Background: Chemokines are important mediators in immune cell recruitment, contributing to allergy development. However, extensive studies of chemokines in the circulation in relation to the presence and development of allergic diseases remain scarce. Our aim was to investigate associations of circulating allergy-related chemokines with development of asthma and sensitisation cross-sectionally and longitudinally in a population-based cohort. Methods: The chemokines CCL17, CCL22, CXCL10, CXCL11 and CCL18 were measured in plasma samples from children in the Manchester Asthma and Allergy Study. Samples were available from cord blood at birth (n=376), age 1 (n=195) and 8 years (n=334). Cross-sectional and longitudinal association analyses were performed in relation to asthma and allergic sensitisation, as well as allergic phenotype clusters previously derived using machine learning in the same study population. Results: In children with asthma and/or allergic sensitisation, CCL18 levels were consistently elevated at ages 1 and/or 8 years. In a longitudinal model including information on asthma from 4 time-points (ages 5, 8, 11 and 16 years), we observed a significant association between increasing CCL18 levels at age 1 and a higher risk of asthma from early school age to adolescence (OR=2.9, 95% CI 1.1-7.6, p=0.028). We observed similar associations in longitudinal models for allergic sensitisation. Asthma later in life was preceded by increased CXCL10 levels after birth, and decreased CXCL11 levels at birth. Conclusion: Elevated CCL18 levels throughout childhood precede the development of asthma and allergic sensitisation. The Th1-associated chemokines CXCL10 and CXCL11 also associated with development of both outcomes, with differential temporal effects.
Background: Internationally, the COVID-19 pandemic severely curtailed access to hospital facilities for those awaiting elective/semi elective procedures. For allergic children in Ireland, already waiting up to 4yr for an elective oral food challenge (OFC), the restrictions signified indefinite delay. At the time of the initiative there were approx 900 children on the Chidren’s Health Ireland(CHI) waiting list. In July 2020, a project was facilitated by short term(6wk) access to an empty COVID stepdown facility built, in a hotel conference centre, commandeered by the Health Service Executive Ireland(HSE). The aim was to the achieve rapid rollout of an off-site OFC service, delivering high throughput of long waiting patients, while aligning with hospital existing policies and quality standards, international allergy guidelines and national social distancing standards. Methods: The working group engaged key stakeholders to rapidly develop an offsite OFC facility. Consultant Paediatric Allergists, Consultant Paediatricians, trainees and Allergy Clinical Nurse Specialists were seconded from other duties. The facility was already equipped with hospital beds, bedside monitors(BP, Pulse, Oxygen saturation) bedside oxygen. All medication and supplies had to be brought from the base hospital. Daily onsite consultant anaesthetic cover was resourced and a resuscitation room equipped. Standardised food challenge protocols were created. Access to onsite hotel chef facilitated food preparation. A risk register was established. Results: After 6wks planning, the remote centre became operational on 7/9/20, with the capacity of 27 OFC/day. 474 challenges were commenced, 465 (98%) were completed, 9(2%) were inconclusive. 135(29.03%) OFC were positive, 25(5%) causing anaphylaxis. No child required advanced airway intervention. 8 children were transferred to the base hospital. The CHI allergy waiting list was reduced by almost 60% in only 24 days. Conclusions: OFCs remain a vital tool in the care of allergic children, with their cost saving and quality of life benefits negatively affected by delay in their delivery. This project has shown it is possible to have huge impacts on a waiting list efficiently, effectively and safely with good planning and staff buy in – even in a pandemic. Adoption of new, flexible and efficient models of service delivery will be important for healthcare delivery in the post-COVID-19 era.
