When sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic questions the role of eosinophils in mediating the clinical expression of the disease: a case report.

BACKGROUND: The advent of biologics has resulted in major progress in the treatment of severe T2 high asthmatics. There are currently several classes of biologics approved for severe asthma including anti-immunoglobulin E, anti-interleukin-5/interleukin 5R, anti-interleukin 4/interleukin 13R, and anti-thymic stromal lymphopoietin. CASE PRESENTATIONS: Here we report the case of a 55-year-old Caucasian man with severe eosinophilic atopic asthma, who sequentially benefited from a treatment with mepolizumab, an anti-interleukin-5 monoclonal antibody, followed by treatment with dupilumab, an anti-interleukin-4/interleukin-13R antibody, the switch being justified by a flare-up of dermatitis while on mepolizumab. Overall, the patient has been followed for 72 months, including 42 months on mepolizumab and 30 months on dupilumab. Close monitoring of exacerbations, asthma control, lung function, asthma quality of life, and biomarkers shows that both biologics reduced asthma exacerbation and provided an improvement in asthma control and quality of life, with the patient achieving remission after 30 months on dupilumab. However, the effects of the two biologics on the biomarkers were very different, with mepolizumab controlling eosinophilic inflammation and dupilumab reducing serum immunoglobulin E and fractional exhaled nitric oxide levels. CONCLUSION: The originality of this case resides in the description of clinical status and biomarker evolution after a sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic. It shows that mepolizumab reduces exacerbation and improves asthma control by curbing eosinophilic inflammation whereas dupilumab provides asthma remission without controlling airway eosinophilic inflammation.

[Probiotics in asthma treatment]. / Les probiotiques dans le traitement de l'asthme.

Asthma is the most prevalent chronic inflammatory airway disease worldwide. The gut microbiota possesses an important link with the development of the immunity in youth and a dysregulation of the gut flora was implicated in the asthmatic disease emergence. Moreover, a dysregulation of the intestinal microbiota exists in asthmatic individual. Probiotics are micro-organisms that can regulate our microbiome conferring potential beneficial effects on health. Thereby, their use in asthma prevention and treatment is attractive and could lead to new therapeutic perspectives. Indeed, they are well tolerated and safe and possess anti-inflammatory and immunoregulatory properties. This article is intended to update the current state of knowledge regarding the use of probiotics in the context of asthma.

: L'asthme est la maladie respiratoire chronique inflammatoire la plus prévalente dans le monde. Le microbiote intestinal est reconnu pour être intimement lié avec le développement de l'immunité dans le jeune âge et un dérèglement de cette flore intestinale a été impliqué dans l'apparition de la maladie asthmatique. De plus, une dérégulation du microbiote existe chez l'individu asthmatique. Les probiotiques sont des micro-organismes qui peuvent réguler notre microbiome, conférant un effet bénéfique potentiel sur la santé. De ce fait, leur utilisation dans la prévention et la prise en charge de l'asthme est attractive et pourrait ouvrir de nouvelles perspectives thérapeutiques. En effet, les probiotiques sont très bien tolérés et présentent une grande sécurité d'emploi, tout en possédant des propriétés anti-inflammatoires et immunorégulatrices. Cet article permet de faire le point sur l'état actuel des connaissances quant à leur utilisation dans le cadre de l'asthme.

[Asthma in clinical practice: from inflammatory phenotypes to personalized treatment]. / L'asthme bronchique en pratique clinique : des phénotypes inflammatoires au traitement personnalisé.

Asthma is a chronic inflammatory disease of the airways. Classification of asthma in different phenotypes has therapeutic implications and may lead to personalized medicine. Induced sputum is the gold standard for asthma phenotyping but is complex, time-consuming and not widely available. The combination of different biomarkers such as exhaled nitric oxide, blood eosinophils and total serum IgE levels allows the prediction of inflammatory phenotype in 58% of asthmatic patients when sputum is not available. We recently demonstrated the interest of measuring volatile organic compounds in exhaled breath to phenotype asthma. These compounds could play an important role in the future to predict the response to expensive biologicals available in severe asthma to reduce exacerbations and the use of systemic corticosteroids.

