Jian Yi Soh

Carbohydrates as food allergens

The literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions. They bind weakly to IgE antibodies and have been termed as cross reactive carbohydrate determinants. These epitopes cause confusion in in vitro IgE testing through nonspecific cross-reactivity. Coincident with the rising trends in food allergy prevalence, there has recently been reports of anaphylaxis induced by carbohydrate epitopes. There are two distinct groups, each with unique characteristics and geographical distribution. Anaphylaxis and acute allergic reactions related to the carbohydrate galactose-α-1,3-galactose (α-Gal) epitope that are present in the monoclonal antibody, cetuximab and red meat have been described in the United States and Europe populations where tick bites have been found to be the primary sensitizer. Another carbohydrate inducing anaphylaxis is galacto-oligosaccharides in commercial milk formula which has been described in the several Asian populations including Singapore. The latter is unique in that the allergen is a pure carbohydrate. We summarize the current literature on carbohydrate-induced food allergy, and evaluate the two new groups of carbohydrate allergy that have defied previous findings on carbohydrates and their role.

The use of inhaled corticosteroids in pediatric asthma: update

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 ICS therapy is a key determinant of asthma control and this mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices. The potential adverse effects of ICS need to be weighed against the benefit of these drugs to control persistent asthma especially that its safety profile is markedly better than oral glucocorticoids. This article reviews the key mechanisms of inhaled corticosteroid action; recommendations on dosage and therapeutic regimens; potential optimization of effectiveness by addressing inhaler technique and adherence to therapy; and updated knowledge on the real magnitude of adverse events.

Rhinitis in the first 18 months of life: Exploring the role of respiratory viruses

Rhinitis is common in early childhood, but allergic rhinitis is considered a later manifestation of the atopic march. This study aimed to evaluate rhinitis (allergic and non‐allergic) in the first 18 months of life, its link with other atopic manifestations and the role of respiratory viruses.

Wheat-dependent exercise-induced anaphylaxis: a retrospective case review from a tertiary hospital

Background Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia. At present, there are no published reports of WDEIA in Singapore. The objective of this study is to characterise the common local clinical and laboratory manifestations of WDEIA. Methods This was a retrospective descriptive study of all WDEIA who presented to a tertiary Singaporean Hospital over a 5-year-period from 1 January 2009 to 30 June 2013. Results Eight patients aged 9–41 years old were characterised. Six were males and the majority (5) was of Chinese ethnicity. An atopic history was found in four patients. The symptoms of anaphylaxis included cutaneous manifestations such as urticaria (n=7), angioedema (n=6), respiratory symptoms of dyspnoea and wheezing (n=5) and hypotension (n=5). The symptoms occurred 20–75 min after consumption of wheat-based products, often upon cessation of exercise [running (n=3), walking (n=4) and swimming (n=1)]. The WDEIA was recurrent in seven patients. The skin prick tests were positive to wheat in seven patients, and ω-5 gliadin test to wheat was positive in five patients. Conclusions With the emergence of wheat allergy in East Asian countries, WDEIA has become an important condition for physicians and Singapore is no exception. Under-recognition combined with life-threatening symptoms warrants better public awareness measures. In addition, further studies are necessary to identify possible unique genetic and environmental exposures that could explain the inter-regional differences of WDEIA.

Ten-year prescription trends of asthma medications in the management of childhood wheeze.

