Bee wah Lee

• National University of Singapore

The Asia Allergy Birth Cohort (A2BC) network consolidates data from multiple independently established birth cohorts across Asia to enhance research on host–environment interactions in allergic diseases. These cohorts, established at different times with various methodologies, are reliable data sources. Our aim is to introduce the content, variable...

Background There has been limited data regarding the incidence of anaphylaxis in Asia. We aim to describe patterns in patient characteristics, triggers and clinical presentation of childhood anaphylaxis in Singapore. Methods This was a retrospective review of emergency electronic medical records of children with anaphylaxis. Patients with the alle...

Background The epidemiology and management of anaphylaxis are not well‐reported in Asia. Methods A regional pediatric anaphylaxis registry was established by the Asia‐Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia‐Paci...

Background: Childhood wheezing is a highly heterogeneous condition with incomplete understanding of the characteristics of wheeze trajectories, particularly for persistent wheeze. Objective: To characterise predictors and allergic comorbidities of distinct wheeze trajectories in a multi-ethnic Asian cohort. Methods: A total of 974 mother-child...

The allergy epidemic has been attributed to environmental influences related to urbanization and the modern lifestyle. In this regard, various theories exploring the role of microbes (hygiene, old friends, microbiota, and biodiversity hypotheses), and the epithelial barrier (epithelial, dual allergen exposure and vitamin D hypotheses) have been pro...

Background and aims: There are significant changes to the maternal inflammatory profile across pregnancy. Recent studies suggest that perturbations in maternal gut microbial and dietary-derived plasma metabolites over the course of pregnancy mediate inflammation through a complex interplay of immunomodulatory effects. Despite this body of evidence...

Background: The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented. Objective: This study aimed to evaluate the prevalence of cow's milk, egg, and pea...

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were...

Background Allergic sensitization is linked to allergy development, with early sensitization often associated with worse outcomes. We aimed to identify if distinct allergic sensitization trajectories existed within a diverse and multi-ethnic Asian cohort. Methods We administered modified ISAAC questionnaires in the first 8 years and conducted skin...

Introduction Short chain fatty acids (SCFAs) are the main intestinal intermediate and end products of metabolism of dietary fibers/polyphenols by the gut microbiota. The aim of this study was to evaluate the biological implication of stool SCFA profiles determined in the first year of life on the clinical presentation of allergic outcomes in childh...

Background Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined. Objective We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pr...

Background: increasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infe...

Introduction: Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents. Methods: Mother-infant dyads in the Singapore PREconception Study of long-T...

The prebiotics, galacto-oligosaccharides (GOS), are small carbohydrate molecules with 1–7 galactose units linked to glucose and have been shown to trigger IgE-mediated anaphylaxis in some cases following ingestion. It is still an unresolved question of how GOS cross-links IgE on basophils. In this study, we examined whether human galectins, a class...

Background Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The...

Eczema or atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with a peak incidence in the first 2 years of life1. Physician diagnosis of AD is still problematic as there is variability in diagnosing AD, especially in young children, and validation studies on diagnostic accuracy and criteria of physician diagnosis of AD are lack...

Exposure to a diverse microbial environment during pregnancy and early postnatal period is important in determining predisposition towards allergy. However, the effect of environmental microbiota exposure on allergy during preconception, pregnancy and postnatal life on development of allergy in the child has not been investigated so far. In the S‐P...

Background: The heterogeneity of childhood atopic dermatitis (AD) underscores the need to understand latent phenotypes that may inform risk stratification and disease prognostication. Objective: To identify AD trajectories across the first 8 years of life, investigate risk factors associated with each trajectory and their relationships with othe...

Background Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. Objective We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated wit...

Background In Western countries, Asian children have higher food allergy risk than Caucasian children. The early‐life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia. Methods We studied children in the Growing Up i...

