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Some patients with pollen-food allergy syndrome (PFAS) develop systemic symptoms along with oral allergy syndrome upon ingesting processed foods as well as raw fruits and vegetables. This study aimed to investigate the efficacy of subcutaneous immunotherapy with birch pollen extract for patients with PFAS associated with soybean allergy. Subcutaneous immunotherapy with birch pollen extract was introduced in 6 patients with PFAS caused by alder/birch pollen and soybean allergy. An oral food challenge for ingestible amount of soy milk was performed before and 1 year after initiating subcutaneous immunotherapy with birch pollen extract. Before the treatment, the median intake of soy milk was 1.5 mL (interquartile range [IQR], 1-2 mL). One year after the treatment initiation, the median intake of soy milk increased significantly to 150 mL (IQR, 20-200 mL). Systemic reactions occurred in 4 of 6 patients in the rapid escalation phase of the treatment. The results thus suggest that subcutaneous immunotherapy with birch pollen extract could be beneficial for patients with PFAS associated with soybean allergy despite concerns regarding systemic reactions.

Food allergy (FA) is a potentially life-threatening condition, food allergen immunotherapy, targeting the underlying mechanisms, is a potentially curative strategy in FA. A 46-year-old woman had an episode of facial angioedema and urticaria after mandarin ingestion and other episode of urticaria, abdominal pain, and facial angioedema after eating hazelnuts and almonds 4 years ago and contact urticaria (CU) with the manipulation of the peach skin. Three years ago, she suffered a facial and glottis angioedema, generalized urticaria, vomiting, and abdominal pain 10-15 minutes after eating green beans. She was treated with intravenous corticosteroids and antihistamines and intramuscular epinephrine, with complete resolution within a few hours. She no longer consumed nuts, and she avoided vegetables or fruits that caused her symptoms. Prick-prick test were performed, being positive with lettuce, eggplant, and cabbage and negative for cauliflower and broccoli. Total IgE (UniCAP method, kU/L) was 39.3, specific IgE Prup3 lipid transfer protein (LTP), 3.9; specific IgE to peanut, peach, pear, lemon, almond, avocado, walnut, cherry, and green bean were also positive. We decided to try to stop the march of the LTP sensitizations. Sublingual immunotherapy with a peach extract quantified in 12 μg/mL of peach allergen Prup3 was then initiated without any adverse event, and she has good adherence to the treatment. After 1 year, single-blind oral challenge test with peach, mandarin, and aubergine, were performed up to a portion dose (approximately 100 g) with all good tolerances.

Background Invariant natural killer T (iNKT) cells are known as the fast responder in allergic inflammation and the source of interleukin (IL)-4, IL-13, and interferon-gamma. Absence of iNKT cells down-regulated thymic stromal lymphopoietin (TSLP) production at the early stage of type 2 immune responses in the airway. However, it has not been reported whether iNKT cells are able to produce TSLP via stimulation of T-cell receptor (TCR). Objective We aimed to evaluate TSLP production from iNKT cells by TCR specific stimulations with anti-CD3/CD28 antibodies and α-galactoceramide (α-GalCer). Methods DN32.D3 iNKT cell line was stimulated with anti-CD3/CD28 antibodies, and TSLP production was measured in culture supernatants. Next, to confirm the TSLP production in primary mouse iNKT cells, the cells were sorted using α-GalCer-CD1d tetramer from mouse liver, and stimulated with anti-CD3/CD28 antibodies and α-GalCer. Then, cytokine productions were evaluated by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Results TCR specific stimulation in DN32.D3 cells induced TSLP production as well as signature cytokines of iNKT cells. On the other hand, isolated primary mouse iNKT cells from liver did not show any induction of TSLP by TCR specific stimulations including anti-CD3/CD28 antibodies and α-GalCer, on the contrary to other cytokines. Conclusion This study suggested the possibility of TSLP production in iNKT cells, especially from DN32.D3 although primary mouse liver iNKT cells showed a different result.

Background The most important infectious trigger of asthma is the virus and patients with immunoglobulin deficiencies are prone to recurrent respiratory infections. Objective We investigated the relationship between immunoglobulin G subclass and recurrent respiratory symptom exacerbation and explored possible therapeutic effects of intravenous immunoglobulin administration. Methods Twenty-eight infants less than 24 months old with 2 or more recurrent wheezing episodes (infantile wheezer group) and 29 asthmatic children aged 24 months to 15 years (bronchial asthma [B-asthma] group) visited our hospital from October 2010 to January 2018. Serum immunoglobulin G, A, M, E, G1, G2, G3, and G4 were measured in each group and compared. In both groups, serum immunoglobulin and symptoms were compared before and after intravenous immunoglobulin administration. Results The 2 study groups exhibited several statistically significant differences when comparing respiratory virus infection rate (p < 0.001), coinfection rate (p < 0.0001), most commonly found viral infection (human bocavirus vs. human rhinovirus), and immunoglobulin A (p < 0.001), E (p = 0.008), G2 (p < 0.001), and G4 (p = 0.011) levels. In the infantile wheezer group, there was an inverse correlation between immunoglobulin G4 levels and wheezing numbers (R = -0.5538, P = 0.0022). Both groups showed significant changes in immunoglobulin levels and respiratory symptom exacerbations (recurrent wheezing, shortness of breath, chest tightness, cough, and fever) over 1 year after intravenous immunoglobulin administration. Conclusion There was an association between recurrent wheezing and specific immunoglobulin G deficiencies. We suggest that intravenous immunoglobulin therapy significantly elevates specific immunoglobulin G levels though it lasts only for short term and might be associated with decreased respiratory symptoms. Therefore, low IgG4 levels among infants with recurrent wheezing may be indicative for intravenous immunoglobulin therapy.

