Background:The use of molecular allergens have greatly improved the clinical relevance of specific IgE serologies during allergy work-up. Very little is known regarding the added value of molecular allergens in the results of the basophil activation test (BAT). Objective:To study the BAT concordance when using similar amounts of molecular allergens against source extracts, and to assess factors associated with BAT discrepancies between extract and related component. Methods:Systematic retrospective monocentric study of all BAT performed at the Trousseau Hospital, Paris, France, with both molecular components and corresponding extract. Results:Data from 213 interpretable extract/component BAT pairs (89 cow milk, 70 wheat, 28 house dust mites (HDM), 12 peanut, 9 hen egg, 3 peach, 1 apple, 1 chicken meat), corresponding to 150 blood samples from 109 patients were analyzed. Among BAT pairs showing allergen sensitizations, the two reagents only showed moderate agreement (κ = 0.62), with 18% (36/201) discordant BAT results. Among 36 cases of discrepant BAT results between extract and molecular component, 69% (25/36) were extract+/component- (p=0.03), in line with genuine allergic status, in contrast with the opposite case. Even in extract+/component+ concordant cases, component-stimulated basophils showed 6% less activation rates than their extract-stimulated counterpart. After stratification by allergen, better performances were confirmed with cow milk extract, but not with other allergens, which display large disparity regarding the propensity of different molecular component to activate basophils. Independently of the considered allergen, other variables such as total IgE, BAT positive control values, and treatment with monoclonal antibody or allergen-specific immunotherapy, appear to further modulate the risk of presenting a discordant BAT result. Conclusion:In our study population, molecular components had lower capacity than the corresponding extract to activate IgE-sensitized basophils, which partly explain higher rates of true positive extract+/component- BAT. Component-based BAT can potentially lead to false-negative results, and extract-based should generally be preferred, especially for cow milk.

BACKGROUND:Interest has grown recently in childhood diet's role in allergy development. However, the studies focusing on organic food consumption are scarce. We address the relationships between such consumption and respiratory/allergic morbidity at school age in the PARIS (Pollution and asthma risk: An infant study) cohort. METHODS:Diet was assessed using a food frequency questionnaire completed by the parents at 8 years. Dietary patterns were identified by cluster analysis based on the consumption frequency of 30 foods (either organic or conventional) and 19 organic foods. Associations between dietary patterns and respiratory/allergic morbidity (asthma, rhinitis, eczema and sensitisation) were studied using multivariable logistic regression models adjusted for potential confounders, including family socioeconomic status and adherence to the Mediterranean diet as a proxy for dietary balance. RESULTS:Among 1258 children, three dietary patterns were identified, which differed significantly in terms of organic food consumption frequency: low frequency in G0 (51% of children), moderate in G1 (28%) and high in G2 (21%). No association was found between dietary patterns and asthma, eczema, rhinitis or sensitisation to food allergens. Children in G2 had lower likelihood of sensitisation to any allergen than those in G0 (adjusted odds ratio [aOR] = 0.60; 95% confidence interval [CI]: 0.40-0.91), particularly to inhalant allergens (aOR = 0.64; 95% CI: 0.42-0.99). CONCLUSIONS:Our findings suggest that frequent organic food consumption may be protective against allergic sensitisation at school age, based on the assumption that organic food consumption at the age of eight reflects consumption at earlier ages. Further research is warranted to explore the underlying mechanisms for this association, including nutritional and environmental exposures.

Background: Several major sensitization profiles have been described in children with asthma, but it remains unclear how these profiles relate to asthma phenotypes. The aim of this study was to determine allergenic sensitization profiles in a megacity cohort (SAMP). Methods: This was a cross-sectional analysis performed from 2011 to 2015 including preschool and school-age children with severe and moderate asthma from the SAMP cohort. We performed ALEX multiplex array and carried out cluster analysis. Results: Data from 367 children were analysed: 224 of preschool age and 143 of school age, respectively 84 (38%) and 114 (80%) presented at least one allergic sensitization. At preschool age, three clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non-type 2 (T2) inflammation (n=61); Cluster 2, Predominant sensitization to HDM molecular families. (n=16); Cluster 3, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n=7). At school age, five clusters were identified: Cluster 1, Few sensitizations to inhaled allergen molecular families and non-T2 inflammation (n=43); Cluster 2, Predominant sensitization to HDM molecular families (n=31); Cluster 3, Predominant sensitization to PR-10 family (n=25); Cluster 4, Severe asthma with predominant sensitization to tropomyosin family (n=11); Cluster 5, Severe asthma with multiple sensitizations to inhaled and food allergen molecular families (n=4). Conclusion: These results underline the heterogeneity of sensitization profiles in severe allergic childhood asthma. The most severe asthma phenotypes were associated with multiple sensitizations to both inhaled and food allergen molecular families as expected, and to the tropomyosin molecular family, a novel finding.

