Pollen as a mediator between environmental greenness during pregnancy and infancy periods and childhood persistent asthma: A nationwide retrospective birth cohort study in Japan.

The association between environmental greenness and childhood asthma remains unclear. Pollen has been proposed as a potential mechanism of detrimental associations. This study aimed to elucidate the mechanisms underlying the association between environmental greenness during the pre-, peri-, and postnatal periods and childhood persistent asthma. A nationwide retrospective birth cohort study was conducted using data from the Japan Medical Data Center (JMDC). Child-mother dyads between January 2010 and January 2017 were identified, and four subcohorts were developed based on the timing of exposure to the highest greenness season. The exposure of interest was environmental greenness levels between June and September, quantified using the normalized difference vegetation index (NDVI). The primary outcome was persistent asthma in children aged 4-5 years. Causal mediation analysis was conducted to evaluate pollen as a mediator between NDVI and asthma. In these analyses, linear and modified Poisson regression models were used to evaluate the association of NDVI with pollen levels and childhood persistent asthma. The analyses were stratified by metropolitan and non-metropolitan areas. Clinically meaningful confounders and predictors of asthma were adjusted in the statistical models. A total of 100,273 child-mother dyads were included in the entire cohort, with 24.1% of the children having persistent asthma at the ages of 4-5 years. Higher environmental greenness was associated with higher pollen levels. The modified Poisson regression models showed higher environmental greenness was associated with a slightly higher risk of persistent childhood asthma. In metropolitan areas, significant detrimental natural direct effects of NDVI were observed; however, the natural indirect effects were uncertain. A large part of the association between environmental greenness and childhood persistent asthma in metropolitan areas was attributed to mechanisms other than those involving pollen. The associations in non-metropolitan areas remain uncertain. Further studies are required to elucidate the underlying mechanisms.

Maternal exercise during pregnancy is associated with reduced risk of asthma in the child: A prospective birth cohort study.

BACKGROUND: The means of primary prevention of asthma are limited. Maternal physical activity during pregnancy promotes fetal lung development and the newborn's lung function; thus, it could lower asthma risk and aid in asthma prevention. The objective of this study is to determine whether maternal physical activity during pregnancy is associated with asthma development in the child. METHODS: The study population included 963 mother-infant pairs from the prospective Kuopio Birth Cohort study. Data on maternal physical activity during pregnancy, confounding factors, and children's asthma at 5 to 7 years of age were obtained from the Kuopio University Hospital birth registry and questionnaires. FINDINGS: Maternal physical activity during pregnancy, when practiced three or more times per week, was associated with a reduced risk of asthma in the child, with an adjusted odds ratio of 0.54 (95% confidence interval 0.33-0.89; p = 0.02). The association was stable across a comprehensive set of adjustments, including length of gestation, mode of delivery, and maternal health indicators (e.g., asthma, smoking, pre-pregnancy body mass index and weight gain during pregnancy, infections, medication, healthy diet, stress), as well as various family environment variables. CONCLUSIONS: Maternal physical activity during pregnancy may be associated with marked protection of asthma in childhood and should be studied further as an applicable measure for asthma prevention. FUNDING: The study has been financially supported by grants from the Academy of Finland (no. 349427), the Emil Aaltonen Foundation, the Finnish Cultural Foundation, the Yrjö Jahnsson Foundation, the Juho Vainio Foundation (no. 202200461), the Kuopio Area Respiratory Foundation, and the Ida Montini Foundation.

Allele-specific micro-RNA-mediated regulation of ADAM33 in childhood allergic asthma.

