Background: Periostin has emerged as a novel biomarker in the pathogenesis of T helper 2-type allergic diseases in the last years. The aim of this study was to investigate the association of serum periostin levels with clinical features in children with asthma. Methods: Children with physician-diagnosed asthma who attended regularly to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to recent GINA guidelines. Results: A total of 158 children (125 with asthma and 33 age and sex-matched control subjects) with a median age of 10.2 years (range 5.9-17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%) and severe in 21 (16.8%) children. Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL; p < 0.001). The mean serum periostin levels of children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (p < 0.001). Serum periostin levels were found to be significantly correlated with asthma severity (Spearman’s rho [r]=0.41, p < 0.001). Results of multivariable logistic regression analysis demonstrated an association between serum periostin levels and asthma severity in children (OR, 1.10; 95% CI, 1.04-1.15; p <0.001) Conclusion: Serum periostin levels may serve clinicians in identifying children with severe asthma.

Abstract Background: Ataxia-telangiectasia (A-T) is a rare genetic disorder characterized by a distinct range of clinical manifestations, including progressive ataxia, immunodeficiency, and radiosensitivity. Methods: Clinical data, laboratory results, and genetic data were collected from forty-three A-T patients. Whole exome sequencing and Sanger sequencing were done for the patients clinically diagnosed as suffering from A-T. Based on the phenotype severity of the disease, patients were divided into severe and mild sub-groups. Results: The median (IQR) age of diagnosis in this cohort was 5 (3-7) years and various types of clinical manifestations, including fever (p= 0.005), lower respiratory tract infection (p= 0.033), diarrhea (p= 0.014), and hepatosplenomegaly (p= 0.032) were significantly higher amongst patients diagnosed with the severe phenotype. Our results showed a strong correlation between phenotype severity and mutation type. The chance of having severe phenotype in patients who have severe mutations, including frameshift and nonsense, was 7.3 times higher compared to patients who were categorized in the mild genotype group (odds ratio= 7.3, p= 0.006). Thirty-four types of mutations including 9 novel mutations, were observed in our study. Conclusion: Molecular analysis provides the opportunity for accurate diagnosis and timely management in A-T patients with chronic progressive disease, especially infections and the risk of malignancies. This study characterizes for the first time, the broad spectrum of mutations and phenotypes in Iranian A-T patients which are required for carrier detection and reducing the burden of disease in future using the patients’ families and for the public health care system. Keywords: Ataxia-telangiectasia (A-T), ATM, Whole-exome sequencing, Class switching recombination (CSR), phenotype severity.

Background: H1-antihistamines (AHs) are widely used for the treatment of allergic diseases, being one of the most commonly prescribed classes of medications in Pediatrics. Newer-generation AHs are associated with fewer adverse effects compared to first-generation. However, their relative harms in the pediatric population still need scrutiny. Methods: We performed a systematic review of randomized controlled trials (RCTs) which included comparisons of safety parameters between an orally administered newer-generation AH with another AH (first- or second- generation), montelukast or placebo in children aged≤12 years. We searched MEDLINE and CENTRAL, independently extracted data on study population, interventions, adverse events (AEs) and treatment discontinuations, and assessed the methodological quality of the included RCTs using the Cochrane’s risk of bias tool. Results: Fourty-five RCTs published between 1989 and 2017 met eligibility criteria. The majority of RCTs included school-aged children with allergic rhinitis and had a follow-up period of up to a month. Four RCTs reported serious AEs in patients receiving a newer-generation AH, but only two patients experienced a possibly drug-related serious AE. The occurrence of AEs, drug-related AEs and treatment discontinuations due to AEs varied between RCTs. Most AEs reported were of mild intensity. Indirect evidence indicates that cetirizine is more sedating than the other newer-generation AHs. Conclusion: Our findings confirm that newer-generation AHs have a favorable safety and tolerability profile. However, we could not draw firm conclusions regarding the comparative safety profile of the newer-generation AHs due to the paucity of head-to-head RCTs, variation in definitions and reporting of AEs, and short follow-up duration.

