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Identification of therapeutic targets other than asthma can guide the choice of biologics in cases of severe asthma. Some of the allergic diseases (atopic dermatitis, food allergies, allergic rhinoconjunctivitis) that may be associated with asthma can be treated with biologics. In this review, we aim to assess the effectiveness of these biologic therapies on the allergic comorbidities of asthma. In the treatment of atopic dermatitis, only Dupilumab, an anti-IL4Rα, has proven its effectiveness and has received reimbursement authorization for this indication. In patients presenting with allergic rhinoconjunctivitis, Omalizumab has shown effectiveness, but has not been approved for this indication. Data from post-hoc analyses of studies on severe asthma likewise suggest the effectiveness of Dupilumab regarding allergic rhinitis. While these two biologic therapies have shown positive signals, inducing oral food tolerance, the relevant data are not robust. Biologic therapies targeting IL-5 or its receptor (Mepolizumab, Benralizumab) have seldom been evaluated in allergic comorbidities, excepting atopic dermatitis, for which their effectiveness has not been proven. Lastly, there are interesting data on the combination of biologic therapy and allergen immunotherapy in cases of allergic rhinitis and food allergies, but they need to be confirmed by randomized studies., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction : L’asthme sévère est un réel problème de santé publique. Le but de notre travail est de mettre en évidence les facteurs influençant la sévérité de l’asthme chez la population jeune. Matériel et méthode : Il s’agit d’une enquête transversale concernant les enfants et adolescents asthmatiques scolarisés âgés de 6 à 19 ans et résidents dans la wilaya de Sidi-Bel-Abbès entre Janvier et Mars 2016. Le questionnaire utilisé reprend les critères d'évaluation du contrôle recommandés par le Global Initiative for Asthma (GINA) 2008. Résultats et discussion : Nous avons colligé 432 enfants et adolescents asthmatiques. La prévalence de l'asthme sévère est de 12,7% et est élevée par rapport à la prévalence de 4% retrouvée dans l’étude de Benallal en 2010 menée en milieu hospitalier. Une relation significative est notée entre la sévérité de l’asthme et le mode de vie urbain de notre population et presque les deux tiers des enfants et adolescents souffrant d’asthme sévère sont exposés au tabagisme passif. Une association très significative est remarquée entre la prévalence relative de l’asthme sévère et le rang dans la fratrie d’une part et la taille de fratrie d’autre part. Dans notre étude, la répartition en fonction du statut pondéral, montre que 22% de nos patients sont en surpoids ou obèses. L’obésité est associée à une inflammation systémique qui module l’inflammation des voies respiratoires et, par conséquent, l’expression de l’asthme chez les obèses. Conclusion : La sévérité de l’asthme peut être causée, déclenchée ou influencée par de nombreux facteurs environnementaux ou liés au patient lui-même

Background: Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases. Methods: The plasma proteome was evaluated using an aptamer‐based affinity proteomics platform (SOMAscan®), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics. Results: Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under‐explored. Conclusion: This investigational study evaluating the plasma proteome in clinically‐phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the development of biomedicines, of which there are currently five available in France, with a safety profile that appears favorable but remains uncertain due to a lack of real-life experience with these new molecules., State of Knowledge: Although relatively benign, the adverse effects of biologics are diverse. Headache, joint pain, skin reactions at the injection site, fever and asthenia are commonly observed during the different treatments. Ophthalmological complications seem restricted to dupilumab, with numerous cases of keratitis and conjunctivitis in patients with atopic dermatitis. Several respiratory complications have also been observed, essentially consisting in pharyngitis and other upper respiratory infections. Hypereosinophilia may occur, mainly with dupilumab, requiring investigation of systemic repercussions or vasculitis. Allergic reactions are uncommon but require careful monitoring during initial injections., Conclusion: Biologics for severe asthma are recent drugs with a favorable safety profile, but with little real-life experience, justifying increased vigilance by prescribing physicians., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Severe asthma patients with persistent airflow obstruction are characterized by functional obstruction due to mucus plugs containing mucins, fibrin, and eosinophil derived Charcot- Leyden crystals. The molecular mechanisms underlying this endotype are not clearly understood. Developing new models is crucial to respiratory research insofar as critical differences exist between human and rodent airway epithelium. We (and other teams) have shown that it is possible to reconstitute in vitro a complex and functional airway epithelium displaying all the features described in vivo from human-induced pluripotent stem cells (hiPSC). Our aim is to establish a human in vitro model of severe asthma that will recapitulate airway epithelium remodeling and mucus plugs., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose., Methods: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%., Results: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders., Conclusions: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

