Proteomic biomarkers of progressive fibrosing interstitial lung disease: a multicentre cohort analysis (PF-ILD Proteomics-BioLINCC)
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PROVIDER: PRJNA1231612 | ENA |
REPOSITORIES: ENA
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Project description:Proteomic biomarkers of progressive fibrosing interstitial lung disease: a multicentre cohort analysis (PF-ILD Proteomics-BioLINCC)
| PRJNA1231611 | ENA
Project description:Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.
| S-EPMC8197477 | biostudies-literature
Project description:ObjectivesProgressive fibrosing interstitial lung disease (PF-ILD) is characterised by increased pulmonary fibrosis, lung function decline, acute exacerbations, decreased quality of life and increased mortality. Nintedanib may slow down disease progression, but long-term outcomes are unknown. We aimed to assess the cost-effectiveness of nintedanib in comparison to placebo, both on top of usual care in patients with PF-ILD.MethodsAn individual PF-ILD patient simulation model was created, using data and extrapolations from the nintedanib and placebo arms of the INBUILD trial. Clinical outcomes (mortality, exacerbations, lung transplants), economic outcomes (direct and indirect costs) and the cost-effectiveness of nintedanib over a 10-year time horizon were forecasted using the Netherlands as a case example. Disease progression was driven by lung function decline, with forced vital capacity (FVC) health states ranging from < 40 to ≥ 110 FVC of % predicted. Sensitivity and scenario analyses were performed to assess the impact of parameter assumptions on the cost-effectiveness and to test model robustness.ResultsOver a 10-year follow-up, nintedanib gained an average of 1.31 discounted life years and an average of 0.87 discounted quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of €60,690 per QALY. Sensitivity analyses showed cost variations had a minor impact on the ICER. Results were mainly driven by mortality probabilities and disease-related utilities. Scenario analyses indicated most sensitivity to the time horizon and lung transplantation costs.ConclusionLong-term treatment with nintedanib could result in considerable health gains for patients with PF-ILD and can be considered cost-effective under the common willingness-to-pay threshold.
| S-EPMC9440187 | biostudies-literature
Project description:GWAS in Fibrosing Interstitial Lung Disease
| PRJNA248931 | ENA
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
2016-08-01 | E-GEOD-81293 | biostudies-arrayexpress
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
2016-08-01 | E-GEOD-81292 | biostudies-arrayexpress
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from 23 patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). 11 samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), 5 samples came from patients with non-specific interstitial pneumonia (NSIP), the remaining from patients with uncharacterized fibrosis and from patients with other ILD variants. B. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.
2011-03-24 | E-GEOD-21369 | biostudies-arrayexpress
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from thirty patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). Ten samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), nine samples came from patients with non-specific interstitial pneumonia (NSIP), four from patients with uncharacterized fibrosis, and the remaining samples came from patients with other ILD variants. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.
2011-04-19 | E-GEOD-21394 | biostudies-arrayexpress
Project description:600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks.Ethics and disseminationThe trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations.Trial registration numberNCT02999178.
| S-EPMC5604725 | biostudies-literature
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.
2016-08-01 | GSE81293 | GEO