Shellfish allergy is more prevalent in South‐East Asia (~5%1) than in Western populations (e.g. United States ~2‐3%.2). Typically commencing in late childhood, it is the leading cause of anaphylaxis in adolescents and adults in Asia. Cross‐sectional studies have demonstrated a high correlation between shellfish and house dust mite (HDM) sensitizati...

There is emerging evidence that the respiratory microbiota influences airway health, and there has been intense research interest in its role in respiratory infections and allergic airway disorders. This review aims to summarize current knowledge of nasal microbiome and virome and their associations with childhood rhinitis and wheeze. The healthy i...

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth,...

Background: Infants with atopic dermatitis (AD) are reported to be at higher risk of early childhood caries (ECC) at 3-years, but the clinical validity of the reported link remains unknown. We investigated if clinical severity of AD in young children is associated with increased ECC risk at 3-years. Methods: In Growing Up in Singapore Towards healt...

Background The natural history of childhood rhinitis is not well described. Objective This study aimed to identify different rhinitis trajectories in early childhood and their predictors and allergic associations. Methods Rhinitis symptoms were ascertained prospectively from birth until 6 years using standardized questionnaires in 772 participant...

Although the direct health impact of Coronavirus disease (COVID-19) pandemic on child health is low, there are indirect impacts across many aspects. We compare childhood vaccine uptake in three types of healthcare facilities in Singapore - public primary care clinics, a hospital paediatric unit, and private paediatrician clinics - from January to A...

Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk. We measured the functionality of the gut microbiome and metabolome o...

In the original PDF online version of this article, the references 22–26 were missing.

We report on 2 Asian siblings with X-linked inhibitor of apoptosis deficiency that arose from a novel deletion that presented with Epstein-Barr virus disease and hemophagocytic lymphohistiocytosis. This disease is ascribed to dysfunction in the nucleotide binding and oligomerization domain receptor pathway, tested using a modified muramyl dipeptide...

Measurements of elastic electron scattering data within the past decade have highlighted two-photon exchange contributions as a necessary ingredient in theoretical calculations to precisely evaluate hydrogen elastic scattering cross sections. This correction can modify the cross section at the few percent level. In contrast, dispersive effects can...

Background: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria...

Background While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria i...

Background: The rapid spread of multidrug- resistant pathogenic bacteria is a worldwide public health concern. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)- producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence and dynamics by studying the longitudinal changes in antibiotic resistance gene (ARG)...

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 in...

Food allergy (FA) is currently a significant health care problem in the developing world. Widely varying study populations and methodologies, the use of surrogate markers such as self report or hospitalization rates due to anaphylaxis rather than objective methods, limits robust estimation of FA prevalence in low income settings. Also, allergy is u...

The development of allergic disease starts prenatally, a vital period during which maternal exposure such as nutrient intake may modulate fetal and infant immune programming [1]. However, the role of various nutrients intake during maternal pregnancy, for instance, carotenoids, vitamin A and vitamin E, in the development of allergic diseases in the...

Blomia tropicalis contains glycoallergens and their carbohydrate moieties are responsible for the IgE cross-reactivity to GOS. Blomia tropicalis is a primary sensitizer of GOS allergy.

Galactooligosaccharides (GOS) are widely used in the food industry as prebiotics in the food industry and in very rare cases, can lead to an allergic reaction. Due to the microheterogeneity of GOS it is very difficult to extract pure and well defined oligosaccharides to establish which component is responsible for the observed allergenicity. Herein...

The “hygiene hypothesis” proposes that microbial exposures in early life ‐ such as a farming lifestyle, early childcare attendance, older siblings and pet ownership protect against atopy by maintaining a balanced Th1/Th2 immune cytokine milieu.1‐3 The newly described “biodiversity hypothesis” or “old friends” hypothesis further suggests that co‐evo...

Background The prevalence of allergic diseases, such as asthma, allergic rhinitis, eczema and food allergy, has been increasing worldwide, as shown in a large number of studies, including the International Study of Asthma and Allergies in Childhood (ISAAC). However, there is significant variation in the prevalence of these diseases in different reg...