BACKGROUND AND OBJECTIVE: A disintegrin and metalloprotease 33 (ADAM33) is associated with asthma susceptibility, and its genetic variations impact susceptibility and disease severity. However, the mechanisms remain unclear. This study aimed to investigate ADAM33 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility and explore their regulatory mechanisms. METHODS: Eleven selected SNPs in ADAM33 were genotyped and identified the association with asthma susceptibility. In the validation cohort, we measured plasma sADAM33 levels and compared them with disease severity among children with different SNP genotypes. Computational predictions identified miRNAs targeting the SNP, and the impact of the SNP on miRNA regulation was confirmed using a dual luciferase reporter system. Finally, we validated the regulatory role of miRNAs on ADAM33 expression using an in vitro model with upregulated ADAM33 expression. RESULTS: Only rs3918400 was associated with asthma susceptibility. In the validation cohort, children with allergic asthma exhibited higher plasma sADAM33 levels. Among asthmatic children, those with the rs3918400 CT/TT genotype had higher sADAM33 levels, poorer asthma control, more severe airway hyper-responsiveness, lower FEV1% and higher dust mite-specific IgE activity compared to those with the CC genotype. miR-3928-5p bound strongly to the rs3918400 C allele and effectively reduced ADAM33 protein expression in CC genotype cells. However, the binding affinity of miR-3928-5p to the T allele was weaker, resulting in diminished negative regulation of protein expression. CONCLUSION: The rs3918400 SNP affects the negative regulation of ADAM33 by miR-3928-5p, potentially participating in a complex interplay of processes related to childhood asthma susceptibility.

Pollen exposures in pregnancy and early life are associated with childhood asthma incidence.

Background: Pollen exposure is an environmental risk factor for asthma symptoms and allergic reactions in children. The extent to which pollen exposure in pregnancy and the first year of life influences the development of childhood asthma and rhinitis is not fully understood. Objective: We aimed to investigate early life exposures to pollen with childhood asthma and rhinitis at age 6 in a longitudinal birth cohort of the United Kingdom. Methods: In this retrospective cohort study, via logistic regressions, we analyzed the associations between pollen exposures in pregnancy and the first year of life with childhood asthma and rhinitis. Results: Higher pollen exposure accumulated during pregnancy and during the first year of life both associated with an increased odds of asthma at age 6 (OR = 1.14, 95% CI 1.03-1.26, p = 0.01; OR = 1.15, 95% CI 1.03-1.29, p = 0.02, respectively). We did not observe statistically significant associations between early life pollen exposures and the odds of rhinitis at the same age. Conclusion: High pollen exposure during early life (prenatal and postnatal) associated with an increased risk of asthma incidence at age 6. Further studies are desired to validate these findings and to elucidate the mechanisms of early life exposures to pollen on asthma etiology.

Mendelian randomization study of childhood asthma and chronic obstructive pulmonary disease in European and East Asian population.

Objective: The present study aimed to explore the potential causal relationship between childhood asthma and chronic obstructive pulmonary disease (COPD) in European and East Asian populations with Mendelian randomization (MR) analysis. Methods: Based on summary data from genome-wide association studies, single nucleotide polymorphisms (SNPs) associated with childhood asthma were used as instrumental variables. The MR analysis employed the inverse variance weighting, MR-Egger regression and weighted median method to estimate the causal effect between childhood asthma and COPD in European and East Asian populations. Cochran's Q test, MR-PRESSO method and MR-Egger intercept were used to detect heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis applied to assess the effect of removing individual SNP on the estimate of causal association. Results: The MR analysis showed no genetic causal relationship between childhood asthma and COPD. The results of Cochran's Q test, MR-PRESSO and MR-Egger regression indicated the absence of heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis showed no significant difference in the statistical results after exclusion of single SNPs. Conclusions: The MR analysis revealed that there is no causal relationship between childhood asthma and COPD at the genetic level in both European and East Asian populations. Additionally, due to the presence of shared confounding factors and pathogenic genes, further research is needed to comprehensively assess the relationship between childhood asthma and COPD.

[Active components and mechanism of Wuhu Decoction in intervening RSV-induced asthma based on network pharmacology and in vivo experiment].

