Systemic biomarkers of collagen and elastin turnover are associated with clinically relevant outcomes in COPD.
; ; 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 ▲]Detailed reference viewed: 14 (1 ULg)
Lung resident eosinophils represent a distinct cell subset with homeostatic functions
Mesnil, Claire ; Raulier, Stéfanie ; et al
Conference (2016, October 21)Detailed reference viewed: 34 (5 ULg)
Raised interferon beta, type 3 interferon and interferon stimulated genes - evidence of innate immune activation in neutrophilic asthma.
; Hilzendeger, Clarissa ; 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 ▲]Detailed reference viewed: 15 (3 ULg)
Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).
; ; 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 ▲]Detailed reference viewed: 14 (4 ULg)
Therapy with proton-pump inhibitors for gastroesophageal reflux disease does not reduce the risk for severe exacerbations in COPD.
; ; et al
in Respirology (Carlton, Vic.) (2016), 21(5), 883-90
BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with ... [more ▼]
BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable COPD. METHODS: A total of 638 patients with stable COPD for >/=6 weeks, >/=10 pack-years of smoking and Global Initiative for Chronic Obstructive Lung Disease II-IV seeking care in tertiary hospitals in eight European countries in the Predicting Outcome using Systemic Markers in Severe Exacerbations-COPD cohort was prospectively evaluated by us. Comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. Median observation time was 24 months. The primary study outcomes were exacerbation and/or death. RESULTS: A total of 85 (13.3%) of COPD patients were on anti-GERD therapy. These patients had higher annual and higher severe exacerbation rates (P = 0.009 and P = 0.002), decreased quality of life (SF-36: activity score P = 0.004, St. George's Respiratory Questionnaire: physical functioning P = 0.013 and social functioning P = 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (P = 0.033) and Modified Medical Research Council scores (P = 0.002), shorter 6-min walking distance (P = 0.0004) and a higher adjusted Charlson score (P < 0.0001). Anti-GERD therapy was associated with a shorter time to severe exacerbation (HR 2.05 95% CI 1.37-3.08). Using three multivariable Cox-regression models, this association was independent of the following: (i) adjusted Charlson score and FEV1% predicted (HR 1.91 95% CI 1.26-2.90); (ii) adjusted Charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and Modified Medical Research Council (HR 1.62 95% CI 1.04-2.54); and (iii) adjusted Charlson score, FEV1% predicted and nine classes of medication for comorbidities (HR 1.63 95% CI 1.04-2.53). CONCLUSION: These findings suggest that patients with stable COPD receiving acid-suppressive therapy with proton pump inhibitors remain at high risk of frequent and severe exacerbations. [less ▲]Detailed reference viewed: 19 (1 ULg)
IgE mediated sensitisation to aeroallergens in an asthmatic cohort: relationship with inflammatory phenotypes and disease severity.
Manise, Maïté ; ; SCHLEICH, FLorence 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 ▲]Detailed reference viewed: 15 (4 ULg)
Reduced sputum expression of interferon-stimulated genes in severe COPD.
Hilzendeger, Clarissa ; ; HENKET, Monique et al
in International Journal of Chronic Obstructive Pulmonary Disease (2016), 11
BACKGROUND: Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients. METHODS: Induced ... [more ▼]
BACKGROUND: Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections. The purpose of our study was to investigate innate immunity in stable COPD patients. METHODS: Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects. Expression of interferons beta (IFN-beta) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology. RESULTS: Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-beta was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%). ISGs were easily detectable in both groups. In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects. No difference was found with respect to MxA. COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients. Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts. IFN-beta expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs. CONCLUSION: ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. [less ▲]Detailed reference viewed: 18 (3 ULg)
Prognostic assessment in COPD without lung function: the B-AE-D indices.
; ; et al
in The European respiratory journal (2016), 47(6), 1635-44
Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our ... [more ▼]
Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function.The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05). Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively). External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk. [less ▲]Detailed reference viewed: 15 (1 ULg)
Investigation of the possible effect of sampling on human exhaled breath sample integrity
Pesesse, Romain ; Stefanuto, Pierre-Hugues ; SCHLEICH, FLorence et al
Poster (2016, May 30)Detailed reference viewed: 46 (3 ULg)
Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis.