: L'asthme est une pathologie inflammatoire chronique des voies respiratoires. Classer l'asthme en différents phénotypes inflammatoires a des implications thérapeutiques importantes et peut conduire à un traitement personnalisé. Le gold standard pour l'établissement du phénotype inflammatoire est l'analyse de l'expectoration induite qui est une technique complexe, difficilement accessible en routine. La combinaison de plusieurs biomarqueurs d'intérêt tels le monoxyde d'azote dans l'air exhalé, l'éosinophilie systémique et le taux d'IgE sérique permet de prédire correctement le phénotype inflammatoire dans 58% des cas. Récemment, nous avons également mis en évidence l'intérêt de la détection de molécules dans l'haleine. Ces composés organiques volatiles pourraient représenter des biomarqueurs futurs de la réponse au traitement, spécialement dans l'asthme sévère, pour lequel des traitements ciblés coûteux sont actuellement disponibles en vue de réduire les exacerbations et le recours aux corticostéroïdes oraux.

[Fixed combination of mometasone, indacaterol, glycopyrronium for the treatment of severe asthma : Enerzair® Breezhaler®]. / Le médicament du mois. Combinaison fixe mométasone, indacatérol, glycopyrronium pour le traitement de l'asthme sévère : Enerzair® Breezhaler®.

Here we present pharmacological and clinical properties of a new fixed triple inhaled combination including an inhaled corticoid, a long acting ?2 agonist and a long acting anticholinergic for the treatment of severe asthma. Enerzair® is the name of this triple combination which contains 160 µg mometasone, 150 µg indacaterol and 50 µg glycopyrronium administered by a Breezhaler®. As compared to an ICS/LABA combination Enerzair® improves expiratory flow rates and reduces exacerbation rate. The Breezhaler® device may be coupled to a sensor (Propeller Health) that, through a bluetooth system, allows to control patient adherence and provides recall to the patient to take his aerosol.

Nous présentons, dans cet article, les propriétés pharmacologiques et les effets cliniques d'une nouvelle triple combinaison fixe inhalée comprenant un corticoïde inhalé, un ?2 mimétique à longue durée d'action et un anticholinergique à longue durée d'action destinée au traitement de l'asthme sévère. Cette combinaison qui porte le nom d'Enerzair® regroupe dans le même dispositif (le Breezhaler®) 160 µg de mométasone, 150 µg d'indacatérol et 50 µg de glycopyrronium. Par rapport à une combinaison corticoïde inhalé et ?2 mimétique, l'Enerzair® améliore la valeur des débits expiratoires et réduit la fréquence des exacerbations. Le dispositif peut être couplé à un capteur (Propeller Health) qui, par un système bluetooth, offre la possibilité de surveiller l'adhérence au traitement et fournit un rappel de prise au patient.

Sputum IL-25, IL-33 and TSLP, IL-23 and IL-36 in airway obstructive diseases. Reduced levels of IL-36 in eosinophilic phenotype.

INTRODUCTION: Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a role in airway remodeling in chronic airway obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD). IL-23 and IL-36 were shown to mediate the neutrophilic airway inflammation as seen in chronic airway obstructive diseases. OBJECTIVES: The purpose of this project was to determine the expression and the production of these cytokines from induced sputum (IS) in patients with chronic airway obstructive diseases including asthmatics and COPD. The relationship of the mediators with sputum inflammatory cellular profile and the severity of airway obstruction was assessed. METHODS: The alarmins (IL-25, IL-33 and TSLP) as well as IL-23 and IL-36 concentrations were measured in IS from 24 asthmatics and 20 COPD patients compared to 25 healthy volunteers. The cytokines were assessed by ELISA in the IS supernatant and by RT-qPCR in the IS cells. RESULTS: At protein level, no difference was observed between controls and patients suffering from airway obstructive diseases regarding the different mediators. IL-36 protein level was negatively correlated with sputum eosinophil and appeared significantly decreased in patients with an eosinophilic airway inflammation compared to those with a neutrophilic profile and controls. At gene level, only IL-36, IL-23 and TSLP were measurable but none differed between controls and patients with airway obstructive diseases. IL-36 and IL-23 were significantly increased in patients with an neutrophilic inflammatory profile compared to those with an eosinophilic inflammation and were correlated with sputum neutrophil proportions. None of the mediators were linked to airway obstruction. CONCLUSIONS: The main finding of our study is that patients with eosinophilic airway inflammation exhibited a reduced IL-36 level which could make them more susceptible to airway infections as IL-36 is implicated in antimicrobial defense. This study showed also an implication of IL-36 and IL-23 in airway neutrophilic inflammation in chronic airway obstructive diseases.