This study aims to explore the active components and mechanism of Wuhu Decoction in treating respiratory syncytial virus(RSV)-induced asthma. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry was used to determine the components of Wuhu Decoction in the blood. By utilizing databases, Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis and Gene Ontology(GO) functional analysis were conducted to investigate the targets of the components of Wuhu Decoction in asthma. Furthermore, the information on target proteins, and metabolite-target-pathway was imported into the STRING database to construct a network interaction diagram to identify the core components and key pathways of Wuhu Decoction. In the in vivo experiment, an asthma model was established using RSV combined with ovalbumin(OVA) in mice. The intervention effect of Wuhu Decoction on RSV-induced asthma in mice was validated through lung function tests, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and immunohistochemistry. The results showed that the main components of Wuhu Decoction in the blood were flavonoids, phenylpropanoids, lignans, and terpenoids. The core components of Wuhu Decoction in treating pediatric asthma included(-)-epigallocatechin, kaempferol, isoliquiritigenin, diosmetin, betulinic acid, ursolic acid, daphnetin, aescin. The main pathways targeted by Wuhu Decoction were calcium signaling pathway, neuroactive ligand-receptor interaction, NOD-like receptor signaling pathway, T cell receptor signaling pathway, and Toll-like receptor signaling pathway. The results of in vivo experiments demonstrated that Wuhu Decoction could improve lung function indicators, down-regulate levels of interleukin-6(IL-6), interleukin-17(IL-17), and tumor necrosis factor-alpha(TNF-α), and reduce the expression of proteins such as NOD-like receptor pyrin domain-containing 3(NLRP3), mitogen-activated protein kinase 1(MAPK1), mitogen-activated protein kinase 14(MAPK14), and nuclear factor kappaB subunit 1(NFKB1) in lung tissue, thereby alleviating neutrophilic inflammation and pulmonary congestion. These findings indicate that Wuhu Decoction intervenes in virus-induced asthma through a synergistic effect on multiple components, targets, and pathways, and it can inhibit the activation of the NOD-like receptor signaling pathway, thereby alleviating airway inflammation and injury in asthmatic mice.

Urinary biomarkers of environmental exposures and asthma morbidity in a school inner city asthma study.

BACKGROUND: The burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations. OBJECTIVE: To determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex. METHODS: This study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2). Metabolites of phenol, paraben, polycyclic aromatic hydrocarbons, and phthalate analytes were analyzed from urine samples collected at baseline. Asthma symptom days over the past 2 weeks were dichotomized to no asthma symptom days or any asthma symptom days. Cross-sectional regression models were adjusted for age, sex, number of colds, household income, prescription control, race and ethnicity, body mass index (BMI) percentile, and smoke exposure. Weighted quantile sum regression was used to analyze each chemical class and a total mixture effect, controlling for the same covariates. Analyses were conducted with the assistance of the National Institute of Environmental Health Sciences Children's Health Exposure Analysis Resource (CHEAR). RESULTS: Participants were mostly Hispanic/Latino and low income with an average age of 7.83 years and the average maximum asthma symptom days over the past two weeks of 2.13 (standard deviation: 3.56). The maximum concentrations indicate extreme values for several chemicals, including bisphenol-3, 2,5-dichlorophenol, propyl and methyl parabens, triclosan, methyl paraben and cotinine. We found a significant interaction effect and differing contributions of analytes for children with allergen sensitivity versus those that did not. For stratified analyses assessing effect modification by child race and ethnicity, weighted quantile sum interaction models showed reduced odds of asthma symptoms to a greater magnitude in children of other races and ethnicities compared to Black, Non-Hispanic children. CONCLUSIONS: Preliminary analyses of the association between environmental chemical exposure and asthma symptoms among inner-city children revealed an inverse association, which may be due to personal care and medication use and can be understood further in future analyses. Beneficial effects were detected for most of the chemicals.

Astragaloside IV promotes the pyroptosis of airway smooth muscle cells in childhood asthma by suppressing HMGB1/RAGE axis to inactivate NF-κb pathway.

Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from Astragalus membranaceus, which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 µM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, in vivo experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.

Enhancers regulate genes linked to severe and mild childhood asthma.

Background: Children with severe asthma suffer from recurrent symptoms and impaired quality of life despite advanced treatment. Underlying causes of severe asthma are not completely understood, although genetic mechanisms are known to be important. Objective: The aim of this study was to identify gene regulatory enhancers in leukocytes, to describe the role of these enhancers in regulating genes related to severe and mild asthma in children, and to identify known asthma-related SNPs situated in proximity to enhancers. Methods: Gene enhancers were identified and expression of enhancers and genes were measured by Cap Analysis Gene Expression (CAGE) data from peripheral blood leukocytes from children with severe asthma (n = 13), mild asthma (n = 15), and age-matched controls (n = 9). Results: From a comprehensive set of 8,289 identified enhancers, we further defined a robust sub-set of the high-confidence and most highly expressed 4,738 enhancers. Known single nucleotide polymorphisms, SNPs, related to asthma coincided with enhancers in general as well as with specific enhancer-gene interactions. Blocks of enhancer clusters were associated with genes including TGF-beta, PPAR and IL-11 signaling as well as genes related to vitamin A and D metabolism. A signature of 91 enhancers distinguished between children with severe and mild asthma as well as controls. Conclusions: Gene regulatory enhancers were identified in leukocytes with potential roles related to severe and mild asthma in children. Enhancers hosting known SNPs give the opportunity to formulate mechanistic hypotheses about the functions of these SNPs.

