From evidence to practice: A systematic review-based diagnostic algorithm for paediatric eosinophilia across socioeconomic context.

AIM: Paediatric eosinophilia is a common clinical dilemma, often leading to resource- and time-consuming assessments. We aim to evaluate the main aetiologies of eosinophilia in children from different socioeconomic settings and propose a diagnostic algorithm. METHODS: A systematic literature review was conducted through PubMed, Embase and the Cochrane Library. Studies published from January 2012 to June 2023 reporting the incidence and aetiology of peripheral eosinophilia in children were included. Evidence from studies on children originating from low- or high-income countries was compared. RESULTS: A total of 15 observational studies, encompassing 3409 children, were included. The causes of eosinophilia varied based on the children's origin and the eosinophilia severity. In children from high-income countries, allergic diseases were the leading cause, with a prevalence of 7.7%-78.2%, while parasitosis ranged from 1.0% to 9.1%. In children from low-income countries, parasitosis was predominant, ranging from 17.7% to 88.3%, although allergic diseases were found in 2.5%-4.8% of cases. Concerning severity, allergic diseases were the leading cause of mild-to-moderate eosinophilia; parasitosis was associated with moderate-to-severe eosinophilia, while immunological disorders were mostly found in severe cases. CONCLUSION: We developed a step-up diagnostic algorithm that considers the child's origin and eosinophilia severity and could optimise resource allocation.

Tocolytic treatment and maternal characteristics, obstetric outcomes, and offspring childhood outcomes among births at and after 37 weeks of gestation: the Japan environment and children's study.

PURPOSE: To evaluate differences in maternal characteristics and obstetric and offspring childhood outcomes between births at and after 37 weeks of gestation (referred to as term and post-term births) according to the use of tocolytic treatment. METHODS: Data for 63,409 women with singleton births at and after 37 weeks of gestation were analyzed using data from the Japan Environment and Children's Study (JECS). We compared maternal characteristics, obstetric outcomes, and offspring childhood outcomes between term and post-term births exposed and not exposed to tocolytic treatment. Additionally, multivariable logistic regression models were used to calculate adjusted odds ratios for offspring childhood outcomes with significant between-group differences in the univariable analysis, with term and post-term births without tocolytic agents as the reference group. RESULTS: We observed differences in maternal characteristics and obstetric outcomes between term and post-term births exposed and not exposed to tocolytic treatment. The incidence of offspring childhood developmental disorders showed no significant between-group differences. However, participants exposed to tocolytic agents had higher incidence of offspring childhood allergic disorders. The adjusted odds ratio for any of the offspring childhood allergic disorders in term and post-term births with tocolytic agents was 1.08 (95% confidence interval, 1.03-1.13). CONCLUSION: This study found no significant difference in the incidence of offspring developmental disorders between term and post-term births exposed and not exposed to tocolytic treatment. However, tocolytic treatment was associated with differences in maternal characteristics and obstetric outcomes, along with a marginal increase in the incidence of childhood allergic disorders in offspring.

KIT as a master regulator of the mast cell lineage.

The discovery in 1987/1988 and 1990 of the cell surface receptor KIT and its ligand, stem cell factor (SCF), was a critical achievement in efforts to understand the development and function of multiple distinct cell lineages. These include hematopoietic progenitors, melanocytes, germ cells, and mast cells, which all are significantly affected by loss-of-function mutations of KIT or SCF. Such mutations also influence the development and/or function of additional cells, including those in parts of the central nervous system and the interstitial cells of Cajal (which control gut motility). Many other cells can express KIT constitutively or during immune responses, including dendritic cells, eosinophils, type 2 innate lymphoid cells, and taste cells. Yet the biological importance of KIT in many of these cell types largely remains to be determined. We here review the history of work investigating mice with mutations affecting the white spotting locus (which encodes KIT) or the steel locus (which encodes SCF), focusing especially on the influence of such mutations on mast cells. We also briefly review efforts to target the KIT/SCF pathway with anti-SCF or anti-Kit antibodies in mouse models of allergic disorders, parasite immunity, or fibrosis in which mast cells are thought to play significant roles.

