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Background\ud Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing.\ud Methods\ud This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993–95), ISAAC Phase III (2001–03), or both. We included individuals from two age groups (children aged 6–7 years and adolescents aged 13–14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders.\ud Findings\ud Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993–2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (–0·37, 95% CI –0·69 to –0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (–1·37, –2·47 to –0·27], in children and –1·67, –2·70 to –0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries.\ud Interpretation\ud Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma.\ud Funding\ud International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

BACKGROUND The number of children presenting with IgE-mediated wheat reactions to academic medical centers in Thailand continues to increase. OBJECTIVE Improved knowledge about the clinical characteristic of wheat allergy is urgently needed to better understand the risk factors and to improve proper treatment in this patient population. METHODS A cross-sectional study using questionnaire review of children who presented with IgE-mediated wheat allergy during 2001 to 2015 was performed. Patients were divided into the wheat anaphylaxis (WA) or the only skin symptoms (SO) group. RESULTS One hundred children were enrolled. Fifty-one and 49 patients were allocated to the WA and SO group, respectively. The median age was 40.5 months (range: 6-200), and the median age of onset was 7 months (range: 3-96). The vast majrity (90%) developed their first reaction after their first ingestion of wheat. Atopic dermatitis (AD) was found to be the only significant difference between groups and found more commonly in SO than in WA (59.2% vs. 35.3%, p = 0.02). Median mean wheal diameter (MWD) of skin prick test (SPT) and median sIgE level to wheat were higher in WA than in SO (8 vs. 3 mm, p < 0.001; and, 33.3 vs. 3.6 kUA/l, p < 0.001). CONCLUSIONS Children with wheat allergy presented very early in life. AD was found in approximately half of the patients, and more commonly in SO. Median MWD of SPT and sIgE level to wheat were significantly higher in WA. These data will aid in further planning for a larger survey and intervention study in wheat allergy.

Background Allergic conjunctivitis (AC) is the most common ocular condition in allergic children. In tropical countries, the study about the clinical features and outcome of treatment is very limited. Objective To review clinical characteristics and outcomes of treatment in children with ocular allergy. Methods Children with history of AC were classified to seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The clinical history and outcome of treatment were recorded. Results One hundred and sixty-four children were recruited. PAC was the most common type (61.6%), followed by SAC (21.3%), VKC (12.2%), and AKC (4.9%). Male preponderance was found in all groups. Mean age of onset was 6.8 ? 2.8 years. Allergic rhinitis was the most common co-morbidity (97.6%). The common sensitized allergen is house-dust mites (86.1%). Standard treatments in all groups were natural tear and topical olopatadine. Add-on medications were usually needed in severe types of AC (VKC, AKC). History of topical corticosteroid use was 68.8% and 12.5% in VKC and AKC, respectively. All of them can discontinue topical corticosteroid when topical tacrolimus was applied. The overall remission was found 35% in VKC group and 63% in AKC group. The median duration of treatment was 20.5 months in VKC group and 11 months in AKC group. Conclusion most Thai children with AC sensitized to house-dust mites. In severe forms of AC, most patients needed addon medication. The use of topical calcineurin inhibitor as an add-on therapy can decrease the use of topical corticosteroid.

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 USA and Europe recommending early peanut introduction for high-risk infants with severe eczema or egg allergy. Peanut allergy is, however, much less prevalent in Asia compared to the West. Varying patterns of food allergy are seen even within Asian countries-such as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in Singapore and the Philippines. Customs and traditions, such as diet and infant feeding practices, also differ between Asian populations. Hence, there are unique challenges in adapting guidelines on early allergenic food introduction to the Asian setting. In this paper, we review the evidence and discuss the possible approaches to guide the timely introduction of allergenic food in high-risk infants in Asia.

Among various routes of immunotherapy for food allergy, oral immunotherapy (OIT) appears to have a promising result due to its ability to modify abnormal immunologic mechanism of IgE-mediated food allergy. Other methods for immunomodulation such as sublingual (SLIT) or epicutaneous (EPIT) immunotherapy which carry lower rates of systemic reactions, may have less efficacy. Wheat has recently been recognized as a more common cause of food-induced anaphylaxis than previously recognized, especially among young children, around the world. In wheat allergic patients, avoidance recommended as standard recommendation is not easy to follow, because wheat has been used as a common constituents in various kinds of consumed foods in every day's life. Therefore, wheat OIT may be considered as an alternative treatments of those in which wheat avoidance is not sufficient to avert frequent events of anaphylaxis resulting from inadvertent exposure to small amount of wheat among this population. Currently, only few clinical trials about wheat OIT are available. In this review, we discuss available protocols of wheat OIT, initial starting dose, maintenance dose, and the strategies to minimize the side effects during the treatment.

BACKGROUND Allergic rhinitis (AR) is a disease with a high global disease burden and significant morbidity and expense. Risk factors are not well understood. OBJECTIVE The objective of our project is to study the prevalence and risk factors of AR in children living in the Bangkok area. METHODS A cross-sectional, multi-center survey using new GAN core questionnaires on current AR and risk factors was completed by 3,074 parents of children aged 6-7 years and by 3,217 children aged 13-14 years, directly. RESULTS The prevalence of current AR in children aged 6-7 years and 13-14 years was 15.0% (95% confidence interval [CI]:13.8-16.3%) and 17.5% (95% CI: 16.2-18.8%), respectively. The prevalence of severe AR in children aged 6-7 years and 13-14 years was 1.0% (95% CI: 0.6-1.3%) and 1.9% (95% CI: 1.4-2.4%), respectively. Co-morbidity with asthma and eczema was 27.1% and 24.6%, respectively. Significant factors associated with AR include parental history of asthma (p = 0.025), parental history of AR (p < 0.001), parental history of eczema (p < 0.001), lower respiratory tract infection in the first year of life (p < 0.001), breastfeeding (p = 0.019), current use of paracetamol (p < 0.001), exercise (p < 0.001), current cat exposure (p = 0.008), and truck traffic on the street of residence (< 0.001). CONCLUSION AR is a common disease among children residing in Bangkok. This study confirms that a family history of atopy (asthma, AR, and eczema), antibiotics given in the first year of life, current paracetamol use, exercise, current cat exposure, and truck traffic on the street of residence are important and significant risk factors for AR symptoms.

Atopic dermatitis (AD), the most common skin disease in children, is the earliestpresentation of allergic diseases among childhood. Although AD is commonly seenwithin the infantile age group, it can manifest its initial presentation in late childhoodand in adulthood. The classic sites of the rash, the chronic relapsing nature of the diseasealong with itching establishes the diagnosis of AD. Despite the fact that ‘atopic’denotes the relationship with IgE-mediated mechanism, atopy could be demonstrated inapproximately 50% of AD cases. Common allergens found in association with infantileAD are food allergens (commonly cow’s milk and eggs) whereas inhalant allergens arefound among AD cases of older ages. Recently, defects of skin barrier proteins whichprotect the transepidermal loss of water were found among skin of AD patients. Theclassic molecule that has been extensively studied was filaggrin. With the combinationof defective skin barrier protein and altered immune mechanism, AD skin became dry,itchy and inflamed. Treatment of AD requires several modalities of approach includinghydration of skin, use of moisturizers, use of anti-inflammatory agents, treatment ofskin infections, and avoidance of allergens. This multilevel approach, although difficultto accomplish, can be adequately arranged even in busy clinics and thus leading to ahigher level of success in the treatment of severe AD cases. Hydration of dry skin is animportant step in the treatment of AD and in severe cases, a more complex hydrationapproach is needed. This can be achieved by comprehensive hydration therapy withprolonged wrapping with saline or water (wet wrap therapy–WWT). This articlereviews important salient points for the pathogenesis of AD and also in-depth discussionon techniques of WWT. Effective therapy of AD can be achieved in a short period oftime using WWT and can help sustain an optimal use of moisturizers and intermittentinflammatory agents.

Background Local allergic rhinitis (LAR) is diagnosed by the positive response to nasal allergen provocation test (NAPT) to aeroallergen and/or local synthesis of specific IgE (sIgE). This entity is found in half of the adults with non-allergic rhinitis (NAR). In children, very few data of the prevalence and characteristics of LAR were reported. Methods Children 8-18 years with NAR were recruited. A NAPT with Dermatophagoides pteronyssinus extract (NAPT-Dp) at 200, 600, and 2000 AU/ml, respectively, at 15-min interval was performed. The immediate response was assessed using the clinical symptom score, peak nasal inspiratory flow (PNIF), and acoustic rhinometry (ARM). The nasal tryptase and sIgE-Dp were measured at baseline and 15 min and 1 h after a positive NAPT-Dp. Two allergic rhinitis (AR) patients were used as positive controls. Results Fifty-four NAR children (61.1% boys) with the mean ± SD age of 11.1 ± 2.1 years were enrolled. The median duration of disease was 6.3 years. The most frequent comorbidity was asthma (38.9%). Eighty-seven percent of patients had mild persistent severity. NAPT-Dp was positive in 2/54 (3.7%) of NAR children who had increased symptom score and decreased minimal cross-sectional area (MCA) on ARM as well as PNIF. However, there was no change in the nasal tryptase and sIgE-Dp. The control AR patients had positive NAPT-Dp and increased nasal tryptase at 15 min without the change of sIgE-Dp. Conclusion LAR is an uncommon condition in children. Further investigation in a large population of children with NAR is needed.