L'asthme est une pathologie inflammatoire chronique touchant les voies aériennes, hétérogène tant dans sa présentation que dans sa physiopathologie. Les données fondamentales et cliniques sur la compréhension de l'asthme se sont considérablement complexifiées au cours des dernières décennies. Dépassant l'archétype de l'asthme allergique de l'adulte jeune, de nouveaux paradigmes sont apparus. Des phénotypes d'asthme déterminés à partir de données cliniques et paracliniques simples ont permis la caractérisation de formes inflammatoires diverses (éosinophiliques et non éosinophiliques) ainsi que de nouveaux phénotypes jusqu'alors peu explorés (obésité, âge avancé, etc.). L'avènement des techniques d'analyses de données à haut débit a rendu possible le développement de nouvelles cohortes de patients visant à préciser les multiples mécanismes physiopathologiques sous-tendant ces nouveaux phénotypes. De nouvelles données apparaissent régulièrement, mais leurs impacts cliniques et thérapeutiques restent à déterminer. Parallèlement, des biothérapies et des techniques innovantes telles que la thermoplastie bronchique se sont développées afin d'améliorer la prise en charge des patients asthmatiques sévères pour lesquels il n'existait jusqu'alors que le recours à une corticothérapie systémique au long cours, non dénuée d'effets indésirables. Le développement de la médecine personnalisée du patient asthmatique sévère est désormais devenu une priorité. L'objectif de cette revue est de tracer un tour d'horizon des nouveaux concepts physiopathologiques et de présenter les nouvelles stratégies thérapeutiques dans l'asthme sévère. Asthma is an inflammatory airway disease which presentation is highly heterogeneous. Last two decades provided new clinical and basic data concerning asthma physiopathology that make global understanding much complex. Phenotypes based on clinical settings and paraclinical investigations from large cohorts confirm old paradigm (eosinophilic vs. non-eosinophilic asthma) but also introduce new concepts (obesity-related asthma, late onset asthma, etc.). Conversely, improvement of big data analytics allows to initiate new cohorts aiming at better understanding the pathophysiology underlying those phenotypes and unraveling new ones. However, clinical and therapeutic impacts of those big data need to be further detailed. In parallel, biotherapies and innovative techniques as bronchial thermoplasty become available for severe asthmatic patients who did not respond to specific treatment in the past. Development of a personalized medicine in severe asthma becomes an important challenge for tomorrow. This review will focus on new pathophysiological concepts arisen from large cohorts and new therapeutic strategies available and in progress for severe asthma. [ABSTRACT FROM AUTHOR]

For patients with difficult-to-control, severe bronchial asthma, highly effective, targeted treatment options are available in addition to inhaled medication. In the presence of eosinophilia, inhibition of the interleukin-5 (IL-5) axis with specific monoclonal antibodies promises to be an effective alternative to continuous systemic steroid therapy with few side effects. This review summarizes the data on benralizumab, a specific antibody against the IL-5 receptor alpha preventing receptor stimulation by IL-5 and activating a NK-cell mediated cytotoxic reaction with apoptosis of eosinophils. The s.c.-application of benralizumab leads within days to a virtually complete depletion of blood eosinophils with consecutive improvement in lung function and stabilization of asthma. For selected severe asthmatics, this is a promising therapy option. [ABSTRACT FROM AUTHOR]

For patients with difficult-to-control, severe bronchial asthma, highly effective, targeted treatment options are available in addition to inhaled medication. In the presence of eosinophilia, inhibition of the interleukin-5 (IL<5) axis with specific monoclonal antibodies promises to be an effective alternative to continuous systemic steroid therapy with few side effects. This review summarizes the data on benralizumab, a specific antibody against the IL-5 receptor alpha preventing receptor stimulation by IL-5 and activating a NK-cell mediated cytotoxic reaction with apoptosis of eosinophils. The s.c.-application of benralizumab leads within days to a virtually complete depletion of blood eosinophils with consecutive improvement in lung function and stabilization of asthma. For selected severe asthmatics, this is a promising therapy option. [ABSTRACT FROM AUTHOR]

