Search Results (322)

Tobacco use disorder (TUD) is a complex multifactorial condition resulting from the interplay between nicotine-induced neurobiological adaptations, behavioral and learning processes, environmental influences, and individual genetic susceptibility. Genetic research has progressively evolved from twin and family studies through candidate-gene approaches to large-scale genome-wide association studies (GWAS), substantially improving our understanding of the genetic architecture of tobacco use and nicotine dependence. This review summarizes the current evidence on the genetic basis of TUD, with particular emphasis on major biological pathways. We also discuss the limitations of early candidate-gene studies and the paradigm shift introduced by large GWAS and meta-analyses, and polygenic risk scores, which indicate that tobacco use and nicotine dependence have a highly polygenic and pleiotropic architecture. Finally, we review the potential clinical applications of genetic information in smoking-cessation treatment, while highlighting current limitations in clinical translation. In the future, it is clear that a multidisciplinary approach—combining genetics, clinical practice, and social sciences—will be necessary to transform tobacco use management into a precision-based model and reduce its impact on public health. Full article

Although exposure to heavy metals such as cadmium and inorganic arsenic has declined in recent decades, they remain prevalent environmental contaminants in food, drinking water, and tobacco smoke. This study aimed to identify and compare molecular endpoints of arsenite and cadmium toxicity at the gene and protein expression levels, with a focus on metal homeostasis, the oxidative stress response and redox-regulated processes. Human bronchial epithelial cells (BEAS-2B) were used as an in vitro model. First, the appropriate exposure conditions were defined by assessing cytotoxicity and intracellular metal accumulation. The cells were then incubated with 1–10 µM NaAsO₂ or 1–5 µM CdCl₂ for 24 h, after which gene and protein expression were analyzed. When compared to arsenite, cadmium was a markedly stronger inducer of metallothionein (MT) expression, indicating distinct effects on metal homeostasis. Both metals induced a concentration-dependent upregulation of oxidative stress-related genes. Cadmium led to a stronger activation of NF-κB signaling, while arsenite decreased selenoprotein-associated gene expression and affected genes involved ferroptosis regulation. Differences in gene and protein expression patterns were also observed, suggesting that transcriptional responses do not necessarily translate into corresponding changes at the protein level after 24 h. These findings highlight shared and compound-specific mechanisms, as well as the importance of multi-level analyses. Full article

Dry eye disease (DED) is a complex ocular surface disorder characterized by tear film instability, discomfort, hyperosmolarity, inflammation, and neurosensory dysfunction. Since individuals spend a significant amount of time inside buildings, exposure to indoor environments has emerged as a noteworthy and adjustable factor influencing ocular surface disorders. This analysis consolidates recent findings connecting indoor air contaminants, such as particulate pollutants, volatile organic substances, formaldehyde, and other gaseous irritants, as well as tobacco and cooking fumes, heavy metals, organophosphate flame retardants, and liquid crystal compounds, with the mechanisms and symptoms associated with DED. Research suggests that indoor environmental factors can exacerbate DED by triggering interconnected mechanisms such as oxidative damage, inflammation, lipid degradation, meibomian gland issues, decreased tear production, impairment of goblet cells and the mucin layer, disruption of tight junctions, and damage to the corneal or conjunctival epithelium. The most robust clinical evidence currently pertains to tobacco smoke, particulate matter, indoor air pollution, low humidity, and poor ventilation. In contrast, although biological plausibility exists for heavy metals, flame retardants, and liquid crystal monomers, the supporting data remain relatively sparse, indirect, and less comprehensive. Harmonized exposure assessments, prospective cohort studies, analyses of pollutant mixtures, and experimental intervention trials are needed to better characterize dose–response relationships and to establish effective preventive measures. Assessment of environmental history and improvement of indoor air quality should be regarded as integral and interrelated components in the prevention and management of DED. Full article