Respiratory allergy often begins in childhood and most commonly manifests as allergic rhinitis (upper airways) and/or asthma (lower airways).) Children with upper respiratory allergy often suffer from coexisting asthma, and other comorbidities ranging from gastrointestinal disorders to emotional/mental health disorders. Consequently, the disease burden is considerable and profoundly impacts a child’s daily life.Early identification and appropriate management are important to reduce disease burden, lower the risk of disease progression and additional comorbidities, and protect the child’s future well-being. A window of opportunity for halting disease progression may open in the early stages of allergic disease and underlines the importance of early diagnosis and treatment of children at risk. This review offers advice on identifying children with a high disease burden who would benefit from early intervention.Allergen immunotherapy (AIT) modifies the cause of respiratory allergy and prevents disease progression. In clinical practice, AIT could be considered as an early treatment for eligible children, to achieve long-term symptom control and disease modification.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) has been identified to be a risk factor for asthma, but its determinants remain unclear.OBJECTIVE: To determine the significance of SE sensitization in children with moderate to severe asthma.METHODS: This was an observational cross-sectional analysis performed from 2011 to 2015 including children from the prospective Severe Asthma Molecular Phenotype cohort: school -age children with severe and moderate asthma or preschool-age children with severe and moderate recurrent wheeze. We evalu-ated sensitization to four SEs (Staphylococcus enterotoxin A, Staphylococcus enterotoxin B, Staphylococcus enterotoxin C, and toxic shock staphylococcic toxin).RESULTS: We analyzed data from 377 children: 233 of preschool age and 144 of school age. Among them, 26 (11.2%) and 59 (41.0%) children, respectively, had sensitization to at least one SE. The burden of sensitization was higher in older children in terms of both specific IgE levels and the number of sensitizations. In multivariable analysis, SE sensitization was associated with elevated total IgE in both populations (odds ratio [OR] = 9.35, P = .01; and OR = 8.06, P < .01), and with bronchoalveolar lavage eosinophilia in both preschool and school-age children (OR = 3.95, P = .03; and OR = 4.11, P = .03, respectively). Classification and regression trees showed an association of SE sensitization with age and with total IgE in the entire population, and with total IgE, bronchoalveolar lavage eosinophilia, and blood eosinophilia in school-age children.CONCLUSIONS: Staphylococcal enterotoxin sensitization was correlated with type 2-high inflammation (eosinophilic inflam-mation and elevated total IgE count) in this population of moderate to severe asthmatic children. (c) 2022 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:564-71)

Immunoglobulin E (IgE) plays a critical role in the allergen-initiated inflammatory pathway and thus serves as a viable therapeutic target in allergic or IgE-mediated diseases such as asthma. Omalizumab, an anti-IgE biologic, has been approved in the United States (US, 2003) and in the European Union (EU, 2005) as an add-on therapy in patients with moderate-to-severe persistent asthma and severe allergic asthma (SAA) aged 6 years and older. The dose and frequency of omalizumab are adjusted based on the patient's body weight and baseline IgE levels, as recommended by its dosing tables. Currently, these dosing recommendations are limited to patients with baseline IgE levels of up to 1500 IU/mL in the European Union and 700 IU/mL in the United States. However, many patients with SAA have IgE levels >1500 IU/mL, highlighting an unmet need. This review presents the current evidence on the treatment benefits of omalizumab in patients with IgE levels >1500 IU/mL. The findings from the reviewed studies which included >3000 patients support the efficacy and effectiveness of omalizumab in reducing exacerbations, and improving asthma control, lung function, and quality of life in patients with severe asthma having IgE levels beyond the current dosing range. Omalizumab was well-tolerated in these patients, with no new safety signals. In addition, high IgE levels (>1500 IU/mL) are also reported in several comorbidities of asthma (allergic rhinitis, atopic dermatitis, allergic bronchopulmonary aspergillosis [ABPA], food allergy, and nasal polyposis) and omalizumab has demonstrated efficacy and safety in these indications. These data suggest that omalizumab may be considered for administration in SAA patients, with high IgE levels outside the current dosing tables. A detailed assessment of patients with high IgE levels is needed before deciding on the optimal treatment approach. A management algorithm for SAA patients with IgE >1500 IU/mL is proposed in this review and a suggestion to follow the Delphi consensus is advised.

