References of "Corhay, Jean-Louis"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailAzithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE). A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial.
Vermeersch, Kristina; Gabrovska, Maria; Aumann, Joseph et al

in American journal of respiratory and critical care medicine (2019), 200(7), 857-868

Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined ... [more ▼]

Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined.Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care.Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for an AECOPD and had a smoking history of >/=10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated the TF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or all-cause mortality.Measurements and Main Results: A total of 301 patients were randomized to azithromycin (n = 147) or placebo (n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% (P = 0.0272), 13% versus 28% (P = 0.0024), and 2% versus 4% (P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal.Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits. [less ▲]

Detailed reference viewed: 33 (1 ULiège)
Full Text
Peer Reviewed
See detailFirst report of probe based confocal laser endomicroscopy during medical thoracoscopy.
BONHOMME, Olivier ULiege; DUYSINX, Bernard ULiege; HEINEN, Vincent ULiege et al

in Respiratory Medicine (2019), 147

Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular ... [more ▼]

Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular level ("optical biopsies"). To the best of our knowledge, this article is the first to present pCLE images during medical thoracoscopy. We present here 3 different patients referred for various health problems. A precise description of pleural cavity pCLE images after intravenous fluorescein injection (a fluorophore) together with corresponding macroscopical and histological studies is performed. This led to the diagnosis of normal pleura in one case, carcinomatous pleuritis in another case and a malignant mesothelioma in the third case. We believe that optical biopsies could help clinicians to make an early diagnosis, thereby allowing rapid therapeutic intervention (talc pleurodesis for example). Furthermore, it could help to guide biopsies when affected zones are not obvious to macroscopic examination. In a near future, new fluorophores could be developed to stain some pathophysiological processes, therapeutic targets, or enzymes activities bringing new insights in endoscopic pleural disease work-up. [less ▲]

Detailed reference viewed: 51 (4 ULiège)
Full Text
Peer Reviewed
See detailLa thoracoscopie médicale en pratique pneumologique: expérience du CHU de Liège
DUYSINX, Bernard ULiege; HEINEN, Vincent ULiege; Corhay, Jean-Louis ULiege et al

in Revue des Maladies Respiratoires (2019), 36

Introduction: The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. Method: We report the retrospective ... [more ▼]

Introduction: The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. Method: We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017. Results: In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis. The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis. Conclusion: Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease. © 2019 SPLF [less ▲]

Detailed reference viewed: 54 (1 ULiège)
Full Text
Peer Reviewed
See detailUne sarcoïdose dans le décours d'une tuberculose. Existe-t-il un lien étiologique entre ces deux maladies granulomateuses ?
Maalioune, Sonia ULiege; Corhay, Jean-Louis ULiege; Delvenne, Philippe ULiege et al

in Revue medicale de Liege (2019), 74(7-8), 394-400

We report the case of a 38-year old non-smoking female who initially presented to the hospital with frequent cough and sputum for several weeks. The investigations confirmed the diagnosis of tuberculosis ... [more ▼]

We report the case of a 38-year old non-smoking female who initially presented to the hospital with frequent cough and sputum for several weeks. The investigations confirmed the diagnosis of tuberculosis and a triple therapy was introduced with clinical improvement. Two years later, the patient reported recurrence of respiratory symptoms. The new investigations concluded initially to a recurrence of tuberculosis and a quadriple therapy was introduced. The treatment was poorly tolerated and rapidly stopped. It was then decided to perform a biopsy through mediastinoscopy in the hilar ganglia, which confirmed the diagnosis of sarcoidosis. The etiology of sarcoidosis is not yet clearly established, one of the hypothesis would be the direct involvement of an infectious agent that would induce an excessive immune response. The clinical case below supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis. [less ▲]

Detailed reference viewed: 41 (4 ULiège)
Full Text
Peer Reviewed
See detailOxygénothérapie de longue durée : survie à 1 an, facteurs prédictifs de mortalité
VAN CAUWENBERGE, Hélène ULiege; Thonnard, Anne-Sophie ULiege; NGUYEN DANG, Delphine ULiege et al

in Revue des Maladies Respiratoires (2018), 35(9), 939-947

OBJECTIVES: The aims of this study were to assess the survival rate at one year of patients receiving long-term oxygen therapy (LTOT) as prescribed by the National Institute for Health and Disability ... [more ▼]