Introduction: Children with allergy may increase a chance to sensitize the allergic pollens with several environmental changes. Purpose of this study was to investigate the correlation with alternation of pollination associated with meteorological changes and increased sensitization rate of pollen allergens of children in Seoul metropolitan area, Korea. Methods: There were recruited 8,295 children who visited the pediatric allergic clinics at Hanyang University Seoul and Guri Hospital for allergy symptoms from January 1st, 1998 to December 31st, 2019. The pollen was collected by Burkard 7 days-sampler in 2 hospitals during the study. Meteorological data was investigated from Korea Meteorological Administration. Results: Allergic sensitization of oak, hazel, and alder pollens had the highest rate of increase among major tree pollens, an increase of 0.28% annually. The sensitization rate to pollen was increased with younger age group yearly. The duration of pollen season was 98 days in 1998, but 140 days in 2019. The duration of the pollen seasons and pollen sensitization rate to trees were positively correlated. The relationship between the sensitization rate to pollens and accumulated temperature were also correlated, positively. Conclusions: This study demonstrates the correlation between the weather changes and consequent changes of pollen seasons with increasing the sensitization rate to allergic pollens in children in Seoul metropolitan area. In addition, there was an increase in the sensitization rate in younger age group from year to year. Continuous changes in distribution of pollens raised from meteorological changes are expected from now on.

A document by Josefina Cernadas. Click on the document to view its contents.

Background: Phthalates can cause respiratory and immunological disorders. However, little is known about the role of serum periostin and YKL-40 levels in mediating the effects of phthalates. We investigated the mediating role of these biomarkers in the relationship between phthalates and airway dysfunction. Methods: A total of 487 children (aged 10 to 12 years-old) were examined. Four high-molecular-weight phthalate (HMWP) [Σ4HMWP] metabolites and 3 low-molecular-weight phthalate (LMWP) [Σ3LMWP] metabolites in urine samples were measured. Serum periostin and YKL-40 levels were measured. Airway function was measured using impulse oscillometry. A mediation model was used to quantify the mediating effects of periostin and YKL-40 on airway dysfunction. Results: After adjustment for height, gender, BMI z-score, aeroallergen sensitization, secondary smoking, and vitamin D level, the level of urinary Σ3LMWP metabolites was significantly associated with respiratory system resistance at 5 Hz (Rrs5; adjusted β: 0.020, 95% CI: 0.005 to 0.034; P = .010). The levels of urinary Σ4HMWP and Σ3LMWP metabolites were significantly associated with periostin level, but not with YKL-40 level. In addition, the periostin level was associated with Rrs5 (adjusted β: 0.048, 95% CI: 0.015 to 0.081; P = .005) and Rrs20-5 (adjusted β: 0.040, 95% CI: 0.011 to 0.069; P =.007). Serum periostin level had a significant effect in mediating the relationship between Σ3LMWP and Rrs5 (13.9%, 95% CI: 10.7 to 77.0; P < .001). Conclusion: Exposure to LMWPs was significantly associated with airway dysfunction, and this effect was partially attributable to increased serum periostin level.

A document by Marisol Perez-Toledo. Click on the document to view its contents.

A document by Ailish Breathnach. Click on the document to view its contents.

Objetives: The rate of eosinophilic esophagitis (EoE) diagnosis is increasing. This study aims to determine the incidence of EoE in the paediatric population residing in the southwestern Madrid and to analyse whether absolute monthly pollen counts, modified or not by the principal atmospheric pollutants, are associated with it. Methods: A prospective observational study was designed to calculate the incidence of EoE in children aged under 15 years who were diagnosed between September 2014 and August 2016 in twelve area hospitals. We collected clinical data, date of endoscopic diagnosis and the number of first-time endoscopies performed. Relative risk estimation was performed to assess the association between the incidence of diagnosis and monthly pollen counts and levels of atmospheric pollutants. Results: One hundred forty-eight patients were included. The most frequent symptoms were abdominal pain 42.57%, dysphagia 42.57% and impaction 39-86%. The average overall monthly incidence was 1.27 (0.41-2.67) cases/100,000 children and the annual average was 15.2. The overall analysis of the relationship between incidence and absolute monthly counts and air pollutants, corrected for the number of first-time endoscopies performed, revealed no statistically significant association. There was a higher frequency of diagnosis during the pollination period of Cupressaceae and during February and November (relative risk 1.67; p<0.01). Conclusions: This study confirms the high incidence of eosinophilic esophagitis and also suggest a period of higher incidence of diagnosis in the months of February and November as well as in the period of high pollination of Cupressaceae.

Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited and spontaneously resolve within days after drug discontinuation, sometime HRs reactions to AEDs can be severe and life threatening. Aim: This paper seeks to show examples on practical management of AEDs HRs in children starting from a review of what it is already known in literature. Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications and genetic factors. The diagnosis work-up consists of in vivo (Intradermal testing and Patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays and granulysin (Grl) in flow cytometry]. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. Conclusion: Dealing with AEDs HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternate anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

Background: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. Methods: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients <18 years and initiating omalizumab between 2006-2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared to the baseline period. Results: Of the 484 patients included, 101 (20.9%) reached six years of treatment. The mean±standard deviation number of exacerbations decreased during the first year of treatment (7.9±6.6 to 1.1±2.0, p<0.001) and remained likewise for up to six years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. Conclusion: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long-term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Background: allergic rhinitis is a common childhood disease responsible for a major impact on quality of life and health care resources. Many hypotheses have been proposed to explain the link between allergy and otitis media, although a definitive mechanism has not been identified yet. One of the major critical points is that authors failed in distinguishing among different phenotypes of middle ear inflammation. This review pointed out evidence from the laboratory and clinical experience to link allergy to different phenotypes of otitis media in children. Methods: we performed a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process. Our search yielded 3010 articles that were finally screened. This resulted in 20 publications of which the full texts included for the qualitative analysis based on different phenotypes of otitis media. Results: clinical evidences and analyses of biomarkers suggested that allergy may be linked to some phenotypes of otitis media and, in particular, to otitis media with effusion and acute re-exacerbations in children with middle ear effusion. It was not possible to perform the analysis for allergy and acute and chronic otitis media because of paucity and heterogeneity of data. Conclusion: Allergy should be considered in the diagnostic work up of different phenotypes of otitis media. Clinicians should evaluate prompt and accurate treatment of allergy in improving outcomes, although futures studies are required to increase evidence supporting that anti-allergy treatment may be effective in the recovery and outcome of otitis media with effusion.

Background: Children with allergic symptoms tend to have behavioral or emotional problems. However, previous studies on this association did not control for factors such as parenting stress, demographic characteristics, or allergy presentation. This study aimed to investigate the relationship between childhood allergic symptoms and behavioral problems, adjusted for confounders such as demographic characteristics, parenting stress, and allergy-related variables. Methods: We conducted an online cross-sectional survey among caregivers of children aged 2-6 years (n=633). The Strengths and Difficulties Questionnaire (SDQ) score was used as the primary measure of children’s behavioral characteristics. Data on history of wheezing, eczema, and rhinitis were collected from the children’s caregivers, using a standardized questionnaire, based on the International Study of Asthma and Allergies in Childhood. Associations were estimated using logistic regression analyses with propensity score to adjust for confounding factors. Results: Univariate analyses showed that history of wheezing was associated with conduct problems, a behavioral component of the SDQ. History of eczema was also associated with hyperactivity. Furthermore, nose symptoms were associated with conduct and emotional problems. After adjusting for potential confounders, history of wheezing (adjusted odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.04-2.75) and nose symptoms (adjusted OR=1.56, 95% CI: 1.05-2.34) remained associated with increased risk of conduct problems. Conclusions: This study revealed that history of wheezing and rhinitis in children are associated with increased risk of behavioral problems, in particular, that of conduct problems. This evidence may inform future research into childhood allergy symptoms and their behavioral problems.

Background: Intravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial and repeated IVIG resistance in KD. Methods: A total of 385 KD patients were prospectively recruited between April in 2015 and May in 2019. Coagulation and other profiles were evaluated between IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess validity of coagulation profiles in predicting both initial and repeated IVIG resistance. Results: PT, APTT and D-dimer were significantly increased in initial IVIG-resistant group with ATIII significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG-resistant patients. PT, APTT, D-dimer and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/l, and 89.5% yielded sensitivities of 73%, 32%, 71%, 81%; specificities of 55%, 88%, 62%, 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%. Multivariate logistic regression analysis showed that PT, APTT, D-dimer and ATIII were independent risk factors for initial IVIG resistant patients with KD. Conclusions: Coagulation profiles were significantly dysregulated in KD patients. Some of them particularly ATIII may serve as complementary laboratory markers for prediction of both initial and repeated IVIG resistance.

