Search Results (1,150)

Background: T2 low asthma in children is an emerging yet underexplored endotype that challenges traditional views of type 2 inflammation. Recent data suggest that it is more prevalent than previously thought and is defined by low type 2 biomarkers, non-allergic clinical profiles, and strong associations with modifiable comorbidities such as obesity, passive smoke exposure, and recurrent respiratory infections. This phenotype often shows a poor response to standard inhaled corticosteroid therapy and T2-targeted biologics, underscoring the urgent need for improved diagnostic and therapeutic approaches. Methods: This narrative review conducted a literature search from PubMed and WoS databases (2020–2025), focusing on T2-low asthma defined by low blood eosinophils (<150–300/µL), FeNO (<20–25 ppb), and absent atopy in children under 18. Results: This review highlights the heterogeneity of T2-low asthma, including subtypes from neutrophilic/Th 17-high to paucigranulocytic airway remodeling and metabolic driven forms, as well as diagnostic challenges from biomarker supresssion by high-dose therapies. Pragmatic phenotyping algorithms using routine tests enable identification, directing comorbidity management over ineffective biologics. Conclusions: Systematic T2-low phenotyping in pediatric practice, alongside prospective studies and non-T2 therapy trials, promises precision medicine to enhance outcomes for these children, moving beyond eosinophil-centric care. Full article

Sulfur dioxide (SO₂) is a colorless, pungent gas that is a significant contributor to air pollution, with well-documented environmental and health impacts. It is emitted both naturally (e.g., in volcanic activities) and anthropogenically (e.g., fossil fuel combustion, sulfuric acid production, papermaking, and wine preservation). Inhalation represents the primary route of human exposure, particularly in urban and industrial settings. Acute SO₂ exposure can lead to airway irritation, laryngospasm, bronchoconstriction, pulmonary edema, and death in severe cases. Chronic exposure, even at low concentrations, can contribute to the development of pulmonary and extrapulmonary diseases. Despite its classification as a hazardous air pollutant, a comprehensive understanding of dose-response relationships, exposure thresholds, and mechanisms of toxicity for SO₂ remains limited. This review synthesizes current knowledge on environmental sources, exposure routes, mechanisms of toxicity, and health impacts of SO₂, highlighting findings from epidemiological, toxicological, and mechanistic studies. We also discuss gaps in knowledge regarding SO₂, approaches to monitor and assess SO₂ exposure in ambient environments, the emerging role of SO₂ as a gasotransmitter, and areas where further research is needed to better understand health risks and support evidence-based public health decision-making. Full article

Nine technology-related metal(loid)s (Ag, Co, Fe, Mo, Pt, Rh, Sb, Se and Y) were monitored in 137 topsoil samples from urban parks, industrial areas and gardens in Alcalá de Henares (Spain) using ICP–MS. Selenium was not detected, while Mo, Sb and Rh showed a high proportion of values below the detection limit, indicating generally low contamination. In contrast, Fe, Co and Y were detected in all samples, with industrial soils showing about two-fold higher median Co and Fe than urban soils. Garden soils displayed marked silver enrichment (median 0.439 vs. 0.068 mg kg⁻¹ in urban soils), with Ag pollution indices up to 71 and enrichment factors up to 69; around 17% of garden samples exceeded EF > 40, and more than one-quarter had EF > 10. Principal component analysis suggested a predominantly geogenic association for Co, Fe and Y and an anthropogenic component for Ag, Mo, Rh and Sb, while Pt was mainly linked to vehicular emissions. Under standard US EPA exposure scenarios applied to the 2001 topsoil concentrations, oral and inhalation hazard quotients for elements with available benchmarks remained <0.2 and inhalation cancer risks for Co were ≤2.5 × 10⁻⁷, indicating low estimated risk within the model assumptions. However, quantitative risk characterisation remains constrained by benchmark gaps for Pt and Rh and by limited consensus toxicity values for Y, which introduces uncertainty for these technology-related elements. These results should therefore be interpreted primarily as a baseline (2001) in surface soils for Alcalá de Henares rather than as a direct representation of current exposure conditions. Full article