Résumé Objectif de l’étude Apprécier les résultats de traitement des patients souffrant d’une forme sévère d’asthme parmi ceux traités dans deux centres de pneumophtisiologie impliqués dans un projet de prise en charge des asthmatiques au Bénin. Patients et méthode Étude de cohorte rétrospective ayant inclus tous les patients enrôlés de 01/2013 à 11/2015. Les caractéristiques du patient, la sévérité de l’asthme, le respect des contrôles planifiés, les résultats de l’évaluation annuelle étaient colligés, enregistrées puis analysées dans EpiData et SPSS 21. Résultats Sur 491 asthmatiques ayant au moins une crise hebdomadaire, 194 (40 %) avaient une forme sévère, sex-ratio = 0,81, âge médian = 47 ans (écart interquartile = 32–60 ans). Parmi eux, la proportion venue aux contrôles avait progressivement diminué : 98 % (15 e jour), 74 % (1 mois), 63 % (3 mois), 54 % (6 mois), 51 % (9 mois) et 41 % (1 an). À l’évaluation annuelle, 115 (59 %) étaient absents. L’état était stationnaire chez 52 (27 %) vus. Seul un âge supérieur à 41 ans (risque relatif = 2,14 ; IC 95 % = 1,11–4,13 ; p = 0,02) était associé à une absence d’amélioration de l’état. Conclusion Les formes d’asthme diagnostiquées sévères dans le projet sont nombreuses. Ces patients honorent de moins en moins leur rendez-vous de contrôle et sont peu améliorés à l’évaluation annuelle. L’application des recommandations de GINA et le subventionnement d’autres molécules devraient aider à améliorer leur état. Objective To assess treatment outcomes of patients with severe diagnosed asthma among those treated in the two major pulmonology-tuberculosis centers involved in an asthma management programme in Benin. Patients and methods This was retrospective cohort study that included all patients enrolled between January 2013 and November 2015. Data on patient's characteristics, asthma severity, compliance with planned control visits, and annual evaluation results were collected, entered and analyzed using the EpiData and SPSS 21 software packages. Results Of the 491 asthmatic patients presenting at least one weekly attack, 194 (40%) had a severe form, with a male-female ratio of 0.81 and a median age of 47 years (interquartile range = 32–60 years). The proportion of those adhering to control visits gradually fell: 98% (2 weeks), 74% (1 month), 63% (3 months), 54% (6 months), 51% (9 months) and 41% (1 year). The annual assessment of 52 (27%) patients showed no improvement. In addition, of the 115 (59%) not attending this appointment, 82 (42%) did not improve, based on their last assessment in the programme. The only factor associated with lack of improvement was being aged over 41 years (adjusted relative risk = 2.14; 95% CI = 1.11–4.13; P = 0.02). Conclusion Many patients in the project were diagnosed with severe asthma. Their attendance of follow-up gradually decreased during and their condition showed little improvement at their annual evaluation visits. Application of the GINA recommendations and subsidizing other drugs would doubtless help to improve their condition. [ABSTRACT FROM AUTHOR]

