Inhalation Toxicology最新文献

{"title":"Risk stratification for myocardial injury and mortality in acute carbon monoxide poisoning: a multivariable predictive model.","authors":"Yongai Ling, Changsheng Ye, Xianwei Xiong, Huihua Huang, Weiguang Wang","doi":"10.1080/08958378.2026.2654002","DOIUrl":"10.1080/08958378.2026.2654002","url":null,"abstract":"<p><p><i>Background:</i> 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. <i>Methods:</i> 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 <i>via</i> ROC analysis. <i>Results</i><b>:</b> Myocardial injury occurred in 132 patients (18.5%). Patients with injury were older (median age: 65 <i>vs.</i> 54 years, <i>p</i> < 0.001), had higher lactate levels (2.5 <i>vs.</i> 1.8 mmol/L, <i>p</i> < 0.001), higher carboxyhemoglobin concentrations (26.65% <i>vs.</i> 21.75%, <i>p</i> < 0.001), and more frequent hypocapnia (50.8% <i>vs</i>. 24.7%, <i>p</i> < 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). <i>Conclusions:</i> 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.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"268-281"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET/CT imaging-based quantification of respiratory tract deposition of small- and large-particle aerosols versus intranasal bolus in rodents.","authors":"Jeremy A Boydston, Hee-Jeong Yang, Steve Mazur, Jordan K Bohannon, Matthew G Lackemeyer, Russ Byrum, Christopher Bartos, Kurt Cooper, Rebecca Reeder, William Kendall, Kathryn Conway, Kristi Partner, Nicholas Vaughan, Claudia Calcagno, Gerald Godwin, Yu Cong, Ian Crozier, Jens H Kuhn, Paul A Dabisch, Venkatesh Mani","doi":"10.1080/08958378.2026.2648617","DOIUrl":"10.1080/08958378.2026.2648617","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"225-236"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-OI improves mitochondria-associated endoplasmic reticulum membrane dysfunction by regulating MFN2 through Nrf2 transcription and alleviates airway inflammation in asthma exposed to PM2.5 early in life.","authors":"Jiaxin Xu, Lei Wang, Rui Zhou, Siwei Wang, Juan Li","doi":"10.1080/08958378.2026.2650614","DOIUrl":"10.1080/08958378.2026.2650614","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a disease that still lacks effective preventive measures with distinctive pathologicfeatures, particularly inflammation, oxidative stress, apoptosis and endoplasmic reticulum (ER) stress. 4-Octyl itaconate (4-OI) has been reported to possess immunomodulatory, anti-inflammatory and antioxidant properties.</p><p><strong>Methods: </strong>In this study, we evaluated the efficacy of 4-OI in airway inflammation and oxidative lung injury in asthmatic mice exposed to PM2.5 using the ovalbumin (OVA)+ PM2.5-induced asthma model in BALB/c mice. In addition, we further evaluated the role of 4-OI in protecting BEAS-2B cells from PM2.5 induction using an in vitro model of asthma.</p><p><strong>Results: </strong>The results showed that 4-OI attenuated airway inflammatory cell infiltration and the levels of mouse whole lung lavage fluid inflammatory factors, and decreased the levels of MDA and ROS, while increasing the activity of SOD. Meanwhile, in in vitro experiments, it was further demonstrated that 4-OI transcriptionally regulated MFN2 via Nrf2, which reduced the intracellular and mitochondrial ROS content, and the fluorescence intensities of Mito Tracker Red⁺ calnexin⁺ and MFN2⁺PERK⁺ were also significantly reduced. Fluo-3 AM experiment showed that 4-OI reduced Ca²⁺ concentration by regulating MFN2 through Nrf2 transcription. In addition, the protein expression of MFN1, MFN2, Bcl-2, and pro-Caspase3 was significantly elevated and that of PERK, GRP78, CHOP, Caspase12, Bax, and cleaved-Caspase3 was significantly decreased by Western Blot.</p><p><strong>Conclusions: </strong>In summary, our research demonstrated found that 4-OI improved the dysfunction of mitochondria-associated endoplasmic reticulum membranes by modulating MFN2 <i>via</i> Nrf2 transcription, thereby reducing the inflammatory response in asthmatic airways during early exposure to PM2.5.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"252-267"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting the Nrf2/HO-1 signaling cascade weakens the pro-inflammatory response induced by gasoline engine exhaust in lung epithelial cells following air-liquid interface exposure.","authors":"Ying Qu, Guoliang Li, Tao Yu, Xueyan Zhang, Wei Zhao, Min Zheng, Bin Li, Ping Bin","doi":"10.1080/08958378.2026.2659193","DOIUrl":"10.1080/08958378.2026.2659193","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the role of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling cascade in the inflammatory responses induced by whole gasoline engine exhaust (GEE) in lung epithelial cells <i>via</i> air-liquid interface (ALI) exposure.