Background: Myocardial injury following carbon monoxide (CO) poisoning is associated with increased mortality, yet early predictors remain poorly characterized. This study aimed to develop predictive models for early risk stratification using readily available clinical data. Methods: In a retrospective analysis of 714 patients with acute CO poisoning (2019–2024), we evaluated clinical and laboratory variables to identify predictors of myocardial injury (defined as cTnI ≥ 0.05 ng/mL) and 90-d mortality. Multivariable logistic regression was used to identify independent predictors, and model performance was assessed via ROC analysis. Results : Myocardial injury occurred in 132 patients (18.5%). Patients with injury were older (median age: 65 vs. 54 years, p < 0.001), had higher lactate levels (2.5 vs. 1.8 mmol/L, p < 0.001), higher carboxyhemoglobin concentrations (26.65% vs. 21.75%, p < 0.001), and more frequent hypocapnia (50.8% vs. 24.7%, p < 0.001). In the multivariable model adjusting for clinically relevant and univariately significant variables, age (per year increase; aOR = 1.02, 95% CI: 1.01–1.03), hypocapnia (aOR = 2.23, 95% CI: 1.23–4.07), and severe neurological impairment (aOR = 3.86, 95% CI: 2.12–7.05) were independently associated with myocardial injury. For 90-day mortality, independent predictors were age (per year increase; aOR = 1.14, 95% CI: 1.08–1.21) and severe neurological impairment (aOR = 7.53, 95% CI: 2.50–22.67). The models demonstrated good predictive accuracy for myocardial injury (AUC = 0.750, 95% CI: 0.703–0.797) and excellent predictive ability for mortality (AUC = 0.895, 95% CI: 0.846–0.944). Conclusions: The clinical risk model incorporating advancing age, severe neurological impairment, and hypocapnia enables risk stratification for myocardial injury, a critical intermediate marker of mortality in acute CO poisoning.

Objectives The size of airborne particles may influence where they deposit in the respiratory tract, the infectious dose, and disease progression. Intranasal bolus administration is often used as a substitute for aerosol exposure. Inhalational and intranasal exposure routes are commonly used in hamster and guinea pig models of infectious diseases. The aim of the present study was to compare regional respiratory tract deposition of small- and large-particle aerosols to intranasal bolus administration. Methods Golden hamsters were exposed to 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG)-radiolabeled aerosols with mass median aerodynamic diameters (MMADs) of 1.3 and 6.1 µm, and Hartley guinea pigs were exposed to 1.4 and 10.4 µm aerosols. Separately, hamsters and guinea pigs received bolus solutions of 18F-FDG (50 µL per naris) intranasally. Positron emission tomography–computed tomography (PET/CT) imaging was used to quantify the deposition of 18F-FDG in the respiratory tracts, including the oronasal cavities, tracheas/esophagi, and lungs. Results Smaller particle aerosols deposited in the lungs more efficiently than larger particle aerosols or intranasal bolus administration. Large-particle aerosol and intranasal bolus administration resulted in greater oronasal deposition than small-particle aerosol. Conclusions PET/CT imaging-based quantification enabled novel characterization of particle deposition in rodents and supports an inverse relationship between aerodynamic particle size and pulmonary deposition. The regional distribution of intranasal bolus administered FDG more closely resembled large-particle aerosols than small-particle aerosols. These findings may aid in understanding the infectivity and pathogenicity of bioaerosols based on particle size and raise concern about substituting intranasal administration for aerosol exposure.

Background Six years since the revised Test Guidelines 412 and 413 (TG412 and TG413) were issued, there are sufficient data to evaluate the relationship between bronchoalveolar lavage (BAL) cytology and biomarkers with histopathology. Objective This retrospective study evaluates the correlation between mandatory endpoints in the BAL fluid (LDH activity, concentration of total protein, inflammatory cell counts) and histopathological changes in the lungs following sub-chronic inhalation exposure in rats. Materials and methods Twenty-eight studies conducted across two Test Facilities from 2018 to 2023 were reviewed to identify trends. Results At baseline, there were no strain differences in BAL fluid total protein, but LDH activity was statistically different between sexes and ages. LDH activity and total protein in BALF at the lowest observed adverse effect concentration showed no pathological pattern following inhalation exposure to the tested chemicals, while immune cell counts shifted in Wistar Han rats. Specifically in studies with adverse lung histopathology, total protein and LDH activity were generally elevated, along with a shift in immune cells toward neutrophils and eosinophils, without correlation to the severity score of adverse microscopic findings. Conclusion These results suggest that BALF parameters are insufficient to independently characterize adversity but may be used in other ways to progress new approach methods.

