Search

Background: Previous studies have demonstrated that salbutamol administration via metered-dose inhaler with spacer (MDI-S) is as effective as using a jet nebulizer (NEB) for treating children experiencing asthma exacerbation. However, a paucity of research focuses on the direct medical costs associated with each mode of salbutamol administration for asthma exacerbation., Objective: This study aims to compare the effectiveness and direct medical costs of salbutamol administration via MDI-S versus NEB., Methods: A retrospective cohort study was conducted on the medical records of children under 18 years old presenting with mild to moderate asthma exacerbation. Clinical responses to salbutamol administration were assessed using the Ramathibodi Pediatrics Asthma Scores. The costs and clinical outcomes (i.e., Asthma score and hospitalization averted) were compared using the Incremental Cost-Effectiveness Ratio (ICER) from a hospital perspective., Results: The study included 95 medical records from 72 children, with 33 records of MDI-S and 62 records of NEB. Both the MDI-S and NEB groups showed significant reductions in asthma scores post-treatment. Children with moderate asthma exacerbation treated with MDI-S had a lower hospitalization rate than those treated with NEB (20% vs 57.5%, p = 0.034). The cost-effectiveness analysis indicated that the MDI-S group incurred lower costs and was considered cost-saving compared to the NEB group, with an ICER of -4.60 US dollars per one-point improvement in asthma score and -20.07 US dollars per hospitalization averted., Conclusions: Salbutamol administration via MDI-S offers clinical effectiveness comparable to NEB and is more cost-effective.

Background: Allergen skin prick test (SPT) and serum specific immunoglobulin E (sIgE) are effective diagnostic tests in allergic rhinitis (AR), however, positive results may not always correlate with clinical allergies. A nasal provocation test (NPT) can identify the causative allergen for immunotherapy, but it's not routinely performed., Objective: To establish the cutoff value for the house dust mite (HDM) SPT mean wheal diameter (MWD) and HDM sIgE level for identifying children with HDM-induced AR diagnosed from NPT., Methods: Children aged 5 to 18 years old with chronic rhinitis were evaluated by HDM SPT, sIgE, and NPT. Children with positive NPT results indicated HDM-induced AR. The cutoff values of the HDM SPT and sIgE level for predicting positive NPT were determined using a receiver operating characteristic curve., Results: A total of 245 children with a mean age of 9.53 ± 3 years were enrolled. HDM SPT results were positive (≥ 3 mm) in 160 (65.3%) children. HDM NPT results were positive in 176 (71.8%) children. Among children with positive HDM SPT (n = 160), 153 children (95.6%) were confirmed as having AR on NPT findings. The cutoff values for positive NPT responses were 6.6 mm for HDM SPT (yielding 100% specificity and 100% positive predictive value) and 17.0 kUA/L for sIgE (98.6% specificity and 99.2% positive predictive value)., Conclusions: This study proposes HDM SPT and sIgE cutoff values for use in the diagnosis of HDM-induced AR based on NPT. These cutoff values can be used to identify HDM-induced AR children who might benefit from immunotherapy.

Objective: To evaluate the impact of peak expiratory flow (PEF) monitoring using a smart peak flow (SPF) device on the quality of life (QoL) and satisfaction among children with asthma., Methods: This 3-month prospective cohort study enrolled 71 children aged 7 to 17 years with physician-diagnosed asthma. Participants used the SPF device twice daily, with measurements recorded automatically. Quality of life was assessed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and asthma control was assessed using the Asthma Control Test (ACT) or Childhood Asthma Control Test (C-ACT). Adherence to PEF measurements and satisfaction with the device were evaluated., Results: Seventy-one children (mean age 11.4 years) completed the study. Adherence to twice-daily PEF measurements decreased significantly over three months (from 50.0% at 1 month to 39.9% at 3 months, p  < 0.001). Children with good adherence (38.0%) showed significant improvements in PAQLQ scores, while those with poor adherence (62.0%) did not. COVID-19 infection resulted in a significant decrease in %PEF rate and increased peak flow variability. Despite device-related issues, overall satisfaction was high (85.19% for good adherence users vs. 88.64% for poor adherence users, p  = 0.671)., Conclusion: Regular PEF monitoring improves QoL in children with asthma by enabling early detection of symptom changes and better management. However, maintaining adherence to regular PEF monitoring is challenging. Further research with control groups is needed to validate these findings.

Background: House dust mite subcutaneous immunotherapy (HDM SCIT) is a therapeutic option for allergic rhinitis (AR) patients who are unable to properly manage symptoms with standard medications., Objective: This study aimed to determine long-term efficacy and identify predictive factors in the clinical remission of AR patients who completed and discontinued HDM SCIT., Methods: This study included 240 AR patients, who completed a three-year course of HDM SCIT at two tertiary hospitals and were currently being discontinued. We followed-up the patients to ask about their current symptoms and allergy medication. Clinical remission was defined by patients who no longer required daily intranasal steroid or oral antihistamine. We compared patients in clinical remission to those still taking medication., Results: The enrolled patients had a median age of 21.0 (11.0-36.0) years at the time they began HDM SCIT. The clinical remission of AR was achieved in 174 (72.5%) patients. Starting HDM SCIT before the age of 15 and not having asthma were identified as significant and independent predictors of remission (aOR 4.44; 95%CI, 1.72-11.50; p-value 0.002, and 2.67, 95%CI 1.00-7.12; p-value 0.049), respectively, as determined by multivariate logistic regression analysis. There were no significant differences in HDM SCIT duration or sensitization patterns between patients in remission and those on medication after discontinuing HDM SCIT for at least one year., Conclusion: HDM SCIT exhibited persistent long-term efficacy after treatment discontinuation. Starting HDM SCIT before the age of 15 and without asthma comorbidity might be predictors of AR remission with HDM SCIT.