</p><p><strong>Materials and methods: </strong>Using an ALI exposure system, human bronchial epithelial cells (BEAS-2B) and type II alveolar epithelial cells (A549) were exposed to whole GEE collected from a two-wheeled motorcycle at various dilution ratios. After a 1 h exposure at 10 mL/min, cell relative viability, intracellular reactive oxygen species (ROS), glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were measured. Inflammatory cytokines (IL-1β, IL-6, and IL-8) were quantified. The Nrf2 inhibitor brusatol (BR, 300 nM) and the antioxidant N-acetyl-L-cysteine (NAC, 5 mM) were used to modulate the Nrf2/HO-1 pathway and oxidative stress, respectively. Protein and gene expression levels were analyzed by Western Blotting and real-time PCR.</p><p><strong>Results: </strong>Exposure to 10%GEE induced oxidative stress and optimally activated Nrf2/HO-1 expression without cytotoxicity, while higher concentrations suppressed this signaling pathway. Significant correlations were observed between Nrf2/HO-1 levels and inflammatory cytokines. Inhibition of Nrf2/HO-1 with BR reduced inflammatory responses which induced by the 10%GEE in both BEAS-2B and A549 cell lines. Furthermore, attenuating oxidative stress with NAC inhibited both Nrf2/HO-1 expression and the GEE-induced inflammatory response.</p><p><strong>Conclusion: </strong>Inhibiting the Nrf2/HO-1 signaling cascade attenuates the pro-inflammatory response induced by GEE in lung epithelial cells following ALI exposure. The Nrf2/HO-1 pathway appears to be a critical regulator of GEE-induced pulmonary inflammation, highlighting its potential as a therapeutic target.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"237-251"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing an air-liquid interface system for exposure of mouse laryngeal epithelial cells to cigarette smoke.","authors":"Akari Kimura, Amirbahador Golchin, Meena Easwaran, Patrick Timothy Kiessling, Mohammed Imran Khan, Joshua D Martinez, Elizabeth Erickson-DiRenzo","doi":"10.1080/08958378.2026.2657360","DOIUrl":"https://doi.org/10.1080/08958378.2026.2657360","url":null,"abstract":"<p><strong>Objective: </strong>The laryngeal epithelium is one of the first lines of defense against inhaled insults, including cigarette smoke (CS). However, a lack of suitable <i>in vitro</i> models has limited mechanistic studies of laryngeal epithelial injury and disease pathogenesis in response to CS. The purpose of this investigation was to establish an air-liquid interface (ALI) system for modeling airborne CS exposure in laryngeal epithelial cells.</p><p><strong>Methods: </strong>Primary mouse laryngeal epithelial cells were harvested, cultured, and transitioned from submerged to ALI conditions to induce epithelial differentiation. ALI cultures were characterized by electrophysiological evaluation of transepithelial resistance (TEER), histology, and immunofluorescent staining and quantification for epithelial markers and compared with native laryngeal tissue. ALI cultures were exposed to increasing doses of CS during differentiation, and epithelial barrier integrity was assessed by evaluating cytotoxicity, TEER, and structure.</p><p><strong>Results: </strong>Submerged laryngeal epithelial cultures were primarily proliferating basal cells. Differentiated ALI cultures demonstrated progressive epithelial maturation, with formation of a multilayered structure and high TEER, indicative of robust barrier integrity. Epithelial marker localization in ALI cultures closely resembled that of native mouse vocal fold epithelium. CS exposure disrupted epithelial barrier integrity in a dose-dependent manner, including increased cytotoxicity and reductions in TEER. Moderate exposure permitted some recovery of function and structure, underscoring the intrinsic resilience of laryngeal epithelial cells.</p><p><strong>Conclusion: </strong>This investigation establishes a physiologically relevant <i>in vitro</i> model system that recapitulates key features of native laryngeal epithelium and provides a robust platform for investigating the cellular and molecular pathways governing CS-induced epithelial injury and repair.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-18"},"PeriodicalIF":2.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to electronic cigarette aerosols triggers alterations in genomic DNA methylation that impacts cancer pathways in mice.","authors":"Christina Awada, Catherine B Klein, Terry Gordon, Amna Raja, Kent E Pinkerton, Morgan Poindexter, Emma Karey, Arul Veerappan, Judith T Zelikoff","doi":"10.1080/08958378.2026.2649516","DOIUrl":"https://doi.org/10.1080/08958378.2026.2649516","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this laboratory study was to characterize the effects of sub-chronic electronic cigarette (E-cig) aerosol exposures on genome-wide DNA methylation in mice to begin to elucidate the pathophysiology of E-cig-related pulmonary diseases and cancer.</p><p><strong>Materials and methods: </strong>Male C57BL/6 and FVBN mice were randomly assigned to one of two treatment groups (n = 6 per group) and exposed daily to either filtered air or a 50:50 mixture of propylene glycol and vegetable glycerol containing 24 mg/mL nicotine (+Nic). Whole-body inhalation exposures were conducted for 3 h/d, 5 d/week, for a total of 1-month. Sequences for ∼285 000 CpG probes were aligned to the mouse genome, and mixed linear models were used to model DNA methylation levels (β values). These evaluations were followed by ingenuity pathway analysis (IPA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analysis.