Background:The prevalence of severe asthma in adolescents is estimated at 6.7%. Transition to adult health services is a vulnerable period for adolescents where there is a risk of poor treatment adherence and loss to follow-up.Purpose:This retrospective study evaluated the maintenance of asthma control in young severe asthmatics, 6 months and 1 year after transition to a specialist adult centre.Methods:Patients with severe asthma treated in a paediatric pulmonology centre in the Île-de-France and referred at least 6 months previously to an adult service were included. Asthma control was evaluated by measuring the ACT score and respiratory function. Patients were asked to answer an on-line questionnaire about their experiences during transition.Results:Fifty-four adolescents with severe asthma underwent transition to the adult service between 2014 and 2021. Thirteen patients (25%) were lost to follow-up after an average of 22.4 months of follow-up. Three-quarters (73%) of patients had well controlled asthma with an ACT score ≥20 during transition and the majority were able to maintain good control and respiratory function (>60% FEV1 >80%) during follow-up in adult pulmonology. Among the patients that answered the questionnaire, 64.8% were satisfied with the transition process.Conclusion:Asthma control and respiratory function were maintained 6 months and 1 year after transition to the adult centre in the majority of patients. Most patients were satisfied with the transition process, but several improvements can be proposed, including early discussion of the medical plan and the implementation of procedures to reduce loss to follow-up.

Background: Immunoglobulin (Ig) E-mediated pathophysiological mechanisms are common in allergic diseases including severe allergic asthma (SAA). The anti-IgE monoclonal antibody omalizumab may be particularly beneficial for patients with SAA and multiple allergic comorbidities (AC) including perennial/seasonal rhinitis, conjunctivitis, atopic dermatitis (AD), and food allergy. Methods: We conducted a post-hoc analysis of the patients from the STELLAIR study (n=872, 149 minors and 723 adults). The patients were classified based on the presence of multiple AC (>= 3 AC or <3 AC) or AD as assessed by questionnaire. Response to omalizumab was assessed after 4-6 months (T4-6) and after 12 months (T-12). Asthma response at T4-6 was based on global evaluation of treatment effectiveness, reduction of >= 40% in annual exacerbation rate, and a combination of both. Asthma response at T-12 was based on change in yearly exacerbation and hospitalization rates. AC improvement at T-12 was based on patient perception. Results: Patients with >= 3 AC demonstrated a higher combined response to omalizumab (74.7% vs 58.3%) at T4-6 and had reduced yearly exacerbation and hospitalization rates (88.9% vs 77.4% and -94.0% vs -70.5%, respectively). Patients with >= 3 AC were more likely to show an improvement in their AC (85.3% vs 51.9%) at T-12. Results were similar in minors and adults. The presence of AD was associated with greater omalizumab effectiveness at T4-6 and a greater AC improvement at T-12. Improvement of AD and food allergies at T-12 were 73.2% and 38.7%, respectively, in the population overall. Conclusion: This post-hoc analysis of the STELLAIR study shows that omalizumab is beneficial for all SAA patients and especially for patients with multiple AC or AD. In patients with >= 3 AC, omalizumab also improved AC outcomes.

Background: The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow-up, we aimed to investigate the adherence of 8-year-old children to the MD and its association with allergic/respiratory morbidity at school age. Methods: Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV1 and FVC), FeNO and specific IgE levels were determined during a health check-up at 8 years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders. Results: A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breast-feeding at 6 months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8 years, as well as higher FEV1 and FVC. Conclusion: This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school-aged children.