Asthma in elderly is characterized by increased sputum neutrophils, lower airway caliber variability and air trapping.

BACKGROUND: Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients. METHODS: We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study. RESULTS: Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration. CONCLUSION: Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.

Asthmatics with concordant eosinophilic disease classified according to their serum IgE status.

BACKGROUND: Eosinophilic inflammation has long been associated with asthma. Looking at systemic and airway eosinophilia, we have recently identified a group of patients exhibiting diffuse eosinophilic inflammation. Among the mechanisms governing eosinophilic inflammation, IgE-mediated mast cell activation is a key event leading to eosinophilia in atopic asthmatics. METHODS: We conducted a retrospective study on our asthma clinic database containing more than 1500 patients and identified 205 asthmatics with successful sputum induction and concordant eosinophilic phenotype. This phenotype was defined as a sputum eosinophil count≥3% and a blood eosinophils concentration≥400cells/mm3. IgE-high atopic phenotype was characterized by the presence of at least one positive specific IgE (>0.35kU/L) to common aeroallergens and a raised total serum IgE (≥113kU/L). RESULTS: The largest group of asthmatics displaying concordant eosinophilic phenotype had a raised total serum IgE and atopy (45%). IgE-low non-atopic concordant eosinophilic asthma was a predominantly late onset disease, exhibited a more intense airway eosinophilic inflammation (P<0.05), required more often maintenance treatment with oral corticosteroids (P<0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P<0.05) despite similar baseline airway calibre impairment. CONCLUSION: The more severe airway eosinophilic inflammation in IgE-low non-atopic asthmatics despite similar treatment with ICS and a higher burden of OCS points to a certain corticosteroid resistance in this asthma phenotype.

[COVID-19 and asthma]. / COVID-19 et asthme.

Given the prominent role of respiratory viruses in asthma exacerbations it has been feared that the SARS-CoV-2 pandemic may result in massive irruption of asthmatic patients in the hospital emergency departments. It seems, however, that asthma is not a particular risk factor for SARS-COV-2 infection nor for death resulting from severe infection. Inhaled corticosteroids (ICS) were found to reduce expression of ACE2 receptor in sputum cells, thereby maybe reducing the risk of lung infection. Only the more severe asthmatic patients treated with oral corticoids or high dose ICS were found to be at risk of death, presumably because of associated comorbidities. Biologicals directed towards IgE or interleukin-5 do not seem to confer an increased risk of severe infection.

Vu le rôle joué par les virus respiratoires dans les exacerbations asthmatiques, nous avons eu les pires craintes au début de l'épidémie de SARS-CoV-2 de voir les patients asthmatiques déferler dans les services hospitaliers. Il semble pourtant que l'asthme ne présente ni un facteur de risque d'infection, ni un facteur de risque de surmortalité. La prise de corticoïdes inhalés pourrait même protéger, en réduisant l'expression du récepteur ACE2, port d'entrée du virus dans les voies respiratoires. Seuls les patients asthmatiques plus sévères, recevant des corticoïdes systémiques ou des hautes doses de corticoïdes inhalés, ont un excès de mortalité, sans doute en raison des comorbidités associées. La prise de traitements biologiques anti-IgE et anti-IL-5 ne semble pas associée à un risque particulier d'infections sévères.

[Yoga to improve asthma control in severe asthmatics treated with biologics]. / Le yoga en vue d'améliorer le contrôle symptomatique des patients asthmatiques sévères traités par biologiques.

We conducted a prospective observational study to evaluate the efficacy of yoga in poorly controlled severe asthmatic patients treated with maximal inhaled therapy and biologics. The objective of yoga was to improve breathing consciousness, exercising controlled ventilation with and without retention, abdominal breathing observation, improvement of inspiratory and expiratory muscles, opening of the chest, diaphragm exercises and relaxation. We measured exhaled nitric oxide, forced expiratory volume in one second, forced vital capacity, asthma control and quality of life questionnaires, anxiety and depression questionnaires before and after the tenth yoga course (performed twice a week). Half of the patients who were invited to participate to the study declined due to organization problems. Two patients were excluded due to bronchitis and arthralgia respectively. The analysis of the data from 12 participants revealed significant improvement in asthma control and asthma quality of life questionnaires and a reduction of anxiety.The regular practice of yoga in severe asthmatics insufficiently controlled despite maximal inhaled treatment and biotherapy seems to be an interesting complementary option to improve asthma control. Our results must be confirmed in larger randomized controlled trials.

