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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.

Cashew and pistachio both belong to the Anarcardiacae family. Cashew and pistachio allergies may cause severe symptoms such as anaphylaxis with a very low eliciting dose1,2 . The cashew 2S albumin r Ana o 3 is the only singleplex component-resolved diagnosis immunoassay currently available in clinical practice3-5 . Its structural similarity with the pistachio 2S albumin may explain the cross-reactivity between cashew and pistachio6 . The main objective of this study was to assess the performance of specific IgE to r Ana o 3 for the diagnosis of pistachio allergy.

International audience; BackgroundOver 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).ObjectiveTo evaluate changes in allergic diseases due to IgE sensitization over 25 years in asthmatic children.MethodsThis 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).Results121 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=0.0002). Allergic rhinitis prevalence was significantly higher in the RC than in the OC (96% vs 52%, respectively, p

International audience; BACKGROUND: As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort. METHODS: Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. RESULTS: Five clusters were identified among 3,446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitisation at 8 years. CONCLUSION: Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.

The hospital admission rate for anaphylaxis is increasing especially among the youngest children and food is the leading cause of anaphylaxis in children. In 2014, an emergency action plan for accidental food allergic reactions in children has been proposed to the medical community by the French Allergology Society. Since its publication, new information (dissemination of recommendations on the management of anaphylaxis, provision of a new dosage of 0.5 mg epinephrine in one of the autoinjector available in France, confirmation of the lack of evidence of the effectiveness of oral corticosteroids in anaphylaxis, experience gained on the use of the current action plan…) has led to an update of the initial emergency action plan. As a result, the “Allergy at school” working group, in conjunction with the task forces“Food allergy” working group of the French Allergology Society, supported by various learned societies, medical and patients’ associations, is proposing an update of the emergency action plan in case of allergic reaction in children and adolescents. The aim of this initiative is to harmonize current practices and to improve the quality of the management of allergic emergencies. The present manuscript combines a rationale on the contents of the emergency kit and the epinephrine autoinjectors.

International audience; The risk of reactions due to the unintentional presence of allergens, such as traces in packaged products, remains difficult to characterize. The aim was to assess the risk regarding unintended traces of peanut in packaged food products in peanut allergic patients using original data from the MIRABEL survey. We developed an integrated Bayesian probabilistic risk model based on relevant data including consumption of a panel of selected products with and without precautionary labelling by peanut allergic patients, and their individual threshold dose at oral food challenge (OFC). 785 patients (

Caroline Dufrois,1 Mélisande Bourgoin-Heck,1 Nathalie Lambert,1,2 Jocelyne Just,1 Aurore Bregeon,1,2 Camille Taillé,3 Stéphanie Wanin1 1Department of Paediatric Allergology, Armand Trousseau University Hospital, Groupe Hospitalier Universitaire, AP-HP Sorbonne-Université, Paris, France; 2Transversal Unit of Therapeutic Education of the Patient, Sorbonne University, Paris, France; 3Department of Respiratory Diseases, Hôpital Bichat, Groupe Hospitalier Universitaire, AP-HP Nord-Université de Paris, Paris, FranceCorrespondence: Stéphanie Wanin, Department of Paediatric Allergology, Armand Trousseau University Hospital, Groupe Hospitalier Universitaire, AP-HP Sorbonne-Université, 26, Avenue Arnold Netter, Paris, 75012, France, Tel +33 1 87 89 27 62, Email stephanie.wanin@aphp.frBackground: 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.Keywords: severe asthma, transition, adolescents, pulmonology, asthma control, adults

National audience

Background Natural course and co-occurrence of asthma, eczema, and allergic rhinitis through childhood are still not fully documented. We aim to identify and characterize profiles based on the time course, severity, and apparent triggers of respiratory/allergy symptoms in school-aged children. Methods Data on occurrence, severity, and triggers of asthma, rhinitis, and dermatitis symptoms were collected annually during the follow-up of the PARIS birth cohort. Children with similar symptom trajectories until 8-9 years were grouped into profiles using multidimensional (all symptoms considered simultaneously) cluster analysis. Associations between profiles and different health outcomes were analyzed using logistic or linear regression models. Results Six distinct symptomatic profiles were identified. A profile was defined by persistent dermatitis symptoms, associated with sensitization to food and aeroallergens. Two profiles were characterized by wheezing: one with early transient wheezing and the other with persistent wheezing related to doctor-diagnosed asthma, airway obstruction, and perennial aeroallergen sensitization. Three profiles were characterized by rhinitis symptoms: one non-allergic and two allergic, either with persistent rhinitis symptoms related to allergic multimorbidity and sensitization to perennial aeroallergens, or with late-onset symptoms, related to both pollen and perennial aeroallergens sensitization as well as low lung function. Conclusion This study brings further insights into the developmental profiles of respiratory/allergic outcomes from birth to school age. The identified profiles clearly differed regarding objective features such as diagnosed morbidity, sensitization, or lung function measurements, thus highlighting their biologic and clinical relevance. Allergic rhinitis profiles deserve particular attention, since they were likely to be involved in multimorbidity patterns.

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, Bronchoalveolar lavage can help characterise severe asthma in children. However, it can be poorly tolerated and, in most cases, its impact on the patient's management remains limited. https://bit.ly/39XOlMt

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 years 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 breastfeeding at 6 months, and consumption of organic food were associated with higher adherence to the MD. Compared to 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/μL 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

BackgroundDaily levels of ambient air pollution and pollen may affect lung function but have rarely been studied together. We investigated short-term exposure to pollen and air pollution in relation to lung function in school-age children from a French population-based birth cohort.MethodsThis study included 1063 children from the PARIS (Pollution and Asthma Risk: an Infant Study) cohort whose lung function and FeNO measurements were performed at age 8 years old. Exposure data were collected up to 4 days before testing. We estimated daily total pollen concentration, daily allergenic risk indices for nine pollen taxa, as well as daily concentrations of three air pollutants (particulate matter less than 10 µm (PM10), nitrogen dioxide (NO2), ozone (O3)). Children with similar pollen and air pollution exposure were grouped using multidimensional longitudinal cluster analysis. Associations between clusters of pollen and air pollution exposure and respiratory indices (FEV1, FVC, FeNO) were studied using multivariable linear and logistic regression models adjusted for potential confounders.ResultsFour clusters of exposure were identified: no pollen and low air pollution (Cluster 1), grass pollen (Cluster 2), PM10(Cluster 3) and birch/plane-tree pollen with high total pollen count (Cluster 4). Compared with children in Cluster 1, children in Cluster 2 had significantly lower FEV1and FVC levels, and children from Cluster 3 had higher FeNO levels. For FEV1and FVC, the associations appeared stronger in children with current asthma. Additional analysis suggested a joint effect of grass pollen and air pollution on lung function.ConclusionDaily ambient chemical and biological air quality could adversely influence lung function in children.

International audience; 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.

RESUME L’heterogeneite de l’asthme et des maladies allergiques dans l’enfance est caracterisee par de multiples phenotypes lies a des mecanismes physiopathologiques differents qui caracterisent les endotypes. Les sensibilisations allergeniques multiples et precoces sont associees a un risque plus eleve d’exacerbations d’asthme. Le risque de persistance de l’asthme a l’âge adulte est un phenotype d’asthme severe notamment a debut precoce avec co-morbiditees allergiques multiples et/ou avec mauvaise fonction respiratoire. A l’inverse, l’inflammation des voies respiratoires a neutrophile n’est pas frequente chez les enfants souffrant d’asthme et n’est pas stable au cours du temps.

Background Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored gene-gene (G-G) interactions. Objective Our aim was to detect new interacting genes involved in eczema. Methods The search for G-G interaction in eczema was conducted using a two-step approach, which included as a first step, a biological selection of genes, which are involved either in the skin or epidermis development or in the collagen metabolism, and as a second step, an interaction analysis of the selected genes. Analyses were carried out at both SNP and gene levels in three asthma-ascertained family samples: the discovery dataset of 388 EGEA (Epidemiological study on the Genetics and Environment of Asthma) families and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families and 207 MRCA (Medical Research Council) families. Results One pair of SNPs, rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P ≤ 10-5 showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P = 1.1 × 10-8 under the significant threshold of 10-7 ). Gene-based analysis confirmed strong interaction between COL5A3 and MMP9 (P = 4 × 10-8 under the significant threshold of 4 × 10-6 ) by meta-analysis of the three datasets. When stratifying the data on asthma, this interaction remained in both groups of asthmatic and non-asthmatic subjects. Conclusion This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility. Further confirmation of this interaction as well as functional studies is needed to better understand the role of these genes in eczema.