Résumé But de l’étude L’asthme sévère concerne 5 à 10 % des patients asthmatiques qui sont mal contrôlés malgré une démarche rigoureuse et systématique et un traitement maximal. Cette population nécessite des techniques de diagnostic phénotypique et des thérapeutiques difficilement accessibles dans nos pays. Le but principal de notre travail est de décrire le diagnostic et la prise en charge de l’asthme sévère dans trois pays du Maghreb (Maroc, Algérie et Tunisie). Patients et méthodes Étude prospective réalisée du 15 septembre au 15 décembre 2016 par des médecins, avec recueil des données via une fiche électronique préétablie, chez tous les asthmatiques âgés de plus de 6 ans, quel que soit leur niveau de contrôle. Résultats Vingt-sept médecins ont participé à l’étude incluant 333 (42 %) patients du Maroc, 291 (36,7 %) d’Algérie et 169 (21,3 %) de Tunisie. Le diagnostic d’asthme sévère a été retenu chez 260 (32,8 %) patients. Chez ces derniers, la démarche diagnostic préalable qui comprend 8 étapes était incomplète. L’exploration fonctionnelle respiratoire, la radiographie thoracique, les IgE totales et la numération formule sanguine étaient réalisées dans respectivement 80 %, 73,5 %, 23,1 % et 18,5 % des cas. La principale conduite à tenir proposée est d’augmenter le palier thérapeutique dans 84,6 % des cas en sachant que 45 % de ces patients n’étaient pas initialement sous bronchodilatateurs longue durée d’action (palier 2 du traitement du GINA au maximum). Conclusion l’asthme sévère apparaît surestimé dans cette étude Maghrébine, plusieurs lacunes existent concernant son diagnostic et sa prise en charge. Objective of the Study Severe asthma concerns 5–10% of asthma patients who are poorly controlled despite a rigorous and systematic approach and maximum treatment. This population requires phenotypic diagnostic techniques and therapeutics that are difficult to obtain in our countries. The main objective of our work is to describe the diagnosis and management of severe asthma in three Maghreb countries (Morocco, Algeria and Tunisia). Patients and methods Prospective study carried out from 15 September to 15 December 2016 by doctors, who collected the data via a pre-established electronic list, in all asthmatic patients aged over 6 years, regardless of their level of control. Results Twenty-seven doctors participated in the study, which included 333 (42%) patients from Morocco, 291 (36.7%) from Algeria and 169 (21.3%) from Tunisia. A diagnosis of severe asthma was made in 260 (32.8%) patients. In the latter, a preliminary 8-step diagnostic approach was incomplete. Investigation of respiratory function, chest X-ray, total IgE and blood count were performed respectively in 80%, 73.5%, 23.1% and 18.5% of patients. The main therapeutic approach consisted of increasing the therapeutic level in 84.6% of patients given that 45% of these patients were not initially on long-acting bronchodilators (GINA treatment stage 2 maximum). Conclusion This Maghreb study shows that severe asthma appears to be overestimated, with several gaps apparent as regards the diagnosis and management of the disease. [ABSTRACT FROM AUTHOR]

Severe childhood asthma is now a clearly defined disease. Although infrequent, it is characterized by persistent symptoms, including severe exacerbations, some of them leading to hospitalization, strongly affects the quality of life, and generates a high health cost. Its management requires a rigorous step by step evaluation, with the aim to reinforce the diagnosis and to adapt an individualized treatment plan. This approach is based on the multidisciplinary skills of a center dedicated to severe childhood asthma. The latter has different characteristics from that of the adult. Allergy is a strong marker: early and multiple and/or unusual sensitizations, weight of the comorbidities. New treatments are emerging, as omalizumab (Xolair®) an anti-IgE biotherapy available in France since 2006. The objective of this review is to detail the diagnosis approach of severe asthma in children, to describe the specific features of the disease, and finally to review the data on the studies evaluating the impact of omalizumab in pediatric severe allergic asthma. [ABSTRACT FROM AUTHOR]

Hypereosinophilic asthma is a severe asthma phenotype with new therapeutic options. The complete exploration of hypereosinophilic asthma is an indispensable preamble in order to eliminate other respiratory pathologies with both hypereosinohilia and asthmatic or pseudo-asthmatic manifestations. Current therapeutic strategies use biotherapies, including anti-IL5. [ABSTRACT FROM AUTHOR]

