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Background Epidemiological studies have demonstrated a wide, unexplained disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes depending on geographical location, ethnicity and other factors. Enthesitis-related arthritis (ERA) is more prevalent in Southeast Asia. Axial involvement in ERA patients is increasingly recognised to occur early in the disease course. Inflammation in the sacroiliac joint (SIJ) observed on MRI seems highly predictive of subsequent structural radiographic progression. The resulting structural damage can have significant impacts on both functional status and spinal mobility. This study aimed to evaluate the clinical characteristics of ERA in a tertiary centre in Hong Kong. The primary objective of the study was to provide a comprehensive description of the clinical course and radiological findings of the SIJ among ERA patients. Method Paediatric patients diagnosed with JIA attending the paediatric rheumatology clinic from January 1990 to December 2020 were recruited from our registry based at the Prince of Wales Hospital. Results In our cohort, 101 children were included. The median age of diagnosis was 11 years, interquartile range (IQR) 8-15 years. The median follow-up duration was 7 years (IQR 2–11.5 years). ERA was the most prevalent subtype (40%), followed by oligoarticular JIA (17%). Axial involvement was frequently reported in our cohort of ERA patients. 78% demonstrated radiological evidence of sacroiliitis. Among those, 81% had bilateral involvement. The median duration from disease onset to confirmation of radiological sacroiliitis was 17 months (IQR 4-62 months). Among the ERA patients, 73% had structural changes of the SIJ. Alarmingly, 70% of these patients had already developed radiological structural changes when sacroiliitis was first detected on imaging (IQR 0-12 months). Erosion was the most common finding (73%), followed by sclerosis (63%), joint space narrowing (23%), ankylosis (7%) and fatty change (3%). The duration from symptom onset to diagnosis was significantly longer in ERA patients with SIJ structural changes (9 vs 2 months, p = 0.009), comparing with those without. Conclusion We found that a high proportion of ERA patients had sacroiliitis and a significant number of them had radiological structural changes during early disease. Our findings illustrate the importance of prompt diagnosis and early treatment in these children.

BACKGROUND AND AIMS: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings.METHODS: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022.RESULTS: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the "Scope and Purpose" and "Rigour of Development" domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the "Applicability" domain were generally low, and only 3 CPGs rated highly in the "Implementability" domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably.CONCLUSION: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders' preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe.PROSPERO REGISTRATION NUMBER: CRD42021265689.

Background Asian carps are popular freshwater fish species in Hong Kong and served as an important protein source for infants. Grass carp parvalbumin was reported to have higher allergenicity than other commercially important fishes (salmon and cod) in terms of IgE reactivity. Objective To identify allergens in Asian carps and study the divergence pattern of allergens. Method Three complete Asian carps’ genomes were constructed by hybrid assembly approach. All the homologs of known and putative allergens were identified based on sequence homology at the genomic level. The gene structures, expression level and protein conformations of parvalbumin were revealed using bioinformatics tools. Results Parvalbumin is the major allergen in grass carp tested by indirect ELISA. Nine homologs of parvalbumin were identified in the genome of grass carp, in which Cid_PV2 exhibited highest sequence similarity to the reported group 1 allergen of grass carp, Cten i 1. Similarly, ten parvalbumin homologs were identified in the genome of bighead and black carp respectively, in which Mpi_PV7 and Hno_PV7 were identified as the putative allergenic homologs. The expression profile of parvalbumin revealed alternative usage of homologs in different tissues of Asian carps. Moreover, gene copy numbers of parvalbumin gradually expanded in bony fish and two gene clusters of parvalbumin were identified inside the genomes of Asian carps. Conclusion All the homologs of Asian carps’ parvalbumin were accurately identified and gene divergence contributed to the formation of allergenic homologs. Together with a comprehensive gene sequence profile of carps’ parvalbumin, those could be applied to achieve a more precise clinical diagnostic test and would ultimately assist the design of preventive treatment by immunotherapy of fish allergy.

