World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

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.

The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children.

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

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.

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.

Utility of biomarkers in the diagnosis and monitoring of asthmatic children.

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited. In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and "omic" approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all "well-known" and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers' use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.

Allergic disease and sensitization disparity in urban and rural China: A EuroPrevall-INCO study.

BACKGROUND: Studies in comparison with allergic diseases and sensitization between rural and urban environments in westernized countries might be biased and not adequately reflect countries undergoing rapid transition. METHODS: A total of 5542 schoolchildren from urban area and 5139 from rural area were recruited for the EuroPrevall-INCO survey. A subsequent case-control sample with 196 children from urban area and 202 from rural area was recruited for a detailed face-to-face questionnaire and assessment of sensitization. Skin prick tests and serum-specific IgE measurements were used to assess sensitizations against food and aeroallergens. Logistic regression analysis was used to determine associations between risk/protective factors, food adverse reactions (FAR), allergic diseases, and sensitizations. RESULTS: Prevalence of self-reported allergic diseases, including asthma (6.6% vs.2.5%), rhinitis (23.2% vs.5.3%), and eczema (34.1% vs.25.9%), was higher in urban than in rural children. Urban children had a significantly higher prevalence of FAR and related allergic diseases, and lower food/inhalation allergen sensitization rate, than those of rural children. In urban children, frequent changing places of residency (odds ratio 2.85, 95% confidence interval: 1.45-5.81) and antibiotic usage (3.54, 1.77-7.32) in early life were risk factors for sensitization, while sensitization and family history of allergy were risk factors for allergic diseases. In rural children, exposure to rural environments in early life was protective against both allergen sensitizations (0.46, 0.21-0.96) and allergic diseases (0.03, 0.002-0.19). CONCLUSION: We observed a disparity in rates of allergic diseases and allergen sensitization between rural and urban children. In addition to family history, the development of allergic diseases and allergen sensitization were associated with specific urban/rural environmental exposures in early life.

Rural environment reduces allergic inflammation by modulating the gut microbiota.

Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.

Stunting as a Risk Factor for Asthma: The Role of Vitamin D, Leptin, IL-4, and CD23.

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Poultry exposure and environmental protection against asthma in rural children.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood, and the prevalence has been increasing over the past few decades. One of the most consistent epidemiological findings is that children living in a farming or rural environment are protected from development of asthma and allergies, but the protective factors in rural China are not clear. METHODS: A community-based, cross-sectional epidemiological study was performed in a total of 17,587 children aged 5-8 years, 3435 from Hong Kong (urban) and 14,152 from Conghua (rural county in southern China). Asthma and allergic symptoms as well as environmental exposures were ascertained by using a standardized and validated questionnaire. RESULTS: The prevalence of current wheeze was significantly lower in rural Conghua than that of urban Hong Kong (1.7% vs. 7.7%, p < 0.001). A lower rate of asthma ever was also reported in rural children compared with their urban counterparts (2.5% vs. 5.3%, p < 0.001). After adjusting for confounding factors, exposure to agricultural farming (adjusted odds ratio 0.74, 95% confidence interval: 0.56-0.97) and poultry (0.75, 0.59-0.96) were the most important factors associated with the asthma-protective effect in the rural area. Further propensity score-adjusted analysis indicated that such protection conferred by living in the rural environment was mainly attributable to poultry exposure. CONCLUSIONS: We confirmed that the prevalence of asthma and atopic disorders was significantly lower in rural children when compared with their urban peers. Exposure to poultry and agricultural farming are the most important factors associated with asthma protection in the rural area.

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.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - XIV - Recommendations on CMA immunotherapy.

Background: The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled "conditional" due to the low certainty about the health effects based on the available evidence. Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

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.

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.

Mitogen-activated protein kinase signaling in childhood asthma development and environment-mediated protection.

BACKGROUND: While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen-activated protein kinase (MAPK) pathway with its negative regulator dual-specificity phosphatase-1 (DUSP1) is presumably associated with asthma development. OBJECTIVES: We aimed to investigate the role of MAPK signaling in childhood asthma and its environment-mediated protection, including a representative selection of 232 out of 1062 children from two cross-sectional cohorts and one birth cohort study. METHODS: Peripheral blood mononuclear cells (PBMC) from asthmatic and healthy children were cultured upon stimulation with farm-dust extracts or lipopolysaccharide. In subgroups, gene expression was analyzed by qPCR (PBMCs, cord blood) and NanoString technology (dendritic cells). Protein expression of phosphorylated MAPKs was measured by mass cytometry. Histone acetylation was investigated by chromatin immunoprecipitation. RESULTS: Asthmatic children expressed significantly less DUSP1 (p = .006) with reduced acetylation at histone H4 (p = .012) compared with healthy controls. Farm-dust stimulation upregulated DUSP1 expression reaching healthy levels and downregulated inflammatory MAPKs on gene and protein levels (PBMCs; p ≤ .01). Single-cell protein analysis revealed downregulated pMAPKs upon farm-dust stimulation in B cells, NK cells, monocytes, and T-cell subpopulations. CONCLUSION: Lower DUSP1 baseline levels in asthmatic children and anti-inflammatory regulation of MAPK in several immune cell types by farm-dust stimulation indicate a regulatory function for DUSP1 for future therapy contributing to anti-inflammatory characteristics of farming environments.

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.

BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.