Immunoglobulin-E mediated-cow's milk allergy (IgE-CMA) is the one of the most frequent IgE mediated-food allergy in children in industrialized countries and may cause life- threatening anaphylaxis. The natural history of CM IgE mediated food allergy is favorable for most children. However, the clinical outcome of CMA seems worse than previously described, with less chance of recovery after the age of 31. This article is protected by copyright. All rights reserved.

Asthma is a heterogeneous disease characterized by numerous phenotypes relating to age of onset, triggers, comorbidities, severity (assessed by multiple exacerbations, lung function pattern) and finally the inflammatory cells involved in the pathophysiologic pathway. These phenotypes can vary over time in relation to changes in the principal triggers involved in the aetiology of the disease. Nevertheless, in a patient with multiple allergies and early-onset disease (defined as multiple sensitizations and allergic comorbidities), the prognosis of asthma is poor with a high risk of persistence and severity of the disease during childhood. Future research will focus on classifying phenotypes into groups based on pathophysiologic mechanisms (endotypes) and the biomarkers attached to these endotypes, which could predict prognosis and lead to targeted therapy. Currently, these biomarkers are related to inflammatory cells associated with the asthma endotype, essentially eosinophils and neutrophils (and related cytokines) attached to Th-2 and non Th-1 pathways, respectively. The most severe asthma (refractory asthma) is linked to neutrophil-derived inflammation (frequently associated with female sex, obesity and possibly disorganized airway microbiota) encountered in very young children or teenagers. Severe asthma is also linked to or a marked eosinophil inflammatory process (frequently associated with multiple atopy and, more rarely, with non-atopic hypereosinophilic asthma in children) and frequently encountered in teenagers. Severe phenotypes of asthma could also play a role in the origin of chronic obstructive pulmonary disease in adult life.

Introduction: STELLAIR1, a real-life retrospective study, demonstrated the efficacy of Omalizumab (OMA) in severe allergic asthma, regardless of blood eosinophil level. The objective of this analysis is to study OMA efficacy in the STELLAR population according to the presence of multiple allergic comorbidities (MAC). Methods: The STELLAIR population was divided into 2 groups: with (>2) or without ( 2 allergic comorbidities were taken into account to differentiate the 2 groups. Efficacy of OMA was evaluated after 4 to 6 months via: physician evaluation (using GETE scale), reduction of >40% exacerbations and combination of both. Results: MAC were more common in children (6-17yrs) than in adults (≥18yrs) (47.5% and 13.9%, respectively). Age of initiation of OMA was lower in patients with MAC (32.3 versus 46.2 years). Patients with MAC had a higher response rate to OMA according to the efficacy evaluation criteria: (1) 81.6% versus 66.6% as assessed by the physician (p Conclusion: MAC are present in both children and adults with severe allergic asthma, which suggests that this phenotype is present throughout life. OMA is beneficial in patients with or without MAC and response is more pronounced in patients with MAC. The presence of MAC might be a factor that predicts the response to OMA. 1Humbert M, et al. Eur Respir J. 2018 10; 51(5)

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care. ispartof: ALLERGY vol:74 issue:7 pages:1219-1236 ispartof: location:Denmark status: published

Background Google Trends (GTs) is a web-based surveillance tool that explores the searching trends of specific queries via Google. This tool proposes to reflect the real-life epidemiology of allergic rhinitis and asthma. However, the validation of GTs against pollen concentrations is missing at the country level. Objectives In the present study, we used GTs (a) to compare the terms related to allergy in France, (b) to assess seasonal variations across the country for 5 years and (c) to compare GTs and pollen concentrations for 2016. Methods Google Trends queries were initially searched to investigate the terms reflecting pollen and allergic diseases. 13- and 5-year GTs were used in France. Then, 5-year GTs were assessed in all metropolitan French regions to assess the seasonality of GTs. Finally, GTs were compared with pollen concentrations (Reseau National de Surveillance en Aerobiology) for 2016 in seven regions (GTs) and corresponding cities (pollen concentrations). Results The combination of searches for "allergy" as a disease, "pollen" as a disease cause and "ragweed" as a plant was needed to fully assess the pollen season in France. "Asthma" did not show any seasonality. Using the 5-year GTs, an annual and clear seasonality of queries was found in all regions depending on the predicted pollen exposure for spring and a summer peak but not for winter peaks. The agreement between GT queries and pollen concentrations is usually poor except for spring trees and grasses. Moreover, cypress pollens are insufficiently reported by GTs. Conclusions Google Trends cannot predict the pollen season in France.

