Complementary feeding practices are related to the risk of food allergy in the ELFE cohort.

BACKGROUND: Conflicting results have been obtained when analyzing the relationship between complementary feeding (CF) practices and allergic diseases in childhood. This study aims to further explore the association between allergic diseases in early childhood (10.1016/j.jaci.2012.02.036) and the age at CF introduction (10.1016/S0140-6736(15)00149-X), food diversity in the first year of life (10.1016/j.ijporl.2019.109759) and the delayed introduction of major allergenic foods. METHODS: This analysis focused on 6662 children from the French nationwide ELFE cohort. Data on feeding practices were collected monthly from 3 to 10 months old. Their age at CF introduction was calculated alongside a diversity score, and the number of major allergenic foods (out of eggs, fish, wheat, and dairy products) not introduced at 8 and 10 months. Their associations with parent-reported allergy-related health events between 1 and 5.5 years were assessed using logistic regressions adjusted for confounding factors. A sensitivity analysis excluding early allergic cases (occurring between 2 months and 1 or 2 years) was conducted. RESULTS: Late CF (>6 months) was related to a higher risk of food allergy (OR [95% CI] = 1.35 [1.02; 1.78]), a low diversity score at 8 months to a higher risk of asthma (OR [95% CI] = 1.22 [1.01; 1.48]), and two allergenic foods or more not being introduced at 10 months to a higher risk of rhinoconjunctivitis (OR [95% CI] = 1.20 [1.00; 1.44]) and food allergy (OR [95% CI] = 2.46 [1.77; 3.42]). Only this last association remained significant after the exclusion of early cases. CONCLUSION: The delayed introduction of major allergenic foods is related to a higher risk of food allergy, which supports the updated guidelines for allergy prevention.

[Food allergy at school: Personalized healthcare project and adrenaline]. / Prise en charge des allergies alimentaires en milieu scolaire en France : projet d'accueil individualisé et adrénaline.

In Europe, the prevalence of food allergy is estimated at 6-8% of children. Ten to 20% of pediatric food-induced anaphylaxis reactions occur at school. Individual healthcare plans (IHP) for food allergy aim at: identifying children at risk of allergic reactions; reducing the risk of allergen exposure; providing emergency kits containing adrenaline auto-injectors (AAI) if needed with emergency action plans and instructions about when and how to use AAI. In France, IHP were introduced into law in 2003 and was updated in 2021. The number of IHP for allergy is increasing since 10 years (50,000 IHP for allergy/year). While the recommendations of the learned societies have resulted in the national harmonization of criteria for the implementation of IHP for allergy and for the prescription of emergency kits with AAI, adrenaline remains underused. In 2019, a national policy stated that all high schools must have a provision of spare AAI in case of anaphylaxis and the promotion of school staff training about food allergy and anaphylaxis was encouraged. These recommendations should be assessed widely and allergy training should be widespread. Pharmacists play an important role to take care of food-allergic children: provision of AAI prescribed for the most at-risk food allergic patients, advice and information on AAI. The pharmacist is therefore a key player in the therapeutic education of the patient to reinforce the key messages on the efficacy and safety of adrenaline used for anaphylaxis.

New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview.

Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult-to-manage patients characterized by early-onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta-analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self-sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population-based, birth and patient cohorts show that early-onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high-risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high-risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss-of-function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components.

Remodelling and inflammation in preschoolers with severe recurrent wheeze and asthma outcome at school age.

BACKGROUND: The influence of airway remodelling and inflammation in preschoolers with severe recurrent wheeze on asthma outcomes is poorly understood. OBJECTIVE: To assess their association with asthma symptoms and lung function at school age. METHODS: Preschoolers (38.4 months) initially investigated with bronchial biopsies were re-assessed for asthma symptoms and lung function at school age. RESULTS: Thirty-six of 49 preschoolers (73.5%) were assessed at 10.9 years. Twenty-six (72.2%) had persistent asthma. Submucosal eosinophil counts were higher in children with severe exacerbations at school age than in those without (16/0.1 mm2 [11.2-30.4] vs 8/0.1 mm2 [2.4-17.6], P = .02), and correlated with the number of severe exacerbations (P = .04, r = .35). Submucosal neutrophil counts correlated with FEV1/FVC (P < .01, r = .47) and FEF25-75% predicted (P = .02, r = .43). Airway smooth muscle (ASM) area correlated with FEV1/FVC (P < .01, r = .51). Vessel numbers negatively correlated with FEV1% predicted and FEV1/FVC (P = .03, r = -.42; P = .04, r = -.41; respectively) and FEF25-75% predicted (P = .02, r = -.46). CONCLUSION: Eosinophilic inflammation in preschoolers with severe recurrent wheeze might be predictive of future severe exacerbations, neutrophilia might be associated with better lung function. Changes in ASM and vascularity might affect lung function at school age.