L'asthme sévère est une pathologie aux multiples phénotypes. Dans cette nouvelle sous-analyse des résultats de l'étude FASE-CPHG, un objectif était de décrire le profil de sensibilisation allergénique des patients asthmatiques sévères et de le confronter aux résultats du phénotypage de cette population. L'étude FASE-CPHG est une étude observationnelle, descriptive et multicentrique portant sur une population de patients asthmatiques sévères suivis dans 70 hôpitaux généraux de France entre mars 2016 et juillet 2017. Parmi les 1502 patients inclus, 1465 étaient analysables et ont fait l'objet de notre étude. Une exploration allergologique a été réalisée, comportant des tests cutanés chez 71 % des patients, et un dosage des IgE spécifiques chez 37 % des patients. Lorsque les tests cutanés ont été effectués, ils se sont révélés positifs pour au moins un allergène dans 71,2 % des cas (sensibilisation aux acariens 79 %, aux graminées 48 %, au chat 40 %, aux bétulacées 15,5 %, aux blattes 7,1 %, à Alternaria 10,9 %). Un dosage sanguin du taux d'éosinophiles a été pratiqué chez 75 % des patients (taux supérieur à 300/mm3 dans 53 % des cas). Cinq phénotypes d'asthme sévère ont été identifiés : asthme allergique précoce (sensibilisation à au moins un allergène dans 87 % des cas), asthme de l'obèse (sensibilisation dans 64 %), asthme tardif obstructif (sensibilisation dans 14 %), asthme tardif éosinophilique (sensibilisation dans 43 %), asthme et intolérance à l'aspirine (sensibilisation dans 66 %). Cette étude révèle que dans la pratique quotidienne, le bilan allergologique n'a été pratiqué que pour 80 % des patients ayant un asthme sévère. La réalisation d'un bilan allergologique paraît souhaitable quel que soit le phénotype d'asthme sévère, la prévalence d'une sensibilisation allergénique étant également importante au sein de phénotypes d'asthme d'apparition tardive réputés non allergiques. Severe asthma is a disease with many phenotypes. In this new subanalysis of the results of the FASE-CPHG study, one objective was to describe the allergenic sensitization profile of patients with severe asthma and to compare this profile with phenotyping in the same population. The FASE-CPHG study is an observational, descriptive, and multicenter study investigating a population of patients with severe asthma cared for in 70 general hospitals in France between March 2016 and July 2017. Of the 1,502 patients included, 1,465 could be analyzed and their data were used for this study. An allergy assessment was undertaken: a skin test in 71% of the patients, and specific IgE assays in 37% of the patients. When the skin tests were done, 71.2% were positive for at least one allergen (sensitization to dust mites, 79%; grasses, 48%; cats, 40%; Betulaceae, 15.5%; cockroaches, 7.1%; Alternaria, 10.9%). A blood eosinophilia count was performed in 75% of the patients (count > 300/mm3 in 53% of the cases). Five severe asthma phenotypes were identified: early allergic asthma (sensitization to at least one allergen in 87% of the cases), obesity and asthma (sensitization in 64%), late-onset obstructive asthma (sensitization in 14%), late-onset eosinophilic asthma (sensitization in 43%), asthma and intolerance to aspirin (sensitization in 66%). This study demonstrated that in daily practice the allergy assessment was only carried out in 80% of patients who had severe asthma. An allergy assessment seems desirable for any phenotype of severe asthma; the prevalence of allergenic sensitization is also important within late-onset asthma phenotypes that are reputed to be non-allergic. [ABSTRACT FROM AUTHOR]

INTRODUCTION: la présente étude vise à déterminer la fréquence de l'asthme sévère chez les patients asthmatiques suivis au Centre National Hospitalier de Pneumo-Phtisiologie (CNHPP) de Cotonou et identifier les facteurs de risque qui lui sont associés. METHODES: l'étude transversale, descriptive et analytique a porté sur 213 patients asthmatiques de la file active 2013 du CNHPP. Les données ont été collectées par l'exploitation des dossiers et l'entretien individuel avec les patients. Elles ont été traitées et analysées à l'aide des logiciels EPIINFO7 et STATA11. Le test Chi2 de Pearson, la régression logistique uni variée et multi variée ont été utilisés au seuil de signification de 0,05. RESULTATS: au total, 154 patients asthmatiques soit 72,7% ont répondu au questionnaire. Parmi eux 20,8% (IC95% :(14,67 ; 28,05)) souffraient d'asthme sévère. L'âge des patients s'étendait de 10 à 76 ans avec une médiane de 41 ans; 51,3% étaient de sexe féminin, 79,9% avaient des antécédents d'allergie, 61,7% ont commencé leur asthme après l'âge de 12 ans et seuls 11% ont consommé ou consommaient du tabac. Les facteurs associés à la survenue de l'asthme sévère étaient : l'âge de 46 à 55 ans (p = 0,04) ; les troisième et quatrième quintiles du bien-être économique (p = 0,01) et le début de l'asthme après l'âge de 12 ans (p = 0,001). CONCLUSION: l'étude a montré une fréquence élevée de l'asthme sévère au Bénin et permettra d'améliorer sa prise en charge au CNHPP.

Introduction: la présente étude vise à déterminer la fréquence de l'asthme sévère chez les patients asthmatiques suivis au Centre National Hospitalier de Pneumo-Phtisiologie (CNHPP) de Cotonou et identifier les facteurs de risque qui lui sont associés. Méthodes: l'étude transversale, descriptive et analytique a porté sur 213 patients asthmatiques de la file active 2013 du CNHPP. Les données ont été collectées par l'exploitation des dossiers et l'entretien individuel avec les patients. Elles ont été traitées et analysées à l'aide des logiciels EPIINFO7 et STATA11. Le test Chi² de Pearson, la régression logistique uni variée et multi variée ont été utilisés au seuil de signification de 0,05. Résultats: au total, 154 patients asthmatiques soit 72,7% ont répondu au questionnaire. Parmi eux 20,8% (IC 95% :(14,67 ; 28,05)) souffraient d'asthme sévère. L'âge des patients s'étendait de 10 à 76 ans avec une médiane de 41 ans; 51,3% étaient de sexe féminin, 79,9% avaient des antécédents d'allergie, 61,7% ont commencé leur asthme après l'âge de 12 ans et seuls 11% ont consommé ou consommaient du tabac. Les facteurs associés à la survenue de l'asthme sévère étaient : l'âge de 46 à 55 ans (p = 0,04) ; les troisième et quatrième quintiles du bien-être économique (p = 0,01) et le début de l'asthme après l'âge de 12 ans (p < 0,001). Conclusion: l'étude a montré une fréquence élevée de l'asthme sévère au Bénin et permettra d'améliorer sa prise en charge au CNHPP. [ABSTRACT FROM AUTHOR]

Asthma is a multifactorial disease with complex pathophysiology. Knowledge of its immunopathology and inflammatory mechanisms is progressing and has led to the development over recent years of increasingly targeted therapeutic strategies. The objective of this review is to pinpoint the different predictive markers of asthma severity and therapeutic response. Obesity, nasal polyposis, gastroesophageal reflux disease and intolerance to aspirin have all been considered as clinical markers associated with asthma severity, as have functional markers such as bronchial obstruction, low FEV1, small daily variations in FEV1, and high FeNO. While sinonasal polyposis and allergic comorbidities are associated with better response to omalizumab, nasal polyposis or long-term systemic steroid use are associated with better response to antibodies targeting the IL5 pathway. Elevated total IgE concentrations and eosinophil counts are classic biological markers regularly found in severe asthma. Blood eosinophils are predictive biomarkers of response to anti-IgE, anti-IL5, anti-IL5R and anti-IL4R biotherapies. Dupilumab is particularly effective in a subgroup of patients with marked type 2 inflammation (long-term systemic corticosteroid therapy, eosinophilia≥150/μl or FENO>20 ppb). Chest imaging may help to identify severe patients by seeking out bronchial wall thickening and bronchial dilation. Study of the patient's environment is crucial insofar as exposure to tobacco, dust mites and molds, as well as outdoor and indoor air pollutants (cleaning products), can trigger asthma exacerbation. Wider and more systematic use of markers of severity or response to treatment could foster increasingly targeted and tailored approaches to severe asthma., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Résumé: L’asthme sévère de l’enfant est maintenant défini par un consensus. Il s’agit d’un asthme se manifestant par l’absence de contrôle, et/ou de fréquentes exacerbations, et/ou un trouble ventilatoire obstructif persistant, malgré un traitement maximal bien conduit. Ses caractéristiques phénotypiques ont été précisées : très majoritairement allergique – polysensibilisation, comorbidités (rhinite, eczéma, allergie alimentaire), fréquentes exacerbations, tendance à l’aggravation du trouble ventilatoire obstructif. Il faut différencier l’asthme difficile de l’asthme sévère résistant au traitement. Des particularités physiopathologiques ont été décrites, en termes de remodelage, profil inflammatoire, immunité innée. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Cahiers Internationaux de Psychologie Sociale is the property of Presses Universitaires de Liege and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Case report: In a 16-year-old teenager hospitalized with a severe asthma attack, the diagnosis of severe asthma associated to allergy and current tobacco smoke and allergen exposure is confirmed. Despite the use of high dose of inhaled antiasthma medication, the disease remains uncontrolled and anti-IgE, omalizumab treatment is started. After few weeks, respiratory symptoms and function dramatically improve. Conclusion: Severe asthma must be readily diagnosed in order to adapt treatment and avoid fatal outcome or respiratory disability. [Copyright &y& Elsevier]

Abstract: Severe asthma is estimated to occur in 9.6% of asthmatics. Even though severe asthma does not occur frequently in asthmatic children, still it accounts for 80% of health expenditures in this group of patients. International guidelines grade the severity of asthma in four stages (intermittent, mild persistent, moderate, severe) according to daytime and night time symptoms, the frequency of exacerbations that affect the patient''s activities, and the forced expiratory volume in the first second (FEV1) before starting treatment. This classification appears insufficient for an evaluation of the severity of asthma in children because it does not take into account their current treatment, namely, inhaled corticoids, as well as previous acute severe exacerbations, the condition of the lower airways, the existence of an atopic terrain, and the importance of the patient''s age and sex on the severity of the asthma. Finally, it must be remembered that in the clinical workup of a child with severe asthma, it is first of all necessary to rule out “false asthma” (by systematic etiologic investigation), to distinguish between severe asthma and poorly controlled asthma related to co-existing conditions not otherwise considered, an inadequate environment, and poor adherence to prescribed therapy. [Copyright &y& Elsevier]

