Evelyn Xiu Ling Loo

Airway Inflammation and IgE Production Induced by Dust Mite Allergen-Specific Memory/Effector Th2 Cell Line Can Be Effectively Attenuated by IL-35

CD4+ memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44highCD62L− and CD127+ (IL-7Rα+) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX–IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX–IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4+ memory/effector Th2 cell-mediated airway inflammation.

Supplementation with probiotics in the first 6 months of life did not protect against eczema and allergy in at-risk Asian infants: a 5-year follow-up.

Background: Healthy gut microflora is essential for oral tolerance and immunity. A promising approach to preventing allergic diseases in genetically at-risk infants is to introduce administration of probiotics early in life when their immune system is still relatively immature. Objective: In this follow-up study, we aim to determine if early-life supplementation with strains of probiotics has any long-term effect on allergic outcomes. Methods: We analyzed the charts and electronic databases of the PROMPT (Probiotics in Milk for the Prevention of Atopy Trial) study cohort. This cohort consisted of 253 infants at risk for allergy who were administered cows milk supplemented with or without probiotics from the first day of life to the age of 6 months. The cohort was then followed up until the children were 5 years old and clinical outcomes were assessed. Results: Of the 253 children recruited into the study, 220 (87%) completed the follow-up. At the age of 5 years, there were no significant differences between the groups in the proportion of children who had developed any asthma, allergic rhinitis, eczema, food allergy and sensitization to inhalant allergens. Similar growth rates were observed in both groups. Conclusions: The supplementation of probiotics in early childhood did not play a role in the prevention of allergic diseases. Clinical/Key Message: Early-life supplementation with probiotics did not change allergic outcomes at 5 years of age.

Etoricoxib: a safe alternative for NSAID intolerance in Asian patients.

BACKGROUND NSAID intolerance is not uncommon. Etoricoxib, a cox-2 inhibitor NSAID, has been shown to be a safe alternative in these patients. This study aims to determine the rate of NSAID intolerant patients who are able to tolerate etoricoxib without adverse reactions. METHODS This study analyzed charts and electronic databases of all patients referred to the allergy clinics of the National University Hospital and Gleneagles Hospital in Singapore from 2006-2011 for oral provocation tests to etoricoxib (cumulative dose of 120 mg), on the background of NSAID intolerance. Demographics, atopic comorbidities, history of chronic urticaria, inciting NSAID, onset and type of reaction, and provocation test outcomes were obtained. RESULTS A total of 74 patients (mean age 37; range: 16-72 years) underwent provocation tests to etoricoxib. Of these, 59% were female. Majority were Chinese (69%), followed by Malay (12%), Caucasian (8%), Indian (5%) and various other races (6%). Forty-six percent of the study population had atopic comorbidities, and 4% had concomitant chronic urticaria. Eighty percent of patients had a history of intolerance to 1 NSAID, while the rest (20%) had intolerance to multiple NSAIDS. Forty-one percent of patients had concomitant acetaminophen intolerance. Some of the patients had multiple symptoms on presentation, the most common of which were periorbital and facial edema (90%), breathing difficulties (26%) and urticaria (25%), with the onset of reaction occurring mostly within 30 minutes to 1 hour. Etoricoxib was tolerated in 95% of the patients. Subjects who reacted to the challenge all had mild reactions which resolved with antihistamines. CONCLUSIONS Etoricoxib is a safe alternative in NSAID intolerant patients. Nevertheless, it is advised that patients should undergo provocation tests to confirm tolerance.

Low Food Allergy Prevalence Despite Delayed Introduction of Allergenic Foods—Data from the GUSTO Cohort

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 introduction of allergenic foods and food allergy outcomes in infants in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. METHODS The GUSTO cohort recruited 1152 mothers of Chinese, Malay, and Indian ethnicity who had singleton, naturally conceived pregnancies and followed their offspring prospectively. Information on demographic characteristics, child health, infant feeding practices, and a convincing history of IgE-mediated food allergy was obtained from interviewer-administered questionnaires at multiple time points. Corroborative skin prick tests to food allergens were performed at 18 and 36 months. RESULTS Most of the infants were introduced to egg (49.6%), peanut (88.7%), and shellfish (90.2%) after age 10 months. Food allergy prevalence was, however, very low between age 12 and 48 months: egg, 0.35% to 1.8%; peanut allergy, 0.1% to 0.3%; and shellfish, 0.2% to 0.9%. There were no significant associations between the timing of introduction of allergenic foods and the development of food allergy, adjusted for confounders including breast-feeding and eczema. CONCLUSIONS Food allergy rates in Singapore are low despite delayed introduction of allergenic foods. Early introduction of allergenic foods may thus not be necessary in populations in which overall food allergy prevalence is low, and thus infant feeding recommendations should be carefully tailored to individual populations.

Effect of maternal dietary patterns during pregnancy on self-reported allergic diseases in the first 3 years of life: Results from the GUSTO study

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 subsequent development of allergic outcomes in the offspring in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort. Exploratory factor analysis was used to characterize maternal dietary patterns during pregnancy. During repeated visits in the first 36 months of life, questionnaires were administered to ascertain allergic symptoms, namely, eczema, rhinitis, and wheeze. At ages 18 and 36 months, we administered skin-prick testing to inhalant and food allergens. Results: Of the 3 maternal dietary patterns that emerged, the seafood and noodles pattern was associated with a reduced risk of developing allergen sensitization at both 18 months (odds ratio [95% confidence interval]: 0.7 [0.5-0.9]) and 36 months (0.7 [0.6-0.9]) after adjustment for a family history of allergy, and ethnicity, sex, and maternal education levels. No associations between the patterns vegetables, fruit, and white rice or pasta, cheese, and processed meat were observed with any of the allergic outcomes in the first 18 and 36 months of life. Conclusion: Maternal diet during pregnancy can influence the subsequent development of allergic outcomes in offspring.