Distinguishing Childhood Asthma Exacerbations from Stable Asthma: The Utility of Inflammatory White Blood Cell Biomarkers.

BACKGROUND: Asthma is a chronic inflammatory condition characterized by episodes of acute asthma exacerbations (AAEs), in addition to chronic airway inflammation, which has a huge impact on both the affected patients and their parents. The main objective of this study was to explore the utility of available white-blood-cell-derived inflammatory markers in diagnosing AAEs and identifying children at risk for severe exacerbations requiring admission to the pediatric intensive care unit (PICU). METHODS: This study was a retrospective cohort study. The medical records of 128 children diagnosed with asthma exacerbation and 131 children with stable asthma between the ages of 2 and 12 years were reviewed. RESULTS: A total of 259 participants were enrolled. Children with AAE demonstrated significantly higher white blood cell counts (WBC: 10.0 ± 4.2 × 103/µL vs. 7.1 ± 2.2 × 103/µL, p < 0.001), absolute neutrophil counts (ANC: 7398.5 ± 4600 cells/µL vs. 2634.8 ± 1448 cells/µL, p < 0.001), and neutrophil-to-lymphocyte ratios (NLR: 7.0 ± 6.8 vs. 0.9 ± 0.7, p < 0.001) but significantly lower absolute lymphocyte counts (ALC: 1794.1 ± 1536 × 103/µL vs. 3552.9 ± 1509 × 103/µL, p < 0.001). Interestingly, blood eosinophil count displayed an opposite trend: children with stable asthma had significantly more eosinophils compared to those experiencing an exacerbation (370.1 ± 342.7 cells/mm3 vs. 0.9 ± 1.9 cells/mm3, p < 0.001). Two criteria that are indicative of AAE were identified: NLR values greater than 1.2, with good discriminative ability (area under the curve [AUC] 0.90; 95% confidence interval [CI] 0.85-0.94; sensitivity 82.5%; specificity 79.5%), and ANC values exceeding 3866, with moderate discriminative ability (AUC 0.86; 95% CI 0.81-0.91; sensitivity 75.0%; specificity 82.3%). Moreover, a comparative analysis of these markers (NLR, ANC, PLR, WBC, AEC, and ALC) in patients with AAE did not demonstrate significant differences between those requiring PICU admission and those who did not require it. CONCLUSIONS: This study contributes two major findings. The first is that NLR, ANC, WBC, and PLR are significantly higher in AAE patients compared to those with stable asthma. The second is that children with stable asthma have higher AEC and ALC levels compared to those with AAE. Furthermore, this study has revealed that the studied markers (NLR, ANC, PLR, WBC, AEC, and ALC) did not differentiate between AAE patients requiring PICU admission and those managed in the general ward, suggesting a need for alternative predictive factors.

Association Between Childhood Asthma and Gastroesophageal Reflux Disease in Children: A Systematic Review.

This study aims to comprehensively investigate the association between childhood asthma and gastroesophageal reflux disease (GERD) in children. A thorough search of pertinent databases was done in order to find studies that satisfied the requirements for inclusion. A thorough search of PubMed, Web of Science, SCOPUS, and Science Direct was conducted to find pertinent literature. Twelve studies, including a total of 176,678 patients - 91,447 (51.8%) of them were males - were included in our data. The prevalence of GERD in asthmatic children ranged from 0.7% to 65.3%, with a total prevalence of 3317 (3.6%). The included studies documented that GERD increases the chance of asthma, while asthma raises the risk of GERD. Obesity in asthmatic patients was an independent risk factor for the incidence of GERD. Controlling asthma is significantly impacted by comorbidities like obesity and GRED. The findings of our comprehensive review point to a possible link between juvenile patients with asthma who are referred to secondary and tertiary care facilities and having GERD. Nevertheless, the evidence for this link is weak in a number of situations. Lack of longitudinal research establishing the proper temporal sequence, studies indicating no severity-response relationship, and insufficient data showing a treatment-response relationship all contribute to the uncertainty around the nature and direction of the association. Our findings highlight the need for additional epidemiologic research to investigate the connection between GERD and asthma, including long-term follow-up.

