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Table 1 Compilation of studies using lung tissue biomarkers with clinical endpoints

From: Tissue is an issue in the search for biomarkers in idiopathic pulmonary fibrosis

Study Patients/sample type Biomarker/method Clinical endpoint Main results
[13] 33 IPF PAR-2 Honeycombing in chest CT Honeycombing, blood neutrophils, and lymphocytes increased in PAR-2-positive cases
Inflammatory cells in blood and BAL All fatal cases were PAR-2-positive
SLB IHC All-cause mortality  
[14] 20 IPF EGFR Lung function EGFR mRNA negatively correlated with FVC and DLCO
15 COP I collagen
15 NSIP  
10 controls  
  IHC
SLB qRT-PCR
[15] 16 IPF Inflammatory cells Lung transplantation Lymphocytes in lung tissue increased during progression
SLB  
Lung transplant HC
[16] 34 IPF α-SMA Survival α-SMA and IL-4 associated with survival
Telomerase
IL-4
TGF-β
β-FGF
SLB IHC
[17] 48 IPF Serpin B3/B4 Cancer, dysplasia High serpin B3/B4 associated with older age and impaired DLCO
Ki-67 Age
TGF-β Lung function
Lung transplant IHC  
RT-PCR
[18] 29 IPF Chymase Change in FVC over 6-month period Mast cell number associated slower rate decline in FVC in IPF
16 HP CAE
9 SSc-ILD Eosinophil peroxidase
10 controls  
SLB  
Lung transplant IHC
[19] 19 UIP SP-A Prognosis SP-A+ ratio lower in UIP cases who died
17 NSIP KL-6
1 COP  
1 RB-ILD  
4 IP  
SLB IHC
[20] 24 UIP Gremlin Lung function Gremlin mRNA correlates negatively with DLCO/VA and BMP-4 mRNA positively with FVC and DLCO
12 NSIP BMP-4 Differential diagnostics
SLB IHC Gremlin + area in IHC correlated negatively with FVC
Lung transplant RT-PCR
[21] 20 IPF-UIP CD68, anti-elastase, CD3, CD4, CD8 Lung function FEV1 and survival correlated with CD3+ TLs, and CD68+ cells correlated with FEV1 in IPF
20 AIP-DAD   Differential diagnostics Survival
20 NSIP  
SLB IHC
[22] 12 IPF CD68, anti-elastase, CD3, CD4, CD8 Lung function CD8+ TLs correlated inversely with FVC% pred, TLC% pred, DLCO% pred, and PaO2
SLB IHC PaO2
Dyspnea score
[23] IPF 29 LMP-1 Survival LMP-1+ associated with death due to respiratory failure and use of systemic steroid
SSc-ILD 5   Differential diagnostics
SLB IHC Systemic steroid treatment
PCR
[24] 28 UIP Tenascin-C Survival High tenascin-C expression correlated with shortened survival in UIP patients
1 NSIP  
6 DIP
6 sarcoidosis
6 BOOP
6 AA
  IHC
IEM
SLB Western blotting
  1. IPF idiopathic pulmonary fibrosis, SLB surgical lung biopsy, IHC immunohistochemistry, CT computed tomography, PAR-2 protease-activated receptor 2, BAL broncho-alveolar lavage, HC histochemistry, α-SMA alpha smooth muscle actin, IL-4 interleukin 4, TGF-β transforming growth factor-beta, FGF fibroblast growth factor, qRT-PCR quantitative reverse transcriptase polymerase chain reaction, DLCO diffusion capacity, HP hypersensitivity pneumonitis, SSc-ILD systemic sclerosis associated interstitial lung disease, CAE chloroacetate esterase, UIP usual interstitial pneumonia, FVC forced vital capacity, NSIP nonspecific interstitial pneumonia, COP cryptogenic organizing pneumonia, BOOP bronchiolitis obliterans organizing pneumonia, RB-ILD respiratory bronchiolitis interstitial lung disease, SP-A surfactant protein A, KL-6 Krebs van den Lungen-6 antigen, BMP-4 bone morphogenic protein 4, AIP acute interstitial pneumonia, DAD diffuse alveolar damage, CD cluster of differentiation, FEV1 forced expiratory volume in 1 s, PaO 2 arterial oxygen tension, LMP-1 latent membrane protein 1, DIP desquamative interstitial pneumonia, IEM immunoelectron microscopy, EGFR epidermal growth factor receptor, TLC total lung capacity, TL T lymphocytes, AA allergic alveolitis.