Background Wheat allergy is not an uncommon event among Thai children. Despite strict avoidance, some patients developed reactions after accidental exposure to minute amount of wheat and thus disturbed their quality of life. Wheat oral immunotherapy (OIT) has been reported to be an alternative treatment for such patients. Objective We designed a new 3-step wheat OIT protocol for treatment of severe wheat allergy in Thai patients. The feasibility of the protocol is evaluated and is reported here in this paper. Methods We retrospectively reviewed medical records of 26 patients who had undergone wheat OIT during a 30-month period. The 3-step protocol consisted of an initial phase of double-blind, placebo-controlled food challenge (DBPCFC) and initiation of OIT, a build-up phase, and a maintenance phase. Patient retention in the protocol was the main outcome for this feasibility study. Adverse effects during OIT were recorded. Correlation between serum specific IgE (SpIgE) to wheat and eliciting dose in phase I was determined. Results Fourteen females and 12 males with a median age of 6 years were studied. Their median age when wheat allergy began was 8 months. Median SpIgE to wheat was high (198 kUA/L). All patients developed reactions during DBPCFC with 17 of 26 patients had moderate to severe reactions required adrenaline injections. Median of eliciting dose of wheat was exceedingly low, i.e., 20 mg of wheat protein. At the end of the study, 23 of 26 patients (88%) were still in the study. Adverse reactions during the build-up phase was frequent (13 patients, 50%), with adrenaline required in 6 occasions. Six patients reached maintenance phase. Conclusion The new 3-step wheat OIT protocol was feasible in these highly wheat-sensitized patients. Despite a high retention rate, a high rate of adverse effects was observed both during DBPCFC and build-up phases.

The standard method for diagnosing immediate wheat allergy is oral food challenge test (OFC). However, OFC can provoke anaphylaxis during the challenge process. Skin prick test (SPT) using commercial wheat extract yielded unsatisfactory result for diagnosis of wheat allergy. As a result, an in-house, alcohol-dissolved (Coca-10% EtOH) wheat extract was developed to improve accuracy of the SPT.To determine the accuracy of in-house, alcohol-dissolved wheat extract in children with immediate wheat allergy.This prospective cross-sectional study included children with history of immediate reaction after wheat ingestion. SPTs with commercial and in-house Coca-10% EtOH wheat extract were performed and wheat and omega-5 (ω-5) gliadin specific IgE (sIgE) were measured. Patients with no history of recent anaphylaxis after wheat ingestion underwent OFC with 31 grams of wheat flour.Thirty children were recruited. Thirteen of those had history of anaphylaxis after wheat ingestion. Eleven of the remaining 17 children (64.7%) had a positive result for wheat challenge test. Wheal size of 3 mm for both in-house and commercial wheat extract yielded the best accuracy for the test. Using these cutoff parameters, in-house Coca-10% EtOH wheat extract yielded 91.7% sensitivity, 66.7% specificity, and 86.7% accuracy. Comparatively, the commercial extract yielded 70.8% sensitivity, 100% specificity, and 76.6% accuracy.SPT using in-house Coca-10% EtOH wheat extract yielded better accuracy than commercial extract for diagnosing immediate type wheat allergy in children.

Background As noted in the reports of ISAAC phase I and III, allergic diseases are very common in Thailand, especially among younger children. Objective The objectives of this project are to study the prevalence and severity of the most common allergic diseases. i.e. asthma, rhinoconjunctivitis and eczema among children living in Bangkok. Methods A cross-sectional multi-centers survey using GAN Core questionnaires on asthma, rhinoconjunctivitis and eczema symptoms were completed by parents of children aged 6-7 years and children aged 13-14 years. Results The total of 6,291 questionnaires were eligible for the analysis. The cumulative vs. 12-month period prevalence of the three conditions for all children were: 24.4% vs. 13.5% for wheezing, 51.1% vs. 43.6% for rhinitis and 15.8% vs. 14.2% for eczema, respectively. The period prevalence of wheezing for younger children (14.6%) was higher than for older children (12.5%). Prevalences of severe wheeze and exercise wheeze were more common among older children (2.9% and 14.8%). The 12-month prevalences of rhinitis (43.6%) and rhinoconjunctivitis (16.3%) were higher in both age groups. Eczema, as the same to the other conditions, occurred more frequently in both groups (period prevalence of 14.3% and 14.0%) comparing to ISAAC phase III. Conclusion Allergic conditions are very common diseases among children residing in Bangkok. There is an urgent need for an in-depth study to define epidemiological factors responsible for this increase.

Background Prevalence of food allergy is increasing all over the world including in Asia. Diagnosis of food allergy in Asia is usually made after family complaints or by elimination and/or reintroduction foods. This could lead to an inaccurate diagnosis and to incorrect information on epidemiology of food allergy. We, herein, reported results of a 16-year experience (1996-2012) of oral food challenge (OFC) performed in pediatric patients at a major teaching hospital in Thailand. Objective The major objectives of this report are to review types of foods selected for oral challenges, frequency of positive/negative challenges to these foods and the clinical reactions during challenges among these children. Methods Medical records of 206 children underwent OFC between 1996 and 2012 for various indications at the Allergy clinic of Pediatric Department, Siriraj Hospital, Mahidol University (age range, 4 months to 17 years) were retrospectively reviewed. Data including clinical data, skin prick test results and specific IgE levels were analyzed with respect to challenge results (positive/negative). During the period of the study, 2 separate investigations on shrimp allergy and wheat allergy were conducted. Results Sixty of 206 children (29%) had positive OFC, whereas 84 out of 306 OFC (27.5%) were positive. The most common food giving positive challenges in this study was shrimp (40%). Among children less than 3 years of age, the most common food with positive challenge was wheat (70%) whereas among children 3 years of age or older, shellfish was the most common food (42%). Cutaneous reactions were the most common reactions observed. Conclusion Only 1 out of 3 children underwent OFC in this study had positive challenges. Shrimp was the most common food causing challenge in this study especially among children older than 3 years of age. Wheat has become another leading food besides cow's milk and egg in causing positive OFC in younger children in Thailand.

