Publications by authors named "Gary W K Wong"

107 Publications

Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study.

Lancet Infect Dis 2021 Jan 18. Epub 2021 Jan 18.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Background: Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan.

Methods: This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect.

Findings: 27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2-16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0-1 years were significantly more likely to be infected than children aged 2-5 years (odds ratio [OR] 2·20, 95% CI 1·40-3·44) and children aged 6-12 years (1·53, 1·01-2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28-1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14-0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30-1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI 0·24-0·26] to 0·12 [0·10-0·13]) and by 63% among secondary cases (from 0·17 [0·16-0·18] to 0·063 [0·057-0·070]).

Interpretation: Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.

Funding: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.
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http://dx.doi.org/10.1016/S1473-3099(20)30981-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833912PMC
January 2021

Increasing incidence of anaphylaxis in Hong Kong from 2009 to 2019-discrepancies of anaphylaxis care between adult and paediatric patients.

Clin Transl Allergy 2020 Nov 19;10(1):51. Epub 2020 Nov 19.

Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Background: Anaphylaxis has been increasing in developed countries but there is very little published data on the burden of anaphylaxis and the pattern of adrenaline autoinjector (AAI) prescription from Asia. We aim to determine the incidence rates of anaphylaxis and prescription rates of AAI over the past decade in Hong Kong.

Methods: Using a centralized electronic database of Hong Kong's sole public-funded healthcare provider, we obtained and analysed all patients between 2009 and 2019 with physician-reported diagnosis of anaphylaxis. Incidence rates were calculated using population statistics as the denominator. Patients' prescriptions on discharge were collected to determine the AAI prescription rates.

Results: The overall 10-year estimated incidence rate of anaphylaxis was 3.57 per 100,000 person-years. An increasing trend over time across both paediatric and adult populations from 2009 to 2014 was found, which remained stable until 2019. This was more marked among the paediatric population (paediatric vs adult incidence rate ratio in 2019: 3.51 [95% CI 1.12-2.66] vs 1.82 [95% CI 1.05-1.60]). There was an overall increasing rate of AAI prescription for patients admitted for anaphylaxis, but the overall AAI prescription rate was less than 15% and was significantly less likely to be prescribed for the adult compared to paediatric patients (36.5% vs. 89.4%, p < 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.
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http://dx.doi.org/10.1186/s13601-020-00355-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677822PMC
November 2020

Rapid Response to an Outbreak in Qingdao, China.

N Engl J Med 2020 12 18;383(23):e129. Epub 2020 Nov 18.

Qingdao Women and Children's Hospital, Qingdao, China.

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http://dx.doi.org/10.1056/NEJMc2032361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722691PMC
December 2020

Cell-Based Functional IgE Assays Are Superior to Conventional Allergy Tests for Shrimp Allergy Diagnosis.

J Allergy Clin Immunol Pract 2021 Jan 12;9(1):236-244.e9. Epub 2020 Sep 12.

Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong. Electronic address:

Background: The diagnosis of shellfish allergy currently relies on patient history, skin prick test (SPT), and serum specific IgE (sIgE) quantification. These methods lack sufficient diagnostic accuracy, whereas the gold standard of oral food challenges is risky and burdensome. Markers of reactivity and severity of allergic reactions to shellfish will improve clinical care of these patients.

Objectives: This study compared the diagnostic performance of SPT, sIgE, basophil activation test (BAT), and IgE crosslinking-induced luciferase expression (EXiLE) test for shrimp allergy.

Methods: Thirty-five subjects with documented history of shrimp allergic reactions were recruited and grouped according to results of double-blind, placebo-controlled food challenge (DBPCFC). In addition to routine diagnostics, BAT (Flow CAST) and EXiLE test with shrimp extract and tropomyosin were performed.

Results: Of 35 subjects, 15 were shrimp allergic with pruritus, urticaria, and itchy mouth on DBPCFC, whereas 20 were tolerant to shrimp. Tropomyosin only accounted for 53.3% of sensitization among subjects with challenge-proven shrimp allergy. BAT using shrimp extract as stimulant showed the highest area under curve value (0.88), Youden Index (0.81), likelihood ratio (14.73), odds ratio (104), and variable importance (4.27) when compared with other assays and tropomyosin diagnosis. Results of BAT significantly correlated with those of EXiLE (r = 0.664, P < .0001).