Integrating multi-omics data of childhood asthma using a deep association model.

Childhood asthma is one of the most common respiratory diseases with rising mortality and morbidity. The multi-omics data is providing a new chance to explore collaborative biomarkers and corresponding diagnostic models of childhood asthma. To capture the nonlinear association of multi-omics data and improve interpretability of diagnostic model, we proposed a novel deep association model (DAM) and corresponding efficient analysis framework. First, the Deep Subspace Reconstruction was used to fuse the omics data and diagnostic information, thereby correcting the distribution of the original omics data and reducing the influence of unnecessary data noises. Second, the Joint Deep Semi-Negative Matrix Factorization was applied to identify different latent sample patterns and extract biomarkers from different omics data levels. Third, our newly proposed Deep Orthogonal Canonical Correlation Analysis can rank features in the collaborative module, which are able to construct the diagnostic model considering nonlinear correlation between different omics data levels. Using DAM, we deeply analyzed the transcriptome and methylation data of childhood asthma. The effectiveness of DAM is verified from the perspectives of algorithm performance and biological significance on the independent test dataset, by ablation experiment and comparison with many baseline methods from clinical and biological studies. The DAM-induced diagnostic model can achieve a prediction AUC of 0.912, which is higher than that of many other alternative methods. Meanwhile, relevant pathways and biomarkers of childhood asthma are also recognized to be collectively altered on the gene expression and methylation levels. As an interpretable machine learning approach, DAM simultaneously considers the non-linear associations among samples and those among biological features, which should help explore interpretative biomarker candidates and efficient diagnostic models from multi-omics data analysis for human complex diseases.

Efficacy and safety of subcutaneous and sublingual allergen immunotherapy in the treatment of asthma in children: a systematic review and meta-analysis.

OBJECTIVE: Asthma is a common chronic condition in children globally. Allergen-specific immunotherapy, such as subcutaneous (SCIT) and sublingual (SLIT) therapies, are promising by increasing allergen tolerance. This meta-analysis compares the efficacy and safety of SLIT and SCIT in pediatric asthma. METHODS: We searched PubMed, Cochrane Library, and Embase for randomized controlled trials and case-control studies comparing SLIT and SCIT in asthmatic children. Meta-analysis was conducted using random-effects models with calculations via R software version 4.3.2 and RevMan version 5.4. Study quality and bias risk were assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. RESULTS: The literature search yielded a total of 1787 records, with 7 studies meeting the inclusion criteria after screening and assessments. There was no significant difference in the Total Asthma Symptoms Score between SLIT and SCIT (mean difference -0.05 [95% CI: -0.21; 0.10]). However, asthma improvement rates were higher in the SLIT group (risk ratio 0.77 [95% CI: 0.64; 0.93]). FEV1 improvement showed no significant difference (mean difference -1.60 [95% CI: -6.27; 3.08]). Adverse events were similar between the treatments (risk ratio 0.56 [95% CI: 0.11; 2.82]). CONCLUSIONS: SLIT and SCIT were generally similarly effective and safe for treating pediatric asthma. SLIT may be preferred due to its noninvasive administration. More research is needed on long-term effects and tailored treatment approaches.

Effects of climate and environmental factors on childhood and adolescent asthma: A systematic review based on spatial and temporal analysis evidence.

