Background: Previous research has predominantly focused on the relationship between individual nutrients and asthma. However, diet involves complex interactions among its various components. Dietary pattern analysis can more accurately reflect the impact of overall diet on disease. Methods: Based on the 2011-2020 National Health and Nutrition Examination Survey data base, this study included 7216 children ages 3-17 years. Principal component analysis was used to extract dietary features, and K-means clustering was used to identify typical dietary patterns. Multivariate weighted logistic regression was used to analyze the association between dietary patterns and the risk of asthma. Subgroup analyses were also conducted. Furthermore, ordinal logistic regression was used to explore the relationship between dietary patterns and asthma exacerbation levels. Results: Two primary dietary patterns were identified: a "refined high red meat and high sugar diet pattern" (characterized by high intake of refined grains, red meat, processed meats, solid fats, and added sugars) and a "fruits and vegetables enrichment-balanced diet pattern" (characterized by a balanced diet with adequate intake of fruits and vegetables). After adjusting for covariates, children who followed the refined high red meat and high sugar diet pattern had a 15% higher risk of asthma compared with those who followed the fruits and vegetables enrichment-balanced diet pattern (odds ratio [OR] 1.15; p = 0.04). Notably, in the 3-5-year-old subgroup, the fruits and vegetables enrichment-balanced diet pattern was associated with a 54% reduction in asthma risk (OR 0.46). However, no significant association was found between dietary patterns and asthma exacerbation severity levels (p > 0.05). Conclusion: The refined high red meat and high sugar diet pattern is a modifiable risk factor for childhood asthma, whereas the fruits and vegetables enrichment-balanced diet pattern seems to have a protective effect. Early childhood (ages 3-5 years) may be a critical period for dietary intervention. Analysis of these findings suggests that modifying dietary patterns could be an important strategy for the primary prevention of childhood asthma.

Congenital lung malformations (CLM) are developmental anomalies that may predispose to respiratory morbidity. Their association with asthma remains unclear, largely due to small series and the lack of population-based controls. To evaluate asthma prevalence and related outcomes in children with CLM compared to population controls. We conducted a population-based case-control study linking CLM patients from a surgical registry to provincial health data. Each CLM patient was linked to up to ten date-of-birth-matched controls. Asthma was defined by ICD-9/10 codes from age ≥5 years. Outcomes included asthma prevalence, time to first diagnosis, recurrent medical encounters, and pharmacotherapy patterns. Analyses yielded risk ratios (RR), adjusted hazard ratios (aHR), and adjusted incidence rate ratios (aIRR). Forty-nine CLM cases and 486 controls were included. Asthma was diagnosed in 19 (38.8%) CLM cases versus 76 (15.6%) controls (RR = 2.48, 95% CI [1.65-3.73]; p < 0.001). The RR did not differ between surgically and conservatively managed CLM cases (RR = 2.87, 95% CI [0.45-18.32]; p = 0.234). CLM cases had a threefold higher hazard of asthma (aHR = 3.24, 95% CI [1.84-5.71]; p < 0.001). Female cases were particularly affected (aHR = 3.92, 95% CI [1.98-7.74]; p < 0.001), with no difference observed in males (aHR = 1.98, 95% CI [0.90-4.37]; p = 0.092). Annually, CLM patients accumulated 71% more asthma-related encounters (aIRR = 1.71, 95% CI [1.28-2.25]; p < 0.001). Children with CLM are at increased risk of asthma, especially females, with earlier onset and more frequent encounters. These findings highlight the need for long-term respiratory follow-up and objective validation of asthma diagnoses in this population.

Oxidized vitamin E metabolites during infancy and childhood asthma risk: too little, too much, or just right?