Conclusions: BAT is a more accurate diagnostic marker for shrimp allergy than SPT and shrimp sIgE, whereas the EXiLE test based on an IgE crosslinking assay is a good alternative to BAT. Tropomyosin may not be the most important shrimp allergen in Chinese, which warrants further investigation to search for other major allergens and diagnostic markers.
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http://dx.doi.org/10.1016/j.jaip.2020.08.057DOI Listing
January 2021

COVID-19: A tale of two pandemics across the Asia Pacific region.

Paediatr Respir Rev 2020 Sep 27;35:75-80. Epub 2020 Jun 27.

Department of Paediatrics, Prince of Wales Hospital, Hong Kong Special Administrative Region; Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region. Electronic address:

The widely diverse impacts of SAR-CoV-2 infection resulting in the COVID-19 pandemic cannot be held in more stark relief when contrasting the devastating impact upon China, Italy, Great Britain, America and Brazil with the considerably milder course in the geographically isolated countries of Australia and New Zealand and the densely populated Vietnam. Children in the Asia-Pacific region, as with children all over the world to date, have fared better than older adults. Other countries in the Asia-Pacific region, including Indonesia and India have struggled to deal with the pandemic because of a lack of health infrastructure, inability to provide sufficient testing and isolation and widespread poverty. This article will provide a snapshot of the impact of COVID-19 upon countries in the Asia-Pacific region in the six months since the first case of the novel zoonotic coronavirus infection appeared in China.
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http://dx.doi.org/10.1016/j.prrv.2020.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319925PMC
September 2020

ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020).

Authors:
Jean Bousquet Marek Jutel Cezmi A Akdis Ludger Klimek Oliver Pfaar Kari C Nadeau Thomas Eiwegger Anna Bedbrook Ignacio J Ansotegui Josep M Anto Claus Bachert Eric D Bateman Kazi S Bennoor Elena Camelia Berghea Karl-Christian Bergmann Hubert Blain Mateo Bonini Sinthia Bosnic-Anticevich Louis-Philippe Boulet Luisa Brussino Roland Buhl Paulo Camargos Giorgio Walter Canonica Victoria Cardona Thomas Casale Sharon Chinthrajah Mübeccel Akdis Tomas Chivato George Christoff Alvaro A Cruz Wienczyslawa Czarlewski Stefano Del Giacco Hui Du Yehia El-Gamal Wytske J Fokkens Joao A Fonseca Yadong Gao Mina Gaga Bilun Gemicioglu Maia Gotua Tari Haahtela David Halpin Eckard Hamelmann Karin Hoffmann-Sommergruber Marc Humbert Nataliya Ilina Juan-Carlos Ivancevich Guy Joos Musa Khaitov Bruce Kirenga Edward F Knol Fanny W Ko Seppo Koskinen Marek L Kowalski Helga Kraxner Dmitry Kudlay Piotr Kuna Maciej Kupczyk Violeta Kvedariene Amir H Abdul Latiff Lan T Le Michael Levin Desiree Larenas-Linnemann Renaud Louis Mohammad R Masjedi Erik Melén Florin Mihaltan Branislava Milenkovic Yousser Mohammad Mario Morais-Almeida Joaquim Mullol Leyla Namazova Hugo Neffen Elisabete Nunes Paul O'Byrne Robyn O'Hehir Liam O'Mahony Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Petr Panzner Nikos G Papadopoulos Gianni Passalacqua Vincenzo Patella Ruby Pawankar Nhân Pham-Thi Bernard Pigearias Todor A Popov Francesca Puggioni Frederico S Regateiro Giovanni Rolla Menachem Rottem Boleslaw Samolinski Joaquin Sastre Jurgen Schwarze Aziz Sheikh Nicola Scichilone Manuel Soto-Quiros Manuel Soto-Martinez Milan Sova Stefania Nicola Rafael Stelmach Charlotte Suppli-Ulrik Luis Taborda-Barata Teresa To Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Omar Usmani Arunas Valiulis Maria Teresa Ventura Giovanni Viegi Theodor Vontetsianos De Yun Wang Sian Williams Gary W K Wong Arzu Yorgancioglu Mario Zernotti Mihaela Zidarn Torsten Zuberbier Ioana Agache

Allergy 2021 Mar 21;76(3):689-697. Epub 2020 Sep 21.

Transylvania University Brasov, Brasov, Romania.

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http://dx.doi.org/10.1111/all.14471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361514PMC
March 2021

Global implementation of the world health organization's International Classification of Diseases (ICD)-11: The allergic and hypersensitivity conditions model.

