scholarly journals Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 21 (22) ◽  
pp. 8812
Author(s):  
Stefania Di Mauro ◽  
Alessandra Scamporrino ◽  
Mary Fruciano ◽  
Agnese Filippello ◽  
Evelina Fagone ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Area Under The Curve ◽  
P Value ◽  
Patient Identification ◽  
Clinical Issue ◽  
Rna Molecules ◽  
Non Invasive ◽  
Non Coding Rnas ◽  
Whole Transcriptome Analysis

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2–5 years after diagnosis. Therefore, IPF patient identification represents an important and challenging clinical issue. Current research is still searching for novel reliable non-invasive biomarkers. Therefore, we explored the potential use of long non-coding RNAs (lncRNAs) and mRNAs as biomarkers for IPF. Methods: We first performed a whole transcriptome analysis using microarray (n = 14: 7 Control, 7 IPF), followed by the validation of selected transcripts through qPCRs in an independent cohort of 95 subjects (n = 95: 45 Control, 50 IPF). Diagnostic performance and transcript correlation with functional/clinical data were also analyzed. Results: 1059 differentially expressed transcripts were identified. We confirmed the downregulation of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) lncRNA, hsa_circ_0001924 circularRNA, utrophin (UTRN) and Y-box binding protein 3 (YBX3) mRNAs. The two analyzed non-coding RNAs correlated with Forced Vital Capacity (FVC)% and Diffusing Capacity of the Lung for carbon monoxide (DLCO)% functional data, while coding RNAs correlated with smock exposure. All analyzed transcripts showed excellent performance in IPF identification with Area Under the Curve values above 0.87; the most outstanding one was YBX3: AUROC 0.944, CI 95% = 0.895–0.992, sensitivity = 90%, specificity = 88.9%, p-value = 1.02 × 10−13. Conclusions: This study has identified specific transcript signatures in IPF suggesting that validated transcripts and microarray data could be useful for the potential future identification of RNA molecules as non-invasive biomarkers for IPF.

scholarly journals The function of non-coding RNAs in idiopathic pulmonary fibrosis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 481-490
Author(s):  
Hui Zhang ◽  
Miao Song ◽  
Jianing Guo ◽  
Junbing Ma ◽  
Min Qiu ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Poor Prognosis ◽  
Biological Functions ◽  
Protein Coding ◽  
Ribonucleic Acids ◽  
Rna Molecules ◽  
Evolutionarily Conserved ◽  
Non Coding Rnas ◽  
Regulate Protein

Abstract Non-coding ribonucleic acids (ncRNAs) are a diverse group of RNA molecules that are mostly not translated into proteins after transcription, including long non-coding RNAs (lncRNAs) with longer than 200 nucleotides non-coding transcripts and microRNAs (miRNAs) which are only 18–22 nucleotides. As families of evolutionarily conserved ncRNAs, lncRNAs activate and repress genes via a variety of mechanisms at both transcriptional and translational levels, whereas miRNAs regulate protein-coding gene expression mainly through mRNA silencing. ncRNAs are widely involved in biological functions, such as proliferation, differentiation, migration, angiogenesis, and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. The etiology of IPF is still unclear. Increasing evidence shows the close correlations between the development of IPF and aberrant expressions of ncRNAs than thought previously. In this study, we provide an overview of ncRNAs participated in pathobiology of IPF, seeking the early diagnosis biomarker and aiming for potential therapeutic applications for IPF.

Patients With Idiopathic Pulmonary Fibrosis Admitted to the ICU With Acute Respiratory Failure—A Reevaluation of the Risk Factors and Outcomes

2021 ◽  
pp. 088506662198924
Author(s):  
Matthew Schrader ◽  
Matheni Sathananthan ◽  
Niranjan Jeganathan
Keyword(s):  
Risk Factors ◽  
Respiratory Failure ◽  
Mortality Rate ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Acute Respiratory Failure ◽  
Small Sample ◽  
Apache Score ◽  
Non Invasive ◽  
Organ Failures

