Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Role of skin management in the prevention of atopic dermatitis and food allergy.

Food allergy is postulated to originate from cutaneous sensitization through a disrupted skin barrier, particularly in atopic dermatitis (AD). Strategies for food allergy prevention currently centre around early allergic food introduction, but there is now increasing evidence for the role of early skin barrier restoration in the form of prophylactic emollient therapy and early aggressive, proactive treatment of established AD for food allergy prevention. Research gaps that remain to be addressed include the type of emollient or anti-inflammatory medication, which confers the greatest efficacy in preventive or proactive skin treatment, respectively, the duration of therapy, and the window of opportunity for these interventions.

Immune modulation by rural exposures and allergy protection.

BACKGROUND: Growing up on traditional farms protects children from the development of asthma and allergies. However, we have identified distinct asthma-protective factors, such as poultry exposure. This study aims to examine the biological effect of rural exposure in China. METHODS: We recruited 67 rural children (7.4 ± 0.9 years) and 79 urban children (6.8 ± 0.6 years). Depending on the personal history of exposure to domestic poultry (DP), rural children were further divided into those with DP exposure (DP+ , n = 30) and those without (DP- , n = 37). Blood samples were collected to assess differential cell counts and expression of immune-related genes. Dust samples were collected from poultry stables inside rural households. In vivo activities of nasal administration of DP dust extracts were tested in an ovalbumin-induced asthma model. RESULTS: There was a stepwise increase in the percentage of eosinophils (%) from rural DP+ children (median = 1.65, IQR = [1.28, 3.75]) to rural DP- children (3.40, [1.70, 6.50]; DP+ vs. DP- , p = .087) and to the highest of their urban counterparts (4.00, [2.00, 7.25]; urban vs. DP+ , p = .017). Similarly, rural children exhibited reduced mRNA expression of immune markers, both at baseline and following lipopolysaccharide (LPS) stimulation. Whereas LPS stimulation induced increased secretion of Th1 and proinflammatory cytokines in rural DP+ children compared to rural DP- children and urban children. Bronchoalveolar lavage of mice with intranasal instillation of dust extracts from DP household showed a significant decrease in eosinophils as compared to those of control mice (p < .05). Furthermore, DP dust strongly inhibited gene expression of Th2 signature cytokines and induced IL-17 expression in the murine asthma model. CONCLUSIONS: Immune responses of rural children were dampened compared to urban children and those exposed to DP had further downregulated immune responsiveness. DP dust extracts ameliorated Th2-driven allergic airway inflammation in mice. Determining active protective components in the rural environment may provide directions for the development of primary prevention of asthma.

Comparative analysis of asian carps parvalbumin reveals the divergence pattern of major fish allergen.

BACKGROUND: Asian carps, a popular freshwater fish globally, are valued for their flavor and serve as a crucial protein source, especially for infants. However, grass carp parvalbumin is highly allergenic, surpassing the allergenicity of fish like salmon and cod. The allergenic potential of parvalbumin in other Asian carps remains unknown, underscoring the need for allergen identification to improve the precision of fish allergy diagnosis and treatment. OBJECTIVE: To identify all parvalbumin homologs in Asian carps and investigate the role of gene divergence in allergenic homolog formation. METHODS: Three annotated genomes of Asian carp, including grass carp, black carp and bighead carp, were constructed using a hybrid assembly approach. Through sequence homology at the genomic level, all the homologs of major fish allergens were identified. Bioinformatics tools were then employed to reveal the gene structures, expression levels, and protein conformations of parvalbumin. RESULTS: Grass carp genome analysis showed nine parvalbumin homologs, with Cid_PV2 most similar to Cten i 1. Bighead and black carp genomes had ten homologs, including potentially allergenic Mpi_PV7 and Hno_PV7. Tissue-specific expression patterns revealed alternative usage of parvalbumin homologs. Gene duplication events expanded parvalbumin copies in bony fish, with two gene clusters identified in Asian carp genomes. 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.

From preschool wheezing to asthma: Environmental determinants.

Wheezing is common among preschool children, representing a group of highly heterogeneous conditions with varying natural history. Several phenotypes of wheezing have been proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. Epidemiological and immunological studies across different populations have revealed the key role of environmental factors in influencing the progression from preschool wheezing to childhood asthma. Significant risk factors include severe respiratory infections, allergic sensitization, and exposure to tobacco smoke. In contrast, a farming/rural environment has been linked to asthma protection in both human and animal studies. Early and intense exposures to microorganisms and microbial metabolites have been demonstrated to alter host immune responses to allergens and viruses, thereby driving the trajectory away from wheezing illness and asthma. Ongoing clinical trials of candidate microbes and microbial products have shown promise in shaping the immune function to reduce episodes of viral-induced wheezing. Moreover, restoring immune training may be especially important for young children who had reduced microbial exposure due to pandemic restrictions. A comprehensive understanding of the role of modifiable environmental factors will pave the way for developing targeted prevention strategies for preschool wheezing and asthma.

Human milk oligosaccharides in Chinese lactating mothers and relationship with allergy development in offspring.