Microbiota of the first-pass meconium and subsequent atopic and allergic disorders in children.

BACKGROUND: Some cohort studies have suggested that gut microbiota composition is associated with allergic diseases in children. The microbiota of the first-pass meconium, which forms before birth, represents the first gut microbiota that is easily available for research and little is known about any relationship with allergic disease development. OBJECTIVE: We investigated whether the bacterial composition of the first-pass meconium is associated with the development of allergic diseases before 4 years of age. METHODS: Prospective birth cohort study. Bacterial composition of first-pass meconium was analysed using bacterial 16S rRNA gene amplicon sequencing. Atopic and allergic diseases were evaluated via online survey or telephone to age 4 years, based on the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: During a 6-week period in 2014, 312 children were born at the Central Finland Central Hospital. Meconium was collected from 212 at a mean of 8-hour age. Outcome data at 4 years were available for 177 (83%) children, and 159 of these had sufficient amplification of bacterial DNA in meconium. Meconium microbiota composition, including diversity indices and relative abundances of the main phyla and genera, was not associated with subsequent atopic eczema, wheezing or cow's milk allergy. Principal components analysis did not identify any clustering of the meconium microbiomes of children with respect to wheezing or cow's milk allergy. CONCLUSIONS: We found no evidence that gut microbiota composition of first-pass meconium is associated with atopic manifestations to age 4 years. However, larger studies are needed to fully exclude a relationship.

Early childhood allergy linked with development of attention deficit hyperactivity disorder and autism spectrum disorder.

BACKGROUND: Previous studies reported controversial results regarding the association between allergic disorders and attention deficit hyperactivity disorder (ADHD)/autism spectrum disorder (ASD). The aim of this article was to investigate whether allergic disorders are associated with ADHD/ASD in a large cohort of pediatric patients. METHODS: A retrospective study using the pediatric (0-18 year) database (ICD-9-CM codes) of Clalit Health Services during the years (2000-2018). Diagnosis of all disorders was made by specialist physicians. RESULTS: A total of 117 022 consecutive non-selective allergic children diagnosed with one or more allergic disorder (asthma, rhinitis, conjunctivitis, skin, food, or drug allergy) and 116 968 non-allergic children were enrolled to our study. The mean follow-up period was 11 ± 6 years. The presence of allergic disorders in early childhood (mean age of allergic diagnosis 4.5 ± 4.3 years) in boys as well as in girls significantly increased the risk to develop ADHD (O.R 2.45, CI 2.39-2.51; p < .0001), ASD (O.R 1.17, CI 1.08-1.27; p < .0001), or both ADHD + ASD (O.R 1.5, CI 1.35-1.79; p < .0001). Children with more than one allergic comorbidity revealed a much higher risk. In a multivariable analysis (adjusted for age at study entry, number of yearly visits, and gender), the risk of allergic children to develop ADHD and ADHD + ASD, but not ASD alone, remained significantly higher. CONCLUSION: Allergic disorder in early childhood significantly increased the risk to develop ADHD, and to a less extend ASD, in later life.

Allergic-like disorders and asthma in patients with common variable immunodeficiency: a multi-center experience.

OBJECTIVE: Common variable immune deficiency (CVID) encompasses a variety of diseases characterized by disturbed immunoglobulin (Ig) production and various immune dysregulations. Scarce data are available regarding relationships between CVID and allergic diseases. Here we examined possible associations between allergies and CVID. METHODS: For this multicenter study, we prospectively enrolled 79 adult CVID patients (≥18 years) who were diagnosed and treated between 2002-2017 at the Hadassah-Hebrew University and Shaare Zedek Medical Centers, Jerusalem, Israel. These patients were examined for allergic manifestations. Patient evaluation comprised medical history, physical examination, skin allergen testing, complete blood count, serum immunoglobulins, IgE levels, and pulmonary function tests. RESULTS: After implementing exclusion criteria, 29 patients were included in the final analysis. Allergic-like disorders were diagnosed in 65% of CVID patients with non-elevated serum IgE levels. Moreover, allergic CVID patients exhibited a higher prevalence of bronchiectasis on chest CT. Autoimmunity was diagnosed in 41.3% of CVID subjects. The type I allergy detected in our study was non-IgE mediated. CONCLUSIONS: Timely diagnosis and stratification of allergy in CVID patients is expected to improve their outcome and quality of life, as well as promote appropriate treatment and better management of pulmonary exacerbations.

Structural and clinical impact of anti-allergy agents: An overview.

Allergic disorders are markedly rising in industrialized countries. The identification of compounds that trigger the immunoglobulin E (IgE)-dependent allergic reaction remain the means to improve the quality of life by limiting patient's exposure to critical allergens. Information concerning the treatment and onset of allergic disorders including atopic dermatitis, allergic rhinitis, and bronchial asthma has been provided by the research over the past decade. Recent studies also indicated that allergic inflammation is associated closely with their exacerbation and progression and indeed is the basic pathophysiology of allergic diseases. As a result of immunological and molecular biological studies our understanding of the mechanism of allergic inflammation with regard to therapeutic agents has improved. While much effort has been paid to developing a new anti-allergic agent, the allergic disease has yet to be completely conquered. The more extensive research will allow the development of new therapeutics to combat allergic diseases. Currently, with respect to mechanism of action anti-allergy drugs are classified into five types including histamine H1 antagonists, leukotriene antagonists, Th2 cytokine inhibitors, thromboxane A2 inhibitors and mediator-release inhibitors. The use of two or more anti-allergy agents together is not acknowledged at present, but this will be the subject of research in the future because with different mechanisms of action anti-allergy agents used at the same time will theoretically increase their effects. This review article focuses on anti-allergy agents highlighting their applications, clinical trials and recent advancement on drugs.

Antihistamines in children and adolescents: A practical update.

Histamine is a chemical mediator, released predominantly by tissue mast cells, circulating basophils, and neurons, which are activated in response to various immunological and non-immunological stimuli. Histamine has to bind to specific receptors to exert its physiological and pathophysiological functions. Endogenous histamine is the main mediator of the immediate allergic response, which moreover, performs other multiple functions, including regulation of gastric secretion, neurotransmission in the central nervous system, and immunomodulatory activity. The involvement of histamine in various disorders and the importance of receptors in the clinical features have relevant implications in clinical practice. Anti-H1 antihistamines contrast the histamine-dependent effects, mainly concerning nasal symptoms and cutaneous itching and wheal. Antihistamines are among the most prescribed drugs in pediatric care. This review updates the practical use of antihistamines in children and adolescents.

Impact of Tree Pollen Distribution on Allergic Diseases in Serbia: Evidence of Implementation of Allergen Immunotherapy to Betula verrucosa.

Background and objectives: The relationship between air pollen quantity and the sensitization of allergic patients is crucial for both the diagnosis and treatment of allergic diseases. Weather conditions influence the distribution of allergenic pollen and increases in pollen concentration may negatively affect the health of allergic patients. The aim of this study was to analyze the implementation of allergen immunotherapy with regard to air pollen concentration. Material and Methods: Here we examined the relationship between Betula air pollen concentration and the usage of Betula verrucosa allergen immunotherapy in Serbia. Examination covered the period from 2015 to 2018. Measurement of airborne pollen concentration was performed with Lanzoni volumetric pollen traps. The evidence of the usage of sublingual allergen immunotherapy (SLIT) was gathered from patients with documented sensitization to specific pollen. Results: During this period tree pollens were represented with 58% ± 21% of all measured air pollen species, while Betula pollen represented 15% ± 8% of all tree pollens. Betula pollination peaked in April. Allergen immunotherapy to Betula verrucosa in Serbia is entirely conducted as sublingual immunotherapy and represents 47.1% ± 1.4% of issued tree pollen SLIT. The use of pollen SLIT increased by 68% from 2015 to 2018, with an even greater increase in usage recorded for Betula SLIT-80%. Conclusions: This analysis shows a clear causative relationship between pollination and the type/prevalence of applied allergen immunotherapy. Information about the flowering seasons of allergenic plants is very important for people who suffer from allergy, for clinical allergologists, as well as for governing authorities. The presented data is of practical importance to the proper timing of immunotherapy initiation and of importance for urban landscaping. The obtained data can be the starting point for the instatement of a thorough epidemiological study and the inclusion of Serbia on the pollen map of Europe.