Food allergy phenotypes: The key to personalized therapy.

Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE-mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE-mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies.

Three peanut-allergic/sensitized phenotypes with gender difference.

BACKGROUND: Peanut-allergic reactions are heterogeneous ranging from mild symptoms to anaphylaxis. OBJECTIVE: Identify peanut-allergic/sensitized phenotypes to personalize patient management. METHODS: A combined factor and cluster analysis was used to study the phenotypes of 696 patients diagnosed with peanut sensitization and enrolled in the MIRABEL survey. The method was first applied to the 247 patients with an oral food challenge (OFC). It was then applied to the 449 patients without OFC to confirm the findings in an independent population. RESULTS: Three independent clusters emerged from the OFC subgroup. Cluster 1, 'Severe peanut allergy with little allergic multi-morbidity' (123 subjects), had the highest proportion of patients with positive OFC (92%), a medium level of peanut protein inducing a positive OFC (235 mg), lower percentage of allergic multi-morbidity (2% asthma plus atopic dermatitis (A + AD), no cases of A + AD + multiple food allergies (MFA)). Cluster 2, 'Severe peanut allergy with frequent allergic multi-morbidity' (62 subjects), had a high proportion of patients with positive OFC (85%) with the lowest level of peanut protein inducing a positive OFC (112 mg), 89% allergic subjects, 100% with allergic multi-morbidity (A + AD) and 84% with A + AD + MFA. Cluster 3, 'Mild peanut-allergic/sensitized phenotype' (62 subjects), had the lowest mean age, the lowest proportion of patients with positive OFC (53%) with a high level of peanut protein inducing a positive OFC (770 mg), a low percentage of allergic multi-morbidity (48% A + AD + MFA). The two severe peanut-allergic phenotypes were more frequent in girls. The same clusters were found in the subgroup of patients without OFC. CONCLUSION & CLINICAL RELEVANCE: Besides the classic markers associated with lower threshold doses of OFC (such as SPT and rAra h 2), allergic multi-morbidity and female gender should also be taken into account to better adapt the progressive dosage of provocation tests.

Peanut-allergic patients in the MIRABEL survey: characteristics, allergists' dietary advice and lessons from real life.

BACKGROUND: The MIRABEL survey is an observational study on peanut allergy in France, Belgium and Luxemburg. The objectives are to provide data on a large population, to analyse the consumer behaviour, to study the presence of peanut traces in pre-packed foods with/without precautionary allergen labelling (PAL), and to combine these data to quantify allergic risk and produce a cost/benefit analysis. This paper reports a real-life observatory of 785 patients (< 16y: 86%): medical characteristics, eliciting doses (ED) in real life and in oral food challenges (OFC), factors associated with severe reactions, allergist dietary advice and patients' anxiety regarding their allergy. METHODS: Age and symptoms at diagnosis, route of exposure, comorbidities, allergy tests, ED (OFC/real life; mg peanut protein), dietary advice about PAL, and anxiety score were recorded. RESULTS: Median age was 3 years; 85% were declared allergic. Severe/potentially severe reactions were reported in 30% of the allergic patients: serious systemic reaction (15%), laryngeal angioedema (8%), shock (4%) and acute asthma (3%); 66% had atopic dermatitis, 58% asthma. Median ara h 2 sIgE level was 11.5 kUA/L. Of the 278 OFCs, 225 were positive (median ED: 67.3 mg). Real-life ED was < 100 mg in 44.3%. Severe reactions were significantly more frequent in teenagers and adults (P = 0.004), asthmatic patients (P = 0.033), and patients who reacted to inhalation (P < 0.001). No significant association was found for OFC ED or ara h 2 sIgE. Factors associated with strict avoidance advice including PAL were OFC ED < 100 mg (P < 0.001), but not severe reaction history (P = 0.051) or asthma (P = 0.34). Anxiety was significantly associated with strict avoidance (P < 0.001). CONCLUSION AND CLINICAL RELEVANCE: Severe/potentially severe reactions, allergic comorbidities, and low EDs in real life are frequent in peanut-allergic patients. Asthma, teenage/adulthood and reaction to inhalation are associated with severe symptoms. PAL and criteria guiding dietary advice need to be improved.

Assessment of microscopic and molecular tools for the diagnosis and follow-up of cryptosporidiosis in patients at risk.