</p><p><strong>Results and discussion: </strong>E-cig inhalation exposure induced significant DNA methylation changes in adult male mice, with a notable impact on cancer-related pathways. A total of 2300 genes in C57BL/6 mice and 6732 genes in FVBN mice were hypomethylated, while 1673 and 5529 genes were hypermethylated, respectively. KEGG and GO analyses highlighted key pathways such as Wnt/β-catenin signaling and proteoglycans in cancer, suggesting that E-cig aerosol exposure could disrupt critical genomic regulation and potentially promote carcinogenesis. These in vivo findings underscore the potential cancer-promoting effects of E-cig aerosols through epigenetic modifications.</p><p><strong>Conclusions: </strong>Findings from this study provide compelling evidence that sub-chronic E-cig exposure induces genomic DNA methylation changes linked to cancer pathways in two strains of adult male mice, highlighting the serious adverse consequences of E-cig use and strain-specific response differences.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-24"},"PeriodicalIF":2.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Numerical investigation of the effects of respiratory modes and ablation lesions on airflow and particle deposition in a pulmonary acinar model.","authors":"Qian Tang, Xin Zheng, Jia Lu, Chang Xu, Shifei Shen","doi":"10.1080/08958378.2026.2639385","DOIUrl":"10.1080/08958378.2026.2639385","url":null,"abstract":"<p><p>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 <i>via</i> 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.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"185-198"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An experimental validation of computational fluid dynamics for airflow in a subject-specific normal human nasal model using a precise 3D-printed replica.","authors":"Yin Cheng, Yajing Zhu, Shenglin Yan, Jianchun Liao, Qinghua Ge, Xiaoli Fu, Hu Peng","doi":"10.1080/08958378.2026.2646671","DOIUrl":"10.1080/08958378.2026.2646671","url":null,"abstract":"<p><strong>Background: </strong>Computational fluid dynamics (CFD) is widely used for studying nasal airflow but is rarely rigorously validated against experimental data. This study aimed to validate a subject-specific CFD model by comparing intranasal air pressure with measurements from a precise physical replica.</p><p><strong>Methods: </strong>1:1 scale resin model of a single healthy human nasal cavity was fabricated using high-precision 3D printing (0.1 mm tolerance). Static pressures at 63 checkpoints within the nasal cavity were measured under three steady-state flow rates (180, 560, and 1100 mL s^-1) corresponding to different respiratory intensities. These experimental data were compared with results from a standard k-ε CFD simulation.</p><p><strong>Results: </strong>At low to moderate flow rates (180 and 560 mL s^-1), pressures showed excellent consistency between experimental and CFD data. Quantitative analysis confirmed a strong correlation (Pearson's <i>r</i> = 0.98) and low error margins (RMSE < 6 Pa). However, at the high flow rate of 1100 mL s^-1, a significant deviation (RMSE = 18.5 Pa) was observed in the posterior nasal cavity during expiration.</p><p><strong>Conclusions: </strong>This study establishes a methodological framework for validating subject-specific nasal airflow simulations using high-fidelity 3D-printed replicas. Our findings confirm the accuracy of the standard k-ε turbulence model for this specific anatomy at low to moderate physiological flow rates. However, deviations at high flow rates highlight the limitations of standard turbulence models and experimental uncertainties in complex regimes. This validated methodology offers a robust tool for future clinical assessments of nasal resistance.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"213-224"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term cardiovascular and respiratory health effects of e-cigarette use: a narrative review of emerging evidence.","authors":"Rachael Obeng, Oluwabunmi Dada, Emmanuel Odame, Tarandeep Arora, Glory Dada","doi":"10.1080/08958378.2026.2644246","DOIUrl":"10.1080/08958378.2026.2644246","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results and discussion: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"173-184"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rat strain differences in bronchoalveolar lavage fluid and minimal association with histopathology findings.","authors":"Nataliia Kovalchuk, Christopher Smith, Emily Hackshaw","doi":"10.1080/08958378.2026.2644247","DOIUrl":"10.1080/08958378.2026.2644247","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Materials and methods: </strong>Twenty-eight studies conducted across two Test Facilities from 2018 to 2023 were reviewed to identify trends.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>These results suggest that BALF parameters are insufficient to independently characterize adversity but may be used in other ways to progress new approach methods.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"199-212"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}