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Idiopathic Pulmonary Fibrosis: Prospective, Case-Controlled Study of Natural History and Circulating Biomarkers.

Abstract：

BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with 3 to 5 years' survival. Although FVC is used to assess disease progression and treatment response, identifying predictive circulating blood biomarkers could help identify specific biologic pathways for treatment. An international, prospective, noninterventional, case-controlled, 52-week study was therefore conducted to identify a clinical and biomarker baseline profile predictive of longitudinal disease behavior. METHODS:Patients with IPF and control subjects had lung function tests and blood sampling for biomarker quantification (control subjects at baseline only). The primary end point was disease progression rate (composite end point: decrease ≥ 10% from baseline in FVC % predicted, decrease ≥ 15% from baseline in diffusing capacity of the lung for carbon monoxide % predicted, lung transplantation, death) at week 52 and its relationship to selected biomarkers at baseline. RESULTS:Altogether, 211 subjects (154 patients with IPF and 57 control subjects) were enrolled; one-third of patients (n = 47) with IPF had progressed by week 52. Biomarkers CC-chemokine ligand 18 (CCL18), intercellular adhesion molecule 1, Krebs von den Lungen-6, surfactant protein (SP)-A, SP-D, matrix metallopeptidase 7, urokinase-type plasminogen activator receptor, and two novel biomarkers, human epididymis protein-4 (HE4) and prostasin, discriminated patients with IPF vs control subjects. There was no difference in baseline CCL18 concentration between progressors and nonprogressors at week 52 (area under the receiver operating characteristic curve, 0.62; corrected P = .161). No biomarkers were predictive for disease progression. CONCLUSIONS:Several biomarkers, including CCL18, were associated with IPF, but none predicted disease progression. Two novel biomarkers, HE4 and prostasin, were identified and warrant further investigation.

journal_name

Chest

journal_title

Chest

authors

Raghu G,Richeldi L,Jagerschmidt A,Martin V,Subramaniam A,Ozoux ML,Esperet CA,Soubrane C

doi

10.1016/j.chest.2018.08.1083

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1359-1370

issue

eissn

0012-3692

issn

1931-3543

pii

S0012-3692(18)32491-7

journal_volume

154

pub_type

杂志文章,多中心研究

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Idiopathic Pulmonary Fibrosis: Prospective, Case-Controlled Study of Natural History and Circulating Biomarkers.