Vitamins A and D regulate numerous genes through intersecting metabolic pathways, influencing lung development and asthma. This article aimed to examine the impact of vitamins A and D on lung function, epigenetic ageing and regulatory epigenetics in children and adults with asthma. Two asthma cohorts, GACRS (Genetic Epidemiology of Asthma in Costa Rica Study; 1165 children) and ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma; 1041 adults) were included. Serum miRNA profiles, blood DNA methylation and plasma/serum vitamin A and D levels were measured. Associations between vitamin levels and lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC), miRNA expression and DNA methylation were evaluated. In adults, mediation analysis assessed whether methylation status and miRNAs mediated the relationship between vitamins and lung function or epigenetic ageing. In children, higher vitamin A was associated with higher FEV1 (β=2.5, p=4.9 × 10-3) and FVC (β=7.6, p=7.7 × 10-14) but lower FEV1/FVC (β=-3.9, p=2.0 × 10-16); vitamin D showed no association. In adults, both vitamins were positively associated with FEV1 (vitamin A: β=4.7, p=9.3 × 10-3, vitamin D: β=0.16, p=8.6 × 10-3) and FVC (vitamin A: β=3.4, p=3.0 × 10-2, vitamin D: β=0.18, p=4.6 × 10-4); only vitamin A was associated with FEV1/FVC (vitamin A: β=2.5, p=3.9 × 10-2). Vitamin D sufficiency corresponded to lower epigenetic ageing in adults. Higher vitamin levels were associated with IRF5 regulatory cytosine hypomethylation at cytosine-guanine dinucleotides (CpG), corresponding to better lung function and lower ageing. Distinct vitamin-associated miRNAs were identified, with shared targets enriched in immune and cell-cycle pathways. Mediation analyses indicated statistical partial effects through methylation and miRNAs. Vitamin A, but not vitamin D, in children was associated with better lung function and lower epigenetic ageing in asthma, with effects mediated by DNA methylation and miRNA regulation.

Draft charter for asthma in children and young people, inspired by Martha's rule.

Inhaled corticosteroid (ICS) use in pregnancy has shown associations with decreased offspring asthma in childhood, whereas exacerbations in pregnancy may increase the risk. However, these findings have not been tested in population-based cohorts with rigorous assessment of confounding structures. The aim was to describe asthma exacerbations and ICS utilisation during pregnancy and to assess causal pathways between pregnancy exacerbations, ICS use and offspring asthma. Register-based cohort study of pregnancies in New South Wales (NSW), Australia and Sweden. Maternal monthly asthma exacerbations (hospital visits and/or oral corticosteroid (OCS) dispensings) and ICS dispensing rates were calculated 12 months prepregnancy to 12 months post partum. Among mothers with asthma (35 194 NSW, 102 248 Sweden), Hazard Ratios (HR)s were calculated for pregnancy exacerbations or ICS use and offspring asthma adjusting for confounders including asthma severity. Associations between paternal exposures and offspring asthma and sibling analyses assessed the likelihood of unmeasured confounding. Maternal asthma prevalence was 8.6% in NSW and 7.1% in Sweden. While ICS use was maintained over the course of pregnancy, a postpartum decline was observed, accompanied by a rise in OCS use. Adjusted HRs for offspring asthma were 1.47 (95% CI 1.32 to 1.64, NSW) and 1.30 (95% CI 1.24 to 1.36, Sweden) following maternal exacerbations, and 1.37 (95% CI 1.26 to 1.49, NSW) and 1.23 (95% CI 1.19 to 1.27, Sweden) following maternal ICS use. Paternal exposures were also associated with offspring asthma, while associations in sibling analyses were not significant. Observed associations between maternal exacerbations, ICS use and offspring asthma appear to be due to unmeasured confounding. Management of maternal asthma remains a priority in pregnancy and post partum.

Air pollution in high-poverty neighborhoods contributes to disparities in asthma morbidity. Housing mobility programs help families move to better-resourced neighborhoods and improve asthma outcomes. Whether housing mobility-related improvements in asthma morbidity are explained by reductions in air pollution is unknown. Evaluate change in concentrations of fine particulate matter and its components and associated changes in asthma morbidity among a cohort of children with asthma who moved out of high-poverty neighborhoods. Caregiver-reported asthma exacerbations, symptoms, and asthma control test scores were examined among 123 children (age 5-17) with persistent asthma participating in the Baltimore Regional Housing Partnership housing mobility program. Exposures considered are annual average concentrations of PM2.5 and major PM2.5 components (black carbon, organic carbon, ammonium, nitrate, and sulfate). Children moved to neighborhoods with 0.64 μg/m3 [95% CI: 0.50-0.82] lower PM2.5 concentrations, with greatest reductions in black carbon and organic carbon. One standard deviation higher exposure to PM2.5 was associated with a 60% [95% CI: 21%-112%] higher odds of exacerbations and 20% [14%-27%] higher odds of symptom days/2 weeks. Reductions in PM2.5 exposure explained 77% [39% - 100%] and 22% [16%-36%] of moving-related reductions in exacerbations and symptom days, respectively. Some PM components were also associated with asthma exacerbations and symptoms and showed mediating effects. Moving from high-poverty neighborhoods to better-resourced neighborhoods through a housing mobility program is associated with lower air pollution exposure, contributing to moving-related asthma improvements. Housing mobility may be a useful complement to pollution-focused environmental justice interventions.

