References of "HENKET, Monique"
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See detailIn vitro modelling of lung inflammatory processes
Zanella, Delphine ULiege; HENKET, Monique ULiege; SCHLEICH, FLorence ULiege et al

Conference (2021, June)

Exhaled breath analysis has a high potential for early non-invasive diagnosis of lung conditions. The inflammation processes associated with oxidative stress yield to the conversion of membranes ... [more ▼]

Exhaled breath analysis has a high potential for early non-invasive diagnosis of lung conditions. The inflammation processes associated with oxidative stress yield to the conversion of membranes components into volatile organic compounds (VOC) secreted by the lungs. The characterization and understanding of the inflammatory metabolic pathways involved into VOC production is necessary to define proper medication. In this study, lung inflammation was simulated in-vitro on lung epithelial cells. We compared the VOC production following a conventional oxidative stress in-vitro using hydrogen peroxide (H2O2) with a biological model using inflammatory sputum from asthmatic patients. The VOC were extracted and analyzed by solid-phase microextraction comprehensive two-dimensional gas chromatography hyphenated to time-of-flight mass spectrometry. In the oxidative stress experiments, we exposed the epithelial cells to 0.1 mM H2O2 for 1 h. In the biological stress experiment, the epithelial cells were exposed to 50 % (v/v) inflammatory and non-inflammatory pool of sputum supernatants for 24 h. These optimal conditions were used to induce metabolic response, releasing specific metabolites, without causing significant cellular apoptosis. According to the type of inflammation induced, different VOCs were produced by the cells. For both chemical and biological challenges, an increase of carbonyl compounds and hydrocarbons was observed. However, 36% of the specific VOCs were produced only after a biological stress. Taken together, these results highlight that in-vitro VOC analysis is a very promising approach to characterize complex lung inflammatory mechanisms. The future implementation of multi-omics screening could reveal new information on the molecular mechanisms involved in lung inflammation. [less ▲]

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See detailSputum IL-25, IL-33 and TSLP, IL-23 and IL-36 in airway obstructive diseases. Reduced levels of IL-36 in eosinophilic phenotype.
Moermans, Catherine ULiege; Damas, K.; Guiot, Julien ULiege et al

in Cytokine (2021), 140

INTRODUCTION: Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a ... [more ▼]

INTRODUCTION: Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a role in airway remodeling in chronic airway obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD). IL-23 and IL-36 were shown to mediate the neutrophilic airway inflammation as seen in chronic airway obstructive diseases. OBJECTIVES: The purpose of this project was to determine the expression and the production of these cytokines from induced sputum (IS) in patients with chronic airway obstructive diseases including asthmatics and COPD. The relationship of the mediators with sputum inflammatory cellular profile and the severity of airway obstruction was assessed. METHODS: The alarmins (IL-25, IL-33 and TSLP) as well as IL-23 and IL-36 concentrations were measured in IS from 24 asthmatics and 20 COPD patients compared to 25 healthy volunteers. The cytokines were assessed by ELISA in the IS supernatant and by RT-qPCR in the IS cells. RESULTS: At protein level, no difference was observed between controls and patients suffering from airway obstructive diseases regarding the different mediators. IL-36 protein level was negatively correlated with sputum eosinophil and appeared significantly decreased in patients with an eosinophilic airway inflammation compared to those with a neutrophilic profile and controls. At gene level, only IL-36, IL-23 and TSLP were measurable but none differed between controls and patients with airway obstructive diseases. IL-36 and IL-23 were significantly increased in patients with an neutrophilic inflammatory profile compared to those with an eosinophilic inflammation and were correlated with sputum neutrophil proportions. None of the mediators were linked to airway obstruction. CONCLUSIONS: The main finding of our study is that patients with eosinophilic airway inflammation exhibited a reduced IL-36 level which could make them more susceptible to airway infections as IL-36 is implicated in antimicrobial defense. This study showed also an implication of IL-36 and IL-23 in airway neutrophilic inflammation in chronic airway obstructive diseases. [less ▲]

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See detailBreathomics to diagnose systemic sclerosis using thermal desorption and comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry
Zanella, Delphine ULiege; GUIOT, Julien ULiege; Stefanuto, Pierre-Hugues ULiege et al

in Analytical and Bioanalytical Chemistry (2021)

Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early ... [more ▼]

Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early diagnosis and prognosis associated with the disease progression are highly needed. Volatile organic compounds in exhaled breath are widely available and non-invasive and have the potential to reflect metabolic processes occurring within the body. Comprehensive two-dimensional gas chromatography coupled to high-resolution mass spectrometry was used to investigate the potential of exhaled breath to diagnose systemic sclerosis. The exhaled breath of 32 patients and 30 healthy subjects was analyzed. The high resolving power of this approach enabled the detection of 356 compounds in the breath of systemic sclerosis patients, which was characterized by an increase of mainly terpenoids and hydrocarbons. In addition, the use of 4 complementary statistical approaches (two-tailed equal variance ttest, fold change, partial least squares discriminant analysis, and random forest) resulted in the identification of 16 compounds that can be used to discriminate systemic sclerosis patients from healthy subjects. Receiver operating curves were generated that provided an accuracy of 90%, a sensitivity of 92%, and a specificity of 89%. The chemical identification of eight compounds predictive of systemic sclerosis was validated using commercially available standards. The analytical variations together with the volatile composition of room air were carefully monitored during the timeframe of the study to ensure the robustness of the technique. This study represents the first reported evaluation of exhaled breath analysis for systemic sclerosis diagnosis and provides surrogate markers for such disease. [less ▲]

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See detailYKL-40 as a new promising prognostic marker of severity in COVID infection.
Schoneveld, Lauranne ULiege; LADANG, Aurélie ULiege; HENKET, Monique ULiege et al

in Critical care (London, England) (2021), 25(1), 66

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See detailChronic infection with Chlamydia pneumoniae in asthma: a type-2 low infection related phenotype.
Calmes, Doriane ULiege; Huynen, Pascale ULiege; Paulus, Virginie ULiege et al

in Respiratory Research (2021), 22(1), 72

BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the ... [more ▼]

BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria. METHOD: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae. RESULTS: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV(1)/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations. CONCLUSION: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation. [less ▲]

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See detailAsthma and COPD Are Not Risk Factors for ICU Stay and Death in Case of SARS-CoV2 Infection
CALMES, Doriane ULiege; Graff, Sophie ULiege; MAES, Nathalie ULiege et al

in Journal of Allergy and Clinical Immunology: In Practice (2021), 9(1), 160-169

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if ... [more ▼]

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19). METHODS: We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic. RESULTS: Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death. CONCLUSION: Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection. [less ▲]

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See detailAre Volatile Organic Compounds Able to Identify Airflow Decline in Asthma?
Graff, Sophie ULiege; Zanella, Delphine ULiege; Stefanuto, Pierre-Hugues ULiege et al

in Journal of Asthma and Allergy (2021), 14

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See detailAsthma in elderly is characterized by increased sputum neutrophils, lower airway caliber variability and air trapping.
Schleich, Florence ULiege; Graff, Sophie ULiege; GUISSARD, Françoise ULiege et al

in Respiratory Research (2021), 22(1), 15

BACKGROUND: Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as ... [more ▼]

BACKGROUND: Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. METHODS: We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. RESULTS: Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV(1)) and FEV(1)/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. CONCLUSION: Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated. [less ▲]

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See detailTranslating breath-based asthma phenotyping into clinical practice
Stefanuto, Pierre-Hugues ULiege; Zanella, Delphine ULiege; SCHLEICH, FLorence ULiege et al

Conference (2020, November)

According to the world health organization, asthma and COPD represent the most common chronic respiratory diseases, with respectively 235 and 65 million of people concerned worldwide. These diseases are ... [more ▼]

According to the world health organization, asthma and COPD represent the most common chronic respiratory diseases, with respectively 235 and 65 million of people concerned worldwide. These diseases are not curable. Nevertheless, various forms of treatment that help to dilate major air passages and improve shortness of breath can help to increase the quality of life for patients. However, disease phenotyping relies on invasive sputum analysis. In addition, neutrophilic and eosinophilic inflammation phenotypes have similar symptoms but requires different treatment approaches. To improve monitoring of patients, they have to be better phenotyped. It would allow quick adjustment of the treatment. In this context, we have been developing a breath-based phenotyping approach using thermal desorption and two-dimensional gas chromatography coupled to high resolution mass spectrometry (TD-GC×GC-HRTOFMS). This method allows patient phenotyping with similar performances than the routine clinical practice (Accuracy 72%, AUROC 0.72). Moreover, the combination of breath with other methods, such as FeNO and blood cell count, significantly increases the model performance (Accuracy 76%, AUROC 87%). Our current efforts are focused on facilitating the translation of the method to the clinic and to better understand the origin of the markers used for the classification. To facilitate such translation, we have been working on direct mass spectrometry approach using full scan SIFT-MS. This method allows to phenotype patients with an accuracy around 75 % in less than 3 min. This work is included in the continuous effort around breath research to develop clinical implementation. [less ▲]

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See detailCould KL-6 levels in COVID-19 help to predict lung disease?
Frix, Anne-Noëlle ULiege; Schoneveld, Lauranne ULiege; LADANG, Aurélie ULiege et al

in Respiratory Research (2020), 21(309),

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of ... [more ▼]

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. MATERIALS AND METHODS: Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. DISCUSSION AND CONCLUSION: Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary. [less ▲]

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See detailNeutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19
Radermecker, Coraline ULiege; Detrembleur, Nancy ULiege; Guiot, Julien ULiege et al

in Journal of Experimental Medicine (2020), 217(12),

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are ... [more ▼]

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are thought to be major causes of respiratory failure and death, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can contribute to inflammation-associated lung damage, thrombosis, and fibrosis. However, whether NETs infiltrate particular compartments in severe COVID-19 lungs remains to be clarified. Here we analyzed postmortem lung specimens from four patients who succumbed to COVID-19 and four patients who died from a COVID-19-unrelated cause. We report the presence of NETs in the lungs of each COVID-19 patient. NETs were found in the airway compartment and neutrophil-rich inflammatory areas of the interstitium, while NET-prone primed neutrophils were present in arteriolar microthrombi. Our results support the hypothesis that NETs may represent drivers of severe pulmonary complications of COVID-19 and suggest that NET-targeting approaches could be considered for the treatment of uncontrolled tissue-damaging and thrombotic responses in COVID-19. © 2020 Radermecker et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). [less ▲]

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See detailComprehensive Cluster Analysis for COPD Including Systemic and Airway Inflammatory Markers
Nekoee Zahraei, Halehsadat ULiege; GUISSARD, Françoise ULiege; Paulus, Virginie ULiege et al

in COPD: Journal of Chronic Obstructive Pulmonary Disease (2020)

Chronic obstructive pulmonary disease (COPD) is a complex, multidimensional and heterogeneous disease. The main purpose of the present study was to identify clinical phenotypes through cluster nalysis in ... [more ▼]

Chronic obstructive pulmonary disease (COPD) is a complex, multidimensional and heterogeneous disease. The main purpose of the present study was to identify clinical phenotypes through cluster nalysis in adults suffering from COPD. A retrospective study was conducted on 178 COPD patients in stable state recruited from ambulatory care at University hospital of Liege. All patients were above 40 years, had a smoking history of more than 20 pack years, post bronchodilator FEV1/FVC <70% and denied any history of asthma before 40 years. In this study, the patients were described by a total of 84 mixed sets of variables with some missing values. Hierarchical clustering on principal components (HCPC) was applied on multiple imputation. In the final step, patients were classified into homogeneous distinct groups by consensus clustering. Three different clusters, which shared similar smoking history were found. Cluster 1 included men with moderate airway obstruction (n¼67) while cluster 2 comprised men who were exacerbation-prone, with severe airflow limitation and intense granulocytic airway and neutrophilic systemic inflammation (n¼56). Cluster 3 essentially included women with moderate airway obstruction (n¼55). All clusters had a low rate of bacterial colonization (5%), a low median FeNO value (<20 ppb) and a very low sensitization rate toward common aeroallergens (0-5%). CAT score did not differ between clusters. Including markers of systemic airway inflammation and atopy and applying a comprehensive cluster analysis we provide here evidence for 3 clusters markedly shaped by sex, airway obstruction and neutrophilic inflammation but not by symptoms and T2 biomarkers. [less ▲]

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See detailAre T2 biomarkers of any help in asthma diagnosis?
Nekoee Zahraei, Halehsadat ULiege; Graulich, Emmanuel ULiege; SCHLEICH, FLorence ULiege et al

Conference (2020, September 07)

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See detailMacrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p
GUIOT, Julien ULiege; Cambier, Maureen ULiege; Boeckx, Amandine ULiege et al

in Thorax (2020), 75(10), 870-881

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs ... [more ▼]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown. Methods: Two independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts. Results: Exosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation analysis revealed a positive association between exosomal miR-142-3p and the percentage of macrophages from sputum of patients with IPF (r=0.576, p=0.012), suggesting macrophage origin of exosomal miR-142-3p upregulation. The overexpression of miR-142-3p in alveolar epithelial cells and lung fibroblasts was able to reduce the expression of transforming growth factor β receptor 1 (TGFβ-R1) and profibrotic genes. Furthermore, exosomes isolated from macrophages present antifibrotic properties due in part to the repression of TGFβ-R1 by miR-142-3p transfer in target cells. Discussion: Our results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts. [less ▲]

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See detailAre type-2 biomarkers of any help in asthma diagnosis?
Nekoee Zahraei, Halehsadat ULiege; Graulich, Emmanuel ULiege; Schleich, Florence ULiege et al

in ERJ Open Research (2020), 6

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