The global prevalence of childhood asthma has undergone profound shifts, marked by a late-20th-century plateau in Western nations and a rapidly emerging epidemic across many developing countries. Traditional risk factors, such as air pollution, allergen exposure, and viral infections-fail to fully explain these trends. Instead, many birth cohorts and migrant studies strongly implicate changing early-life environments. Grounded in the hygiene and biodiversity hypotheses, this review explores the critical environmental determinants of childhood asthma. We synthesize global epidemiological data highlighting stark urban-rural disparities, drawing on seminal studies of European farming cohorts, US Amish and Hutterite communities, and cross-border Chinese populations. These populations collectively demonstrate the protective effects of early-life microbial exposure. We detail the current understanding of how environmental microbes and their metabolites dictate the maturation of the infant immune system, fostering systemic tolerance and preventing allergic trajectories. Furthermore, we evaluate emerging prospective primary intervention trials, including the ORBEX, TIGER, and MARTHA studies, which leverage microbial strategies in an attempt to alter the natural history of asthma development. Ultimately, the loss of environmental microbial diversity could be a primary driver of the allergy epidemic. Elucidating the underlying biological mechanisms of immune-microbe crosstalk and advancing prospective intervention trials will be essential for developing effective primary prevention strategies against childhood asthma.

Early-life environmental exposures are critical determinants of the onset of childhood asthma, with risk patterns demonstrating significant heterogeneity across geographical and socioeconomic landscapes. While the “hygiene hypothesis” has long framed the rural-urban disparity—where urban children typically show higher asthma prevalence than their rural counterparts—this dichotomy is being reshaped by rapid globalization and urbanization. Furthermore, this pattern differs markedly between high-income countries (HICs) and low- and middle-income countries (LMICs). In HICs, the environmental distinction is sharp, with urban environments often characterized by a scarcity of protective microbial factors coupled with an accumulation of anthropogenic pollutants. In contrast, within developing economies undergoing rapid transition, the boundaries between rural and urban areas are increasingly blurred, and environmental exposures often involve a complex interaction among protective and risk factors. These divergent pathways are further complicated by socioeconomic inequities. This review summarizes the global burden of asthma, compares the multi-dimensional determinants across rural and urban environments in HICs (the West) and LMICs (the East), and constructs a refined risk map. It also seeks to identify key characteristics with potential for public health intervention, thereby providing a scientific basis for developing targeted asthma prevention strategies tailored to varying socioeconomic contexts.

Asthma affects over 262 million people worldwide. Current therapies target downstream inflammation but fail to prevent upstream alarmin TSLP production, underscoring the need for novel strategies. Gut microbiota and their metabolites offer a promising avenue for asthma prevention. Lacticaseibacillus paracasei Zhang (L. paracasei Zhang) is a probiotic that remodels gut microbiota and increases butyrate. Butyrate is depleted in asthma and can decrease TSLP, yet the mechanism remains unclear. PARP1-mediated parthanatos drives TSLP expression in other inflammatory conditions, but whether this pathway operates in asthma has not been explored. We hypothesized that L. paracasei Zhang alleviates asthma by remodeling gut microbiota and promoting butyrate to suppress PARP1-mediated parthanatos and TSLP. By integrating mouse experiments, network pharmacology, and in vitro studies, we found that L. paracasei Zhang dose-dependently attenuated asthmatic phenotypes, inflammation, and immune imbalances in OVA-induced mice, achieving efficacy comparable to dexamethasone (DEX). The probiotic remodeled gut microbiota and restored butyrate across fecal, plasma, and lung, while inhibiting lung parthanatos and TSLP. Butyrate exhibited inverse associations with parthanatos markers and TSLP, and network pharmacology identified it as the top metabolite bridging gut microbiota to asthma. Mechanistically, in OVA-treated human bronchial epithelial cells, butyrate suppressed parthanatos and TSLP in a dose-dependent manner, with 1 mM butyrate showing effects comparable to the PARP1 inhibitor PJ34, and this protection was abolished by the PARP1 activator MNNG. These findings demonstrate that L. paracasei Zhang suppressed TSLP expression in asthma via the butyrate-PARP1-parthanatos axis, indicating its potential as a functional food for asthma prevention.