Allergy 2020 09 14;75(9):2206-2218. Epub 2020 Jul 14.

University Hospital of Montpellier, Montpellier, France.

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 subsections 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.
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http://dx.doi.org/10.1111/all.14468DOI Listing
September 2020

COVID-19, asthma, and biological therapies: What we need to know.

World Allergy Organ J 2020 May 16;13(5):100126. Epub 2020 May 16.

Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona Health Sciences, Tucson, AZ, USA.

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV-2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID-19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers.
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http://dx.doi.org/10.1016/j.waojou.2020.100126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229954PMC
May 2020

Acute asthma management during SARS-CoV2-pandemic 2020.

World Allergy Organ J 2020 May 14;13(5):100125. Epub 2020 May 14.

Chinese University of Hong Kong, Hong Kong.

Background: The current COVID-19 pandemic has changed many medical practices in order to provide additional protection to both our patients and healthcare providers. In many cases this includes seeing patients through electronic means such as telehealth or telephone rather than seeing them in person. Asthma exacerbations cannot always be treated in this way.

Problem: Current emergency unit asthma guidelines recommend bronchodilators be administered by metered dose inhaler (MDI) and spacer for mild-moderate asthma and include it as a choice even in severe asthma, but many emergency units continue to prefer nebulised therapy for patients who urgently require beta-agonists. The utilization of nebulised therapy potentially increases the risk of aerosolization of the coronavirus. Since nosocomial transmission of respiratory pathogens is a major threat in the context of the SARS-CoV-2 pandemic, use of nebulised therapy is of even greater concern due to the potential increased risk of infection spread to nearby patients and healthcare workers.

Practical Implications: We propose a risk stratification plan that aims to avoid nebulised therapy, when possible, by providing an algorithm to help better delineate those who require nebulised therapy. Protocols that include strategies to allow flexibility in using MDIs rather than nebulisers in all but the most severe patients should help mitigate this risk of aerosolised infection transmission to patients and health care providers. Furthermore, expedient treatment of patients with high dose MDI therapy augmented with more rapid initiation of systemic therapy may help ensure patients are less likely to deteriorate to the stage where nebulisers are required.
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http://dx.doi.org/10.1016/j.waojou.2020.100125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221365PMC
May 2020

Brief report: International perspectives on the pediatric COVID-19 experience.

Pediatr Pulmonol 2020 07 1;55(7):1598-1600. Epub 2020 May 1.

Department of Paediatrics and Child Health, SA MRC Unit on Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa.

The 2019 novel coronavirus (SARS-CoV-2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence-based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID-19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control.
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http://dx.doi.org/10.1002/ppul.24800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267574PMC
July 2020

Personal strategies to minimise effects of air pollution on respiratory health: advice for providers, patients and the public.

Eur Respir J 2020 06 4;55(6). Epub 2020 Jun 4.

Faculty of Medicine, National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield NHS Foundation Trust, London, UK.

As global awareness of air pollution rises, so does the imperative to provide evidence-based recommendations for strategies to mitigate its impact. While public policy has a central role in reducing air pollution, exposure can also be reduced by personal choices. Qualified evidence supports limiting physical exertion outdoors on high air pollution days and near air pollution sources, reducing near-roadway exposure while commuting, utilising air quality alert systems to plan activities, and wearing facemasks in prescribed circumstances. Other strategies include avoiding cooking with solid fuels, ventilating and isolating cooking areas, and using portable air cleaners fitted with high-efficiency particulate air filters. We detail recommendations to assist providers and public health officials when advising patients and the public regarding personal-level strategies to mitigate risk imposed by air pollution, while recognising that well-designed prospective studies are urgently needed to better establish and validate interventions that benefit respiratory health in this context.
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http://dx.doi.org/10.1183/13993003.02056-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270362PMC
June 2020

Overcoming Shellfish Allergy: How Far Have We Come?

Int J Mol Sci 2020 Mar 23;21(6). Epub 2020 Mar 23.

Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.

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.
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http://dx.doi.org/10.3390/ijms21062234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139905PMC
March 2020

Toward personalization of asthma treatment according to trigger factors.

J Allergy Clin Immunol 2020 06 18;145(6):1529-1534. Epub 2020 Feb 18.

Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia; NRC Institute of Immunology FMBA of Russia, Moscow, Russia; Division of Immunology and Allergy, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Karl Landsteiner University, Krems, Austria. Electronic address:

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.
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http://dx.doi.org/10.1016/j.jaci.2020.02.001DOI Listing
June 2020

Comparative Study of Food Allergies in Children from China, India, and Russia: The EuroPrevall-INCO Surveys.

J Allergy Clin Immunol Pract 2020 04 16;8(4):1349-1358.e16. Epub 2019 Dec 16.

Department of Pediatrics, Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Background: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food allergy in the developed world.

Objective: We used a standardized methodology to determine the prevalence and types of food-specific allergic sensitization and food allergies in schoolchildren from urban and rural regions of China, Russia, and India.

Methods: The current study is a multicenter epidemiological survey of children recruited from 5 cities in China (Hong Kong and Guangzhou), Russia (Tomsk), and India (Bengaluru and Mysore) and 1 rural county in Southern China (Shaoguan). A total of 35,549 children aged 6 to 11 years from 3 countries participated in this survey. Random samples of children from 3 countries were first screened by the EuroPrevall screening questionnaire. Children with and without a history of adverse reactions to foods were then recruited for the subsequent case-control comparative studies. We determined the prevalence rates of food-specific IgE sensitization and food allergies using the predefined criteria.

Results: The prevalence rates of food-specific IgE sensitization (≥0.7 kU/L) to at least 1 food were 16.6% in Hong Kong, 7.0% in Guangzhou, 16.8% in rural Shaoguan, 8.0% in Tomsk, and 19.1% in India. Using a definition of probable food allergy as reporting allergic symptoms within 2 hours of ingestion of a specific food plus the presence of allergic sensitization to the specific food (positive IgE and/or positive skin prick test result), the prevalence of food allergy was highest in Hong Kong (1.50%), intermediate in Russia (0.87%), and lowest in Guangzhou (0.21%), Shaoguan (0.69%), and India (0.14%). For children recruited from Hong Kong, both sensitization and food allergy were significantly higher in children who were born and raised in Hong Kong when compared with those who were born in mainland China and migrated to Hong Kong, highlighting the importance of early-life exposures in affecting the subsequent development of food sensitization and food allergy.

Conclusions: There are wide variations in the prevalence of food-specific IgE sensitization and food allergy in the 3 participating countries. Food allergy appears to be less common when compared with developed countries. The variations in the prevalence of food allergen sensitization cannot be explained by the differences in the degree of urbanization. Despite the high prevalence of food-specific IgE sensitization in India and rural China, food allergy is still extremely uncommon. In addition to IgE sensitization, other factors must play important roles resulting in the clinical manifestations of food allergies.
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http://dx.doi.org/10.1016/j.jaip.2019.11.042DOI Listing
April 2020

TNF-α-induced protein 3 is a key player in childhood asthma development and environment-mediated protection.

J Allergy Clin Immunol 2019 12 2;144(6):1684-1696.e12. Epub 2019 Aug 2.

Pediatric Allergology, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany; Member of the German Center for Lung Research-DZL, LMU Munich, Munich, Germany. Electronic address:

Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection.

Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors.

Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective" farms or LPS. NF-κB signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns.

Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P < .05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling-associated gene expression toward an anti-inflammatory state (P < .001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma.

Conclusion: Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment.
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http://dx.doi.org/10.1016/j.jaci.2019.07.029DOI Listing
December 2019

Anaphylaxis - Lessons learnt when East meets West.

Pediatr Allergy Immunol 2019 11;30(7):681-688

Department of Pediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Sha Tin, Hong Kong, China.

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.
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http://dx.doi.org/10.1111/pai.13098DOI Listing
November 2019

How Should We Treat Patients with Mild Asthma?

Authors:
Gary W K Wong

N Engl J Med 2019 05 19;380(21):2064-2066. Epub 2019 May 19.

From the Department of Pediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.1056/NEJMe1905354DOI Listing
May 2019

Food allergy in the developing world.

J Allergy Clin Immunol 2018 01 22;141(1):76-78.e1. Epub 2017 Nov 22.

Allergy and Immune Disorders, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Department of Allergy and Immunology, The Royal Children's Hospital, Melbourne, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.11.008DOI Listing
January 2018

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

Pediatr Allergy Immunol 2018 03 22;29(2):166-173. Epub 2017 Dec 22.

Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.