Cryptosporidiosis is an important though underreported public health concern. Molecular tools might be helpful in improving its diagnosis. In this study, ZR Fecal DNA MiniPrep™ Kit (ZR) and NucliSens® easyMAG® (EM) were compared using four Cryptosporidium-seeded feces and 29 Cryptosporidium-positive stools. Thereafter, ZR was selected for prospective evaluation of Cryptosporidium detection by 18S rDNA and LAXER quantitative PCR (qPCR) in 69 stools from 56 patients after Cryptosporidium detection by glycerin, modified Ziehl-Neelsen (ZN) and auramine-phenol (AP) stainings. The combination of any of the two extraction methods with 18S qPCR yielded adequate detection of Cryptosporidium in seeded stools, but the ZR kit showed the best performance. All 29 Cryptosporidium-positive samples were positive with 18S qPCR, after both ZR and EM extraction. However, false-negative results were found with LAXER qPCR or nested PCR. Cryptosporidiosis was diagnosed in 7/56 patients. All the microscopic methods enabled the initial diagnosis, but Cryptosporidium was detected in 12, 13, and 14 samples from these seven patients after glycerin, ZN, and AP staining respectively. Among these samples, 14 and 12 were positive with 18S and LAXER qPCR respectively. In two patients, Cryptosporidium DNA loads were found to be correlated with clinical evolution. Although little known, glycerin is a sensitive method for the initial detection of Cryptosporidium. When combined with 18S qPCR, ZR extraction, which had not been evaluated so far for Cryptosporidium, was an accurate tool for detecting Cryptosporidium and estimating the oocyst shedding in the course of infection.

Asthma control assessment in a pediatric population: comparison between GINA/NAEPP guidelines, Childhood Asthma Control Test (C-ACT), and physician's rating.

BACKGROUND: Guidelines recommend regular assessment of asthma control. The Childhood Asthma Control Test (C-ACT) is a clinically validated tool. AIM: To evaluate asthma control according to GINA2006, NAEPP, pediatrician's assessment (PA), and C-ACT in asthmatic children visiting their ambulatory pediatrician or tertiary care pediatric pulmonologist. METHODS: Demographic data, treatment, and number of severe exacerbations during the previous year were collected. Control was assessed using (i) strict GINA 2006 criteria, (ii) GINA without taking into account the exacerbation item, (iii) NAEPP criteria, and (iv) PA. Children and parents filled out the C-ACT. RESULTS: Five hundred and twenty-five children completed the survey (mean age: 7.7 years; 28% ≤ 6 years). 78% had a controller treatment. 58% reported ≥ 1 severe exacerbation. C-ACT was ≤ 19 in 29.5%. Control was not achieved in 76.5%, 55%, 40%, and 34% according to GINA 2006 guidelines, NAEPP guidelines, GINA 2006 without exacerbation criteria, and PA, respectively. C-ACT was significantly lower in children ≤ 6 years old (P = 0.002) or with severe exacerbations (P < 0.0001). According to PA, 89% of patients with a C-ACT > 21 were controlled and 85% of patients with a C-ACT < 17 not controlled. CONCLUSION: We observed discrepancies between the different tools applied to assess asthma control in children, and the impact of age and exacerbations. Cutoff point of 19 of C-ACT was not associated with the best performance compared to PA. Assessment of control should take into account symptoms and lung function as suggested by the latest GINA guidelines as well as exacerbation over a long period.

Survey of hospital procedures for parapneumonic effusion in children highlights need for standardised management.

AIM: This study sought to evaluate the initial management of children with parapneumonic effusion admitted to all French university hospitals. METHODS: A nationwide survey of all 35 university hospitals took place in 2011 to assess practices for children with parapneumonic effusion, using a hypothetical clinical vignette and a standardised questionnaire. Two to four paediatricians per hospital were interviewed and asked about their initial management, probabilistic antibiotic therapy and its adaptation to microbiological results and subsequent course. Answers from paediatricians working in emergency departments, intensive care units and conventional paediatric units were compared. RESULTS: Of the 100 paediatricians contacted, 95 responded. Of these, 98% would order an initial blood test, 70% would order diagnostic thoracentesis, and all would start immediate antibiotic therapy: 31% with a single drug, 67% with two drugs and 2% with three drugs. The most frequent initial choices were third-generation cephalosporin alone (17%) or combined with rifampicin (34%) or vancomycin (24%). Adaptation varied according to drug used, dose and duration, especially when the microorganism was not Streptococcus pneumoniae. Practices did not differ significantly among the different groups of paediatricians. CONCLUSION: Standardised management of parapneumonic effusion, including routine thoracentesis and more consistent prescription of antibiotics, is needed.

[Managing late-effects after allogeneic stem cell transplantation in children: recommendations from the SFGM-TC]. / Prise en charge des séquelles après greffe de cellules souches hématopoïétiques chez l'enfant : recommandations de la SFGM-TC.

In this report, we address the issue of late-effects after allogeneic stem cell transplantation in children. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille.

Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations.