Background: Anxiety from accidental exposure and vigilant dietary monitoring impair the quality of life (QoL) of food-allergic patients. A comprehensive food allergy-specific questionnaire allows patients to accurately report their QoL. This study validated the Food Allergy Quality of Life Questionnaire (FAQLQ) series and assessed the QoL of Chinese food-allergic patients and their caregivers.Methods: FAQLQ series developed by EuroPrevall consists of four separate questionnaires for parents, children, adolescents and adults. All questionnaires were translated into traditional Chinese by standard forward and backward methods. A cross-sectional study was conducted on food-allergic patients and children's parents using an age-appropriate questionnaire. The performance indices of FAQLQ and their correlation with independent measures of food allergy were analyzed, and factor analysis was performed to confirm the factor structure of FAQLQ questionnaires.Results: Cross-sectional validation was performed on 214 participants, with 40 reassessed for test–retest reliability. Overall scores for the FAQLQ series had good internal consistency with Cronbach's α ≥.90. Good construct validity was demonstrated by correlations between FAQLQ-Parent Form, FAQLQ-Child Form, FAQLQ-Teenager Form, FAQLQ-Adult Form and Food Allergy Independent Measure (FAIM) scores, except in 0- to 3-year-old children. Test–retest analyses revealed a significant correlation between total FAQLQ score, parent-reported FAIM and food anxiety domain in 4–6 years, and between total score and FAIM in 7–12 years. Exploratory factor analysis categorized items in the FAQLQ series into three to four domains.Conclusion: FAQLQ series provide a valid and reliable measure for QoL in Chinese food-allergic patients and caregivers, except for parents of children aged 0–3 years. Items for all FAQLQ questionnaires are categorized into different functional domains in our population.

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of

A proportion of asthmatic children outgrow their disease by adulthood, but there are limited data on predictors for asthma persistence. This prospective study characterized the trajectory of spirometric indices and identified predictors for the persistence of childhood asthma.Chinese asthmatic children aged 6-15 years from pediatric allergy clinic underwent annual visits for ≥5 years and until their adulthood. Pre-bronchodilator spirometry and anti-asthma medications were recorded at baseline and then at least annually. Asthma resolution was defined when patients were free from asthma symptoms and use of anti-asthma drugs for ≥2 years. Logistic regression was used to identify predictors for asthma persistence. Generalized estimating equation was used to analyze longitudinal changes in lung function parameters in relation to asthma persistence.181 asthmatic children aged [mean (SD)] 10.0 (2.7) years were followed for [mean (SD)] 12.5 (2.8) years. One third of them outgrew asthma during follow-up. Female was 3.36 times more likely to have persistent asthma. Inhaled corticosteroid (ICS) treatment ever and frequent asthma exacerbation (AE) predicted asthma persistence with respective odds ratios of 3.19 (95% confidence interval [CI] 1.44-7.09) and 3.05 (95% CI 1.39-6.68). Persistent asthma was inversely associated with baseline forced expiratory volume in 1-second (FEVFemale, ICS ever, and frequent AE predicted persistent asthma. Patients with persistent asthma had lower forced expiratory indices and poorer lung function growth into adulthood.

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BACKGROUND Anaphylaxis is a significant health burden in most Western countries, but there are little published data on the incidence and pattern of anaphylaxis in Asia. We aim to determine the incidence rate and pattern of anaphylaxis over the past decade among the pediatric population in Hong Kong. METHODS Medical records of patients presenting with allergy-related symptoms during the period 2010 to 2019 were examined. Pediatric patients aged below 18 years who fulfilled the diagnostic criteria for anaphylaxis laid out by the NIAID/FAAN were analyzed. Incidence rates were calculated using population statistics as the denominator. All information pertaining to the anaphylaxis events and patients' characteristics was retrieved using standardized data collection forms. RESULTS The overall 10-year estimated incidence of anaphylaxis was 9.76 per 100,000 person-years, with a rising trend of anaphylaxis incidence across time. Food-induced anaphylaxis accounted for the majority of hospital presentations, of which peanut and shellfish were the top food triggers in our population. Majority of anaphylaxis episodes were of Grade 4 severity, and young age was a significant predictor of severe allergic reactions. Half of the anaphylaxis episodes were misdiagnosed and adrenaline was only utilized in 42.2% of cases, of which 9.4% were administered adrenaline prior to hospital arrival. CONCLUSIONS An increasing trend of anaphylaxis incidence over the past decade is evident in Hong Kong children, with a discrepantly low accuracy in diagnosis and suboptimal management of anaphylaxis. There is a pressing need to heighten public and physicians' awareness of the distinctive features of anaphylaxis in the pediatric age-group.