Abstract: Severe asthma represents a heterogeneous entity for which the immunopathology is poorly understood, in part because of the difficulty of obtaining material in situ material from patients. There are two types of severe asthma, depending on the presence or absence of eosinophils. The pathophysiology of severe asthma of early onset with eosinophilia is similar to that of less severe asthma, with infiltration of Th2 lymphocytes; such cases are more likely to have exacerbations. When the onset occurs later, asthma is much more like the hypereosinophilic syndromes. Severe asthma without eosinophilia is more often accompanied by neutrophil infiltration; this type of asthma responds poorly to corticoids. Induced sputum can be used for non-invasive longitudinal follow-up of bronchial inflammation in severe asthma, allowing evaluation of cellular activation during and between exacerbations. The ISEA study (Induced Sputum in Exacerbations of Asthma) revealed that simultaneous activation of Th1 and Th2 lymphocytes and a greater deficiency of T regulatory lymphocytes occur during the course of exacerbations. This type of approach is indispensable for the identification of relevant therapeutic targets, and ultimately for the identification of early markers that are predictive of exacerbations. [Copyright &y& Elsevier]

Asthma is a chronic airway condition defined by hyperresponsiveness, bronchial remodeling and chronic inflammation. A significant proportion of severe asthmatic patients remain uncontrolled despite recent therapeutic breakthroughs (biotherapies). Better understanding of the signaling pathways involved in the pathophysiological mechanisms underlying severe asthma could successfully address this unmet need. Rac GTPase acts as a molecular switch and has already been convincingly associated with airway hyperresponsiveness and bronchial remodeling in asthma. Having been elucidated by acquired knowledge regarding other pathologies. Its role in the inflammation mechanisms characterizing asthma is currently under specific evaluation., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Association of asthma with myasthenia gravis presents a twofold peculiarity. First, as dyspnea characterizes both conditions, diagnostic orientation is difficult. Second, from a therapeutic standpoint, the initiation of anticholinesterase treatment requires a multidisciplinary approach due to possible contraindication for asthma. We report on the case of a patient monitored for severe asthma and treated with biotherapy, and also monitored for myasthenia gravis, and treated with anticholinesterase., (Copyright © 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Data on severe asthma in France are scarce. The aim of this study was to evaluate adherence to asthma treatments and its determinants in a population of severe asthmatics., Methods: From May 2016 to June 2017, the French Collège des Pneumologues des Hôpitaux Généraux organized a large-scale prospective, cross-sectional, multicenter study on this topic; 1502 patients with severe asthma were included., Results: The average number of substantive treatments was 2.5±1.1. Assessed by self-questionnaire in 1289 patients, overall adherence was 64.8%, in good agreement with the findings of the pneumologist in charge (p<0.0001). Control of asthma according to the GINA criteria was more successful in compliant patients (p<0.01). In univariate analysis, the most compliant participants were frequent exacerbator patients (p=0.02), those with nasal polyposis (p=0.01) and those receiving an anticholinergic agent (p<0.01), anti-IgE biotherapy (p<0.0001) or oral corticosteroids (p<0.01). The least compliant participants were younger (p<0.0001), active smokers (p<0.001), with shorter average disease duration (24.2±15.7 vs 29.1±18.7 years, p<0.0001) and a lower number of substantive asthma treatments (2.2±1 vs 2.6±1, p<0.0001). In multivariate analysis, age, length of disease and anti-IgE treatment were the only factors affecting therapeutic compliance., Conclusion: In this large-scale study of severe asthmatic patients, 64.8% were compliant according to the MMAS-4© self-administered questionnaire and appeared to be better monitored according to the criteria defined in our study. Overall, adherence was more satisfactory among older patients and those whose disease had been evolving over a long period of time or were receiving anti-IgE biotherapy., (Copyright © 2021. Published by Elsevier Masson SAS.)