Background Pet ownership is increasing rapidly and as growing numbers of dogs in household, clinicians are facing more allergic patients and so as in young children. Objective This study aims to profile the IgE recognition patterns to aeroallergen components in young children sensitized to dogs. Methods Through retrospective chart reviews, we evaluated the clinical, environmental, and laboratory findings of patients sensitized to dogs in early life. We further evaluated specific IgE to dog component allergens (Can f 1, Can f 2, and Can f 3) and other aeroallergens using a microarray. Results The median age of 28 patients sensitized to dogs (dog-specific IgE ≥ 0.35 kU/L; 0.38-101 kU/L) was 61 months and underlying diseases included doctor diagnosed atopic dermatitis (n = 17), asthma (n = 7), and allergic rhinitis (n = 5). Twenty patients (71.4%) had experienced self-reported dog allergy and 70.0% of them were symptomatic after exposed to dogs from others. Component-resolved diagnosis was performed on 18 patients. Can f 1 positivity was the most common (77.8%) but had no value in symptom prediction. The most common cosensitized aeroallergen was house dust mites (44.5%). The symptomatic group tended to be poly-sensitized to Can f 1, Can f 2, and Can f 3. Conclusion Can f 1 was dominantly detected and poly-sensitized to Can f 2 and/or Can f 3 simultaneously tend to develop hypersensitivity to dogs in young children. Most of them were exposed to dogs not living with.

Adverse reactions of subcutaneous low molecular weight heparin or unfractionated heparin could be complications by bleeding, heparin-induced thrombocytopenia, drug-induced liver injury, osteoporosis, and cutaneous reactions. Heparin-induced skin lesions vary from allergic reactions like erythema, urticaria, eczema to intradermal microvascular thrombosis associated with heparin-induced thrombocytopenia. There is a rare cutaneous complication, called bullous hemorrhagic dermatosis. We experienced this rare case of the cutaneous complication caused by enoxaparin. Several tense bullous hemorrhagic lesions occurred after 3 days of enoxaparin in a known bullous pemphigoid patient who had aortic valve replacement surgery with a mechanical prosthesis. The bullous hemorrhagic lesions were regressed after the discontinuation of enoxaparin but recurred after re-administration. The lesions were controlled by the administration of systemic corticosteroid and alternative anticoagulant. To date, less than 20 cases have been reported worldwide. This is the first case of bullous hemorrhagic dermatosis induced by enoxaparin, a low-molecular-weight heparin in Korea. This is also the first case of bullous hemorrhagic dermatosis in a known bullous pemphigoid patient.

Background Pollen allergy may be frequently associated with fruit-vegetables: the so-called pollen food syndrome. Pru p 3 is the most relevant peach allergen. Previously, it has been reported that serum specific IgE level to Pru p 3 depends on age in a limited geographic area. Objective This study aimed to to test the hypothesis about the differences of Pru p 3 sensitization across Italy, mainly concerning the impact of age. Methods The current study was retrospective and multicentre, involving 2 labs in Northern Italy (709 subjects), 1 in Genoa (1,040 subjects), and 1 in Southern Italy (2,188 subjects). All of them referred to labs for IgE testing because of suspected food allergy. Serum IgE to Pru p 3 was assessed in all subjects. Results Sixteen point seven percent (16.7%) of subjects were sensitized to Pru p 3. Sensitization percentage sigificantly decreased over time. The serum IgE levels increased up to young adulthood and then decreased until aging. Conclusion Our experience demonstrates that Pru p 3 sensitization and production are closely age-dependent phenomena.

Background Asthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence. Objective We aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly. Methods Consecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score. Results Total of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected. Conclusion One-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated.

Background The influence of bathing in asthma patients is not yet fully known. Objective We conducted an observational study to investigate changes in symptoms and their degree by bathing in asthmatic patients. Methods A questionnaire focusing on ever experienced bathing-induced symptom changes and their degree, as well as contributing factors, was designed and administered to asthmatic patients in the outpatient department of our institute between January 2012 and November 2013. Results Two hundred fifteen cases were recruited. In 60 cases (27.9%), asthmatic symptoms appeared, including 20 cases of chest discomfort (33.3%), 19 cases of cough (31.7%), and 21 cases of wheezing (35.0%). The triggering factors included vapor inhalation (32 cases, 53.3%), hydrostatic pressure on the thorax due to body immersion in the bathtub (26 cases, 43.3%), and sudden change of air temperature (16 cases, 26.7%). Thirty-eight cases (17.7%) experienced improvement in active asthmatic symptoms by bathing. Vapor inhalation was the most common contributing factor (34 cases, 89.5%), followed by warming of the whole body (13 cases, 34.2%). There was no relationship between asthma severity and the appearance of bathing-induced symptoms or improvement of active asthmatic symptoms by bathing. Conclusion The effects of bathing in asthmatic patients widely differed from patient to patient and their etiology includes several factors. For those who suffer from bathing-induced asthma symptoms, preventive methods, such as premedication with bronchodilators before bathing, should be established. This study is registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan with the registration number UMIN000015641.