Association between infection with Helicobacter pylori and atopy in young Ethiopian children: A longitudinal study.

BACKGROUND: Epidemiological evidence from developed countries indicates that Helicobacter pylori infection correlates with a reduced risk of atopy and allergic disorders; however, limited data are available from low-income countries. OBJECTIVE: We examined associations between H. pylori infection in early childhood and atopy and reported allergic disorders at the age of 6.5 years in an Ethiopian birth cohort. METHODS: A total of 856 children (85.1% of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half years. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Questions on allergic disease symptoms were based on the International Study of Asthma and Allergies in Children (ISAAC) core allergy and environmental questionnaire. Serum samples were analysed for total IgE levels and anti-H. pylori cytotoxin-associated gene A (CagA) IgG antibody using commercially available ELISA kits. Stool samples were analysed for H. pylori antigen using a rapid immunochromatographic test. The independent effects of H. pylori infection (measured at age of 3, 5 and 6.5 years) on prevalence and incidence of atopy and reported allergic disorders (measured at age of 6.5 years) were determined using multiple logistic regression. RESULTS: In cross-sectional analysis, current H. pylori infection at age 6.5 years was inversely, though not significantly, related to prevalence of atopy and "any allergic condition" at age 6.5 years. However, detection of H. pylori infection at any point up to age 6.5 years was associated with a significantly reduced odds of both atopy and "any allergic condition" (adjusted OR AOR, 95% CI, 0.54; 0.32-0.92, P = .02, and .31; 0.10-0.94, P = .04, respectively). In longitudinal analyses, H. pylori infection at age 3 was inversely associated with incidence of atopy (AOR, 95% CI, 0.49; 0.27-0.89, P = .02). Furthermore, among H. pylori-infected children, those with a CagA+ strain had a more pronounced reduction in odds of atopy (AOR = 0.35 vs 0.63 for CagA+ vs CagA-), and this reduction reached borderline significance. CONCLUSION: These data are consistent with the hypothesis that early exposure to H. pylori is inversely associated with atopy and allergic conditions. A possible modest protective association against atopy was observed in those infected with a more virulent CagA+ strain of H. pylori.

Optimization and simplification of the Allergic and Hypersensitivity conditions classification for the ICD-11.

BACKGROUND: Since 2013, an international collaboration of Allergy Academies, including first the World Allergy Organization (WAO), the American Academy of Allergy Asthma and Immunology (AAAAI), and the European Academy of Allergy and Clinical Immunology (EAACI), and then the American College of Allergy, Asthma and Immunology (ACAAI), the Latin American Society of Allergy, Asthma and Immunology (SLAAI), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), has spent tremendous efforts to have a better and updated classification of allergic and hypersensitivity conditions in the forthcoming International Classification of Diseases (ICD)-11 version by providing evidences and promoting actions for the need for changes. The latest action was the implementation of a classification proposal of hypersensitivity/allergic diseases built by crowdsourcing the Allergy Academy leaderships. METHODS: Following bilateral discussions with the representatives of the ICD-11 revision, a face-to-face meeting was held at the United Nations Office in Geneva and a simplification process of the hypersensitivity/allergic disorders classification was carried out to better fit the ICD structure. RESULTS: We are here presenting the end result of what we consider to be a model of good collaboration between the World Health Organization and a specialty. CONCLUSION: We strongly believe that the outcomes of all past and future actions will impact positively the recognition of the allergy specialty as well as the quality improvement of healthcare system for allergic and hypersensitivity conditions worldwide.

