References of "Louis, Renaud"
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See detailTentative differentiation of asthma phenotypes using GC×GC-TOFMS
Zanella, Delphine ULiege; Pesesse, R; SCHLEICH, FLorence ULiege et al

Conference (2018, January)

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See detailThe lung microbiome in idiopathic pulmonary fibrosis: A promising approach for targeted therapies
Fastrès, Aline ULiege; Felice, Florence ULiege; Roels, Elodie ULiege et al

in International Journal of Molecular Sciences (2017), 18(12), 2735

This review focuses on the role of the lung microbiome in idiopathic pulmonary fibrosis. Although historically considered sterile, bacterial communities have now been well documented in lungs both in ... [more ▼]

This review focuses on the role of the lung microbiome in idiopathic pulmonary fibrosis. Although historically considered sterile, bacterial communities have now been well documented in lungs both in healthy and pathological conditions. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. Existing published data suggesting that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. Taken altogether, published literature suggests that the lung microbiome might serve in the future as a prognostic biomarker, a therapeutic target, and/or provide an explanation for disease pathogenesis in IPF. [less ▲]

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See detailTD-GCxGC-HRTOFMS in biological applications 
Focant, Jean-François ULiege; Pesesse, Romain ULiege; Dubois, Lena ULiege et al

Conference (2017, September)

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See detailBlood Biomarkers in Idiopathic Pulmonary Fibrosis.
GUIOT, Julien ULiege; Moermans, Catherine; Henket, Monique et al

in Lung (2017)

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ... [more ▼]

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. METHODS: This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). CONCLUSION: Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers. [less ▲]

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See detailSputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7.
GUIOT, Julien ULiege; Henket, Monique; Corhay, Jean-Louis ULiege et al

in PLoS ONE (2017), 12(2), 0171344

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin leading rapidly to death. This paper addresses the issue of whether sputum induction is a suitable tool to study ... [more ▼]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin leading rapidly to death. This paper addresses the issue of whether sputum induction is a suitable tool to study respiratory tract inflammation and potential biomarkers in IPF compared to COPD, a fibrosing airway wall disease. METHODS: In a cross-sectional analysis, 15 IPF patients, 32 COPD and 30 healthy subjects underwent sputum induction. Total sputum cell counts and the amount of TGF- beta, IGF-1, IGF-2, IGFBP-1, IGFBP-2, IGFBP-3, IL-8, IL-13, MMP-7, MMP-9, YKL-40, TNF-alpha and KL-6 in sputum supernatant were analysed. We also profiled gene expression of cells in the induced sputum for TGF-beta, MMP-7, YKL-40, IGFBP-2, IL-6, IL-8 and TNF-alpha. RESULTS: IPF patients, like COPD, had increased sputum absolute number of neutrophils, eosinophils, macrophages and epithelial cells compared to HS. IPF sputum supernatants had increased concentrations of IGFBP-2, IL-8, TGF-beta, MMP-7, MMP-9 and KL-6 (p<0.05, p<0.0001, p<0.05, p<0.05, p<0.0001, p<0.05 respectively) when compared to healthy subjects where COPD had higher IL-6 and TNF-alpha levels than IPF (p<0.05 and p<0.05 respectively) and HS (p<0.0001 and p<0.001 respectively) and higher IL-8 and MMP-9 than HS (p<0.0001 and p<0.001 respectively). Conversely to IL-6 and TNF-alpha, MMP-7 was increased in IPF compared to COPD (p<0.05). The KL-6 and MMP-7 protein levels in sputum were inversely correlated with total lung capacity (TLC, % of predicted) in IPF patients (r = -0.73 and r = -0.53 respectively). Sputum gene expression analysis identified a significant increase for IGFBP-2, IL-6, IL-8 and MMP-7 in IPF compared to HS (p<0.05, p<0.01, p<0.05 and p<0.0001 respectively) and for IGFBP-2, YKL-40, IL-6, IL-8 and MMP-7 compared to COPD (p<0.01, p<0.01, p<0.05, p<0.01 and p<0.0001 respectively). Furthermore, gene expression of TGF-beta was increased in IPF compared to COPD (p<0.001) but not to HS. CONCLUSION: Our data show clear increase in expression and production of IGFBP-2, IL-8 and MMP-7 in sputum from patients with IPF that may contribute to the disease. [less ▲]

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See detailEGFR tyrosine kinase inhibitors overcome resistance to chemotherapy in malignant pleural mesothelioma.
Staumont, Bernard ULiege; Costa, Christostome; Vandermeers, Fabian et al

Poster (2017, February 01)

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See detailLe nintedanib (OFEV) : nouveau traitement remboursé dans la fibrose pulmonaire idiopathique
GUIOT, Julien ULiege; CORHAY, Jean-Louis ULiege; Louis, Renaud ULiege

in Revue médico-chirugicale du CHU de Charleroi (2017), 2017-1

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See detailIs it possible to claim or refute sputum eosinophils ≥ 3% in asthmatics with sufficient accuracy using biomarkers?
Demarche, Sophie ULiege; Schleich, Florence ULiege; PAULUS, Virginie ULiege et al

in Respiratory Research (2017), 18(1), 133-139

The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of ... [more ▼]

The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of inflammatory phenotypes, is however not widely available. Several studies have proposed to use surrogate exhaled or blood biomarkers, like fractional exhaled nitric oxide (FENO), blood eosinophils and total serum immunoglobulin E (IgE). However, taken alone, each of these biomarkers has moderate accuracy to identify sputum eosinophilia. Here, we propose a new approach based on the likelihood ratio to study which thresholds of these biomarkers, taken alone or in combination, were able to rule in or rule out sputum eosinophils ≥3%. We showed in a large population of 869 asthmatics that combining FENO, blood eosinophils and total serum IgE could accurately predict sputum eosinophils ≥ or <3% in 58% of our population. © 2017 The Author(s). [less ▲]

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See detailAsthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.
Demarche, Sophie ULiege; SCHLEICH, FLorence ULiege; PAULUS, Virginie ULiege et al

in Journal of Allergy and Clinical Immunology: In Practice (2017), 5(5), 1335-13435

BACKGROUND: Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice ... [more ▼]

BACKGROUND: Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. OBJECTIVE: To investigate the relationship between asthma control and sputum eosinophils in clinical practice. METHODS: A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. RESULTS: A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P < .001). In patients with intermittent/persistently eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P < .001) or 3.4-fold (AUC, 0.65; P = .003) for a significant improvement in asthma control and a minimal important increase of 3.5% (AUC, 0.67; P = .004) or 1.8-fold (AUC, 0.63; P = .02) for a significant worsening in asthma control. The association between asthma control and sputum eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. CONCLUSIONS: At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time. [less ▲]

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See detailA Belgian survey on the diagnosis of asthma-COPD overlap syndrome.
Cataldo, Didier ULiege; Corhay, Jean-Louis ULiege; Derom, Eric et al

in International Journal of Chronic Obstructive Pulmonary Disease (2017), 12

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse ... [more ▼]

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. METHODS: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by >/=70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. RESULTS: To diagnose ACOS in COPD patients, major criteria were "high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second >/=400 mL)" and "high degree of response to bronchodilators (>200 mL and >/=12% predicted above baseline)". Minor criteria were "personal/family history of atopy and/or IgE sensitivity to >/=1 airborne allergen", "elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide", "diagnosis of asthma <40 years of age"; "symptom variability", and "age (in favor of asthma)". To diagnose ACOS in asthma patients, major criteria were "persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)" and "exposure to noxious particles/gases, with >/=10 pack-years for (ex-)smokers"; minor criteria were "lack of response on acute bronchodilator test"; "reduced diffusion capacity"; "limited variability in airway obstruction"; "age >40 years"; "emphysema on chest computed tomography scan". CONCLUSION: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD. [less ▲]

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See detailSystemic biomarkers of collagen and elastin turnover are associated with clinically relevant outcomes in COPD.
Stolz, Daiana; Leeming, Diana Julie; Edfort Kristensen, Jacob Hull et al

in CHEST (2017)

BACKGROUND: Extracellular matrix remodeling (ECM) of the lung tissue releases protein fragments into the blood, where they may be detected as serological surrogate markers of disease activity in chronic ... [more ▼]

BACKGROUND: Extracellular matrix remodeling (ECM) of the lung tissue releases protein fragments into the blood, where they may be detected as serological surrogate markers of disease activity in chronic obstructive pulmonary disease (COPD). We aimed to assess the association of ECM turnover with severity and outcome of COPD. METHODS: In a prospective, observational, multicenter study including 506 patients with COPD, GOLD grades II-IV, we analyzed serum samples at stable state, exacerbation and 4 weeks after exacerbation, for a panel of 5 novel neo-epitopes including fragments of collagen type-III (C3M) and type-VI (C6M), pro-forms of collagen type-III (Pro-C3) and type-VI (Pro-C6) and neutrophil elastase-generated fragments of elastin (EL-NE) by ELISA. These neo-epitopes were also measured at stable state in a derivation cohort including 100 COPD patients. RESULTS: Serum levels of C3M, C6M, Pro-C3, Pro-C6 and EL-NE were associated with lung function. Patients with the lowest levels of Pro-C3 and Pro-C6 had more severe airflow limitation, hyperinflation, air trapping, and emphysema. Degradation of collagen type-III and -VI was associated with dyspnea. All ECM biomarkers, except Pro-C6, were increased at exacerbation as compared to stable state but, except EL-NE, did not differ between stable state and exacerbation follow-up in the crude and adjusted analyses. In Cox regression adjusted analyses, Pro-C3 was associated with a shorter time to exacerbation (HR 0.72[0.59-0.89] p=0.002) and Pro-C6 with survival (HR 2.09[1.18-3.71], p=0.011). CONCLUSIONS: Serum biomarkers of ECM turnover are significantly associated with disease severity and clinically relevant outcomes in COPD. [less ▲]