OBJECTIVES: The aims of this study were to assess the survival rate at one year of patients receiving long-term oxygen therapy (LTOT) as prescribed by the National Institute for Health and Disability Insurance's imposed criteria based on international recommendations, to search for short-term predictive factors for mortality and to measure the impact of LTOT on the frequency of hospitalization due to COPD exacerbations. METHODS: We conducted a retrospective analysis of 416 patients suffering from chronic respiratory insufficiency and started on long-term oxygen therapy between 2012 and 2014. The survival curves were estimated by the Kaplan-Meier method. Cox regression models were used to estimate the impact of the variables on survival. The evolution of patients hospitalized for COPD exacerbation was analysed by the McNemar test. RESULTS: The average age of our cohort was 70+/-10 years. It included 57% women and 78% patients with COPD. The one-year survival rate (n=416) under LTOT was 75%. Identified predictive mortality factors were coronary insufficiency [HR (95% CI): 1.8 (1.2-2.8); P=0.0083], reduction of the left ventricular ejection fraction [HR (95% CI): 2.5 (1.3-4.9); P=0.0080], the presence of osteoporosis [HR (95% CI): 1.7 (1.0-2.9); P=0.040]. There was a 28% reduction in the frequency of hospitalization for exacerbations of COPD during the year after starting LTOT. CONCLUSIONS: Mortality at one year with LTOT was about 25%. Factors predictive of mortality at one year included coronary insufficiency, reduction of the left ventricular ejection fraction and osteoporosis. LTOT seems to reduce hospitalizations due to exacerbations of COPD. [less ▲]

Detailed reference viewed: 30 (4 ULiège)
Full Text
Peer Reviewed
See detailHow resources determine pulmonary rehabilitation programs : a survey among Belgian chest physicians
Janssens, Wim; Corhay, Jean-Louis ULiege; Bogaerts, Peter et al

in Chronic Respiratory Disease (2018)

Despite overwhelming evidence of its benefits, a widespread implementation of pulmonary rehabilitation (PR) is lacking and the landscape of multidisciplinary programs remains very scattered. The objective ... [more ▼]

Despite overwhelming evidence of its benefits, a widespread implementation of pulmonary rehabilitation (PR) is lacking and the landscape of multidisciplinary programs remains very scattered. The objective of this study is to assess how PR is organized in specialized care centres in Belgium and to identify which barriers may exist according to respiratory physicians. A telephone and online survey was developed by a Belgian expert panel and distributed among all active Belgian chest physicians ( n = 492). Data were obtained from 200 respondents (40%). Seventy-five percentage of the chest physicians had direct access to an ambulatory rehabilitation program in their hospital. Most of these programs are organized bi or triweekly for an average period of 3-6 months. Programs focus strongly on chronic obstructive pulmonary disease patients from secondary care, have a multidisciplinary approach and provide exercise capacity and quality of life measures as main outcomes. Yet large differences were observed in process and outcome indicators between the programs of centres with standard funding and those of specialized centres with a larger allocated budget. We conclude that multidisciplinary PR programs are available in the majority of Belgian hospitals. Differences in funding determine the quality of the team, the diversity of the interventions and the monitoring of outcomes. More resources for rehabilitation will directly improve the utilization and quality of this essential treatment option in respiratory diseases. [less ▲]

Detailed reference viewed: 42 (1 ULiège)
Full Text
Peer Reviewed
See detailLe concept d'exacerbation dans l'asthme et la BPCO : enquête sur les critères de prescription de corticoïdes systémiques et d'antibiotiques chez les généralistes et les pneumologues
Louis, Renaud ULiege; ZIANT, Stéphanie ULiege; Duchesnes, Christiane ULiege et al

in Revue Médicale de Liège (2018), 73(11), 570-574

Exacerbations in asthma and chronic obstructive pulmonary disease (COPD) are critical events in the evolution of the disease. They are generally defined by the need to be temporarily treated by systemic ... [more ▼]

