Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children

Gender influences clinical presentations and markers in inflammatory diseases. In many chronic conditions, frequency of complications is greater in females, suggesting that continuous inflammatory reaction may induce greater damage in targeted organs and functions.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Allergies alimentaires: Exploration clinique et apport de la biologie

SCOPUS: sh.jinfo:eu-repo/semantics/publishe

Les allergies alimentaires de l'enfant: quel régime?

Food allergies are very frequent in children (between 4 and 8% of population). There are many clinical manifestations, that can be lifethreatening. In children, compared to adults, a limited number of food allergens are responsible for the disease: egg, cow milk, peanuts, nuts (hazelnut, nut, ), fish, cereals, exotic fuits, and soya. Eviction of the offending food is the first treatment of allergy. This eviction diet is sometimes difficult to organize and can alter the quality of life (child and family). Diagnosis must be well established; sensitivity to an allergen must be differenciated from real allergy. This can lead to perform a provocation test (oral challenge) in the hospital. It is now proposed that the eviction diet will be less strict than before, adapted according to the allergen, symptoms in each case, age of patient and ideally to the reacted dose of the offending allergen. A collaboration with a dietist is necessary to optimalize the nutritionnal schedule. Induction of oral tolerance seems to be an interesting optional treatment for patients presenting persistant food allergy.English AbstractJournal ArticleReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prévention et traitement de l'asthme chez l'enfant

Asthma is a chronic inflammatory disorder of the airways with an impact on the life of the patient, his family and the society. Asthma is the most common chronic disease of the childhood. Consequently, prevention and treatment of asthma are real challenges in public health. Treatment includes two levels: prevention and medication treatment. Prevention is to avoid one or several causes of asthma and risk factors of exacerbations particularly in high risk population. Medication treatment includes the reliever treatment and the maintenance treatment. Bronchodilatator treatment will be used in first line treatment in asthma attacks. Inhaled glucocorticosteroids are the most effective controller medications. No treatment is curative for asthma, establishing of therapeutic objectives is necessary. The reliever treatment, the maintenance treatment, the new classification of asthma and the new recommendations of therapeutic management will be discussed.SCOPUS: re.jinfo:eu-repo/semantics/publishe

La dyspnée aiguë chez l'enfant.

Acute respiratory dyspnea is very frequent in children and must be quickly treated to obtain the best prognosis. The diagnosis depends from the natural history of the disease and from the quality of clinical assessment. The use of an algorithm according to the presence of stridor or bronchospasm is very contributive to the diagnosis. The paper reviews the pathophysiology of dyspnea in children and the more common diseases that are causing respiratory distress. Finally, treatment of respiratory failure and management of specific diseases are defined.English AbstractJournal ArticleSCOPUS: sh.jinfo:eu-repo/semantics/publishe

Immuno-allergologie chez l'enfant: diagnostic et traitement.

Atopy is the most frequent allergic disease in western countries: about 30% of children are suffering from various forms of its manifestations. During the 20th century, its frequency gradually increased. This is not only true for sensitization (presence of specific immunoglobulin E (IgE) in the skin or in the serum), but also for clinical symptoms associated with sensitization. It is usually a disease of skin and mucosae, but atopy can also become systemic (anaphylaxis). Hygienist hypothesis (reduction of infectious diseases and Th1 pressure) gives a possible explanation to the impressive increase of allergic diseases during the last decades. In the child, atopic dermatitis and food allergies are first observed (allergic march): 5 allergens explain more than 85% of cases (white egg, milk, peanuts, fish and nuts). Skin prick tests are more sensible than specific IgE measurements in the serum; they are usually done before. Provocation tests (labial and oral) can confirm the diagnosis when necessary. Four families of aeroallergens are described (pollens, house dust mites, pets and moistures). Eviction is the first line of treatment, than drugs are prescribed to reduce symptoms and inflammation (corticosteroids, antihistamine). Desensitization and immunomodulators that can induce tolerance are also proposed in defined situations.English AbstractJournal ArticleSCOPUS: re.jinfo:eu-repo/semantics/publishe

L'allergie alimentaire chez l'enfant: étude d'une cohorte belge.

Food Allergy is a public health problem because of its increasingly prevalence, its severity and the difficulty of diagnosis.English AbstractJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Flow cytometry for basophil activation markers: the measurement of CD203c up-regulation is as reliable as CD63 expression in the diagnosis of cat allergy.

The flow cytometric basophil activation test (BAT), based on the detection of allergen-induced CD63 expression, has been proved effective in the diagnosis of various IgE-mediated allergies. However, there is not yet consensus about the suitability of CD203c expression as a specific basophil activation marker and its diagnostic reliability. The goal of the present study was to compare measurement of CD63 and CD203c expression using BAT in a model of cat allergy and to determine optimal experimental conditions for both markers. Heparinized whole blood samples from 20 cat allergic patients and 19 controls were incubated with Fel d1 (relevant allergen) or anti-FcepsilonRI (positive control) either in IL-3 or IL-3-free conditions. An optimal gating of basophils was achieved in triple staining protocols: anti-IgE PE/anti-CD45 PerCP/anti-CD63 FITC or anti-IgE FITC/anti-CD45 PerCP/anti-CD203c PE. We demonstrated that IL-3 significantly enhanced CD63-induced expression by basophils obtained from cat allergic patients in response to Fel d1. Sensitivity was found to be 100%. The CD203c protocol, when performed under IL-3-free conditions, also demonstrated 100% sensitivity. Only one of the control subjects was positive in both tests. In conclusion, using well-defined experimental conditions, the measurement of CD203c up-regulation on basophils in response to specific allergens is as reliable as CD63-BAT for the in vitro diagnosis of patients with IgE-mediated allergy.Evaluation StudiesJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Basophil activation tests for the diagnosis of food allergy in children.

BACKGROUND: Positive skin prick tests (SPT) for food allergens and specific IgE (sIgE) in serum indicate sensitization but do not enable distinction between sensitized but tolerant and clinically allergic patients. OBJECTIVE: Herein, we evaluate the clinical relevance of basophil activation tests (BATs) for peanut or egg allergy diagnosis. METHODS: Thirty-two peanut-allergic, 14 peanut-sensitized (sIgE(+) and/or SPT(+) to peanuts) but tolerant children and 29 controls with no history of an adverse reaction to peanuts were included. Similarly, 31 egg-allergic, 14 egg-sensitized children (sIgE(+) and/or SPT(+) to egg white) and 22 controls were studied. Flow cytometric analysis of CD63 expression or CD203c upregulation on basophils and the production of leukotrienes (LT) were performed in response to an in vitro crude peanut extract or ovalbumin (OVA) challenge. RESULTS: After in vitro peanut challenge, the basophils from peanut-allergic children showed significantly higher levels of activation than those from controls (P<0.001). After OVA challenge, a similar distinction (P<0.001) was observed between egg-allergics and controls. Interestingly, the majority of egg- or peanut-sensitized children failed to activate basophils, respectively, in response to OVA and peanut challenge. The sensitivity of the CD63, CD203c and LT assay was 86.7%, 89.5% and 76.0% with a specificity of 94.1%, 97.1% and 94.6% for peanut allergy diagnosis. The corresponding performances of BATs applied to egg allergy diagnosis were 88.9%, 62.5% and 77.8% for the sensitivity and 100%, 96.4% and 96.4% for the specificity. CONCLUSION: Neither conventional tests nor BATs are sensitive and specific enough to predict food allergy accurately. However, BATs may helpfully complete conventional tests, especially SPT, allowing improved discrimination between allergic and non-allergic individuals.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe