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.

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.

High airborne level of Aspergillus fumigatus and presence of azole-resistant TR34/L98H isolates in the home of a cystic fibrosis patient harbouring chronic colonisation with azole-resistant H285Y A. fumigatus.

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in the domestic environment of patients at risk for aspergillosis. Here, we assessed the mother's and father's homes of an 18-year-old cystic fibrosis patient harbouring chronic colonisation with H285Y CYP51A azole-resistant isolate, in order to explore the link between environmental exposure and ARAF infection. In one dwelling, a very high overall contamination level was found (710-7.240 CFU/m3), with a predominance of A. fumigatus (640-6.490 CFU/m3), and ARAF showing the TR34/L98H mutation was isolated. Mycological follow-up of the patient showed the persistence of H285Y isolates, but no acquisition of TR34/L98H isolates was observed. This could be due to the low proportion of TR34/L98H isolates (<3%), or the establishment of preventative measures and dwelling remediation taken after the environmental investigation. Our data underlines the value of an environmental assessment to establish preventative measures and limit the risk of A. fumigatus exposure and ARAF acquisition.

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.

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.

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.

[The interactions between microorganisms and the small airways. A paediatric focus]. / Interactions micro-organismes et voies aériennes distales : spécificités pédiatriques.

The spectrum of respiratory viruses is expanding and emerging diseases have been described regularly over the last fifteen years. The origin of these emerging respiratory viruses may be zoonotic (by crossing species barrier, after changes to RNA viruses such as avian influenza virus type A or coronaviruses), or related to the use of new identification techniques (metapneumovirus, bocavirus). The relationship between bronchiolitis and asthma is now better understood thanks to prospective follow up of birth cohorts. The role of rhinovirus has become predominant with respect to respiratory syncytial virus. The identification of predisposing factors immunological, functional, atopic and genetic, for the onset of asthma after rhinovirus infection suggests that viral infection reveals a predisposition rather than itself being a cause of asthma. The role of bacteria in the natural history of asthma is also beginning to be better understood. The results of the COPSAC Danish cohort have shown the frequency of bacterial identification during wheezy episodes before 3 years, and the impact of bacterial colonization at the age of one month on the onset of asthma by age 5 years. The role of bacterial infections in severe asthma in young children is also discussed.

[Anaphylaxis in children: What pediatricians should know]. / Anaphylaxie de l'enfant : ce que le pédiatre doit savoir.

Anaphylaxis is a severe potentially life-threatening allergic emergency that has been increasing over the last two decades, especially in young children. Anaphylaxis deaths remain rare, in particular in children, and their frequency is stable during this period. Food is the main anaphylaxis trigger in children, notably to cow's milk, peanuts, and tree nuts. In infants, the recognition of anaphylaxis may be difficult. Vomiting, urticaria, and laryngeal edema are more frequent at this age. Cardiovascular involvement is rare, most often encountered in adolescence. A history of asthma or atopy, allergy to particular foods such as peanuts and tree nuts, and adolescence are some risk factors for anaphylaxis and more severe reactions. First-line treatment is intramuscular adrenaline for all patients experiencing anaphylaxis. There are no absolute contra-indications. Guidelines for the prescription of the adrenaline auto-injector and for establishing a personalized care project in allergic children at school have recently been updated. Recognition of anaphylaxis and treatment should also be improved.

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.