Association of fluoride exposure with disease burden and neurodevelopment outcomes in children in South Korea.

BACKGROUND: Community water fluoridation is an effective public health strategy for preventing dental caries, yet. Concerns exist about potential health problems. This study explores associations between tap water fluoride levels and pediatric disease burden, as well as neurodevelopmental outcomes at 6 years of age. METHODS: This nationwide population-based cohort study included children born in Korean cities with and without tap water fluoridation projects, between 2006 and 2012, aiming for a fluoride concentration of 0.8 ± 0.2 mg/L in treated tap water. Data from the National Health Insurance Service were used, spanning from birth to 2018. The relationship between exposure to fluoridated tap water and incidence of 16 childhood diseases that were previously identified as potentially linked to fluoride exposure were examined. Additionally, we evaluated the neurodevelopmental outcomes across various domains, including gross motor, fine motor, cognition, language, social skills, and self-help functions. These assessments were performed using data from a comprehensive national health screening program for children aged six years. RESULTS: A fluoride-unexposed group included 22,881 children, whereas a fluoride-exposed group comprised 29,991 children (52% males). Children in the fluoride-exposed group had a decreased risk of dental caries and bone fractures [hazard ratio (95% confidence interval, CI), 0.76 (0.63-0.93) and 0.89 (0.82-0.93), respectively] and increased risk of hepatic failures [1.85, (1.14-2.98)] compared to those in the unexposed group. Additionally, the risk ratio of abnormal neurodevelopmental screening outcomes increased by 9%, but this was statistically uncertain (95% CI, 0.95-1.26). CONCLUSIONS: Fluoridated tap water was associated with an increased risk of hepatic failure but a decreased risk of bone fractures in children. The association between fluoridated tap water and neurodevelopmental screening outcomes at 6 years remains unclear, highlighting the need for further studies to clarify this association.

KLF15-activated MARCH2 boosts cell proliferation and epithelial-mesenchymal transition and presents diagnostic significance for hepatocellular carcinoma.

PURPOSE: Membrane associated ubiquitin ligase MARCH2 majorly involves in inflammation response and protein trafficking. However, its comprehensive role in hepatocellular carcinoma (HCC) is largely unknown. METHODS: Firstly, multiple bioinformatic analyses were applied to determine MARCH2 mRNA level, its expression comparison in diverse molecular and immune subtypes, and diagnostic value in HCC. Subsequently, RNA-seq, real-time quantitative PCR, immunohistochemistry and cell proliferation assay are used to explore the epithelial-mesenchymal transition (EMT) and proliferation by gene-silencing or overexpressing in cultured HCC cells or in vivo xenograft. Moreover, dual luciferase reporter assay and immunoblotting are delved into verify the transcription factor that activating MARCH2 promoter. RESULTS: Multiple bioinformatic analyses demonstrate that MARCH2 is upregulated in multiple cancer types and exhibits startling diagnostic value as well as distinct molecular and immune subtypes in HCC. RNA-seq analysis reveals MARCH2 may promote EMT, cell proliferation and migration in HepG2 cells. Furthermore, overexpression of MARCH2 triggers EMT and significantly enhances HCC cell migration, proliferation and colony formation in a ligase activity-dependent manner. Additionally, above observations are validated in the HepG2 mice xenografts. For up-stream mechanism, transcription factor KLF15 is highly expressed in HCC and activates MARCH2 expression. CONCLUSION: KLF15 activated MARCH2 triggers EMT and serves as a fascinating biomarker for precise diagnosis of HCC. Consequently, MARCH2 emerges as a promising candidate for target therapy in cancer management.

Consumption of sugar-sweetened beverages before 2 years of age and attention-deficit/hyperactivity disorder.

INTRODUCTION: This study examined the association between sugar-sweetened beverage consumption before the first 24 months of life and attention-deficit/hyperactivity disorder (ADHD). METHODS: A population administrative cohort study was conducted in Korea (2008-2019) using linked national insurance data and a health screening survey. The cohort included 25,305 children in the exposed group with high sugar-sweetened beverage drinks (≥200 ml) and 339,931 in the reference groups (<200 ml) at 24 months of age. The primary outcome was the development of ADHD based on the International Classification of Disease (ICD) codes. Cox proportional model was used to identify the association between sugar-sweetened beverage consumption during early childhood and the later development of ADHD while controlling for multiple risk factors. RESULTS: Over a mean follow-up period of 9.2 years, the incidence rates of ADHD were 29.6 and 23.8 per 10,000 person-years (PY) in the exposed and reference groups, respectively. Compared with the reference group, children consuming high-sugar drinks were at an increased risk of ADHD (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] 1.08-1.27). These associations remained significant even after applying alternative ADHD definitions or adjusting for confounding variables. CONCLUSION: Children who consume sweetened beverages during early childhood are at increased risk of developing ADHD later in life.