Background There are few prospective studies on the natural course of chronic urticaria (CU) in children. Objective We sought to examine the natural history of CU in children and to identify predictors for remission. Methods Children 4 to 15 years of age with CU were investigated with a complete blood cell count, erythrocyte sedimentation rate, antinuclear antibody titer, complement CH 50 level, thyroid studies, autologous serum skin test, skin-prick tests, food challenges, and stool examination for parasites. They were considered to be in remission if symptoms did not recur for at least 12 months without medication. Results In all, 92 children (53.3% female) with CU were recruited and followed up for a median duration of 4.3 years (range 2.5-5.8 years). Chronic autoimmune urticaria (CAU) was identified in 40% of the patients. Food allergy was found in 8.7% and parasitic infestations in 5.4%. Remission rates at 1, 3, and 5 years after the onset of CU symptoms were 18.5%, 54%, and 67.7%, respectively. The remission rate did not differ in CAU compared with non-CAU. No predictor of CU remission was identified. Limitations The basophil histamine release assay was not performed. Conclusion Children with CU have a favorable outcome. CAU did not have an intractable course.

Summary We herein report a case of antiphospholipid syndrome (APS) primarily presenting with asthma-like symptoms that had been misdiagnosed as severe asthma. Patients presenting with severe asthma symptoms along with systemic thrombosis should be systematically evaluated for APS. Pediatr Pulmonol. 2015; 50:E1–E4. © 2014 Wiley Periodicals, Inc.

We reported a successful oral immunotherapy (OIT) in 2 children with high wheat sensitivity (4 and 14 years old boys). Oral challenges indicated eliciting doses of 300 mg, and wheat flour of 30 mg. The OIT protocol includes 5 days of build-up phase in the hospital, intervening with 2 to 5 months of home maintenance phase. Patients could tolerate 45 g, and 60 g of wheat flour per day, respectively. We have demonstrated that OIT to a large amount of wheat in extremely sensitized patients could be achieved with a stepwise multi oral/maintenance regimen.

Purpose In the USA and Europe, hypovitaminosis D is associated with increased asthma severity, emergency department (ED) visit, and impaired pulmonary function in asthmatic patients. However, in tropical countries, data on the effect of vitamin D status on asthma is limited. This study evaluates the relationship between vitamin D status and the level of asthma control as well as other asthmatic parameters. Methods Asthmatic children were evaluated for serum 25-hydroxyvitamin D, pulmonary function tests, a skin prick test, and the level of asthma control. Results A total of 125 asthmatic children were recruited (boys, 66.4%). Their mean age±SD was 10.8±3.0 years. Vitamin D statuses were: deficiency (30 ng/mL) in 36%. The vitamin D levels were 25.9±9.4 ng/mL in uncontrolled patients, 29.2±8.6 ng/mL in partly controlled patients, and 27.9±8.0 ng/mL in controlled patients (P>0.05). There were no significant differences in pulmonary function, asthma exacerbation, inhaled-corticosteroid (ICS) dose, anti-inflammatory drugs, or ED visit or hospitalization between different vitamin D statuses. Vitamin D deficiency patients were older and had a delayed onset of asthma than insufficiency or sufficiency patients. There was no significant correlation between serum vitamin D and pulmonary function/doses of ICS. Conclusions High prevalences of vitamin D deficiency and insufficiency were found in asthmatic children in Thailand; however, there was no significant relationship between vitamin D status and the level of asthma control or other asthma parameters.

Recurrent acute rhinosinusitis (RARS) is characterized by multiple episodes of acute rhinosinusitis between which symptoms and signs resolve completely. The role of antibiotic prophylaxis to prevent RARS in children with nonallergic rhinitis (NAR) has not been investigated.To evaluate the effect of azithromycin to prevent RARS in children with NAR.A randomized, double-blind, placebo-controlled study was conducted in NAR children (5-15 years) with RARS. Azithromycin (5 mg/kg/d) 3 d/wk for 12 months or placebo was assigned to the study group and the control group, respectively. Patients with allergic rhinitis were excluded. Number of rhinosinusitis episodes in 12 months, visual analog scale score of nasal symptoms, and adjunctive medication score were recorded.Forty patients were enrolled and 20 patients were assigned randomly to the azithromycin and placebo groups. IgG subclass and specific antibody deficiencies were found in 83% and 2.5% of patients, respectively. After 12 months, the number of rhinosinusitis episodes/y in the azithromycin group reduced significantly from 5 to 0.5 (P.001) in contrast to the placebo group. Number needed to treat using azithromycin prophylaxis to prevent 1 patient from having RARS was 2. The average visual analog scale score and the average adjunctive medication score in the azithromycin (but not in the placebo) group reduced significantly compared with baseline (2.2 ± 1.4 vs 5.4 ± 1.8) and (3.9 ± 1.7 vs 5.4 ± 1.1), respectively (P.001).Azithromycin prophylaxis can reduce the number of rhinosinusitis episodes and medication score, and improve nasal symptoms in NAR children with RARS.