Background: Previous house dust mite subcutaneous immunotherapy (HDM SCIT) placebo-controlled trials have small sample sizes and lack a consensus on baseline treatment., Objective: To determine the efficacy of HDM SCIT in moderate-to-severe allergic rhinitis (AR) patients treated with an intranasal corticosteroid at baseline., Methods: We conducted a randomized, placebo-controlled trial comparing HDM SCIT against placebo in Dermatophagoides pteronyssinus (Der p) sensitized. All patients received standard of care according to Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, including an intranasal steroid (INCS) at baseline. The primary endpoint was the comparison of a composite score, combining the total nasal symptom score and medication score, assessed at the twelfth month post-treatment., Results: Of the 144 subjects, 108 received HDM-SCIT and 36 received a placebo. The median age was 30 years (range 11-61), with 60% being female. The mean Der p wheal diameter was 9.4 mm (SD 4.4). After one year of treatment, the composite score median (IQR) in the HDM SCIT group and the placebo group was 0.75 (0.50-1.13) and 0.63 (0.50-1.25), respectively (p > 0.05). Both groups exhibited a significant mean change in the composite score from baseline (p < 0.001), but there was no significant difference between the groups. The median (IQR) serum Der p-specific immunoglobulin G4 level significantly increased only in the HDM SCIT arm (p ≤ 0.001)., Conclusion: One-year HDM SCIT significantly reduced both symptoms and medication use in HDM-allergic rhinitis patients. However, the changes were not significantly different from those in the placebo group, who also received an INCS at baseline. A longer-term study is warranted to assess disease modification factors.

Background: Anaphylaxis is a life-threatening allergic reaction with rising incidence worldwide. Young children's limited ability to express symptoms adds unique diagnostic challenges., Objective: To study on anaphylaxis in children, including triggers, symptoms, treatment, atopic status impact, and adrenaline injection time intervals., Methods: In-patient medical records of children who were diagnosed with anaphylaxis during 2014-2021 were reviewed., Results: One hundred thirty-three anaphylaxis events were identified. Food (47%) was the most common trigger, followed by drugs (31%), blood components (17%), insects (3%), and idiopathic causes (2%). Ten cases of refractory anaphylaxis, 2 cases of biphasic reactions, and 1 case of persistent anaphylaxis were found. There were no reported fatalities. The most common presentations involved the skin (94%), followed by the respiratory (73%), gastrointestinal (47%), and cardiovascular (42%) systems. In atopic patients, wheezing was more prominent than in those without atopy (p-value = 0.017). In the non-atopic patients, there was a higher incidence of cardiovascular symptoms, particularly hypotension (p-value = 0.001), compared to individuals with atopy. Children under 5 years old with mild-moderate anaphylaxis required more time to reach the hospital (147.0 vs. 45.0 minutes, p = 0.033) and to receive adrenaline injections (35.0 vs. 9.0 minutes, p-value = 0.017) than those with severe anaphylaxis., Conclusion: Childhood anaphylaxis is prevalent. Children with mild-moderate anaphylaxis experienced delays in hospital visits and adrenaline administration. Education on allergies is needed to improve the identification and prompt response to anaphylactic reactions, especially in young children.

Background: Food allergies pose serious health risks, including life-threatening anaphylactic reactions, increased morbidity, and reduced quality of life. Wheat allergy is a common concern in Asia. There is growing interest in understanding the potential association between dysregulation of the gut microbiome and the development of food allergies., Objective: This study aimed to explore the gut microbiome of Thai children with wheat allergy and its potential association with allergic responses., Methods: Microbial abundance was assessed using Quantitative Insights into Microbial Ecology 2 (QIIME2) microbiome analysis based on 16S rDNA data. The correlation between microbial richness and relevant parameters was evaluated using the Spearman correlation analysis. Additionally, the microbial community functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2)., Results: The gut microbiome analysis revealed significant differences between the two groups at the phylum and genus levels. Firmicutes (p = 0.012) and Verrucomicrobia (p < 0.001) were enriched in wheat-allergic children, whereas specific gut microbes such as Megamonas (p = 0.04), Romboutsia (p < 0.001), Fusobacterium (p < 0.001), Clostridium senso stricto1 (p < 0.001), and Turicibacter (p < 0.001) were more abundant in healthy children. Anaerostripes (p = 0.011), Erysipelatoclostridium (p < 0.001), Prevotella 2 (p < 0.001), Ruminiclostridium 5 (p < 0.001), and Clostridium innnocuum (p < 0.001) were enriched in children with a confirmed wheat allergy. Functional analysis indicated disparities in the pathways related to arginine and polyamine biosynthesis., Conclusion: These findings offer valuable insights into the gut microbiome of children with wheat allergy and its potential impact on symptom severity, laying the groundwork for further research and interventions aimed at addressing this health concern.