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure.

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Age-related effects of Mycoplasma pneumoniae infection and subsequent asthma exacerbation in children.

BACKGROUND: Mycoplasma pneumoniae causes community-acquired pneumonia in children and increases asthma risk, but large studies are lacking. OBJECTIVE: To assess the link between M. pneumoniae infection and to asthma exacerbation, in children with allergies, and age of infection impact. METHODS: This retrospective cohort study analyzed medical records of South Korean children between January 2002 and December 2017. The study's exposure was hospitalization with an M. pneumoniae-related diagnosis, and the outcome was defined as asthma exacerbation, confirmed by hospitalization at least 6 months after M. pneumoniae infection, with alternative validation using asthma diagnosis and systemic steroid prescription records. Hazard ratios (HRs) for asthma exacerbation risk were estimated for the matched cohort using a Cox proportional hazards model stratified by allergic comorbidities. Time-dependent covariates and age-stratified exposure groups were used to calculate odds ratios. RESULTS: The study included 84,074 children with M. pneumoniae infection and 336,296 unexposed children. Follow-up for 12.2 ± 2.3 years found the exposed group had a significant risk of asthma exacerbation (HR 2.86, 95% confidence interval [CI] 2.67-3.06) regardless of allergic comorbidities. The risk was highest (over threefold) in children infected between 24 and 71 months. Sensitivity analysis using an alternative definition of the outcome showed an HR of 1.38 (95% CI 1.35-1.42), further supporting the association between M. pneumoniae infection and asthma exacerbation. CONCLUSION: M. pneumoniae infection was significantly associated with an increased risk of subsequent asthma exacerbation regardless of allergic comorbidities. Further research needed for understanding and confirmation.

Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old-Population-based cohort study.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.

Population-based retrospective cohort study on community-acquired pneumonia hospitalization in children with a ventricular septal defect.

The cohort consisted of 9400 exposed children diagnosed with ventricular septal defect (VSD). The risk of community-acquired pneumonia (CAP) or asthma with VSD was assessed using the Cox proportional hazard model with an inverse probability of treatment weighting. During a mean follow-up of 6.67 years (starting from 12 months after birth), there were 2100 CAP admission cases among exposed patients (incidence rate: 33.2 per 1000 person-years) and 20,109 CAP admission cases among unexposed children (incidence rate: 29.6 per 1000 person-years), with hazard ration of 1.09 (95% CI 1.04-1.14).

Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure.

INTRODUCTION: Studies investigating the potential impact of systemic steroid exposure during early infancy on neurological development in full-term infants with normal birth weight are lacking. METHODS: This population-based administrative cohort study used data of national health insurance and a health-screening program for infants and children and included full-term infants who were born in Korea between 2008 and 2012 with normal birth weight and did not have any specific perinatal or neurodevelopmental diseases. The prescription of systemic steroids within the first 3 months of age was mainly considered. The neurological development of children was assessed using the Korean Development Screening Test (K-DST) at 6 years of age. To balance the baseline characteristics of the control and exposed groups, stabilized inverse probability of treatment weighting with trimming was performed in the main cohort. Ordinal logistic regression was used to assess the association between systemic steroid exposure and unfavorable results in the K-DST. RESULTS: The control and exposure groups had 246,168 and 5,083 children, respectively. The K-DST suggested unfavorable results in 8.1% and 8.6% children in the control and exposure groups, respectively (weighted odds ratio, 95% confidence interval, 1.03, 0.93-1.14). When each domain of the K-DST was considered separately, the risk of unfavorable results in the exposed group was not significantly different from that in the control group. CONCLUSIONS: No significant association was observed between exposure to systemic steroids during early infancy and neurodevelopmental impairment at 6 years of age.

The association between phthalate exposure and pubertal development.