Introduction: Idiopathic pulmonary fibrosis (IPF) patients admitted to the ICU with acute respiratory failure (ARF) are known to have a poor prognosis. However, the majority of the studies published to date are older and had small sample sizes. Given the advances in ICU care since the publication of these studies, we sought to reevaluate the outcomes and risk factors associated with mortality in these patients. Methods: Retrospective study using a large multi-center ICU database. We identified 411 unique patients with IPF admitted with ARF between 2014-2015. Results: Of all IPF patients admitted to the ICU with ARF, 81.3% required mechanical ventilation (MV): 48.9% invasive and 32.4% non-invasive alone. The hospital mortality rate was 34.5% for all patients; 48.8% in patients requiring invasive MV, 21.8% in those requiring non-invasive MV and 19.5% with no MV. In multiple regression analyses, age, APACHE score, invasive MV, and hyponatremia at admission were associated with increased mortality whereas post-op status was associated with lower mortality. In patients requiring invasive MV, baseline PaO2/FiO2 ratio was also predictive of mortality. Non-pulmonary organ failures were present in less than 20% of the patients. Conclusions: Although the overall mortality rate for IPF patients admitted to the ICU with ARF has improved, the mortality rates for patients requiring invasive MV remains high at approximately 50%. Older age, high APACHE score, and low baseline PaO2/FiO2 ratio are factors predictive of increased mortality in this population.

scholarly journals Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs

2020 ◽  
Vol 21 (2) ◽  
pp. 524 ◽  
Author(s):  
Marina R. Hadjicharalambous ◽  
Mark A. Lindsay
Keyword(s):  
Chronic Disease ◽  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Lung Fibroblast ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Non Coding Rnas

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as the secretion of fibrotic and inflammatory mediators, have been strongly associated with the development and progression of IPF. Significantly, long non-coding RNAs (lncRNAs) are emerging as modulators of multiple biological processes, although their function and mechanism of action in IPF is poorly understood. LncRNAs have been shown to be important regulators of several diseases and their aberrant expression has been linked to the pathophysiology of fibrosis including IPF. This review will provide an overview of this emerging role of lncRNAs in the development of IPF.

scholarly journals Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 7 ◽  
Author(s):  
Norihito Omote ◽  
Maor Sauler
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Disease ◽  
Cell Fate ◽  
Cellular Senescence ◽  
Cellular Stress ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Non Coding Rnas

Cellular senescence is a cell fate implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Cellular senescence occurs in response to cellular stressors such as oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction. Whether these stresses induce cellular senescence or an alternative cell fate depends on the type and magnitude of cellular stress, but also on intrinsic factors regulating the cellular stress response. Non-coding RNAs, including both microRNAs and long non-coding RNAs, are key regulators of cellular stress responses and susceptibility to cellular senescence. In this review, we will discuss cellular mechanisms that contribute to senescence in IPF and COPD and highlight recent advances in our understanding of how these processes are influenced by non-coding RNAs. We will also discuss the potential therapeutic role for targeting non-coding RNAs to treat these chronic lung diseases.

scholarly journals The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tetsuya Hanaka ◽  
Takashi Kido ◽  
Shingo Noguchi ◽  
Sohsuke Yamada ◽  
Hirotsugu Noguchi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Healthy Volunteers ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Lung Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Inflammatory Changes

Abstract Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. Methods Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. Results Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. Conclusions PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.

scholarly journals Non-invasive screening for pulmonary hypertension in idiopathic pulmonary fibrosis

2016 ◽  
Vol 117 ◽  
pp. 65-72 ◽  
Author(s):  
Laith Alkukhun ◽  
Xiao-Feng Wang ◽  
Mostafa K. Ahmed ◽  
Manfred Baumgartner ◽  
Marie M. Budev ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Non Invasive

scholarly journals An updated approach to determine minimal clinically important differences in idiopathic pulmonary fibrosis

2021 ◽  
pp. 00142-2021
Author(s):  
Mohleen Kang ◽  
Srihari Veeraraghavan ◽  
Greg S. Martin ◽  
Jordan A. Kempker
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Short Form ◽  
Area Under The Curve ◽  
Receiver Operating Curve ◽  
Physical Component Score ◽  
Sf 36 ◽  
Patient Related Outcome ◽  
Randomised Controlled