The association between paracetamol use and asthma: causation or coincidence?

A better understanding of the causation of asthma and allergic disorders could potentially lead to intervention strategies that reduce their prevalence and severity. One potential causative factor is the use of paracetamol. Most of the evidence for the link with asthma is from non-experimental studies of paracetamol exposure in utero, infancy, childhood and adult life; however, it has been difficult to rule out confounding and bias in the associations observed. The two randomized clinical trials of the effect of paracetamol in patients with asthma have been difficult to interpret, due to methodological issues. There have been no randomized controlled trials of paracetamol use and the development of asthma. Both asthma and paracetamol use are common, and so even if there is a relatively small effect of paracetamol exposure on the development of asthma or its severity, then such an effect would be of major public health significance. It is proposed that randomized controlled trials of the effect of paracetamol on the development of asthma and its severity are a high research priority.

Development and psychometric testing of a chinese version of the caregiver burden index for parents of children with allergies.

UNLABELLED: BACKGROUNG: No specific instrument has thus far been developed for measuring the caregiver burden perceived by parents of children with allergies (CWA). OBJECTIVES: To determine the psychometric properties of the Caregiver Burden Index (CBI). METHODS: A mixed-methods design was adopted to evaluate the psychometric properties of the scale. RESULTS: The content validity index was 0.89, and the internal consistency was high with a coefficient alpha of 0.98. Three factors were extracted after exploratory factor analysis. CONCLUSION: The study findings suggest that the CBI has sufficient reliability and validity to evaluate the caregiver burden of parents of CWA.

Atopic disorders are more common in childhood migraine and correlated headache phenotype.

BACKGROUND: The supportive clinical and pathophysiological data about the correlation between migraine and atopic disorders are far from a coincidence. In order to determine and investigate the correlates of atopic disorders in a specific dataset, we performed this retrospective cross-sectional clinical-based study. METHODS: The dataset was composed from three tertiary center web-based databases (http://www.childhoodheadache.org). Headache diagnosis and differential diagnosis were made according to the International Classification of Headache Disorders, 2nd version and the Diagnostic Statistical Manual of Mental Disorders, 5th edition. Migraine with aura, migraine without aura, chronic migraine and episodic and chronic tension type headache (TTH) patients were included. All other causes of headache disorders, including comorbid headache disorders like migraine plus TTH or "possible" causes of headache, were excluded. RESULTS: The study included 438 patients with migraine and 357 patients with TTH, whose age and sex distribution were identical. After descriptive statistics accordingly, 80 migraine (18.2%) and 23 TTH (6.4%) patients were found to have specific atopic disorders (P < 0.001). Atopic disorders are more commonly reported in patients with migraine with aura (21.6%) than those with migraine without aura and TTH (P < 0.001). The most common atopic disorders were seasonal rhinitis, conjunctivitis and asthma. There was also a close correlation between TTH with atopic disorders and psychiatric comorbid disorders of the patients. CONCLUSIONS: Although the International Classification of Headache Disorders, 2nd version, does not specify, atopic disorders should be suspected in all migraine patients and their relatives, not only for accurate diagnosis but also for planning prophylactic medications, such as ß-blockers.

Temporal Trends of Asthma Among Children in the Western Pacific Region From 1990 to 2045: Longitudinal Observational Study.

