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

Rapid Low-Cost Microarray-Based Genotyping for Genetic Screening in Primary Immunodeficiency

Background: Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods: Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), w

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

Analysis of the infant gut microbiome reveals metabolic functional roles associated with healthy infants and infants with atopic dermatitis using metaproteomics

The infant gut microbiome consists of a complex and diverse microbial community. Comprehensive taxonomic and metabolic functional knowledge about microbial communities supports medical and biological applications, such as fecal diagnostics. Among the omics approaches available for the investigation of microbial communities, metaproteomics-based analysis is a very powerful approach; under this method, the activity of microbial communities is explored by investigating protein expression within a sample. Through use of metaproteomics, this study aimed to investigate the microbial community composition of the infant gut to identify different key proteins playing metabolic functional roles in the microbiome of healthy infants and infants with atopic dermatitis in a Thai population-based birth cohort. Here, 18 fecal samples were analyzed by liquid chromatography-tandem mass spectrometry to conduct taxonomic, functional, and pathway-based protein annotation. Accordingly, 49,973 annotated proteins out of 68,232 total proteins were investigated in gut microbiome samples and compared between the healthy and atopic dermatitis groups. Through differentially expressed proteins (DEPs) analysis, 130 significant DEPs were identified between the healthy and atopic dermatitis groups. Among these DEPs, eight significant proteins were uniquely expressed in the atopic dermatitis group. For instance, triosephosphate isomerase (TPI) in Bifidobacteriaceae in the genus Alloscardovia and demethylmenaquinone methyltransferase (DMM) in Bacteroides were shown to potentially play metabolic functional roles related to disease. PPI network analysis revealed seven reporter proteins showing metabolic alterations between the healthy and disease groups associated with the biosynthesis of ubiquinone and other quinones as well as the energy supply. This study serves as a scaffold for microbial community-wide metabolic functional studies of the infant gut microbiome in relation to allergic disease

Pediatric Prediction Model for Low Immunoglobulin G level based on Serum Globulin and Illness Status

Hypogammaglobulinemia is a condition that requires prompt diagnosis and treatment. Unfortunately, serum immunoglobulin (Ig) measurements are not widely accessible in numerous developing countries. Serum globulin is potentially the best candidate for screening of low IgG level (IgGLo) due to its high availability, low cost, and rapid turnover time. However, multiple factors may influence the probability of prediction. Our study aimed to establish a simple prediction model using serum globulin to predict the likelihood of IgGLo in children. For retrospective data of patients who were suspected of having IgGLo, both serum IgG and globulin were simultaneously collected and measured. Potential factors interfering with serum globulin and IgG levels were investigated for their impact using bivariate binary logistic regression. A multivariate binary logistic regression was used to generate a formula and score to predict IgGLo. We obtained 953 samples from 143 pediatric patients. A strong positive correlation between serum globulin and IgG levels was observed (r=0.83, p < 0.001). A screening test model using serum globulin and illness status was constructed to predict IgGLo. The formula for predicting IgGLo was generated as follows; Predicted score = (2 x globulin (g/dl)) – illness condition score (well=0, sick=1). When the score was <4, the patient has the probability of having IgGLo with a sensitivity of 0.78 (0.71, 0.84), a specificity of 0.71 (0.68, 0.74), PPV of 0.34 (0.29, 0.40) and NPV of 0.94 (0.92, 0.96). This formula will be useful as rapid and inexpensive screening tool for early IgGLo detection, particularly in countries/locations where serum IgG measurement is inaccessible

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

Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level