Nous avons conduit une étude pilote prospective observationnelle en vue d'évaluer l'efficacité de la pratique du yoga chez le patient asthmatique sévère insuffisamment contrôlé sous traitement de fond inhalé maximal et traitement biologique. L'objectif des séances de yoga était la prise de conscience de la respiration habituelle, le travail de la respiration contrôlée avec et sans temps de rétention, l'observation de la respiration abdominale, le travail des muscles inspiratoires et expiratoires, l'ouverture de la cage thoracique, le travail du diaphragme et la relaxation. Nous avons évalué le monoxyde d'azote dans l'air exhalé, le volume expiré maximal par seconde, la capacité vitale forcée, l'indice de Tiffeneau, les questionnaires de contrôle de l'asthme, de qualité de vie et d'anxiété et dépression avant la première séance et après la dixième séance de yoga (réalisées à raison de deux fois par semaine). La moitié des patients invités à participer à l'étude a refusé l'inclusion suite à des problèmes organisationnels. Deux patients ont été exclus, respectivement, suite à une surinfection bronchique et à des douleurs ostéo-articulaires. L'analyse des données des 12 participants a révélé une amélioration significative des questionnaires de contrôle, de qualité de vie et d'anxiété. La pratique régulière du yoga chez le patient asthmatique sévère insuffisamment contrôlé sur le plan symptomatique sous traitement de fond maximal semble donc être une option complémentaire intéressante. Les résultats de notre étude doivent être confirmés dans une étude contrôlée randomisée à plus large échelle.

Chronic oral corticosteroids use and persistent eosinophilia in severe asthmatics from the Belgian severe asthma registry.

BACKGROUND: Severe asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment. METHODS: In a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile. RESULTS: At enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients. CONCLUSION: These data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

[Asthma : the contribution of biotherapies]. / Une décennie d'avancées dans l'asthme : l'apport des biothérapies.

Asthma is a chronic heterogeneous airway disease. There are different asthma inflammatory phenotypes with various responses to treatment and different disease severities. When asthma requires chronic systemic corticosteroids or hospitalizations despite maximal inhaled therapies in asthmatic patients in whom comorbidities have been managed and who are considered as compliant, the pulmonologist may propose biological treatment to reduce exacerbations and the dose of systemic corticosteroids. During the last ten years, the number of biologics for the management of type-2 severe asthma has increased. Anti-IgE monoclonal antibodies (omalizumab) are available for more than ten years and recommended in severe allergic asthma. New biologics are now available to block IL-5 (mepolizumab, reslizumab) or its receptor (benralizumab). These treatments allow a reduction of exacerbations and of the dose of systemic corticosteroids, an improvement in asthma control, in asthma quality of life and for some of them, an increase in lung function. New biologics will soon be available in Belgium for the management of severe asthma. In addition to the improvement of asthma control in severe asthma, biological treatments have improved the understanding of the mechanisms leading to severe asthma.

L'asthme est une maladie hétérogène chronique des voies aériennes. Il existe, en effet, différents phénotypes inflammatoires d'asthme induisant une réponse variable aux traitements et différents degrés de sévérité. Lorsque l'asthme est sévère et requiert le recours aux corticostéroïdes systémiques ou à des hospitalisations malgré un traitement de fond maximal chez un patient asthmatique bon observant dont les comorbidités ont été prises en charge, le pneumologue peut proposer un traitement biologique en vue de réduire les exacerbations et la dose de corticostéroïdes systémiques. Au cours des dix dernières années, les traitements biologiques dans la prise en charge de l'asthme sévère de type 2 se sont étoffés. A côté du traitement par anti-IgE (omalizumab), disponible depuis plus de 10 ans et recommandé dans l'asthme sévère extrinsèque, d'autres traitements bloquant l'IL-5 (mépolizumab, reslizumab) ou son récepteur (benralizumab) ont vu le jour. Ces traitements permettent une réduction des exacerbations et de la dose de corticostéroïdes systémiques, une amélioration du contrôle, des paramètres de qualité de vie et, pour certains d'entre eux, de la fonction respiratoire. D'autres traitements ciblés prometteurs seront bientôt disponibles en Belgique. En plus d'améliorer le contrôle symptomatique des patients asthmatiques sévères, les traitements biologiques ont permis de mieux comprendre les mécanismes conduisant au développement d'un asthme sévère.

