Evaluating the efficacy and safety of pozelimab in patients with CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy disease: an open-label phase 2 and 3 study.

BACKGROUND: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is an ultra-rare genetic disorder characterised by intestinal lymphatic damage, lymphangiectasia, and protein-losing enteropathy caused by overactivation of the complement system. We assessed the efficacy and safety of pozelimab, an antibody blocking complement component 5. METHODS: This open-label, single-arm, historically controlled, multicentre phase 2 and 3 study evaluated ten patients with CHAPLE disease. This study was conducted at three hospitals in Thailand, Türkiye, and the USA. Patients aged 1 year or older with a clinical diagnosis of CHAPLE disease and a CD55 loss-of-function variant identified by genetic analysis and confirmed by flow cytometry or western blot of CD55 from peripheral blood cells were eligible for this study. Patients received a single intravenous loading dose of pozelimab 30 mg per kg of bodyweight, followed by a once-per-week subcutaneous dose over the treatment period based on bodyweight at a concentration of 200 mg/mL as either a single injection (<40 kg bodyweight) or two injections (≥40 kg bodyweight). The primary endpoint was proportion of patients with serum albumin normalisation with an improvement in active clinical outcomes and no worsening in inactive clinical outcomes (frequency of problematic abdominal pain, bowel movement frequency, facial oedema severity, and peripheral oedema severity) at week 24 compared with baseline, assessed in the full analysis set. This study is registered with ClinicalTrials.gov (NCT04209634) and is active but not recruiting. FINDINGS: 11 patients were recruited between Jan 27, 2020, and May 12, 2021, ten of which were enrolled in the study and included in the analysis populations. The efficacy data corresponded to all patients completing the week 48 assessment and having at least 52 weeks of treatment exposure, and the safety data included an additional 90 days of follow-up and corresponded to all patients having at least 72 weeks of treatment. Patients were predominantly paediatric (with a median age of 8·5 years), and originated from Türkiye, Syria, Thailand, and Bolivia. Patients had markedly low weight-for-age and stature-for-age at baseline, and mean albumin at baseline was 2·2 g/dL, which was considerably less than the local laboratory reference range. After pozelimab treatment, all ten patients had serum albumin normalisation and improvement with no worsening in clinical outcomes. There was a complete inhibition of the total complement activity. Nine patients had adverse events; two were severe events, and one patient had an adverse event considered related to pozelimab. INTERPRETATION: Pozelimab inhibits complement overactivation and resolves the clinical and laboratory manifestations of CHAPLE disease. Pozelimab is the only currently approved therapeutic drug for patients with this life-threatening, ultra-rare condition. In patients with protein-losing enteropathy where known causes have been excluded, testing for a CD55 deficiency should be contemplated. A diagnosis of CHAPLE disease should lead to early consideration of treatment with pozelimab. FUNDING: Regeneron Pharmaceuticals and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

A germline STAT6 gain-of-function variant is associated with early-onset allergies.

BACKGROUND: The signal transducer and activator of transcription 6 (STAT6) signaling pathway plays a central role in allergic inflammation. To date, however, there have been no descriptions of STAT6 gain-of-function variants leading to allergies in humans. OBJECTIVE: We report a STAT6 gain-of-function variant associated with early-onset multiorgan allergies in a family with 3 affected members. METHODS: Exome sequencing and immunophenotyping of T-helper cell subsets were conducted. The function of the STAT6 protein was analyzed by Western blot, immunofluorescence, electrophoretic mobility shift assays, and luciferase assays. Gastric organoids obtained from the index patient were used to study downstream effector cytokines. RESULTS: We identified a heterozygous missense variant (c.1129G>A;p.Glu377Lys) in the DNA binding domain of STAT6 that was de novo in the index patient's father and was inherited by 2 of his 3 children. Severe atopic dermatitis and food allergy were key presentations. Clinical heterogeneity was observed among the affected individuals. Higher levels of peripheral blood TH2 lymphocytes were detected. The mutant STAT6 displayed a strong preference for nuclear localization, increased DNA binding affinity, and spontaneous transcriptional activity. Moreover, gastric organoids showed constitutive activation of STAT6 downstream signaling molecules. CONCLUSIONS: A germline STAT6 gain-of-function variant results in spontaneous activation of the STAT6 signaling pathway and is associated with an early-onset and severe allergic phenotype in humans. These observations enhance our knowledge of the molecular mechanisms underlying allergic diseases and will potentially contribute to novel therapeutic interventions.

Orodental health status of patients with inborn errors of immunity.

BACKGROUND: Various orodental problems affect patients with inborn errors of immunity (IEI), but there are limited studies on these issues. AIM: To study orodental status and its confounding factors in patients with IEI. DESIGN: Caries, enamel defects, gingival, and soft tissue conditions were examined. Data on patient characteristics, dental hygiene habits, dental attendance, and household income were collected. Statistical analysis and logistic regression were performed. RESULTS: Forty-five participants with a mean age of 9.20 ± 6.41 years were included. Almost all participants had gingivitis (42 of 45; 93.3%), whereas a small number had periodontitis (five of 45; 11.1%). Calculus was found in 33 (73.3%) and caries in 30 (66.7%). Mucosal ulcers, enamel defects, and candidiasis were observed in 23 of 45 (51.1%), 16 of 43 (37.2%), and six of 43 (14.0%), respectively. Chances of having caries, moderate-to-severe gingivitis, periodontitis, calculus, and ulcers increased with age. Taking antibiotics in the last two months increased the risk of caries by five times. Lower income increased the risk of calculus deposit by nine times. CONCLUSION: Gingivitis, calculus, caries, and mucosal ulcers were the most common orodental findings in patients with IEI. Antibiotics increased the risk of caries, and low-income children had higher calculus accumulation.

Outcomes of young children hospitalized with acute wheezing.

BACKGROUND: Wheezing in preschool children is a common symptom. OBJECTIVE: The study aimed to determine an incidence of recurrent wheezing among young children who had been hospitalized with acute wheezing after 12 months. Factors associated with recurrent wheezing were explored. METHODS: A longitudinal study was conducted among 236 children, aged between 6 months and 5 years, who were hospitalized with acute wheezing in 4 hospitals located in Bangkok and adjacent provinces, Thailand. Demographics, house environments and clinical characteristic data were collected at entry. Serum specific IgE levels against common food and inhalant allergens and serum 25-hydroxyvitamin D (25OHD) concentrations were measured. RESULTS: At entry, the mean age was 24.4 months (SD = 15.7 months). Of 236 hospitalized children with acute wheezing, ninety-four cases (39.8%) were the first wheezing episode of life. By laboratory results, 197 (83.5%) and 56 (23.7%) children were atopic and had vitamin D insufficiency respectively. There were 195 cases completely followed for 12 months. One-year risk of emergency visits and hospitalization due to recurrent wheezing were 49.7% and 23.1% respectively. By multivariable analysis, being the second born child or more, vitamin D insufficiency, "ever wheeze", and allergic rhinitis were significantly associated with recurrent wheezing within 12 months with adjusted odds ratios of 2.5 (95% confidence interval: 1.3-5.3), 2.3 (95% confidence interval: 1.1-4.4), 1.9 (95% confidence interval: 1.2-3.5), and 1.6 (95% confidence interval: 1.3-2.9) respectively. CONCLUSIONS: Being the second born child or more, vitamin D insufficiency, ever wheeze, and allergic rhinitis were significant risks of recurrent wheezing.

Characteristics and Laboratory Findings of Food-Induced Anaphylaxis in Children: Study in an Asian Developing Country.

INTRODUCTION: Food allergy is the major cause of pediatric anaphylaxis. Characteristics and triggers may be different in different geographical regions. Studies focusing on food-induced anaphylaxis (FIA) in Asian developing countries are limited. Our study aimed to study characteristics of FIA in a tertiary care center in an Asian developing country. METHODS: Retrospective review of pediatric anaphylaxis admission and outpatient visit at a tertiary care hospital in Bangkok, Thailand during 2008-2018 was performed. Data regarding clinical presentation, place reaction occurred, time of onset, investigations (serum tryptase, specific immunoglobulin E, and skin test), treatment, and follow-up periods were collected. RESULTS: One hundred seventy-four anaphylaxis admission records of which 61 episodes of FIA were retrieved. Data from outpatients visit consisted of 17 patients. Most patients were male (76.7%). The median age was 7.1 years (interquartile range 1.9-12.4). The major causes of FIA were shrimp/shellfish (37%), wheat (15.1%), and cow's milk (11%). Food causing anaphylaxis varied according to age-group: infants had anaphylactic reactions to egg, wheat, and cow's milk, preschools to wheat and peanut, and older children to shrimp/shellfish. Cutaneous manifestations occurred in all patients, followed by lower respiratory tract symptoms (83.6%) and gastrointestinal symptoms (50.8%). There was no biphasic anaphylaxis reported. Elevated serum tryptase was found in only 4 patients (7%). CONCLUSION: Recognizing characteristics of pediatric FIA is crucial. The common causes of FIA in our study in Asian children were egg in infants, wheat and peanut in preschool children, and shrimp/shellfish in school-age children and adolescents. Skin manifestation presented in all patients with FIA.

MetGEMs Toolbox: Metagenome-scale models as integrative toolbox for uncovering metabolic functions and routes of human gut microbiome.

Investigating metabolic functional capability of a human gut microbiome enables the quantification of microbiome changes, which can cause a phenotypic change of host physiology and disease. One possible way to estimate the functional capability of a microbial community is through inferring metagenomic content from 16S rRNA gene sequences. Genome-scale models (GEMs) can be used as scaffold for functional estimation analysis at a systematic level, however up to date, there is no integrative toolbox based on GEMs for uncovering metabolic functions. Here, we developed the MetGEMs (metagenome-scale models) toolbox, an open-source application for inferring metabolic functions from 16S rRNA gene sequences to facilitate the study of the human gut microbiome by the wider scientific community. The developed toolbox was validated using shotgun metagenomic data and shown to be superior in predicting functional composition in human clinical samples compared to existing state-of-the-art tools. Therefore, the MetGEMs toolbox was subsequently applied for annotating putative enzyme functions and metabolic routes related in human disease using atopic dermatitis as a case study.

Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort.

BACKGROUND: Inborn errors of immunity (IEI) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunologic, and genetic features of Thai pediatric patients with IEI. The use of whole-exome sequencing (WES) in diagnosis and clinical decision making was also assessed. METHODS: Thirty six unrelated patients with clinical and laboratory findings consistent with IEI were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. RESULTS: The median age of disease onset was 4 months (range: 1 month to 13 years), and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). CONCLUSION: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in IEI genes were identified. The clinical usefulness of WES in IEI was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?

BACKGROUND: Neanderthals were a species of archaic humans that became extinct around 40,000 years ago. Modern humans have inherited 1-6% of Neanderthal DNA as a result of interbreeding. These inherited Neanderthal genes have paradoxical influences, while some can provide protection to viral infections, some others are associated with autoimmune/auto-inflammatory diseases. OBJECTIVE: We aim to investigate whether genetic variants with strong detrimental effects on the function of the immune system could have potentially contributed to the extinction of the Neanderthal population. METHODS: We used the publically available genome information from an Altai Neanderthal and filtered for potentially damaging variants present in genes associated with inborn errors of immunity (IEI) and checked whether these variants were present in the genomes of the Denisovan, Vindija and Chagyrskaya Neanderthals. RESULTS: We identified 24 homozygous variants and 15 heterozygous variants in IEI-related genes in the Altai Neanderthal. Two homozygous variants in the UNC13D gene and one variant in the MOGS gene were present in all archaic genomes. Defects in the UNC13D gene are known to cause a severe and often fatal disease called hemophagocytic lymphohistiocystosis (HLH). One of these variants p.(N943S) has been reported in patients with HLH. Variants in MOGS are associated with glycosylation defects in the immune system affecting the susceptibility for infections. CONCLUSIONS: Although the exact functional impact of these three variants needs further elucidation, we speculate that they could have resulted in an increased susceptibility to severe diseases and may have contributed to the extinction of Neanderthals after exposure to specific infections.

COVID-19 in children: Heterogeneity within the disease and hypothetical pathogenesis.

The disease course of coronavirus disease 2019 (COVID-19) is usually mild and self-limiting in previously healthy children, but they may also develop severe disease. Severe COVID-19 infection is especially observed in very young children or those with underlying comorbidities. Moreover, a multisystem inflammatory syndrome that mimics the Kawasaki disease shock syndrome can develop in children that are genetically predisposed to displaying an overactive immune response to SARS-CoV-2 infection. In this review, we describe the clinical phenotypes of mild and severe COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We also discuss the possible immunobiological mechanisms that may be involved in the protection of children against COVID-19 and the development of multisystem inflammatory syndrome.

Prevalence and severity of asthma, rhinoconjunctivitis and eczema in children from the Bangkok area: The Global Asthma Network (GAN) Phase I.

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

Prevalence and risk factors of allergic rhinitis in children in Bangkok area.

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

Comparison of specific IgE detection by immunoblotting and fluorescence enzyme assay with in vivo skin prick test.

BACKGROUND: Diagnostic tools to identify allergens that cause allergic symptom is important part in the care of allergic patients. Detection of causative allergen can be performed by in vivo skin prick test (SPT) or in vitro tests for detection serum specific immunoglobulin E (sIgE). The common methods used are fluorescent enzyme assay and immunoblotting assay. OBJECTIVE: We aim to evaluate performance of the two sIgE determination systems, immunoblotting assay (Euroline) and fluorescent enzyme assay (ImmunoCAP) in comparison with SPT. METHODS: Two hundred and two participants with allergic diseases were enrolled. Sensitization to common allergens was identified using skin prick test and serum specific IgE assays with Euroline and ImmunoCAP. Both systems provide the result in the same unit and the same cut-off value (0.35 kUA/L). The specific IgE levels of 4 aeroallergens, 6 food allergens and 3 food allergen components were analyzed to evaluate the performance of both sIgE assays with SPT. RESULTS: When compared with the result of SPT, ImmunoCAP has 63.9-93.2% agreement and Euroline has 68.4-86.2% agreement for allergen detection. Both sIgE assays have significant correlation in measuring sIgE of almost all allergens (r=0.626-0.901, p< 0.001) except for dog. For food allergen components, both sIgE tests have outstanding correlation and agreement (r=0.816-0.952, p< 0.001; agreement =87.0-92.9%, respectively). The receiver-operating characteristic curve analysis indicated slight discrepancy of both sIgE assays. CONCLUSIONS: Both sIgE determination systems demonstrate fair to good performance when compared to SPT depending on type of allergens. The two sIgE determination systems had favorable correlation and agreement.

The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity.

BACKGROUND: The in-depth characterization of the recently identified house dust mite (HDM) major allergen Der p 23 requires the production of its recombinant counterpart because the natural allergen is poorly extractable from fecal pellets. This study aimed to provide a detailed physico-chemical characterization of recombinant Der p 23 (rDer p 23) as well as to investigate its IgE reactivity in a cohort of HDM-allergic patients from Thailand. METHODS: Purified rDer p 23, secreted from recombinant Pichia pastoris, was characterized by mass spectrometry and circular dichroism analyses as well as for its chitin-binding activity. The IgE-binding frequency and allergenicity of Der p 23 were determined by ELISA and RBL-SX38 degranulation assays, respectively. RESULTS: Purified intact rDer p 23 carried O-mannosylation and mainly adopted a random coil structure. Polyclonal antibodies to rDer p 23 can detect the corresponding natural allergen (nDer p 23) in aqueous fecal pellet extracts, suggesting that both forms of Der p 23 share common B-cell epitopes. Despite its homologies with chitin-binding proteins, both natural Der p 23 and rDer p 23 were unable to interact in vitro with chitin matrices. Of 222 Thai HDM-allergic patients tested, 54% displayed Der p 23-specific IgE responses. Finally, the allergenicity of rDer p 23 was confirmed by the degranulation of rat basophil leukemia cells. CONCLUSION: Our findings highlighted important levels of Der p 23 sensitizations in Thailand. Our study clearly suggested that rDer p 23 is likely more appropriate for HDM allergy component-resolved diagnosis than HDM extracts.

Dust mite infestation in cooking flour: experimental observations and practical recommendations.

BACKGROUND: The first documented case of oral mite anaphylaxis has recently been reported in Thailand, with mites possibly originating from cooking flour. OBJECTIVE: Our study was designed to assess the effects of cooking flours enhancement and storage conditions on mite proliferation and to provide practical recommendations to prevent mite anaphylaxis. METHODS: In a factorial experiment, six commercial brands of cooking flours were selected and either inoculated or set free of mites and stored in one of the four containers chosen for the study: original package, plastic bag, plastic box and glass bottle. The resulting experimental units where then stored at either room temperature or in a refrigerator (+4C). In order to determine levels of Der f 1 allergen, 0.1 gram of flour was sampled from each experimental unit and tested by ELISA. Sampling was carried out immediately after inoculation and subsequently at week 2, 4, 6, 8, 10, 12, 16 and 20. RESULTS: Levels of Der f 1 allergen in the inoculated samples increased significantly in all conditions 6 weeks after inoculation (p <0.001) and reached the highest levels at week 8. While experimental units left at room temperature showed higher levels of mite growth (p <0.001), no statistical differences were found among types of containers. The highest amount of Der f 1 was observed for Gogi, followed by Gold Label, tempura flour, corn flour, wheat flour and tapioca starch, respectively (p <0.01). CONCLUSIONS: In the context of our experiment, mites preferably grew in cooking flours containing high amounts of wheat at room temperature, particularly after 8 week of storage. According to our results, we thus advise to keep household cooking flour refrigerated and while the type of container does not matter, storage should not exceed 20 weeks.

Component-resolved diagnostics for the evaluation of peanut allergy in a low-prevalence area.

BACKGROUND: Major allergenic components of peanut from distinct geographical regions are widely dispersed. Most of the diagnostic studies are from countries with a high prevalence. There have been only few reports of allergen component sensitizations from countries with a low prevalence of peanut allergy. We aimed to investigate roles of component-resolved diagnostic (CRD) to differentiate peanut allergy and peanut tolerance in the Asian population from a country with low prevalence of peanut allergy. METHODS: Participants with peanut sensitization were enrolled. Clinical reactions were determined. Skin prick test (SPT) and specific IgE (sIgE) to peanut and related allergen components were performed. RESULTS: Forty subjects with peanut sensitization were included. The mean wheal sizes of SPT and peanut sIgE were not good predictors for differentiating peanut reactions. SIgE to rAra h 2 was more often found in patients with peanut allergy and anaphylaxis. sIgE to rAra h 9 was also more frequent in the peanut-allergic group but not related to severe reactions. In the peanut-tolerant group, despite positive SPT and/or sIgE to peanut, 90% had negative sIgE to rAha h 2 and rAra h 9. Combining rAra h 2 and rAra h 9 resulted in high performance of the test with sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 90%, 0.89, and 0.86, respectively. The ratio between rAra h 2 sIgE to peanut sIgE of 0.6 can be helpful in predicting patients who will develop severe reaction. SIgE to cross-reactive carbohydrate determinants (CCD) was exclusively found in the peanut-tolerant group (33.3% vs. 0%, p = 0.012). CONCLUSIONS: Our study identifies three allergen components: rAra h 2, rAra h 9, and CCD as important components in the diagnosis of peanut allergy in an Asian country with low prevalence. The ratio between rArah h 2 sIgE to peanut sIgE can be used for predicting patients who will develop anaphylaxis.

Cost-effectiveness of therapeutic infant formulas for cow's milk protein allergy management.

Cow's milk protein allergy (CMPA) is children's most common food allergy. Therapeutic infant formulas for CMPA lead to symptom-free and potentially benefit early tolerance induction and reducing the allergic march in non-breastfed babies. This study assessed the cost-effectiveness of CMPA management with different therapeutic infant formulas in Thailand, which may reflect situations in developing countries throughout Asia. An analytic decision model was developed to simulate the occurrence of eczema, urticaria, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA over 36 months. Extensively hydrolyzed casein formula with added probiotic Lacticaseibacillus rhamnosus (previously Lactobacillus rhamnosus) strain GG (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), soy protein-based formula (SPF), and amino acid formula (AAF) were compared from the healthcare payer perspective. The results from a prospective cohort study were used for comparative effectiveness measures, while local experts were interviewed to estimate the healthcare resource used in the management of CMPA. The costs of healthcare resources were obtained from standard, publicly available sources. The direct medical cost of CMPA management was lowest for EHCF+LGG (USD 1,720), followed by SPF (USD 2,090), EHWF (USD 2,791), and AAF (USD 7,881). Compared with other formulas, EHCF+LGG was expected to save USD 370 (SPF), USD 1,071 (EHWF), and USD 6,161 (AAF) in the total cost of CMPA management over 36 months. In conclusion, EHCF+LGG was the most cost-effective strategy for managing non-breastfed infants with CMPA. This strategy was associated with more children developing immune tolerance to cow's milk and being symptom-free, contributing to overall cost-saving potential.

Feeding Difficulties and Feeding Behaviors of Thai Children with Cow's Milk Protein Allergy.

Background: Cow's milk protein allergy (CMPA) is a common food allergy in infants and young children and may be a risk factor for feeding difficulties. Studies exploring feeding difficulties and feeding behaviors in Thai children with CMPA are scarce. Objectives: To determine the prevalence of feeding difficulties and feeding behaviors in Thai children with CMPA compared to healthy controls. Methods: A cross-sectional study was performed comparing children aged 1-6 years old diagnosed with CMPA and had eliminated cow's milk for at least 4 months with age-matched healthy children. Feeding difficulties were evaluated using the Montreal Children's Hospital Feeding Scale questionnaire, and feeding behaviors were measured using the Child Eating Behavior Questionnaire (CEBQ). Results: One hundred and twenty-two participants were recruited (30 children with CMPA and 92 controls). The median age of the CMPA and control groups was 31.0 (14.0, 43.3) and 40.0 (28.0, 53.8) months, respectively (p value = 0.01). The CMPA group had lower calcium, phosphorus, and zinc intake than the healthy controls. The prevalence of feeding difficulties between the two groups did not show a significant difference (36.7 vs. 43.5%, p value = 0.70). The slowness in the eating subscale of feeding behaviors exhibited a lower score in the CMPA group than in the healthy group. Feeding difficulties was positively correlated with the desire to drink (ß 3.079, p value = 0.011) but negatively correlated with the enjoyment of food subscale of CEBQ among the CMPA children (ß -10.684, p value < 0.001). Conclusion: Despite a similar prevalence of feeding difficulties between CMPA and healthy children, the CMPA group demonstrated some differences in feeding behaviors. The lower score of enjoyment of food and a higher score of desire to drink correlated with a higher degree of feeding difficulties in the CMPA children. The provision of appropriate nutrition for this group of children should be prioritized.

Exploring Longitudinal Gut Microbiome towards Metabolic Functional Changes Associated in Atopic Dermatitis in Early Childhood.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease that has been associated with changes in gut microbial composition in early life. However, there are limited longitudinal studies examining the gut microbiome in AD. This study aimed to explore taxonomy and metabolic functions across longitudinal gut microbiomes associated with AD in early childhood from 9 to 30 months of age using integrative data analysis within the Thai population. Our analysis revealed that gut microbiome diversity was not different between healthy and AD groups; however, significant taxonomic differences were observed. Key gut bacteria with short-chain fatty acids (SCFAs) production potentials, such as Anaerostipes, Butyricicoccus, Ruminococcus, and Lactobacillus species, showed a higher abundance in the AD group. In addition, metabolic alterations between the healthy and AD groups associated with vitamin production and host immune response, such as biosynthesis of menaquinol, succinate, and (Kdo)2-lipid A, were observed. This study serves as the first framework for monitoring longitudinal microbial imbalances and metabolic functions associated with allergic diseases in Thai children during early childhood.

Transition practice for primary immunodeficiency diseases in Southeast Asia: a regional survey.

Introduction: With increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians' opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries. Methods: We adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries. Results: Regionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer. Discussion and conclusion: Our study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.