Background: We have previously reported that more than half of the patients who achieved desensitization after wheat rush oral immunotherapy (OIT) developed exercise-induced allergic reaction on desensitization (EIARD). However, data on EIARDs after slow OIT are lacking. Therefore, this study aimed to investigate the results of exercise provocation tests (EPTs) in patients after slow OIT for cow’s milk and wheat allergies. Methods: This was a retrospective chart review of 87 EPTs in 74 patients. The EPTs were performed in patients who were desensitized to at least 6,600 mg cow’s milk protein or 5,200 mg wheat protein with slow OIT and were identified to be at a high risk of EIARDs. EPTs were performed after ingestion of the maximum desensitization dose. The patients’ clinical characteristics and symptoms were analyzed. Results: The EPT results were positive for cow’s milk in 49% (21/43) of the patients and for wheat in 48% (15/31) of the patients. There was no significant difference in the clinical characteristics between the EIARD-positive and EIARD-negative groups. The specific IgE (sIgE) levels before OIT and the reduction rates of sIgE before and after OIT did not correlate with the outcomes of the EPTs. Among the EIARD-positive patients, 13 patients (cow’s milk, n=7; wheat, n=6) underwent a second EPT, and the EIARD disappeared in 8 patients (cow’s milk, n=4; wheat, n=4). Conclusion: EIARDs were observed after slow OIT for cow’s milk and wheat. Further research into the predictive factors of EIARDs in these patients is needed to understand its clinical manifestations.

Background: Chronic spontaneous urticaria is well-described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. Methods: This retrospective study followed children up to 18 years-old, diagnosed with chronic spontaneous urticaria, between the years 2002-2018 and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments and outcomes was extracted from electronic medical records. Results: Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25±15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty-seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2% and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Conclusions and clinical relevance: Chronic spontaneous urticaria in children is a self-limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population; increasing the possibility of a special subgroup of TH2-related chronic urticaria in children.

Background: Selective IgM deficiency (sIgMD), classified under primary immunodeficiencies, is characterized by low serum IgM(<2SD for age), normal IgG and IgA levels. The aim of this study was to define immunologic and clinical features of sIgMD. Method: We assessed a retrospective medical record of patients who fullfilled the criteria for sIgMD in a Pediatric Immunology department. Results: There were 55 patients with sIgMD. Out of 55 patients, thirteen(23.6%) diagnosed with a well-defined primary immunodeficiency (PID) during the follow-up.The ratio of the sIgMD was %0.12 in the out-patient clinic of pediatric immunology. Out of 33 patients, 8(23.5%) were asymtomatic during the follow-up period. Fifteen(45.4%) patients presented with several type of infections). Six patients (18%) had chromosomal anomaly, or syndrome (trisomy 21, 22q11.2 deletion 1p deletion, CHARGE syndrome, and Cohen Syndrome). Six (18%) had autoimmune/inflammatory diseases, such as Behcet’s disease, immune thrombocytopenic purpura, Crohn disease, Guillain Barre syndrome, and diabetes mellitus. Five(15%) had allergic disorders. Three(9%) have developed malignancy. The diagnoses of thirteen PID patients were combined immunodeficiency, common variable immunodeficiency, autoimmune lymphoproliferative syndrome, chronic granulomatous disease, adenosine deaminase deficiency, and congenital neutropenia. Genetic disorders, autoimmune/inflammatory and allergic diseases may accompany sIgMD. Approximately one third of the patients were asymptomatic in our series. Malignancy risk is relatively increased. We observed that an important ratio of patients with low IgM (23.6%) got sooner the diagnosis of a specific PID in the follow-up period. Conclusion: Thus, patients with sIgMD should be followed regularly in immunology clinics.