Total bilirubin possesses antioxidant and immunomodulatory properties, and its role in childhood asthma is a topic of ongoing debate. We employed both a cross-sectional study and Mendelian randomization (MR) analysis to explore the link between serum total bilirubin and childhood asthma. In the cross-sectional study from the National Health and Nutrition Examination Survey 2007 to 2018, weighted logistic regression models were utilized to investigate the association between serum total bilirubin and childhood asthma. We also used restricted cubic splines to explore the dose-response relationship between the 2. The inverse-variance weighted method was used as the main method of MR analysis to explore the causal effect of exposure on outcomes. A total of 3238 participants were included in the cross-sectional study. Weighted logistic regression analysis encompassing all participants revealed no significant association between total bilirubin levels and the risk of childhood asthma (P > .05). The same results were obtained after categorizing participants into tertiles based on total bilirubin levels. The restricted cubic splines curve revealed an S-shaped relationship between total bilirubin levels and childhood asthma. MR analysis reveals no causal association between serum total bilirubin and childhood asthma (odds ratio [OR] = 0.974, P = .752), peak expiratory flow (OR = 1.002, P = .831), and forced expiratory volume in 1-second (OR = 1.005, P = .554). Our study did not support a causal relationship between serum total bilirubin and childhood asthma. Further studies with a larger number of cases are crucial to validate our findings.

The modelled impact of Low Traffic Neighbourhoods (LTNs) on air pollution: findings from 5 schemes in London.

Chronic cough is a frequent symptom of pediatric Long COVID, hypothetically driven by viral neurotropism and sensory nerve sensitization. We investigated the neuro-immune axis in pediatric asthma to determine if the magnitude of post-SARS-CoV-2 humoral immunity correlates with objective airway afferent nerve hypersensitivity. This prospective observational study included 61 pre-pubertal children (aged 8 to < 12years) with well-controlled, predominantly inhaled corticosteroid (ICS)-treated (93.4%) bronchial asthma and confirmed past SARS-CoV-2 infection. Systemic humoral memory was quantified via anti-Spike IgG and IgA titers. Objective cough reflex sensitivity was measured using a capsaicin challenge test, establishing C2 and C5 values. Subjective symptom burden was evaluated using parent-proxy questionnaires (PCQ, VAS, PedsQL). Stratification by median anti-Spike IgG (125.77 BAU/ml) revealed no significant differences in basal (C2, p = 0.301) or motor response (C5, p = 0.714) capsaicin thresholds between robust and waning humoral memory states. IgA stratification yielded identical results. Spearman's correlation confirmed a complete lack of association between absolute IgG titers and neurophysiological markers (p > 0.05). Crucially, parent-reported chronic cough severity (PCQ, VAS) and asthma-specific quality of life demonstrated a complete dissociation from objective capsaicin thresholds across all evaluated domains (all p > 0.05). Supplementary subgroup analysis revealed no significant differences in cough thresholds based on acute COVID-19 severity (p > 0.05). A robust post-viral humoral immune response to SARS-CoV-2 does not precipitate peripheral airway nerve hypersensitivity in properly controlled, ICS-treated asthmatic children. The complete uncoupling of subjective parent-reported symptoms from objective neurophysiology cautions against diagnosing neurogenic Long COVID based solely on questionnaires, emphasizing the necessity of objective testing and evaluation of alternative atopic etiologies.

