Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis.

BACKGROUND: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. METHODS: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. RESULTS: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. CONCLUSIONS: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations.

Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy.

BACKGROUND: Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations. METHODS: Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA. RESULTS: Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients. CONCLUSION: Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.

Changing pattern of pediatric anaphylaxis in Hong Kong, 2010-2019.

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.

The role of the environment in shaping the trends of childhood asthma - An Asian perspective.

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.

Overcoming Shellfish Allergy: How Far Have We Come?

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.

Anaphylaxis - Lessons learnt when East meets West.

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.

Trajectory of spirometric and exhaled nitric oxide measurements in Chinese schoolchildren with asthma.

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.

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G.

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC â€‹= â€‹0.91, 95% CI 0.88-0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

Updated grading system for systemic allergic reactions: Joint Statement of the World Allergy Organization Anaphylaxis Committee and Allergen Immunotherapy Committee.

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

Real-World Sensitization and Tolerance Pattern to Seafood in Fish-Allergic Individuals.

BACKGROUND: Seafood is a common cause of food allergy and anaphylaxis, but there are limited published real-world data describing the clinical presentation of fish and shellfish allergies. OBJECTIVE: This study aimed to examine the clinical characteristics, immunological profile, and tolerance pattern to fish, crustaceans, and mollusks in fish-allergic individuals. METHODS: Patients presenting with IgE-mediated fish allergy between 2016 and 2021 were recruited. A comprehensive sensitization profile including specific IgE and skin prick test to various fish and shellfish species and a detailed clinical history including individuals' recent seafood consumption were evaluated. RESULTS: A total of 249 fish-allergic individuals (aged 4.2 ± 5.8 years) were recruited from 6 allergy clinics in Hong Kong, and they had experienced their fish-allergic reaction 2.2 ± 3.4 years before enrollment. Seventy-five subjects (30%) reacted to either grass carp, salmon, grouper, or cod in oral food challenges. We identified an IgE sensitization gradient that corresponded to the level of ß-parvalbumin in fish. In total, 40% of fish-allergic individuals reported tolerance to 1 or more types of fish, more commonly to fish with a lower ß-parvalbumin level such as tuna and salmon, compared with ß-parvalbumin-rich fish such as catfish and grass carp. Despite fish and shellfish cosensitization, 41% of individuals reported tolerance to crustaceans, mollusks, or both, whereas shellfish avoidance occurred in half of the fish-allergic individuals, of whom 33% lacked shellfish sensitization. CONCLUSIONS: Fish allergy commonly presents in early childhood. A considerable proportion of fish-allergic patients are selectively tolerant to certain fish, typically those with lower levels of ß-parvalbumin. There is an unmet need to promote precision medicine for seafood allergies.

Interactive effects between CDHR3 genotype and rhinovirus species for diagnosis and severity of respiratory tract infections in hospitalized children.