Graded home introduction of egg is safe, well received and cost effective when managing childhood egg allergyTo the Editor,In Australia, an IgE mediated allergy to egg is a common food allergy in children.1-2 The 2011 HealthNuts study determined that 8.9% of children in Australia have an egg allergy.1-2IgE mediated allergy to egg can be mild and most children may outgrow this by 4-5 years of age.3-4 Almost 80% of children with IgE mediated egg allergy are tolerant of egg in a baked form with wheat being used as a matrix.1,3 Turner et al. suggests that the outcome of baked egg challenges can be unpredictable and can lead to anaphylaxis even in children with prior mild symptoms.5 Tolerance to baked egg is generally confirmed by a baked egg food challenge in hospital after which patients are encouraged to introduce baked egg products at home.6 Patients are reassessed and subsequently undergo a lightly cooked egg challenge in hospital where resolution is confirmed if successful.6Whereas there is evidence that majority of children with an egg allergy are tolerant to baked egg, there is debate as to whether it can reduce the duration of egg allergy.7-9 Recently, Gotesdyner et al found that a structured graded exposure using baked egg followed by lightly cooked egg compared to complete avoidance helped achieve tolerance to egg.3 Their findings suggest that an egg ladder may promote a faster resolution of egg allergy. However, due to the case control study design and small sample size definite conclusions could not be drawn.3Our Paediatric Allergy Service is a busy tertiary level clinic with more than 2000 outpatient interactions annually. To reduce the burden on tertiary resources, an egg tolerance ladder was developed (Appendix 1). It has been offered to patients considered low risk which includes (but is not limited to) patients with a single food allergy; mild or no eczema; mild, well controlled or no coexisting asthma; and/or a history of IgE mediated egg allergy without anaphylaxis. It has been designed to allow slow introduction of baked egg followed by foods containing small amounts of cooked egg and finally lightly cooked egg at home. Support throughout the home introduction process is provided by the treating team via email and phone contact.The aim of this study was to evaluate the use of this structured “egg ladder” with regards to its safety as well as user satisfaction and barriers that arose in negotiating it. We also attempted to determine potential risk factors which increased likelihood of clinical reaction to foods containing egg and rates of eventual tolerance to lightly cooked and raw egg achieved in the home environment. This study was approved by the Ethics Committee at John Hunter Children’s Hospital (2020/ETH01192).Patients with mild to moderate IgE mediated egg allergy aged 0-18 years seen in the Paediatric Allergy Clinic and commenced on an egg tolerance ladder by the Paediatric Immunologist were recruited retrospectively. Verbal and written education on the use of the ladder had been provided at the time of clinic review. Patients were excluded from home introduction if they had a history of anaphylaxis to any food containing egg or a non-IgE mediated egg allergy.A file audit identified a total of 98 patients for inclusion in this study who had been commenced on the egg ladder between September 2018 and June 2020. Patients were contacted by email and phone, and offered participation in a telephone survey to evaluate the use of the egg tolerance ladder. Almost half (47 patients) consented to the study. At the time of commencing the egg ladder, patients had a mean age of 40 months (IQR: 12-60 months). Six children did not have a skin prick test (SPT). The majority were sensitised with a mean SPT of 3.1mm. Most (66%) had at least one atopic comorbidity and almost half had more than one food allergy. The vast majority (87.2%) of patients commenced the egg ladder at home. This includes 23 patients already tolerant to baked egg prior to clinic presentation, based on clinical history. Only 3 (6%) used the resources of an inpatient challenge.Patients had spent an average of 15.5 months (IQR: 9-21.5 months) on the ladder. At the time of review, 43% of patients had completed the egg ladder but interestingly, four parents believed their child was still allergic to egg. The mean age of commencement on the egg ladder was higher than expected (40 months), and around the age a child is expected to outgrow an allergy to egg.3-4 Despite this, many patients reported reactions while using the egg ladder. A mild reaction was reported by 18 (38%) parents, 16 required treatment and of those one was given adrenaline. This child was 6 years of age, had an isolated egg allergy and small skin test (3.5mm). They reacted to Step 5 and have continued Step 4 at home successfully. Both families reporting a severe reaction recommenced the ladder and were able to subsequently progress successfully to Step 5 or 6. The majority had a mild skin response (rash or hives). Skin testing was a poor differentiator for clinical reaction with 38% of those with negative skin testing reporting a mild reaction with baked egg.Parental satisfaction was high with 78.7% satisfied or very satisfied with the egg ladder. Most of the remaining families were neutral with no families dissatisfied with the ladder use. Many stated that they valued the structured approach of introducing egg which helped identify their child’s level of tolerance, and allowed them to progress at their own pace. A number of parents identified the main barrier to progressing the ladder was the taste and/or texture of egg after successfully completing the ladder and subsequent difficulty maintaining regular lightly cooked egg in the diet. These families continued egg as an ingredient in cooked or baked food.There were some