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV ( p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT ( p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.

Background: Unintentional exposure is common in children with food allergies., Objective: To assess the benefits of newly developed food allergy application., Methods: Caregivers of children with confirmed immediate reactions to food were enrolled to use the "Kinchew" application for one month. Kinchew provides the detail of food allergens after typing the name of specific food in the chat box. Then, the app provides the product image and detail of food allergens. Kinchew also has a menu for recording food diaries and videos on managing food allergies. Kinchew users were asked to assess their confidence in dealing with food allergies assessed by the questionnaire using 5 points Likert scale. The number of patients who experienced allergic reactions from unintentional food exposure was recorded after using Kinchew., Results: Seventy caregivers were enrolled. Wheat was the most common causative food in 67% of the participants. All participants used Kinchew with a total use of 1,754 times, classified as food items searching 1080 times (62%), and recorded their food diary 674 times (38%). The number of patients who experienced allergic reactions from unintentional exposure significantly decreased from 61 (87%) to 31 (44%), p < 0.001.The user's confidence in choosing food improved significantly compared to the baseline score. In the subgroup analysis of the type of causative food, a significant improvement in confidence in food choosing was demonstrated in wheat and multiple food allergy groups., Conclusions: Well-designed food allergy mobile applications could improve caregivers' confidence in dealing with food allergies and reduce unintentional food exposure.

Objective: The purpose of this study is to examine the effect of chronic rhinitis treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children with ADHD., Methods: Children and adolescents with ADHD were screened for chronic rhinitis symptoms. Participants with positive chronic rhinitis screening underwent the skin prick test and received rhinitis treatment for 3 months. All participants were evaluated using the parent's and teacher's Vanderbilt ADHD rating scales, total nasal symptom score, and Quality of Life Questionnaire (OSA-18) for pediatric obstructive sleep apnea at pretreatment and posttreatment., Results: Overall, 140 children and adolescents with ADHD were enrolled and screened for chronic rhinitis. Fifty-four children and adolescents with positive screening results underwent the skin prick test and received rhinitis treatment. After 3 months of treatment, inattentive, hyperactive/impulsive, and total ADHD symptom scores were significantly decreased as reported by parents ( p = 0.031 to <0.001) and teachers ( p = 0.001 to <0.001) compared with those before treatment. A subgroup analysis also showed improvement in ADHD symptoms as reported by parents and teachers in the allergic and nonallergic rhinitis groups. Pearson's correlation coefficient analyses showed positive correlations between improvement in the ADHD symptom scores reported by parents and improvement in the quality of life related to sleep problems from the OSA-18 questionnaire (r = 0.377-0.387)., Conclusion: Treating chronic rhinitis can improve ADHD symptoms in children and adolescents with ADHD. Pediatricians should be aware of and treat chronic rhinitis to maximize ADHD symptom control., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Rush venom immunotherapy (VIT) is the recommended treatment for patients with Hymenoptera anaphylaxis. Specific data regarding regulatory T cell and cytokine changes in children receiving rush VIT are sparse., Objective: To study the changing of CD4+CD25+FOXP3+ regulatory T cells (Treg) and serum cytokines in children undergoing 3 days rush VIT., Methods: Children younger than 15 years with systemic reaction to Hymenoptera who had evidence of IgE sensitization to Hymenoptera were enrolled for 3 days rush VIT. Peripheral blood CD4+CD25+FOXP3+ Treg and serum IL-4, IL5, IL-13, IFN-γ, and IL-10 were measured at baseline before rush VIT, achieving maintenance dose, 6 months, and 12 months after reaching maintenance dose. Specific IgE to Hymenoptera was measured at baseline and 12 months after VIT., Results: A total of 15 children (11 boys and 4 girls) aged 6-15 years (mean age, 10 years) were enrolled. Four children were allergic to bee and 11 children were allergic to Vespid. The levels of CD4+CD25+FOXP3+ Treg were significantly increased at 6 months after maintenance dose compared with baseline (6.58% VS 4.01%, p = 0.001). Serum IL-13, IFN-γ, and IL-10 levels did not change significantly from baseline. However, there was a significant reduction of IL-4 in the serum at 12 months after MN when compared to the baseline levels. The systemic reaction requiring epinephrine intramuscular injection occurred only in 1 case who was on Vespid venoms rush VIT., Conclusions: Three days rush VIT provide acceptable systemic reaction and able to increase the number of CD4+CD25+FOXP3+ Treg in children.

Background: Dyslipidemia and obesity contribute to a pro-inflammatory state. Eosinophilic airway inflammation can be indirectly measured by fractional exhaled nitric oxide (FeNO) produced in the airways of asthmatic subjects., Objective: To compare exhaled nitric oxide (NO) and alveolar NO in asthmatic children with and without dyslipidemia., Methods: Asthmatic children (5-18 years old) had fasting serum low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) concentrations measured. FeNO was measured at constant flow rates of 20, 50, 100, and 300 ml/s by the chemiluminescence method. NO concentrations in tissue of the upper airways (CawNO) and the total flux of NO in the conducting airways (JawNO) were determined through FeNO at 20, 100, and 300 ml/s using a mathematical model. The atopic status was assessed using the skin prick test for aero-allergens., Results: One hundred forty-one asthmatic children were enrolled with a mean (standard deviation) age of 11.82 (3.38) years. Sixty-four (45.4%) children had dyslipidemia and 20 (14.2%) were obese. Children with low HDL-C concentrations had significantly higher CawNO and JawNO than those with normal HDL-C concentrations (both p = 0.03). Asthmatic children with obesity had higher CRP concentrations than those with a normal weight (p < 0.001). Atopic children had a significantly higher FeNO, CawNO, and JawNO than non-atopic children (all p < 0.05)., Conclusions: This study suggests an effect of HDL-C on CawNO and JawNO in asthmatic children. An intervention that normalizes HDL-C concentrations may be beneficial for airway inflammation in asthmatic children.

