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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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See detailHeterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).
SCHLEICH, FLorence ULg; Brusselle, G.; Louis, Renaud ULg et al

in Respiratory medicine (2014), 108(12), 1723-32

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its ... [more ▼]

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. METHODS: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. RESULTS: Mean age was 55 +/- 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (>/=40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm(3). The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO >/= 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos >/= 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu >/= 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. CONCLUSION: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies. [less ▲]

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See detailThermoplastie bronchique : une réelle avancée dans le traitement de l'asthme
HEINEN, Vincent ULg; SCHLEICH, FLorence ULg; DUYSINX, Bernard ULg et al

in Revue Médicale Suisse (2014), 10(439), 1544-1548

New treatments are needed to improve the care of severe asthmatic patients. Bronchial thermoplasty aims to lessen the airway smooth muscles via the heating of bronchial walls by radiofrequency. The ... [more ▼]

New treatments are needed to improve the care of severe asthmatic patients. Bronchial thermoplasty aims to lessen the airway smooth muscles via the heating of bronchial walls by radiofrequency. The preliminary studies showed a good tolerance and some good efficacy. Randomized controlled trials have been undertaken on moderate to severe asthmatic patients, demonstrating an improvement in quality of life, rate of severe exacerbations and unscheduled medical visits. The main side-effects consist of asthma exacerbations, atelectasis and infections. Bronchial thermoplasty is an innovative treatment with good efficacy and acceptable tolerance for moderate to severe asthmatic patients. More studies are needed to better understand its mechanism of action and more clearly delineate the precise indications of this innovative technique. [less ▲]

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See detailPhenotypes de la broncho-pneumopathie chronique obstructive.
Corhay, Jean-Louis ULg; SCHLEICH, FLorence ULg; Louis, Renaud ULg

in Revue medicale de Liege (2014), 69(7-8), 415-21

Chronic Obstructive Pulmonary Disease (COPD) is a multi-dimensional disorder with multiple phenotypes. The GOLD guidelines, used for the diagnosis, staging and treatment of COPD, do not fully reflect the ... [more ▼]

Chronic Obstructive Pulmonary Disease (COPD) is a multi-dimensional disorder with multiple phenotypes. The GOLD guidelines, used for the diagnosis, staging and treatment of COPD, do not fully reflect the heterogeneous nature of the disease. Historically, the two most recognized clinical phenotypes of COPD are emphysema and chronic bronchitis. Most COPD patients encountered in practice actually share, both of these features. Genetic background, clinical presentation, variation in the response to treatment and propensity to exacerbations may also identify other phenotypes. Recently, using a mathematical approach, such as cluster analysis, which is based on pre-selected parameters, other interesting phenotypes were identified. A precise definition of COPD phenotypes should lead to a more targeted therapeutic approach based on these phenotypes. The purpose of this article is to point out that COPD is a heterogeneous disease and to summarize the current data available about the phenotypes of this disease. [less ▲]

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See detailImportance of concomitant local and systemic eosinophilia in uncontrolled asthma - Letter from the authors to editor
SCHLEICH, FLorence ULg; LOUIS, Renaud ULg

in The European respiratory journal (2014), 44(4), 1098-9

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