Chronic obstructive pulmonary disease (COPD) is strongly associated with the inhalation of harmful particulate matter in ambient air. This study examined 786,290 COPD-related hospital admissions among patients aged 45–64 in Istanbul from 2013 to 2015, using a Generalized Linear Model (GLM) with meteorological variables included as covariates and air pollutant effects evaluated across lag days 0–9. Daily mean concentrations of PM₁₀, PM_2.5, and NO₂ were used as air pollution indicators, while average temperature and relative humidity were considered as meteorological variables. Relative risk (RR) and excess relative risk (ERR) estimates were calculated for a 10 μg/m³ increase in pollutant concentrations across the lag period. Significant associations were found between air pollution and COPD-related hospital admissions in overall analyses as well as seasonal assessments, especially for temperature-related effects. A 10 μg/m³ increase in PM_2.5 was associated with an ERR of 1.26% in females and 1.07% in males at lag 1, while NO₂ exposure showed ERRs of 1.31% in males and 1.30% in females. The effects of PM₁₀ were comparatively smaller, peaking at about 1.13% ERR at lag 5. Stronger associations were observed in both summer and winter seasons. PM_2.5 demonstrated the highest overall impact, particularly among females, with an excess risk of 1.7%. Pollutant effects were more pronounced at ambient temperatures around 0 °C and 25 °C. Full article

Microplastics (MPs) are pervasive environmental pollutants, widely distributed from aquatic ecosystems to the terrestrial food chain, and represent a potential route of human exposure. Although several reviews have addressed MP contamination, a critical synthesis focusing on pathways through which consumer goods directly enter food and beverages, along with corresponding industry and regulatory responses, is lacking. This review fills this gap by proposing the direct release of MPs from common sources such as food packaging, kitchen utensils, and household appliances, linking the release mechanisms to human health risks. The release mechanisms of MPs under thermal stress, mechanical abrasion, chemical leaching, and environmental factors, as well as a risk-driven framework for MP release, are summarized. Human exposure through ingestion is the predominant route, while inhalation and dermal contact are additional pathways. In vitro and animal studies have associated MP exposure to inflammatory responses and oxidative stress, neurotoxicity, and genomic instability as endpoints, though direct causal evidence in humans remains lacking, and extrapolation from model systems necessitates caution. This review revealed that dietary intake from kitchen sources is the primary pathway for MP exposure, higher than the inhalation pathway. Most importantly, this review critically sheds light on the initiatives that should be taken by industries with respect to global strategies and new policies to alleviate these challenges. However, while there has been an upsurge in research commenced in this area, there are still research gaps that need to be addressed to explore food matrices such as dairy products, meat, and wine in the context of the supply chain. In conclusion, we pointed out the challenges that limit this research with the aim of improving standardization; research approaches and a risk assessment framework to protect health; and the key differences between MP and nanoplastic (NP) detection, toxicity, and regulatory strategies, underscoring the need for size-resolved risk assessments. Full article

Titanium dioxide (TiO₂) nano- and submicrometric particles’ widespread use in different sectors raised concerns about human and environmental exposure. The validation of analytical methods is essential to ensure reliability in risk assessment studies. In this study, a single-particle inductively coupled plasma mass spectrometry (spICP-MS) method was validated for the detection, quantification, and dimensional characterization of TiO₂ particles in biological tissues. Tissue samples collected after exposure to TiO₂ particles underwent mild acidic digestion using a HNO₃/H₂O₂ mixture to achieve complete matrix decomposition while preserving particle integrity. The resulting digests were analyzed by ICP-MS operated in single-particle mode to quantify and size TiO₂ particles. Method validation was conducted according to ISO/IEC 17025:2017 and included linearity, repeatability, recovery, and detection limit assessments. The limit of detection for TiO₂ particles was 0.04 µg/g, and 55.7 nm was the size the detection limit. Repeatability was within 0.5–11.5% for both TiO₂ mass concentrations and particle size determination. The validated method was applied to tissues from inhalation-exposed subjects, showing TiO₂ levels of 80 ± 20 µg TiO₂/g and particle number concentrations of 5.0 × 10⁵ ± 1.2 × 10⁵ part. TiO₂/mg. Detected TiO₂ particles’ mean diameter ranged from 230 to 330 nm. The developed and validated spICP-MS method provides robust and sensitive quantification of TiO₂ particles in biological matrices, supporting its use in human biomonitoring and exposure assessment studies. Full article

Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human placenta allows for easier transfer of nutrients and antibodies from the mother’s blood to the fetal circulation through the direct contact of maternal blood with the fetal chorion. During the third trimester of pregnancy, immunoglobulin G (IgG) is actively transferred through the placenta into the fetal via neonatal FcRN receptor (FcRN). In addition, monomeric immunoglobulin E (IgE) cannot cross the placenta Aim: The objective of our study is to track intrauterine sensitization to essential food proteins at birth in umbilical cord blood in mothers with established peripheral blood eosinophilia and in their infants using allergen-specific IgE and IgG. Methods: An observational study was carried out in a cohort of 22 mothers with eosinophilia and their babies. Differences in expression between groups were assessed. Blood samples were collected to determine serum IgE and IgG specific to a set of inhalant and food allergens. Results: We did not find a significant correlation between specific IgE to cow’s milk (p = 0.857), egg white (p = 0.926) and egg yolk (p = 0.096) in umbilical cord blood and maternal blood samples taken immediately before birth. Spearman’s correlation of the specific IgE and IgG in umbilical cord blood showed no dependence between the two variables. In contrast, statistical analysis showed that maternal eosinophilia in peripheral blood could be a risk factor for the development of allergy in the offspring (χ², p = 0.0347). However, given the small number of patients, this claim needs to be confirmed with further studies. Conclusions: Due to the functional immaturity of the developing immune system of the fetus, the generation and maintenance of an independent immune response to allergens are incomplete. Maternal IgG (specific) passes to the baby and high maternal IG to a specific allergen reduces babies IgE production. In addition, low maternal specific IgG may promote IgE production in the baby under the influence of microenvironmental factors (cytokine background). The main limitation of our study is the small number of patients. Further research is needed in this direction to clarify the mechanisms and risk factors for early sensitization in newborns. Full article

The long-term inhalation of free silica dust causes silicosis—a prevalent occupational hazard—yet its systemic effect on male reproductive toxicity remains underexplored. Tetrandrine (Tet) is the only plant-derived anti-silicosis drug approved in China. This study investigates silica (SiO₂) -induced male reproductive damage and evaluates Tet’s protective effects. Sixty male C57BL/6 mice (6–8 weeks) were divided into control, SiO₂ exposure, and SiO₂ + Tet groups. SiO₂ was administered via intranasal infusion and Tet via gavage. Mice were sacrificed at day 7 (male reproductive injury model corresponding to the pulmonary inflammation stage) and day 42 (male reproductive injury model corresponding to the pulmonary fibrosis stage). Analyses included sperm morphology, testicular transcriptome sequencing, RT-qPCR, and immunofluorescence. At day 7, SiO₂ exposure upregulated testicular inflammatory markers, which were partially mitigated by Tet. At day 42, SiO₂ increased sperm deformity and testicular fibrosis markers (fibronectin and vimentin); Tet intervention reduced these abnormalities. Transcriptome analysis revealed distinct gene expression patterns at day 7 versus day 42, indicating time-dependent injury mechanisms. Tetrandrine alleviates silica-induced reproductive damage in male mice, suggesting potential therapeutic applications for occupational silica exposure and expanding the understanding of silica toxicity beyond the respiratory system. Full article

Glioblastoma (GBM) remains one of the most lethal brain tumors, with current therapies offering limited benefits and high relapse rates. This study presents the first preclinical evidence that pretreatment with inhaled cannabidiol (CBD) before tumor establishment can markedly inhibit GBM progression. We hypothesized that early CBD exposure could prime the immune and molecular landscape to resist tumor growth. C57BL/6 mice were pretreated with inhaled CBD for 3 or 14 days, or with placebo, prior to intracranial implantation of glioblastoma cells. Tumor growth, immune checkpoint expressions (IDO, PD-L1), and key biomarkers (MGMT, Ki67) were analyzed to evaluate tumor dynamics and immune modulation. Fourteen-day CBD pretreatment significantly reduced tumor burden compared with both placebo and 3-day CBD groups, accompanied by decreased IDO, PD-L1, MGMT, and Ki67 expression, which are signatures of a less aggressive tumor phenotype. These findings suggest that prolonged CBD exposure can precondition the tumor microenvironment toward an anti-tumor state, improving disease control and potentially lowering relapse risk. This study introduces a novel concept of CBD pretreatment as an immune-modulatory strategy with high translational potential for glioblastoma management. Full article

