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Biomarker signatures for progressive idiopathic pulmonary fibrosis
PP-PDPI, 28 Okt 2021 06:16:32

Abstract

Rationale Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers has the potential for guiding management in clinical practice.

Objectives We assessed the prognostic role of serum biomarkers in three independent IPF cohorts, the Australian IPF Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).

Methods In the AIPFR, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. Least absolute shrinkage and selection operator (LASSO) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at one-year in AIPFR, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in PROFILE. Four significantly replicating biomarkers were aggregated into a progression index (PI) model based on tertiles of circulating concentrations.

Main Results One-hundred and eighty-nine participants were included in the AIPFR cohort, 205 participants from the TLF, and 122 participants from the PROFILE cohorts. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at one-year. Proteomic data did not replicate. The PI in the AIPFR, TLF and PROFILE predicted risk of progression, mortality and progression-free survival. A statistical model incorporating PI demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP model alone in all cohorts, and significantly so within incidence based TLF and PROFILE cohorts.

Conclusion A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

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