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

Kaarteenaho, Riitta; Lappi-Blanco, Elisa

doi:10.1186/s13069-015-0020-2

Fibrogenesis & Tissue Repair

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
	33 IPF	PAR-2	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
	Lung transplant	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		Gremlin + area in IHC correlated negatively with FVC
[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
	SLB	IHC	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
	SLB	PCR	Systemic steroid treatment
[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

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.

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ISSN: 1755-1536

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