BACKGROUND: Asthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. OBJECTIVE: This study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged <20 years by leveraging the latest data from the Global Burden of Disease Study 2019. Findings from this study can help inform priority areas for intervention to alleviate the rising burden of childhood asthma globally. METHODS: The study used data from the Global Burden of Disease Study 2019, concentrating on children aged 0 to 14 years with asthma. We conducted an in-depth analysis of asthma, including its age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs), across diverse demographics, such as region, age, sex, and sociodemographic index, spanning 1990 to 2019. We also projected the future burden of the disease. RESULTS: Overall, in the Western Pacific Region, the age-standardized prevalence rate of asthma among children increased slightly, from 3898.4 cases per 100,000 people in 1990 to 3924 per 100,000 in 2019. The age-standardized incidence rate of asthma also increased slightly, from 979.2 to 994.9 per 100,000. In contrast, the age-standardized death rate of asthma decreased from 0.9 to 0.4 per 100,000 and the age-standardized DALY rate decreased from 234.9 to 189.7 per 100,000. At the country level, Japan experienced a considerable decrease in the age-standardized prevalence rate of asthma among children, from 6669.1 per 100,000 in 1990 to 5071.5 per 100,000 in 2019. Regarding DALYs, Japan exhibited a notable reduction, from 300.6 to 207.6 per 100,000. Malaysia also experienced a DALY rate reduction, from 188.4 to 163.3 per 100,000 between 1990 and 2019. We project that the burden of disease in countries other than Japan and the Philippines will remain relatively stable up to 2045. CONCLUSIONS: The study indicates an increase in the prevalence and incidence of pediatric asthma, coupled with a decrease in mortality and DALYs in the Western Pacific Region between 1990 and 2019. These intricate phenomena appear to result from a combination of lifestyle shifts, environmental influences, and barriers to health care access. The findings highlight that nations such as Japan have achieved notable success in managing asthma. Overall, the study identified areas of improvement in view of persistent disease burden, underscoring the need for comprehensive collaborative efforts to mitigate the impact of pediatric asthma throughout the region.

Impact of Climate Change on Dietary Nutritional Quality and Implications for Asthma and Allergy.

Asthma and allergic disorders are common in childhood with genetic and environmental determinants of disease that include prenatal nutritional exposures such as long-chain polyunsaturated fatty acids and antioxidants. Global climate change is implicated in asthma and allergic disorder morbidity with potential mechanisms including perturbations of ecosystems. There is support that environmental and climatic changes such as increasing global temperate and carbon dioxide levels affect aquatic and agricultural ecosystems with subsequent alterations in long-chain polyunsaturated fatty acid availability and nutrient quality and antioxidant capacity of certain crops, respectively. This article discusses asthma epidemiology and the influence of global climate change.

Migraine, Allergy, and Histamine: Is There a Link?

The relationship between migraines and allergies is controversial. Though they are epidemiologically linked, the underlying pathophysiological connection between them remains unclear. Migraines and allergic disorders have various underlying genetic and biological causes. As per the literature, these conditions are epidemiologically linked, and some common pathophysiological pathways have been hypothesized. The histaminergic system may be the clue to understanding the correlation among these diseases. As a neurotransmitter in the central nervous system with a vasodilatory effect, histamine has a well-documented influence on the allergic response and could be involved in the pathophysiology of migraines. Histamine may influence hypothalamic activity, which may play a major role in migraines or may simply influence their severity. In both cases, antihistamine drugs could prove useful. This review examines whether the histaminergic system, particularly H3 and H4 receptors, may provide a mechanistic link between the pathophysiology of migraines and allergic disorders, two common and debilitating conditions. Identifying their connection could help identify novel therapeutic strategies.

Association between exposure to chemical mixtures in relation to serum total IgE among adults 19-86 years old.