Exacerbations in asthma and chronic obstructive pulmonary disease (COPD) are critical events in the evolution of the disease. They are generally defined by the need to be temporarily treated by systemic corticoids and/or antibiotics. Very few studies have examined the criteria on which clinicians including general practitioners (GP) and chest physicians are basing their decision to prescribe. Here we report the results of a survey conducted in GP and chest physicians that looked at the clinical criteria judged as important to initiate a course of systemic corticoids or antibiotics in asthma and COPD. Our finding show discrepancy between GP and chest physicians regarding systemic corticoids but also, more surprisingly, within the same professional group. In contrast, criteria to prescribe antibiotics are more coherent between and within the groups. [less ▲]

Detailed reference viewed: 44 (7 ULiège)
Full Text
Peer Reviewed
See detailLe medicament du mois Trimbow(R) ou triple association bronchodilatatrice et anti-inflammatoire en aérosol dans la broncho-pneumopathie chronique obstructive
Corhay, Jean-Louis ULiege; BONHOMME, Olivier ULiege; GUIOT, Julien ULiege

in Revue Médicale de Liège (2018), 73(9), 480-484

Single-inhaler triple therapy in extrafine solution combining an inhaled corticosteroid (ICS), the dipropionate of beclometasone, a long acting ss2-agonist (LABA), the fumarate of formoterol and an long ... [more ▼]

Single-inhaler triple therapy in extrafine solution combining an inhaled corticosteroid (ICS), the dipropionate of beclometasone, a long acting ss2-agonist (LABA), the fumarate of formoterol and an long-acting muscarinic antagonist (LAMA), the bromide of glycopyrronium, was developed for the treatment of the chronic obstructive pulmonary disease (COPD). Trimbow(R) is the first triple therapy in spray with fixed dose and containing 3 pharmacological agents (LABA-LAMA-ICS). Clinical trials show that Trimbow(R) improves numerous parameters such as the respiratory function, the quality of life, the symptoms and the rate of moderate to severe exacerbations while being tolerated well. These results justify its use in severe and very severe COPD with exacerbations in spite of treatment by LABA-LAMA or LABA-ICS. In this article, we present a brief synthesis of the main recent clinical trials on Trimbow(R), its comparison with other pharmacological agents/associations regularly used in the treatment of COPD, as well as some practical information on its use in routine. [less ▲]

Detailed reference viewed: 55 (1 ULiège)
Full Text
Peer Reviewed
See detailSputum exosomes: promising biomarkers for idiopathic pulmonary fibrosis.
Njock, Makon-Sébastien ULiege; GUIOT, Julien ULiege; HENKET, Monique ULiege et al

in Thorax (2018)

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology which leads rapidly to death. As diagnosis of IPF is complex, we aimed to characterise ... [more ▼]

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology which leads rapidly to death. As diagnosis of IPF is complex, we aimed to characterise microRNA (miRNA) content of exosomes from sputum of patients with IPF. Using miRNA quantitative PCR array, we found a substantial dysregulation of sputum exosomal miRNA levels between patients with IPF and healthy subjects and identified a unique signature of three miRNAs. Interestingly, we found a negative correlation between miR-142-3p and diffusing capacity of the lungs for carbon monoxide/alveolar volume. This is the first characterisation of miRNA content of sputum-derived exosomes in IPF that identified promising biomarkers for diagnosis and disease severity. [less ▲]

Detailed reference viewed: 117 (15 ULiège)
Full Text
Peer Reviewed
See detailComment j'explore... Techniques diagnostiques invasives des pneumopathies interstitielles diffuses
DUYSINX, Bernard ULiege; GUIOT, Julien ULiege; PELLEGRINI, Ivan ULiege et al

in Revue Médicale de Liège (2018), 73(3), 147-155

Interstitial lung diseases represent a very heterogeneous group of diseases mainly affecting connective lung tissue even if alveolar space may sometimes be involved. The identification of their etiology ... [more ▼]

