RNA sequencing of transplant-stage idiopathic pulmonary fibrosis lung reveals unique pathway regulation

Idiopathic pulmonary fibrosis (IPF), the scarring of lung parenchyma resulting in the loss of lung function, remains a fatal disease with a significant unmet medical need. Patients with severe IPF often develop acute exacerbations resulting in the rapid deterioration of lung function, requiring transplantation. Understanding the pathophysiological mechanisms contributing to IPF is key to develop novel therapeutic approaches for end-stage disease.We report here RNA-sequencing analyses of lung tissues from a cohort of patients with transplant-stage IPF (n=36), compared with acute lung injury (ALI) (n=11) and nondisease controls (n=19), that reveal a robust gene expression signature unique to end-stage IPF. In addition to extracellular matrix remodelling pathways, we identified pathways associated with T-cell infiltration/activation, tumour development, and cholesterol homeostasis, as well as novel alternatively spliced transcripts that are differentially regulated in the advanced IPF lung versus ALI or nondisease controls. Additionally, we show a subset of genes that are correlated with percent predicted forced vital capacity and could reflect disease severity.Our results establish a robust transcriptomic fingerprint of an advanced IPF lung that is distinct from previously reported microarray signatures of moderate, stable or progressive IPF and identifies hitherto unknown candidate targets and pathways for therapeutic intervention in late-stage IPF as well as biomarkers to characterise disease progression and enable patient stratification.

Download Full-text

Effect of baseline FVC on decline in lung function with nintedanib in patients with idiopathic pulmonary fibrosis (IPF): results from the INPULSIS® trials

Pneumologie ◽

10.1055/s-0036-1572000 ◽

2016 ◽

Vol 70 (S 01) ◽

Author(s):

M Pfeifer ◽

M Kolb ◽

T Kimura ◽

S Stowasser ◽

C Hallmann ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis

Download Full-text

Analysis of patients with Idiopathic Pulmonary Fibrosis (IPF) with more severe lung function impairment treated with pirfenidone in RECAP

Pneumologie ◽

10.1055/s-0037-1619244 ◽

2018 ◽

Vol 72 (S 01) ◽

pp. S47-S48

Author(s):

U Costabel ◽

C Albera ◽

KU Kirchgaessler ◽

F Gilberg ◽

U Petzinger ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Function Impairment ◽

Lung Function Impairment ◽

Severe Lung

Download Full-text

Chemotherapy in idiopathic pulmonary fibrosis and small-cell lung cancer with poor lung function

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01489-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiyue Zhang ◽

Wei Li ◽

Chunyan Li ◽

Jie Zhang ◽

Zhenzhong Su

Keyword(s):

Lung Cancer ◽

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

High Resolution Computed Tomography ◽

Chemotherapeutic Regimen

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with unclear pathogenesis. IPF is considered as a risk factor for lung cancer. Compared to other lung cancers, small-cell lung cancer (SCLC) has a lower incidence, but has a more aggressive course. Patients with IPF and SCLC have a lower survival rate, more difficult treatment, and poorer prognosis. Case presentation Case 1 was of a 66-year-old man with IPF for 5 years, who was admitted to our hospital for dyspnea. Case 2 was of a 68-year-old woman, who presented with chest pains, cough, and dyspnea. Both patients had extremely poor lung function. High-resolution computed tomography and pathology revealed that both patients had IPF and SCLC. Chemotherapy comprising nedaplatin (80 mg/m2) and etoposide (100 mg for 5 days) was initiated for both patients. Antifibrotic agents were continued during the chemotherapeutic regimen. Both patients showed improvement in their condition after treatment. Conclusion The favorable outcomes in these 2 cases suggests that chemotherapy is worth considering in the management of patients having SCLC and IPF with poor lung function.

Download Full-text

Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics

Scientific Reports ◽

10.1038/s41598-021-89531-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stevan D. Stojanović ◽

Maximilian Fuchs ◽

Chunguang Liang ◽

Kevin Schmidt ◽

Ke Xiao ◽

...

Keyword(s):

Data Mining ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Rna Sequencing ◽

In Silico ◽

Rna Binding ◽

Human Lung ◽

Model Systems ◽

Lung Fibroblasts ◽

Sequencing Analysis

AbstractThe family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.

Download Full-text

Defining the Cell Types That Drive Idiopathic Pulmonary Fibrosis Using Single-Cell RNA Sequencing

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201901-0197ed ◽

2019 ◽

Vol 199 (12) ◽

pp. 1454-1456 ◽

Cited By ~ 1

Author(s):

Joanna M. Poczobutt ◽

Oliver Eickelberg

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Single Cell ◽

Rna Sequencing ◽

Cell Types ◽

Single Cell Rna Sequencing

Download Full-text

P238 Preserved lung parenchyma of idiopathic pulmonary fibrosis patients has increased expiratory CT densities- a sign for increased alveolar collapsibility?

CHEST Journal ◽

10.1016/j.chest.2017.04.145 ◽

2017 ◽

Vol 151 (5) ◽

pp. A138

Author(s):

M. Funke ◽

V. Petroulia ◽

P. Zumstein ◽

L. Ebner ◽

T. Geiser ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Parenchyma

Download Full-text

Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis

Respiration ◽

10.1159/000509557 ◽

2020 ◽

pp. 1-8

Author(s):

Pierre-Henri Aussedat ◽

Nader Chebib ◽

Kais Ahmad ◽

Jean-Charles Glerant ◽

Gabrielle Drevet ◽

...

Keyword(s):

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Forced Vital Capacity ◽

Lung Biopsy ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Surgical Lung Biopsy ◽

Before And After ◽

The Impact

Background: Video-assisted surgical lung biopsy (SLB) is performed in 10–30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). Objectives: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. Methods: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. Results: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. Conclusion: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

Download Full-text