Background Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. Methods This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. Results Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67–29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12–9.51) and 21.22 (95% CI, 13.78–32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38–12.53) and 37.32 (95% CI, 26.98–51.25) per 100 000 persons vaccinated. Conclusions There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Background: Combined treatment with probiotic and peanut oral immunotherapy (PPOIT) was shown to induce sustained unresponsiveness (SU) in a proof-of-concept randomized trial. Additional data on safety and long-term outcomes are needed. This study aimed to evaluate the safety and long-term effects of PPOIT in children with peanut allergy. Methods: Open-label study of 20 children aged 1-12 years with challenge-confirmed peanut allergy; all children received 18-months of PPOIT. Efficacy endpoints were desensitization, 8-week SU, and persistence of 8-week SU at 3-years post-treatment, assessed by double-blind placebo-controlled food challenge (cumulative 4950mg peanut protein). Treatment emergent adverse events and relationship to study treatment were recorded. Immunologic measures and health related quality of life (HRQL) were evaluated at screening, end-of-treatment and 3-years post-treatment. Results: Sixteen children (75%) completed treatment. By intention-to-treat analysis, 75% (15/20) achieved desensitization and 60% (12/20) achieved 8-week SU. Ten of 12 participants with SU at end-of-treatment consented to the 3-year SU challenge; 6 (60%) had persistence of SU. PPOIT was associated with significantly reduced peanut skin prick test wheal size and serum peanut specific-IgE levels at end-of-treatment, 12-months and 3-years post-treatment. There were no serious adverse events. HRQL scores improved (exceeding the Minimal Clinically Important Difference of 0.45) at 12-months post-treatment with benefit sustained at 3-years post-treatment. Conclusions: Eighteen months of PPOIT induced high rates of desensitization and SU, and SU persisted to 3-years post-treatment in a majority of initial responders. PPOIT led to long-lasting suppression of peanut sIgE and long-lasting clinically important improvement in HRQL.

Background: Anaphylaxis is a significant health burden in most Western countries but there is little published data on the incidence and pattern of anaphylaxis in Asia. We aim to determine the incidence rate and pattern of anaphylaxis over the past decade among the paediatric population in Hong Kong. Methods: Medical records of patients presenting with allergy-related symptoms during the period 2010 to 2019 were examined. Paediatric patients aged below 18 years who fulfilled the diagnostic criteria for anaphylaxis laid out by the NIAID/FAAN were analysed. Incidence rates were calculated using population statistics as the denominator. All information pertaining to the anaphylaxis events and patients’ characteristics were retrieved using standardized data collection forms. Results: The overall 10-year estimated incidence of anaphylaxis was 7.70 per 100,000 person-years, with a rising trend of anaphylaxis incidence across time. Food-induced anaphylaxis accounted for the majority of hospital presentation, of which peanut and shellfish were the top food triggers in our population. Comorbid asthma and young age were risk factors associated with wheeze at presentation. Misdiagnosis of anaphylaxis occurred in up to half the anaphylaxis cases and adrenaline was only utilised in 45% of cases. Conclusions: An increasing trend of anaphylaxis incidence over the past decade is evident in Hong Kong children, with a discrepantly low accuracy in diagnosis and suboptimal management of anaphylaxis. There is a pressing need to heighten public and physicians’ awareness of the distinctive features of anaphylaxis in the paediatric age group.