Background The gut microbiome harbors antibiotic resistance genes (ARGs), known as the resistome, that has the potential to spread and contribute to the global crisis of antibacterial resistance. Little is known about the genomic traits of the infant resistome, especially in areas with high endemic antibacterial resistance. Methods We analyzed ARG...

There is increasing evidence to support the Developmental Origins of Health and Disease (DOHaD) concept that fetal life and early life exposures are important determinants of fetal immune regulation and the development of disorders in later life, including allergies. Among the early life exposures, maternal vitamin D [25(OH)D] status during pregnan...

[Background] Two-photon exchange contributions have become a necessary ingredient in theoretical calculations trying to precisely calculate hydrogen elastic scattering cross sections. This correction typically modifies the cross section at the few percent level. In contrast, dispersive effects can cause significantly larger changes from the Born ap...

Background: The pathogenesis of allergic diseases in childhood may be attributed to influences of early environmental stimuli on fetal and neonatal immune regulation. Neonatal hyperbilirubinemia is common in the Asian population and up to 20% of infants require phototherapy. We examined the hypothesis that phototherapy for neonatal hyperbilirubine...

Background: The dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and the susceptibility to childhood respiratory disorders. Objective: The aim of this case-control study was to monitor, evaluate and compare the development of the nasal microbiota of infants who developed rhinitis and wheeze in...

Background: The study objective was to compare age-related differences in the cause and clinical presentation of anaphylaxis. Methods: We conducted a prospective study of patients visiting the emergency department for anaphylaxis. Data were collected from 3 emergency departments from 1 April 2014 to 31 December 2015. Patient electronic records w...

Introduction: Previous trials have demonstrated reductions in atopic dermatitis (AD) incidence when healthy, high-risk, non-exclusively breastfed infants were fed until four months of age with 100% whey-based partially hydrolysed formula (PHF-W) versus standard cow's milk formula (CMF). We assessed this intervention's cost-effectiveness in Singapo...

[This corrects the article DOI: 10.1186/s40413-016-0122-3.].

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma...

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9–14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at mo...

Gut microbiota play an important role in human immunological processes, potentially affecting allergic diseases such as eczema. The diversity and structure of gut microbiota in infants with eczema have been previously documented. This study aims to evaluate by comparative metagenomics differences in genetic content in gut microbiota of infants with...

Rarefaction curves of metagenomic reads that encode the V9 region of 16S rRNA genes from each community. Curves represent the number (y-axis) of unique OTUs (defined at the 97% nucleotide sequence identity level) obtained per the number (x-axis) of sequences analyzed within each community (figure key). The rarefaction curves were produced using MOT...

Genomic features of Bifidobacterium populations. a Source denotes the sample ID of a metagenomic dataset where the draft genome was recovered. b Only contigs and genes longer than 300 bases were counted. c Genome completeness was estimated using MaxBin3. d The genome sequences were deposited in GenBank under the accession numbers. (DOCX)

Occurrence of five immune-stimulatory DNA motifs (See references 2 and 3 in S1 File) in C and E metagenomic datasets. a The value represent an average occurrence of the DNA motifs per 106 metagenomic sequences. b P values were estimated by Mann-Whitney U test. (DOCX)

Phylogenetic composition of microbial communities. Relative abundance of major phyla (see key) based on best match analysis of V9 regions of 16S rRNA gene sequences (left bar) and all metagenomic reads (right bar). ‘Others’ represents the combined fraction of the remaining minor phyla. (TIF)

Occurrence of the TCAGCTTGA motifs in complete genomes of the eight genera. The occurrence was estimated based on the complete genome sequences available in GenBank database and the number (n) of genomes analyzed is shown in parentheses. The bars represent average occurrence of the TCAGCTTGA motifs per 106 bases. The error bars represent one standa...