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See detailLung resident eosinophils represent a distinct cell subset with homeostatic functions
Mesnil, Claire ULiege; Raulier, Stéfanie ULiege; Paulissen, Geneviève et al

Conference (2016, October 21)

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See detailRaised interferon beta, type 3 interferon and interferon stimulated genes - evidence of innate immune activation in neutrophilic asthma.
da Silva, J.; Hilzendeger, Clarissa ULiege; Moermans, Catherine et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (2016)

BACKGROUND: Interferons play an important role in innate immunity. Previous studies report deficiency in virus-induction of interferon (IFN)-alpha, -beta and -lambda in bronchial epithelial and bronchial ... [more ▼]

BACKGROUND: Interferons play an important role in innate immunity. Previous studies report deficiency in virus-induction of interferon (IFN)-alpha, -beta and -lambda in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection. OBJECTIVE: The aim of the study was investigate if the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation. METHODS: Here we investigate the expression of IFN-beta, IFN-lambda1 (IL-29), IFN-lambda2/3 (IL-28A/B) and the interferon-stimulated genes (ISGs) myxovirus resistance 1 (Mx1), oligoadenylate synthetase (OAS) and viperin in unstimulated sputum cells in 57 asthmatics (including 16 mild, 19 moderate and 22 severe asthma patients) and compared them with 19 healthy subjects. RESULTS: We observed increased expression of IFN-beta, IFN-lambda1/IL-29, OAS and viperin in asthmatic compared to healthy subjects while IL-28 was not expressed in any group. The overexpression was restricted to neutrophilic asthmatics (sputum neutrophils >/= 76%) while eosinophilic asthmatics (sputum eosinophils >/= 3%) did not differ from healthy subjects or even showed a lower expression of Mx1. No difference in interferon or ISG expression was seen according to clinical asthma severity. CONCLUSION AND CLINICAL RELEVANCE: Neutrophilic, but not eosinophilic, asthmatics display overexpression of IFN-beta, IFN-lambda1/IL-29 and ISGs in their sputum cells that may reflect ongoing innate immune activation. This article is protected by copyright. All rights reserved. [less ▲]

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See detailScaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).
Bousquet, J.; Farrell, J.; Crooks, G. et al

in Clinical and translational allergy (2016), 6

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic ... [more ▼]

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing. [less ▲]

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See detailIgE mediated sensitisation to aeroallergens in an asthmatic cohort: relationship with inflammatory phenotypes and disease severity.
Manise, Maïté ULiege; Bakayoko, B.; SCHLEICH, FLorence ULiege et al

in International Journal of Clinical Practice (2016), 70(7), 596-605

BACKGROUND: Atopy is known to play an important role in the asthmatic disease. The main objective of this study was to evaluate the frequency of sensitisation to common aeroallergens in a cohort of ... [more ▼]

BACKGROUND: Atopy is known to play an important role in the asthmatic disease. The main objective of this study was to evaluate the frequency of sensitisation to common aeroallergens in a cohort of asthmatics with different inflammatory phenotypes and disease severity. METHODS: We have conducted a retrospective cross-sectional study including 772 asthmatics recruited between 2003 and 2014 in our Asthma Clinic. The patients were defined as asthmatics on the basis of respiratory symptoms together with a positive methacholine test (PC20M) < 16 mg/ml and/or a reversibility to short-acting beta2-agonists (salbutamol) >/= 12% and 200 ml. Sensitisation to house dust mites, grass and birch pollens, cats, dogs and moulds was assessed by RAST and a specific immunoglobulin E (IgE) > 0.35 kU/l was considered as significant. Inflammatory phenotypes were subdivided between pauci-granulocytic (n = 309) (40%), eosinophilic (n = 311) (40%), neutrophilic (N = 134) (17%) and mixed-granulocytic (N = 18) (3%) asthmatics. Severe asthmatics (n = 118) were defined according to the American Thoracic Society (ATS 2000) criteria and compared with mild-to-moderate asthmatics (N = 654). RESULTS: The eosinophilic phenotype was associated with higher levels of total serum IgE compared with neutrophilic and pauci-granulocytic asthma (p < 0.001 for both). Sensitisation rate to dogs and cats was higher in eosinophilic asthmatics (31% and 37%, respectively, p < 0.01 both) compared with neutrophilic (18% and 23% respectively) and pauci-granulocytic asthmatics (20% and 24%, respectively), while sensitisation rate to house dust mites and moulds were rather similar between the groups (ranging from 33% to 40% and from 10% to 16%, respectively). Severe asthmatics had slightly increased total serum IgE compared with mild-to-moderate asthmatics (p < 0.05) without any difference in the sensitisation rate to common aeroallergens. CONCLUSION: Eosinophilic asthma exhibits higher total serum IgE and sensitisation rate towards animal dander while clinical severity, though also associated with higher total IgE, did not preferentially relate to any type of common aeroallergens. [less ▲]

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