Antiandrogenic effect of phthalates have been reported; however, results regarding the effect of phthalate exposure in pubertal children have been inconsistent. We aimed to investigate the relationship between phthalate exposure and pubertal development, especially whether high molecular weight phthalates (HMWP) and low molecular weight phthalates (LMWP) are differently associated in boys and girls. Urinary phthalate metabolites (4 HMWPs and 3 LMWPs) in Korean children (236 boys and 202 girls, aged 10 to 12 years) were measured. The association between phthalate levels and pubertal development (pubertal stages self-reported by parents and sex steroid levels) was analyzed by generalized linear regression after adjusting for age, body mass index z score, and premature birth and/or low birth weight. Both the highest quartile of HMWP (Q4 vs Q1, adjusted odds ratio [OR], 0.238; 95% confidence interval [CI], 0.090-0.627; p = 0.004) and LMWP (Q4 vs Q1, adjusted OR, 0.373; 95% CI, 0.151-0.918; p = 0.032) were inversely associated with pubertal stages in boys, whereas the highest quartile of LMWP (Q4 vs Q1, adjusted OR, 2.431; 95% CI, 1.024-5.768; p = 0.044) was significantly related to advanced pubertal stages in girls. Testosterone levels in boys were significantly lower at the highest quartile of HMWP (adjusted ß = - 0.251; 95% CI, - 0.476 to - 0.027; p = 0.028). However, in girls, we could not find any significant relationship between HMWP or LMWP and estradiol levels. CONCLUSIONS: Our results suggest that phthalate exposure, especially exposure to the HMWP, may have inverse association with male pubertal development. Further investigation is required to verify the relationship of phthalate exposure and pubertal development in girls. WHAT IS KNOWN: • Exposure to phthalates may have antiandrogenic effects. • Studies on the association between phthalates and pubertal development have yielded inconsistent results. WHAT IS NEW: • Phthalate levels were inversely associated with self-reported pubertal stages in boys. • Exposure to phthalates might have a negative influence on male pubertal development.

Unraveling the link between atopic dermatitis and autoimmune diseases in children: Insights from a large-scale cohort study with 15-year follow-up and shared gene ontology analysis.

BACKGROUND: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. METHODS: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. RESULTS: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23-1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. CONCLUSIONS: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.

A Novel and Highly Efficient Microextraction Method for the Determination of Aflatoxin Precursor Averantin in Fatty Grain Samples.

Averantin (AVN) is an important aflatoxin biosynthetic precursor and has been listed in the screening range of mycotoxins. Herein, a novel ionic liquid-based one-, two-, and three-phase transition microextraction (IL-OTTPTME) method was combined with high-performance liquid chromatography for the extraction and determination of AVN in fatty grain samples. The formation of a homogeneous solution and three-phase system during the IL-OTTPTME process allowed both efficient extraction and coextracted lipid cleanup. Density functional theory calculations and distribution coefficient determination results demonstrated that AVN extraction by IL mainly occurred through hydrogen-bond and π-π interactions. Under optimized conditions, the LOD and LOQ of the proposed method were 0.5 and 1.5 ng/g, respectively. Finally, the method was used to determine AVN in several grains with different fat contents, achieving satisfactory relative recoveries (86.0-107.8%) and RSDs (1.2-6.2%, n = 3).

Simple and rapid ionic liquid-based one-, two-, three-phase transition microextraction for efficient extraction of trace organic pollutants and elimination of lipid co-extractives from fatty food matrices.

Extraction of trace contaminants from fatty food matrices is challenging in food analysis. Herein, a new ionic liquid-based one-, two-, three-phase transition microextraction (IL-OTTPTME) was proposed to efficiently extract trace targets while simultaneously eliminating lipid co-extractives. The method performance was illustrated through the determination of chrysoidine in fatty soybean products using high-performance liquid chromatography-ultraviolet/visible detection. The strong interactions and infinite contact between IL and chrysoidine in the one-phase system ensured ultra-high extraction efficiency (∼100 %). Density functional theoretical calculations confirmed the presence of strong hydrogen bonding and π-π interactions. The formation of the three-phase system during extraction could completely eliminate lipid co-extractives. The IL-OTTPTME integrated extraction, enrichment and cleanup steps into one step, making it rapid and extremely easy to operate. The method had a wide linear range of 0.5-5000 µg/kg and low limit of detection (0.15 µg/kg). It also had satisfactory relative recoveries (95.1 %-104.0 %) and low RSDs (≤5.0 %, n = 5).

Cascade of atopic dermatitis comorbidities in children after birth for 15 years.

BACKGROUND: Individuals with atopic dermatitis often develop other conditions. OBJECTIVE: This study aimed to determine how atopic dermatitis comorbidities develop in children over time. METHODS: This population-based administrative cohort study used national health insurance data. We traced individuals born in Korea between 2002 and 2003 to 2018. The date of initial atopic dermatitis diagnosis was set as the index date. Fifty-three childhood comorbidities of atopic dermatitis were identified as outcomes of interest by performing a comprehensive literature search and comparing the prevalence of diagnostic codes in children with and without atopic dermatitis. Four control children per individual in the atopic dermatitis group were randomly matched based on sex and index date. The association between atopic dermatitis and the development of each specified disease was assessed using proportional hazard assumption, followed by mapping of the temporal sequences of interconnected comorbidities. RESULTS: The atopic dermatitis and control groups contained 67,632 and 270,528 individuals, respectively. The median age at the index date was 10 months, whereas the median follow-up period was 15 years. Twenty diseases that were associated with a higher risk of atopic dermatitis were identified and a chain of interconnected conditions created. The progression began in childhood with febrile seizures, constipation, and asthma, and was later associated with the emergence of food allergy, allergic rhinitis, psychiatric disorders, and autoimmune diseases. CONCLUSION: Our study highlights the temporal nature of atopic dermatitis comorbidities in children, and indicates that an understanding of the comorbidities may inform its clinical management and treatment.

Investigating the occurrence of autoimmune diseases among children and adolescents hospitalized for Mycoplasma pneumoniae infections.

Background: Mycoplasma pneumoniae infection is common in the general population and may be followed by immune dysfunction, but links with subsequent autoimmune disease remain inconclusive. Objective: To estimate the association of M. pneumoniae infection with the risk of subsequent autoimmune disease. Methods: This retrospective cohort study examined the medical records of South Korean children from 01/01/2002 to 31/12/2017. The exposed cohort was identified as patients hospitalized for M. pneumoniae infection. Each exposed patient was matched with unexposed controls based on birth year and sex at a 1:10 ratio using incidence density sampling calculations. The outcome was subsequent diagnosis of autoimmune disease, and hazard ratios (HRs) were estimated with control for confounders. Further estimation was performed using hospital-based databases which were converted to a common data model (CDM) to allow comparisons of the different databases. Results: The exposed cohort consisted of 49,937 children and the matched unexposed of 499,370 children. The median age at diagnosis of M. pneumoniae infection was 4 years (interquartile range, 2.5-6.5 years). During a mean follow-up time of 9.0 ± 3.8 years, the incidence rate of autoimmune diseases was 66.5 per 10,000 person-years (95% CI: 64.3-68.8) in the exposed cohort and 52.3 per 10,000 person-years (95% CI: 51.7-52.9) in the unexposed cohort, corresponding to an absolute rate of difference of 14.3 per 10,000 person-years (95% CI: 11.9-16.6). Children in the exposed cohort had an increased risk of autoimmune disease (HR: 1.26; 95% CI: 1.21-1.31), and this association was similar in the separate analysis of hospital databases (HR: 1.25; 95% CI 1.06-1.49). Conclusion: M. pneumoniae infection requiring hospitalization may be associated with an increase in subsequent diagnoses of autoimmune diseases.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Associations Between Phthalate, Eosinophil, and Aeroallergen Sensitization in Schoolchildren.

BACKGROUND: Phthalates and bisphenol A (BPA) are endocrine-disrupting chemicals and may cause immunological disorders in children. Therefore, according to the region, we investigated urinary phthalates and BPA levels and the relationship between urinary phthalate, aeroallergen sensitization, and eosinophil count during the coronavirus disease 2019 pandemic. METHODS: In total, 203 schoolchildren (134 residential and 69 industrial) aged 7-10 years were enrolled between July 2021 and July 2022. The BPA, metabolites of four high-molecular-weight phthalates (Σ4HMWP) and three low-molecular-weight phthalates (Σ3LMWP), were measured in the urine samples. Total eosinophil count and transepidermal water loss (TEWL) were also measured along with the skin prick test. RESULTS: The two groups had no differences in terms of BPA. The industrial group had significantly more plastic container usage, and there was a difference in the Σ3LMWP (P < 0.001) between the two groups but no difference in the Σ4HMWP (P = 0.234). The quartiles of urinary Σ4HMWP and Σ3LMWP (P < were not associated with the total eosinophil count, vitamin D level, or TEWL. After adjusting for cofactors, the quartiles of urinary Σ4HMWP and Σ3LMWP were significantly associated with total eosinophil count (P < 0.001) but not with aeroallergen sensitization or vitamin D. CONCLUSION: Exposure to phthalates was significantly associated with eosinophil count but not with aeroallergen sensitization or vitamin D. Therefore, reducing the use of plastic containers may effectively prevent exposure to phthalates and reduce Th2 cell-mediated inflammation in children.