of SP-A and SP-D are useful biomarkers for ILDs in patients with progressive SSc | Yes SP-A: 43.8 ng/ml SP-D: 110 ng/ml |
SP-A: 33-100% SP-D: 77- 100% |
Small number of patients |
Greene et al. 58 | 427 95 |
Serum SP-A and SP-D as biomarkers in PF of different etiologies | No | Not estimated | Evaluation of serial measurement not definitive |
Yanaba et al. 59 | 39 | Longitudinal analysis of serum KL-6 levels in patients with SSc: association with the activity of PF | No | Not estimated | Small number of patients / Retrospective study / No ROC curve analysis / cut-off levels |
Yanaba et al. 60 | 42 | Comparative study of serum SP-D and KL-6 concentrations in patients with SSc as markers for monitoring the activity of PF | No | KL-6: 100 - 39% Sp-D: 88 - 91% |
Small number of patients / Retrospective study |
Fujita et al. 62 | 37 15 |
Elevation of CK19 serum levels in patients with IPF associated with CVD | No | Not estimated | Small number of patients / Non ILD-specific marker |
Dobashi et al. 64 | 27 10 |
Elevated serum and BAL CK19 levels in PF and AIP | No | Not estimated | Small number of patients / Discrepancies with other serum parameters |
Nakayama et al. 65 | 413 21 |
CK19 serum levels in patients with nonmalignant respiratory diseases | Yes CK19: 3.5 ng/ml |
CK19 : 30 - 50% | Low specificity and sensitivity values / No adjustment with disease severity |
Abbreviations: AIP: Acute Interstitial Pneumonia, BAL: Bronchoalveolar lavage, CK19: Cytokeratin fragment 19, CVD: Collagen Vascular Disease, ILD: Interstitial Lung Disease, IPF: Idiopathic Pulmonary Fibrosis, KL-6: Krebs von den Lungen-6, MCP-1: Monocyte Chemoattractant Protein-1, ROC: Receiver Operating Characteristic, SP: Surfactant Protein, SSc: Systemic Sclerosis