Background Environmental tobacco smoke (ETS) exposure is recognized as a risk factor for the development of various respiratory diseases. Objective In this study, the effect of ETS on allergen-immunized and allergen-specific Th2 cell-transferred murine eosinophilic inflammation models and that of cigarette smoke extract (CSE) and nicotine on allergen-induced Th2 cell proliferation and interleukin (IL)-4 production were investigated. Methods Ovalbumin (OVA)-immunized and OVA-specific Th2 cell-transferred BALB/c mice were exposed to ETS and were challenged with OVA. Then, the number of inflammatory cells in the nasal mucosa and nasal hyperresponsiveness (NHR) were assessed. The effects of CSE and nicotine on the allergen-induced proliferative response of and IL-4 production by Th2 cells were determined in vitro. Results In OVA-immunized and Th2 cell-transferred mice, allergen-induced NHR and nasal eosinophil infiltration were significantly suppressed by ETS exposure, whereas the accumulation of neutrophils was rather enhanced. Allergen-specific Th2 cell proliferation and IL-4 production were inhibited by coculture with CSE. The same effects were induced by nicotine, though the effect on proliferation was relatively weak. Conclusion Regardless of its harmful effect, ETS suppresses NHR, probably through the inhibition of Th2 cell responses.

Background Banana fruit has been recognized as an important food allergen source. Nowadays banana hypersensitivity had been reported more frequently with various presentations from oral allergy syndrome to anaphylaxis. Objective This study aims to describe the pattern of banana hypersensitivity and the sensitivity of diagnostic test. Methods Six patients who experienced banana hypersensitivity were recruited from adult allergy clinic, Ramathibodi Hospital, Mahidol University between 2015-2018. Demographic data, pattern of banana allergy consisted of the onset of reaction, symptoms, severity, cross-reactivity to kiwi, avocado, latex including type and amount of banana were collected. Skin test, serum specific IgE to banana and open-label food challenge test had been applied. Results All patients experienced multiple episodes of banana anaphylaxis. Regarding the diagnostic investigation, prick-to-prick skin test had higher sensitivity (sensitivity, 100%; 95% confidence interval [CI], 54.07%-100%) than the commercial banana extract (sensitivity, 83.33%; 95% CI, 35.88%-99.58%) and serum specific IgE to banana (sensitivity, 50%; 95% CI, 11.81%-88.19%). The discordance between skin prick test using commercial banana extract and skin test was reported. The cross-reactivity between the species of banana, kiwi, the avocado was documented in all patients. Latex skin prick test and application test were applied with negative results. From the oral food challenge test, a case of banana anaphylaxis patient can tolerate heated banana. Conclusion The various phenotypes of banana hypersensitivity were identified. The prick-to-prick test showed the highest sensitivity for diagnosis of banana allergy. However, component resolved diagnostics might be needed for conclusive diagnosis.

Food allergy has an estimated prevalence of 6%-8% in children. Meat allergy and multiple food allergy due to sensitization to cross-reactive components in infancy is, however, less frequent. A 5-year-old girl was referred to our department with a multiple food allergy history. She had severe immediate worsening of her atopic dermatitis with hen's egg (6 months) and cow's milk introduction (7 months). At the age of 9 months, she presented with recurrent and reproducible atopic dermatitis' worsening and lip edema with the introduction of different meats (chicken, turkey, cow, pork, and rabbit), having the same complaints with fish at 12 months (salmon and hake). At her first appointment she was avoiding hen's egg, cow's milk, meat, and fish (except fresh tuna, codfish, and pollock). We performed skin prick tests (commercial extract and prick-to-prick with whole food) and specific IgE, which revealed sensitization to hen's egg, raw meat (cow, pork, chicken, turkey, duck, lamb, goat, and rabbit; negative for cooked meat), codfish and cow's milk (mild). ISAC was performed, revealing sensitization to 3 cross-reactive components (serum albumins Bosd6, Canf3, and Feld2) and specific food components of chicken's egg/meat (Gald1, 2, 3, and 5), cod (Gadc1), hazelnut (Cora9), and kiwi (Actd1). We present a rare case of multiple food allergy in infancy, where sensitization to cross-reactive components was responsible for most of the children complaints. The detection of serum albumins' involvement was especially important, because it can possibly mean tolerance to these foods in well-cooked forms, substantially improving patient and family's quality of life.

Background Atopic dermatitis (AD) in infants is often related to food allergies (FA). The beneficial effects of lactic acid bacteria towards allergic diseases have been reported, but there are few reports on their effect and preferable dosages on AD in young children with concomitant FA. Objective To examine additional effects of two different dose of paraprobiotic Lactobacillus acidophilus L-92 (L-92) on the clinical treatment in young children afflicted by AD with diagnosed or suspected FA. Methods Fifty-nine AD young children from 10 months to 3 years old, with FA or who had not started to ingest specific food(s) because of high specific IgE levels, were recruited and randomly allocated into L-92 group (daily intake of 20 mg L-92/day) and placebo group. Participants were given test sample with conventional treatment for AD over a 24-week period. The severity of eczema was evaluated using SCORing Atopic Dermatitis (SCORAD) index before intervention, and at 4, 12, and 24 weeks after intervention. Results After 24 weeks of intervention, a significant decrease in SCORAD was observed only in the L-92 group when compared with the baseline values. Significant decreases in thymus and activation-regulated chemokine (TARC) and total IgE were also detected 24 weeks after intake in the L-92 group compared with the placebo group. Conclusion It was suggested that intake of sufficient amounts of L-92 works as an adjunctive treatment of young children afflicted by AD with diagnosed or suspected FA.