IntroductionCurrent medications for idiopathic pulmonary fibrosis (IPF) have not been shown to have impact on patient related outcome measures (PROMs) highlighting the need for accurate Minimal Clinically Important Differences (MCID) values. Recently published consensus standards for MCID studies support using anchor-based over distribution-based methods. The aim of this study was to estimate MCID values for worsening in IPF using only an anchor-based approach.MethodsWe conducted secondary analyses of three randomised controlled trials with different inclusion criteria and follow-up intervals. The Health Transition question in the Short Form Health Survey 36 (SF-36) questionnaire was used as the anchor. We used receiver operating curve to assess responsiveness between the anchor and ten variables (four physiologic measures and six PROMs). We used an anchor-based method to determine the MCID values of variables that met the responsiveness criteria (area under the curve≥0.70).ResultsSix minute walk distance (6 MWD), the St. George's Respiratory Questionnaire (SGRQ), physical component score of SF-36 (SF-36 PCS), and University of California, San Diego, Shortness of Breath Questionnaire (UCSD SOBQ) met the responsiveness criteria. The MCID value for 6 MWD was −75 meters. The MCID value for SF-36 PCS was −7 points. MCID value for SGRQ was 11points. MCID value for the UCSD SOBQ was 11 points.ConclusionsThe MCID estimates of 6 MWD, SGRQ, SF-36, UCSD SOBQ using only anchor-based methods were considerably higher compared to previously proposed values. A single MCID value may not be applicable across all classes of disease severity or durations of follow-up time.

scholarly journals Associations between resources and practices of ILD centers and outcomes in patients with idiopathic pulmonary fibrosis: data from the IPF-PRO Registry

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Joao A. de Andrade ◽  
Tejaswini Kulkarni ◽  
Megan L. Neely ◽  
Anne S. Hellkamp ◽  
Amy Hajari Case ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Transplant ◽  
Online Survey ◽  
Case Mix ◽  
P Value ◽  
Patient Case ◽  
Improvement Project ◽  
The Us ◽  
Event Rates

Abstract Background Performance benchmarks for the management of idiopathic pulmonary fibrosis (IPF) have not been established. We used data from the IPF-PRO Registry, an observational registry of patients with IPF managed at sites across the US, to examine associations between the characteristics of the enrolling sites and patient outcomes. Methods An online survey was used to collect information on the resources, operations, and self-assessment practices of IPF-PRO Registry sites that enrolled ≥ 10 patients. Site variability in 1-year event rates of clinically relevant outcomes, including death, death or lung transplant, and hospitalization, was assessed. Models were adjusted for differences in patient case mix by adjusting for known predictors of each outcome. We assessed whether site-level heterogeneity existed for each patient-level outcome, and if so, we investigated potential drivers of the heterogeneity. Results All 27 sites that enrolled ≥ 10 patients returned the questionnaire. Most sites were actively following > 100 patients with IPF (70.4%), had a lung transplant program (66.7%), and had a dedicated ILD nurse leader (77.8%). Substantial heterogeneity was observed in the event rates of clinically relevant outcomes across the sites. After controlling for patient case mix, there were no outcomes for which the site variance component was significantly different from 0, but the p-value for hospitalization was 0.052. Starting/completing an ILD-related quality improvement project in the previous 2 years was associated with a lower risk of hospitalization (HR 0.60 [95% CI 0.44, 0.82]; p = 0.001). Conclusions Analyses of data from patients with IPF managed at sites across the US found no site-specific characteristics or practices that were significantly associated with clinically relevant outcomes after adjusting for patient case mix. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511

NOVEL NON-INVASIVE SEVERITY MARKERS IN IDIOPATHIC PULMONARY FIBROSIS

2020 ◽  
Vol 16 (73) ◽  
pp. 091
Author(s):  
V.V. Rodionova ◽  
O.V. Karasova ◽  
O.E. Bekh ◽  
V.A. Tkachenko ◽  
Iu.A. Gordiienko
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Non Invasive
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