Childhood asthma disproportionately affects Hispanic children in the United States. Nevertheless, few longitudinal cohorts exist in Gulf Coast communities where environmental exposures may compound sociodemographic vulnerabilities. Corpus Christi, a majority-Hispanic city with high levels of petrochemical industrial operations, reports higher asthma prevalence than state and national averages. BREATHE-CC (Bridging Respiratory Exposures, Asthma, and Environmental Health in Corpus Christi) is a prospective cohort designed to investigate the role of air pollutants, household conditions, and social determinants of health in asthma exacerbations and wheezing phenotypes. Approximately 200 children less than 10 years of age with asthma will be enrolled from Driscoll Children's Hospital. Enrolled participants complete baseline assessments and are followed monthly for up to 18 months using a parent-reported modified ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire that captures household exposures, asthma exacerbations, and wheezing episodes. Questionnaire responses will be validated and supplemented with electronic health record (EHR) reviews. Daily air pollutant concentrations (PM2.5, PM10, O3, SO2) from the Texas Commission on Environmental Quality (TCEQ) and U.S. Environmental Protection Agency (EPA) monitoring stations will be linked to participants' addresses. Generalized Additive Models (GAMs) and Poisson regressions will assess the associations between air pollutant exposures, household risk factors, asthma exacerbations, and wheezing phenotypes, adjusting for age, sex, body mass index (BMI), and other sociodemographic indicators. Group-Based Trajectory Modeling (GBTM) will identify latent phenotypes of wheezing. This is a longitudinal cohort examining Hispanic children residing in the Gulf Coast petrochemical corridor. In particular, the study integrates granular geospatial environmental monitoring to link daily air pollutant exposure levels with asthma exacerbation risk. GBTM will also be used to identify latent wheezing phenotypes, especially focusing on differences between infectious and non-infectious wheezing. Recruitment will occur at a single hospital in the Coastal Bend region with a modest sample size, which may limit generalizability. Clinical trial number: not applicable. Open Science Framework [https://osf.io/tbg6y/overview?view_only=87309518c35b4d78a7bbe79d5fa70ceb].

The objective of this study was to examine the association between parental education and the occurrence of asthma, allergic rhinitis, and eczema in children, while accounting for potential confounding factors. Data were collected through questionnaires completed by 379 children aged 10 to 12. Maternal, paternal, and combined parental educational levels were assessed. Logistic regression models were used to evaluate associations with the odds of atopic diseases, adjusting for confounders. High parental educational level was significantly associated with a lower occurrence of allergic rhinitis in children (adjusted odds ratio [aOR] = 0.52, 95% CI: 0.27-0.99, P = .048), particularly when mothers had high, and fathers had low educational levels (aOR = 0.30, 95% CI: 0.13-0.71, P = .006). In addition, children with highly educated fathers were less likely to develop eczema (aOR = 0.56, 95% CI: 0.33-0.93, P = .028). These findings suggest that parental education influences atopic diseases in children, reflecting the complex role of social determinants of health.

Antibiotics have deleterious consequences for the gut microbiome and can increase the risk of childhood asthma. While the effects of antibiotics on the bacterial microbiome and asthma risk are well characterized, their impact on the fungal microbiome (mycobiome) remains vastly unexplored. We investigated the effect of antibiotic use on the gut mycobiome in an observational, prospective clinical study of young infants. Antibiotic treatment resulted in increased fungal abundance and expansion of the yeast Malassezia spp. in the infant mycobiome. Based on these findings, we colonized germ-free mouse pups with a defined consortium of mouse-derived bacteria (Oligo-MM12) with or without Malassezia restricta. Colonization with this yeast increased myeloid and lymphoid intestinal immune responses deemed critical in atopy development, and elevated airway inflammation in house-dust mite (HDM)-challenged mice and respiratory syncytial virus (RSV)-infected mice. Further evaluation in eosinophil-deficient mice revealed that the observed immune response is partially dependent on this cell type. This translational work demonstrates that expansion of Malassezia spp. is a previously overlooked collateral effect of infant antibiotic use, which may offer a potential strategy to prevent or mitigate pediatric asthma and related conditions.