Background: The prevalence of allergic conditions is increasing in most countries. One possible explanation may be childhood nutrition. Objective: The aim of the study was to investigate the relationship between consumption of pre-specified types of food in school-aged children and presence of respiratory and allergic symptoms. Methods: A total of 191 students aged 9–11 years were recruited from 5 schools to geographically cover all of Malta. Data was collected between October 2011 and February 2012. This was part of a bigger study which included clinical and environmental tests besides standardized health questionnaires. For the purposes of this part of the study only the health questionnaires were used. These standardized health questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) were used to identify the presence of respiratory and allergic symptoms and to identify the types of foods and the frequency of consumption of various types of foods. Results: We found that milk, meat, butter, olive oil, and yoghurt consumption had a negative association with allergic symptoms in children, whilst fish consumption had a detrimental effect. These relationships remained significant after correction for paternal level of education. Conclusion: The study highlights the fact that nutrition in early childhood may have a significant effect on the risk of allergic conditions. Our results, taken together with data in the literature, suggest that different types of fish might have had different effects. This is probably related to their different fatty acid constitution thus warranting further studies., peer-reviewed

Background Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. Objective The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. Methods A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0℃ and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. Results A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0℃, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. Conclusion YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity.

Chlorpheniramine is a widely prescribed H1-antihistamine for relieving urticaria or histamine-mediated allergic reactions. However, although rare, it may cause immediate hypersensitivity reactions. The diagnosis is usually made by provocation test, but its application is often limited due to comorbidities or potential risk of severe reactions. In those cases, skin tests and basophil activation tests can be considered as additional diagnostic tests for the drug allergy. Here, we report a 33-year-old female with underlying chronic urticaria, who recurrently developed anaphylaxis after chlorpheniramine administration. Intradermal test showed positive responses in the patient at 0.02 mg/mL of chlorpheniramine, but not in healthy controls. Basophil activation test showed significant up-regulation of CD63 and CD203c by chlorpheniramine. The present case reminds the rare but potential allergic risk of chlorpheniramine, and also suggests the potential utility of basophil activation test in making the diagnosis.

Background Human rhinoviruses are the major cause of asthma exacerbation in both children and adults. Recently, impaired antiviral interferon (IFN) response in asthmatics has been indicated as a primary reason of the susceptibility to respiratory virus, but the mechanism of defective IFN production is little understood to date. The expression of IFN regulatory factor 7 (IRF7), a transcriptional factor for virus-induced type I IFN production is known to be regulated epigenetically by DNA methylation. Objective We aimed to investigate the expression of IFN-α, IFN-β, and IRF7 in response to rhinovirus infection in the adult asthmatics and evaluate DNA methylation status of IRF7 gene promotor. Methods Twenty symptomatic adult asthmatics and 10 healthy subjects were enrolled and peripheral blood was collected from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and ex vivo stimulated with rhinovirus-16. The mRNA expressions of IFN-α, IFN-β, and IRF7 were analyzed using real time quantitative polymerase chain reaction. Genomic DNA was isolated from untreated PBMCs and the methylation status of IRF7 gene promotor was investigated using bisulfite pyrosequencing. Results The mean age of asthmatics was 45.4 ± 15.7 years and 40% was male, which were not different with those of control group. Asthmatics showed significantly decreased mRNA expressions (relative expression to beta-actin) of IFN-α and IFN-β compared with normal control. The mRNA expression of IRF7 in the asthmatics was also significantly lower than those in the normal control. No significant difference of DNA methylation was observed between asthmatics and controls in all analyzed positions of IRF7 promotor CpG loci. Conclusion The mRNA expression of type I IFN in response to rhinovirus was impaired in the PBMCs of adult asthmatics. The mRNA expression of IRF7, transcriptional factor inducing type I IFN was also reduced, but not caused by altered DNA methylation in the IRF7 gene promotor.

Background Eosinophilic otitis media (EOM) is often associated with comorbid asthma. The middle ear cavity is part of the upper airway. Therefore, EOM and asthma can be considered to be a crucial part of the "one airway, one disease" phenomenon. Based on the concept of one airway, one disease in the context of allergic rhinitis and asthma, optimal level of inhalation therapy for better asthma control leads to improvement in allergic rhinitis. Objective We conducted a pilot study to determine whether appropriate strengthening of inhalation therapy for asthma is effective for EOM. Methods Fifteen patients with EOM and comorbid asthma were enrolled in this study. Eight patients were randomly selected and administered appropriately strengthened inhalation therapy for asthma (strengthened group). The effect of the therapy on EOM was assessed by comparing a questionnaire for ear symptoms, clinical characteristic score, pure tone audiometry, blood tests and temporal bone computed tomography (CT) examination before and after the therapy. Seven other EOM + asthma patients without the above mentioned therapy were included as controls. Results In the strengthened group, the score of ear symptoms, clinical characteristics score, peripheral blood eosinophil count, CT score, and air conduction hearing level improved significantly after strengthening the inhalation therapy, but not in the control group. The lung function tests (forced vital capacity [%predicted], forced expiratory volume in 1 second [FEV1] [L], and FEV1 [%predicted]) significantly increased in the strengthened group after the therapy, but not in the control group. Conclusion In this study we demonstrated that EOM improved along with improved lung function when appropriately optimal inhalation therapy was implemented in patients with EOM and asthma. Administration of optimizing therapy for asthma might be effective for concomitant EOM.

The skin of individuals with atopic dermatitis has a susceptibility to be colonized with Staphylococcus aureus. This has been associated with increased frequency and severity of exacerbations of atopic dermatitis. Therefore, there is a growing interest in the use of antiseptic agents to target primary bacterial colonization and infection. Antiseptic agents have been found to be better tolerated and less likely to induce bacterial resistance as compared to antibiotics. There is also a wide variety of antiseptic agents available. The efficacy of antiseptic agents has yet to be established as the studies reviewed previously have been small and of suboptimal quality. This review discusses the rationale behind targeting S. aureus with antiseptic agents and presents findings from a review of studies assessing the efficacy of antiseptics in atopic dermatitis in the last five years. Four studies were found, including a bleach bath study which has already been reviewed elsewhere. The remaining 3 studies assessed the efficacy of sodium hypochlorite containing cleansing body wash, sodium hypochlorite baths and 1% triclosan in leave on emollient. These studies suggested some benefit for the inclusion of antiseptic use with the mainstay management of atopic dermatitis, including a potential steroid sparring effect. However, there are many limitations to these studies which therefore warrant further investigation on the impact of antiseptic use in atopic dermatitis.