Interstitial lung diseases represent a very heterogeneous group of diseases mainly affecting connective lung tissue even if alveolar space may sometimes be involved. The identification of their etiology is the key stage in their management. It requires the integration of anamnestic, clinical, biological, radiological data and, sometimes relies on, cytology or histology. In this review, we assess the contribution and feasibility of the different invasive techniques used for interstitial lung disease diagnosis. In particular we focus on the yield of lung endoscopy in casting light on the multidisciplinary confrontation, which is the gold standard of the interstitial lung disease care management. [less ▲]

Detailed reference viewed: 98 (8 ULiège)
Full Text
Peer Reviewed
See detailMethodology for Sputum Induction and Laboratory Processing.
GUIOT, Julien ULiege; Demarche, Sophie ULiege; HENKET, Monique ULiege et al

in Journal of Visualized Experiments (2017), (130),

The technique of sputum induction and processing is a recognized non-invasive method allowing the collection and analysis of cells from the airways, which is interesting in various respiratory diseases ... [more ▼]

The technique of sputum induction and processing is a recognized non-invasive method allowing the collection and analysis of cells from the airways, which is interesting in various respiratory diseases like asthma, chronic obstructive pulmonary disease (COPD), chronic cough, or idiopathic pulmonary fibrosis. This technique is well tolerated, safe and non-invasive, but is currently limited to research services and specialized centers in clinical practice because it is technically demanding, time-consuming, and requires trained staff. The success rate of sputum induction and analysis is about 80%. Here, we describe the induction and laboratory processing of sputum samples. Sputum is induced by inhalation of hypertonic or isotonic saline with salbutamol. For the processing, we use the whole sputum technique. Dithiothreitol (DTT) is used to allow mucolysis of sputum samples. The primary aim of sputum processing is to obtain a differential cell count to study the cell types present in the airway lumen. Additional analyses may also be performed on sputum supernatant and sputum cells, which may allow further investigation into inflammatory processes and immune mechanisms. Examples include studying mediators in sputum supernatant and performing a large spectrum of analysis on sputum cells such as flow cytometry, genomics, or proteomics. Finally, representative results of sputum analysis in healthy controls, asthmatics, and COPD patients are presented. [less ▲]

Detailed reference viewed: 76 (31 ULiège)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 57 (11 ULiège)
Full Text
Peer Reviewed
See detailClinical experience in idiopathic pulmonary fibrosis: a retrospective study
GUIOT, Julien ULiege; CORHAY, Jean-Louis ULiege; LOUIS, Renaud ULiege et al

in Acta Clinica Belgica (2017)

Introduction Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with an increased incidence since the last few years. Here, we report our eight-year clinical experience in CHU of Liège, Belgium ... [more ▼]

Introduction Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with an increased incidence since the last few years. Here, we report our eight-year clinical experience in CHU of Liège, Belgium. Methods We have studied retrospectively patients recruited from our ambulatory care polyclinic at CHU of Liège from 1 January 2009 to 1 January 2017. We have excluded all patients treated with a specific anti-fibrotic therapy due to incomplete follow-up. The diagnosis of IPF was made according to the ATS/ERS international recommendations (2015). Results Out of the 114 patients initially selected, 82 cases were found to be suitable for the analysis. The average age was 71.1 ± 9.35 years with a male predominance. The median survival was 43.7 months (23.6–71.7) with a majority (45%) of patients in the group II of the GAP index. The median rate of annual decline in diffusion capacity of CO (DLCO) was 11%, whereas the sub analysis for group III (according to GAP index) showed a decrease annual rate of 30%. Conclusion Our results are in keeping with the literature. One of our major finding is that patients in GAP III exhibit an annual rate of mortality of 42% and a median annual decline in DLCO of 30%. This observation highlights the fact that this specific subgroup of patients presents a high risk of morbi-mortality. [less ▲]