Predictors of a good response to inhaled corticosteroids in obesity-associated asthma.

INTRODUCTION: Asthma in obese subjects is poorly understood. According to GINA guidelines, pulmonologists increase ICS in case of poor asthma control but lung volume restriction may also worsen respiratory symptoms in obese asthmatics leading to overtreatment in this subpopulation. METHODS: We conducted a retrospective study on 1217 asthmatics recruited from University Hospital of Liege. 92 patients with a BMI ≥30 came at least two times at the asthma clinic (mean interval: 335 days). In this obese population, we identified predictors of good (decrease in ACQ ≥0.5) versus poor response (rise in ACQ ≥0.5) to ICS step-up therapy. RESULTS: Obese asthmatics had a poorer asthma control and quality of life as compared to non-obese and exhibited reduced FVC, higher levels of blood leucocytes and markers of systemic inflammation. The proportion of asthma inflammatory phenotypes was similar to that observed in a general population of asthmatics. Among uncontrolled obese asthmatics receiving ICS step-up therapy, 53% improved their asthma control while 31% had a worsening of their asthma. Uncontrolled obese asthmatics showing a good response to increase in ICS had higher ACQ, lower CRP levels, higher sputum eosinophil counts and higher FeNO levels at visit 1. Uncontrolled obese asthmatics that worsened after increasing the dose of ICS had lower FVC, lower sputum eosinophil counts and higher sputum neutrophil counts. CONCLUSION: We observed poorer asthma control in obese asthmatics despite similar bronchial inflammation. Managing obese asthmatics according to ACQ alone seems to underestimate asthma control and the contribution of restriction to dyspnea. Increasing the dose of ICS in the absence of sputum eosinophilic inflammation or in the presence of restriction or bronchial neutrophilia led to poorer asthma control. In those patients, management of obesity should be the first choice.

Assessment of diagnostic accuracy of lung function indices and FeNO for a positive methacholine challenge.

Demonstration of bronchial hyperresponsiveness is a key feature in asthma diagnosis. Methacholine challenge has proved to be a highly sensitive test to diagnose asthma in patients with chronic respiratory symptoms and preserved baseline lung function (FEV1 > 70% pred.) but is time consuming and may sometimes reveal unpleasant to the patient. We conducted a retrospective study on 270 patients recruited from the University Asthma Clinic of Liege. We have compared the values of several lung function indices and fractional exhaled nitric oxide (FeNO) in predicting a provocative methacholine concentration ≤16 mg/ml on a discovery cohort of 129 patients (57 already on ICS) and on a validation cohort of 141 patients (66 already on ICS). In the discovery study (n = 129), 85 patients (66%) had a positive methacholine challenge with PC20M ≤ 16 mg/ml. Those patients had lower baseline % predicted FEV1 (92% vs. 100%; p < 0.01), lower FEV1/FVC ratio (79% vs. 82%; p < 0.05), higher RV/TLC ratio (114% vs. 100%; p < 0,0001), lower SGaw (specific conductance) (0.76 vs. 0.95; p < 0,001) and higher FeNO (29 ppb vs. 19 ppb; p < 0,01). When performing ROC curve the RV/TLC ratio provided the greatest AUC (0.74, p < 0.001), sGAW had intermediate AUC of 0.69 (p < 0.001) while FeNO, FEV1 and FEV1/FVC ratio were modestly predictive (AUC of 0.65 (p < 0.05), 0,67 (p < 0.001) and 0,63 (p < 0.001). These results were confirmed in the validation study (n = 141). Based on a logistic regression analysis, significant variables associated with positive methacholine challenge were FeNO and RV/TLC (% Pred). A combined application of FeNO and RV/TLC (% Pred) for predicting the PC20M had a specificity of 85%, a sensitivity of 59% and an AUC of 0.79. In the validation study, three variables (RV/TLC, FeNO and FEV1) were independently associated with positive methacholine challenge and the combination of these three variables yielded a specificity of 77%, a sensitivity of 39% and an AUC of 0.77. The RV/TLC ratio combined to FeNO may be of interest to predict significant methacholine bronchial hyperresponsiveness.

Effectiveness of omalizumab on patient reported outcomes, lung function, and inflammatory markers in severe allergic asthma.