Background Asthma is a heterogeneous disease in which the interaction between genetic and environmental factors plays a major role. The significance of blood eosinophil is unclear. The aim of the study was to determine the significance of blood eosinophil count in moderate-to-severe asthmatic children of preschool age and school age. Methods This was a prospective cross-sectional study performed from 2011 to 2015 including children from the severe asthma molecular phenotype (SAMP) cohort at Trousseau Hospital (Paris, France). We included children with severe and moderate asthma, or severe and moderate recurrent wheeze, aged from 1 to 15 years at the time of exploration. Results We analyzed data from 402 children: 248 of preschool age and 154 of school age. Blood eosinophil count third quartile thresholds were 322 and 600 cells/mu L for the preschool- and school-age groups, respectively. In multivariate analysis, a blood eosinophil count over this threshold was associated with elevated total IgE (OR = 5.33, P < .01), multiple hospitalizations for asthma attacks (OR = 4.96, P = .03), and a maternal history of asthma (OR = 4.91, P = .01) in preschool children; and with staphylococcal toxin-specific IgE (OR = 2.75, P = .03) in children of school age. Random forest analysis reinforced these results. Conclusion High blood eosinophil count is linked to both atopic features and control of asthma with different parameters associated with these features depending on age.

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Background: In France, from 30% to 35% of children suffer from multiple food allergies (MFA). The gold standard to diagnosis a food allergy is the oral food challenge (OFC) which is conducted in a hospital setting due to risk of anaphylaxis. The aim of this study was to evaluate an algorithm to predict OFCs at low risk of anaphylaxis that could safely be performed in an office-based setting. Methods: Children with MFA and at least one open OFC reactive or non-reactive to other allergens were included. The algorithm was based on multiple clinical and biological parameters related to food allergens, and designed mainly to predict “low-risk” OFCs i.e., practicable in an office-based setting. The algorithm was secondarily tested in a validation cohort. Results: Ninety-one children (median age 9 years) were included; 94% had at least one allergic comorbidity with an average of three OFCs per child. Of the 261 OFCs analyzed, most (192/261, 74%) were non-reactive. The algorithm failed to correctly predict 32 OFCs with a potentially detrimental consequence but among these only three children had severe symptoms. One hundred eighty-four of the 212 “low-risk” OFCs, (88%) were correctly predicted with a high positive predictive value (87%) and low negative predictive value (44%). These results were confirmed with a validation cohort giving a specificity of 98% and negative predictive value of 100%. Conclusion: This study suggests that the algorithm we present here can predict “low-risk” OFCs in children with MFA which could be safely conducted in an office-based setting. Our results must be confirmed with an algorithm-based machine-learning approach.

Background Although bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management. Material and methods The study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included. Results In total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p<0.001). BAL induced a therapeutic modification only for azithromycin and omalizumab prescriptions. The practice of a BAL decreased bronchoscopy tolerance (p=0.037), especially in the presence of tracheobronchial malacia (p<0.01) and when performed in a symptomatic patient (p=0.019). Discussion and conclusion Although BAL may provide interesting information in characterising severe asthma, in most cases its impact on the patient's management remains limited. Moreover, BAL can be poorly tolerated and should be avoided in the case of tracheobronchial malacia or current asthma symptoms.

BACKGROUND:Over the last few decades, the level of pollen from birch and homologous trees has increased in parts of Europe. Sensitization to birch pollen allergens (principally Bet v 1) has been associated with food cross-reactivity called pollen food allergy syndrome (PFAS). OBJECTIVE:To evaluate changes in allergic diseases due to IgE sensitization over 25 years in asthmatic children. METHODS:This was a cross-sectional retrospective study conducted in Paris. We analyzed two cohorts of asthmatic children with similar characteristics explored between 1993-1999 (old cohort = OC) and 2012-2018 (recent cohort = RC). RESULTS:121 children were in the OC and 120 in the RC. An increase in sensitization to tree pollens was found especially for birch pollen, which was 11.6% in the OC and 31% in the RC (P = .0002). Allergic rhinitis prevalence was significantly higher in the RC than in the OC (96% vs 52%, respectively, P < .0001). IgE-mediated food allergy increased from 6% to 16% in the OC and RC, respectively, (P = .01) mainly due to PFAS. In the RC, a higher mean Bet v 1-specific IgE level was observed in children with PFAS compared to children without (105.7 KU/L ± 17.8 and 48.9 kU/L ± 15.7, respectively, P < .05). CONCLUSION:Allergic rhinitis and food allergy with tree pollen sensitization have increased in Paris over 25 years mainly due to PFAS. Environmental factors could be responsible for these modifications as described in the literature.