Lung cancer mortality is a critical issue in Northern Thailand, where incidence rates significantly exceed the national average. Key risk factors include tobacco smoking and seasonal air pollution from biomass burning, which releases carcinogenic polycyclic aromatic hydrocarbons (PAHs). This study aims to analyze the accumulation of 16 priority PAHs in human lung tissues to explore links between environmental exposure, smoking habits, and cancer development. Tissue samples (normal, para-cancerous, and adenocarcinoma) were collected from 30 surgical participants (15 lung cancer patients, 15 non-cancer controls) at Chiang Mai University Hospital. Compounds were extracted via ultrasonication and quantified using gas chromatography-mass spectrometry. Carcinogenic potency was evaluated using Benzo[a]pyrene equivalents, with concentrations compared across tissue types and patient groups using generalized estimating equations. High-molecular-weight PAHs were the dominant species, accounting for over 50% of total accumulation in all tissues, aligning with regional biomass burning profiles. Total concentrations and carcinogenic potency were significantly higher in smokers, particularly within normal lung tissues. Furthermore, high-molecular-weight PAH concentrations positively correlated with tissue cholesterol levels (R = 0.66). Source analysis indicated exposure primarily from pyrogenic sources, alongside petroleum emissions. In conclusion, high-molecular-weight carcinogens significantly accumulate in human lungs in Northern Thailand, reflecting substantial environmental exposure, while tissue lipid content modulates toxin bioaccumulation. Smoking facilitates compound retention in normal tissues, underscoring an urgent need for targeted public health strategies addressing both environmental pollution and tobacco use. Full article

Secondhand smoke exposure (SHSE) remains a major environmental health risk among university students, particularly in socially shared settings. In the United Arab Emirates, culturally embedded practices such as shisha and midwakh use, combined with variable policy enforcement, sustain persistent exposure. This cross-sectional study examined SHSE-related knowledge and protective health behaviors among 360 university students and their sociodemographic correlates, using a self-report questionnaire with documented internal consistency in comparable populations. Data were analyzed using SPSS version 28. SHSE was highly prevalent, occurring mainly in public and university settings; knowledge was moderate and protective behavior varied. Knowledge emerged as a moderate-to-strong correlate of protective behavior (r = 0.70, p < 0.001, R² = 0.49). Age, employment, marital status, and number of children were associated with knowledge; age, gender, marital status, and income, but not employment, remained associated with behavior after adjusting for knowledge. Confirmatory factor analysis showed poor absolute fit for both the one- and two-factor solutions, and the behavioral-response factor did not satisfy the Fornell–Larcker criterion (√AVE = 0.750 < latent r = 0.836), providing only partial support for the empirical distinctiveness of the two constructs. Bootstrapped mediation analysis shows that knowledge partially mediated the employment–behavior association (~62% of the total effect); employment status was not, however, independently associated with behavior once knowledge was included, so this pathway is reported as hypothesis-generating. Still, more than a quarter of participants reported poor protective behavior, suggesting that unmeasured social and environmental factors, and possible overlap between the two constructs, may influence this relationship. Findings support integrated interventions combining health education, policy enforcement, and culturally tailored strategies. Full article

Background: “Third-hand” exposure produced by “second-hand” environmental vaping aerosol (EVA) has been reported as a parallel analogue of “third-hand smoke” (THS) produced by residues of environmental tobacco smoke (ETS). Methods: To assess the plausibility and scope of “third-hand” vaping exposure, we examine the available evidence on THS phenomenology and the physicochemical properties of EVA. We also evaluate daily intake doses from direct dermal exposure to nicotine under simplified but minimally realistic scenarios for vaping and smoking. Results: The only THS phenomenology fully reproduced in EVA is the adsorption of nicotine and its byproducts on indoor surfaces. Unlike significant, measurable THS exposures in normal environments (homes, hospitality venues, cars), third-hand exposures from vaping have only been found under special conditions: laboratory-generated aerosols or in vape shops where excessively abnormal and intense vaping activity takes place. Conclusions: The physicochemical properties of EVA are incompatible with an aging process leading to a THS analogue under the environmental conditions in which vaping normally takes place. However, objectively and rigorously evaluating the risks of dermal exposure from smoking and vaping remains an open issue. Full article

