Molecular biomarkers

Alveolar epithelial cell dysfunction
 KL-6Correlation 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-DStrong predictors of early mortality[15–17, 20, 23–32]
 CC16Correlation with baseline PFTs[17, 33, 34]
 CK18Distinguish between IPF and other ILDs[35]
Immune dysregulation and inflammation
 CCL18Predictor of increased mortality[24, 36–38]
 YKL-80Predictor of worse outcome[39–45]
 CXCL2, CXCL4, CXCL13Predictors of worse outcome[46–51]
 S100A8, S100A9, S100A12Predictors of increased mortality[52, 53]
 HSP70, HSP47Correlation with baseline PFTs; predictors of worse outcome; HSP47 higher in AE-IPF compared with stable IPF[54, 55]
 Regulatory T-cellsAssociation with progressive disease[56, 57]
 α-DefensinsHigher in AE-IPF compared with stable IPF[58, 59]
 IL-2, IL-12, IL-13, IL-16, IL-17, IL-23Correlation with disease activity and baseline PFTs[60–69]
Extracellular matrix remodelling and fibroproliferation
 MMP-3, MMP-7, MMP-9, MMP-12Correlation with disease severity; predictors of worse outcome[23, 51, 53, 70–75]
 LOXL2Association with risk of progression and higher mortality[76]
 PeriostinCorrelation with physiological progression[77, 78]
 FibrocytesCorrelation with PFTs; increased level associated with worse survival[79–81]
 ChitotriosidaseCorrelation 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.