not-yet-known not-yet-known not-yet-known unknown Background: IgE-mediated fish allergy has long been considered an umbrella term due to the high cross-reactivity of parvalbumin, the major fish allergen. Yet, clinical tolerance to certain fish highlights allergenicity differences. In this study, we sought to construct a fish allergenicity ladder and identify fish parvalbumin epitopes to improve the diagnosis of fish allergy. Methods: Reported clinical history and the serum-specific IgE (sIgE) responses of 200 fish allergic patients were collected and analyzed, while the relative parvalbumin content in different fish were measured for the construction of fish allergenicity ladder. Double-blind placebo-controlled food challenge (DBPCFC) and open challenge against salmon, grass carp and grouper were performed in 58 selected patients for validation of the ladder. Epitope mapping was performed by peptide array against parvalbumins of salmon (both β-1 and β-2), cod, grouper, and grass carp with sera from fish allergic (n=11), partial fish tolerant (n=12), and complete fish tolerant (n=5) patients diagnosed based on oral food challenge outcome. Results: The distribution pattern of clinical, sIgE and molecular data and their strong positive correlation led to the construction of a 4-step fish allergenicity ladder comprising: step 1 of the least allergenic fishes (tuna, halibut, salmon), steps 2 (cod) and 3 (herring and grouper) of moderately allergenic fishes to step 4 of highly allergenic fishes (catfish, grass carp and tilapia). Epitope mapping revealed one epitope from grouper parvalbumin (AA64-78) for diagnosing general fish allergy and one epitopic region from salmon parvalbumin (AA19-33) as biomarker of specific fish tolerance. Only epitope-specific IgE differentiated these patients but not sIgE to fish extract or parvalbumin. Conclusion: The fish ladder and epitopes discovery can precisely differentiate fish-allergic and tolerant subjects and guide fish reintroduction by stepping up the ladder, which innovate fish allergy care in the next millennium.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization and natural history review. Numerous factors that may affect disease activity and patient wellbeing need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even ‘real-time’, monitoring between visits. Following an approach that included needs assessment, evidence appraisal and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Background: Recent studies indicated that fish-allergic patients may safely consume certain fish species. Multiplex IgE testing facilitates the identification of species tolerated by individual patients. Methods: Sera were collected from 263 fish-allergic patients from Austria, China, Denmark, Luxembourg, Norway and Spain. Specific (s) IgE to parvalbumins (PVs) from 10 fish species along with IgE to 7 raw and 6 heated fish extracts was quantified using a research version of the ALEX 2 assay. IgE-signatures of individual patients and patient groups were analyzed using SPSS and R. Results: sIgE to alpha-PV from ray, a cartilaginous fish, was not detected in 78% of the patients while up to 41% of the patients, depending on their country of origin, tested negative for at least one beta-PV. sIgE values were highest for mackerel and tuna PVs (>10 kUA/L) and significantly lower for cod (4.9 kUA/L) and sole PVs (2.55 kUA/L). 17% of the patients, although negative for PVs, tested positive for the respective fish extracts. Based on the absence of IgE to PVs and extracts, up to 21% of the patients were identified as potentially tolerating one or more bony fish. Up to 90% of the patients tested negative for ray. The probability of negativity to one fish based on negativity to others was calculated. Negativity to tuna and mackerel emerged as a good marker of negativity to additional bony fish. Conclusion: Measuring sIgE to PVs and extracts from evolutionary distant fish species indicates bony and cartilaginous fish species for tolerance-confirming food challenges.

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 towards the identified allergens 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.

Background There is substantial interest in allergen-specific immunotherapy in food allergy. We systematically reviewed its efficacy and safety. Methods We searched six bibliographic databases from 1946 to 30 April 2021 for randomised controlled trials about immunotherapy alone or with biologicals in IgE-mediated food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. Results We included 36 trials with 2,126 participants, mainly children. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5. to 21.4, high certainty); cow’s milk (RR 5.7, 1.9 to 16.7, moderate certainty) and hen’s egg allergy (RR 8.9, 4.4 to 18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300mg or 1000mg peanut protein was 2. In peanut allergy, oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0 to 1.2, low certainty) or severe reactions (RR 1,6, 0.7 to 3.5, low certainty). It may increase adverse reactions in cow’s milk (RR 3.9, 2.1 to 7.5, low certainty) and hen’s egg allergy (RR 7.0, 2.4 to 19.8, moderate certainty), but reactions tended to be mild and gastrointestinal. Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8 to 3.8, moderate certainty). Results were unclear for other allergies and administration routes. Conclusions Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow’s milk and hen’s egg allergy. However, our review found little about whether this improves quality of life, is sustained or cost-effective.

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.

Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 on childhood asthma outcomes. Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4-18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.

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. Objectives: 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 pediatric and adult populations from 2009 to 2019 was found which was more marked among the pediatric population. There was an overall increasing rates 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 pediatric patients (36.5% vs. 89.4%, p<0.001). 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.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019 and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the sub-sections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.