Background: HLA-matched hematopoietic stem cell transplantation (HSCT) is the curative treatment for chronic granulomatous disease (CGD)., Objective: To report a case of X-linked CGD with active infection successfully treated by haploidentical HSCT with post-transplant high dose cyclophosphamide (PTCY)., Methods: A 5-year-old Thai boy with CGD was undergone for haploidentical HSCT using PTCY with correction of the phagocytic function. He presented with Chromobacterium violaceum liver abscess at the age of 9 months and experienced recurrent perianal abscess and invasive pulmonary aspergillosis even receiving antimicrobial prophylaxis. PTCY was given on day 3 and 4, after CD34+ cells infusion., Results: The peripheral blood-nucleated cell chimerism showed 100% on day 16 and remained 100%. Dihydrorhodamine (DHR) assay on day 108 and day 214 showed normal results. Currently at 22 months post HSCT, he does not receive antibiotic and anti-fungal prophylaxis., Conclusions: Haploidentical HSCT with PTCY could be an effective treatment option for children with CGD.

Background: One of the factors associated with uncontrolled pediatric asthma is inadequate delivery of inhaled medication to the lungs. Incorrect inhaler technique has been reported. We developed a 2-minute cartoon video instruction aiming to improve dry powder inhaler (DPI) technique., Objective: To assess the efficacy of video instruction in improvement of DPI technique in Thai children with asthma., Methods: The prospective multicenter cohort study was conducted during March 2018 - February 2019. Children with asthma aged 6-15 years were recruited from the outpatient departments. Five videotapes demonstrated how the patients use DPI devices were recorded as the followings: before and after watching video (V₁pre and V₁post), at one-month (V₂post), at three-month (V₃post) after watching the video and at 5-month follow-up without watching the video (V₄pre). Scoring of correct DPI steps were evaluated by two independent respiratory specialists., Results: Of 57 patients recruited, 30 used Accuhaler™ while 27 used Easyhaler™. In Accuhaler™ group, the median age (range) of 10 (8, 11) year. The mean score of V₁pre, V₁post, V₂post and V₃post were 10.7, 12.3, 12.4, and 12.2 out of 14 respectively. In Easyhaler™ group, the median age (range) of 11 (9-12) year. The mean score of V₁pre, V₁post, V₂post and V₃post were 8.6, 10.4, 11.2 and 11.4 out of 12 respectively. At the five-month follow-up, without watching video, the V₄pre score was still as high as 12.9 ± 1.3 in Accuhaler™ and 11.8 ± 0.4 in Easyhaler™., Conclusions: Our video instruction could improve Accuhaler± and Easyhaler± technique among Thai children with asthma.

Wiskott-Aldrich syndrome (WAS)/X-linked thrombocytopenia (XLT) is a rare X-linked disease characterized by thrombocytopenia, eczema, and recurrent infection. In addition, WAS/XLT increases incidence of autoimmune diseases and malignancies. We reported 7 male patients, 2 with WAS and 5 with XLT, from 6 different families. Two novel mutations, p.Gly387GlufsTer58 and p.Ala134Asp, were identified in patients with WAS. Both patients had severe clinical phenotypes compatible with classic WAS and developed lethal outcomes with intracranial hemorrhage. Other than that, one patient with XLT developed pineoblastoma.

Background: One of the pathophysiologic mechanisms involved in asthma is the increase in oxidative stress. Zinc (Zn), vitamin C (VC), and vitamin E (VE) have antioxidant functions. However, the status of oxidative stress, Zn, VC, and VE in Thai asthmatic children have not been reported., Objective: We aimed to evaluate the status of oxidative stress, Zn, VC, VE, pulmonary function tests, and airway inflammation in Thai asthmatic children with persistent asthma., Methods: In this cross-sectional study, the data was collected from asthmatic children aged 7-17 years. The plasma PGF2α concentration as a marker of oxidative stress was measured using an ELISA kit. Plasma Zn concentration was measured through atomic absorption spectrophotometry. Plasma VC and VE concentrations were determined using HPLC. Pulmonary function tests were evaluated as forced expiratory volume in first second (FEV₁) and forced vital capacity (FVC), using a spirometer. The status of airway inflammation was determined by measuring fractional exhaled nitric oxide., Results: There were 76 asthmatic children in this study. Seventy-two participants had high oxidative stress. All participants had Zn deficiency. Nearly 40% of participants had VC deficiency. VC deficiency was associated with severe asthma and airway obstruction. Plasma Zn concentrations were positively correlated with FEV₁ (r = 0.27) and FEV₁/FVC ratio (r = 0.65)., Conclusions: Deficiency of Zn and/or VC was related to severe asthma and decreased pulmonary function. Nutrition assessment and management should be considered to alleviate asthma burden.

Objectives: Rhinitis treatment may improve attention-deficit/hyperactivity symptoms in children. The current study evaluated changes in inattentive and hyperactive symptoms after treatment in children with chronic rhinitis., Methods: Children aged 5-18 years with chronic rhinitis were enrolled in a 3-month prospective study. The nasal provocation test for house dust mites (HDM) and evaluation of allergen sensitization, including the skin prick test and the Phadiatop test, were performed. The severity of rhinitis was assessed according to the ARIA guideline. The total nasal symptom score and the Vanderbilt ADHD Diagnostic Rating Scale (VADRS) score for assessing inattentive and hyperactive symptoms were recorded at baseline and at 1 and 3 months after rhinitis treatment. Children with rhinitis were classified into the following two groups: HDM-induced allergic rhinitis (AR group) and non-allergic rhinitis to HDM (NAR group) based on the NPT., Results: Overall, 83 children completed the 3-month prospective study, and they had a mean age of 9.12 ± 2.89 years and 44.6% were boys. After rhinitis treatment, VADRS scores assessed by the parents and teachers were significantly decreased compared with those at baseline (p = 0.005). In subgroup analysis, 61 (73.49%) children had AR, and 22 (26.5%) children had NAR. No significant difference in the baseline VADRS score was found between the AR and NAR groups. After treatment, VADRS scores assessed by the parents and teachers were significantly decreased only in the AR group (p < 0.001). Forty-five (54.2%) children had moderate persistent rhinitis, 29 (34.9%) had mild persistent rhinitis, and 9 (10.8%) had mild intermittent symptoms. There were no differences in baseline VADRS scores assessed by the parents and teachers among children with mild intermittent, mild persistent, or moderate persistent symptoms. The total nasal symptom score and VADRS score were significantly decreased after treatment for all severities of rhinitis compared with those at baseline. A greater baseline VADRS score was associated with substantial improvement of inattentive and hyperactive symptoms after treatment., Conclusion: Early treatment for rhinitis may improve inattentive and hyperactive symptoms in school-aged children., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Rhinitis is a common problem in children. Airway nitric oxide (NO) was proposed to represent eosinophilic inflammation., Objectives: To evaluate airway NO level in children with house dust mite (HDM)-induced allergic rhinitis., Methods: Children aged 5 to 18 years old with moderate-severe persistent rhinitis and positive result for the HDM nasal provocation test (NPT) was enrolled. The nasal symptoms evaluated by total nasal symptom score (TNSS) and visual analog scale (VAS) were recorded. Skin prick test (SPT) to common aeroallergens, fractional exhaled nitric oxide (FeNO), nasal nitric oxide (nNO), and blood test for specific IgE (sIgE) to HDM was measured. Rhinitis severity was categorized as severe if the VAS score > 7., Results: Forty-eight children with HDM-induced allergic rhinitis with the mean age of 9.3 ± 2.4 years were enrolled. nNO levels and VAS score were significantly correlated (R = 0.398, P  = .005). Children with severe rhinitis had significantly higher nNO levels than moderate rhinitis (1652.05 vs 941.30 parts per billion [ppb], P  = .002), while there was no difference in FeNO level. ROC curve analysis demonstrated the cut-off value of nNO at 1350 ppb (AUC 0.764, 95% CI: 0.616-0.911, P  = .002) for detecting severe HDM-induced allergic rhinitis with the sensitivity of 78% and the specificity of 71%. The level of FeNO in children who had HDM mean wheal diameter (MWD) > 8 mm was significantly higher than those with HDM MWD of 3 to 8 mm and those with a negative test (39.7 vs 14.3 vs 14.4 ppb; P  = .006, respectively). Children who had sIgE to HDM < 0.35 KUA/L had significantly lower FeNO than those with sIgE to HDM 0.35 to 50 KUA/L and >50 KUA/L (9.5 vs 19.7 vs 40.4 ppb; P  = .029, respectively)., Conclusions: Cut-off value for the diagnosis of severe HDM-induced chronic rhinitis was proposed. Rhinitis children who had a higher degree of HDM sensitization had a higher level of FeNO.

Background: The acceptable fine particulate matter (PM 2.5 ) level in Thailand is double the recommendation of the World Health Organization. It is necessary to have an accurate measure of PM 2.5 exposure and its association with health problems in vulnerable groups such as asthma exacerbation in Thai children to urge the Clean Air Act in Thailand, which is currently in the process of revision., Objective: To study the association between PM 2.5 exposure and asthma exacerbation in children living in Bangkok Metropolitan Region and Chiang Mai Province., Methods: A pilot prospective observational study was conducted at the Chest and Allergy clinic at Ramathibodi Hospital, Mahidol University, Bangkok and at the Chest Clinic at Nakornping Hospital, Chiang Mai, Thailand, from June 2020 to February 2021. Children with asthma, aged 5-18 years old, were recruited. Respiratory symptoms, including cough, chest tightness, dyspnea or wheezing, peak expiratory flow rate, and asthma exacerbation, were recorded twice daily by caregivers. Estimated average daily PM 2.5 exposure levels were calculated using ArcGIS® at exacerbation day, three days before exacerbation (lag day 3), and 7 days before exacerbation (lag day 7). Regression analysis was applied to examine the association between PM 2.5 exposure and asthma exacerbation., Findings: Seventy asthmatic patients were enrolled. The median age was 9.7 (IQR 5-18) years old. There were 53 respiratory symptoms, 5 admissions, and 1 intensive care unit admission. Daily PM 2.5 levels above 12 mcg/m 3 (the US cut-off level for the sensitive group) has higher sensitivity to detect asthma exacerbation compared to Thai cut-off level for the sensitive group (37 mcg/m 3 ) (sensitivity 98.2% vs 32.1%). The average daily PM 2.5 level exposure at lag day 3 in the exacerbation vs the non-exacerbation group was 27.5 and 13.6 mcg/m 3 (p < 0.01), respectively. The daily PM 2.5 level at lag day 3 was also correlated with an acute asthmatic attack (r = 0.62, p < 0.01) with the 0.2 events increasing of asthmatic exacerbation every 10 mcg/m 3 of increment of daily PM 2.5 level., Conclusions: Our findings suggest that asthmatic children are sensitive to daily PM 2.5 levels above 12 mcg/m 3 . Exposure to high daily PM 2.5 levels can lead to asthma exacerbation within three days. Further participant recruitment is needed to emphasize this association and establish the national data., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Background: The role of vitamin D and asthma in pulmonary function changes showed conflicting result., Objective: To evaluate if vitamin D treatment would improve lung function assessed by forced oscillation technique (FOT) in vitamin D deficient asthmatic children., Methods: A randomized double-blind placebo-controlled trial was performed in children, aged 3-18 years with well controlled asthma. Serum total 25(OH)D and FOT parameters including respiratory resistance at 5 Hz (R5), at 20 Hz (R20), respiratory reactance at 5 Hz (X5) and area of reactance (ALX), resonance frequency (Fres) were evaluated at baseline, 1 month and 3 months. Vitamin D deficient patients (serum total 25(OH)D < 20 ng/ml) were randomized to receive treatment with vitamin D2 (tVDD) or placebo (pVDD). Non-vitamin D deficient patients (nVDD) received placebo as a control group., Results: A total of 84 children were recruited, 43 patients in nVDD group, 20 in tVDD group and 21 in pVDD group. There were no significant differences in age, sex, height and weight among groups. There were no significant differences of FOT parameters among groups at all visits. There was a trend toward decrease in R5/R20 from baseline to 1 month and 3 months visit in all groups, but the statistically significant improvement was observed only in nVDD group. Serum 25(OH)D showed no correlation with % predicted of FOT measures., Conclusions: Vitamin D treatment in asthmatic children who had vitamin D deficiency may have no short term beneficial effect on pulmonary function assessed by FOT. Vitamin D supplementation in all asthmatic patient needs further study.

Purpose: This study aimed to evaluate the associations between dyslipidemia and pulmonary function parameters assessed by spirometry and the forced oscillation technique in asthmatic children., Methods: Asthmatic children (5-18 years old) had fasting serum lipid profiles including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) measured. Pulmonary function tests were assessed by spirometry and the forced oscillation technique (FOT)., Results: One hundred forty-one asthmatic children were enrolled with a mean (SD) age of 11.82 (3.38) years. Eighty-eight (62.4%) children were boys, 64 (45.4%) had dyslipidemia, and 20 (14.2%) were obese. Among the children with dyslipidemia, a high LDL-C concentration (65.6%) was the most common form of dyslipidemia, followed by high TC (57.8%), high TG (35.9%), and low HDL-C concentrations (15.6%). Multivariable analysis showed significant associations between HDL-C concentrations and respiratory resistance at 5 Hz (R 5 ) and respiratory resistance at 20 Hz (R 20 ), and TC concentrations were modestly associated with reactance at 5 Hz (X 5 ), the frequency of resonance (Fres), and the area of reactance (ALX). Asthmatic children who had high LDL-C concentrations had a significantly higher expiratory phase R 5 , whole breath R 20 , and expiratory phase R 20 than those in children with normal LDL-C concentrations., Conclusion: This study suggests an association of blood cholesterol, especially HDL-C and LDL-C, and respiratory resistance measured by the FOT, irrespective of the obesity status. An intervention for improving LDL-C and HDL-C concentrations may be beneficial on lung function parameters in asthmatic children., Clinical Trial Registration: TCTR20200305005; date of registration: 03-04-2020 (retrospectively registered)., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: House dust mites (HDM) are the major causative allergen for allergic rhinitis. The sole disease-modifying therapy for allergic rhinitis is allergen immunotherapy (AIT). Rush immunotherapy is the accelerated build-up schedules to reach the target maintenance dose., Objective: To evaluate the kinetic changes of peripheral blood CD4+CD25+FOXP3+ regulatory T cells (Treg) and serum cytokines in children undergoing 2-day modified rush HDM AIT., Methods: Children aged 5-15 years with allergic rhinitis were enrolled for a 2-day modified rush HDM AIT. Peripheral blood CD4+CD25+FOXP3+ Treg, serum interleukin (IL)-4, IL-13, interferon-γ, and IL-10 were measured at baseline, finishing rush, achieving maintenance dose, 6 months, and 12 months after reaching maintenance dose. Specific IgE (sIgE) to HDM was evaluated at baseline and 12 months after getting the maintenance dose. Rhinitis symptoms were assessed daily using a daily card., Results: A total of 12 children with a mean age of 13 years were enrolled. Rhinitis symptom-free days per month increased significantly after reaching the maintenance dose compared to baseline (from 9.5 days to 19.5 days, p = 0.002), and the maximum improvement was seen at 1 year. The levels of Treg were significantly increased at 6 months after maintenance dose compared to baseline level (6.27%±1.63% vs. 3.83%±1.80%, p < 0.001). After treatment, there were significantly decreased serum IL-13 at 1 year after maintenance but no significant changes in sIgE to HDM. The systemic reaction during AIT occurred 7 episodes from 119 shots (5.9%)., Conclusion: Two-day modified rush HDM AIT provides acceptable systemic reactions and increases the number of CD4+CD25+FOXP3+ Treg in children., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Introduction: Wheezing is a common problem in preschool children. Currently, there are no reliable biomarkers that can predict subsequent wheezing in preschool children. This study aimed to compare serum periostin levels between preschool children with and without recurrent wheezing and investigate its utility for predicting acute wheezing exacerbation., Methods: Children aged 2-5 years with recurrent wheezing and healthy control children were enrolled. They were evaluated for serum periostin level at enrollment and subsequently followed for wheezing episodes in a 1-year prospective study., Results: A total of 122 children were enrolled. Children in the recurrent wheezing group (n = 80) had a greater median serum periostin level (1,122.32 pg/mL [<10-6,978.93]) than that of the healthy control group (n = 40) (<10 pg/mL [<10-2,116.69]), p value = 0.006. After 1-year follow-up, subjects who experienced subsequent wheezing exacerbation episodes had a greater median of periostin level (5,321 pg/mL) compared with those with no exacerbation (<10 pg/mL), p value = 0.014. ROC curve analysis revealed that the level of serum periostin >1,200 pg/mL, corresponding to 78.9% sensitivity and 64.6% specificity, with an AUC of 0.701, p value = 0.009, could be a predictor for acute wheezing exacerbation within 1 year. Besides, subjects with serum periostin >1,200 pg/mL had greater odds of subsequent wheezing episodes compared with those with lower levels of serum periostin (adjusted odds ratio 10.0, 95% confidence interval: 2.3-43.5)., Conclusions: Preschool children with recurrent wheezing have a greater serum periostin level than healthy control. Serum periostin may be a valuable biomarker for predicting acute wheezing exacerbations in the following year., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: The authors declare no conflict of interest.

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: The reference values of Forced Oscillation Technique (FOT) parameters of the inspiratory and expiratory phase for preschool children have not yet been established., Objective: To evaluate FOT measures in Thai healthy preschool children., Methods: Preschool children, aged 3-6 years, were screened. Children who were positive for the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire for asthma, positive family history of allergic diseases, recent lower respiratory tract infections, and environmental tobacco smoke were excluded. FOT parameters, including resistance (Rrs), reactance (Xrs), frequency of resonance (Fres) and area of reactance (ALX), were measured., Results: A total of 390 healthy children with the mean age of 5.1 ± 0.9 years were enrolled. FOT was successfully performed in 378 children (96.9%). The mean (SD) for the whole breath (WB) resistance at 5Hz (R5), 20 Hz (R20) and R5-20 were 11.49 (2.69) cmH2O/L/s, 9.46 (2.19) cmH2O/L/s and 2.02 (0.82) cmH2O/L/s, respectively. The median (IQR) for WB reactance at 5Hx (X5), Fres and ALX were -1.51 (-2.37 to -0.96) cmH2O/L/s, 11.17 (8.50-15.65) Hz, and 7.53 (3.72-14.32) cmH2O/L/s, respectively. Significantly difference in WB R5, R20, X5, Fres and ALX between male and female children were demonstrated. The expiratory phase R5, R20, R5-20 were significantly higher than those of the inspiratory phase (p < 0.001). There are significant correlations between the height and FOT parameters. Reference curve for the FOT parameters was generated based on height using the lambda-mu-sigma (LMS) method., Conclusions: Reference curve of FOT parameters measured in healthy preschool children were demonstrated. Majority of preschool children could perform FOT method.

Background: Children with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need., Methods: Eighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant., Results: Proteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1β was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1β may be involved with neuroinflammation., Conclusions: Alterations in plasma haptoglobin, IFN-γ, and IL-1β were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization., Objective: To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard., Methods: Children aged 5-18 years with rhinitis symptoms more than 6 times in the past year were enrolled. SPT to 13 common aeroallergens, serum for Phadiatop, and NPT to Dermatophagoides pteronyssinus (Der p) were performed. NPT to mixed cockroach (CR) were performed in children who had CR sensitization and negative NPT to Der p. Children who had a disagreement between the result of SPT and Phadiatop or having negative results were evaluated for specific IgE (sIgE) to common aeroallergens., Results: One hundred-forty children were enrolled with the mean age of 9.8 ± 3 years, 56% were male. Of 92 children (65.7%) with positive SPT to any aeroallergens, 88 children (95.6%) were sensitized to house dust mite (HDM). NPT showed positive results in 97 children (69.3%). Of 48 children who showed negative SPT, 4 children (8.3%) had sIgE to aeroallergens but NPT was positive in 1 child. Eighty-eight children (62.9%) had positive tests for Phadiatop and 4 (4.5%) of them had negative results for NPT to Der p. Among 52 children who had negative results for Phadiatop, 4 children (7.6%) had sIgE to aeroallergens but NPT was positive in 2 children (3.8%). SPT and Phadiatop showed 94.2% agreement: with Kappa 0.876, p < 0.001. Using NPT as a comparative standard for diagnosis for AR, SPT showed a sensitivity of 89.6% and specificity of 88.3% and Phadiatop provided the sensitivity of 88.6% and specificity of 95.3%., Conclusions: SPT to aeroallergen and Phadiatop have good and comparable sensitivity and specificity for the diagnosis of AR in children.

X-linked hyper IgM (X-HIGM) syndrome is a combined immunodeficiency disease caused by mutations in the CD40LG gene, leading to a defect in immunoglobulin (Ig) class switching recombination and effector T-cell responses. X-HIGM patients usually present in early life with pyogenic bacterial and opportunistic infections. Herein, we report a previously healthy 13-year-old Thai boy who first presented with cutaneous and meningoencephalitis cryptococcosis. Whole-exome sequencing revealed that he was hemizygous for a missense c.514T>C (p.Tyr172His) in CD40LG, confirming a diagnosis of X-HIGM. This report demonstrates that X-HIGM could have an age of onset in teens and systemic cryptococcosis could be its presenting symptoms.

Purpose: Phenytoin (PHT) is a common causative drug for severe cutaneous adverse drug reactions (SCARs) in children. SCARs, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are associated with a variation in HLA genotypes. Blood screening for specific HLA allele before PHT prescription would help in the reduction of the incidence of PHT induced SCARs. This study was to investigate the association between variations of HLA genotypes and PHT induced SCARs in Thai children., Methods: Cases were Thai children aged between 0-18 years diagnosed with SCARs from PHT. Control groups were Thai children of corresponding age who had taken PHT for a least 12 weeks without any hypersensitivity reaction and healthy population controls. Blood samples from both groups were collected for HLA genotyping using a reverse-sequence specific oligonucleotide (SSO) probes method. Carrier rates of HLA alleles were compared between 22 cases (17 DRESS and 5 SJS-TEN), 60 tolerant controls and 649 population controls., Results: Two HLA alleles includingHLA-B*51:01 and HLA-C*14:02 were significantly associated with PHT induced DRESS (OR 5.83; 95 % CI 1.36-25.00, p = 0.022 and OR 5.85; 95 % CI 1.16-29.35, p = 0.039). HLA-B*38:02 was significantly associated with PHT induced SJS-TEN (OR12.67; 95 % CI 1.50-106.89, p = 0.044). Haplotype analysis demonstrated the association of HLA haplotype A*11:01-B*51:01-C*14:02 and PHT induced DRESS compared to tolerant controls and the healthy population control group (OR 8.92; 95 % CI 1.47-54.02, p = 0.019, and OR 10.2; 95 % CI 3.04-34.21, p = 0.002). HLA haplotype B*38:02-C*07:01 in PHT induced SJS-TEN was significantly higher than those in tolerant controls and the healthy population control group (40 % vs 3.3 % vs 0.3 %; OR 19.33; 95 % CI 1.98-188.59, p = 0.027 and OR 215.67; 95 % CI 22.40-2076.04, p = 0.0003. HLA-B*15:02 was not associated with PHT induced SCARs., Significance: An association betweenHLA-B*51:01 and HLA-C*14:02 and PHT induced DRESS and HLA-B*38:02 and PHT induced SJS-TEN has been demonstrated in Thai children., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Mosquito allergy is common in tropical countries but remains under-diagnosed. This may be due to the lack of knowledge and diagnostic tools for tropical mosquito allergens., Objective: We aimed to characterize allergens from tropical mosquito species and investigate IgE reactivity in mosquito-allergic patients to the salivary gland proteins from these mosquitoes., Methods: Salivary gland extract (SGE) from 4 mosquito species, highly distributed in the tropics, including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles dirus b, were studied. SGE-specific IgE and IgG ELISA were developed, and serum from 64 mosquito-allergic and 22 non-allergic healthy control subjects was assayed. Further investigations using IgE-immunoblots followed by mass spectrometry analysis were performed to identify and characterize allergens from each species., Results: Mosquito-allergic subjects have detectable serum IgE to SGE derived from local mosquito species, while the IgE levels to Aedes communis using commercially available ELISA were mostly minimal. IgE-immunoblot analysis and mass spectrometry identified 5 novel mosquito allergens from A. albopictus (Aed al 2, Aed al 3), C. quinquefasciatus (Cul q 2.01, Cul q 3), and A. dirus b (Ano d 2). Interestingly, 4 of the 5 new allergens belong to the D7 protein family., Conclusions & Clinical Relevance: Five novel allergens from 3 tropical mosquito species were characterized. The majority of mosquito-allergic subjects who live in the tropics have IgE reactivity to these allergens. Our study paves the way for the development of diagnostic tests, component-resolved diagnostics, and future immunotherapy for mosquito allergy in tropical countries., Competing Interests: Authors declared no conflict of interest., (© 2020 The Authors.)