To the Editor:Severe asthma (SA) affects less than 5% of the pediatric asthma population but is considered to account for approximately half of total pediatric asthma healthcare costs. Allergic comorbidities, including food allergies (FA) and allergic rhinitis (AR), are frequent in children with SA (1). The presence of FA and AR increases asthma severity (1–6) and medication use (4–6). Treating AR improves asthma symptoms (3). However, the economic burden of allergy in children with SA has been poorly studied. We aimed to determine the economic contribution of allergy for the French national health insurance (NHI) for the treament of children with SA at the individual level.Children with SA, defined as those requiring step 4 or 5 of treatment of the Global Initiative for Asthma (GINA), regularly followed in the Department of Pediatric Pulmonology of Necker Hospital were included as previously described (7). The diagnosis of SA, FA, and AR were made by a physician according to guidelines (8-10). A physician-guided questionnaire was completed with parents to assess individual expenditures related to asthma and allergic comorbidities in the previous six months. Parental claims were confirmed by analysis of the medical records. The methods are detailed elsewhere (7). First, we determinated the direct, indirect, and global costs of SA over a six-month period (7) and then assessed the allergy-related costs. The costs related to allergy included anti-allergic medications (oral antihistamines, steroid nasal sprays, anti-allergic eye drops, adrenaline autoinjectors, and allergen immunotherapy), anti-IgE treatment, scheduled ambulatory or hospital outpatient visits to an allergist, pulmonologist, ophthalmologist, or dermatologist, skin tests, blood tests for allergy-specific IgE, and day care unit (DCU) admissions for oral food challenge (OFC) (7). Finally, we compared the economic burden of allergy between children with SA and those without (NSA) (7). Parents were informed and accepted to participate in the study. The local ethical committee confirmed that Institutional Review Board approval was not required.Forty-eight children with SA and 26 with NSA were included. Their general characteristics are summarized in Table 1. The individual global cost of SA was \euro3,982 (4,422) over the six-month study period (7). For children with allergic SA, the cost attributed to allergy was \euro2,803 (3,709), representing 48.1% (35.2) of the direct SA costs and 45.8% (34.9) of the global SA costs. Overall, the number of allergic comorbidities for children with SA weakly correlated with global (r = 0.33, p = 0.02) and direct SA costs (r = 0.35, p = 0.01). The global and direct costs of SA were higher for children with allergic comorbidities than for those without (\euro4,646 (4,635) vs. \euro1,107 (1,173), p = 0.02; respectively). However, these figures partially reflect the actual economic contribution of allergy in children with allergic SA. For those requiring omalizumab, the economic burden of allergy was \euro5,057 (3,809) representing 74.1% (24.4) of direct SA costs and 71.6% (24.3) of global SA costs. In this group, omalizumab was the main driver of costs, representing 73.6% of direct SA costs and 71.5% of global SA costs. For children with allergic SA not requiring omalizumab, the economic burden of allergy was \euro174.50 (289.7), representing 17.8% (16.1) of direct SA costs and 15.8% (15.9) of global SA costs. Regardless of omalizumab use, the economic burden of allergy was similar among children with allergic SA (\euro153.3 (159.4) vs \euro174.50 (289.7), p = 0.99). However, the burden of allergy expressed as a percentage of direct and global SA costs was lower for children with SA requiring omalizumab than those who did not (3% (4.2) vs. 17.8% (16.1), p < 0.01 and 2.9% (4.2) vs. 15.8% (15.9), p < 0.01, respectively).Global, direct, and indirect costs did not differ between children with NSA, with or without allergic comorbidity (Table 3). For children with allergic NSA, the cost of allergy was \euro134.40 (213.90), representing 40.8% (33.3) of the asthma direct costs and 34.7 % (32.2) of the asthma global costs. Thus, regardless of omalizumab use, the cost of allergy for children with allergic SA and that for those with allergic NSA was similar (\euro163.1 (225.9) vs . \euro134.40 (213.9) (p = 0.19). However, the economic burden of allergy was greater for children with NSA than those with SA: 40.8% vs 9.8% of direct costs and 34.7% vs. 8.9% of global costs, respectively (both p < 0.01). Finally, the economic burden of allergy was similar between children with allergic SA not requiring omalizumab and those with allergic NSA (\euro174.5 (289.7 vs. \euro134.4 (213.9), p = 0.29).This study shows that the costs attributed to allergy for children with SA are substantial and mostly driven by omalizumab, but are minor when omalizumab is not taken into account. The economic burden of allergy was similar between children with allergic SA not requiring omalizumab and those with allergic NSA, suggesting a low cost-effectiveness ratio, at least in the latter group. The global and direct costs of children with allergic SA were higher than those of children with non-allergic SA. This finding confirms that the presence of allergic comorbidities increases the costs of asthma management (11) and supports that allergy is associated with asthma severity. Our study had several limitations. Only a small number of children were included. However, we included children with well-defined doctor-confirmed SA, with and without omalizumab, reflecting the heterogenity of this population. In addition, our study was performed in a tertiary-care center. Thus the children with NSA may not be representative of community children. Our estimation was based on parental declarations, with a potential memory bias and a risk of misestimation of certain expenditures. We limited this risk by analyzing the medical records, which confirmed the parental claims. The best design would have been to obtain the data of children selected by a physician from the NHI. However, this approach is rarelly authorized in France. Moreover, the study covered a short period of time including winter and two months of spring, which may lead to underestimation of costs related to seasonal allergy treatments. In addition, the number of children under allergen immunotherapy was small (1 in the group of children with allergic SA vs. 4 children with allergic NSA (p = 0.03)).In summary, this study is the first to precisely analyse the proportion of costs attributed to allergy in pediatric SA. As expected, allergy-related costs are mainly driven by omalizumab. However, for children with allergic SA who do not require omalizumab, the economic contribution of allergy to SA costs is relatively small, suggesting a low cost-effectiveness ratio.