There is a scarcity of studies on the effects of mixed chemicals on total IgE. We aim to assess whether there is a link between chemical mixtures (blood and urine of 26 chemicals including lead, mercury, cadmium, t,t-muconic acid, benzylmercapturic acid , 1-hydroxypyrene, 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-n-butyl phthalate, mono-benzyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-carboxyoctyl phthalate, mono-carboxy-isononly phthalate, mono (3-carboxypropyl) phthalate, bisphenol A, bisphenol F, bisphenol S, triclosan, methylparaben, ethylparaben, propylparaben, 3-phenoxybenzoic acid, and cotinine), and total IgE in 3,642 Korean adults aged ≥ 19. The effects of mixed chemical exposure on total IgE were identified using linear regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). The most relevant factors linked with IgE, according to the linear regression models, were blood or urine mercury and urine bisphenol A levels, with significant trends detected for these chemical tertiles (p < 0.01). The WQS index was significantly linked with ln2-transformed levels of serum total IgE (ß = 0.30, 95 %CI 0.25-0.32). The qgcomp index also found a significant link between chemicals and ln2-transformed levels of serum total IgE (ß = 0.52, 95 %CI 0.21-0.82), and elevated serum total IgE levels (OR = 2.55, 95 %CI 1.14-5.71). In BKMR analysis, the overall effect of the mixture was significantly associated with ln2-transformed levels of serum total IgE. The cutoff levels for exposure levels related to serum total IgE levels/elevated serum total IgE levels were reported. We discovered that whole-body exposure to 26 chemicals was associated with serum total IgE levels after assessing the findings of these four models. More research is needed in the future to gain a better understanding of the impact of mixed chemical exposure on allergic disorders and how to minimize chemical exposure, especially for people under the age of 18.

Gut microbiota in various childhood disorders: Implication and indications.

Gut microbiota has a significant role in gut development, maturation, and immune system differentiation. It exerts considerable effects on the child's physical and mental development. The gut microbiota composition and structure depend on many host and microbial factors. The host factors include age, genetic pool, general health, dietary factors, medication use, the intestine's pH, peristalsis, and transit time, mucus secretions, mucous immunoglobulin, and tissue oxidation-reduction potentials. The microbial factors include nutrient availability, bacterial cooperation or antagonism, and bacterial adhesion. Each part of the gut has its microbiota due to its specific characteristics. The gut microbiota interacts with different body parts, affecting the pathogenesis of many local and systemic diseases. Dysbiosis is a common finding in many childhood disorders such as autism, failure to thrive, nutritional disorders, coeliac disease, Necrotizing Enterocolitis, helicobacter pylori infection, functional gastrointestinal disorders of childhood, inflammatory bowel diseases, and many other gastrointestinal disorders. Dysbiosis is also observed in allergic conditions like atopic dermatitis, allergic rhinitis, and asthma. Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders, including heart failure. Probiotic supplements could provide some help in managing these disorders. However, we are still in need of more studies. In this narrative review, we will shed some light on the role of microbiota in the development and management of common childhood disorders.

Impact of Comorbidities on the Prognosis of Pediatric Postural Tachycardia Syndrome.

OBJECTIVE: To investigate the influence of comorbidities on the prognosis of pediatric postural tachycardia syndrome (POTS). METHODS: In this retrospective cohort study, 275 children with POTS admitted to the Department of Pediatrics at Peking University First Hospital were recruited from 2016 to 2019 and followed up. The participants were divided into simple POTS (S-POTS, n=156 cases) and POTS with comorbidities (Co-POTS, n=119 cases) groups according to whether they were complicated with comorbidities. A Cox regression analysis was used to identify the prognostic risk factors for children with POTS, while Kaplan-Meier curves were applied to compare the cumulative symptom remission rate (CSRR) between the two groups. The rehospitalization of the children between the two groups was also compared to explore the influence of comorbidities. RESULTS: Twenty-one participants (7.6%) were lost during a median follow-up of 24 months. The Cox regression model showed that comorbidities and body mass index (BMI) were associated with the CSRR of the children with POTS. The CSRR of pediatric POTS alone was 1.748 times higher than that of patients with comorbidities, and the CSRR was decreased by 5.1% for each 1 kg/m2 increase in BMI. The most common comorbidity in children with POTS in this study was allergic disorders, followed by the psychological diseases. The patients in the Co-POTS group had a lower CSRR than those in the S-POTS group (log rank P=0.0001). In addition, compared with those of the S-POTS group, the total number of rehospitalizations was high (P=0.001), and the total hospital stays were long in the Co-POTS group (P<0.001). CONCLUSION: Complicating with comorbidities, pediatric patients with POTS had lower CSRR and more rehospitalizations than those without comorbidities. More attention should be given to comorbidities when managing pediatric POTS.