Detailed reference viewed: 115 (10 ULiège)
Full Text
Peer Reviewed
See detailIncreased production of TGF-β1 from sputum cells of COPD: Relationship with airway obstruction
Godinas, L.; Corhay, Jean-Louis ULiege; HENKET, Monique ULiege et al

in Cytokine (2017), 99

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by a profound airway remodelling that leads to airway obstruction. A role for transforming growth factor-β1 (TGF-β1 ... [more ▼]

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by a profound airway remodelling that leads to airway obstruction. A role for transforming growth factor-β1 (TGF-β1) has been proposed in airway remodelling of COPD. Regarding the TGF-β1 production at local level, the results seemed to be controversial. In this study, an original model of sputum cell culture thought to maintain important cells interactions, was used. We investigated the production of TGF-β1 from sputum cell culture in 33 COPD encompassing the whole severity spectrum and compared the results with those found in 39 healthy controls. Sputum was induced by inhalation of saline, the cellular fraction cultured for 24 h and the spontaneous production of total TGF-β1 was assessed by ELISA. Using, a TGF-β1 reporter cell assay, we also compared the levels of active and total TGF-β1 in the sputum cell culture supernatants of COPD and controls. Moreover, as a combination of tumor necrosis factor-α (TNF-α) and TGF-β1 have been shown to have a cumulative impact on the severity of airflow limitation in COPD, the TNF-α release was also measured in a representative subgroup of patients. Our results indicated that the use of sputum cell culture was a reliable and reproducible method to assess TGF-β1 production at airway level. Sputum cells from COPD produced greater amount of total TGF-β1 than those of healthy controls (p < 0.001). This result was confirmed using the cell reporter assay which also showed a higher level of active TGF-β1 in the COPD group compared to controls. In addition, total TGF-β1 production was increased according to GOLD stage and was inversely related to FEV1/FVC ratio (p < 0.05). By contrast, the production of this growth factor was not correlated with the functional markers of emphysema nor with demographic characteristics such as age, BMI or smoking status. Interestingly, the production of total TGF-β1 was inversely related to that of TNF-α (r = −0.53, p < 0.05) which was decreased in COPD. In summary, COPD patients displayed a raised production of total and active TGF-β1 from their airway cells. Total TGF-β1 correlates with the severity of airway obstruction without evidence of a link with emphysema.. © 2017 Elsevier Ltd [less ▲]

Detailed reference viewed: 65 (4 ULiège)
Full Text
Peer Reviewed
See detailComment je traite ⋯ une fibrose pulmonaire idiopathique
GUIOT, Julien ULiege; Duysinx, Bernard ULiege; BONHOMME, Olivier ULiege et al

in Revue Médicale de Liège (2017), 72(9), 381-383

Idiopathic pulmonary fibrosis (IPF) is a rare disorder of unknown origin, which is associated with a high mortality and whose incidence has been increasing for several years. Nowadays there are two anti ... [more ▼]

Idiopathic pulmonary fibrosis (IPF) is a rare disorder of unknown origin, which is associated with a high mortality and whose incidence has been increasing for several years. Nowadays there are two anti-fibrotic therapies (pirfenidone - nintedanib) known to reduce significantly the decline in respiratory function tests of patients suffering from this condition. The only curative therapeutic option remains the pulmonary transplantation whose accessibility remains limited. Pulmonary rehabilitation is also central in the treatment of patients. A major challenge for patients remains early and aggressive management to reduce as early as possible the evolution towards severe pulmonary fibrosis. [less ▲]