Particulate atmospheric pollution poses a global threat to human health. Metals enter the body through inhalation attached to these particles. Certain vulnerable groups are more susceptible to toxicity because of age, physiological changes, and chronic and metabolic diseases and also workers because of high and cumulative exposure to metals. A narrative review was conducted to examine the effects of key metals—arsenic, cadmium, chromium, copper, lead, mercury, manganese, nickel, vanadium, and zinc—on vulnerable populations, analyzing articles published over the past decade. Some of these metals are essential for humans; however, excessive levels are toxic. Other non-essential metals are highly toxic. Shared mechanisms of toxicity include competing with other minerals, oxidative stress and inflammation, and interacting with proteins and enzymes. Prenatal and childhood exposures are particularly concerning because they can interfere with neurodevelopment and have been associated with epigenetic changes that have long-term effects. Occupational exposure has been studied, but current exposure limits for specific metals appear dangerous, emphasizing the need to revise these standards. Older adults, pregnant women, and individuals with metabolic diseases are among the least studied groups in this review, underscoring the need for more research to understand these populations better and create effective public health policies. Full article

Molecular hydrogen (H₂) exhibits anti-inflammatory and antioxidant properties. However, its role in ultraviolet B (UVB)-induced skin carcinogenesis remains unclear. Male HR-1 hairless mice received continuous H₂ (2% hydrogen gas inhalation plus hydrogen-rich water (HRW)) or control treatment (normal air plus dehydrogenated water) during chronic dorsal UVB exposure (270 mJ/cm², three times per week, 20 weeks), followed by a 10-week observation period. This protocol was replicated independently. H₂ exposure consistently delayed the onset of papilloma and reduced cumulative tumor counts in both series, whereas prolonged survival and delayed squamous cell carcinoma (SCC) development each reached statistical significance in only one of the two experimental series. The cyclobutane pyrimidine dimer (CPD) levels remained unchanged, indicating no reduction in DNA photolesions. H₂ exposure decreased epidermal T-cell infiltration, dermal IL-6 levels, and nuclear phosphorylated STAT3 levels. ERK and JNK phosphorylation levels were decreased. H₂ preserved the GSH/GSSG ratio following acute UVB exposure and reduced nuclear Nrf2 accumulation during chronic exposure. Epidermal thickness and proliferation markers (Ki-67 and PCNA) were decreased. These findings suggest that continuous H₂ administration attenuates inflammation-associated early UVB carcinogenesis through modulation of the IL-6/STAT3 and ERK/JNK pathways, supporting its use as a chemopreventive approach. Full article

Background: Carbon dioxide (CO₂) is traditionally regarded as a metabolic by-product; however, growing evidence indicates that it plays an active regulatory role across multiple physiological systems. Acute hypercapnia elicits respiratory, cardiovascular, metabolic, immune, and neurocognitive responses, some of which may transiently influence exercise performance. This narrative review summarizes current evidence on CO₂ inhalation in healthy individuals and critically evaluates whether controlled hypercapnia may serve as a targeted stimulus in sport and exercise contexts. Methods: A narrative review of peer-reviewed English-language articles indexed in PubMed and Web of Science was conducted. A narrative approach was chosen due to the marked heterogeneity of study designs, hypercapnia-induction methods (e.g., CO₂ inhalation, voluntary hypoventilation, increased respiratory dead space), participant characteristics, and outcome measures, which precluded systematic synthesis. The review focused on studies involving healthy or physically active individuals and examined acute or short-term hypercapnic exposure. No strict publication date limits were applied. Studies conducted exclusively in clinical populations were excluded. Results: Short-term, controlled hypercapnia reliably increases ventilation, sympathetic activation, cerebral and muscular blood flow, and metabolic stress. Certain hypercapnia-based interventions—such as voluntary hypoventilation or added respiratory dead space—may enhance buffering capacity, reduce lactate accumulation and improve maximal oxygen uptake (VO₂max) during submaximal efforts and repeated-sprint performance during high-intensity, short-duration exercise. However, CO₂ inhalation frequently induces dyspnea, anxiety, and cognitive disruption, and higher concentrations pose clear safety risks. Current evidence does not support long-term improvements in VO₂max or long-duration endurance performance following hypercapnia-based interventions. Conclusions: Controlled, intermittent hypercapnia may provide a targeted metabolic and ventilatory stimulus that enhances tolerance to high-intensity exercise, yet its application remains experimental and context-dependent. The risks associated with CO₂ inhalation in healthy individuals currently outweigh its potential benefits, and safe, effective training protocols have not been fully established. Further research is needed to clarify the mechanisms, long-term adaptations, and practical utility of hypercapnia-based training strategies. Full article