Background: Intestinal parasitic infections are common in tropical settings and may influence immune regulation, allergic responses, and respiratory health. In children with sickle cell disease (SCD), respiratory morbidity is multifactorial, and the contribution of intestinal parasites remains uncertain. This study assessed whether documented intestinal parasitic infections, particularly helminth infections, were associated with asthma-like respiratory phenotypes and clinical morbidity in children with SCD in French Guiana. Methods: We conducted a multicenter cross-sectional analysis of children and adolescents younger than 18 years with confirmed SCD who were being followed by the pediatric SCD centers of Saint-Laurent-du-Maroni, Cayenne, and Kourou between January 2022 and December 2025. Clinical, respiratory, and parasitological data were extracted from routine-care medical records. Intestinal parasitic infection was defined as at least one documented stool parasitology result identifying Strongyloides stercoralis, hookworm, or Entamoeba histolytica, according to the variables consistently available in the database. Respiratory outcomes included physician-diagnosed asthma, bronchial obstruction, bronchodilator reversibility, and an asthma-like respiratory phenotype. Results: Among 233 included children, 105 (45.1%) had at least one documented intestinal parasitic infection and 82 (35.2%) had a helminth infection. Hookworm was the most common parasite (75/233, 32.2%), followed by Entamoeba histolytica (33/233, 14.2%) and Strongyloides stercoralis (24/233, 10.3%). An asthma-like respiratory phenotype was observed in 32/105 infected children (30.5%) versus 44/128 non-infected children (34.4%). Bronchial obstruction and bronchodilator reversibility were also similar between groups. After adjustment for age, sex, genotype, hydroxyurea treatment, rural residence, site of follow-up, and environmental tobacco smoke exposure, intestinal parasitic infection was not associated with asthma-like respiratory phenotype (adjusted OR: 0.94, 95% CI: 0.51–1.72; p = 0.844), recurrent hospitalization, or history of acute chest syndrome. Conclusions: In this routine-care multicenter pediatric SCD cohort from French Guiana, intestinal parasitic infections were common but were not associated with respiratory phenotype or selected morbidity outcomes. Because testing and respiratory assessment were not systematic, these findings should be interpreted as showing that routine parasitological status alone could not identify children with respiratory morbidity. Prospective studies with standardized repeated parasitological, immunological, environmental, and respiratory assessments are needed. Full article

Background/Objectives: Pregnancy is characterized by profound metabolic and physiological adaptations that influence systemic redox balance. Longitudinal data assessing trimester-specific changes in antioxidant status and oxidative stress markers remain limited. Methods: In this longitudinal study, plasma levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) and oxidative stress markers (malondialdehyde, conjugated dienes, protein carbonyls, and DNA strand breaks) were analyzed in 31 healthy non-smoking pregnant women during the first, second, and third trimester. Environmental tobacco smoke exposure was evaluated using urinary cotinine. Statistical analyses were performed using Friedman repeated-measures tests followed by Dunn’s post hoc comparisons with Benjamini–Hochberg false discovery rate correction. Results: Vitamin A was the only antioxidant that consistently decreased across all trimesters and represented the only antioxidant marker showing a consistent decline. In contrast, α-tocopherol, γ-tocopherol, xanthophylls, and lycopene increased significantly during gestation, whereas vitamin C remained relatively stable. Markers of oxidative damage, including malondialdehyde, conjugated dienes, protein carbonyls, and DNA strand breaks, showed significant trimester-dependent increases. Total antioxidant capacity (FRAP) remained unchanged throughout pregnancy. Conclusions: Physiological pregnancy is characterized by coordinated, marker-specific adaptations in systemic redox balance. Vitamin A was the only antioxidant showing a consistent decline across gestation, whereas several lipid-soluble antioxidants increased and total antioxidant capacity remained stable. These findings indicate that pregnancy is associated with increased oxidative activity accompanied by preservation of systemic antioxidant capacity rather than global antioxidant depletion. Full article

