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RationaleAsthma and Chronic Obstructive Pulmonary Disease (COPD) are the two main chronic airway inflammatory diseases related to aging. Cellular aging is prevented by telomeres and their shortening induces cellular senescence. Human Telomerase Reverse Transcriptase Enzyme (hTERT) can act directly on DNA and prevent telomere shortening. The goal of this study was to assess hTERT expression in the bronchial mucosa of patients suffering from chronic airway obstructive diseases and to relate the hTERT expression to demographics and lung function characteristics.MethodsWe collected bronchial biopsies from 38 patients suffering from chronic airway diseases including 21 severe asthmatics and 17 COPD who underwent bronchoscopy in routine practice. hTERT expression was assessed by immunochemistry and co-immunostaining was performed to identify hTERT positive cells within the different immune cell populations.ResultshTERT expression in airway mucosa was essentially found in structural cells. Among leukocytes, lymphocytes were the principal cells expressing hTERT. On the whole cohort, hTERT expression score was not different between men and women and not influenced by the age nor by the smoking history as reflected by the pack years. Total airway hTERT positive staining score positively correlated with post-bronchodilation (post-BD) FEV1% predicted and FEV1/FVC. (r=0.38, p1/FVC (r=0.37, pConclusionsIn patients with chronic airway diseases, total and lymphocyte hTERT expressions inversely correlate with the degree of airway obstruction and are reduced in patients with fixed airway obstruction, which supports a role of hTERT in airway remodeling.

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.

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.

The friction torque of rotor blade bearings is a required parameter for the design of pitch actuators and may provide information about continued degradation and impending failure of the bearing. The torque is heavily influenced by the operating conditions and external loads acting on the bearing. Test results for real-size bearings under realistic loads are rare. This paper presents test results of various double-row four-point bearings of three different diameters, ranging from 0.7m up to 5m. They are loaded with bending moments and axial loads, and their behavior at different speeds is compared. For the same bearing type, large differences are observed at zero load that decrease for higher loads. At lower contact pressures, the change from four-point into two-point contact is clearly visible and results in a temporary decrease of the torque. To monitor potential degradation of the bearing, an empirical model that can be fit to a particular bearing is proposed.

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.

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.

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.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.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.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.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 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.

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.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/mmThe 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 (P0.05), required more often maintenance treatment with oral corticosteroids (P0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P0.05) despite similar baseline airway calibre impairment.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.

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.

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.

Asthma and obesity are both common diseases in western world. According to the data from our asthma clinic 20 % of our patients are obese and this rate increases up to 25 % in severe asthmatics included in the Belgian Severe Asthma national Registry. Alteration of thoracic mechanics contributes to greater symptom burden and poor asthma control in obese asthmatics. In particular the response to inhaled corticoids is attenuated. Weight loss results in a dramatic improvement in asthma control and should be a major goal in the asthma management of these patients.Asthme et obésité sont deux pathologies courantes dans les pays occidentaux. Selon les données de notre clinique de l’asthme, 20 % des patients asthmatiques sont obèses, mais ce taux monte à 25 % lorsqu’on considère les patients sévères inclus dans le Registre national belge de l’Asthme sévère. L’altération de la mécanique ventilatoire consécutive à l’excès pondéral rend l’asthme plus symptomatique et plus difficilement contrôlable chez le patient obèse. En particulier, il existe une réponse atténuée à la corticothérapie inhalée. La perte pondérale s’accompagne d’une amélioration spectaculaire de la symptomatologie et doit constituer un objectif thérapeutique primordial chez les patients asthmatiques obèses.

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.

Asthma is a complex chronic inflammatory disease of the airways. Eosinophilia is a recognized feature of asthma. Asthma is no more considered as a single disease, but there are several subtypes of bronchial asthma, also called phenotypes, that have therapeutic and prognostic implications. Asthmatics are now classified according to inflammatory phenotypes that allow a personalized therapy. Phenotype identification requires induced sputum analysis that is not widely available. In this context, we have identified surrogate markers for inflammatory phenotypes. An eosinophilic phenotype can lbe suspected in case of concomitant increase of exhaled nitric oxide, blood eosinophils, IgE levels and airway obstruction. We have also identified a subgroup of asthmatics exhibiting diffuse local and systemic eosinophilia. This subgroup has a more severe asthma,a lower asthma control and a higher number of exacerbations.

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.

Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype.

Asthma is a chronic inflammatory disease of the airways. The inflammatory process is driven by different pathways involving cytokines and other protein mediators. Patients with severe asthma are at high risk of severe exacerbations and death and have few therapeutic options available. Therefore, biological agents have been developed to help patients with refractory asthma by interfering with several compounds of the asthma inflammatory cascade. In addition to decreasing exacerbations, some of those treatments have a steroid sparing role and many beneficial effects in asthmatics.

Asthma is a chronic inflammatory disease which can be most often adequately controlled by current medications as demonstrated by multiple randomised clinical trials. Yet most of the recent surveys conducted in the real life setting point to an inadequate control in the majority of asthmatics. In addition to factors linked to the hygiene of life, clinician's inertia and patient's lack of adherence to the treatment certainly contribute to poor asthma control.

Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern.The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-gamma, and tumor necrosis factor alpha was measured by immunotrapping after 24 h sputum or blood cell culture.Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count.Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics.