BACKGROUND:Wheezing and asthma exacerbations are leading causes of pediatric hospital admissions. Predicting which children will experience persistent exacerbations remains challenging. Prior research has identified immune endotypes in the nasal epithelium of children with acute asthma and wheezing, characterized by varying balances of interferons and inflammatory markers. Notably, children exhibiting low interferon responses coupled with high inflammation are at an increased risk for recurrent respiratory exacerbations. OBJECTIVE:This study aimed to determine if blood-based gene network biomarkers can detect immune endotypes in children presenting with acute wheeze and asthma, potentially serving as predictive tools for future exacerbations. METHODS:We conducted gene expression analysis using microarrays of peripheral blood mononuclear cell samples from pediatric patients who presented to hospital for acute wheeze and asthma. Personal network inference was used to discern gene expression patterns, facilitating the classification of patients' disease into distinct immune endotypes. RESULTS:Three immune endotypes were identified. One endotype, characterized by low interferon responses and elevated expression of both innate and adaptive immune pathways, was significantly associated with an increased risk of subsequent hospital respiratory presentations and a persistent pattern of respiratory exacerbations over time. CONCLUSION:Peripheral blood mononuclear cell-based personal gene network biomarkers can effectively identify immune endotypes correlating with clinical outcomes in pediatric asthma. The high-risk endotype represents a potential treatable trait in acute wheezing episodes. Therapeutic strategies aimed at enhancing interferon responses and/or reducing inflammation may benefit this subgroup.

Background Children are disproportionately affected by the negative health effects of climate change. We did a systematic review to synthesise the available evidence on tested interventions to improve child health in response to the impacts of climate change.Methods We searched PubMed, Medline, Embase and Google Scholar for relevant literature of any study type published up to 14 March 2024. We applied the mixed-methods appraisal tool to assess the quality of evidence of each study, excluding reviews.Results Of 4381 records we identified, 52 met the eligibility criteria. Interventions addressed health outcomes relating to: (1) heat (n=14), (2) water, sanitation and hygiene (n=3), (3) food insecurity and undernutrition (n=4), (4) disasters and extreme weather (n=6), (5) respiratory illness (n=3), (6) mental health (n=2) and (7) vector-borne diseases (n=5). 15 studies examined the co-benefits of mitigation on child health outcomes. Maternity ward relocation and high school sport guidelines reduced heat-related morbidity. Cash transfers to pregnant women, rainwater collection and access to green spaces reduced the incidence of low birth weight. Household-level livelihood diversification reduced the incidence of being underweight during childhood. Retrofitting buildings with insulation and administering pneumococcal conjugate vaccines improved respiratory outcomes. Insecticide-treated nets, indoor residual spraying and artemisinin-based combination therapy reduced malaria complications. Classroom-based sessions related to climate change and post-bushfire counselling increased mental well-being, knowledge of climate risks and adaptive behaviours. Reports of mitigation policies found co-benefits in improving infant mortality, and respiratory and adverse birth outcomes.Conclusions Current evidence reporting which interventions are successful is scarce, heterogenous and of inconsistent quality. More robust scientific demonstrations of effectiveness are needed for interventions within climate change policies to ensure they improve child health.

Background Rising global temperatures have resulted in an increase in the frequency and severity of heatwaves. Pregnancy is a time of substantial physiological change and thus maternal and neonatal health outcomes are susceptible to adverse effects of heat. There is a lack of knowledge about thermoregulation in pregnancy, including how effectively pregnant people adapt in different climate contexts and what specific environmental conditions present the largest thermoregulatory challenges. The primary aim of this study is to examine the associations between exposure to heatwaves during pregnancy and maternal, neonatal, and child health outcomes in Western Australia climatic regions. Methods All neonates born in Western Australia between 1991 and 2023 will be identified from perinatal records (~960,000 neonates). Perinatal records will be linked to weather data from the ERA5 database using Statistical Area 2 geocoding to identify heatwave exposed pregnancies. Commonly used definitions of heatwave exposure will be tested against three neonatal outcomes (pre-term birth, low birth weight, and congenital anomalies). From this, a single definition will be selected to examine maternal, neonatal, and child health outcomes using linked hospital, emergency department, and education assessment data, as well as data from the Western Australian congenital anomalies and death register. The association between heatwaves during pregnancy and health outcomes will be performed using generalised estimating equations, adjusting for covariates including, but not limited to, cigarette smoking, parity, maternal age, socio-economic status, and Aboriginality where appropriate. Stratification by socio-economic status and geographic region will also be carried out. Discussion Examining the association between exposure to heatwaves in pregnancy and maternal, neonatal and child outcomes is important given the increasing frequency of heatwaves. The study will highlight which heat definitions confers the highest vulnerability as well as demographic and geographic subgroups who are particularly vulnerable to the effects of heatwaves. It will provide valuable information for future public health planning, including targets for intervention.

Asthma affects millions worldwide. Long non-coding RNA (lncRNA) are emerging as important factors in the pathophysiology of asthma and respiratory illnesses. LncRNA serve important regulatory roles in numerous pathways, especially gene expression. Nuclear paraspeckle assembly transcript 1 (NEAT1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) are two of the most well-studied lncRNA. This review highlights the current evidence of mechanisms involving lncRNA, particularly NEAT1 and MALAT1, in asthma pathophysiology and viral-induced exacerbations, and as novel targets for therapies targeting asthma, asthma-related symptoms and airway remodelling.

National policies are essential for countries to adapt to the negative health impacts of climate change. Children are disproportionately affected by these impacts and must be at the heart of adaptation policies to address their vulnerabilities. Adaptation commitments worldwide are integrated into national adaptation plans, nationally determined contributions, national communications, and other multisectoral policies. We aimed to evaluate how effectively national climate change policies worldwide plan to protect child health, considering a range of determinants for successful child-health adaptation. We collated each country’s most recent national climate change adaptation plan published up to 12 July 2024. We created a checklist to assess how effectively policies were designed to protect child health, considering five determinant areas: policy background, goals, resources, monitoring evaluation, and implementation. We assigned each policy quality categories (weak, needs improvement, or strong) for each determinant area, and an overall score (0–23) based on how many items were achieved from the checklist. National adaptation policies worldwide had poor planning to adapt to the harms climate change will cause child health, with 43

Diarrhoea remains a leading cause of mortality among children under five years of age, with over 99 % of deaths occurring in low- and middle-income countries. Poor water quality, inadequate sanitation, poverty, undernutrition, and limited healthcare access contribute to this lingering problem, together with emerging environmental stressors driven by climate change. We analysed long-term spatial relationships between environmental, socio-economic, and maternal/child factors using Demographic and Health Surveys and WorldClim data across eight South and Southeast Asian countries (n = 66,545 clusters; 3,143,811 child-level observations). We employed boosted regression trees to assess variable importance across five thematic phases: socio-economic, maternal, child, climate, and combined. We selected variables based on biological plausibility, collinearity checks, and completeness. We addressed uncertainty through multiple imputation and stochastic resampling, and we evaluated model performance using cross-validation. The main predictors of diarrhoea incidence included annual temperature variability, precipitation in the wettest month, maternal education, and household size. Higher annual temperature range (30-40 °C) was associated with a ∼ 39 % increase in diarrhoea probability, while lower precipitation in the wettest month (< 600 mm) increased risk by ∼ 29 %, highlighting the role of drier conditions. We found that maternal education < 8 years increased diarrhoea probability by ∼ 18 %, and household sizes exceeding six members increased it by ∼ 9 %. Our findings emphasise the need for climate-resilient public-health policies that integrate social and environmental determinants of diarrhoea. Targeted interventions - including improved maternal education, water and sanitation infrastructure, and resource management in densely populated households - are necessary to mitigate diarrhoea risk in vulnerable regions under changing climate conditions.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

IntroductionRecurrent wheezing disorders including asthma are complex and heterogeneous diseases that affect up to 30% of all children, contributing to a major burden on children, their families, and global healthcare systems. It is now recognized that a dysfunctional airway epithelium plays a central role in the pathogenesis of recurrent wheeze, although the underlying mechanisms are still not fully understood. This prospective birth cohort aims to bridge this knowledge gap by investigating the influence of intrinsic epithelial dysfunction on the risk for developing respiratory disorders and the modulation of this risk by maternal morbidities, in utero exposures, and respiratory exposures in the first year of life.MethodsThe Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) study is nested within the ORIGINS Project and will monitor 400 infants from birth to 5 years. The primary outcome of the AERIAL study will be the identification of epithelial endotypes and exposure variables that influence the development of recurrent wheezing, asthma, and allergic sensitisation. Nasal respiratory epithelium at birth to 6 weeks, 1, 3, and 5 years will be analysed by bulk RNA-seq and DNA methylation sequencing. Maternal morbidities and in utero exposures will be identified on maternal history and their effects measured through transcriptomic and epigenetic analyses of the amnion and newborn epithelium. Exposures within the first year of life will be identified based on infant medical history as well as on background and symptomatic nasal sampling for viral PCR and microbiome analysis. Daily temperatures and symptoms recorded in a study-specific Smartphone App will be used to identify symptomatic respiratory illnesses.DiscussionThe AERIAL study will provide a comprehensive longitudinal assessment of factors influencing the association between epithelial dysfunction and respiratory morbidity in early life, and hopefully identify novel targets for diagnosis and early intervention.