Most patients presenting with allergies are first seen in the primary care setting. However, inadequacies in training and available guidance for general practitioners (GP) have been identified as significantly impacting the quality of care for these patients, resulting in inefficient use of healthcare resources. To address the lack of available guidance, a working group of French allergists has developed a series of online tools aimed at GPs. The expert panel developed algorithms for the diagnosis and treatment of common allergies by incorporating deliberations based on clinical guidelines and experience. In addition, they developed tables of common symptoms and detailed clinical cases that guide GPs through the typical decisions they are faced with in line with current best practice. These tools translate evidence-based recommendations from international clinical guidelines, outlining the key steps involved and assisting the physician in making decisions at each step. In addition to targeting improvements in diagnosis and standard of primary care, the tools also aim to reduce the burden on specialist allergy services by enabling GPs to diagnose and treat mild and moderate allergies, referring only severe and/or atypical cases to secondary care. The tools are adapted to the high primary care workload, enabling the physician to access essential information rapidly without unnecessary referrals to specialist allergy services. Keywords: Allergy, Primary care, Diagnosis

Background: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms. Methods: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined. Results: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV1 for an inter-quartile range of 1160 ng/m3 exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase]. Conclusion: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure. The study in Sabadell was funded by grants from Instituto de Salud Carlos III Red INMA (G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 19995GR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació la Marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), EU Commission (261357, 308333 and 603794), the European Community's Seventh Framework Programme (FP7/2007/2013) under grant agreements 308333-HELIX Project and 308610-EXPOSOMICS Project. Dr Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). The study in Valencia was funded by grants from European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (FIS-FEDER funds: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/02032, PI14/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), and Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249).

BackgroundA positional cloning study of bronchial hyper-responsiveness (BHR) at the 17p11 locus in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families showed significant interaction between early-life environmental tobacco smoke (ETS) exposure and genetic variants located in DNAH9. This gene encodes the heavy chain subunit of axonemal dynein, which is involved with ATP in the motile cilia function.Our goal was to identify genetic variants at other genes interacting with ETS in BHR by investigating all genes belonging to the ‘ATP-binding’ and ‘ATPase activity’ pathways which include DNAH9, are targets of cigarette smoke and play a crucial role in the airway inflammation.MethodsFamily-based interaction tests between ETS-exposed and unexposed BHR siblings were conducted in 388 EGEA families. Twenty single-nucleotide polymorphisms (SNP) showing interaction signals (p≤5.10−3) were tested in the 253 Saguenay-Lac-Saint-Jean (SLSJ) families.ResultsOne of these SNPs was significantly replicated for interaction with ETS in SLSJ families (p=0.003). Another SNP reached the significance threshold after correction for multiple testing in the combined analysis of the two samples (p=10−5). Results were confirmed using both a robust log-linear test and a gene-based interaction test.ConclusionThe SNPs showing interaction with ETS belong to the ATP8A1 and ABCA1 genes, which play a role in the maintenance of asymmetry and homeostasis of lung membrane lipids.

Asthma is no longer considered as a single disease but rather as a syndrome corresponding to different entities and pathophysiologic pathways. A targeted strategy is part of personalized medicine which aims to better define each patient's phenotype and endotype so as to prescribe the most suitable treatment at an individual level. Omalizumab and, more recently, mepolizumab are the first biologics approved for children (6-18 years). Omalizumab is now widely used to treat severe allergic asthma in children and is highly effective for asthma exacerbations and asthma control with a good safety profile. Moreover, several other drugs-lebrikizumab, dupilumab, tezepelumab, mepolizumab, reslizumab, benralizumab-are used or are being studied in both teenagers and adults and could benefit younger children in the near future. We hypothesize that defining the asthma phenotype/endotype regarding the type and intensity of inflammation, association with allergic or non-allergic comorbidities, and airway remodeling should contribute to the choice of a specific biologic. Pediatric specificities have to be addressed and validated by studies in children. Long-term effectiveness and particularly the impact on the natural history of asthma should also be investigated. Severe asthma in children is a complex disease, and patients have to be referred to a specialized pediatric asthma center to confirm diagnosis and initiate the best treatment strategy which could include biologics while taking into account their high cost.