BACKGROUND: Omalizumab arose as a therapeutic option in patients suffering from moderate to severe refractory allergic asthma. It acts as a humanized monoclonal antibody neutralizing circulating IgE antibodies. Randomized clinical trials and real life clinical studies have already confirmed benefits, cost-effectiveness and applicability of the medication. METHOD: Our study retrospectively reports on the clinical outcomes and airway inflammation in 157 severe allergic asthmatics who were initiated with omalizumab between 2007 and 2019. RESULTS: After 4 months of therapy, 76% of the patients were judged to have benefited from omalizumab and were admitted to prolonged treatment. During follow-up, we observed an improvement in asthma control, quality of life and spirometric performance. There was also a sustained reduction in exacerbation rate over the years. As for T2 biomarkers, FeNO significantly decreased and, in a subgroup of patients who had repeated sputum inductions, there was also significant reduction in sputum eosinophils but no change in blood eosinophil count. Lastly, we found a correlation between high FeNO levels at baseline and reduction in ACQ scores at 1 year. CONCLUSION: We conclude that omalizumab shows effectiveness in severe allergic asthma in a real life setting, by reducing exacerbation rate, improving patient perspective outcomes and airway calibre, together with reducing type-2 airway inflammation.

[Sarcoidosis following tuberculosis. Is there a link between these granulomatous diseases?] / Une sarcoïdose dans le décours d'une tuberculose. Existe-t-il un lien étiologique entre ces deux maladies granulomateuses ?

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.

Nous rapportons le cas d'une patiente âgée de 38 ans, non fumeuse, qui s'est présentée à l'hôpital pour une symptomatologie de toux et d'expectorations depuis plusieurs semaines. Les différentes investigations ont permis d'établir un diagnostic de tuberculose et une trithérapie a été introduite avec une évolution favorable de la patiente. Deux ans plus tard, la patiente rapporte une récidive des plaintes respiratoires. Les nouveaux examens menés concluent, dans un premier temps, à une récidive de tuberculose et une quadrithérapie est instaurée. Le traitement fut mal toléré et stoppé rapidement. Il est alors décidé de réaliser une biopsie par médiastinoscopie au niveau des ganglions hilaires qui permettra de confirmer le diagnostic de sarcoïdose. L'étiologie de la sarcoïdose n'étant pas encore clairement établie, une des hypothèses est l'implication directe d'un agent infectieux qui induirait une réaction immunitaire excessive. Le cas clinique ci-dessous étaye la théorie selon laquelle le Mycobacterium tuberculosis pourrait être un des agents étiologiques de la sarcoïdose.

Multimodal chemometric approach for the analysis of human exhaled breath in lung cancer patients by TD-GC × GC-TOFMS.

Lung cancer is the deadliest cancer in developed countries. To reduce its mortality rate, it is important to enhance our capability to detect it at earlier stages by developing early diagnostic methods. In that context, the analysis of exhaled breath is an interesting approach because of the simplicity of the medical act and its non-invasiveness. Thermal desorption comprehensive two-dimensional gas chromatography time of flight mass spectrometry (TD-GC × GC-TOFMS) has been used to characterize and compare the volatile content of human breath of lung cancer patients and healthy volunteers. On the sampling side, the contaminations induced by the bags membrane and further environmental migration of VOCs during and after the sampling have also been investigated. Over a realistic period of 6 h, the concentration of contaminants inside the bag can increase from 2 to 3 folds based on simulated breath samples. On the data processing side, Fisher ratio (FR) and random forest (RF) approaches were applied and compared in regards to their ability to reduce the data dimensionality and to extract the significant information. Both approaches allow to efficiently smooth the background signal and extract significant features (27 for FR and 17 for RF). Principal component analysis (PCA) was used to evaluate the clustering capacity of the different models. For both approaches, a separation along PC-1 was obtained with a variance score around 35%. The combined model provides a partial separation with a PC-1 score of 52%. This proof-of-concept study further confirms the potential of breath analysis for cancer detection but also underlines the importance of quality control over the full analytical procedure, including the processing of the data.

[Bronchial thermoplasty in the management of severe asthma : retrospective analysis of 10 cases treated at academic hospital of Liège]. / Thermoplastie bronchique dans le traitement de l'asthme sévère. Analyse rétrospective de 10 cas traités au CHU de Liège.