Some children with severe asthma develop frequent exacerbations despite intensive treatment. We sought to assess the outcome (severe exacerbations and healthcare use, lung function, quality of life and maintenance treatment) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy. 50 children with severe uncontrolled asthma were enrolled in a 12-month prospective study and were randomised into two groups: 1) treatment managed with daily home spirometry and medical feedback (HM) and 2) conventional treatment (CT). The children's mean age was 10.9 yrs (95% confidence interval 10.2-11.6). 44 children completed the study (21 in the HM group and 23 in the CT group). The median number of severe exacerbations per patient was 2.0 (interquartile range 1.0-4.0) in the HM group and 3.0 (1.0-4.0) in the CT group (p=0.38 with adjustment for age). There were no significant differences between the two groups for unscheduled visits (HM 5.0 (3.0-7.0), CT 3.0 (2.0-7.0); p=0.30), lung function (pre-ß(2)-agonist forced expiratory volume in 1 s (FEV(1)) p=0.13), Paediatric Asthma Quality of Life Questionnaire scores (p=0.61) and median daily dose of inhaled corticosteroids (p=0.86). A treatment strategy based on daily FEV(1) monitoring with medical feedback did not reduce severe asthma exacerbations.

Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank.

INTRODUCTION: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted. METHODS AND ANALYSIS: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank. PROSPERO REGISTRATION NUMBERS: CRD42020132990, CRD42020171624.

Asthma: specific clinical and functional characteristics in childhood. Results of a national program in Romanian asthmatic children.

UNLABELLED: Childhood asthma presents with specific clinical and functional characteristics. The aim of our study was the description of a large cohort of asthmatic children. It was also to assess their outcome with maintenance therapy according to guidelines, and to analyze the relationship with baseline's characteristics. We focused particularly on clinical and functional pediatric specificities. METHODS: Prospective study driven on asthmatic children, without treatment, recruited during a hospitalization for exacerbation or a visit for uncontrolled asthma, treated according to GINA guidelines and followed for one year. RESULTS: 412 children (mean age: 11.6 years +/- 2.7), were included. The level of severity was: intermittent asthma for 30% and persistent asthma for 70% (40.5% mild, 28% moderate, 1.5% severe). Mean prebeta2-FEV1 was 88.5% +/- 10.5 (PV) with mean beta2-reversibility of 10.8% +/- 7.8 (> 12% for 42% patients). 374 patients ended the study. After one year, we observed an improvement of clinical symptoms (p < 0.0001), rate of hospitalization (p < 0.0001), and lung function (mean prebeta2-FEV1: 91.2% +/- 7.9, p < 0.001). Asthma control was obtained for only 24.6%. Multivariate analysis show that decrease of symptoms was significantly related to younger age, higher level of initial severity and number of days of hospitalization. CONCLUSION: This study confirms pediatric specificities of asthma, as a normal FEV1 level and a limited beta2-reversibility of FEV1, and the large part of uncontrolled asthma after one year of treatment. It emphasizes the risk of undertreatment in a strategy based on severity. It argues for the regular assessment of control as now recommended, taking into account the pediatric asthma specificities.

Oral food challenge in children: an expert review.

Oral food challenges are indicated for the diagnosis of food allergy and the double-blind, placebo-controlled oral food challenge is considered the gold standard diagnostic method in children with suspected food allergy. This practice parameter for oral food challenges in children was prepared by a workgroup at the request of the French Society for Allergology and Clinical Immunology (SFAIC) and the French Paediatric Society for Allergology and Pulmonology (SP2A). We aimed to develop practical guidelines for oral food challenges in children for the diagnosis of suspected food allergy or the evaluation of food tolerance. We also considered the safety measures to be implemented during testing and management of the potentially serious allergic reactions that may arise during the test. The strength of the recommendations was established, using the GRADE evidence-based approach. We considered four issues: (1) the selection of children for oral food challenges (indications and contraindications); (2) the procedure used (material, where the test should be carried out, technique and management of reactions); (3) interpretation of the test and (4) consequences of the test.

[Resistance to platelet antiaggregants: the cardiologist's point of view]. / Résistance aux antiagrégants plaquettaires : le point de vue du cardiologue.

The concept of resistance to aspirin and clopidogrel, initially described in the laboratory, has currently been reinforced with recent epidemiological clinical data. One of the elements of particular importance for the cardiologist is the possible participation of this resistance in the process of coronary stent thrombosis, a problem which appeared to be solved early in the 1990s with the introduction of thienopyridines. This complication has however become preoccupying again, particularly when occurring late, notably since the widespread use of biologically active coronary endoprostheses. Nevertheless, the debate continues concerning the usefulness of the biological definition of this concept since we still do not have correctly standardized coherent biological tools that can be used in the clinical setting to detect "resistant" patients. Since there is no real therapeutic strategy which should be applied in the event of resistance, there still is little interest in developing screening methods. But the cardiology community can learn from this concept. We should revisit the principles of revascularization within the framework of the rules of good clinical practice, without speculating about the possible therapeutic finality which might develop should such and such a phenomenon occur.