Introduction: Prevalence of food allergy is rising in different regions of the world. Asia has not been spared from this epidemic, but epidemiological data have revealed a different pattern of food allergens in this continent. Allergen-specific immunotherapy (AIT) for food allergy, which has been revolutionary as the main focus of research in recent years, needs to be adapted for the different populations in Asia. Areas covered: Recent evidence shows increasing popularity and superiority of AIT over strict food avoidance as the cornerstone of food allergy management. Asia is a distinctive continent with specific food allergy triggers, in particular, seafood, and wheat. Peanut, on the contrary, is not a common food allergen in most parts of Asia. The common Asian food allergens, as well as the rapidly developing food-specific AIT in this region will be covered in this article. Expert commentary: Evidence on oral immunotherapy for wheat allergy and preclinical data on shellfish AIT are promising. Further work should be done on resolving cross-sensitization between environmental allergens with wheat and shellfish allergens, and a modified AIT approach to enhance the safety and effectiveness of food-specific immunotherapy.

Background: Mass coronavirus disease 2019 (COVID-19) vaccination to achieve herd immunity is an effective means to mitigate the current COVID-19 pandemic. Reports of COVID-19 vaccine-associated allergic reactions and lack of clear local guidance are contributing factors leading to a low vaccine acceptance rate in the community. A task force of experts from the Hong Kong Institute of Allergy (HKIA) has been formed to address current needs.Objective: To formulate a set of consensus statements (CS) on COVID-19 vaccine allergy safety (VAS) in Hong Kong.Methods: A nominated task force of experts managing patients with drug and vaccine allergies in Hong Kong formulated the CS by the Delphi method. An agreement was a priori defined as ≥80% consensus.Results: A total of 11 statements met the criteria for consensus with good overall agreement among task force members, including seven statements on pre-vaccination recommendations and four statements on vaccination and post-vaccination guidance. Individuals with a history of suspected allergic reaction to prior COVID-19 vaccination should not receive further COVID-19 vaccination, and other groups at risk of COVID-19 vaccine-associated allergic reactions have been identified. The importance of pre-vaccination and post-vaccination assessment by frontline healthcare workers and evaluation by allergists are highlighted.Conclusion: The CS provides pragmatic and timely guidance for local frontline healthcare providers on decisions regarding COVID-19 VAS.

Asthma has now become one of the most common atopic disorders not only in developed countries but also in many developing countries. The etiology is likely due to a complex interaction between genetic and environmental factors. In many Asian countries, the prevalence of asthma has also been documented by validated instruments to be increasing rapidly over the past two decades. However, studies in rural areas in Asia with a traditional farming environment revealed markedly lower asthma prevalence when compared with residents in nearby cities despite having similar genetic background. Among the environmental factors implicated in the pathogenesis of asthma, air pollution, dietary patterns, viral infections, and early microbial exposure have been studied extensively around the world. Asia provides many opportunities to study these potential factors as there are many ethnic groups living in distinctly different environments. The understanding of the roles of these factors in affecting the early immune system and subsequent development of asthma will enable us to develop potential primary preventive strategies against a disease which affects millions worldwide.

Background Anaphylaxis has been increasing in developed countries but there is very little published data on the burden of anaphylaxis and the pattern of adrenaline autoinjector (AAI) prescription from Asia. We aim to determine the incidence rates of anaphylaxis and prescription rates of AAI over the past decade in Hong Kong. Methods Using a centralized electronic database of Hong Kong’s sole public-funded healthcare provider, we obtained and analysed all patients between 2009 and 2019 with physician-reported diagnosis of anaphylaxis. Incidence rates were calculated using population statistics as the denominator. Patients’ prescriptions on discharge were collected to determine the AAI prescription rates. Results The overall 10-year estimated incidence rate of anaphylaxis was 3.57 per 100,000 person-years. An increasing trend over time across both paediatric and adult populations from 2009 to 2014 was found, which remained stable until 2019. This was more marked among the paediatric population (paediatric vs adult incidence rate ratio in 2019: 3.51 [95% CI 1.12–2.66] vs 1.82 [95% CI 1.05–1.60]). There was an overall increasing rate of AAI prescription for patients admitted for anaphylaxis, but the overall AAI prescription rate was less than 15% and was significantly less likely to be prescribed for the adult compared to paediatric patients (36.5% vs. 89.4%, p Conclusions An increasing trend of anaphylaxis incidence rates over the past decade is evident in Asian populations, with a discrepantly low rate of AAI prescription, particularly in the adult patients.