Background The rapid rise in e-cigarette use has generated increasing public health concern regarding its long-term effects on the cardiopulmonary system. Although e-cigarettes are often marketed as a safer alternative to traditional tobacco products, growing evidence suggests they may contribute to chronic respiratory and cardiovascular diseases. Methods This contemporary narrative review synthesizes current research published between 2015 and 2025 on the long-term respiratory and cardiovascular consequences of e-cigarette use, integrating findings from epidemiologic, clinical, and mechanistic studies. Results and Discussion Evidence consistently links frequent e-cigarette use to elevated risks of chronic obstructive pulmonary disease (COPD), asthma exacerbation, impaired lung function, myocardial infarction, arrhythmias, and endothelial dysfunction. Mechanistic data reveal nicotine-induced sympathetic activation, oxidative stress, and vascular injury as key biological pathways underlying these effects. Older adults and daily users appear particularly vulnerable due to cumulative exposure and reduced physiological resilience. Despite these concerning trends, substantial gaps remain, including limited longitudinal data, inconsistent exposure characterization, and inadequate distinction between exclusive and dual users. Conclusions Addressing these gaps through well-designed cohort and mechanistic studies will be critical to refining clinical guidance, informing regulatory policy, and shaping evidence-based public health messaging.

Objective Nebulizers are medical devices that convert liquid solutions, such as saline or medication, into aerosols for direct airway delivery. Their effectiveness relies on interfaces, typically made from polymeric materials containing additives to enhance functionality and durability. This study aimed to characterize emissions of volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) from different components of five nebulizers, considering two exposure routes: inhalation and dermal contact. Materials and Methods Five nebulizers were assessed by analyzing emissions from individual components and from complete system configurations. VOC and SVOC emissions were quantified and short-term exposure (20 minutes) was assessed for infants and children. Estimated exposure levels were compared with toxicological reference values, including inhalation Derived No-Effect Levels (DNELs), to evaluate potential health risks via inhalation and dermal contact. Results All tested components emitted VOCs, with the highest concentrations detected in masks and whole-system configurations. Some identified compounds, including toluene, styrene, siloxane D4, and 2-ethylhexanoic acid, are suspected or recognized reproductive toxicants. Although measured levels were very low, inhalation represents a potential exposure route warranting a precautionary approach. Phenol, a suspected mutagen, reached concentrations up to 65.9 μg/m³, corresponding to 11.7% of the inhalation DNEL for a 20-minute exposure in infants and children. Dermal exposure levels were very low compared with toxicological reference values. Nevertheless, compounds such as benzyl alcohol and 2-ethylhexyl acrylate, both recognized as EU-classified skin sensitizers, were detected. Cyclic siloxanes D5, D6, and D7 were also detected, with D6 showing the highest dermal intake. As these siloxanes are classified as Persistent, Bioaccumulative and Toxic (PBT) in the EU, long-term effects from bioaccumulation and environmental persistence should be considered. Discussion and Conclusions Although measured VOC and SVOC concentrations were low and below established toxicological thresholds, these findings underscore the need for preventive measures, particularly for sensitive populations such as infants and children. Inhalation appears to be the most relevant exposure pathway during use, while dermal exposure, though minimal, may contribute to sensitization risks. The presence of PBT-classified siloxanes further emphasizes the need to consider long-term human health and environmental implications. Overall, these findings support the implementation of preventive strategies and continued monitoring of material emissions in medical devices intended for vulnerable users.

