NOVEL NON-INVASIVE SEVERITY MARKERS IN IDIOPATHIC PULMONARY FIBROSIS

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21228812 ◽

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.

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Non-invasive ventilation (NIV) in acute respiratory failure in patients with idiopathic pulmonary fibrosis (IPF)

10.1183/13993003.congress-2015.pa2177 ◽

2015 ◽

Author(s):

Rania Bouneb ◽

Jamila Baroudi ◽

Ahmed Khedher ◽

Jihene Ayachi ◽

Abdelbaki Azouzi ◽

...

Keyword(s):

Respiratory Failure ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Acute Respiratory Failure ◽

Invasive Ventilation ◽

Non Invasive ◽

Non Invasive Ventilation

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Non-invasive screening for pulmonary hypertension in idiopathic pulmonary fibrosis

Respiratory Medicine ◽

10.1016/j.rmed.2016.06.001 ◽

2016 ◽

Vol 117 ◽

pp. 65-72 ◽

Cited By ~ 18

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

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Failure of noninvasive prediction of pulmonary hypertension in patients with idiopathic pulmonary fibrosis

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2011.218 ◽

2015 ◽

Vol 75 (3) ◽

Author(s):

F. Salajka ◽

V. Bartoš ◽

J. Novosad ◽

J. Št'ásek ◽

J. Bis ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Ultrasound Examination ◽

Published Data ◽

Noninvasive Method ◽

Non Invasive ◽

Invasive Method ◽

The Mean ◽

Made In

Background. Pulmonary hypertension (PH) in patients with advanced idiopathic pulmonary fibrosis (IPF) is a complication connected with unfavorable prognosis. Great efforts have been made in attempting to establish a reliable non-invasive method which would enable detection of this complication. In this context a formula using pulmonary function parameters was published with outstanding results. Methods. We tested the formula in 27 IPF patients who underwent a lung function examination, cardiac ultrasonography and catheterisation on the same day. Results. Pulmonary hypertension was detected by catheterisation in 17 patients (63%). In our group, contrary to the published data, the aforementioned formula was neither useful for detecting patients with a high probability of PH nor as a means of calculating the mean pulmonary artery pressure in individual patients (p=0.502 and p=0.833, respectively). Ultrasound examination reached borderline correlation with the values measured by catheterisation when we compare patients with relevant results (r=0.531, p=0.051). However, the examination gave no usable results in 13 patients (48%). Conclusion. Our data suggests that no reliable, noninvasive method is currently available for detecting and confirming PH in IPF patients. We did not confirm the usefulness of the published formula. Further carefully organised studies will be necessary to verify or refute it.

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Evaluation of recently validated non- invasive formula using basic lung functions as new screening tool for pulmonary hypertension in idiopathic pulmonary fibrosis patients

Annals of Thoracic Medicine ◽

10.4103/1817-1737.56013 ◽

2009 ◽

Vol 4 (4) ◽

pp. 187 ◽

Cited By ~ 3

Author(s):

MahaK Ghanem ◽

HodaA Makhlouf ◽

GamalR Agmy ◽

HishamM.K Imam ◽

DoaaA Fouad

Keyword(s):

Pulmonary Hypertension ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Screening Tool ◽

Non Invasive ◽

Lung Functions

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Telomeric repeat-containing ribonucleic acid (TERRA) expression in patients with idiopathic pulmonary fibrosis

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-021-00141-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Manal M. El-Desoky ◽

Asem A. Hewidy ◽

Ahmed M. Fouda ◽

Fatma Azzahraa Hisham

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Telomeric Repeat ◽

Expression Level ◽

Strongly Correlated ◽

High Resolution Computed Tomography ◽

Non Invasive ◽

Non Coding Rna ◽

Extent Score ◽

Long Non Coding Rna

Abstract Background Idiopathic pulmonary fibrosis (IPF) represents a chronic disease with a progressive course. It is characterized by excessive lung scarring that ultimately contributes to irreversible lung function reduction. Interestingly, a type of long non-coding RNA termed as telomeric repeat-containing RNA (TERRA) is linked to fibrosis pathophysiology, including IPF. In this study, the expression profile of TERRA was investigated in IPF patients on radiological diagnosis [unusual interstitial pattern (UIP) in high-resolution computed tomography (HRCT)] to evaluate whether it could be employed as a reliable diagnostic biomarker. Results TERRA expression level was significantly higher in IPF patients over healthy controls. The expression level was significantly inversely correlated with the percentage of forced vital capacity predicted (FVC% predicted). By contrast, it was significantly directly correlated with HRCT reticular extent score. Conclusion TERRA expression is an essential biomarker in peripheral blood of IPF patients, providing a valuable non-invasive tool for IPF diagnosis. Moreover, TERRA expression is strongly correlated with UIP in HRCT reticular extent score.

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A novel protein signature from plasma extracellular vesicles for non-invasive differential diagnosis of idiopathic pulmonary fibrosis

10.1101/2021.05.07.21256811 ◽

2021 ◽

Author(s):

Raju SR Adduri ◽

Kai Cai ◽

Karen V Alzate ◽

Ravikiran Vasireddy ◽

Jeffrey W Miller ◽

...

Keyword(s):

Mass Spectrometry ◽

Differential Diagnosis ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Interstitial Pneumonia ◽

Extracellular Vesicles ◽

Molecular Pathways ◽

Non Invasive ◽

Independent Cohort ◽

Protein Signature

Background: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia of unknown etiology often leading to respiratory failure. Over half of IPF patients present with discordant features of usual interstitial pneumonia on high-resolution computed tomography at diagnosis which warrants surgical lung biopsy to exclude the possibility of other interstitial lung diseases (ILDs). Therefore, there is a need for non-invasive biomarkers for expediting the differential diagnosis of IPF. Methods: Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in a cohort of subjects with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects (HS). A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. We evaluated the concordance between plasma EV proteome and the lung transcriptome data. Lastly, we compared the molecular pathways overrepresented in IPF by differentially expressed proteins and transcripts from EVs and lung tissues, respectively. Results: The five-protein signature derived from mass spectrometry data showed area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from HS, respectively. We also found that the EV protein expression profiles mirrored their corresponding mRNA expressions in IPF lungs. Further, we observed an overlap in the EV proteome- and lung mRNA-associated molecular pathways. Conclusions: We discovered a plasma EV-based protein signature for differential diagnosis of IPF and validated this signature in an independent cohort. The signature needs to be tested in large prospective cohorts to establish its clinical utility.

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