Patients with 22q11.2 deletion syndrome have a variable decrease in immunological parameters, especially regarding T cell counts. The aim of this study was to investigate immunological change over time and factors associated with immunological recovery among patients with 22q11.2 deletion syndrome. Patients with 22q11.2 deletion syndrome diagnosed by fluorescence in situ hybridization (FISH) were studied. Immunological parameters were evaluated every 6 months until patients returned to normal. Infection and vaccination histories were recorded and analyzed, and Kaplan-Meier survival curves were plotted to describe resolution of immunodeficiency. Forty-nine patients with an age range of 4 to 222 months were included. Twenty-five (51%) patients were female. In hypocalcemia, the odds ratio for CD4 lymphopenia was 17.03 (95%CI 1.82–159.23; p value = 0.01). Thirty patients (61.2%) exhibited decreased CD4+ T cell numbers, which returned to normal level in 18 (60%) patients. Median age of CD4+ T cell resolution was 2.5 years. T cell functions were abnormal in three patients. T cell functions returned to normal in all patients at a median age of 1.1 years. Six patients (13.5%) had abnormal serum immunoglobulin levels, with levels improving in four patients at 1.4 years of age. The most common infection was pneumonia (69.4%). BCG vaccination was administered in 47 of 49 patients at birth. Among 32 patients who had T cell defect, one patient developed BCGitis and one developed disseminated BCG. Immunodeficiencies identified among patients with 22q11.2 deletion syndrome were T cell defect (65.3%) and decreased immunoglobulin levels (12.2%). Median age of CD4 resolution was 2.5 years.

The natural history of wheat allergy varies among different countries.To study the age of resolution from IgE-mediated wheat allergy and to define the predictors of wheat tolerance.Patients with a history of immediate reactions after wheat ingestion were enrolled. Skin prick test (SPT) and measurement of serum specific IgE (sIgE) to wheat and ω-5 gliadin were performed. Oral challenge to wheat was performed to determine wheat tolerance.Fifty-five patients, aged 6 months to 12 years, were studied. The median age of wheat tolerance was 76 months (range 37-114 months). The percentage of children with wheat tolerance was 14.7% at age 2 years, 27% by age 4, 45.7% by age 5 and 69% by age 9. Predictors for wheat tolerance were SPT for wheat less than 3 mm of wheal diameter (hazard ratio 8.9), sIgE levels of wheat and ?-5 gliadin less than 0.35 (HR 4.3) and 0.35 kAU/L (HR 44), respectively, duration of onset of symptoms to time of physician diagnosis less than 36 months (HR 7.6) and no history of allergic rhinitis (HR 4.8).Forty percent of children with IgE-mediated wheat allergy develop tolerance by the age of 5 years. Size of SPT, IgE level of wheat and ω-5 gliadin, time from onset of symptoms to physician diagnosis and history of allergic rhinitis are helpful for predicting wheat tolerance.

Asthma has become the most common chronic disease in childhood. Significant advances in epidemiological research as well as in therapy of pediatric asthma have been made over the past 2 decades. In this review, we look at certain aspects therapy of childhood asthma, both in the past and present. Literature review on allergen avoidance (including mites, cockroach and cat), intensive therapy with β(2)-agonists in acute asthma (administering via continuous nebulization and intravenous routes), a revisit of theophylline use and its action, the use of inhaled corticosteroids in various phases of childhood asthma and sublingual immunotherapy in asthma are examined. Recent facts and dilemmas of these treatments are identified along with expression of our opinions, particularly on points of childhood asthma in the Asia-Pacific, are made in this review.

History of the World Allergy Organization: In 1951, the leaders in allergy from all over the world came together to form the International Association of Allergology and Clinical Immunology (IAACI). For the next 60 years, the allergy world converged at the IAACI triennial meetings, which became biennial in 2003. The international meetings, originally named the International Congress of Allergology and Clinical Immunology (ICACI), are now the World Allergy Congress (WAC) hosted by the World Allergy Organization (WAO). Everyone who has aspired to have worldwide recognition has played a part in IAACI-WAO. The History of the World Allergy Organization traces the global arc of the allergy field over the past 60 years. The current officers of WAO elected to focus on this rich history, inviting prominent leaders who are interested in being part of this history project to write about their time with IAACI-WAO. This series will be presented in Cancun, Mexico, as part of the XXII World Allergy Congress (December 4-8, 2011). Leading up to the Congress in Cancun, the World Allergy Organization Journal is presenting segments of the History as part of the "Notes of Allergy Watchers Series." Please enjoy. —Michael A. Kaliner, MD Historian, and Past President (2006-2007) World Allergy Organization