limitations to this study. Firstly, this was a retrospective small sized survey and some patients were unable to accurately recall timelines. As a voluntary survey there is also a risk of ascertainment bias. Baseline patient demographics (age, sex, SPT size, comorbid allergy diagnoses) of non-responders were compared to the study cohort with no significant differences identified. The initial education on commencing on the egg ladder was provided by multiple clinicians and information therefore was unable to be standardised. As expected, a number of patients at the time of the survey were still navigating the egg ladder and therefore had not had enough time to reach their individual threshold to determine if their child had outgrown their allergy. This may lead to under-reporting of egg tolerance on the ladder. Finally, follow up or assistance with the egg ladder was not provided unless the parent contacted the team. This may have resulted in less children completing the ladder due to parental anxiety over mild reactions.We have shown that the use of a structured egg ladder for egg allergic children without a history of anaphylaxis can be safe, is well tolerated and is a positive experience for families. It can prevent time consuming and costly inpatient supervised challenges unnecessarily consuming valuable and scarce resources in busy allergy clinics. Future prospective studies will help establish the role of home egg introduction in childhood egg allergy management in both tertiary and secondary health care settings.Conflicts of InterestNo conflicts to be declared.Leah Thomas1Jan Belcher1Rachael Phillips1Kahn Preece, MBBS, FRACP1Rani Bhatia, MBBS, FRACP11Department of Paediatric Allergy and Immunology, John Hunter Children’s Hospital, Newcastle, AustraliaReferences1. Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. Journal of Allergy and Clinical Immunology. 2011;127:668-76.2. Dang TD, Peters RL, Koplin JJ, et al. Egg allergen specific IgE diversity predicts resolution of egg allergy in the population cohort HealthNuts. Allergy. 2019; 74: 2.3. Gotesdyner L, Zeldin Y et al. A structured graduated protocol with heat denatured eggs in the treatment of egg allergy. Pediatric Allergy and Immunology. 2019;30:824-832.4. Leonard SA, Sampson HA, Sicerer SH, et al. Dietary baked egg accelerates resolution of egg allergy in children. Journal of Allergy and Clinical Immunology. 2012;13:2.5. Turner PJ, Mehr S, Joshi P et al. Safety to food challenges to extensively heated egg in egg-allergic children: a prospective cohort study. Pediatric Allergy and Immunology. 2013;24:450-455.6. Clark A, Islam S, King Y. A longitudinal study of resolution of allergy to well-cooked and uncooked egg. Clinical & Experimental Allergy. 2011;41:706-712.7 Lambert R, Grimshaw K, Elis B et al. Evidence that eating baked egg or milk influences egg or milk allergy resolution: A Systematic Review. Clin Exp Allergy. 2017;47(6):829-837.8. Upton J, Nowak-Wegrzyn A. The impact of baked egg and baked milk diets on IgE and Non-IgE mediated allergy. Clinical Reviews in Allergy & Immunology. 2018;55(2):118-138.9. Leonard SA, Caubet JC, Kim, JS, Groetch M, Wegrzyn AN. Baked Milk- and Egg-Containing Diet in the Management of Milk and Egg Allergy. Journal of Allergy and Clinical Immunology. 2015;1:13 – 23.
Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled LTB4, characterizes childhood asthma. While FeNO has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15-HETE, but not TXB2, showed significant difference between asthmatics (N=318) and healthy controls (N=97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver Operating Characteristic (ROC) analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 and FeNO, whilethe 15-HETE/LTB4 ratio was significantly lower in subjects with severe asthma (p<0.01). Analysis of asthmatics (N=75) during exacerbation and convalescence showed significant improvement in lung function (FEV1; p<0.001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p<0.001) and reduced levels of TXB2 (p<0.05) after therapy, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and LXA4 at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15-HETE were prominent after treatment.
Background: Quantifying age trends in healthcare costs of pediatric asthma leads to better understanding of the natural history of the disease and informed decision-making on the allocation of healthcare resources. Methods: We identified children with incident asthma from the health administrative data of British Columbia, Canada (Jan 1998 to Dec 2015), and followed them from their first diagnosis of asthma or wheezing until age 18. We estimated direct medical costs (in 2016 Canadian dollars [$]), including inpatient and outpatient encounters and pharmacy costs, attributed to asthma (primary outcome) and other respiratory diseases (secondary outcome). We assessed the impact of sex and socioeconomic status on age trends, adjusting for calendar effect. Results: The final analysis included 44,552 children with asthma (62% boys). From age 0 to 18, costs of asthma/wheezing and other respiratory conditions decreased from $1,036 to $29/child-year, and from $1,145 to $31/child-year, respectively. Children under 3 years of age incurred 4–fold higher costs for asthma/wheezing and other respiratory conditions. In particular, costs of asthma hospitalizations were 10 times higher in this age group compared to older children. Age trends were generally similar between sex groups and across socioeconomic status. However, medication costs for asthma/wheezing decreased in boys, whereas those in girls declined during childhood but increased during adolescence. Conclusions: The highest costs of pediatric asthma are concentrated in children younger than 3. Age trends were generally consistent between sex and across socioeconomic status.