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 FEV /FVC and FEF , respectively. Patients who received inhaled corticosteroid (ICS) had 2.4% lower baseline FEV /FVC but 0.81% higher annual increase in FEV . Body mass index (BMI) was associated inversely with FEV /FVC but positively with FEV % and FVC% changes. Asthma exacerbation was associated with lower FEV % and FVC% but not their longitudinal changes. When classified by FEV 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 FEV /FVC change.

Conclusion: Asthmatic children have annual decline in FVC and increase in FEV /FVC and FEF . 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.
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http://dx.doi.org/10.1111/pai.12836DOI Listing
March 2018

Reducing antibiotic prescriptions for childhood upper respiratory tract infections.

Authors:
Gary W K Wong

Lancet Glob Health 2017 12 5;5(12):e1170-e1171. Epub 2017 Nov 5.

Department of Paediatrics, Prince of Wales Hospital, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. Electronic address:

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http://dx.doi.org/10.1016/S2214-109X(17)30423-0DOI Listing
December 2017

Pediatric allergy and immunology in China.

Pediatr Allergy Immunol 2018 03 20;29(2):127-132. Epub 2017 Nov 20.

Children's Hospital of Capital Institute of Pediatrics, Beijing, China.

Over the past 30 years, China has enjoyed rapid economic development along with urbanization at a massive scale that the world has not experienced before. Such development has also been associated with a rapid rise in the prevalence of allergic disorders. Because of the large childhood population in the country, the burden of childhood allergic disorders has become one of the major challenges in the healthcare system. Among the Chinese centers participating in the International Study of Asthma and Allergies in Childhood, the data clearly showed a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic eczema. However, the discipline of pediatric allergy in mainland China is still in its infancy due to the lack of formal training program and subspecialty certification. Clinicians and researchers are increasingly interested in providing better care for patients with allergies by establishing pediatric allergy centers in different regions of the country. Many of them have also participated in national or international collaborative projects hoping to answer the various research questions related to the discipline of pediatric allergy and immunology. It is our hope that the research findings from China will not only improve the quality of care of affected children within this country but also the millions of patients with allergies worldwide.
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http://dx.doi.org/10.1111/pai.12819DOI Listing
March 2018

Changing trends and challenges in the management of asthma in Asia.

J Allergy Clin Immunol 2017 11 28;140(5):1272-1274. Epub 2017 Sep 28.

Department of Paediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.09.008DOI Listing
November 2017

Drug Treatment for Early-Stage COPD.

N Engl J Med 2017 09;377(10):988-989

From the Departments of Medicine and Therapeutics (F.W.S.K.) and Pediatrics (G.W.K.W.), Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, China.

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http://dx.doi.org/10.1056/NEJMe1707929DOI Listing
September 2017

Allergen sensitization affected the change trend of prevalence of symptoms of rhinitis coexisting with wheeze among adolescents in Guangzhou City from 1994 to 2009.

Pediatr Allergy Immunol 2017 06;28(4):340-347

Department of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Few studies have assessed the time trends of prevalence of symptoms of rhinitis (SR) with wheezing and their associations in Chinese adolescents.

Objective: To explore the trend of prevalence of SR with wheezing and allergen sensitization in adolescents during the past 15 years.

Methods: A total of 6928 adolescents aged 13-14 years in 2009 were recruited for the study using the Phase III Protocol of the International Study of Asthma and Allergic disease in Childhood (ISAAC) and allergic sensitization to seven inhalant allergens in 2531 was assessed by skin prick test in 2010. The results were compared to those obtained in the Phase I (1994/95) and III (2001/02) ISAAC studies.

Results: The prevalence of 'SR ever' and 'current symptoms of rhino-conjunctivitis' increased from 46.3% and 8.7% in 1994 to 53.2% and 11.1% in 2001 (p < 0.001), respectively, and remained stable at 52.6% and 10.4% in 2009 (p > 0.05). The prevalence of 'SR ever and wheeze ever' and 'SR ever and current wheeze' increased from 6.2% and 3.4% in 1994 to 8.6% and 4.8% in 2001 (p < 0.001) to 10.9% and 5.9% in 2009 (p < 0.05). The sensitization rate to common inhaled allergens was higher in 2010 than in 2002 (p < 0.001). Sensitization to house dust mites (HDMs) was associated with increases in the prevalence of SR (OR, 2.06-2.86), especially with coexistence of wheeze (OR, 6.07-7.43).