Tuberculosis (TB) remains a leading infectious killer, increasingly complicated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) disease; current regimens, although effective, are prolonged, toxic, and often fail to reach intracellular bacilli in heterogeneous lung lesions. This narrative review synthesizes how next-generation antimycobacterial strategies can be translated “from molecule to patient” by coupling potent therapeutics with delivery platforms tailored to the lesion microenvironment. We survey emerging small-molecule classes, including decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) inhibitors, mycobacterial membrane protein large 3 (MmpL3) inhibitors, and respiratory chain blockers, alongside optimized uses of established agents and host-directed therapies (HDTs). These are mapped to inhalable and nanocarrier systems that improve intralesional exposure, macrophage uptake, and targeted release while reducing systemic toxicity. Particular emphasis is placed on pulmonary dry powder inhalers (DPIs) and aerosols for direct lung targeting, stimuli-responsive carriers that trigger release through pH, redox, or enzymatic cues, and long-acting depots or implants that shift daily dosing to monthly or quarterly schedules to enhance adherence, safety, and access. We also outline translational enablers, including model-informed pharmacokinetic/pharmacodynamic (PK/PD) integration, device formulation co-design, manufacturability, regulatory quality frameworks, and patient-centered implementation. Overall, aligning stronger drugs with smart delivery platforms offers a practical pathway to shorter, safer, and more easily completed TB therapy, improving both individual outcomes and public health impact. Full article

Microplastics (MPs) and nanoplastics (NPs) are widespread environmental contaminants with documented impacts on human health, particularly on the female reproductive system. Defined as polymeric fragments smaller than 5 mm, MPs (typically ranging from 1 µm to 5 mm) and NPs (smaller than 1 µm, often <100 nm) originate either from primary sources—intentionally manufactured for specific industrial applications—or from secondary sources through physical, chemical, or biological degradation of macroplastics. Human exposure occurs via multiple routes, including ingestion, inhalation, dermal absorption, and iatrogenic introduction, with growing evidence that these particles can accumulate in the ovaries, oocytes, and placental tissue. Experimental studies in rodents demonstrate that MPs and NPs induce oxidative stress, trigger inflammatory responses, and promote granulosa cell apoptosis, ultimately diminishing ovarian reserve and impairing folliculogenesis. Clinical and pilot human studies have confirmed the presence of MPs in placentas, umbilical cord blood, and meconium, indicating exposure from the earliest stages of development. Moreover, MPs and NPs may disrupt the hypothalamic–pituitary–ovarian axis, contributing to endocrine dysregulation and hormonal imbalance. Analytical methods such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and scanning electron microscopy enable detection of these particles in biological samples, although methodological standardization remains insufficient. This paper summarizes current evidence on the exposure pathways, toxicological effects, and reproductive consequences of MPs and NPs in women. It further highlights existing research gaps and evaluates available analytical approaches to support future studies and develop strategies aimed at mitigating their detrimental impact on women’s reproductive health and fertility. Full article

Industrial air emissions are major contributors to human exposure to toxic pollutants, posing significant health risks. Life cycle assessment (LCA) is increasingly used to quantify human toxicity impacts from industrial processes. Conventional LCA often overlooks spatial and temporal variability, limiting its ability to capture actual inhaled doses and exposure-driven impacts. To address this, we developed a site-dependent dynamic LCA (SdDLCA) framework that integrates conventional LCA with Enhanced Structural Path Analysis (ESPA) and atmospheric dispersion modeling. Applied to the production of double-glazed PVC windows for a residential project, the framework generates high-resolution, site-specific emission inventories for three key pollutants: nitrogen oxides (NO_x), sulfur dioxide (SO₂), and fine particulate matter (PM_2.5). Local concentration fields are compared with World Health Organization (WHO) air quality thresholds to identify hotspots and periods of elevated exposure. By coupling these fields with the ReCiPe 2016 endpoint methodology and localized demographic and meteorological data, SdDLCA quantifies human health impacts in Disability-Adjusted Life Years (DALYs), providing a direct measure of inhalation toxicity. This approach enhances LCA’s ability to capture exposure-driven effects, identifies populations at greatest risk, and offers a robust, evidence-based tool to guide industrial planning and operations that minimize health hazards from air emissions. Full article