BACKGROUND: Asthma is a prevalent chronic respiratory disease among children, influenced by various climate and environmental factors. Despite its prevalence, the specific effects of these factors on asthma remain unclear. This study aims to systematically assess the epidemiological evidence using spatial and temporal methods on the impact of climate and environmental factors on childhood asthma. METHODS: A systematic review was conducted to analyse the impact of climate and environmental factors on childhood asthma and wheezing, focusing on spatial and temporal trends. Searches were carried out in PubMed, Embase, and CINAHL databases for studies published from January 2000 to April 2024, using key search terms 'asthma/wheezing', 'extreme weather, 'green space', 'air pollution' and 'spatial or temporal analyses". RESULTS: The systematic review analysed 28 studies, with six employing spatial and 22 using temporal analysis methods; however, none incorporated spatio-temporal analysis in their models. The findings reveal that extreme weather events, including heatwaves and heavy rainfall, elevate childhood asthma risks across various climates, with significant effects observed during summer and winter months. Dust storms in arid and subtropical regions are linked to immediate spikes in hospital admissions due to asthma exacerbations. The effects of green spaces on childhood asthma are mixed, with some studies indicating protective effects while others suggest increased risks, influenced by local environmental factors. Air pollutants such as PM2.5, NO2, and ozone can exacerbate asthma symptoms and along with other environmental factors, contribute to seasonal effects. High temperatures generally correlate with increased asthma risks, though the effects vary by age, sex, and climate. CONCLUSION: Future research should integrate spatial and temporal methods to better understand the effects of environmental and climate changes on childhood asthma.

circUQCRC2 promotes asthma progression in children by activating the VEGFA/NF-κB pathway by targeting miR-381-3p.

This study targeted to explore circUQCRC2's role and mechanism in childhood asthma. A mouse model of ovalbumin-induced asthma was established to evaluate the effects of circUQCRC2 on childhood asthma in terms of oxidative stress, inflammation, and collagen deposition. The effects of circUQCRC2 on platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cells (SMCs) were evaluated, the downstream mRNA of miRNA and its associated pathways were predicted and validated, and their effects on asthmatic mice were evaluated. circUQCRC2 levels were upregulated in bronchoalveolar lavage fluid of asthmatic mice and PDGF-BB-treated SMCs. Depleting circUQCRC2 alleviated tissue damage in asthmatic mice, improved inflammatory levels and oxidative stress in asthmatic mice and PDGF-BB-treated SMC, inhibited malignant proliferation and migration of SMCs, and improved airway remodeling. Mechanistically, circUQCRC2 regulated VEGFA expression through miR-381-3p and activated the NF-κB cascade. circUQCRC2 knockdown inactivated the NF-κB cascade by modulating the miR-381-3p/VEGFA axis. Promoting circUQCRC2 stimulates asthma development by activating the miR-381-3p/VEGFA/NF-κB cascade. Therefore, knocking down circUQCRC2 or overexpressing miR-381-3p offers a new approach to treating childhood asthma.

Contribution of Gestational Weight Gain to Childhood Asthma Phenotypes: A Prospective Cohort Study.

BACKGROUND: The contribution of prenatal anthropometric measures to the development of specific childhood asthma phenotypes is not known. OBJECTIVE: We aimed to evaluate associations between prepregnancy body mass index (BMI) and gestational weight gain (GWG) with allergic and nonallergic asthma phenotypes in childhood. METHODS: Our study population included term, healthy infants in the middle Tennessee region of the United States. Prepregnancy BMI and GWG were ascertained from questionnaires administered during early infancy and categorized based on World Health Organization and Institute of Medicine recommendations, respectively. Allergic asthma was defined as 5-year current asthma and a positive skin test or specific IgE to aeroallergen(s). We used multivariable logistic regression models for asthma and multinomial logistic regression models for nonasthma, allergic asthma, and nonallergic asthma. RESULTS: A total of 1266 children were included. At the 5-year follow-up, 194 (15.3%) had asthma; among them, 102 (52.6%) had allergic asthma. Both inadequate and excessive GWG, compared with adequate GWG, were associated with increased odds of asthma (inadequate: adjusted odds ratio [aOR]: 1.76 [95% confidence interval (CI): 1.03-2.98]; excessive: aOR: 1.70 [95% CI: 1.12-2.57]) and increased odds of allergic asthma compared with no asthma (inadequate: aOR: 3.49 [95% CI: 1.66-7.32]; excessive: aOR: 2.55 [95% CI: 1.34-4.85]). Prepregnancy BMI was not associated with asthma nor with asthma phenotypes. CONCLUSIONS: Both inadequate and excessive GWG were associated with allergic asthma risk. These results support the benefits of optimal GWG during pregnancy on child health outcomes.

