References of "SCHLEICH, FLorence"
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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 ULg; 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 detailIgE mediated sensitisation to aeroallergens in an asthmatic cohort: relationship with inflammatory phenotypes and disease severity.
Manise, Maïté ULg; Bakayoko, B.; SCHLEICH, FLorence ULg 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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See detailReduced sputum expression of interferon-stimulated genes in severe COPD.
Hilzendeger, Clarissa ULg; da Silva, Jane; HENKET, Monique ULg 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 ▲]

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See detailAsthma inflammatory phenotypes show differential microRNA expression in sputum.
Maes, Tania; Cobos, Francisco Avila; SCHLEICH, FLorence ULg 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 ▲]

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See detailBlood eosinophil count to predict bronchial eosinophilic inflammation in COPD.
SCHLEICH, FLorence ULg; CORHAY, Jean-Louis ULg; LOUIS, Renaud ULg

in The European respiratory journal (2016), 47(5), 1562-4

No abstract available.

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See detailDetailed analysis of sputum and systemic inflammation in asthma phenotypes: are paucigranulocytic asthmatics really non-inflammatory?
Demarche, Sophie ULg; SCHLEICH, FLorence ULg; HENKET, Monique ULg 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 ▲]

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See detailVolatile organic compounds discriminate between eosinophilic and neutrophilic inflammation in vitro.
SCHLEICH, FLorence ULg; Dallinga, Jan W.; HENKET, Monique ULg 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 ▲]

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See detailAsthma Control and Sputum Eosinophils: a Longitudinal Study in Daily Practice
Demarche, Sophie ULg; SCHLEICH, FLorence ULg; HENKET, Monique ULg et al

Scientific conference (2015, June 12)

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See detailClinically relevant subgroups in COPD and asthma.
Turner, Alice M.; Tamasi, Lilla; SCHLEICH, FLorence ULg et al

in European respiratory review : an official journal of the European Respiratory Society (2015), 24(136), 283-98

As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options ... [more ▼]

As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options for both diseases were limited; thus, there was less need to define subgroups. As treatment options have grown, so has our need to predict who will respond to new drugs. To date, identifying subgroups has been largely reported by detailed clinical characterisation or differences in pathobiology. These subgroups are commonly called "phenotypes"; however, the problem of defining what constitutes a phenotype, whether this should include comorbid diseases and how to handle changes over time has led to the term being used loosely. In this review, we describe subgroups of COPD and asthma patients whose clinical characteristics we believe have therapeutic or major prognostic implications specific to the lung, and whether these subgroups are constant over time. Finally, we will discuss whether the subgroups we describe are common to both asthma and COPD, and give some examples of how treatment might be tailored in patients where the subgroup is clear, but the label of asthma or COPD is not. [less ▲]

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See detailTraitement personnalisé dans l'asthme : le cas des anticorps monoclonaux dirigés contre l'interleukine-5.
LOUIS, Renaud ULg; Demarche, Sophie ULg; Van Hees, Thierry ULg et al

in Revue Médicale de Liège (2015), 70(5-6), 306-9

Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab ... [more ▼]

Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. When administered monthly by intravenous or subcutaneous injection in severe eosinophilic asthmatic patients, they reduce severe exacerbation rate by 50 %, improve asthma control and quality of life, and have an oral glucocorticoids sparing effect in those requiring oral corticoids as maintenance therapy. [less ▲]

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See detailEtude du phénotype mixte BPCO-asthme dans une série de patients BPCO en état stable
Nguyen, M.-S.; NGUYEN DANG, Delphine ULg; SCHLEICH, FLorence ULg et al

in Revue Médicale de Liège (2015), 70(1), 37-43

Résumé : Le but de ce travail était d’évaluer la prévalence et de décrire les caractéristiques du phénotype mixte BPCO-asthme parmi les patients BPCO stables de stade II à IV selon la classification de ... [more ▼]

Résumé : Le but de ce travail était d’évaluer la prévalence et de décrire les caractéristiques du phénotype mixte BPCO-asthme parmi les patients BPCO stables de stade II à IV selon la classification de GOLD. Matériel et méthodes : entre mai 2013 et avril 2014, 46 patients consécutifs furent recrutés à partir des consultations de Pneumologie du CHU de Liège. Ils étaient considérés comme présentant un syndrome mixte BPCO-asthme si leur indice de Tiffeneau était < 70% après bronchodilatation et s’accompagnait soit d’un antécédent d’asthme avant l’âge de 40 ans, soit d’au moins deux des trois critères suivants: 1) réversibilité bronchique significative (changement du VEMS après la bronchodilatation ≥ 200 ml et ≥ 12%), 2) inflammation éosinophilique: éosinophiles dans les expecto-rations ≥ 3% ou/et éosinophiles dans le sang ≥ 400/μl ou/et FENO ≥ 45 ppb, 3) histoire d’allergie respiratoire, ou IgE sériques totales ≥ 113 KU/l, ou RAST ≥ 0,35 KU/l à l’égard d’un des principaux aéroallergènes. Le phénotype mixte BPCO-asthme fut observé chez 37% des patients. L’expression symptomatique était plus marquée dans le groupe de phénotype mixte que dans le groupe de BPCO pure (CAT 24,6 ± 8,1 vs 19,4 ± 8, p < 0,05) en dépit d’un déficit spiro-métrique identique. Le coefficient de transfert alvéolo-capillaire (DLCO/VA%) était préservé dans le phénotype mixte (97 ± 24%) et supérieur à celui mesuré chez les patients BPCO pure (80 ± 20%) (p < 0,05). La prévalence du phéno-type mixte est voisine d’un tiers chez les patients BPCO et ces sujets ont une expression symptomatique plus marquée, sans signe d’obstruction bronchique plus sévère. [less ▲]

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See detailLes corticoïdes inhalés sont-ils suffisants pour traiter l'asthme? Perspective historique
LOUIS, Renaud ULg; Demarche, Sophie ULg; SCHLEICH, FLorence ULg

in Vaisseaux, Coeur, Poumons (2015), 20(4), 66-68

Cet article retrace l'évolution du traitement médicamenteux de l'asthme depuis l'avènement des corticoïdes inhalés à la fin des années 80. Une meilleure compréhension de la maladie, de ses différents ... [more ▼]

Cet article retrace l'évolution du traitement médicamenteux de l'asthme depuis l'avènement des corticoïdes inhalés à la fin des années 80. Une meilleure compréhension de la maladie, de ses différents phénotypes et des cytokins et médiateurs protéiques impliqués dans les différentes voies inflammatoires, a ouvert la porte à une prise en charge plus pointue de la maladie et plus particulièrement de ses formes sévères. A l'heure actuelle, le traitement des patients atteints d'asthme sévère requiert une caractérisation plus poussée de la maladie. [less ▲]

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See detailDiagnosis and clinical interest of asthma inflammatory phenotypes
SCHLEICH, FLorence ULg

Doctoral thesis (2014)

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