Climate and air pollution are associated with pediatric allergic diseases; however, their relative impacts remain poorly understood, particularly in subtropical climates. This study quantified and compared the contributions of meteorological variables and air pollutants to childhood allergic rhinitis (AR), asthma and atopic dermatitis (AD). We analyzed 1,516,996 pediatric hospital visits in Chongqing, China (2014-2019, 2023-2024), including AR (n = 456,807), asthma (n = 775,181), and AD (n = 285,008). Using distributed lag non-linear models, we examined associations with temperature, humidity, atmospheric pressure, wind speed, PM₂.₅, PM₁₀, NO₂, SO₂, CO, and O₃, comparing effect magnitudes through standardized coefficients and attributable disease burdens. Temperature demonstrated the strongest associations across all diseases, with opposing effects: positive associations with respiratory allergies (AR: RR = 1.25, 95% CI: 1.16-1.35 at 30°C, attributing 84,640 cases [18.5% of total burden]; asthma: RR = 1.10, 95% CI: 1.05-1.16 at 32°C, attributing 58,058 cases [7.5%]) versus inverse association with AD (RR = 0.75, 95% CI: 0.68-0.83 at 30°C, associated with 58,270 fewer cases [20.4% reduction]). Seasonal analyses demonstrated marked heterogeneity: summer concentrated AR burden (temperature attributing 18,896 cases, 22.3% of annual burden), while winter concentrated asthma NO₂ effects (21,558 cases, 11.1% of winter burden). Individual air pollutants showed substantially smaller effects than temperature. Temperature demonstrated stronger short-term associations with childhood allergic disease burden than individual air pollutants in subtropical settings. Disease-specific environmental susceptibility patterns (opposing temperature effects for respiratory versus dermatological allergies) necessitate tailored prevention strategies. These results support integrating climate adaptation measures alongside air quality management in pediatric environmental health policies, with season-specific interventions during high-burden periods.

Emerging evidence indicates that early-life lung injuries-including bronchopulmonary dysplasia, childhood asthma, recurrent respiratory infections, and environmental tobacco smoke exposure-are significantly associated with an increased risk of neurodevelopmental disorders such as cognitive impairment, autism spectrum disorder, attention-deficit/hyperactivity disorder, and emotional or behavioral affections. The developing brain is particularly vulnerable during infancy and childhood, and pulmonary insults during this critical window may disrupt normal neurodevelopment through multiple interconnected mechanisms along the lung-brain axis. These mechanisms include the hypoxia-oxidative stress axis, which impairs oligodendrocyte maturation and myelination; pulmonary microvascular injury leading to neuronal energy metabolism dysregulation; systemic inflammation-mediated disruption of the blood-brain barrier; and a cascade from pulmonary inflammation to neuroinflammation, characterized by microglial activation, synaptic dysfunction, and impaired myelination. Together, these pathways converge to produce long-lasting neurodevelopmental consequences. Understanding the lung-brain axis provides a novel theoretical framework for explaining this comorbidity and highlights the need to integrate neurodevelopmental risk assessment and early intervention into the clinical management of early-life lung diseases. Future research should focus on longitudinal cohorts, identification of critical developmental windows, and targeted therapeutic strategies that address both pulmonary and neurological health.

Timing of High-Risk Asthma Specialist Enrollment and Severe Asthma Exacerbations in Children.

Sleep duration influences metabolic health, but the impact of daily sleep variation on next-day glycaemia in healthy individuals under real-world conditions is poorly understood. We studied 206 adolescents (18years) from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) cohort with 2245 person-days of overlapping accelerometer-derived sleep and continuous glucose monitoring (CGM) recordings (median 13days, IQR 9-13). Sleep duration was assessed using wrist-worn accelerometry, and glycaemic concentration, variability, and risk indices were derived from CGM during the accelerometer-defined waking period. Associations were examined using linear mixed-effects models adjusted for sociodemographic, behavioural, circadian, and cardiometabolic factors, with random effects of individuals across repeated days. Each additional hour of sleep was associated with higher next-day glycaemic concentration (median β 0.39mg/dL [0.15, 0.63], p= .002), lower variability (standard deviation (SD) mg/dL β -0.12 [-0.23, -0.01], p= .036), and reduced deviation risk (Average Daily Risk Range (ADRR), indicating lower risk of extreme glucose excursions; β -0.27 [-0.43, -0.10], p= .002). Within-person deviations in sleep predicted next-day glycaemic concentration and deviation risk, whereas habitual between-person differences were more strongly associated with variability. Higher daytime glycaemic variability predicted shorter subsequent sleep (β -0.11h [-0.18, -0.05], p< 0.001). The early-morning pre-wake glucose rise partly mediated the link between longer sleep and higher next-day median glucose (indirect effect 5.0%, p= 0.036). These findings indicate dynamic, bidirectional coupling between sleep and glucose regulation in free-living adolescents, with longer sleep associated with lower next-day glycaemic variability and reduced risk of extreme glucose excursions.