The interindividual phenotypic heterogeneity in Alpha-1 Antitrypsin Deficiency (AATD), despite a shared genetic etiology (the Z-allele of SERPINA1), is explained by the interaction of dual pathogenic mechanisms (gain-of-function vs. loss-of-function), additional genetic modifiers, and environmental or metabolic factors. Building on recent evidence suggesting divergent disease trajectories, we investigated whether pulmonary and hepatic impairments represent coupled manifestations or independent clinical dimensions within a large European cohort. Methods: This international multicenter study utilized the European Alpha-1 Research Collaboration (EARCO) registry (n = 1217). Pulmonary and hepatic severities were quantified using concurrent 0.0–10.0 composite indices. Independence was evaluated via partial Spearman correlations, multivariable multinomial regression, and geometric mapping across a continuous phenotypic space. Results: Cross-domain correlations between respiratory metrics and liver stiffness were near zero (r = −0.03), demonstrating statistical independence. Phenotypic dominance classification isolated distinct profiles; the lung-dominant group exhibited a higher age (57.0 vs. 54.0 years; p < 0.001) and tobacco exposure, while the liver-dominant group registered a higher body mass index (25.8 vs. 24.4 kg/m²; p < 0.001). Multivariable models identified age (OR 1.03; 95% CI 1.02–1.05) and smoking as independent predictors of lung dominance, whereas body mass index was independently associated with liver dominance (OR 1.04; 95% CI 1.01–1.07). Geometric mapping revealed advanced disease clusters at orthogonal margins rather than forming a systemic continuum. Conclusions: Hepatic and pulmonary impairments in AATD operate as independent clinical dimensions modulated by distinct metabolic and environmental factors. Risk stratification must transition toward organ-specific prognostic models. Full article

Background: Adolescent tobacco, e-cigarette, and alcohol use are important public health concerns in China. However, the associations of specific types and cumulative exposure to childhood family violence with different substance use outcomes remain insufficiently understood. This study examined these associations among Chinese adolescents. Methods: We analyzed data from a cross-sectional school-based survey of 41,146 students aged 10–19 years conducted from October 2022 to March 2023 in a mountainous city in western Guangdong Province, China. Childhood family violence was assessed using the validated Chinese Family Violence Questionnaire and a cumulative exposure index. Descriptive analyses and logistic regression models were conducted, with adjustment for demographic and environmental factors. Results: The mean age of participants was 14.8 years, and 51.7% were female. Overall, 25.1% of adolescents reported at least one type of childhood family violence. Verbal insults (18.6%) and emotional neglect (16.3%) were the most frequently reported types and were consistently associated with tobacco, e-cigarette, and alcohol use (adjusted odds ratios [ORs] = 1.4–1.5, p < 0.001). A cumulative exposure pattern was also observed. Compared with adolescents reporting no childhood family violence, those exposed to three or more types had higher odds of tobacco use (OR = 3.81; 95% CI: 3.42–4.23), e-cigarette use (OR = 3.90; 95% CI: 3.39–4.48), and alcohol use (OR = 3.95; 95% CI: 3.59–4.35). Peer smoking and access to tobacco products were also significantly associated with substance use. Conclusions: Childhood family violence, particularly verbal insults and emotional neglect, was associated with adolescent tobacco, e-cigarette, and alcohol use. The findings highlight the importance of considering emotional maltreatment, cumulative adversity, peer influences, and access to tobacco products in future prevention research and practice. Full article