Background: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. Methods: This study retrospectively analyzed data from the Japan Environment and Children’s Study, a nationwide birth cohort study, conducted between 2011 and 2014. Data of women with singleton births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, a logistic regression model was used to calculate adjusted odds ratios for “wheezing ever,” diagnosis of asthma in the last 12 months, and “asthma ever” in women with MRA, with women who did not receive MRA as the reference. Participants were stratified by term births, and adjusted odds ratios for outcomes were calculated using a logistic regression model. Results: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing ever was 1.17 (95% confidence interval, 1.12–1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. Conclusion: MRA was associated with an increased incidence of childhood wheezing up to three years, irrespective of term births or preterm births. It is important that perinatal physicians consider both the adverse maternal side effects of MRA and its potential effects on the offspring’s childhood.
BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.
1 Conflicts of interestESC has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma; is a member of the healthcare advisory board for Food Allergy Canada; was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Guidelines for Peanut Allergy Prevention; and was co-lead of the CSACI oral immunotherapy guidelines.SJ has been on speaker’s bureaus for Aralez, Novartis, Astra Zeneca, and Sanofi, and on the advisory board for Sanofi.MH has provided speaker services for Pfizer, Pediapharm, and has been part of an advisory board for ALK and provides privately funded OIT.VC has been a participant on advisory boards for Sanofi Genzyme, Bausch Health, and ALK, speaker services for Aralez Pharmaceuticals and CSL Behring.DM has provided consultation and speaker services for Pfizer, Aimmune, Kaleo, Merck, Covis and Pediapharm, and has been part of an advisory board for Pfizer and Bausch Health. He sits on the editorial board for the Journal of Food Allergy.EA Section Head of Anaphylaxis/Food Allergy for the Canadian Society of Allergy and Clinical Immunology; sits on steering committee for Canada’s National Food Allergy Action Plan; moderator/speaker fees from Novartis, GSK, Sanofi, AstraZeneca.LS NoneTW speaking engagements for Pfizer and Stallergenes Greer, Advisory Board member for ALK and Leo PharmaJP is the Section Head of Allied Health for the Canadian Society of Allergy and Clinical Immunology; and sits on the steering committee for Canada’s National Food Allergy Action Plan
Background: Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association of EVs with allergic sensitization and disease in early childhood. Methods: The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and asked with ISAAC questionary. We screened for the presence of serotype specific antibodies against 41 EVs at 1 to 5 years of age and assessed their association with allergic sensitization and disease. Results: The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95 % CI 0.36-0.99), P = 0.048. Conclusion: This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.
BACKGROUND: Exercise-induced respiratory symptoms are frequently reported by asthmatics and exercise-induced bronchospasm (EIB) is a frequent cause that requires objective testing for diagnosis. Eucapnic voluntary hyperventilation (EVH) is recommended as an exercise surrogate stimulus for this purpose, but its short-term reproducibility is not yet established in young asthmatics. OBJECTIVE: To evaluate the short-term test-retest agreement and reproducibility of FEV1 changes after EVH in young asthmatics. METHODS: Asthmatics aged between 10 and 20 years underwent EVH for EIB diagnosis on two occasions 2-4 days apart at a specialized university clinic. FEV1 was measured 5, 15 and 30 minutes after EVH with a target ventilation rate 21 times baseline FEV1. EIB was diagnosed as a decrease >10% in FEV1 from baseline. RESULTS: Twenty-six of 62 recruited individuals tested positive for EIB on both visits (positive group) and 17 on one visit only (divergent group); and 19 tested negative on both visits (negative group). The overall agreement was 72.5% (95%CI 61.6%, 83.6%) and positive and negative agreement was 41.9% and 30.6% respectively. Despite overall low bias in FEV1 response between test days (0.87%), the limits of agreement were wide (+20.72%). There were no differences in pre-challenge FEV1 or achieved ventilation rate, between visits either between groups (p=0.097 and p=0.461) or within groups, (p=0.828 and p=0.780). No test was interrupted by symptoms and there were no safety issues. CONCLUSIONS: More than one EVH test should be performed in young asthmatics with a negative test to exclude EIB and minimize misdiagnosis and mistreatment.