Asthma is the most common chronic disorder of childhood. The aim of this study was to assess prescription trends of asthma medications to provide a measure to evaluate treatment practices and compliance with established international practice guidelines. A retrospective study of data obtained from outpatient prescription databases (2001-2010) of the University Childrens Medical Institute for children aged 0-18 years was performed. The following drugs were included: short-acting beta-agonists (SABAs), long-acting beta-agonists in combination with inhaled corticosteroids (LABA-ICSs), ICS, and leukotriene receptor antagonists. Statistical analysis of prescription trends was performed with linear regression to determine the trends in prescription of controller medications. From 2001 to 2010, the number of patients who were prescribed SABA increased significantly by 72% (p = 0.016). The increases in ICS patient numbers and ICS/SABA drug unit ratios were significant only in the school-going (>5 years) age group. There was a trend away from the use of nebulized SABA and ICS, although this was statistically insignificant. LABA-ICS patient numbers decreased significantly by 32.4% (p = 0.003), especially in preschoolers (1-5 years). There was a corresponding rise in montelukast patient numbers by 194.6% (p = 0.009) and montelukast/SABA ratio by 345.3% (p = 0.032) in preschoolers (aged 1-5 years). Montelukast patient numbers, but not the montelukast/SABA ratio, increased in school-going children. The move away from LABA-ICS combination especially in younger children and a tendency toward more montelukast usage is a reflection of practice preferences in accordance with current international guidelines in young children.

Establishment of the nasal microbiota in the first 18 months of life: Correlation with early-onset rhinitis and wheezing

Background: Dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and susceptibility to childhood respiratory disorders. Objective: The aim of this case‐control study was to monitor, evaluate, and compare development of the nasal microbiota of infants with rhinitis and wheeze in the first 18 months of life with those of healthy control subjects. Methods: Anterior nasal swabs of 122 subjects belonging to the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were collected longitudinally over 7 time points in the first 18 months of life. Nasal microbiota signatures were analyzed by using 16S rRNA multiplexed pair‐end sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2) patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control subjects (n = 60). Results: Maturation of the nasal microbiome followed distinctive patterns in infants from both rhinitis groups compared with control subjects. Bacterial diversity increased over the period of 18 months of life in control infants, whereas infants with rhinitis showed a decreasing trend (P < .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family (Actinobacteria phylum) and early colonization with the Staphylococcaceae family (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects (adjusted P < .05). The only difference between the rhinitis and control groups was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05). Determinants of nasal microbiota succession included sex, mode of delivery, presence of siblings, and infant care attendance. Conclusion: Our results support the hypothesis that the nasal microbiome is involved in development of early‐onset rhinitis and wheeze in infants.

Novel strategies in immunotherapy for allergic diseases

Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended.

An unusual cause of food-induced anaphylaxis in mothers

BackgroundGalacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region.Case presentationsWe describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions.ConclusionsThe supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.

Cause and Clinical Presentation of Anaphylaxis in Singapore: From Infancy to Old Age

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 with the diagnoses of allergy, angioedema, urticaria, and anaphylaxis (ICD-9 codes 9953, 9951, 7080, 9950, 7089) were screened and cases fulfilling World Allergy Organisation criteria for anaphylaxis were included. Results: A total of 426 cases of anaphylaxis were identified with a median age of 23 years (range 3 months to 88 years and 9 months). The causes of anaphylaxis were food (n = 236, 55%), drugs (n = 85, 20%), idiopathic (n = 64, 15%), and insect bites or stings (n = 28, 7%). The most common food was shellfish (n = 58, 14%) and the most common drugs were non-steroidal anti-inflammatory drugs (n = 26, 6%). There were more cases of food anaphylaxis in children than in adults (72 vs. 42%, p < 0.001) and more cases of drug anaphylaxis in adults than in children (28 vs. 10%, p < 0.001). Compared to patients of other ages, infants and young children had more gastrointestinal symptoms (adjusted odds ratio [aOR] 2.1, 95% CI 1.1-3.9), while schoolchildren and adolescents had more respiratory symptoms (aOR 2.7, 95% CI 1.4-5.2). Adults had more cardiovascular symptoms (aOR 2.9, 95% CI 1.8-4.6) and hypotension (aOR 3.7, 95% CI 2.1-6.8) compared to children. However, 42% of the infants lacked blood pressure measurements. Conclusions: Knowledge of age-related variation in the cause and clinical presentation of anaphylaxis aids in diagnosis and acute management.