BACKGROUND:Allergic diseases represent a significant global health burden. Beyond traditional treatments, which have limitations, biologics provide targeted, effective add-on therapies. However, despite its importance, the research landscape of allergy biologics has not been thoroughly examined. METHODS:English publications were collected from Web of Science, Scopus, and PubMed. After screening, 4141 research articles published between 1981 and 2024 were analyzed using Python, Tableau, and Gephi. RESULTS:Our results support the growing relevance of biologics in the treatment of allergic diseases. The volume of publications has witnessed a 25-fold increase since 2001. International collaboration has also accelerated substantially since 2015. The United States led in English research output, with the University of California system being the most prolific institution and Novartis as the largest funder. The Journal of Allergy and Clinical Immunology was the most cited journal. Simpson, E.L. and Pirozzi, G. were the most prolific and most cited authors, respectively. Keyword analysis revealed four major research clusters: 1) eczema and dupilumab, 2) asthma and omalizumab, 3) severe asthma and biologic, as well as 4) food allergy and monoclonal-antibody. Keyword bursts pinpointed eczema, dupilumab, and upadacitinib as dominant research hotspots as of 2024. CONCLUSIONS:Our study reveals rapid growth in research on allergy biologics, characterized by expanding global collaborations, distinct thematic communities, and emerging topics on targeted therapies for atopic conditions. While the findings primarily reflect trends in English publications, the prominent research themes and patterns provide an informative framework for future research, collaboration, and next-generation therapies.

BACKGROUND:Food allergies (FA) represent an emerging public health concern in developing nations, with schools being critical settings for preventing life-threatening anaphylaxis. This study assesses the FA preparedness in China's primary and pre-primary institutions to identify key determinants of readiness and inform evidence-based policy. METHODS:A national cross-sectional survey was conducted between June and December 2024. A principal-designated staff member from 4769 schools across 32 provinces and 300 cities completed an online questionnaire. Data were collected on school demographics, existing FA policies, staff training protocols, emergency medication access (specifically epinephrine), and staff knowledge of allergy management. RESULTS:Significant disparities in FA preparedness were identified between government-funded (public) and self-funded (private) institutions. Public schools demonstrated superior preparation regarding emergency medication availability (adjusted odds ratio [aOR] = 1.392, p < .001) and policy implementation (aOR = 1.161, p = .029). Preparedness drivers also differed by school type: public schools were primarily influenced by the presence of students with known allergies (aOR = 1.806), whereas private schools were more strongly driven by the presence of a school physician (aOR = 8.608). Furthermore, private schools reported greater barriers to policy implementation (τj: 2.253 for public vs. 2.540 for private, p < .001). CONCLUSIONS:A school's funding model is a key determinant of its FA emergency preparedness. These findings underscore the urgent need for uniform national standards for FA management in schools. In countries where there is no standardized FA management policy, a nationally approved evidence-based policy would not only enhance student safety but also empower the staff at school to manage severe food allergic reaction. The establishment of such policy are of particular importance in developing countries where the prevalence of FA will increase with economic advancement.

Food allergies(FAs)have increasingly become a concern around the world,with rates and food triggers differing sub-stantially across countries[1,2].Certain industrialized and westernized regions seem to be disproportionately affected,along with an increasing number of countries that were once classified as developing[3].

BackgroundPopulation aging represents a pressing challenge for China, given its vast population and the growing proportion of adults aged 65 years and older. The study aimed to assess burden of ageing spectrum of diseases in China from 1990 to 2021.MethodsThe main outcome measures were disability-adjusted life years (DALYs), summary exposure values (SEVs), and attributable risk. The average annual percent change (AAPC) in number and age specific rate (ASR) were calculated to quantify the temporal trends. The decomposition analysis was utilized to assess the impact of population aging on the burden of disease.ResultsFrom 1990 to 2021, The ASR of all-cause DALYs in China decreased by 35.94% overall and by 33.99% among individuals ≥65 years. However, the number of DALYs attributed to population ageing among people aged 65 and older has been increasing by 10.45 million. Chronic obstructive pulmonary disease, stroke, and ischemic heart disease are most significantly affected by the aging trend. Notably, the older adults population exhibited the most pronounced increase in HIV/AIDS-related DALYs, especially in the 70–74 years group (AAPC: 7.96, 95% CI 6.69, 9.24). Additionally, notable changes in COVID-19-related DALYs became evident beginning in 2019. Regarding risk factors, particulate matter pollution, smoking, and high sodium diets emerged as the top three contributors to health risks among the older adults.ConclusionTo address burden of ageing spectrum of diseases, China should leverage complementary roles of public and private insurance to manage cardiovascular and pulmonary disease, promote healthy environments and diets and prioritize prevention of HIV/AIDS.

Asthma and allergies have emerged as some of the most common chronic diseases, particularly in developed countries. Epidemiological studies have consistently demonstrated that children growing up in farming/rural environments are less likely to develop these conditions. Over the past three decades, China has experienced unprecedented economic development and urbanisation, accompanied by a rapid rise in the prevalence of allergic disorders. Despite the substantial number of affected individuals, allergy management in China remains inconsistent and often inadequate, compounded by variations in diagnostic criteria and limited healthcare access in less developed regions. Furthermore, the vast population, regional disparities, and methodological inconsistencies in data collection have hindered the acquisition of comprehensive, large-scale epidemiological data. This review examines the factors contributing to asthma and allergies from their early origins, focusing on modifiable factors from a specific perspective of China. Factors related to traditional lifestyle, such as early-life exposure to agricultural farming and poultry, diverse dietary patterns, and early introduction of allergenic foods, appear to offer protection against allergies. Conversely, exposure to open-fire cooking, incense burning, tobacco smoke, as well as early-life antibiotic use and perinatal factors like Caesarean section delivery and prematurity may represent potential risks. A clear understanding of the role of these factors would pave the way for developing effective interventions to mitigate the substantial health and socioeconomic burdens associated with asthma and allergies.

Food allergies have surged in Western countries since the late 20th century. Despite the steady rate of food allergy prevalence since the 21st century, anaphylaxis incidence continues to rise. Recent studies indicated that food allergies and anaphylaxis are not uncommon in the developing world, but the trend in food allergy is marked by significant regional differences and urban-rural disparity. Globally, there is a discernible pattern of evolving allergen triggers associated with food protein-induced enterocolitis syndrome (FPIES), alongside the emergence of new food allergies, such as alpha-gal syndrome. Effective management of these allergies faces numerous challenges, including a lack of comprehensive data from developing nations. The global shortage of allergists, coupled with inconsistent access to care—particularly in low- to middle-income regions where epinephrine auto-injectors are often unavailable—further complicates the situation. Addressing these issues requires enhancing training for healthcare providers and establishing standardized practices to ensure comprehensive support for individuals with food allergies. The increasing instances of anaphylaxis underscore the need for strategies that extend beyond simple allergen avoidance. Recent innovations in food allergy treatment, including allergen immunotherapy (AIT) and alternative delivery methods like oral, epicutaneous, and sublingual immunotherapy, show great promise in desensitizing patients, particularly young children. Nonetheless, there remains a pressing need for more long-term safety studies and inclusive clinical trials. This article aims to examine the evolving landscape of food allergies globally and highlight critical gaps in our understanding and management, inspiring a collective effort to improve.

Since the lifting of COVID-19 control measures, infections by common respiratory pathogens have emerged as a public health issue, and the impacts on vulnerable children with wheezing illnesses remain uncertain. This prospective study enrolled children (< 18 years) hospitalized for wheezing disorders in Hong Kong (2016‒2025). Nasopharyngeal aspirates collected within 12 h of admission were tested via rapid antigen detection, viral culture, and multiplex polymerase chain reaction (PCR) for respiratory viruses. Bacterial pathogens were identified through cultures of blood/airway specimens or PCR, including Chlamydia pneumonia and mycoplasma pneumoniae detection via PCR. A total of 2499 children [66.8

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications which exerts detrimental effects on mothers and children. Emerging evidence has pointed to the important role of the fatty acid transporter protein CD36 in the pathogenesis of GDM. As a heavily glycosylated transmembrane protein, CD36 is widely expressed in diverse cell types, including placental trophoblasts, monocytes/macrophages, adipocytes, and pancreatic cells et al. CD36 plays a key role in lipid metabolism and signal transduction in the pathophysiological mechanism of GDM. The modified expression and functionality of CD36 may contribute to inflammation and oxidative stress in maternal tissues, interfere with insulin signaling, and subsequently influence maternal insulin sensitivity and fetal growth, increasing the risk for GDM. This review provides an overview of the current knowledge regarding the expression and function of CD36 in various tissues throughout pregnancy and explores how CD36 dysregulation can activate inflammatory pathways, worsen insulin resistance, and disrupt lipid metabolism, thereby complicating the necessary metabolic adjustments during pregnancy. Furthermore, the review delves into emerging therapeutic approaches targeting CD36 signaling to alleviate the impacts of GDM. Understanding the involvement of CD36 in GDM could yield crucial insights into its mechanisms and potential interventions for enhancing maternal and fetal health outcomes.

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS) in which macrophages play a pivotal and multifaceted role. These highly plastic immune cells are key effectors in the immunopathology of MS, contributing to both inflammatory-driven demyelination and subsequent tissue repair. Historically, macrophage function was viewed through the binary lens of pro-inflammatory M1 and anti-inflammatory M2 polarization. However, recent research reveals a far more complex spectrum of activation states within the dynamic microenvironment of MS lesions. Understanding the intricate signals and molecular pathways that govern macrophage polarization in the CNS represents a critical frontier for therapeutic innovation. Interventions aimed at rebalancing macrophage phenotypes have yielded encouraging results in preclinical models, and some therapeutic agents are now advancing into clinical trials. Future investigations are focused on the diverse functions of macrophages in MS pathogenesis, including their involvement in oxidative stress, antigen presentation, and myelin debris clearance. A particularly innovative approach involves harnessing macrophages as cellular vehicles for targeted drug delivery across the blood-brain barrier, offering a potential solution to one of the most significant challenges in CNS therapeutics. The primary challenge now lies in the safe and effective clinical translation of these macrophage-centered therapies. Successfully navigating this transition from bench to bedside holds the potential to deliver transformative treatments that can halt disease progression and restore neurological function for individuals living with this debilitating disease.

Asthma and allergies are some of the most common chronic disorders affecting children, the prevalence of which has been increasing in countries and regions undergoing rapid development like China. To curb the rising tide of allergies and safeguard the health of future generations, it is of critical importance to understand how asthma inception is influenced by factors acting at different life stages. Birth cohorts represent a powerful tool to investigate the temporal sequence of exposures along the natural course of asthma. We examined recent evidence on birth cohort studies of asthma and allergic diseases and evaluated their strengths and weaknesses. Essential elements for a successful birth cohort are proposed to further elucidate asthma etiology and pathogenies. Initiating new cohorts in understudied populations with the application of advanced analytical approaches will be needed. Moreover, fostering collaborative networks using standardized methodologies should be prioritized to enable integration of findings across diverse cohorts. There remains an urgent and unmet need to further translate the seminal findings from asthma birth cohort studies into targeted primary prevention strategies to eradicate the disease.

Background and aimsThe impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women, especially those with gestational diabetes mellitus (GDM), has yet to be fully understood. This review aims to examine the interaction between GDM and COVID-19 and to elucidate the pathophysiological mechanisms underlying the comorbidity of these two conditions.MethodsWe performed a systematic literature search using the databases of PubMed, Embase, and Web of Science with appropriate keywords and MeSH terms. Our analysis included studies published up to January 26, 2023.ResultsDespite distinct clinical manifestations, GDM and COVID-19 share common pathophysiological characteristics, which involve complex interactions across multiple organs and systems. On the one hand, infection with severe acute respiratory syndrome coronavirus 2 may target the pancreas and placenta, resulting in β-cell dysfunction and insulin resistance in pregnant women. On the other hand, the hormonal and inflammatory changes that occur during pregnancy could also increase the risk of severe COVID-19 in mothers with GDM. Personalized management and close monitoring are crucial for treating pregnant women with both GDM and COVID-19.ConclusionsA comprehensive understanding of the interactive mechanisms of GDM and COVID-19 would facilitate the initiation of more targeted preventive and therapeutic strategies. There is an urgent need to develop novel biomarkers and functional indicators for early identification and intervention of these conditions.