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Bronchoalveolar Cell Transcriptome of Acute Exacerbation in Idiopathic Pulmonary Fibrosis

 
: Prasse, Antje; Jäger, Benedikt; Schupp, Jonas C.; Kaminski, Naftali; Carleo, Alfonso

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American Journal of Respiratory and Critical Care Medicine 199 (2019), Abstract A5259, 1 pp.
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2019, Dallas/Tex.>
English
Abstract
Fraunhofer ITEM ()

Abstract
Introduction: Acute exacerbation is the main cause of death in IPF. Median survival time after acute exacerbation was reported with 2.2 months. The underlying pathomechanisms are poorly understood. Objective: to test the gene expression profile of BAL cells in IPF patients with or without acute exacerbation. Methods. BAL cells from 62 patients with IPF and 8 patients with IPF at the time of acute exacerbation were harvested during routine diagnostic bronchoscopy at the University Medical Centre Freiburg. The study was approved by the local ethic committee. BAL cell gene expression was detected using Whole Human Genome microarrays and an Agilent platform. Results: Baseline characteristics of patients with or without acute exacerbation did not statistically significantly differ. We found 794 genes differentially expressed (FDR< 0.05) by BAL cells derived from IPF patients at the time of acute exacerbation compared to BAL cells derived from IPF patients without acute exacerbation. Among the top genes were IL-1beta, CCL7, CXCL1, CCL2, TLR2 and NLRP3. Kegg pathway analyses revealed enrichment for the pathways of cytokine-cytokine receptor interaction and chemoattraction of macrophages and granulocytes. RNA data were confirmed by measuring protein levels of several top genes using ELISA. We also compared the gene expression profile of acute exacerbation with our recently published gene signature predictive of mortality in IPF. Of interest, all 794 genes differentially expressed in BAL at the time of acute exacerbation were also part of our outcome signature which was obtained at initial diagnosis. Conclusions: We found many inflammatory pathways involved in macrophage and neutrophil activation up-regulated in acute exacerbation of IPF. Our data also suggest that underlying molecular mechanisms of acute exacerbation in IPF do not significantly differ from molecular mechanisms present in more stable IPF. It appears that the mechanisms which are increased in acute exacerbation are the same that drive disease activity at initial diagnosis.

: http://publica.fraunhofer.de/documents/N-569281.html