Linkage of serum ITIH4 with Th2 signature cytokine, inflammation, exacerbation risk and severity in childhood asthma.

Aim: ITIH4 has anti-inflammatory properties toward eosinophilic/neutrophilic inflammation. This study aimed to explore clinical value of ITIH4 in childhood asthma.Materials & methods: Serum ITIH4 and inflammatory cytokines were determined in 120 childhood asthma patients by enzyme-linked immunosorbent assay.Results: In the entire and acute exacerbation patients, ITIH4 positively associated with IFN-γ, but negatively related to proinflammatory cytokines. ITIH4 was lowest in patients with acute exacerbation, followed by chronic persistent, and highest in clinical remission. By receiver-operating characteristic analysis, ITIH4 potentially estimated acute exacerbation asthma risk. Moreover, ITIH4 negatively related to exacerbation severity in acute exacerbation patients.Conclusion: Serum ITIH4 negatively links with Th2 cell signature cytokine, proinflammatory cytokines, exacerbation risk and severity in childhood asthma.

[Box: see text].

Outdoor Air Pollution and Pediatric Respiratory Disease.

Outdoor air pollution is ubiquitous, and no safe level of exposure has been identified for the most common air pollutants such as ozone and particle pollution. Children are uniquely more susceptible to the harms of outdoor air pollution, which can cause and exacerbate respiratory disease. Although challenging to identify the effects of outdoor air pollution on individual patients, understanding the basics of outdoor air pollution is essential for pediatric respiratory health care providers. This review covers basic information regarding outdoor air pollution, unique considerations for children, mechanisms for increased susceptibility, and association with incident and exacerbation of respiratory disease in children.

Dietary intake, antioxidants, minerals and vitamins in relation to childhood asthma: a Mendelian randomization study.

Background: Currently, there is limited and inconsistent evidence regarding the risk association between daily dietary intake, antioxidants, minerals, and vitamins with Childhood Asthma (CA). Therefore, this study employs Mendelian Randomization (MR) methodology to systematically investigate the causal relationships between daily dietary intake, serum antioxidants, serum minerals, and the circulating levels of serum vitamins with CA. Methods: This study selected factors related to daily dietary intake, including carbohydrates, proteins, fats, and sugars, as well as serum antioxidant levels (lycopene, uric acid, and ß-carotene), minerals (calcium, copper, selenium, zinc, iron, phosphorus, and magnesium), and vitamins (vitamin A, vitamin B6, folate, vitamin B12, vitamin C, vitamin D, and vitamin E), using them as Instrumental Variables (IVs). Genetic data related to CA were obtained from the FinnGen and GWAS Catalog databases, with the primary analytical methods being Inverse Variance Weighting (IVW) and sensitivity analysis. Results: Following MR analysis, it is observed that sugar intake (OR: 0.71, 95% CI: 0.55-0.91, P: 0.01) is inversely correlated with the risk of CA, while the intake of serum circulating magnesium levels (OR: 1.63, 95% CI: 1.06-2.53, P: 0.03), fats (OR: 1.44, 95% CI: 1.06-1.95, P: 0.02), and serum vitamin D levels (OR: 1.14, 95% CI: 1.04-1.25, P: 0.02) are positively associated with an increased risk of CA. Conclusion: This study identified a causal relationship between the daily dietary intake of sugars and fats, as well as the magnesium and vitamin D levels in serum, and the occurrence of CA. However, further in-depth research is warranted to elucidate the specific mechanisms underlying these associations.

Joint associations of air pollutants during pregnancy, infancy, and childhood with childhood persistent asthma: Nationwide database study in Japan.

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02-1.05; p<0.001), 1.02 (95 % CI: 1.01-1.03; p<0.001), and 1.03 (95 % CI: 1.01-1.04; p<0.001), respectively. Moreover, particulate matter with an aerodynamic diameter ≤ 2.5 µm was assigned the highest weight across all three exposure periods. Relatively high weights were assigned to suspended particulate matter and photochemical oxidants during pregnancy, carbon monoxide during infancy, and photochemical oxidants during childhood. Our study showed that a mixture of low-level air pollutants has a detrimental association with childhood persistent asthma.