Understanding particle deposition patterns in the pulmonary acinus is essential for early intervention and treatment in acinar diseases. This study numerically investigated the effects of respiratory modes and emphysematous alveolar wall ablation on airflow and particle deposition in a physiologically representative pulmonary acinar model. A heterogeneous acinar model was developed, incorporating alveolar expansion and contraction via the dynamic meshing method, and its validity was confirmed by comparison with published particle deposition data. Airflow and particle transport patterns were then analyzed under varying respiratory modes and degrees of alveolar wall ablation. For particles smaller than 1 μm, deposition decreased with higher breathing frequency and increased with larger tidal volume. Smaller particles penetrated deeper and deposited more uniformly due to strong airflow coupling. Compared with the normal acinus, the lesioned acinus exhibited reduced airflow variability, lower expansion capacity, and a decreased deposition fraction. Alveolar wall ablation impaired lung expansion and restricted distal airflow penetration, leading to localized particle deposition near the acinar entrance. As lesion severity increased, the deposition progressively declined due to altered flow patterns and a reduced surface-to-volume ratio. The particle deposition declined nonlinearly with lesion severity. A 30% wall ablation reduced total deposition by over 40%, whereas further increases to 60% and 90% caused only minor additional decreases, indicating a nonlinear response in which early structural damage disproportionately affects acinar particle deposition. These findings underscore the importance of early intervention to preserve alveolar drug deposition efficiency and improve therapeutic outcomes in patients with progressive pulmonary diseases such as emphysema.

Objective Pulmonary surfactant proteins (SP-A, SP-B, SP-C, and SP-D) are essential regulators of alveolar surface tension and pulmonary immune defense, forming a critical frontline barrier against airborne xenobiotics. This study aimed to evaluate the molecular interactions between environmentally prevalent airborne pollutants and human surfactant proteins. Materials and Methods A multi-tiered computational framework assessed interactions between 87 airborne pollutants and surfactant proteins. Structure-based molecular docking using AutoDock Vina identified benzo[a]pyrene and crotonic acid as highest-affinity ligands (binding energies up to −8.1 kcal/mol). The top ligands underwent 200 ns molecular dynamics simulations with SP-A, SP-B, SP-C, and SP-D using the CHARMM36 force field in GROMACS. Structural metrics (RMSD, RMSF, SASA, and Rg), principal component analysis (PCA), and MM-GBSA binding free energy calculations were performed. Results and Discussion Analyses demonstrated sustained ligand-protein interactions and moderate conformational shifts, particularly within SP-A and SP-C domains. PCA revealed ligand-induced conformational changes, while MM-GBSA confirmed thermodynamic favorability (ΔGbind −26.5 to −32.8 kcal/mol). These findings suggest a novel mechanism of respiratory toxicity via molecular disruption of surfactant proteins. Conclusions This integrated in-silico approach highlights pollutant-induced surfactant protein alterations as potential biomarkers of pulmonary toxicant exposure and underscores the need for experimental validation and further mechanistic studies.

Objective The presence of fine dusts in the industrial working environment has significant implications for occupational safety. As a result, legislators have implemented regulations to protect employees from adverse lung effects. The establishment of limits aims to prevent health hazards, particularly lung diseases, even with prolonged exposure. Niobium, a chemical element widely used in the industry, is commonly found as an additive in various alloy products. Materials and Methods Given the inhalation potential during manufacturing and the substantial volume of niobium used, a 90-day-nose-only inhalation study of diniobium pentaoxide (Nb2O5) was conducted in rats. Following exposure of rats to 1.5, 6, and 24 mg/m3 Nb2O5, various endpoints were examined to assess potential lung toxicity and exposure–concentration–response relationships associated with the inhaled test substance. Results Analysis of polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid (BALF) in the treated groups showed levels close to clean air control levels. Histopathological analysis revealed the presence of particle-laden macrophages in lung alveoli, bronchus- and nose-associated lymphoid tissue, and lung-associated lymph nodes in the group exposed to the highest concentration. Additionally, activation of pneumocytes type 2 was observed. Discussion and Conclusions All findings were interpreted as adaptive and non-adverse. Therefore, no adverse effects were observed in any of the endpoints, including the group exposed to the highest concentration. Under the conditions of this study, a NOAEC (no observed adverse effect concentration) of 24 mg/m3 was determined. Diniobium pentaoxide is thus considered a newly discovered nuisance dust.