Background Nowadays, there are many methods to reduce microorganisms in the air, such as dehumidifier, air purifier or humidity and temperature controller. The Precise Climate Controller is an instrument for controlling humidity and temperature, a concept that is demonstrated. Objective To determine the efficacy of this device, in order to reduce the quantity of the fungi and bacteria in the closed system. Methods This study is a perspective experimental study and is conducted as follows - the air sample in the closed system, a 42-cubic-meter room, is collected before the installation of the Precise Climate Controller. Next, the room is fumed with Aspergillus flavus and closed for 2 days. Then the instrument is in use in order to keep the relative humidity (RH) and the temperature constant at 55% RH and 25 degrees Celsius (℃). The air samples are collected every 3 days for 5 times during the period of 15 days to identify the type and calculate the quantity of the microorganisms. Results Before the Precise Climate Controller has been installed. Three species of bacteria are found in the air samples, but none of the fungus exists in the testing room. Once the room has been fumed with a large amount of A. flavus and the instrument is in use for 3 days, nine colonies of A. flavus are identified, but later on when the instrument is in use for 6, 9, 12, and 15 days, the air samples contain neither fungus nor bacteria. Conclusion After keeping the RH and temperature of the closed system constant at 55% RH and 25℃ by using the Precise Climate Controller, it is found that the efficaciousness in controlling the quantity and species of fungi and bacteria is clinically significant.

Background Over the last 10-20 years, international guidelines and consensus statements for the management of common allergic diseases (e.g. allergic rhinitis and asthma) have been developed and disseminated worldwide. However, their impact on knowledge and standard of clinical practice among primary care physicians and specialists is unknown. Objective To investigate need for an improvement in the dissemination of international guidelines for the diagnosis and management of allergic rhinitis. Methods Seven medical students who attended 3-day 1st International Basic Allergy Course (2010) took down all questions raised during the entire course. A systemic analysis of these questions was performed to identify areas for improvement in diagnosis and management of allergic diseases mainly in the Association of Southeast Asian Nations (ASEAN) region. Results 268 participants, 143 males and 125 females, comprising Ear, Nose and Throat (ENT) specialists (n = 106) and trainees (n = 34), general practitioners (n = 87), and other healthcare professionals (n = 41) attended the course. Of the 103 questions recorded, 59 were regarding treatment modalities in allergy practice such as immunotherapy (n = 38), pharmacologics (n = 15), nasal surgery (n = 2), and others (n = 4). 41 questions (39.8%) have answers based in the Allergic Rhinitis and its Impact on Asthma guidelines (2001 and 2008). Certain questions were selected for further analysis because they appeared to be (a) more commonly asked (e.g. immunotherapy) or (b) were deemed to be challenging or, even controversial (e.g. food allergy and differential diagnosis between vasovagal and anaphylaxis reaction), as the recommendations in current international guidelines were less well-defined. Conclusion Our study identified several problems that, if tackled, could help minimize confusion and provide better care for patients suffering from allergic diseases especially in the ASEAN region.

Background The Pink peppercorn belongs to the same Anacardiaceae family as cashew and pistachio. However, the cross-reactivity of pink peppercorn with cashew and pistachio has yet to be studied. To date, there has been a single case report of anaphylaxis to pink peppercorn in a cashew and pistachio allergic individual. Objective We aim to demonstrate cross-sensitization to pink peppercorn in cashew and/or pistachio allergic children. Methods A small descriptive cohort study looking at cross-sensitization of pink peppercorn in cashew and/or pistachio allergic children was conducted. Children with a history of reaction to pistachio and/or cashew nut underwent skin prick tests to the pink peppercorn species Schinus terebinthifolius to determine cross-sensitization. Results Out of the 21 cashew and/or pistachio allergic subjects, 16 (76.2%) demonstrated cross-sensitization to pink peppercorn. None of the subjects had any knowledge of previous exposure or allergic reactions to pink peppercorn. Discussion This study demonstrates potential cross-reactivity between pink peppercorn and cashew and pistachio. While an oral food challenge to pink peppercorn would have been important in demonstrating clinical cross-reactivity, this was not performed due to ethical constraints. We hope to increase the awareness of pink peppercorn as a potential and hidden source of allergen and encourage further studies to demonstrate the clinical cross-reactivity and to better delineate the major allergen involved.

Background Peanut allergy is an increasing problem in Singapore and strict avoidance is difficult as peanut is ubiquitous in Asian cuisine. Objective We aimed to assess the efficacy and safety of peanut oral immunotherapy (OIT) in children with obvious peanut allergy in Singapore. Methods This was an open-label study of peanut OIT in children living in Singapore, with 2 weekly dose escalation until final maintenance dose of 3,000 mg of peanut protein and a maintenance phase of 12 months. An oral food challenge was performed at 6 months to assess for desensitisation and at 4 weeks after discontinuation of OIT having completed 12 months of maintenance therapy to assess for possible sustained unresponsiveness. The adverse events were monitored using the symptom diaries. Results Nine subjects were started on OIT, with 7 managing to complete maintenance phase of therapy. Of these 7, all were able to tolerate at least 3,000 mg of peanut protein by 6 months of maintenance therapy, showing that the OIT was effective. Of these 7, 3 patients complied with the 4-week abstinence period after completion of OIT before another peanut challenge; 2 of the 3 subjects showed a significant decrease from the initial ability to tolerate 3,000 mg of peanut protein. Side effects were mainly gastrointestinal in nature and were more common during the updosing phase than the maintenance phase. No episodes of anaphylaxis were observed in this study. Conclusion Peanut OIT seemed to be effective and safe in our cohort of Singaporean children.

The increase in the incidence of food allergy is a growing problem for the western world. This review will focus on the findings from several macromolecular epithelial transport experiments and drug permeability studies to provide a recent comprehension of food allergen intestinal epithelial cell transport and the allergen-epithelial relationship. Specifically, this review will aim to answer whether allergens can permeate the intestinal barrier directly via intestinal epithelial cells, and whether this mode of transport affects downstream immune reactions. By improving our understanding of the interactions which take place during exposure of food allergens with the intestinal epithelium, we can begin to understand whether the epithelial barrier plays a major role in the allergic sensitization process rather than simply restricting the entry of allergens to the underlying lamina propria.

Background We reported that level of lipopolysaccharide (LPS) exposure determined the type of airway inflammation in a murine model of asthma. Objective The purpose of this study is to evaluated the role of IL-13 in low dose LPS induced murine model of asthma using IL-13 and signal transducer and activator of transcription 6 (STAT6) deficient mice. Methods Mice were sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and different doses of LPS (0.1 and 10 µg), and then challenged intranasally with OA alone. The phenotype changes between wild type (WT) and IL-13-/- mice and between WT and STAT6-/- mice were evaluated. Results We confirmed again that low and high dose LPS resulted in different phenotypes of murine asthma. In the present study, we observed that phenotypes of murine asthma induced by low dose LPS were abolished in the homozygous null mutation of the IL-13 and STAT6 gene. However, those changes were not shown in mice sensitized OA plus high dose LPS. Conclusion IL-13 plays an important role in low dose LPS induced murine model of asthma. Our results provided a new insight in understanding of the potential role of IL-13 in innate immunity in human allergic asthma.

Background Recent literature suggests that Staphylococcal enterotoxin specific IgE may be a risk factor for asthma. Objective To investigate the associations between Staphylococcal enterotoxin sensitization and asthma. Methods A systematic review and meta-analysis was performed for relevant case-control or population-based studies, published in the peer-reviewed journals until February 2013. Data were extracted on study designs, subjects, definitions and the prevalence of Staphylococcal enterotoxin sensitization. Results A total of 683 studies were initially identified, of which 7 studies finally met the inclusion criteria (5 case-control and 2 population-based studies). All the included studies reported higher prevalence of the sensitization in asthmatics than in controls, despite clinical and methodological heterogeneity. In a meta-analysis, the pooled odds ratio of the sensitization for asthma was 2.95 (95% confidence intervals 2.28-3.82). Conclusion Staphylococcal enterotoxin sensitization was significantly associated with asthma. The mechanisms of associations warrant further elucidation.

Background Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far. Objective We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule. Methods To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times. Results Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR. Conclusion This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.

BACKGROUND The symptoms of allergic rhinitis (AR) greatly affect the quality of life (QoL) in the patients with AR. The correlations of nasal response to leukotriene D4 (LTD4) and histamine nasal provocation with health related QoL in AR are not clear. OBJECTIVE To evaluate the correlations of nasal response to LTD4 and histamine nasal challenge with QoL in AR. METHODS Patients randomly underwent LTD4 and histamine nasal challenge tests, completed the rhinoconjunctivitis quality of life questionnaire (RQoLQ), and rating the symptom severity score (total symptom score 4, TSS4) in the previous week. The correlations between nasal challenge tests induced nasal responses and QoL in RQoLQ were analyzed. RESULTS A total of 25 eligible AR patients enrolled and finished both LTD4 and histamine nasal challenge and completed the questionnaire of RQoLQ. Histamine nasal challenge induced sneezing, increased nasal resistant were correlated with most of the dimensions (general, practical, nasal, eye problems, and quality of sleep, p < 0.05), while LTD4 nasal challenge induced sneeze, increased nasal resistant only correlated with nasal and ocular problems. On the contrary, the severity of the sneeze assessed by TSS4, was not correlated with QoL, while the severity of rhinorrhea, congestion, and nasal pruritus were correlated with nasal and practical problems, and nasal congestion was also correlated with ocular problems (r = 0.60, p = 0.01). CONCLUSION LTD4 and histamine nasal challenge induced nasal responses were correlated with different clinical symptoms severity and QoL, which can be used as a good diagnosis and evaluation methods for the management of AR.

Background There are little objective data regarding the optimal practice methods of bathing, although bathing and the use of moisturizers are the most important facets to atopic dermatitis (AD) management. Objective We performed this study to evaluate the effect of bathing on AD. Methods Ninety-six children with AD were enrolled during the summer season. Parents were educated to bathe them once daily with mildly acidic cleansers, and to apply emollients for 14 days. Parents recorded the frequency of bathing and skin symptoms in a diary. Scoring AD (SCORAD) scores were measured at the initial and follow-up visits. Patients were divided into two groups, based on the compliance of bathing; poor compliance was defined as ≥ 2 bathless days. Results There was an improvement of SCORAD score, itching, and insomnia in the good compliance group (all p < 0.001). The mean change in SCORAD score from the baseline at the follow-up visit was greater in the good compliance group than the poor compliance group (p = 0.038). Conclusion Daily bathing using weakly acidic syndets can reduce skin symptoms of pediatric AD during the summer season.

Recent technical approaches to investigating drug hypersensitivity have provided a great deal of information to solve the mechanisms that remain poorly understood. First, immunological investigations and in silico analysis have revealed that a novel interaction between T cells and antigen-presenting cells, namely the pharmacological interaction concept, is involved in drug recognition and the hapten theory. Second, progress in immunology has provided a new concept of CD4+ T cell subsets. Th17 cells have proven to be a critical player in acute generalized exanthematous pustulosis. Our recent findings suggest that this subset might contribute to the pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis. Third, alarmins, molecules associated with innate immunity, are also associated with exaggeration and the persistence of severe drug hypersensitivity. The latest innovative techniques are providing a new landscape to examine drug hypersensitivity.

Growing Up in Singapore Towards healthy Outcomes (GUSTO) is Singapore's largest birth cohort study to date. The main aim of GUSTO is to evaluate the role of developmental factors in the early pathways to metabolic compromise. Detailed data is collected for a range of environmental exposures in the parents and offspring, and allergic disorders are among a number of outcomes assessed in infancy and childhood. Under the Allergy domain of GUSTO, this integrated study will describe the epidemiology of allergic manifestations and different phenotypes in the Asian context and help shed light on the association of metabolic disease to allergy. Epigenetic mechanisms and associations with other childhood disorders will also be explored. The aim of this report is to focus on methodology of GUSTO, and to suggest similar approaches (i.e., integrated cohort studies on pediatric allergy) worldwide. Recruitment commenced in 2009 with a cohort of 1,163 pregnant mothers in their first trimester. The mothers and children were followed throughout pregnancy and follow-up will continue until the child reaches 3 years of age. Preliminary results showed that 39.8% of the mothers had a personal history of having at least one allergic disease, which included asthma, eczema and allergic rhinitis. Further data collection and analyses are still ongoing. Allergy is a complex spectrum of disorders with numerous poorly-understood aspects. The ongoing GUSTO cohort study, with its longitudinal design and multi-disciplinary nature, may provide new insights into developmental influences on allergy. As a Singapore-based study, it will be the first integrated allergy cohort in Southeast Asia, of which recruitment started during pregnancy.

Poor adherence to asthma medication treatment is a dilemma as it decreases the chance of achieving and maintaining a proper asthma control. Another dilemma is that there seems to be a small range of functional interventions that enhance adherence to long-term medication treatments. The aim was to review the last five years of published educational interventions for improving adherence to asthma medication. Through systematic database searches 20 articles were identified, which matched the inclusion criteria and described educational interventions to improve asthma self-management including adherence. The current review showed that addressing unintentional non-adherence in terms of incorrect inhaler technique by recurrent education improved the technique among many patients, but not among all. Phoning patients, as a means to remove medication beliefs as adherence barriers, seemed to be an effective educational strategy, shown as increased adherence. Involving patients in treatment decisions and individualising or tailoring educational support also seemed to have favourable effect on adherence. To conclude, addressing specific adherence barriers such as poor inhaler technique or medication beliefs could favour adherence. To change adherence behavior, the current review proposes that educational adherence support should be a collaborative effort between the patient and the health-care professional based on each individual patient's needs and patient factors, including elements such as personality traits.

The prevalence of allergic diseases is high globally, but especially in developed countries, with one in five to one in four individuals affected worldwide. The World Health Organization's "Allergic Rhinitis and its Impact on Asthma 2008 Update" guidelines stated explicitly that over 600 million patients from all countries, all ethnic groups and all ages suffer from allergic rhinitis (AR). There are clear evidences to support the concept that allergic diseases are influenced by genetic predisposition and environmental factors. The genetic basis of AR has been evaluated more intensively in the recent 10-20 years. Advances in technology and statistical methods, such as genome-wide association studies (GWAS) have enabled millions of single nucleotide polymorphisms (SNPs) to be genotyped at rapid pace and for less cost. However these studies have not yet answered the entire heritability profile of the disease. Additionally, environmental influences on these genetic variants cannot be discounted. Hence these allergic diseases must be evaluated as a complex interplay between genetic and environmental factors. This review focuses on the genetic basis of AR, with special emphasis on studies performed in Singapore. Candidate gene based studies and GWAS performed in Singapore cohorts have been discussed to suggest how these diseases could be understood better in a Singapore context which is still applicable to research in AR globally.

BACKGROUND Environmental pollutants are thought to be one of major triggers of atopic dermatitis (AD). OBJECTIVE We attempted to evaluate the clinical effects of environment with low indoor pollutant levels on AD management. METHODS Fifty-one children (mean age 1.7 years) with moderate to severe AD who failed to show improvement with conventional management were recruited. Disease severity was assessed by SCORAD (Scoring of AD) indices. They were admitted in a low pollutant oom for 3-4 days (mean 3.3 days) which was designed to keep low levels of dust, house dust mites, micro-organisms, and indoor air pollutants such as total volatile organic compounds (TVOCs), particulate matter (PM), and so on. Air pollutant levels in the low pollutant room were lower than primary standards defined by the Korean Ministry of Environment. we compared disease severity on admission and after discharge, and the pollutant levels of each patient's home and low pollutant room. RESULTS The SCORAD was significantly reduced from 42.0 ± 11 .5 to 29.8 ± 8.9 (p < 0.001) by management in a low pollutant room. PM(2.5), PM(10), formaldehyde, TVOCs, carbon dioxide, bacterial suspensions, and indoor molds were significantly higher in the patient's home than low pollutant room. Out of 29 patients who deteriorated after discharge to their home, 8 patients were admitted again, and their SCORAD was rapidly decreased from 53.1 ± 16.2 to 39.2 ± 9.8 (p = 0.036). CONCLUSION Indoor air pollutants are likely to affect AD in susceptible individuals. Environmental control to lower indoor air pollutant levels might be necessary for better management of AD in some patients.

Background Infants with chronic respiratory symptoms should be evaluated thoroughly because there are various causes which are different from those of children and adolescents. Objective This study was designed to investigate the relationship between chronic respiratory symptoms and bedtime bottle feeding in infants after the age of 6 months. Methods We conducted a prospective study that included 44 infants who presented with respiratory symptoms for more than 8 weeks and also had been bottle-fed during bedtime even after 6 months of age. The infants were divided into 2 groups; infants who discontinued bedtime bottle feeding and those who did not. Respiratory symptom scores were graded with a four-point scale at 0, 1, 2 and 3 months, and were compared between the 2 groups. Results Twenty eight infants (63.6%) stopped being bottle-fed during bedtime and 16 infants (36.4%) were still bottle-fed. The respiratory symptom scores were significantly decreased in infants who stopped bedtime bottle feeding (p = 0.0003). Conclusion It is suggested that prolonged bedtime bottle feeding might be one of the causes of chronic respiratory symptoms in infants.

Background Elimination diets are used to treat eosinophilic esophagitis (EoE), with success (remission) defined at endoscopy and oesophageal biopsy as fewer than 15 eosinophils per high power field (HPF). Response is assessed after 6 weeks of treatment by convention, but we have observed that this period of time may be insufficient. Objective To characterise a subset of patients with EoE who require prolonged (>6 weeks) of dietary therapy to achieve histologic remission. Methods A retrospective search of electronic medical records of 2 cohorts with EoE attending the Department of Gastroenterology, University of Chapel Hill North Carolina, and Eastern Health, Melbourne Australia. Patients who underwent elimination diet, had esophageal biopsy after 6 or more weeks of dietary restriction that demonstrated ongoing esophageal inflammation (>15 eosinophils per HPF), and who then continued dietary therapy followed by repeat endoscopy demonstrating remission (

Background Asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is an increasingly recognized clinical entity. ACOS significantly impacts on patient outcome compared to isolated asthma or COPD. However, ACOS definition and diagnosis criteria have not been well standardized. ACOS prevalence and clinical features in Thailand has never been studied. Objective: To investigate the prevalence and clinical features of ACOS compared to isolated asthma or COPD among patients with clinician-diagnosis of obstructive airway diseases. Objective To investigate the prevalence and clinical features of ACOS compared to isolated asthma or COPD among patients with clinician-diagnosis of obstructive airway diseases. Methods Spirometry, skin prick test (SPT) and allergens specific IgE (sIgE) were done. Serum total IgE, exhaled nitric oxide (FeNO) and blood eosinophils were measured. High resolution computed tomography (HRCT) was performed. Smoking history, pollution, biomass exposure and symptoms (Asthma Control Test [ACT], COPD assessment test [CAT], Modified Medical Research Council Dyspnea Scale [MMCR]) were assessed. Patients were classified to isolated asthma, COPD or ACOS according to predefined definitions for this study. Results A total 92 patients were enrolled: 58 patients with clinician-diagnosed of late onset asthma and 34 with clinician-diagnosed COPD. The mean age was 67.4 years. Thirty-four asthma patients (58.6%) were considered to have ACOS with postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio

Background: Cyclooxygenase-2 (COX-2) inhibitors have been found to be safe alternatives in adults with cross-intolerant hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). However they are usually not prescribed in children and there is little information about their tolerance in the pediatric age group. Objective: This study aims to evaluate the tolerance to etoricoxib in children with hypersensitivity to multiple antipyretics. Methods: A retrospective case series of children diagnosed with hypersensitivity reactions to NSAIDs and/or paracetamol who underwent a drug provocation test (DPT) with etoricoxib. Information on atopy, family history of allergic diseases, and medication usage was collected. Outcomes of the DPTs and tolerance to etoricoxib were also evaluated. Results: A total of 24 children, mean age 13.5 years, had a diagnosis of cross-intolerant hypersensitivity to NSAIDs and/or paracetamol. All except one patient successfully tolerated an oral challenge with etoricoxib. Of those who passed the DPT, the majority continued to use etoricoxib with no problems. It was found to be moderately effective in reducing fever and pain. Conclusion: Etoricoxib can be used as a safe alternative in older children with hypersensitivity to multiple antipyretics.

Background Immunoglobulin G4 (IgG4)-related sclerosing disease is a recently described clinicopathological entity with diverse manifestations including, amongst others, autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis and retroperitoneal fibrosis. Elevated serum IgG4 concentration has been described as the hallmark of this condition with reported good sensitivity and specificity. Objective We sought to establish the utility of serum IgG4 concentrations in the diagnosis of IgG4-related sclerosing disease by determining how many serum samples with elevated IgG4 from an unselected population would originate from patients who fulfilled criteria for this diagnosis. Methods The clinical features and laboratory characteristics of patients whose serum IgG4 concentration was greater than 1.30 g/L were analysed retrospectively from a total of 1,258 IgG subclass measurements performed in a tertiary hospital diagnostic laboratory. Results Eighty patients (6.4%) had elevated IgG4 concentrations greater than 1.30 g/L. Nine of 61 patients had the diagnosis of IgG4-related sclerosing disease, giving a poor positive predictive value of 15%. The median serum IgG4 concentrations of those with and without IgG4-related sclerosing disease were 2.16 g/L and 1.86 g/L, respectively (p = 0.22). Conclusion Serum IgG4 concentration has poor positive predictive value in the diagnosis of IgG4-related sclerosing disease and, therefore, the clinical significance of elevated serum IgG4 concentration alone must be interpreted with caution.