Prognostic accuracy of a peripheral blood transcriptome signature in chronic hypersensitivity pneumonitis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE319562 | GEO | 2026/04/15
REPOSITORIES: GEO
Similar Datasets
Project description:We performed longitudinal plasma proteomics analysis and determined absolute protein levels in a Canadian cohort (n=74) at admission day to hospital for acute COVID-19 and at 3 and 6 months after diagnosis of acute COVID-19. We measured plasma protein on a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode and used internal standards to deduce protein absolute concentrations. We used a validated panel of 269 surrogate heavy labeled peptides. We also measured % predicted forced vital capacity (FVC, %) and diffusing capacity of the lungs for carbon monoxide (DLCO, %) by routine pulmonary function testing. We did functional enrichment and pathway analyses and determined proteins that were increased or decreased from hospital admission to 3-months and 6-months, compared females to males and determined associations of proteins with FVC% and DLCO%.
2024-01-26 | PXD041762 | Pride
Project description:Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial disease of unknown cause. It remains impractical to conduct early diagnosis and predict IPF progression just based on gene expression information. Moreover, the relationship between gene expression and quantitative phenotypic value in IPF keeps controversial. To identify biomarkers to predict survival in IPF, we profiled protein-coding gene expression in peripheral blood mononuclear cells (PBMCs). We linked the gene expression level with the quantitative phenotypic variation in IPF, including diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC) percent predicted. In silico analyses on the expression profiles and quantitative phenotypic data allowed for the generation of a set of IPF molecular signature that predicted survival of IPF effectively.
2014-06-30 | GSE38958 | GEO
Project description:Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. These results demonstrate that the peripheral blood transcriptome can distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted DLCO, but not FVC. Gene expression profiles of peripheral blood RNA from 93 IPF patients were collected on Agilent microarrays. Blood was collected in PAXRNA tubes. 30 healthy controls are compared to IPF patients classified by disease severity when categorized by DLCO or FVC.
2012-06-30 | E-GEOD-33566 | biostudies-arrayexpress
Project description:Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of CHP subjects have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF). However, the molecular relationship between CHP and IPF is not well understood. We report an RNA-seq based transcriptomic analysis for whole lung tissues from CHP, IPF and control subjects.
2020-07-01 | GSE150910 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial disease of unknown cause. It remains impractical to conduct early diagnosis and predict IPF progression just based on gene expression information. Moreover, the relationship between gene expression and quantitative phenotypic value in IPF keeps controversial. To identify biomarkers to predict survival in IPF, we profiled protein-coding gene expression in peripheral blood mononuclear cells (PBMCs). We linked the gene expression level with the quantitative phenotypic variation in IPF, including diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC) percent predicted. In silico analyses on the expression profiles and quantitative phenotypic data allowed for the generation of a set of IPF molecular signature that predicted survival of IPF effectively. Total RNA was isolated from PBMCs using standard molecular biology protocols without DNA contamination or RNA degradation. Sample processing (e.g., cDNA generation, fragmentation, end labeling, hybridization to Affymetrix GeneChip Human Exon 1.0 ST arrays) was performed per manufacturer’s instructions. A total of 45 healthy controls and 70 IPF patients were included in the microarray analysis.
2014-06-30 | E-GEOD-38958 | biostudies-arrayexpress
Project description:Background: HIV infection is associated with impaired gas transfer in the lung as indicated by a low diffusing capacity (DLCO). Mechanisms for reduced DLCO in the setting of HIV infection are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood gene expression. Methods: A total of 40 HIV-infected (HIV+) and uninfected (HIV-) men with preserved versus reduced DLCO were selected from a larger cohort study of lung function. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from peripheral blood leukocytes (PBLs) and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV+ vs. HIV- subjects with preserved DLCO and those with impaired DLCO to identify differentially activated pathways. Results: Using pathway-based analyses we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. When we applied a similar analysis to subjects with low DLCO, we identified a much broader repertoire of inflammatory and immune-related pathways in HIV+ patients relative to HIV- subjects, with up-regulation of multiple interleukin pathways, interferon signaling, Toll-like receptor signaling, and T cell/B cell receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV+ patients with reduced DLCO relative to the other groups. Conclusions: Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated pulmonary gas exchange impairment. Total RNA was isolated from peripheral blood leukocytes in four subject groups: 1. HIV-, low DLCO (N = 11); 2. HIV+, low DLCO (N = 10); 3. HIV-, preserved DLCO (N = 9); 4. HIV+, preserved DLCO (N = 9). Each sample was hybridized to an Affymetrix PrimeView Human Gene Expression microarray for a total of 39 experiments.
2016-04-01 | E-GEOD-76403 | biostudies-arrayexpress
Project description:Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. These results demonstrate that the peripheral blood transcriptome can distinguish normal individuals from patients with IPF, as well as extent of disease when samples were classified by percent predicted DLCO, but not FVC.