Jirapongsananuruk O, Pongpreuksa S, Sangacharoenkit P, Visitsunthorn N, Vichyanond P. Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients. Pediatr Allergy Immunol 2010: 21: 508–514. © 2009 John Wiley & Sons A/S The etiologies of chronic urticaria (CU) in childhood remains incompletely understood because of limited data in children. The objective of this study was to examine some of the possible etiologies of CU in children by focusing on the functional autoantibody to FceRIα and IgE, thyroid autoimmunity, urticarial vasculitis, parasitic infestation and food allergy. Children 4–15 yr of age with CU were investigated for complete blood count, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), CH50, free-T4 (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin and anti-microsomal antibody, autologous serum skin test (ASST), skin prick tests (SPT) for foods, food challenges, and stool examination for parasites. Ninety-four children who met the criteria for CU were recruited. Patients with physical urticaria were excluded. Eosinophilia and elevated ESR were found in 23% and 13%, respectively. High ANA titers were found in 2%. None of these patients had clinical features of urticarial vasculitis, abnormal CH50 level, abnormal TSH and FT4. Anti-thyroglobulin and anti-microsomal antibodies were not detected. Positive ASST was found in 38%. There were no differences in medication requirement and CU remission between patients with positive and negative ASST. Parasites were found in 5% without clinical correlation. SPT to foods was positive in 35%. Positive food challenges were found in six/nine patients with positive history of food allergy and two/seven patients with negative history. Food avoidance was beneficial to the subgroup of patients with positive history of food allergy only.

s Introduction Early diagnosis and treatment are keys to improve survival of patients with primary immunodeficiency diseases (PID). The clinical characteristics of these patients in Thailand were not well defined. Objective This study aimed to determine the clinical characteristics and outcomes of patients with PID in Thailand. Methods Medical records of PID patients in the past 18 years were reviewed. Results Sixty-seven children were registered. Antibody deficiencies were the most common PID (52.2%), followed by combined T cell and B cell immunodeficiencies (25.4%), other well-defined immunodeficiency syndromes (11.9%), and phagocytic defects (10.4%). The most common presentations of antibody deficiencies, combined T cell and B cell immunodeficiencies, and phagocytic defects were infection in the upper respiratory tract (74.3%), gastrointestinal tract (82.4%), and skin (85.7%), respectively. The highest mortality rate (52.9%) was found in severe combined immunodeficiency. Conclusion These results provide clinical features of PID in Thailand. Knowing these features will lead to prompt diagnosis and appropriate management.

Rationale Severe cases of VKC often do not readily respond to currently available treatment. We conducted an open-label trial with 0.1% ophthalmic FK-506 ointment to determine its efficacy in VKC. Methods Ten recalcitrant cases of VKC were enrolled. There were 9 boys and 1 girl (mean ages ± SD=9.12 ± 2.45 years). Their duration of VKC was 3.97 ± 1.96 years. CBC, renal and liver functions were obtained at baseline and at the end of treatment. Complete physical and ophthalmologic examination was undertaken at baseline and at weekly interval. FK506 ointment was applied, once to twice daily, for 4 weeks. Eye symptoms and side effect were recorded daily. Blood levels of FK506 were determined after 4 weeks of use. Results Rapid resolution of eye symptoms was observed. Mean symptoms score at the end of the first week reaching 31% of baseline-mean (p=0.015) and at the end of the therapy (4th) was 20% of baseline-mean. Mild eye stinging was noted (7 patients). There was a significant reduction of size of tarsal papilla (from a mean ± SD of 1.09 ± 0.64 mm at the beginning to 0.63 ± 0.57 mm at 4 weeks, p Conclusion FK506 is a highly effective treatment in this study. A study with longer treatment duration and with a comparison to other drugs is warranted.

Prevalence of childhood asthma appears to be increasing worldwide. In Thailand, the prevalence of childhood asthma increased from 4.2% to 13% within the past decade. The last epidemiologic survey in Thailand utilized the International Study of Asthma and Allergies in Childhood (ISAAC) phase I questionnaire translated into Thai language. Language in the questionnaire can affect the reliability and validity of results of the survey. The purpose of this study is to determine common Thai wordings actually used by Thai children and adolescents to describe wheeze, chest tightness, shortness of breath and dyspnea. Sixty asthmatic Thai children, aged 9.2-18 years with asthmatic attacks less than 1 yr prior to the study, and 178 age-matched controls were recruited into the study. Asthmatic children spontaneously expressed their terms describing their asthma symptoms (in Thai) and then answered a preoutlined questionnaire regarding asthma terminology during an interview session after viewing the severe attack scene of the International ISAAC video questionnaire. Controls responded only to the preoutlined questionnaire after viewing the video scene. Of the 60 asthmatic children (38 males and 22 females, mean age 11.9 yr), 75% had their last asthmatic attacks within 2 months prior to the study. Wheeze was referred to as ' /??:??/ (??) ' and '/wi:d/' in 50% and 33% of patients, respectively, and ' /??:??/ (??) ' in 93.8% among controls. Using only the word '/wi:d/' in our previous ISAAC-I survey, as it sounded like the English word 'wheeze', it appears that up to 67% of the cases could have been missed. Dyspnea was referred to as rapid breathing and feeling tired in 78.2% of cases and as rapid and difficult breathing in 76.3% of controls. Chest tightness was referred to as chest discomfort in 65.7%. Shortness of breath was referred to as not being able to catch a breath, too short a breath, not enough breath and feeling suffocated in 88.8%. Local terms for asthma symptoms should be established and validated into each language to obtain reliable epidemiologic data.