Rhinovirus (RV) is the leading pathogen causing childhood wheezing, with rhinovirus C (RV-C) species reported to cause asthma exacerbation. Allele A of single-nucleotide polymorphism (SNP) CDHR3_rs6967330 upregulates epithelial expression of RV-C receptors which results in more severe asthma exacerbations in children. Nevertheless, there are limited data on interactions between CDHR3 variants and their impact on severity of RV-related pediatric respiratory tract infections (RTIs). Medical records of RV-related RTIs in children aged below 18 years who were hospitalized in two public hospitals in 2015-2016 were independently reviewed by two paediatricians. Archived nasopharyngeal aspirates were retrieved for RV detection and sequencing as well as CDHR3 genotyping. HaploView v.5.0 and generalized multifactor dimensionality reduction (GMDR) analysis were employed for haplotypic assignment and gene-environment interaction analyses. Among 1019 studied cases, our results confirmed the relationship between RV-C species and more severe RTIs. Besides the top risk variant rs6967330-A, we identified rs140154310-T to be associated with RV-C susceptibility under the additive model [odds ratio (OR) 2.53, 95% CI 1.15-5.56; P = 0.021]. Rs140154310 was associated with wheezing illness (OR 2.38, 95% CI 1.12-5.04; P = 0.024), with such association being stronger in subjects who wheezed due to RV-C infections (OR 2.71, 95% CI 1.32-5.58; P = 0.007). Haplotype GAG constructed from rs4730125, rs6967330, and rs73195665 was associated with increased risk of RV-C infection (OR 1.71, 95% CI 1.11-2.65; P = 0.016) and oxygen supplementation (OR 1.93, 95% CI 1.13-3.30; P = 0.016). GMDR analyses revealed epistatic interaction between rs140154310 and rs6967330 of CDHR3 for RV-C infection (P = 0.001), RV-C-associated lower RTI (P = 0.004), and RV-C-associated wheeze (P = 0.007). There was synergistic gene-environmental interaction between rs3887998 and RV-C for more severe clinical outcomes (P < 0.001). To conclude, rs140154310-T is another risk variant for RV-C susceptibility and more severe RTIs. Synergistic epistatic interaction is found between CDHR3 SNPs and RV-C for RTI severity, which is likely mediated by susceptibility to RV-C. Haplotypic analysis and GMDR should be included in identifying prediction models of CDHR3 for childhood asthma and RTIs. IMPORTANCE This case-control study investigated the interaction between CDHR3 genotypes and rhinovirus (RV) species on disease severity in Hong Kong children hospitalized for respiratory tract infection (RTI). There were synergistic effects between RV-C and CDHR3 SNPs for RTI severity, which was mainly driven by RV-C. Specifically, rs6967330 and rs140154310 alone and their epistatic interaction were associated with RV-C-related and severe RTIs in our subjects. Therefore, genotyping of CDHR3 SNPs may help physicians formulate prediction models for severity of RV-associated RTIs.

Hong Kong-Macau Severe Hives and Angioedema Referral Pathway.

Background: Urticaria (defined as the presence of hives, angioedema, or both) can be caused by a variety of etiologies ranging from more common conditions such as chronic spontaneous urticaria (CSU) to rarer conditions such as hereditary angioedema (HAE). Specialist referral may be necessary in cases of severe urticaria or HAE, but access to specialist services remains limited in certain regions, such as the Greater Bay Area (GBA) of China. To address this, the Hong Kong-Macau Severe Hives and Angioedema Referral Pathway (SHARP) was initiated by the Hong Kong Institute of Allergy and Macau Society of Dermatology to promote multidisciplinary collaboration and regional exchange of expertise in the diagnosis and management of severe urticaria. Methods: A nominated task force of dermatologists and immunologists who manage patients with severe urticaria formulated the consensus statements (CS) using the Delphi method. The consensus was defined a priori as an agreement of ≥80%. Results: A total of 24 CS were formulated, including four statements on classifications and definitions, seven statements on diagnosis, and 13 statements on management and referral. The definitions for acute/chronic urticaria and severe CSU were stated. Unnecessary investigations and inappropriate medications were discouraged. The characteristics and recommended approach to suspected bradykinergic angioedema were specified. Stepwise treatment options using second-generation antihistamines, omalizumab, or cyclosporin for patients with CSU were addressed, and the importance of access to HAE-specific medications was emphasized. Furthermore, an integrated referral pathway for patients with severe hives and angioedema was constructed. Conclusion: The SHARP provides guidance for the management and specialist referral of patients with severe hives and angioedema in Hong Kong and Macau.

Development of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort.

IMPORTANCE: Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.

Effectiveness of mRNA and inactivated COVID-19 vaccines: A test-negative study in an infection-naïve Hong Kong population.