Background The diagnosis of shellfish allergy currently relies on patient history, skin prick test (SPT), and serum specific IgE (sIgE) quantification. These methods lack sufficient diagnostic accuracy, whereas the gold standard of oral food challenges is risky and burdensome. Markers of reactivity and severity of allergic reactions to shellfish will improve clinical care of these patients. Objectives This study compared the diagnostic performance of SPT, sIgE, basophil activation test (BAT), and IgE crosslinking–induced luciferase expression (EXiLE) test for shrimp allergy. Methods Thirty-five subjects with documented history of shrimp allergic reactions were recruited and grouped according to results of double-blind, placebo-controlled food challenge (DBPCFC). In addition to routine diagnostics, BAT (Flow CAST) and EXiLE test with shrimp extract and tropomyosin were performed. Results Of 35 subjects, 15 were shrimp allergic with pruritus, urticaria, and itchy mouth on DBPCFC, whereas 20 were tolerant to shrimp. Tropomyosin only accounted for 53.3% of sensitization among subjects with challenge-proven shrimp allergy. BAT using shrimp extract as stimulant showed the highest area under curve value (0.88), Youden Index (0.81), likelihood ratio (14.73), odds ratio (104), and variable importance (4.27) when compared with other assays and tropomyosin diagnosis. Results of BAT significantly correlated with those of EXiLE (r = 0.664, P Conclusions BAT is a more accurate diagnostic marker for shrimp allergy than SPT and shrimp sIgE, whereas the EXiLE test based on an IgE crosslinking assay is a good alternative to BAT. Tropomyosin may not be the most important shrimp allergen in Chinese, which warrants further investigation to search for other major allergens and diagnostic markers.

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a “cure “for shellfish allergy is within reach.

Background Grass carp is the most commonly consumed fish species in Hong Kong. The allergenicity of grass carp and its allergen content are yet to be reported. This study characterized the major allergen in grass carp and investigated its allergenicity. Methods Sixty-nine subjects with history of IgE-mediated allergic reaction to grass carp were recruited. The protein content in steamed grass carp extract was resolved by SDS-PAGE, and the major allergen was identified by immunoblotting with serum from subjects allergic to grass carp. The identity of allergen was elucidated by mass spectrometry and amino acid sequence obtained by amplifying the specific gene from cDNA library of grass carp. The cross-reactivity between parvalbumins from grass carp and other phylogenetically close (common carp) or commercially important (cod and salmon) species was investigated by competitive inhibition ELISA. Results A major IgE-binding protein was found at approximately 9 kDa and identified as parvalbumin by immunoblotting and mass spectrometry. Grass carp parvalbumin was more allergenic than common carp, salmon, and cod parvalbumins despite sharing high sequence homology. This newly identified major allergenic parvalbumin isoform from grass carp was registered as Cten i 1 in the World Health Organization and International Union of Immunological Societies allergen database. Conclusions Grass carp parvalbumin is identified as the major fish allergen in Hong Kong. The strong allergenicity of Cten i 1 contributes to the high IgE reactivity of grass carp. Grass carp, among other fish species, should be considered when managing fish-allergic patients.