Detailed reference viewed: 119 (15 ULiège)
Full Text
Peer Reviewed
See detailAltered epigenetic features in circulating nucleosomes in idiopathic pulmonary fibrosis.
GUIOT, Julien ULiege; Struman, Ingrid ULiege; CHAVEZ, Viviana ULiege et al

in Clinical Epigenetics (2017), 9

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disorder of unknown origin with a highly variable and unpredictable clinical course. Polymorphisms and environmentally induced ... [more ▼]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disorder of unknown origin with a highly variable and unpredictable clinical course. Polymorphisms and environmentally induced epigenetic variations seem to determine individual susceptibility to the development of lung fibrosis. METHODS: We have studied circulating epitopes on cell-free nucleosomes (cfnucleosomes) in 50 IPF patients. We have compared untreated IPF (n = 23) with IPF receiving antifibrotic therapy (n = 27) and healthy subjects (HS) (n = 27). We analyzed serum levels of five cfnucleosomes including bound HMGB1 (nucleosomes adducted to high-mobility growth protein B1), mH2A1.1 (nucleosomes containing the histone variant mH2A1.1), 5mC (nucleosomes associated with methylated DNA), and H3K9Ac and H3K27Ac (nucleosomes associated with histone H3 acetylated at lysine 9 or 27 residue). RESULTS: Our findings showed that serum levels of bound HMGB1, mH2A1.1, 5mC, H3K9Ac, and H3K27Ac were significantly lower in IPF patients than in HS (p < 0.001, p < 0.001, p < 0.01, p < 0.001, and p < 0.0001, respectively). Moreover, we found differences in epigenetic profiles between untreated IPF patients and those receiving anti-fibrotic therapy with mH2A1.1 and 5mC being significantly lower in untreated than in treated patients (p < 0.01 and p < 0.05, respectively). Combination of four cfnucleosomes (HMGB1, 5mC, H3K9Ac, and H3K27Ac) allow to discriminate IPF vs HS with a good coefficient of determination (R(2) = 0.681). The AUC for the ROC curve computed by this logistic regression was 0.93 (p < 0.001) with 91% sensitivity at 80% specificity. CONCLUSION: Our observations showed that cfnucleosomes (bound HMGB1, mH2A1.1, 5mC, H3K9Ac, and H3K27Ac) might have potential as biomarkers for diagnosis and treatment response. These results deserve further validation in longitudinal cohorts. [less ▲]

Detailed reference viewed: 33 (5 ULiège)
Full Text
Peer Reviewed
See detailBlood Biomarkers in Idiopathic Pulmonary Fibrosis.
GUIOT, Julien ULiege; Moermans, Catherine ULiege; 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 ▲]

Detailed reference viewed: 123 (14 ULiège)
Full Text
Peer Reviewed
See detailInhaled treatment of COPD : a Delphi consensus statement.
Ninane, Vincent; Corhay, Jean-Louis ULiege; Germonpre, Paul et al

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

BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy (2015) provides guidance for the treatment of chronic obstructive pulmonary disease (COPD) with different first ... [more ▼]

BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy (2015) provides guidance for the treatment of chronic obstructive pulmonary disease (COPD) with different first-choice options per GOLD category without specification. OBJECTIVES: To evaluate the level of medical experts' consensus on their preferred first-choice treatment within different COPD categories. METHODS: A two-round Delphi Panel consisting of 15 questions was completed by Belgian pulmonologists (n=31) and European (n=10) COPD experts. RESULTS: Good consensus was reached by both expert groups for long-acting bronchodilators instead of short-acting bronchodilators as first-choice treatment in GOLD A. Single bronchodilation with long-acting muscarinic antagonist (LAMA) was preferred over long-acting beta2-agonist (LABA) and LABA/LAMA as first-choice treatment in GOLD B and GOLD C. For GOLD D patients based on the forced expiratory volume in 1 second (FEV1)<50%, a very good consensus was reached for LAMA/LABA as first-choice treatment. For GOLD D patients based on frequent or severe exacerbations, there was a good consensus for LABA/LAMA/inhaled corticosteroids (ICS) as first choice in the Belgian group. According to the European experts, both LABA/LAMA and LABA/LAMA/ICS could be the first choice for these patients. CONCLUSION: Belgian and European experts recommend long-acting bronchodilators as first-choice treatment. Treatment containing ICS was found only appropriate in patients with FEV1<50% and >/=2 moderate exacerbations or 1 severe exacerbation/year. [less ▲]

Detailed reference viewed: 26 (2 ULiège)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 86 (11 ULiège)
Full Text
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

Detailed reference viewed: 283 (10 ULiège)