Background/Objectives: Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, driven by invasive behavior and frequent resistance to systemic therapies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit patients with EGFR-mutant NSCLC, but their efficacy is often limited by tumor-intrinsic and environmental resistance mechanisms. Benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon from tobacco smoke, combustion, and dietary sources, is a known carcinogen; however, its role in modulating therapeutic responses is poorly understood. Studies, including ours, implicate the platelet-activating factor-receptor (PAFR) pathway in mediating environmental pollutant and therapy-induced effects on tumor growth and microvesicle particle (MVP) release. We hypothesized that PAFR activation mediates BaP-induced NSCLC progression and influences EGFR-TKI responses. Methods: We assessed the effects of BaP, PAFR agonist CPAF, EGFR-TKIs, and their combinations on cell viability, proliferation, migration, anchorage-independent growth, and MVP secretion. Results: BaP did not alter cell survival but significantly increased migration, growth, colony formation, and MVP release, similar to CPAF, and these effects were blocked by a PAFR antagonist or acid sphingomyelinase inhibitor. Notably, BaP did not significantly reduce EGFR-TKI efficacy at tested concentrations. Conclusions: These results show that environmental carcinogens modulate NSCLC behavior through PAFR signaling without compromising EGFR-TKI responsiveness, highlighting PAFR as a potential therapeutic target. Full article

Background: Radon exposure is the second most important risk factor for lung cancer after tobacco smoking and represents a significant but often underestimated public health problem. Due to the absence of specific clinical manifestations at early stages, the identification of molecular biomarkers reflecting early radon-induced carcinogenic processes is of particular importance. The aim of this study was to identify protein biomarkers associated with radon exposure in lung cancer patients residing in settlements of the Akmola and North Kazakhstan regions of Kazakhstan. Methods: Indoor radon exposure was assessed using CR-39 detectors to measure radon concentrations in residential dwellings during summer and autumn periods. The study included 57 lung cancer patients and 73 control subjects residing in areas characterized by varying levels of radon exposure. Plasma samples were collected and analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to identify differentially expressed proteins associated with lung cancer and radon exposure. Statistical analyses were performed to evaluate differences between groups and associations between radon exposure and molecular biomarkers. Results: Seasonal variability in indoor radon concentrations was observed, with several settlements demonstrating levels exceeding international reference values. Proteomic analysis identified multiple proteins differentially expressed between lung cancer patients and controls, as well as between radon-exposed and non-exposed lung cancer patients. Several proteins involved in inflammation, lipid metabolism, oxidative stress, and immune regulation pathways demonstrated significant differences in expression levels, suggesting potential associations with radon-induced carcinogenic mechanisms. LC–MS/MS proteomic profiling identified multiple differentially expressed proteins associated with lung cancer and radon exposure after false discovery rate correction. Proteins involved in inflammation, oxidative stress, immune regulation, and lipid metabolism, including ORM2, AZGP1, PRDX2, IRF7, and APOC3, demonstrated significant expression differences between radon-exposed and low-exposure groups. Conclusions: The identified protein biomarkers demonstrated significant associations with both radon exposure and lung cancer status, indicating their potential relevance for early detection and risk assessment of radon-induced lung cancer. The integration of environmental exposure assessment with proteomic profiling may provide new insights into the molecular mechanisms of radon-associated carcinogenesis and support the development of preventive strategies. Full article

Background and Aim: Passive smoking (PS) is a well-established risk factor associated with systemic and oral health impairments in children. However, its influence on perioperative physiological stability and recovery profiles during pediatric dental sedation remains insufficiently elucidated. This study investigated the association between PS exposure and perioperative vital parameters, recovery characteristics, and emergence behavioral outcomes in children undergoing dental extractions under sedation. Methods: This prospective cohort study (ClinicalTrials.gov: NCT06780189) included 100 ASA I children aged 4–6 years scheduled for primary molar extraction under midazolam-remifentanil-propofol sedation. Participants were stratified into three groups: no exposure, caregiver and household exposure, and household exposure only. An exposure-related relationship was evaluated based on daily household cigarette consumption. Perioperative vital signs (HR, blood pressure, and SpO₂) were continuously monitored. Postoperative recovery and emergence profiles were assessed using the Modified Aldrete Recovery Score (MASS), Richmond Agitation–Sedation Scale (RASS), and Pediatric Anesthesia Emergence Delirium (PAED) scale. Results: Children exposed to PS demonstrated significantly lower SpO₂ levels across all perioperative phases compared with non-exposed counterparts (p < 0.001), reflecting an exposure-related effect. In contrast, no statistically significant differences were observed in cardiovascular parameters (p > 0.05). Recovery time was significantly prolonged in PS-exposed children (p = 0.002). Furthermore, PS exposure was associated with significantly higher RASS and PAED scores, indicating increased agitation and emergence delirium (p < 0.001). Conclusions: Passive smoking adversely affects perioperative oxygenation, delays recovery, and exacerbates emergence neurobehavioral disturbances in children undergoing dental sedation. Environmental tobacco exposure must be integrated into preoperative risk assessments. Full article