Background Egg allergy is one of the most common food allergies in childhood with increasing prevalence in Hong Kong. While ample studies were published on its optimal diagnosis, there was limited data on predictors for the natural history of egg allergy in Asian populations. Objective This study aimed to characterize the clinical course and outcome of children with egg allergy and identify its prognostic factors. Methods All Chinese children with immediate-type egg allergy being followed since ≥3 years old in allergy clinic of our university-affiliated teaching hospital were reviewed to determine if they outgrew egg allergy at the latest follow-up. The predictive values of clinical and atopic factors for resolution of egg allergy were analyzed on Kaplan-Meier curves, and factors independently associated with persistent egg allergy was analyzed by logistic regression. Results Seventy-six patients with median (interquartile range) age 8.9 years (6.3–13.0 years) were recruited. They initially presented with egg-allergic reactions at 1.0 years (0.7–1.7 years). Fifty-four children (71%) were able to tolerate egg at a median of 36 months from initial reaction. Patients with concomitant peanut allergy and those with initial reaction at ≥1 year old were more likely to have persistent egg allergy (p = 0.015 and p = 0.027 respectively). Skin prick test wheal ≥6 mm to egg yolk and egg white individually as well as to both egg yolk and egg white were predictors for egg allergy persistence (respective, p < 0.001, p = 0.001, and p = 0.001 by log-rank tests). Logistic regression showed that initial SPT ≥ 6 mm to egg yolk was the only independent predictor for persistent egg allergy (B = 2.59 ± 0.98, p = 0.008). Conclusion Most Chinese children with immediate-type egg allergy can tolerate egg in long run. SPT wheal size to egg, concomitant peanut allergy and initial presentation after infancy may predict egg allergy persistence.

IntroductionEgg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo.Methods and analysis80 participants aged 5–30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms—probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group.Ethics and disseminationThis study has been approved by the Human Research Ethics Committees at the Royal Children’s Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.Trial registration numberACTRN12619000480189.

BACKGROUND A missense variant (rs6967330) of the gene encoding cadherin-related family member 3 (CDHR3) was associated with recurrent severe exacerbations in pre-schoolers. However, there were limited data on its relationship with pre-school lung function and school-age asthma. This study replicated the association between polymorphic markers at the region of CDHR3 around rs6967330 and wheezing phenotypes in two independent cohorts of Chinese children. METHODS Ten tagging SNPs located 10 kb around rs6967330 were selected by HaploView 5.0 based on 1000 Genomes database for Southern Han Chinese. Their associations with wheezing and lung function were examined in 1341 Chinese pre-school children, while those for asthma phenotypes were examined in an independent group of 2079 school-age children. Genotypic and haplotypic associations were analyzed by multivariate regression, and generalized multifactor dimensionality reduction was used to examine epistatic interactions for wheezing traits. RESULTS The mean (SD) age of pre-school cohort was 4.7 (1.0) years. Rs6967330 was associated with current wheeze (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.09-2.43) and its severity (OR 1.64, 95% CI 1.10-2.44) among pre-school children. This SNP was also associated with school-age asthma (OR 1.32, 95% CI 1.04-1.69). The minor allele of rs408223 was associated with lower FEV0.5 (β = -2.411, P = .004) and FEV0.5 /FVC (β = -1.292, P = .015). Lower spirometric indices were also associated with minor allele of rs140154310. GAC haplotype from rs4730125, rs6967330, and rs408223 was associated with pre-school current wheeze and school-age asthma. Epistatic interaction was found between unrelated CDHR3 SNPs for FEV0.5 among pre-schoolers. CONCLUSION CDHR3 is a candidate gene for early-life wheezing, school-age asthma, and lung function in Chinese children.

The rapidly increasing prevalence of allergic disorders over the past 2 decades highlights the need to understand the epidemiology of anaphylaxis. In Europe, the United States, and Australia, the incidence of anaphylaxis is estimated to be between 60 and 950 cases per 100 000 population, with a lifetime prevalence of anaphylaxis of 0.05%-2%. The incidence appears to be increasing over time. Although the existing Asian literature is heterogeneous and limited by under-reporting, it also suggests a similar increasing trend in anaphylaxis incidence in Asia. Anaphylaxis triggers in Asia, such as the predominance of shellfish and wheat in older children and adolescents, differ from those seen in Western populations. Triggers unique to Asia such as traditional Chinese medications, galacto-oligosaccharides, and food delicacies have also been reported. Low usage of adrenaline as first-line treatment of anaphylaxis is evident across all countries and is particularly concerning. There is a need to establish prospective, standardized protocols for anaphylaxis data collection and reporting, to enhance the collective understanding of anaphylaxis and its burden, gaps in management and to identify areas for future research and intervention in each region. Understanding of the underlying reasons explaining the difference between East and West will facilitate future primary preventive strategies.