Objective: Recurrent acute rhinosinusitis (RARS) is defined as multiple episodes of acute rhinosinusitis in which the symptoms and signs of infection resolve completely between episodes. Limited data are available on the characteristics and preventive therapy of RARS. This study evaluated the clinical characteristics and predisposing factors of RARS in children as well as the preventive therapy. Methods: Medical records of children with RARS diagnosed between January 2010 and December 2012 were obtained. Demographic data, presenting symptoms, predisposing factors and preventive therapy were reviewed. Results: Ninety-four children with RARS were recruited. The mean age was 7.7±2.6 years, with a mean age of onset of 4.0±1.4 years. Sixty-one patients (64.9%) were boys and 56 patients (59.6%) had family history of atopy. The most common presenting symptom of RARS was purulent nasal discharge (100.0%), followed by nasal congestion (68.1%) and postnasal drainage (31.9%). The most common predisposing factor for RARS was immunoglobulin G subclass deficiency (78.7%), followed by non-allergic rhinitis (64.9%) and allergic rhinitis (35.1%). Sixty-five children (69.1%) received preventive therapy for RARS. The responses to preventive measures were: 80.0% (32/40 patients) to oral antibiotic prophylaxis, 50.0% (11/22 patients) to adenotonsillectomy, 91.7% (11/12 patients) to specific allergen immunotherapy, 27.3% (3/11 patients) to gentamicin nasal irrigation, and 66.7% (4/6 patients) to intravenous immunoglobulin. Conclusion: The most common presenting symptoms of RARS in children were purulent nasal discharge, nasal congestion and postnasal drainage. Children with RARS should be evaluated for the presence of underlying conditions such as immunodeficiency and allergic disease, which led to the appropriate management for these children.

We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations.Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. Keywords: Sublingual immunotherapy, Allergen-specific immunotherapy, Mechanisms of SLIT, Safety of SLIT, Efficacy of SLIT, Clinical trials methodology in SLIT

The most effective measure in house dust mite antigen reduction is mattress encasing with an impermeable membrane. A reduction in encasing costs will help increase patients' compliance in mite antigen avoidance.To investigate the effectiveness of partial mattress encasing with a nylon sheet produced in Thailand on the reduction of group I mite antigens from beddings.Sixty regularly-used beds from the house officers' dormitory of the Siriraj Hospital Mahidol University, Thailand, were randomly matched into two groups according to mite antigen levels. The control group (CG) used only regular cotton bed sheets whereas the partial encasing group (PG) used mattresses partially covered with a locally produced nylon sheet underneath the regular cotton bed sheets. Dust collection from the beddings was performed at baseline, 2, 4 and 6 months after application of the nylon sheet. Mite antigen levels were detected by a two step monoclonal antibody ELISA.Mite antigen levels in both groups were not different at the beginning of the study. The PG had significantly lower group I antigen levels on regular bed sheet surfaces than the CG (P.004) at the 2, 4 and 6 month timepoints. However, antigen levels on the mattress surface of the PG was significantly higher than the CG at the end of the study (P.004). The barrier efficacy of the nylon sheet in preventing migration of group I mite antigens from the mattress to the surface of the regular cotton bed sheet was 94% whereas that of the regular cotton bed sheet was 66% (P = .007).Partial mattress encasing with a locally made nylon sheet can reduce mite antigens on the regular cotton bed sheet surfaces for up to 6 months.

Mite allergens Derpl and Derfl were tested in 200 house dust samples using a nitrocellulose membrane- based dot-blot assay. The assay enables the mite allergens in a dust extract to be detected with results that can be visually read semiquantitatively within 30min. Positive results obtained with this method were easily observed as brown dots. The Derp1 and Derf1 allergens were also precisely quantitated by a two-site monoclonal antibody based enzyme-linked immunosorbent assay. Results of Derp1 and Derf1 mite allergens measured from the two methods were compared. The semiquantitative analysis using Spearman's correlation yielded a correlation coefficient of 0.892 (P