2012-07-01 | GSE33566 | GEO
Project description:We conducted a small cross-sectional proteomic study aiming to identify potential biomarkers of emphysema, as well as to identify COPD- and smoking-related biomarkers. This study was approved by the University Hospital Dubrava's Institutional Ethics Committee (approval no. 2022/2908‐05), as well as by the School of Medicine, University of Zagreb's Institutional Ethics Committee (approval no. 251-59-10106-24-111/119). This study included a total of 40 participants, divided into four equal age and gender-matched groups (N=10 participants per group): 1.) patients with COPD and radiologically verified emphysema on chest CT (CE group), confirmed by a radiologist, 2.) patients with COPD without radiological signs of emphysema on chest CT (CN group), confirmed by a radiologist, 3) healthy smokers (active smokers (>20 pack-years) without respiratory symptoms and normal spirometry) (HS group), 4) healthy never-smokers (without respiratory symptoms and with normal spirometry) (HN group). A graphic study outline is shown in Figure 1. Participants were included in the study in a non-probabilistic manner (in order to be age, gender, comorbidity and body mass index matched – so group homogeneity in these regards could be achieved). Patients with COPD (CE and CN groups) were GOLD 2B patients as defined by GOLD 2023, active smokers (>20 pack-years), on dual inhalation therapy (combination of long-acting β2 agonist (LABA) and long-acting muscarinic antagonist (LAMA)). Exclusion criteria were: reversible airflow limitation, positive bronchodilator test (either by the GINA criteria or by the ERS/ATS technical standard 2022; acute exacerbation of COPD in the last 6 months, concomitant malignancy, autoimmune disease or concomitant asthma, as well as alpha-1-antitrypsin deficiency. Patients that consumed tobacco products other than classical cigarettes (including e-cigarettes, heat not-burn tobacco products, vape, cigars and cigarillos) were also excluded from the study. None of the participants were taking glucocorticoids or other immunosuppressive medications. All subjects in the study signed an informed consent form. Comorbidities were assessed using the Charlson's comorbidity index and also a modified Charlson's comorbidity index in which “chronic pulmonary disease“ was excluded. The participants underwent spirometry testing and all COPD patients had a chest CT no older than 3 months prior to inclusion. Spirometry with a subsequent bronchodilator test (with 400mcg of salbutamol) was performed according to the international standards, using the Global Lung Initiative (GLI) reference values. Expiratory airflow limitation was determined using the proposed GOLD criteria with a fixed FEV1/FVC ratio of 0.7.
2026-04-06 | PXD074107 | Pride
Project description:The Rationale: Molecular markers of disease activity that are predictive of forced vital capacity (FVC) progression in idiopathic pulmonary fibrosis are needed. Objectives: Develop a predictor using longitudinal within-patient gene expression differences (ΔGE) in peripheral blood mononuclear cells (PBMC) to predict of FVC progression. Methods: Patients in the training cohort (n=74) experiencing ≥10% relative reduction in FVC% of predicted over 12 months were categorized as progressors in contrast to the remaining stable patients. Baseline to 4-month within-patient ΔGE were correlated with FVC status. FVC-predictor genes were prioritized by two-group comparison with FDR<5%, logistic LASSO regression with p<0.05, and 10-Fold Cross-Validation with ≥50% support. Receiver operating characteristic with area under the curve (AUC) analyses were conducted in training subsets and independent validation cohorts from UChicago (n=27), UPMC (n=35), and Imperial (n=24) where different transcriptome assay platforms and varying transcriptome sampling times were used to derive ΔGE. Results: Intra-subject Compared to cross-sectional analysis of baseline GE, our longitudinal ΔGE variation approach demonstratedlargely reduced within-group sample variation and increased statistic power fin progressor and stable groups for prediction model development. A 25-gene FVC-predictor separated “progressors” from “stable” by Principal Component Analysis in the training and subsets of the training cohort. The resulting FVC-predictor consistently demonstrated high discriminatory performance independent of transcriptome assay platforms and varying sampling times in validation cohorts (AUC= 0.77-0.80). TGF beta was the highest-ranking canonical pathway by Gene Set Enrichment Analysis. Conclusions: Our novel short-term longitudinal within-patient ΔGE approach identified a FVC-predictor which may reflect disease activity and prove to be a reliable biomarker predictive of future FVC decline.
2019-09-30 | GSE132607 | GEO
Project description:Background: HIV infection is associated with impaired gas transfer in the lung as indicated by a low diffusing capacity (DLCO). Mechanisms for reduced DLCO in the setting of HIV infection are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood gene expression. Methods: A total of 40 HIV-infected (HIV+) and uninfected (HIV-) men with preserved versus reduced DLCO were selected from a larger cohort study of lung function. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from peripheral blood leukocytes (PBLs) and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV+ vs. HIV- subjects with preserved DLCO and those with impaired DLCO to identify differentially activated pathways. Results: Using pathway-based analyses we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. When we applied a similar analysis to subjects with low DLCO, we identified a much broader repertoire of inflammatory and immune-related pathways in HIV+ patients relative to HIV- subjects, with up-regulation of multiple interleukin pathways, interferon signaling, Toll-like receptor signaling, and T cell/B cell receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV+ patients with reduced DLCO relative to the other groups. Conclusions: Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated pulmonary gas exchange impairment.
2016-04-01 | GSE76403 | GEO