Résumé: La thermoplastie bronchique est une technique ciblant spécifiquement le muscle lisse bronchique dans le traitement de l’asthme. Au cours d’une endoscopie, on applique une sonde de radiofréquence sur la paroi des bronches de calibre>3mm. À 65°C, on observe une disparition élective du muscle lisse bronchique, remplacé en quelques semaines par un tissu conjonctif lâche. Ceci est associé à une réduction de la réactivité bronchique, qui expliquerait les effets cliniques. Les études chez l’homme, encore peu nombreuses, montrent que la thermoplastie permet de réduire le nombre des exacerbations, d’améliorer la qualité de vie et le contrôle de l’asthme, y compris chez des asthmatiques sévères. Les complications immédiates (exacerbations d’asthme essentiellement) ne sont pas négligeables et sont plus fréquentes et plus graves chez les patients sévères. La tolérance à long terme semble bonne, sans modification parenchymateuse ou bronchique à 5ans. La place de la thermoplastie dans l’arsenal des traitements reste à déterminer. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Severe asthma in children is defined by the persistence or exacerbation of asthmatic symptoms or persistence of bronchial obstruction in spite of treatment that is considered to be optimal. Management requires, first of all, that cases of false asthma, asthma lacking appropriate treatment, poor compliance and/or preventive education, asthma made worse by the persistence of an unrecognized factor and/or asthma that has not been treated must be recognized. Severe asthma calls for evaluation in specialized centers where the importance of bronchial inflammation and airway remodeling can be appreciated. That evaluation is based on data obtained by broncho-alveolar lavage and endobronchial biopsy; non-invasive methods such as measurement of exhaled NO and thoracic tomodensitometry are still being evaluated. [Copyright &y& Elsevier]

Bronchial thermoplasty has been developed over the past fifteen years and is the first endoscopic technique approved in the management of severe asthma. This procedure uses radiofrequency applied to the airway wall to target bronchial smooth muscle. Patients treated in randomized controlled trials have experienced significant decreases in the use of rescue medications, urgent care visits, and exacerbations rate. The lack of reliable predictive markers of response to this expensive, minimally-invasive technique currently makes it a last-line treatment option. We review the principles and supposed mechanisms of action of this treatment, the results from the main trials and clinical registry data and discuss the place of bronchial thermoplasty in the current management of severe asthma. We also discuss perspectives to better characterize the mechanisms of action and identify the responder phenotype, the main challenge of current studies., (Copyright © 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Data on physical activity in severe asthma are scarce. From May 2016 to June 2017, 1502 adult patients with severe asthma visiting a pulmonologist practicing in one of the 104 non-academic hospitals participating in the study were included in this prospective, cross-sectional, multicenter study, provided they gave consent. Physical activity was classified according to 4 levels: 1 (no activity), 2 (occasional), 3 (regular), or 4 (frequent). Clinical and therapeutic parameters were described according to these levels., Results: Respectively, 440, 528, 323, and 99 patients had physical activity of level 1, 2, 3, and 4. The percentage of patients with controlled asthma increased with physical activity. Treatment adherence did not differ with physical activity. Percentages of obese patients, patients with FEV1 <60%, and patients with anxiety, depressive syndrome, gastro-esophageal reflux disease, arterial hypertension, diabetes, obstructive sleep apnoea-hypopnoea syndrome, and osteoporosis decreased with physical activity. Respiratory rehabilitation was offered to only 5% of patients., Conclusions: In this large study, physical activity is associated with disease control in severe asthma and with less comorbidity. Its practice should be encouraged and respiratory rehabilitation offered more often., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

In a woman's life, asthma can affect her in a variety of ways, with the onset of premenstrual asthma currently under-diagnosed. It is estimated that about 20% of women with asthma have premenstrual asthma, which is more common in patients with severe asthma. Women with asthma are at high risk of exacerbations and of severe asthma. Asthma is the most common chronic disease during pregnancy with potential maternal and foetal complications. Asthma medications are safe for the foetus and it is essential to continue pre-existing treatment and adapt it to the progress of asthma during the pregnancy. Sex steroids modulate the structure and function of bronchial and immune cells. Understanding their role in asthma pathogenesis is complicated by the ambivalent effects of bronchodilating and pro-inflammatory oestrogens as well as the diversity of response to their association with progesterone. Menopausal asthma is a clinical entity and is part of one of the phenotypes of severe non-allergic and low steroid-sensitive asthma. Targeted assessment of the domestic and professional environment allows optimization of asthma management., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)