This multicenter cohort study investigated the association between neonatal Respiratory Distress Syndrome (RDS) and wheezing in preschool-aged preterm infants. A total of 525 children born at < 32-weeks' gestation were enrolled from three tertiary hospitals in Southwest China and classified into RDS (n = 275) and non-RDS (n = 250) groups. Current wheezing (≥ 1 parental-reported episode in the past year) outcomes were assessed using the International Study on Asthma and Allergy in Childhood (ISAAC) questionnaire at 3-6 years of age. The RDS group showed a significantly higher incidence of current wheezing (11.3% vs. 5.6%; aOR = 2.45, 95% CI 1.20-4.98). Subgroup analyses revealed particularly elevated risks among females, infants born at 28⁺⁰-29⁺⁶ weeks, those with birth weights of 1000-1499g, non-IVF conceptions, those with bronchopulmonary dysplasia, and those with < 14-days of oxygen therapy. Sensitivity analyses supported the robustness of these findings. The study indicates that RDS is an independent risk factor for wheezing in preterm preschoolers and highlights the need for targeted respiratory monitoring in this population.

To investigate the predictive value of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) levels in bronchoalveolar lavage fluid (BALF) for the development of asthma in children under 6 years of age with recurrent wheezing. A prospective cohort study was conducted from May 1 to September 30, 2024. Fifty children under 6 years of age with recurrent wheezing were enrolled as the wheezing group from the Department of Respiratory Medicine at Children's Hospital of Chongqing Medical University, while 51 age-matched children with bronchial foreign bodies were recruited as controls during the same period. Levels of IL-25, IL-33, and TSLP in BALF were measured by enzyme-linked immunosorbent assay (ELISA). Children in the wheezing group were followed for one year and were subsequently categorized into an asthma group or a non-asthma group based on the follow-up outcomes. Integrating these clinical data with BALF cytokine levels, we constructed a predictive model for asthma development using receiver operating characteristic (ROC) curve analysis. Univariate analysis revealed significant differences between the wheezing group and the control group in terms of clinical characteristics (the number of wheezing episodes, age, history of allergy, breastfeeding), peripheral blood eosinophil count, BALF parameters (nucleated cells, red blood cells, neutrophils, macrophages), and cytokine levels (IL-25, IL-33, TSLP) (P < 0.05). Of the 47 children in the wheezing group who completed the follow-up, 17 were diagnosed with asthma (asthma group) and 30 did not develop asthma (non-asthma group). Univariable analysis revealed significant differences between these two groups in terms of age, the number of wheezing episodes, levels of IL-25, IL-33, and TSLP in BALF (P < 0.05). Logistic regression analysis confirmed that these factors were significant predictors for the progression to asthma in children with recurrent wheezing (P < 0.05).ROC curve analysis demonstrated that the combination of the number of wheezing episodes with IL-25, IL-33, or TSLP levels yielded higher predictive values, with area under the curve (AUC) values of 0.90 (95% CI: 0.788-1.000), 0.946 (95% CI: 0.855-1.000), and 0.86 (95% CI: 0.698-1.000), respectively. These were superior to predictions based on wheezing episodes alone (AUC: 0.705) or individual cytokine levels (IL-25 AUC: 0.779; IL-33 AUC: 0.857; TSLP AUC: 0.841). In children under 6 years with recurrent wheezing, the levels of IL-25, IL-33, and TSLP in BALF are elevated and hold predictive value for the subsequent development of asthma, providing a reference for the early clinical identification of at-risk children.

Epigenetic gestational age acceleration in cord blood is associated with activated inflammatory gene pathways and childhood asthma.