Regularity is a key element of maintenance drug treatment; compliance is crucial for treatment success. Once- or twice-daily intake of a drug is always easier to comply with than regimens requiring more frequent dosing. Bronchodilating treatment was used as an example to illustrate how sustained duration of effect can be achieved by two different approaches: oral administration of the terbutaline prodrug bambuterol and inhalation of formoterol. Bioanalytical methods were employed to monitor the kinetic fate of bambuterol and formoterol in plasma, urine, or faeces. Generated terbutaline in plasma was used as a marker of effect for bambuterol. Established clinical laboratory tests were used to assess local and systemic effects of inhaled formoterol compared with salbutamol. Recommended doses of bambuterol, 10-20 mg once daily in adults, normally produced plasma concentrations of the active moiety terbutaline within therapeutically relevant limits. Dose proportionality for terbutaline makes dosing with bambuterol predictable. Compared with adults, children should be given higher doses than indicated by their lower body weight. Pharmacokinetic analysis indicated that absorption of bambuterol was slow and multi-phasic and that slow biotransformation to terbutaline occurred both presystemically and systemically. Systemically circulating formoterol was rapidly eliminated, the inactive (S;S)-formoterol more rapidly than the active (R;R)-formoterol. An inactive phenol glucuronide was the main metabolite, and a previously unknown sulphate metabolite was discovered. Duration of systemically mediated cardiovascular or metabolic side-effects of inhaled formoterol seemed not to differ from those of an inhaled systemically equieffective dose of salbutamol. There was a trend suggesting that the magnitude of systemic side-effects may be less pronounced after inhalation of formoterol compared with a locally equieffective dose of inhaled salbutamol. Both approaches to sustaining stimulation of β2-adrenoceptors have their pros and cons. Bambuterol can be dosed orally once daily, but full effect is reached slowly. The effect of formoterol is reached within a few minutes, but administration must occur via the lungs, often twice daily. Both treatments, however, give 24-h symptom relief during regular treatment.

Objective: The primary objective was to compare the efficacy of two dosages of bambuterol, a once-daily oral bronchodilator, with placebo in Asian children with asthma. The secondary objective was to assess the tolerability of bambuterol in this population. Design: This was a multicentre, randomised, double-blind, placebo-controlled crossover study, with a run-in period of 2 weeks. The study consisted of three treatment periods of 2 weeks each, separated by washout periods of 2 weeks, with 7 clinic visits in total. Setting: Outpatients were recruited from 10 centres in Indonesia, Malaysia, The Philippines, Singapore and Thailand. Patients: Seventy Asian children aged 6 to 12 years (53 boys and 17 girls) with asthma for at least 6 months were randomised to treatment, and 62 patients completed the study. Interventions: During the three treatment periods, patients received either placebo or 5 or 10mg bambuterol tablets once daily for 2 weeks. Morning peak expiratory flow (PEF) was the primary efficacy variable. Secondary efficacy variables were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diary card data including evening PEF. Results: At baseline, FEV1 predicted was 82.9% and the reversibility was 22.2%. The study results suggest that the change from baseline in both morning and evening PEF recorded on the diary cards on days 4 to 14 of each treatment period was dose dependent, but only the difference in morning PEF between bambuterol 10mg and placebo was statistically significant (9.1 L/min; 95% confidence interval 0.2 to 18.0 L/min). FEV1, FVC, asthma symptom scores and the use of supplementary β2-agonists did not differ significantly between placebo and the two bambuterol treatments. Blood pressure and pulse rate remained consistent throughout the study. The number of spontaneously reported adverse events was similar for the three treatment groups. Conclusions: Bambuterol 10mg once daily is an effective bronchodilator in 6-to 12-year-old Asian children in terms of improvement in morning PEF.

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.

Vernal keratoconjunctivitis is a sight-threatening inflammatory disease of conjunctiva and cornea. It is frequently observed in young children with the onset usually occurring in the first decade of life. Mild cases of VKC tend to remit with nonspecific and supportive therapy. In contrast, severe cases are usually more protracted with remission/relapse occurring for a prolonged period of time. Although VKC is classified as an allergic eye condition, the role of allergens as an inciting factor is not clear. Pathogenesis of VKC involves roles for IgE, cytokines, chemokines, and inflammatory cells (T and B lymphocytes, mast cells, basophils, neutrophils, and eosinophils) with the release of their granular proteins, proliferation of fibroblasts, and laying down exuberant amounts of collagen fibers in the conjunctival tissue. In severe VKC cases—often of tarsal VKC—diagnostic giant papilla are classically observed on the upper tarsal plate, giving the classic ‘cobble-stone’ appearance. Corneal ulcer can occur from the effect of eosinophilic granular proteins on corneal epithelium and by physical trauma by intense eye rubbing. Topical corticosteroids, often required for controlling symptoms and signs in severe VKC, can lead to serious ocular complications. Immunomodulators that have been investigated for VKC treatment include topical ocular preparations of cyclosporine A and tacrolimus. Severe VKC responds promptly to topical cyclosporine A and tacrolimus, mostly within 1 month of therapy. Prolonged use of cyclosporine A and tacrolimus in VKC is safe and is tolerated by most patients without significant side effects. Recent investigations on the use of these two agents in VKC are the main purpose of this review. The use of cyclosporine A and tacrolimus are a major breakthrough in treatment for severe VKC, a debilitating allergic eye disease in children.