GUIOT, Julien ; ; HENKET, Monique et al
in BMC pulmonary medicine (2016), 16(1), 86
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder of unknown origin, which ultimately leads to death. Several growth factors such as IGFs (insulin-like-growth factor) and IGFBPs ... [more ▼]
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder of unknown origin, which ultimately leads to death. Several growth factors such as IGFs (insulin-like-growth factor) and IGFBPs (insulin like growth factor binding proteins) seem to take part to the pathogenesis. We evaluated IGFs and IGFBPs in serum from patients with IPF and healthy subjects including 24 untreated IPF and 26 IPF receiving anti-fibrotic therapy and to compare them with healthy subjects. METHODS: Serum of 50 idiopathic pulmonary fibrosis and 55 healthy subjects (HS) were analysed by ELISA for IGFs and IGFBPs, TGF-beta and KL-6, the latter being tested as positive control in IPF. RESULTS: Serum levels of IGFBP-1 and IGFBP-2 and KL-6 were significantly higher in the IPF group than in the healthy subjects (p < 0.05, p < 0.001 and p < 0.0001 respectively) while the picture was inversed regarding IGFs. By contrast there was no significant difference between the groups with respect to TGF-beta. IGFBP-2 was significantly reduced in the patients with specific anti-fibrotic therapy pirfenidone and nintedanib compared to untreated patients (p < 0.05) but still significantly elevated in comparison to HS (p < 0.001). CONCLUSION: Serum IGFBP-1 and -2 are increased in idiopathic pulmonary fibrosis and IGFBP-2 may be reduced by anti-fibrosing therapy. IGFBPs may be promising biomarkers in IPF. [less ▲]Detailed reference viewed: 46 (3 ULg)
Asthma inflammatory phenotypes show differential microRNA expression in sputum.
; ; SCHLEICH, FLorence et al
in The Journal of allergy and clinical immunology (2016), 137(5), 1433-46
BACKGROUND: Asthma is classified according to severity and inflammatory phenotype and is likely to be distinguished by specific microRNA (miRNA) expression profiles. OBJECTIVE: We sought to associate ... [more ▼]
BACKGROUND: Asthma is classified according to severity and inflammatory phenotype and is likely to be distinguished by specific microRNA (miRNA) expression profiles. OBJECTIVE: We sought to associate miRNA expression in sputum supernatants with the inflammatory cell profile and disease severity in asthmatic patients. METHODS: We investigated miRNA expression in sputum supernatants of 10 healthy subjects, 17 patients with mild-to-moderate asthma, and 9 patients with severe asthma using high-throughput, stem-loop, reverse transcriptase quantitative real-time PCR miRNA expression profiling (screening cohort, n = 36). Differentially expressed miRNAs were validated in an independent cohort (n = 60; 10 healthy subjects and 50 asthmatic patients). Cellular miRNA origin was examined by using in situ hybridization and reverse transcriptase quantitative real-time PCR. The functional role of miRNAs was assessed by using in silico analysis and in vitro transfecting miRNA mimics in human bronchial epithelial cells. RESULTS: In 2 independent cohorts expression of miR-629-3p, miR-223-3p, and miR-142-3p was significantly upregulated in sputum of patients with severe asthma compared with that in healthy control subjects and was highest in patients with neutrophilic asthma. Expression of the 3 miRNAs was associated with sputum neutrophilia, and miR-223-3p and miR-142-3p expression was associated also with airway obstruction (FEV1/forced vital capacity). Expression of miR-629-3p was localized in the bronchial epithelium, whereas miR-223-3p and miR-142-3p were expressed in neutrophils, monocytes, and macrophages. Transfecting human bronchial epithelial cells with miR-629-3p mimic induced epithelial IL-8 mRNA and protein expression. IL-1beta and IL-8 protein levels were significantly increased in sputum of patients with severe asthma and were positively associated with sputum neutrophilia. CONCLUSIONS: Expression of miR-223-3p, miR-142-3p, and miR-629-3p is increased in sputum of patients with severe asthma and is linked to neutrophilic airway inflammation, suggesting that these miRNAs contribute to this asthma inflammatory phenotype. [less ▲]Detailed reference viewed: 29 (6 ULg)
Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD.
SCHLEICH, FLorence ; CORHAY, Jean-Louis ; LOUIS, Renaud
in The European respiratory journal (2016), 47(5), 1562-4
No abstract available.Detailed reference viewed: 12 (1 ULg)
Detailed analysis of sputum and systemic inflammation in asthma phenotypes: are paucigranulocytic asthmatics really non-inflammatory?
Demarche, Sophie ; SCHLEICH, FLorence ; HENKET, Monique et al
in BMC Pulmonary Medicine (2016), 16
BACKGROUND: The technique of induced sputum has allowed to subdivide asthma patients into inflammatory phenotypes according to their level of granulocyte airway infiltration. There are very few studies ... [more ▼]
BACKGROUND: The technique of induced sputum has allowed to subdivide asthma patients into inflammatory phenotypes according to their level of granulocyte airway infiltration. There are very few studies which looked at detailed sputum and blood cell counts in a large cohort of asthmatics divided into inflammatory phenotypes. The purpose of this study was to analyze sputum cell counts, blood leukocytes and systemic inflammatory markers in these phenotypes, and investigate how those groups compared with healthy subjects. METHODS: We conducted a retrospective cross-sectional study on 833 asthmatics recruited from the University Asthma Clinic of Liege and compared them with 194 healthy subjects. Asthmatics were classified into inflammatory phenotypes. RESULTS: The total non-squamous cell count per gram of sputum was greater in mixed granulocytic and neutrophilic phenotypes as compared to eosinophilic, paucigranulocytic asthma and healthy subjects (p < 0.005). Sputum eosinophils (in absolute values and percentages) were increased in all asthma phenotypes including paucigranulocytic asthma, compared to healthy subjects (p < 0.005). Eosinophilic asthma showed higher absolute sputum neutrophil and lymphocyte counts than healthy subjects (p < 0.005), while neutrophilic asthmatics had a particularly low number of sputum macrophages and epithelial cells. All asthma phenotypes showed an increased blood leukocyte count compared to healthy subjects (p < 0.005), with paucigranulocytic asthmatics having also increased absolute blood eosinophils compared to healthy subjects (p < 0.005). Neutrophilic asthma had raised CRP and fibrinogen while eosinophilic asthma only showed raised fibrinogen compared to healthy subjects (p < 0.005). CONCLUSIONS: This study demonstrates that a significant eosinophilic inflammation is present across all categories of asthma, and that paucigranulocytic asthma may be seen as a low grade inflammatory disease. [less ▲]Detailed reference viewed: 30 (10 ULg)
AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from concept to implementation.
; ; et al
in European Respiratory Journal (2016), 47(4), 1028-33
Chronic respiratory diseases (CRDs) are major non-communicable diseases (NCDs) that induce a significant burden. Asthma often occurs along the life cycle from early childhood, affecting 30 million ... [more ▼]
Chronic respiratory diseases (CRDs) are major non-communicable diseases (NCDs) that induce a significant burden. Asthma often occurs along the life cycle from early childhood, affecting 30 million children and adults under 45 years of age in Europe. Chronic obstructive pulmonary disease (COPD) has an estimated annual death rate of over 3 million people globally. The annual direct and indirect costs in the 28 European Union (EU) countries due to COPD or asthma are estimated at 48 billion euros and 34 billion euros respectively. Rhinitis occurs in over 100 million people in Europe, and indirect costs are enormous. Asthma is a common risk factor for COPD. CRDs impact ageing and should be prevented, recognised and managed across the life cycle to promote active and healthy ageing (AHA). There is an urgent need to act globally. European Innovation Partnerships (EIPs) aim to enhance EU competitiveness and tackle societal challenges through research and innovation. To tackle the potential of ageing in the EU, the European Commission, within its Innovation Union policy, launched the EIP on AHA (between the Directorate General for Health and Food Safety (DG Santé) and Directorate General for Communications Networks, Content and Technology (DG CONNECT)). The B3 Action Plan promotes integrated care models for chronic diseases, including the use of remote monitoring. The initiative AIRWAYS-ICPs (integrated care pathways for airway diseases) has been approved by the EIP on AHA as the model of chronic diseases of the B3 Action Plan. It is a Research Demonstration Project of the World Health Organization's Global Alliance against Chronic Respiratory Diseases (GARD). AIRWAYS-ICPs was initiated in 2013 by the WHO Collaborating Centre of Montpellier and the EIP on AHA Reference Site MACVIA-LR (Contre les MAladies Chroniques Pour un Vieillissement Actif en Languedoc-Roussillon, France) led by the Région Languedoc-Roussillon (France). [less ▲]Detailed reference viewed: 21 (1 ULg)
LE CAS CLINIQUE DU MOIS. Granulomatose sarcoidose-like chez les patients traites par anti-TNFalpha.
; ; Louis, Renaud et al
in Revue Médicale de Liège (2016), 71(3), 124-8
Over recent years, anti-TNFalpha have been used to treat rheumatoid arthritis. The principal secondary effect of anti-TNFalpha is tuberculosis infections. Another paradoxical effect, previously less well ... [more ▼]
Over recent years, anti-TNFalpha have been used to treat rheumatoid arthritis. The principal secondary effect of anti-TNFalpha is tuberculosis infections. Another paradoxical effect, previously less well understood, is the development of sarcoid-like granulomatous reactions. We report the case of a 36 year old woman who had been treated for 9 years with anti-TNF alpha. She developed a pulmonary sarcoid-like gra-nulomatosis, complication that is rare but not exceptional in patients treated with TNF-blockers. Discontinuation of anti TNF usually led to recovery. It has been suggested that these reactions mainly occur with etanercept, but this requires further confirmation. [less ▲]Detailed reference viewed: 49 (10 ULg)
From Valeriana officinalis to cancer therapy: the success of a bio-sourced compound
Hamaïdia, Malik ; Barez, Pierre-Yves ; Carpentier, Alexandre et al
in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment (2016), 20
Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story ... [more ▼]
Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story of one of these compounds, 2-propylpentanoic acid, derived from the Valeriana officinalis flowering plant and its path to validation as a cancer treatment. [less ▲]Detailed reference viewed: 187 (53 ULg)
Volatile organic compounds discriminate between eosinophilic and neutrophilic inflammation in vitro.
SCHLEICH, FLorence ; ; HENKET, Monique et al
in Journal of breath research (2016), 10(1), 016006
Inflammation associated oxidative stress leads to peroxidation of polyunsaturated fatty acids thereby generating volatile organic compounds (VOCs). The integrative analysis of the total amount of VOCs ... [more ▼]
Inflammation associated oxidative stress leads to peroxidation of polyunsaturated fatty acids thereby generating volatile organic compounds (VOCs). The integrative analysis of the total amount of VOCs released by eosinophils and neutrophils in vitro enables the search for those compounds that discriminates between various inflammatory conditions. The approach comprises isolating eosinophils and neutrophils from 30 ml of blood of healthy non-smoking volunteers by gradient centrifugation, using lymphoprep. Eosinophils are separated from neutrophils by immunomagnetic cell separation using anti-CD16. Cells are activated with phorbol 12-myristate 13-acetate and VOCs from the headspace are collected at time 0', 30', 60' and 90' by introduction of ultra-pure nitrogen in the closed flasks at a flow rate of 200 ml min(-1) during 10 min. The gases are trapped onto a sorption tube and analyzed by gas chromatography-time-of-flight-mass spectometry (GC-TOF-MS) in order to identify VOCs released in the headspace by activated neutrophils and eosinophils. Eosinophils and neutrophils were isolated from 26 healthy non-smoking volunteers. The average absolute number of eosinophils and neutrophils upon isolation was 3.5 x 10(6) and 19.4 x 10(6), respectively. The volatome in headspace consisted of 2116 compounds and those compounds present in at least 8% of the samples (1123 compounds) were used for further discriminant analysis. Discriminant analysis showed that two VOCs were able to distinguish between eosinophilic and neutrophilic cultures in the unactivated state with 100% correct classification of the entire data set and upon cross validation while five VOCs were able to discriminate between activated eosinophils and neutrophils with 96% correct classification in the original set and upon cross-validation. Analysis of VOCs seems to be a very promising approach in identifying eosinophilic and neutrophilic inflammation but it needs further development and in vivo confirmation. [less ▲]Detailed reference viewed: 19 (1 ULg)
Yellow nail syndrome after allogeneic haematopoietic stem cell transplantation in two patients with multiple myeloma
Grégoire, Céline ; GUIOT, Julien ; Vertenoeil, Gaëlle et al
in Acta Clinica Belgica (2016), 6
Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have ... [more ▼]
Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have been reported, but a lot of patients probably elude proper diagnosis because of both variability of symptoms and ignorance of this syndrome by many physicians. The pathogenesis remains unclear, and could involve functional lymphatic abnormalities, microvasculopathy or lymphocyte deficiency, but none of these hypotheses seems fully satisfactory. Clinical Presentation: We report for the first time two cases of YNS associated with multiple myeloma relapsing after non-myeloablative haematopoietic cell transplantation (HCT). In these two cases, onset or worsening of YNS symptoms followed graft-versus-host disease (GvHD) manifestations. Intervention: Corticosteroids given to treat GvHD also improved YNS manifestations. Conclusion: YNS after HCT might be a microvascular manifestation of endothelial GvHD and corticosteroids might be an effective treatment. [less ▲]Detailed reference viewed: 31 (8 ULg)
Characterization of human exhaled breath for non-invasive detection of diseases by GC×GC-TOFMS
Pesesse, Romain ; Stefanuto, Pierre-Hugues ; SCHLEICH, FLorence et al
Conference (2016, January 28)Detailed reference viewed: 38 (6 ULg)