The interplay between the environmental exposome and the cancer genome remains a critical gap in precision oncology. While somatic mutational signatures—genomic fossils imprinted by exposures such as ultraviolet radiation; tobacco smoke; and industrial pollutants—are well characterised for their etiological significance; their functional impact on therapeutic efficacy remains largely unexplored. We hypothesised that these environmental genomic scars induce distinct pharmacogenomic vulnerabilities and resistance mechanisms that vary by geographical exposure patterns. This study employs two complementary analytical frameworks. First, a linear regression-based pharmacogenomic screen across four datasets (GDSC1, GDSC2, CTRP, CCLE; 1001 cell lines, 31 cancer types) identified 608 statistically significant (p < 0.01) mutational signature–drug interactions, revealing that UV-associated signature SBS7a is associated with broad-spectrum therapeutic resistance, including to BRAF inhibitors (PLX-4720, p < 10⁻⁴), while pollution-driven oxidative stress (SBS18) is associated with sensitivity to p38 MAPK inhibition (VX-702, r = −0.45, p < 10⁻⁹). Second, an XGBoost predictive model trained exclusively on 33,679 GDSC2 records using a 1265-feature matrix integrating 40 SBS signatures, drug chemistry descriptors, proteomic features, and two satellite-derived environmental variables (NASA PM_2.5 and UV)—achieved R² = 0.7973 on a 20% holdout set (grouped cross-validation R² = 0.7296). SHAP analysis revealed that satellite-derived PM_2.5 (Zone_PM25) ranked 7th of 1265 features, exceeding all 40 individual SBS mutational signatures. Synthesising these findings with satellite-derived atmospheric data, we constructed an exploratory spatially interpolated risk surface spanning 122 nations, generating the hypothesis that uniform drug efficacy assumptions may not apply globally. These findings suggest that a patient’s environmental exposure history may constitute a measurable pharmacogenomic variable. This exploratory framework warrants validation in independent datasets and with individual-level geographic data before clinical application. Full article

Background: Smoking cessation outcomes vary widely across individuals, yet clinic-based services often rely on uniform intervention strategies. Understanding heterogeneity in smoking behaviors, co-occurring health behaviors, and cessation-related psychological profiles may help refine community-based cessation services. This study aimed to identify distinct subgroups of smokers enrolled in public health center-based smoking cessation clinics and to examine differences in cessation outcomes and related characteristics across subgroups. Methods: Data from 21,105 newly enrolled adults attending 16 public health center-based smoking cessation clinics in C Province were drawn from the Smoking Cessation Service Integrated Information System of the National Tobacco Control Center. Latent class analysis was conducted using five indicators: time to first cigarette, cigarettes per day, prior quit attempts, alcohol use, and physical activity. Associations between latent class membership, covariates, and distal outcomes were examined using a three-step approach. Results: Four distinct latent classes were identified: Sedentary heavy smokers (46.8%), Active social heavy smokers (34.6%), Inactive-nicotine addictive-light smokers (13.6%), and Active lifestyle light smokers (5.0%). The latent classes showed different socioeconomic, smoking-related, and cessation-related confidence. Six-month cessation successes differed across classes, with higher abstinence among light-smoking classes and among Sedentary Heavy Smokers relative to Active Social Heavy Smokers. Conclusion: These findings highlight the value of person-centered profiling for informing more precise, context-sensitive cessation strategies and support the integration of behavioral and environmental considerations into community-based tobacco control programs. Full article