The earliest respiratory function assessments, within or close to the neonatal period, consistently show correlations with lung function and with the development of asthma into adulthood. Measurements of lung function in infancy reflect the in utero period of lung development, and if early enough, show little influence of postnatal environmental exposures. Later in the preschool and school age periods, influences of the environment are superimposed on initial levels. Fetal exposures before birth such as maternal smoking during pregnancy, lead to reduced lung function and an increased risk of asthma in females particularly those with certain glutathione S-transferase genotypes. Lung function measurements later in the preschool period are also associated with development of asthma. Although lung function in preschoolers does help predict asthma in later life and these observations have increased our understanding of the physiology underlying asthma, the findings have not led to thewidespread use of lung function measurements being in preschoolers as clinical predictors of asthma due to the practicalities of testing in this age group.

Background: Children are more vulnerable than adults to climate-related health threats, but reviews examining how climate change affects human health have been mainly descriptive and lack an assessment of the magnitude of health effects children face. This is the first systematic review and meta-analysis that identifies which climatehealth relationships pose the greatest threats to children. Objectives: We reviewed epidemiologic studies to analyse various child health outcomes due to climate change and identify the relationships with the largest effect size. We identify population-specific risks and provide recommendations for future research. Methods: We searched four large online databases for observational studies published up to 5 January 2023 following PRISMA (systematic review) guidelines. We evaluated each included study individually and aggregated relevant quantitative data. We used quantitative data in our meta-analysis, where we standardised effect sizes and compared them among different groupings of climate variables and health outcomes. Results: Of 1301 articles we identified, 163 studies were eligible for analysis. We identified many relationships between climate change and child health, the strongest of which was increasing risk (60 % on average) of preterm birth from exposure to temperature extremes. Respiratory disease, mortality, and morbidity, among others, were also influenced by climate changes. The effects of different air pollutants on health outcomes were considerably smaller compared to temperature effects, but with most (16/20 = 80 %) pollutant studies indicating at least a weak effect. Most studies occurred in high-income regions, but we found no geographical clustering according to health outcome, climate variable, or magnitude of risk. The following factors were protective of climate-related child-health threats: (i) economic stability and strength, (ii) access to quality healthcare, (iii) adequate infrastructure, and (iv) food security. Threats to these services vary by local geographical, climate, and socio-economic conditions. Children will have increased prevalence of disease due to anthropogenic climate change, and our quantification of the impact of various aspects of climate change on child health can contribute to the planning of mitigation that will improve the health of current and future generations.

Abstract Background Several studies on the serum level of vitamin D and the percentage of vitamin D deficiency in children with asthma have been conducted in Asia and Africa, but the results have been inconsistent and inconclusive, requiring a systematic review and meta-analysis to assess the strength of the evidence. Objective The objective of this review is to synthesize evidence on serum levels of vitamin D and the percentage of vitamin D deficiency among children with asthma in Asia and Africa. Methods To identify relevant articles, a comprehensive search was conducted across various databases and repositories such as PubMed, Google Scholar, Hinary, Web of Science, ResearchGate, as well as gray literature sources. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed during the retrieval process. Data extraction was performed following a standardized format based on the JBI (Joanna Briggs Institute) data extraction guidelines. Microsoft Excel was utilized for data extraction, and subsequently, the data was exported to STATA 17 for further analysis. To assess the heterogeneity among the included studies, Cochrane Q-statistics and the I2 tests were employed. Publication bias was assessed using the Egger test and funnel plot. Result This meta-analysis investigated 33 articles encompassing a total of 3432 children diagnosed with asthma. The findings demonstrated that in low- or middle-income countries across Africa and Asia, children with asthma had an average serum vitamin D level of 21.9 ng/ml (95% confidence interval [CI]: 18.0–25.9 ng/ml), with 53.7% (95% CI: 40.5–66.9) experiencing vitamin D deficiency. Additionally, when considering the continent, children with asthma in Asia had an average serum vitamin D level of 18.5 ng/ml (95% CI: 13.8–23.3), while those in Africa had a level of 28.7 ng/ml (95% CI: 22.7–34.8). The analysis further explored different sub-group analyses. Depending on the study design, case–control studies yielded an average serum vitamin D level of 20.3 ng/ml (95% CI: 18.2–22.4), whereas cross-sectional studies resulted in 23.8 ng/ml (95% CI: 17.5–30.1). Based on publication year, studies published on or before 2015 had an average serum level of 21.0 ng/ml (95% CI: 18.0–24.0), while those published after 2015 had a level of 22.4 ng/ml (95% CI: 17.2–27.7). Moreover, when considering sample size, studies with 100 participants or less had an average serum level of 21.7 ng/ml (95% CI: 17.3–26.1), while studies with more than 100 participants had a level of 22.1 ng/ml (95% CI: 18.6–25.6). Conclusion Children with asthma in Asia and Africa were found to have low serum levels of vitamin D and a high percentage of vitamin D deficiency. This highlights the importance of early detection and monitoring of vitamin D levels in these children to prevent potential complications associated with vitamin D deficiency. Taking proactive measures to address and manage vitamin D deficiency is crucial for the well-being of children with asthma in these regions.