Sublingual immunotherapy in patients with house dust mite allergic rhinitis: prospective study of clinical outcomes over a two-year period.

BACKGROUND Sublingual immunotherapy in patients with allergic rhinitis sensitised to house dust mites is safe, but its efficacy is controversial and sublingual immunotherapy with Blomia tropicalis has not yet been studied. This study sought to evaluate the efficacy of sublingual immunotherapy with house dust mite extract in children and adults with house dust mite allergic rhinitis over a period of two years. METHODS A prospective observational study was conducted of children and adults diagnosed with house dust mite allergic rhinitis who were treated with sublingual immunotherapy from 2008 to 2012. Total Nasal Symptom Scores, Mini Rhinoconjunctivitis Quality of Life scores and medication usage scores were assessed prospectively. RESULTS Thirty-nine patients, comprising 24 children and 15 adults, were studied. Total Nasal Symptom Scores and Mini Rhinoconjunctivitis Quality of Life scores dropped significantly at three months into therapy, and continued to improve. Medication usage scores improved at one year into immunotherapy. CONCLUSION Sublingual immunotherapy with house dust mite extracts, including B tropicalis, is efficacious as a treatment for patients with house dust mite allergic rhinitis.

Clinical phenotype and allergen sensitization in the first 2 years as predictors of atopic disorders at age 5 years

IntroductionFrom a birth cohort of at-risk Asian infants, we prospectively investigated the role of early onset allergen sensitization and clinical phenotypes as risk factors for atopic disorders at the age of 5 years.Methods and materialsThe study recruited 253 families with a history of allergic disease in a first degree relative from an antenatal clinic in Singapore. The children were followed prospectively to assess clinical outcomes and skin prick test was performed at 2 and 5 years of age.ResultsAllergen sensitization (food and/or house dust mites) alone at 2 years of age was not associated with increased risk of wheeze and eczema at 5 years. However, the clinical phenotype (eczema and wheeze) with or without the presence of concomitant allergen sensitization at 2 years increased this risk. For eczema, eczema alone at year 2 increased the risk of eczema at year 5 (adjOR = 7.1; 95 % CI: 1.8–27.8) and this was further increased by the presence of allergen sensitization (adjOR = 25.4; 95 % CI: 4.7–138.5) and the concomitant presence of both wheeze and allergen sensitization (adjOR = 64.9; 95 % CI: 4.7–900.0). For wheeze, wheeze alone at 2 years (adjOR = 4.5; 95 % CI: 1.4 -14.8), and wheeze with concomitant allergen sensitization and eczema (adjOR = 13.9; 95 % CI: 1.2–168.5) increased the risk of wheeze at 5 years. The exception was rhinitis, where allergen sensitization alone at 2 years (adjOR = 5.6; 95 % CI: 1.1–29.2) increased the risk of rhinitis at 5 years. Early onset of eczema at 2 years also increased the risk of rhinitis (adjOR = 6.8; 95 % CI: 2.0–23.1).ConclusionIn this Asian birth cohort, the clinical phenotype (eczema and wheeze) with or without concomitant allergen sensitization in the first 2 years of life were strong predictors of atopic disorders at 5 years.

A review of oral food challenges in children presenting to a single tertiary centre with perceived or true food allergies.

INTRODUCTION The prevalence of perceived food allergies exceeds that of true food allergies. Unnecessary food avoidance may increase parental and patient anxiety, reduce quality of life and increase the risk of nutritional deficiency. An oral food challenge (OFC) can provide an objective measure regarding the presence or absence of food allergies in a child. This study reviews the indications for and outcomes of OFCs performed on children. METHODS A retrospective review was performed on all children who underwent OFCs at the Allergy Unit of the National University Hospital, Singapore, over a three-year period. RESULTS A total of 197 OFCs were performed among 58 patients (34 male, 24 female). Most of the tests were for allergies to tree nuts (n = 107). Among the OFCs, 43.1% were for foods that were avoided and never eaten due to perceived food allergies, 25.9% were for foods that had previously resulted in positive skin prick tests (SPTs) and/or immunoassay results, 16.2% were for foods thought to worsen eczema and 14.7% were for foods thought to have caused a previous reaction. Of all the OFCs, 5% were positive, although adverse reactions were mostly cutaneous. Challenge-positive patients had either positive SPTs (wheal > 3 mm) or raised serum immunoglobulin E levels to specific foods that they reacted to during the challenges. No episodes of anaphylaxis were reported after the challenge. Most of the patients were able to safely introduce the avoided foods into their diets. CONCLUSION OFCs provide an objective assessment for suspected food allergies.

Relation of infant dietary patterns to allergic outcomes in early childhood

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 development. Infant nutrition is a major environmental influence in early life as the immature gut is exposed to a variety of food proteins. However, results from studies examining the early introduction of allergenic food and allergic outcomes have been conflicting. This article is protected by copyright. All rights reserved.

Associations between maternal vitamin D levels during pregnancy and allergic outcomes in the offspring in the first 5 years of life

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 pregnancy, in particular 25(OH)D insufficiency (25(OH)D concentration of 50-75nmol/l) and/or 25(OH)D deficiency (25(OH)D concentration <50nmol/l) has been associated with allergic outcomes such as eczema, asthma and rhinitis in their offspring. This article is protected by copyright. All rights reserved.