As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) - ie. bronchoscopic procedure delivering a thermic form of energy through radiofrequency to the bronchi, in order to interfere with the components of the smooth muscle layer - arose as a promising technique. Our study followed the path of 10 patients from CHU Liège (University Hospital), who underwent this procedure in a context of severe asthma. We compared clinical and spirometric and treatment data in patients at 0 - 6 and 12 months post-procedural intervals, in order to determine whether thermoplasty had been improving asthma. Overall, we observed a stabilization and possibly a clinical improvement while reducing the total amount of exacerbation rate, and the burden of maintenance oral corticoids.

En raison du défi médico-économique que représente le traitement des formes sévères d'asthme, les recherches concernant de nouvelles thérapies dans ce domaine sont multiples et variées. Récemment, la thermoplastie bronchique - correspondant à un acte bronchoscopique permettant de délivrer une énergie par radiofréquence au niveau des bronches, afin d'interférer avec les composants de la couche musculaire lisse - s'annonçait comme une procédure prometteuse. Nous avons étudié 10 patients, suivis au CHU de Liège dans un contexte d'asthme sévère, et ayant bénéficié de cette technique. Nous avons comparé des données cliniques, spirométriques et thérapeutiques aux intervalles de 6 et 12 mois après procédure, afin de de déterminer si celle-ci avait été bénéfique sur leur pathologie asthmatique. Globalement, nous observons une stabilisation, voire une amélioration clinique, avec, notamment, une diminution des exacerbations, tout en réduisant la charge en corticoïdes systémiques.

[Exacerbations in asthma and chronic obstructive pulmonary disease (COPD) Survey on the criteria of pescription of systemic corticoids and antibiotics by general practicioners and chest physicians]. / Le 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.

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.

Les exacerbations dans l'asthme et la bronchopneumopathie chronique obstructive (BPCO) sont des événements importants qui rythment l'évolution clinique de ces deux maladies obstructives. Elles sont généralement définies par la nécessité d'un recours temporaire aux corticoïdes systémiques ou aux antibiotiques. Peu d'études se sont cependant penchées sur les critères précis qui motivaient les cliniciens à prescrire ces médications en cas de maladies obstructives déstabilisées. Nous rapportons ici les résultats d'une enquête menées auprès de médecins généralistes et de pneumologues sur les raisons précises de prescription de cure d'antibiotiques et de corticoïdes. Nos résultats concernant la prescription de corticoïdes systémiques montrent des divergences entre les deux groupes professionnels, mais aussi à l'intérieur d'un même groupe alors que les critères de prescription d'antibiotiques sont nettement plus cohérents entres les praticiens qu'ils soient généralistes ou pneumologues.

[Asthma and obesity : preventable therapeutic trap, with careful follow-up]. / Le cas clinique du mois. Asthme et obésité : piège thérapeutique évitable, moyennant un suivi aguerri.

Nowadays, more and more obese asthmatics visit a pulmonologist. It is proven that overweight stirs up the severity of the bronchopathy. It is a concept that is now anchored in the minds of most modern practitioners. Nevertheless, the idea that in some patients, excess weight can be an independent cause of the persistence of respiratory complaints, is sometimes neglected. This case report is about a severely obese poorly controlled asthmatic man, who turns out to be suffering from a concomitant obesity-hypoventilation syndrome. His clinical history confirms the necessity of quickly detecting this restrictive syndrome within an obstructive background, before its evolution towards a severe acute respiratory failure, where therapeutic approximations can have dramatic repercussions on the patient's health.

A notre époque, de plus en plus de patients asthmatiques obèses se présentent en consultation de pneumologie. Il est prouvé que le surpoids attise la sévérité de la bronchopathie. C'est un concept qui est désormais ancré dans l'esprit de la plupart des praticiens modernes. Néanmoins, l'idée que, chez certains patients, l'excès pondéral puisse constituer une cause indépendante de la persistance des plaintes respiratoires, reste parfois négligée. Ce cas clinique concerne un homme sévèrement obèse dont l'asthme est mal contrôlé, qui, in fine, se révèle être porteur d'un syndrome obésité-hypoventilation concomitant. Le récit de son histoire clinique confirme l'intérêt de déceler rapidement ce syndrome restrictif au sein du tableau obstructif connu, avant qu'il n'évolue vers une insuffisance respiratoire aiguë sévère, où des approximations thérapeutiques peuvent avoir des répercussions gravissimes.