Biomarker | Significance | [Ref.] |
Alveolar epithelial cell dysfunction | ||
KL-6 | Correlation with disease severity (imaging and PFTs); increased levels suggest worse prognosis; higher levels in AE-IPF compared with stable IPF | [13–22] |
SP-A, SP-D | Strong predictors of early mortality | [15–17, 20, 23–32] |
CC16 | Correlation with baseline PFTs | [17, 33, 34] |
CK18 | Distinguish between IPF and other ILDs | [35] |
Immune dysregulation and inflammation | ||
CCL18 | Predictor of increased mortality | [24, 36–38] |
YKL-80 | Predictor of worse outcome | [39–45] |
CXCL2, CXCL4, CXCL13 | Predictors of worse outcome | [46–51] |
S100A8, S100A9, S100A12 | Predictors of increased mortality | [52, 53] |
HSP70, HSP47 | Correlation with baseline PFTs; predictors of worse outcome; HSP47 higher in AE-IPF compared with stable IPF | [54, 55] |
Regulatory T-cells | Association with progressive disease | [56, 57] |
α-Defensins | Higher in AE-IPF compared with stable IPF | [58, 59] |
IL-2, IL-12, IL-13, IL-16, IL-17, IL-23 | Correlation with disease activity and baseline PFTs | [60–69] |
Extracellular matrix remodelling and fibroproliferation | ||
MMP-3, MMP-7, MMP-9, MMP-12 | Correlation with disease severity; predictors of worse outcome | [23, 51, 53, 70–75] |
LOXL2 | Association with risk of progression and higher mortality | [76] |
Periostin | Correlation with physiological progression | [77, 78] |
Fibrocytes | Correlation with PFTs; increased level associated with worse survival | [79–81] |
Chitotriosidase | Correlation with disease activity in sarcoidosis (PFTs, chest radiography, serum angiotensin converting enzyme) | [82–86] |
KL: Krebs von den Lungen; SP: surfactant protein; CCL: C-C chemokine ligand; YKL-80: secreted chitinase-like protein; CXCL: C-X-C chemokine ligand; HSP: heat shock protein; IL: interleukin; MMP: matrix metalloproteinase; LOXL: lysyl oxidase-like; PFT: pulmonary function test; AE: acute exacerbation; IPF: idiopathic pulmonary fibrosis; ILD: interstitial lung disease.