BACKGROUND: The health benefits of breastfeeding are partly contributed by human milk oligosaccharides (HMOs), but there is limited data on breast milk (BM) HMO composition in Chinese. OBJECTIVE: This study investigated the association between early-life HMO intake and allergy occurrence in Chinese children. METHODS: 103 healthy Chinese pregnant women regardless of allergy history were recruited into this birth cohort. Their babies were followed until 24 months old. Concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), -sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) in BM collected at 1-month postpartum were measured by liquid chromatography-mass spectrometry. The associations between these HMOs and allergy occurrence by 24 months were analyzed by multivariate regression analyses. RESULTS: Twenty-nine percent and 19% of participants had eczema at 12 and 24 months old respectively. Eighty BM samples were analyzed, with 2'-FL being the most abundant HMO (median 1447 ppm, interquartile range [IQR] 291-1906 ppm), and median (IQR) levels of LNnT, 6'-SL and 3'-SL in ppm were 738 (580-950), 20.5 (12.7-38.8) and 23.0 (17.8-27.6) respectively. Participants with eczema by 24 months consumed BM with higher 2'-FL concentration at 1-month (P = 0.008), and also lower 6'-SL concentration in exclusively breastfed infants (P = 0.012) but higher 6'-SL concentration for those with mixed feeding at 1 month (P = 0.043). Food allergic children at 12 months consumed BM with higher 2'-FL concentrations at 1 month (P = 0.048). CONCLUSIONS: BM 2'-FL concentration is higher in children who develops eczema by 24 months and food allergy during infancy. The relationship for 6'-SL is divergent depending on mode of feeding in infants.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination.

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.

Prospective study of disease persistence and lung function trajectories of childhood asthma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (FEV1 %) with an odds ratio of 0.96 (95% CI 0.93-1.00). Throughout follow-up, patients with persistent asthma had generally lower forced expiratory indices than those with asthma resolution. Children with persistent asthma experienced poorer lung function growth. CONCLUSIONS: Female, ICS ever, and frequent AE predicted persistent asthma. Patients with persistent asthma had lower forced expiratory indices and poorer lung function growth into adulthood.

Validation of the food allergy quality of life questionnaire series in Chinese families with food-allergic children.

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.

Molecular and immunological characterization of grass carp (Ctenopharyngodon idella) parvalbumin Cten i 1: A major fish allergen in Hong Kong.

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.

Cadherin-related family member 3 gene impacts childhood asthma in Chinese children.

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 (ß = -2.411, P = .004) and FEV0.5 /FVC (ß = -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.

A novel infant microbiome formula (SIM03) improved eczema severity and quality of life in preschool children.

Altered gut microbiome composition has been reported in children with eczema and interventions that restore beneficial bacteria in the gut may improve eczema. This open-label pilot study aimed to investigate the efficacy of a novel infant microbiome formula (SIM03) in young children with eczema. Pre-school Chinese children aged 1-5 years old with eczema received SIM03 twice daily for three months. The novelty of SIM03 consists of both the use of a patented microencapsulation technology to protect the viability of unique Bifidobacterium bifidum and Bifidobacterium breve strains identified through big data analysis of large metagenomic datasets of young Chinese children. Paired stool samples at baseline and following SIM03 were analyzed by metagenomics sequencing. Generalized estimating equation was used to analyze changes in eczema severity, skin biophysical parameters, quality of life and stool microbiome. Twenty children aged 3.0 ± 1.6 years (10 with severe eczema) were recruited. Treatment compliance was ≥ 98%. SCORing Atopic Dermatitis score decreased significantly at two months (P = 0.008) and three months (P < 0.001), while quality of life improved significantly at 1, 2, and 3 months. The relative abundance of B. breve and microbial pathways on acetate and acetyl-CoA synthesis were enriched in stool samples at one month (P = 0.0014). Children who demonstrated increased B. bifidum after SIM03 showed improvement in sleep loss (P = 0.045). Relative abundance of B. breve correlated inversely with eczema extent (P = 0.023) and intensity (P = 0.019) only among patients with increased B. breve at Month 3. No serious adverse event was observed. In conclusion, SIM03 is well tolerated. This patented microbiome formula improves disease severity and quality of life in young eczematous children by enhancing the delivery of B. bifidum and B. breve in the gut. SIM03 is a potential treatment option for childhood eczema.

Perspectives and gaps in the management of food allergy and anaphylaxis in the Asia-Pacific Region.

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region. Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia. Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey. Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories. Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.

High prevalence of sacroiliitis and early structural changes in the sacroiliac joint in children with enthesitis-related arthritis: findings from a tertiary centre in Hong Kong.

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.

Development and validation of assessment tools for food allergy-related knowledge and management confidence.

Background: Given the life-threatening nature of food allergy (FA), it is important to assess the level of knowledge among families with food-allergic patients and their ability to cope with anaphylaxis. This study constructed a FA knowledge questionnaire (FAKQ) and confidence in FA management skills (CIFAMS) questionnaire to assess understanding and attitudes toward FA management in food-allergic families. Methods: Items from literature review and expert panel showing ≥80% content validity index and semantic equivalence were selected for translation into Chinese. These questionnaires underwent feasibility pilot testing followed by cross-sectional validation to assess their psychometric properties of internal consistency, test-retest reliability, and construct validity with a FA quality-of-life questionnaire and discriminant validity. Exploratory factor analysis was performed to confirm their factor structure. Results: A total of 155 subjects (104 patients and 51 parents) completed a 20-item FAKQ and 10-item CIFAMS. Both tools showed acceptable internal consistency in baseline and retest groups. FAKQ and CIFAMS correlated for all subjects (P = .002) and for adults (P = .002), and similarly between CIFAMS and parent-reported FA independent measure (P = .005). Total score of FAKQ was sensitive to within-group differences of patients hospitalized for FA (P < .001). FAKQ and CIFAMS items were factored into 4 and 2 domains, respectively. Subjects scored the lowest on FAKQ items about signs of allergic reaction and CIFAMS items on epinephrine autoinjector use. Conclusion: FAKQ and CIFAMS developed by our group are valid and reliable in assessing knowledge and confidence in FA management in patients and parents. These tools are crucial for formulating education programs and advocacy campaigns for FA.