OBJECTIVE: Assess real-world effectiveness of vaccines against COVID-19. METHODS: A test-negative study was conducted in January-May 2022 during an Omicron BA.2 wave in Hong Kong. COVID-19 was identified by RT-PCR. 1-1 case-control matching was based on propensity score with vaccine effectiveness adjusted for confounders. RESULTS: Altogether, 1781 cases and 1737 controls aged 3-105 years were analysed. The mean lag time from the last dose of vaccination to testing for SARS-CoV-2 was 133.9 (SD: 84.4) days. Two doses of either vaccine within 180 days offered a low effectiveness against COVID-19 of all severity combined (VEadj [95% CI] for BNT162b2: 27.0% [4.2-44.5], CoronaVac: 22.9% [1.3-39.7]), and further decreased after 180 days. Two doses of CoronaVac were poorly protective 39.5% [4.9-62.5] against severe diseases for age ≥ 60 years, but the effectiveness increased substantially after the third dose (79.1% [25.7-96.7]). Two doses of BNT162b2 protected age ≥ 60 years against severe diseases (79.3% [47.2, 93.9]); however, the uptake was not high enough to assess three doses. CONCLUSIONS: The current real-world analysis indicates a high vaccine effectiveness of three doses of inactivated virus (CoronaVac) vaccines against Omicron variant, whereas the effectiveness of two doses is suboptimal.

Updated consensus statements on COVID-19 Vaccine Allergy Safety in Hong Kong.

Due to global concerns over coronavirus disease 2019 (COVID-19) vaccine-associated allergic reactions; the Hong Kong Institute of Allergy (HKIA) formulated an initial set of consensus statements (CS) on COVID-19 Vaccine Allergy Safety (VAS) in early 2021. Following accumulation of both local and international experience on and COVID-19 VAS, the HKIA task force reformed to update the Hong Kong consensus on COVID-19 VAS. A nominated task force of experts managing patients with drug and vaccine allergies in Hong Kong formulated the updated CS by unanimous decision. A total of 9 new statements were established. Individuals with history of food allergies and anaphylaxis unrelated to the components of COVID-19 vaccines do not require allergist review prior to vaccination. Individuals with history suspicious of an excipient allergy may now be vaccinated with a non-PEG containing vaccine without prior allergist assessment. Individuals with suspected mild allergic reactions following prior COVID-19 vaccination can proceed with the next dose. Only individuals who present with immediate-type allergic reaction with systemic symptoms or more severe nonimmediate type reactions should defer their next dose until allergist review. The remaining statements regarding adequate safety during vaccination and advocation for legislative changes regarding excipient disclosure in Hong Kong remained unchanged from the prior CS. The updated CS are updated in accordance with local and international experience thus far and serve as guidance for local frontline healthcare providers to further promote safe COVID-19 vaccine uptake in Hong Kong.

Seafood Allergy in Asia: Geographical Specificity and Beyond.

Asian countries have unique ways of food processing and dietary habits that may explain the observed differences in the prevalence, natural history, epidemiology and sensitization pattern of food allergic diseases when compared to western countries. Per capita consumption of seafood, including fish and shellfish, is well above the global average for many Asian countries because of their coastal geographical location and rich seafood supply. The wide availability and high abundance of seafood in Asian countries have shaped a diverse way of processing and eating this major food group. Such unique features have significant impact on the sensitization profile and allergenicity of Asians to fish and shellfish. For example, fish and shellfish are eaten raw in some countries that may promote sensitization to heat-labile allergens not otherwise seen in other regions. Fermented fish sauce is commonly used as a condiment in some countries which may promote fish sensitization. Shrimp head and shrimp roe are regarded as delicacies in some countries, but their allergen profiles are yet to be characterized. Freshwater fish and shellfish are a common food source in many Asian countries but the allergenicity of many such species remains unknown. In this review, we discuss factors that may contribute to differences in molecular profile and sensitization pattern for fish and shellfish that are observed in Asian populations and revisit the current status of seafood allergy in this part of the world. Acknowledging the similarities and differences of seafood allergy patterns between Asian and western populations can help us refine a better strategy for diagnosing and managing seafood allergy.