Objective Volatile organic compounds (VOCs) are prevalent in both indoor and outdoor environments and have been linked to health effects. This study aimed to assess VOC-induced effects on the respiratory epithelium using an in vitro human bronchial epithelial air–liquid interface (ALI) model. Methods A human bronchial epithelial cell line, 16HBE, was cultured at ALI and exposed to relevant concentrations of two representative VOCs, acrolein or formic acid, and matched filtered air (control) in a CelTox exposure system for two hours to replicate an acute inhalation exposure. Cells were allowed to recover for 24 h before cell lysate and culture media were collected for analysis. Results Cytotoxicity, based on LDH activity, significantly increased at the highest doses tested for both VOCs. A dose-dependent increase in barrier permeability was observed for confluent cells exposed to acrolein and formic acid. Acrolein and formic acid exposure induced IL-8, TNFα, and HMOX-1 expression, genes indicative of proinflammatory signaling and oxidative stress, respectively. Formic acid, but not acrolein, exposure also increased expression of PINK1, a gene indicative of mitophagy. Benchmark concentration (BMC) modeling of in vitro acrolein data yielded a BMCL (benchmark concentration lower confidence limit) that substantiates the stringency of OSHA’s 8-hour permissible exposure limit (PEL). In contrast, BMC modeling of in vitro formic acid data produced BMCLs below existing regulatory exposure thresholds. Conclusion Collectively, these findings demonstrate that this model is a plausible in vitro tool to investigate VOC-induced effects on the airway and supports its utility in VOC safety evaluation.

Background Ozone (O3) and nitrogen dioxide (NO2) are highly reactive gases associated with all cause-mortality. Epidemiology studies suggest that the risk from O3 and NO2 exposure is modified by sex. O3 is more strongly associated with declines in pulmonary function in males, but females show stronger associations with cardiovascular disease (CVD). For NO2 exposure, females show stronger associations for increased risk of CVD, loss of lung function, and mortality. It remains unclear if these differences stem from social constructs or underlying biologic responses. Methods To investigate sex differences after pollutant exposure, we used a single blind, randomized crossover, controlled exposure study to examine the pulmonary, inflammatory, and clotting/fibrinolysis response after exposure to O3 and NO2 relative to clean air. Healthy adult participants (n = 22 male = 10, female = 12) underwent separate two-hour exposures to clean air, 300 ppb O3, and 500 ppb NO2 exposures while exercising intermittently. Results Compared to air, exposure to O3 resulted in a mean percent change in FEV1 (-5.74%, 95%CI: −7.83, −3.65, p < 0.001), FVC (-3.94%, 95%CI: −5.59, −2.30, p < 0.001), and FEV1/FVC (-1.90%, 95%CI: −3.54, −0.25, p < 0.01), and elevated IL-6 (16.3%, 95%CI: 0.51, 32.14, p < 0.01), C-Reactive Protein (CRP) (44.54%; 95%CI: 15.44, 73.65, p < 0.001), and Serum amyloid A (SAA) (33.6%; 95%CI: 7.30, 60.0, p < 0.01). NO2 exposure resulted in a mean percent change of D-dimer (10.9%, 95%CI: −0.23, 21.93, p < 0.05). When stratified by sex, after O3 exposure, males displayed greater decrements in FEV1 (males; −7.81% (95%CI: −11.45, −4.19) females: −4.00% (95%CI: −6.20, −1.80; p < 0.05)) and CRP increased in males by 78.50% (95%CI: 27.50, 129.50) compared to 16.20% (95%CI: −10.43, 42.84) in females (p < 0.01) and SAA increased in males by 60.25% (95%CI: 12.02, 108.48) compared to 15.18% (95%CI: −14.53, 44.90) in females (p = 0.051). TNFα was elevated in females by an average of 10.9% (95%CI: 0.75, 21.23) compared to males (-2.29%, 95%CI: −12.32, 7.75) (p < 0.05). After NO2, D-dimer was elevated in females by 18.98% (95%CI: 4.69, 33.26) compared to males (1.52%, 95%CI: −16.12,19.16) (p = 0.062). Conclusions Sex modified the pulmonary and inflammatory response to O3 and NO2, a finding consistent with epidemiological observations of sex differences after O3 and NO2 exposure.