Conclusion: The prevalence of symptoms of rhinitis and coexistence with wheezing has increased significantly since 1994. Sensitization to HDMs is the main risk factor associated with this increase.
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http://dx.doi.org/10.1111/pai.12709DOI Listing
June 2017

Making An Impact on Clinical Practice and Research in China.

N Engl J Med 2016 12 21;375(24):2391-2392. Epub 2016 Nov 21.

From NEJM Group (R.-P.X., G.W.K.W., J.M.P., M.G., G.Z., J.M.D.) and NEJM (R.-P.X., J.Z., J.W., G.Z.).

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http://dx.doi.org/10.1056/NEJMe1614121DOI Listing
December 2016

Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial.

Lancet 2017 01 9;389(10066):276-286. Epub 2016 Dec 9.

Division of Allergy, Department of Medical Subspecialties, National Center for Child Health and Development; Okura, Setagaya-Ku, Tokyo, Japan. Electronic address:

Background: Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age.

Methods: In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673.

Findings: Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder.

Interpretation: Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy.

Funding: Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan.
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http://dx.doi.org/10.1016/S0140-6736(16)31418-0DOI Listing
January 2017

Aberrant Expression of Novel Cytokine IL-38 and Regulatory T Lymphocytes in Childhood Asthma.

Molecules 2016 Jul 18;21(7). Epub 2016 Jul 18.

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.

We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4⁺CD25⁺CD134⁺ T lymphocytes as well as CD4⁺CD25(high)FoxP3⁺ and CD4⁺CD25(high)CD127(-) Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. Serum and supernatant cytokines/chemokines were determined by multiplex assay. Serum IL-38, IL-5, IL-17, IL-6, interferon-γ, periostin, IL-1β and IL-13 concentrations were significantly higher in asthmatic patients with or without steroid treatment than those in controls (all p < 0.05). The percentages of both CD4⁺CD25(high)FoxP3⁺ and CD4⁺CD25(high)CD127(-) Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p < 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients with high level (>40 ng/mL) of periostin (p < 0.05). Although the comparable mRNA levels of IL-38 and its receptor IL-36R were found between patients and controls, the mRNA level of IL-38 positively correlated with IL-36R and negatively correlated with IL-10 in all asthmatic patients (both p < 0.05). The percentage of CD4⁺CD25⁺CD134⁺ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in controls (p < 0.05). This cross-sectional study demonstrated that the overexpression of circulating IL-38 may play a role in the immunopathogenesis in asthma.
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http://dx.doi.org/10.3390/molecules21070933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274345PMC
July 2016

Prevalence of food sensitization and probable food allergy among adults in India: the EuroPrevall INCO study.

Allergy 2016 07 6;71(7):1010-9. Epub 2016 Apr 6.

Department of Respiratory Epidemiology and Public Health, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Data are lacking regarding the prevalence of food sensitization and probable food allergy among general population in India. We report the prevalence of sensitization and probable food allergy to 24 common foods among adults from general population in Karnataka, South India.

Methodology: The study was conducted in two stages: a screening study and a case-control study. A total of 11 791 adults in age group 20-54 were randomly sampled from general population in South India and answered a screening questionnaire. A total of 588 subjects (236 cases and 352 controls) participated in the case-control study involving a detailed questionnaire and specific IgE estimation for 24 common foods.

Results: A high level of sensitization (26.5%) was observed for most of the foods in the general population, higher than that observed among adults in Europe, except for those foods that cross-react with birch pollen. Most of the sensitization was observed in subjects who had total IgE above the median IgE level. A high level of cross-reactivity was observed among different pollens and foods and among foods. The prevalence of probable food allergy (self-reports of adverse symptoms after the consumption of food and specific IgE to the same food) was 1.2%, which was mainly accounted for cow's milk (0.5%) and apple (0.5%).

Conclusion: Very high levels of sensitization were observed for most foods, including those not commonly consumed in the general population. For the levels of sensitization, the prevalence of probable food allergy was low. This disassociation needs to be further explored in future studies.
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http://dx.doi.org/10.1111/all.12868DOI Listing
July 2016

Preventing Food Allergy in Infancy--Early Consumption or Avoidance?

Authors:
Gary W K Wong

N Engl J Med 2016 May 4;374(18):1783-4. Epub 2016 Mar 4.

From the Department of Pediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Sha Tin, Hong Kong, China.

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http://dx.doi.org/10.1056/NEJMe1601412DOI Listing
May 2016