BACKGROUND:Longitudinal studies assessing the association of profiles of allergen-specific IgE (sIgE) sensitization to a large range of allergen molecules and respiratory health are rare. We aimed to assess trajectories of molecular sIgE sensitization profiles from childhood to adulthood and their associations with respiratory health.METHODS:IgE reactivity to microarrayed allergen molecules were measured in childhood (EGEA1) and 12 years later in adult life (EGEA2) among 291 EGEA participants (152 with asthma). At each time point, sIgE sensitization profiles were identified by latent class analysis (LCA) by considering IgE-reactivity to the 38 most prevalent respiratory allergens. The LCA-defined profiles were then studied in association with respiratory health.RESULTS:At baseline, the mean (min-max) age of the population was 11 (4.5-16) years. The LCA identified four sIgE sensitization profiles which were very similar at both time points (% at EGEA1 and EGEA2); A: "no/few allergen(s)" (48%, 39%), B: "pollen/animal allergens" (18%, 21%), C: "most prevalent house dust mite allergens" (22%, 27%) and D: "many allergens" (12%, 13%). Overall, 73% of the participants remained in the same profile from childhood to adulthood. The profiles were associated with asthma and rhinitis phenotypes. Participants of profiles C and D had lower FEV1 % and FEF25-75 % as compared to profile A. Similar patterns of associations were observed for participants with asthma. There was no association with change in lung function.CONCLUSION:Using high-resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health.

Introduction: Bronchoscopy is part of severe asthma explorations in children. However, the benefit of a bronchoalveolar lavage (BAL) is unknown. This study aims at deciphering if a systematic BAL during a flexible bronchoscopy procedure could improve phenotyping severe asthma. Secondary objectives were to evaluate BAL impact on asthma control and on flexible bronchoscopy morbidity. Patients and methods: The study was held in two departments of Armand Trousseau University Hospital in Paris, France. Children who underwent a flexible bronchoscopy for severe asthma exploration were retrospectively included between April 2017 and September 2019. Results: A total of 203 children were included, 107 had a BAL and 96 did not. BAL fluid cell count showed no abnormality in most cases. Eosinophils count was increasing with age, independently from atopy. BAL increased up to 1.5 times the rate of identified bacterial infection when comparing to bronchial aspiration only. As expected, non-atopic patients had more bacterial infections (p < 0.001). BAL realization was not associated with improved asthma control (p = 0.62). BAL was correlated with a therapeutic change only for azithromycin and omalizumab. Bronchoscopy tolerance was lower when a BAL was performed (p = 0.037), especially when (i) a tracheobronchial malacia was present (p < 0.01) and (ii) BAL was performed during an asthma exacerbation (p = 0.019). Discussion and conclusion: BAL may add interesting phenotype information in severe asthma. However, in this study, performing a BAL did not seem to be associated with improved asthma control. BAL can be poorly tolerated and should thus be avoided in case of tracheobronchial malacia or asthma exacerbation.

wheezing in the last 12 months" (W12) prevalence was on average 24.9% (IC 95% 24.0-25.8)and 10.3% (IC 95% 9.7-10.9)respectively, significantly higher in the ISAAC study with a percentage difference of 5.6% and 2.9% respectively.Additionally, the antibiotics use in the first year of life was associated with a significantly increased risk of (WE) with an OR 2.38 (2.16-2.63)and W12 with an OR 1.95 (1.7-2.26), a statistically significant correlation was found in both (p<0.01). CONCLUSIONSIn our population, there is an association between antibiotic use in the first year of life and current asthma in children 6 and 7 years old.Further research is required to determine the reasons for these associations.