Characteristics of metagenomic datasets. All DNA samples were sequenced using both HiSeq 2500 and MiSeq V2 sequencers. Four samples (157, 176, 161, and 221) were further sequenced using a 454 FLX Titanium sequencer. The total size of combined metagenomic datasets from a sample ranged from 14 to 23 Gb. a Only contigs and genes longer than 300 bases...

Phylogenetic tree of the six Bifidobacterium populations based on polA (DNA polymerase I) genes. The phylogenetic tree was built using MEGA 6.0 based on the maximum likelihood method with the Tamura-Nei model. Black circles represent B. sp. whose draft genomes were recovered in this study (S3 Table); the GI numbers of the remaining representative s...

Supporting information reference list. (DOCX)

Correction to the article published in Frontiers In Immunology, vol 8:798. doi: 10.3389/fimmu.2017.00798 - regarding a mistake in the authorship.

Emerging evidence for the early introduction of allergenic foods for the prevention of food allergies, such as peanut allergy in Western populations, has led to the recent publication of guidelines in the US and Europe recommending early peanut introduction for high-risk infants with severe eczema or egg allergy. Peanut allergy is, however, much le...

Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of...

Mutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been ob...

Background Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. Objective The aim of this study was to identify the clinical featu...

Distribution of age at diagnosis and time to diagnosis of patients with genetic diagnosis (n = 83). Distribution of age at diagnosis of patients with chronic diarrhea (A), severe infections (B), and lymphopenia (C) and distribution of time to diagnosis of patients with chronic diarrhea (D) and lymphopenia (E).

Background: There is mounting evidence that early introduction of allergenic food decreases the risk of food allergy development, especially in high-risk infants with eczema. However, there is a lack of data to suggest whether this association holds true in Asian populations. Objective: To investigate the relationship between the timing of intro...

Background The association between early weight gain and later allergic outcomes has not been well studied. We examined the relation between weight gain and the subsequent development of allergic outcomes in the first 36 months of life in a Singapore birth cohort. Methods In repeated visits in the first 15 months, we measured infant weight and adm...

Allergic disorders result from the complex interplay between genetic predisposition and environmental influences. According to the Developmental Origins of Health and Disease hypothesis, environmental pressures at critical or early periods of development can evoke persisting changes in gene regulation and expression (1), affecting disease developme...

Background: Maternal diet during pregnancy has been suggested to be an important early-life exposure that influences immune tolerance and the development of allergic diseases in offspring. Methods: We examined the relationship between maternal dietary patterns assessed using 24-h recalls and food diaries at 26-28 weeks of pregnancy and the subse...

A novel liquid chromatography tandem mass spectrometry (LCMSMS) method for the quantitative measurement of gut microbial-derived short-chain fatty acids (SCFAs) in human infant stool has been developed and validated. Baseline chromatographic resolution was achieved for 12 SCFAs (acetic, butyric, caproic, 2,2-dimethylbutyric, 2-ethylbutyric, isobuty...

Despite the availability of several formulations of inhaled corticosteroids (ICS) and delivery devices for treatment of childhood asthma and despite the development of evidence-based guidelines, childhood asthma control remains suboptimal. Improving uptake of asthma management plans, both by families and practitioners, is needed. Adherence to daily...

One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing), deliberate induction in the office of alle...

Background Immune responses in allergic diseases begin with allergen sensitization, which usually occurs in childhood. Allergen sensitization involves a complex interplay of genetic and environmental factors, and sensitization patterns may change with age. Objective To determine the predictors of allergen sensitization in the first 3 years of life...

Allergic diseases are distributed worldwide and their risk factors and triggers vary according to geographical and socioeconomic conditions. Allergies are frequent in the Tropics but aspects of their prevalence, natural history, risk factors, sensitizers and triggers are not well defined and some are expected to be different from those in temperate...

Background: Studies have reported that early febrile episodes and febrile episodes with infections are associated with a decreased risk of developing atopy. Objective: To examine further the association between presence of and number of febrile episodes are with atopy and atopic diseases and if there was a difference between all fevers and fever...

Introduction: This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. Materials and methods: Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral...