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Previous studies provide evidence for an association between modifications of the gut microbiota in early life and the development of food allergies. We studied the faecal microbiota composition (16S rRNA gene amplicon sequencing) and faecal microbiome functionality (metaproteomics) in a cohort of 40 infants diagnosed with cow's milk allergy (CMA) when entering the study. Some of the infants showed outgrowth of CMA after 12 months, while others did not. Faecal microbiota composition of infants was analysed directly after CMA diagnosis (baseline) as well as 6 and 12 months after entering the study. The aim was to gain insight on gut microbiome parameters in relation to outgrowth of CMA. The results of this study show that microbiome differences related to outgrowth of CMA can be mainly identified at the taxonomic level of the 16S rRNA gene, and to a lesser extent at the protein-based microbial taxonomy and functional protein level. At the 16S rRNA gene level outgrowth of CMA is characterized by lower relative abundance of Lachnospiraceae at baseline and lower Bacteroidaceae at visit 12 months. [ABSTRACT FROM AUTHOR]

Background: Beta-lactam (BL) antibiotics hypersensitivity is common in children. Clinical manifestation of BL hypersensitivity varies from mild to severe cutaneous adverse drug reactions (SCARs)., Objective: To determine the association of HLA genotype and BL hypersensitivity and the prevalence of true drug allergy in patients with history of BL hypersensitivity., Methods: A case-control study was performed in 117 children with aged 1-18 years. Children with history of non-SCARs BL hypersensitivity were evaluated for true drug hypersensitivity including skin test and drug provocation test. Tolerant control patients were children who could tolerate BL for at least 7 days without hypersensitivity reaction. HLA genotype (HLA-A, HLA-B, HLA-C and HLA-DRB1) were performed in 24 cases and 93 tolerant controls using PCR-SSO (polymerase chain reaction - sequence specific oligonucleotide probes)., Results: There were association of HLA-C*04:06 (OR = 13.14, 95%CI: 1.3-137.71; p = 0.027), and HLA-C*08:01 (OR = 4.83, 95%CI: 1.93-16.70; p = 0.016) with BL hypersensitivity. HLA-B*48:01 was strongly associated with immediate reaction from BL hypersensitivity (OR = 37.4, 95%CI: 1.69-824.59; p = 0.016) while HLA-C*04:06, HLA-C*08:01 and HLA-DRB1*04:06 were associated with delayed reaction (p < 0.05). Among 71 cases who were newly evaluated for BL hypersensitivity, only 7 cases (9.8%) had true BL hypersensitivity., Conclusions: Less than 10% of children with suspected of BL hypersensitivity have true hypersensitivity. There might be a role of HLA-B, HLA-C and HLA-DRB1 genotype in predicting BL hypersensitivity in Thai children.

Background: Food allergy (FA) prevalence is increasing in pediatric liver transplantation (LT). However, the clinical course is still limited., Objective: This retrospective cohort study aimed to identify the prevalence, risk factors, and the natural history of de novo FA in children post LT., Methods: Medical records of pediatric LT recipients from Jan 2001 - Dec 2014 were reviewed. De novo FA was diagnosed by symptoms after exposure to culprit food occurring after LT, and improvement after diet elimination. FA was confirmed if reproduced symptoms after re-challenge or documented sensitization or indicated gastrointestinal eosinophilia., Results: Among 46 post LT children, 54.3% developed de novo FA at a median time of 12.2 months [Interquartile range (IQR) 6.2, 21.3 months] post LT. The confirmed FA was 39.1%. Gastrointestinal symptom was the most common manifestation followed by skin, anaphylaxis, and others. Culprit foods were cow's milk, shellfish, egg, wheat, soybean, peanut, coconut, fish and monosodium glutamate. The risk factors of FA were transplantation during age below 2 years [hazard ratio (HR), 2.62; 95% confidence interval (CI), 1.04 - 6.59; p = 0.03), atopic history in family (HR, 5.67; 95% CI, 1.33 - 24.12; p = 0.01), and Epstein-Barr (EBV) viremia (HR, 2.39; 95% CI, 1.02 - 5.63; p = 0.04)., Conclusions: de novo FA in pediatric LT is not uncommon. Age at LT younger than 2 years, family history of atopy, and EBV viremia are associated with developing FA. Development of tolerance after elimination culprit diets for 3 years is similar to general population.

Background: Intramuscular epinephrine is the first line drug in the treatment of anaphylaxis. This study was to identify the appropriateness of 1 inch needle length for epinephrine prefilled syringes in children., Methods: Children aged 1 month to 18 years were enrolled. Skin to muscle depth (STMD) and skin to bone depth (STBD) were measured using an ultrasonography at the mid-anterolateral thigh. A 1 inch needle was considered as being appropriate if the STBD was more than 1 inch and the STMD was less than 1 inch., Results: Seventy five infants, 75 pre-school aged children, 75 school aged children and 147 adolescent were enrolled: 196 (52.7%) children were male. A 1 inch needle length was appropriate for 61% of the infants, for 88% of the preschool children, for 99% of the school aged children and for 95% of the adolescents. Thigh circumference ≥23 cm, BMI ≥16 kg/m2 and BW ≥ 6 kg in infants provided the sensitivity of 74%-96% in predicting the appropriateness of 1 inch needle. In preschool group, thigh circumference ≥25 cm, BMI ≥13.5 kg/m2 and BW ≥ 10 kg provided the sensitivity of 98.5-100% in predicting the appropriateness of 1 inch needle. Thigh circumference ≥ 49 cm in adolescents provided the sensitivity of 75% in predicting that a 1 inch needle was too short., Conclusion: One inch needle length may not be appropriated for intramuscular injection at thigh in all children. Thigh circumference, BMI and body weight are useful for predictor for using the 1 inch needle.

Background: The prevalence of asthma in Bangkok increased steadily over the last couple of decades and warrants an assessment of the costs associated with its treatment, particularly in the case of children., Objective: To estimate the direct medical costs of asthma care in children at the Allergy unit of the Department of Pediatrics, Ramathibodi hospital., Methods: In this retrospective study, we included asthmatic children aged less than 20 year-old having visited the allergy unit at least 4 times in 12 months between January and December, 2011. Cost data, retrieved from the allergy unit electronic database included billing invoices of inpatient care, outpatient and emergency room visits. From this dataset we estimated drug costs, physician and nursing services, diagnostic tests and procedures, supplies and room charges, and assessed an overall asthma-related direct medical cost., Results: Ninety-seven asthmatic children (aged 11.5 ± 3.7 years) were included in the study. Annual median direct medical cost was 8,537.9 Baht or 278 USD per patient. Annual direct medical cost was the highest in patients younger than 5 years old (p < 0.001). Moreover, expenses of patients who had at least one exacerbation increased significantly compared to patients without exacerbation (p = 0.02). Furthermore, direct medical cost was the highest when patients had exacerbation requiring hospitalization (p = 0.03)., Conclusions: Cases of patients having asthma exacerbation or being diagnosed with asthma before 5 years of age were associated with higher treatment expenses. Policies developed to achieve asthma control and prevention should identify young children and patients presenting risk factors for asthma exacerbation as high risk groups deserving particular attention.

Background: Anaphylaxis is a life-threatening condition. There are limited data about its etiology and clinical characteristics in Asian children with anaphylaxis., Objective: To investigate triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children., Method: Medical record of children who were diagnosed with anaphylaxis between 2004 and 2013 at Ramathibodi Hospital, Bangkok, Thailand were reviewed., Results: One hundred-seventy two episodes of anaphylaxis occurred in 160 children (91 boys, 69 girls) aged 3 months to 18 years. Anaphylaxis increased from 2.7 cases/1000 pediatric admission to 4.51 cases/1000 pediatric admission between 2004-2008 and 2009-2013. The main causes were food (34.92%), drug (33.1%), blood components (23.8%), insect sting (9%), and unidentified causes (2.8%). Allergy to the triggers was known prior to anaphylaxis in 42 episodes (24.6%). Treatment consisted of epinephrine intramuscularly (93.8%), corticosteroids (92.5%), H₁antihistamines (96%), H₂antihistamines (50%), and β₂agonists nebulization (35.1%). Biphasic anaphylaxis occurred in 8.7% of the documented episodes and severe anaphylaxis in 34.3% of the documented episodes. Biphasic anaphylaxis and severe anaphylaxis were associated with fewer administrations of intramuscular epinephrine (OR 0.08 [95% CI 0.014-0.43]; p =0.01 and OR 9.36 [95% CI 2.5-34.7]; p <0.001 respectively). There were no fatality cases. There were associations between triggers of anaphylaxis and atopic histories, patients with severe anaphylaxis and cardiovascular involvement (p <0.01)., Conclusions: The incidence of anaphylaxis in Thai children is increasing. Anaphylaxis in children commonly occurred without the histories of prior reaction to the causative agent. Less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphylaxis. A better knowledge of patterns and causes of anaphylaxis might contribute to a better management.

Background: House dust mite avoidance is advised in dust mite sensitized patients to decrease the risk to develop allergic symptoms. Maintaining a relative humidity (RH) of less than 50% in households is recommended to prevent dust mite proliferation., Objective: To investigate the efficacy of a novel temperature and humidity machine to control the level of dust mite allergens and total nasal symptom score (TNSS) in dust mite sensitized allergic rhinitis children., Method: Children (8-15 years) with dust mite sensitized persistent allergic rhinitis (AR) were enrolled. The temperature and humidity control machine was installed in the bedroom where the enrolled children stayed for 6 months. TNSS was assessed before and every month after machine set up and the level of dust mite allergen (Der p 1 and Der f 1) from the mattress were measured before and every 2 months after machine set up using enzyme-linked immunosorbent assay (ELISA)., Results: A total of 7 children were enrolled. Noticeable reduction of Der f 1 was observed as early as 2 months after installing the machine, but proper significant differences appeared 4 months after and remained low until the end of the experiment (p <0.05). Although no correlation was observed between TNSS and the level of dust mite allergens, there was a significant reduction in TNSS at 2 and 4 months (p <0.05) and 70% of the patients were able to stop using their intranasal corticosteroids by the end of the experiment., Conclusions: The level of house dust mite in mattresses was significantly reduced after using the temperature and humidity control machine. This machine may be used as an effective tool to control clinical symptoms of dust mite sensitized AR children.

Background: Patients with chronic liver disease have been shown to have impaired immune statuses. Liver transplantation (LT) is the standard treatment for end-stage liver disease patients and immunosuppressive drugs are commonly used to prevent graft rejection. There is an increasing evidence of de novo food allergies post LT., Objective: To investigate the cytokine response of peripheral blood mononuclear cells (PBMCs) of pediatric LT recipients before and six months after transplantation., Method: PBMCs collected before and six months after LT were stimulated with phytohemagglutinin (PHA), beta-lactoglobulin (BLG), tacrolimus (Tac), dexamethasone (Dex), and a combination of BLG and Dex (B+D), BLG and Tac (B+T), BLG and Tac plus Dex (B+T+D). Culture supernatants were measured for IL-5, IFN-γ and IL-10. Blood for liver function tests, complete blood counts, total IgE and specific IgE (sIgE) to cow's milk were recorded., Results: A total of five pediatric LT recipients were enrolled in the study. There were no food allergy cases. Total IgE and sIgE to cow's milk decreased significantly after LT. After transplantation, there was a significant increase in IL-5, IFN-γ and IL-10 in culture supernatants of PHA-stimulated PBMCs. Among different stimulations in post transplantation's PBMCs, the level of IL-5 significantly increased in B+D was suppressed with the combination of B+T+D. The level of IL-10 significantly increased in all conditions containing BLG both before and after transplantation., Conclusion: There was an improvement of the in vitro-cytokine responses after liver transplantations. Immunosuppressive drugs used in post transplantation had an effect on the cytokine responses.

Objective: To study changes in immunological responses in patients with CMPA during symptomatic and asymptomatic episodes of cow's milk protein tolerance status., Methods: 27 CMPA patients were enrolled and underwent diagnostic evaluation, including CM challenge test, skin prick test and specific IgE to CM. Blood samples were collected in two periods from those who became tolerant (n = 13) and those with persistent CMA (n = 14), in order to measure in vitro PBMC responses to cow's milk protein (IL-10, IFN-γ, IL-5), IgG4 to β-lactoglobulin, casein, BLG-IgG4/IgE ratio and the CAS-IgG4/IgE ratio., Results: Seventy percent of CMPA patients in our study were male with a mean age at diagnosis of 8 months and mean age of onset of 3 months. The reaction time to CM ranged from within 7 minutes to within 14 days. Positive IgE-sensitization was defined as either a specific IgE to CM of more than 0.35 kUA/L (N=11) or SPTs positive for CM and/or fresh cow's milk (N=20). Forty-eight percent of the patients (n = 13) could tolerate CM by 13.38 months (8-19 months). Mean specific-IgE levels to CM were 4.1 kUA/L (range 0.35-14.3 kUA/L). Determination of the cytokine (IL-10, IFN-γ, IL-5) response to BLG revealed significantly higher IL-10 levels during the tolerance phase (212.93 vs 142.46 pg/ml, P = .011). There was a significant increase in BLG-IgG4 and the BLG-IgG4/IgE ratio in the tolerance phase when compared to the symptomatic phase., Conclusions: IL-10, BLG-IgG4 and the BLG-IgG4/IgE ratio were higher in CMPA patients during the tolerance phase compared to the symptomatic phase.

Asthma is a chronic inflammatory disease of the airway. Pathological repair of chronic inflammation leads to airway remodeling. Transforming growth factor-beta (TGF-beta), a profibrotic cytokine, plays an important role in promoting the structural changes of airway remodeling. TGF-beta effects on the proliferation, differentiation and extracellular matrix (ECM) metabolism of airway structural cells. This study assessed serum TGF-beta1 in different severity of atopic asthma compared to non-atopic controls. Thirty-one atopic asthmatic patients and 34 non-atopic controls, aged 7-18 years, were recruited as to the asthma severity: steroid naïve mild asthma, moderate asthma, and asthma in remission. Serum TGF-beta1 was measured by enzyme-linked immunosorbent assay. There was a significant difference between serum TGF-beta1 in asthmatic patients and that in control patients (39.59 ng/ml vs. 0.26 ng/ml, p < 0.001). Serum TGF-beta1 was highest in steroid naïve mild asthma group when compared to the moderate asthma and asthma in remission groups (47.44 ng/ml vs. 38.64 ng/ml and 47.44 ng/ml vs. 35.94 ng/ml, p = 0.013 and 0.001, respectively). There were no correlations among serum TGF-beta1 and pulmonary function test parameters, duration of asthma, and duration of inhaled corticosteroid treatment. These data support the role of TGF-beta1 in airway remodeling in asthma.