Background: Impaired interferon response and allergic sensitization may contribute to virus -induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity as critical producers of type I interferons. pDCs also express the highaffinity IgE receptor through which type I interferon production may be negatively regulated. Whether antiviral function of pDCs is associated with recurrent episodes of wheeze in young children is not well understood. Objective: We sought to evaluate the phenotype and function of circulating pDCs in children with a longitudinally defined wheezing phenotype. Methods: We performed multiparameter flow cytometry on PBMCs from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDCs from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database. Results: We observed a significant depletion of circulating pDCs in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the Fc epsilon RI on their pDCs. Based on transcriptomic analysis, pDCs from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a nonrecurrent wheezing phenotype. Conclusions: Our data suggest that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of high -affinity IgE receptor is increased and their function as major interferon producers is impaired during acute exacerbations of wheeze. (J Allergy Clin Immunol 2024;153:1083-94.)

Of the 3 rhinovirus (RV) species, RV-A and RV-C most frequently cause illnesses, and RV-C is closely associated with childhood wheezing. The large number of RV types (> 160) presents a challenge for vaccine development. Little is known about RV type-specific age predilection. Multicenter data were pooled from 14 cohorts (n = 4344 patients aged 0-18, 10329 samples) including partial sequencing of nasal swab samples collected from 1997-2018. We identified RV of each species that were consistently most prevalent. Mean age of infection for each type was evaluated amongst the top circulating viruses (Tukey's test). The top 5 circulating RV-C types were: C2(4.8%), C11(4.7%), C6(4.0%), C43(3.7%), and C15(3.4%). The top 5 circulating RV-A types were: A78(5.4%), A12(4.4%), A101(4.4%), A21(3.6%), and A36(3.4%). The frequency of these predominant types remained highly stable over the study period. Types C2 and C40 showed the lowest mean ages of infection, 1.54 and 2.31 years respectively. RV types A12, A78, and A56 demonstrated the lowest mean age of infection among RV-A viruses, 1.9, 2.2 and 2.4 years, respectively. This age variation was statistically significant when compared against other commonly circulating RVs. Species of viruses with the lowest mean age of infection were observed to be closely related phylogenetically. We documented remarkable stability of predominant types of all 3 RV species over 20 years. and a lower mean age of infection for certain types. The close phylogenetic relationship between RV with the lowest mean age of infection suggests a possible biologic mechanism for their age-related infectivity patterns.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health.Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

Modern living conditions and the recent surge in global urbanization have transformed the human microbiome. This transformation is believed to be a significant factor in the recent spike of common chronic inflammatory diseases like asthma and allergies worldwide, evident in both developed and developing nations. Immigrants from less developed regions who settle in highly urbanized and affluent areas present an ideal demographic for research. Investigating immigrant populations can yield valuable insights, particularly when studying microbiome changes that occur as individuals transition from areas with low asthma prevalence to regions with a high prevalence of the condition. The application of prebiotics and probiotics as potential treatments for asthma and allergies faces challenges. This is due to the complex interplay of numerous factors that contribute to their aetiology. Exploring the interaction between the human microbiome and potential epigenetic changes in specific populations, such as immigrants adapting to new, urbanized environments, may offer crucial insights. Such research could underscore the role of prebiotics and probiotics in preventing allergic conditions. Recognizing the changes in the human microbiome in the context of a Western/modern environment might be essential in addressing the increasing prevalence of allergic diseases. Persistent research in this domain is pivotal for devising effective interventions such as dietary supplementation with prebiotics and probiotics.

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Copy DOI