Background: Although atopic dermatitis (AD) is associated with certain gene variants, the rapidly increasing incidence of AD suggests that environmental factors contribute to disease development. In this study, we investigated the association of AD incidence and phenotype with antibiotic exposure within 6 months of age, considering the dose administered and genetic risk. Methods: This study included 1,637 children from the COCOA birth cohort. Pediatric allergists assessed the presence of AD at each visit and obtained information about antibiotic exposure for more than 3 days. IL-13 (rs20541) polymorphism was genotyped by the TaqMan method. We stratified the AD phenotypes into 4 groups and used multinomial logistic regression models for analysis. Results: Antibiotic exposure within 6 months of age was found to increase the risk of AD within 3 years of life (aOR=1.40, 95%, CI 1.09–1.81) in dose-dependent manner. Antibiotic exposure more than twice increased the risk of the early-persistent AD phenotype (aOR=2.50, 95% CI 1.35–4.63). There was a weak interaction between genetic polymorphisms and environmental factors on the development of AD (p for interaction=0.06). Children with the IL-13 (rs20541) GA+ AA genotype have a higher risk of the early-persistent AD phenotype when exposed to antibiotics more than twice than those with the IL-13 (rs20541) GG genotype and without exposure to antibiotics (aOR=4.73, 2.01–11.14). Conclusion: Antibiotic exposure within 6 months was related to the incidence of early-persistent AD and a dose-dependent increase in the incidence of AD in childhood, whose effect was modified by the IL-13 (rs20541) genotype.
Background: Food allergy is a major health problem that significantly impacts quality of life (QoL). There is growing focus to evaluate food allergy related QoL and treatment value beyond the clinical effectiveness perspective by engaging patients and caregivers. We aimed to identify and prioritize outcomes important to food allergy parents of children and patients allergic to milk, egg, and/or peanut, to guide comparative effectiveness research (CER) that focuses on evaluating food allergy treatment decisions. Methods: We conducted a modified 3-round Delphi study to identify and derive consensus on priority treatment outcomes for parents of children and adult patients with diagnosed allergies to at least one of three major allergenic foods (milk, egg, and peanut) from across the United States. Results: Round 1 yielded 44 statements for round 2, and 39 statements reached the agreement level for round 3 ranking. Statements were organized under 4 sections: 1) food allergy problems, 2) treatment experiences, 3) important treatment outcomes, and 4) value of different treatment options. Conclusion: Food allergy parents and patients face several social, psychological, medical, healthcare, financial, food selection, and awareness challenges. The areas of consensus on important treatment outcomes revealed shared priority for reducing the risk of potentially fatal allergic reactions and having reliable treatments. The most valued treatment options reflect hope for permanent cure and fear of serious allergic reactions.
Background: Safely liberalizing the diet to include an allergenic food may accelerate resolution of food allergy. The outcome of liberalization, however, varies among patients. Methods: We conducted a prospective observational study to identify factors associated with outcome for egg allergy 1 year after oral food challenge (OFC). We enrolled children < 72 months-old who had egg allergy and underwent OFC for determination of the safe intake quantity of egg allergen. At enrollment, each child’s clinical background was recorded. The Food Allergy Quality of Life Questionnaire–Parent Form (FAQLQ–PF) was administered to the caregivers to assess their children’s QoL. Dietary advice based on the OFC result was then provided to support safe consumption of eggs. At 1 year after OFC, the quantity of egg each child safely consumed in daily life was surveyed. We classified the egg allergy outcome as Outgrowing (Group O) if the quantity increased during the 1 year, or as Non-outgrowing (Group N) if it did not. Factors associated with the outcome were investigated by multivariate logistic regression analysis. Results: A total of 93 children were enrolled, and after 1 year 57 finished in Group O and 36 in Group N. The mean FAQLQ-PF score at baseline was significantly lower (i.e., better QoL) in group O than in group N. Multivariate logistic regression analysis identified comorbid asthma, comorbid atopic dermatitis and a poor QoL as factors predicting an unfavorable outcome. Conclusion: QoL may affect food allergy outcome. Intervention focusing on QoL may promote outgrowing food allergies.
Background: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated if school-aged children with and without FLG mutations have differences in immune cell numbers. Methods: This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg) and CD27+ and CD27- memory B cells. Sensitivity analysis was performed in 102 AD cases, assessed by parental questionnaires. Results: FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg or memory B cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cells or their subsets. Conclusions: School-aged children with FLG mutations have higher Th22 cell, which might suggest an immunological defense mechanism to an altered skin barrier function. No associations between Th or Treg cells and FLG mutations suggests that FLG mutations do not otherwise affect immune composition in a general pediatric population.
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.