Background Lung function growth occurs in most asthmatic children. A subgroup has subnormal lung function trajectory, but such data are limited in children. This prospective study characterized longitudinal changes of spirometric indices and fractional exhaled nitric oxide level (FeNO) among asthmatic children and identified their genetic and environmental determinants. Methods Chinese asthmatic children recruited from pediatric clinics underwent 5-year follow-up for pre-bronchodilator spirometric indices and FeNO. Fourteen asthma-associated single nucleotide polymorphisms (SNPs) were genotyped. Generalized estimating equation was used to analyze longitudinal changes of spirometric indices and FeNO. Results One hundred and ninety-three asthmatic children, aged 9.7 (1.9) years, had significant annual decline of 1.3% for forced vital capacity (FVC) and annual increase of 1.2% and 3.6% for FEV1 /FVC and FEF25-75 , respectively. Patients who received inhaled corticosteroid (ICS) had 2.4% lower baseline FEV1 /FVC but 0.81% higher annual increase in FEV1 . Body mass index (BMI) was associated inversely with FEV1 /FVC but positively with FEV1 % and FVC% changes. Asthma exacerbation was associated with lower FEV1 % and FVC% but not their longitudinal changes. When classified by FEV1 curve, one-quarter of patients had reduced lung function growth which was associated with female gender and lower spirometric and higher FeNO values at baseline. IL33_rs1342326 was associated with spirometric indices and FeNO, whereas GSDMB_rs2305480 was significantly associated with FEV1 /FVC change. Conclusion Asthmatic children have annual decline in FVC and increase in FEV1 /FVC and FEF25-75 . Their lung function trajectory is influenced by gender, ICS treatment, BMI, and asthma exacerbations. IL33 and GSDMB may be candidate genes for their lung function growth.

Background and Aims Mycoplasma pneumoniae (MP) is a common childhood pathogen associated with atypical pneumonia (AP). It is often a mild disease and seldom results in paediatric intensive care (PICU) admission. In 2003, World Health Organization (WHO) coined the word SARS (severe acute respiratory syndrome) in patients with severe acute respiratory symptoms (sars) for an outbreak of AP in Hong Kong due to a novel coronavirus. In 2012, another outbreak of coronavirus AP occurred in the Middle East. Confusing case definitions such as MERS (Middle East respiratory syndrome) and SARI (severe acute respiratory infections) were coined. This paper aims to present a case of MP with sars, ARDS, pneumonia and pleural effusion during the MERS epidemics, and review the incidence and mortality of severe AP with MP. Methods We presented a case of MP with sars, acute respiratory distress syndrome (ARDS), pneumonia and pleural effusion during the MERS epidemics, and performed a literature review on the incidence and mortality of severe AP with MP requiring PICU care. Results In early 2013, an 11-year-old girl presented with sars, ARDS (acute respiratory distress syndrome), right-sided pneumonia and pleural effusion. She was treated with multiple antibiotics. Streptococcus pneumoniae was not isolated in this girl with ‘typical’ pneumonia by symptomatology and chest radiography, but tracheal aspirate identified MP instead. The respiratory equations are computed with PaO2/FiO2 consistent with severe lung injury. Literature on the incidence and mortality of severe AP with MP requiring PICU care is reviewed. Six, 165 and 293 articles were found when PubMed (a service of the U.S. National Library of Medicine) was searched for the terms ‘mycoplasma’ and ‘ICU’, ‘mycoplasma’ and ‘mortality’, and ‘mycoplasma' and ‘severe’. Mortality and PICU admission associated with MP is general low and rarely reported. Experimental and clinical studies have suggested that the pathogenesis of lung injuries in MP infection is associated with a cell-mediated immune reaction, and high responsiveness to corticosteroid therapy has been reported especially for severe disease. Management of severe mycoplasma infection in the PICU includes general cardiopulmonary support and specific antimicrobial treatment. Macrolide resistance genotypes have been detected. Conclusion We urge health organizations to refrain from the temptation of coining unnecessary new terminology to describe essentially the same conditions each and every time when outbreaks of AP occur.