Table 4.

Ongoing clinical studies on biomarkers in IPF.

		Primary Outcome	Secondary Outcomes	Biomarkers Considered	Type of Biomarker
Early Diagnosis of Pulmonary Fibrosis—Use of Biomarkers in IPF NCT02755441 Year: 2016	Type: observational perspective N. part: 300 IPF cohort	Disease progression or mortality at 1 year	Hospitalizations Exacerbations LFTs Mortality QoL Combined endpoints of disease progression Progression in serum/plasma biomarker levels	Unspecified multiple biomarkers	Prognostic
Immunopathologic Profiles of the Lung Micro-Environment Using Cryobiopsies and Identification of Blood Biomarkers in Patients With IPF NCT04187079 Year: 2017	Type: observational prospective N. part: 100 IPF cohort vs. other ILD cohort	Expression of PD-L1 in the epithelial cells in lungs	/	PD-L1, PD-L2, Beta- catenin, B-cell follicles and Tenascin- C in cryobiopsies from the lungs anti HSP 70, p-ANCA, c-ANCA, CD4+/CD28- and CD8+/CD28- cells in blood samples	Diagnostic
Development of Airway Absorption Sampling Methods for Biomarker Assessment in Probable IPF Patients NCT04494334 Year: 2020	Type: observational cross-sectional study N. part: 60 IPF vs. sarcoidosis vs. healthy controls	Levels of the of biomarker/mediator SP-D, CCL18, CXCL13 and periostin in bronchial Lining fluid in IPF and sarcoidosis patients	Levels of Periostin, SP-D, CCL18 and CXCL13 in nasosorption samples within and across the 3 groups of participants Levels of Periostin, SPD, CCL18 and CXCL13 in blood within and across the 3 groups of participants	SP-D, CCL18, CXCL13 and periostin	Diagnostic
Pulmonary Fibrosis Biomarkers During Exacerbation N CT04442711 Year: 2020	Type: observational prospective N. part: 50 IPF cohort	Mortality at 30 and 90 days	Biomarkers level, change in oxygen need, QoL, need for respiratory support, decline of LFTs at 30 days. Treatment during and after hospitalization	Multiple biomarkers on blood serum and plasma collected within 24 h of hospital admission	Diagnostic Prognostic
LOCK-IPF NCT04268485 Year: 2020	Type: observational prospective N. part: 60 IPF cohort	Change in serum KL-6 level between baseline and 12 months	Change in serum KL-6 level between baseline and 3 and 6 months. Correlation of KL-6 and FVC, DLCO, symptoms, response to antifibrotic therapy and GAP stage at 3, 6 and 12 months to baseline Correlation between KL-6 levels and CPI Difference in KL-6 levels between patients with indeterminate, probable and definite UIP on HRCT	KL-6 on blood	Prognostic
Cardiovascular fibrosis in IPF NCT04177251 Year: 2019	Type: observational case-control prospective study N. part: 168 IPF cohort vs. healthy controls	Presence of cardiac fibrosis in a population of patients with overt IPF at diagnosis in comparison with healthy controls Presence of vascular fibrosis in a population of patients with overt IPF at diagnosis in comparison with healthy controls	Levels of biomarkers analyzed (galectins-3, osteopontin and periostin) IPF progression after 1 year from diagnosis in IPF patients Blood proteomic and metabolomic biomarkers	galectins-3, osteopontin and periostin Proteomic and metabolomic biomarkers	Diagnostic Prognostic
The Role of the miR200 Family in the Restoration of Normal Lung Homeostasis and Detection of Early IPF NCT03457935 Year: 2018	Type: observational prospective N. part: 450 IPF vs. non-IPF ILD vs. healthy controls	Determine miR200 levels (fold change) in blood samples to identify biomarkers for IPF	/	miR200	Diagnostic
IPF and Serum Bank NCT04016168 Year: 2014	Type: observational prospective N. part: 500 Diffuse idiopathic ILD cohort	Determination of circulating CD163 serum concentration	/	CD163	n/a
Role of Genetics in IPF NCT01088217 Year: 2010	Type: observational cross-sectional study (family based) N. part: 8000 IPF, familial pulmonary fibrosis cohort, Idiopathic Interstitial Pneumonia Familial Interstitial Pneumonia	Identify a group of genetic loci that play a role in the development of familial interstitial pneumonia and idiopathic interstitial pneumonia.	Develop biomarkers using proteomic and genomic approaches that will facilitate establishing the diagnosis and prognosis of both familial and sporadic forms of idiopathic interstitial pneumonia	Multiple biomarkers	Diagnostic Prognostic
ELFMEN Study NCT04016181 Year: 2007	Type: observational prosepective N. part: 800 IPF and other ILDs	Time to death	Biomarkers that are associated with increased rate of decline in vital capacity, increased lung-related mortality and that predict rate of change in gas transfer	Multiple biomarkers	Prognostic
Genomic and Proteomic Analysis (GAP) of Disease Progression in IPF NCT00373841 Year: 2006	Type: observational N. part: 500 IPF cohort	Identify genetic and biologic markers that may predict the loss of lung function due to idiopathic pulmonary fibrosis through comparison of genetic and biologic markers of samples to changes in symptoms	/	Multiple biomarkers	Prognostic
EXCHANGE-IPF NCT03584802 Year: 2018	Type: RCT N. part: 40 Therapeutic plasma exchanges vs. conventional treatment in AE of IPF	Overall mortality at day 28 after initiation of therapy	[…] Changes in lung injury biomarkers in plasma (KL-6, SP-D) between day 1 and day 90 Changes in circulating autoantibodies levels (anti-periplakin, anti-HSP70 and anti-vimentin antibodies) between day 1 and day 90	Injury biomarkers Circulating fibrocytes Auto-antibodies	Therapeutic

RCT: randomized controlled trial; IPF, idiopathic pulmonary fibrosis; ILD, interstitial lung disease; LFTs, lung function tests; QoL, quality of life; PD-L1/2, Programmed Death-Ligand ½; HSP 70, heat shock protein 70; ANCA, Antineutrophil Cytoplasmic Antibodies; CD 4-28-8-163, cluster of differentiation 4-28-8-163; SP-D/A, surfactant protein D/A; CCL18/2, chemokine ligand 18/2; CXCL13, CXC motif chemokine 13; KL-6/MUC1, Krebs von den Lungen 6/Mucin 1; FVC, forced vital capacity; DLCO, diffusion capacity for carbon monoxide; GAP, Gender, Age, and Physiology score; UIP, usual interstitial pneumonia; HRCT, high resolution computed tomography; C1M, Collagen 1 Degraded by Matrix Metalloproteinase-2/9/13.