Inhalation Toxicology最新文献

Objective: To investigate the associations between long-term exposure to ambient air pollutants and incident cardiovascular disease (CVD) in a high-exposure setting and to evaluate whether multimorbidity affects this relationship in middle-aged and older Chinese individuals.

Methods: Data from 7,692 adults in the China Health and Retirement Longitudinal Study (CHARLS), with up to 8 years of follow-up, were used. Long-term exposure to particulate matter ≤1 μm (PM₁), ≤2.5 μm (PM₂.₅), ≤10 μm (PM₁₀), nitrogen dioxide (NO₂), and ozone (O₃) was analyzed using high-resolution satellite-based estimates. Next, a least absolute shrinkage and selection operator regression multipollutant index was constructed. Hazard ratios for incident CVD were estimated using Cox proportional hazards models, and effect modification by multimorbidity was examined.

Results: During follow-up, a total of 1,759 participants developed CVD. Compared with those in the lowest quartile, participants in the highest quartile of PM₁, PM₂.₅, PM₁₀, and NO₂ exposure had hazard ratios of 1.35 (95% CI: 1.18-1.54), 1.58 (95% CI: 1.38-1.81), 1.63 (95% CI: 1.42-1.87), and 1.25 (95% CI: 1.09-1.44), respectively. Combined multipollutant exposure had the strongest effect, with an HR of 2.05 (95% CI: 1.78-2.37). The corresponding HRs were 2.27 (95% CI: 1.89-2.72) among participants without multimorbidity and 3.02 (95% CI: 2.44-3.73) among those with multimorbidity (P for interaction = 0.029).

Conclusion: Long-term exposure to ambient air pollutants is associated with a substantially increased risk of CVD, particularly among individuals with multimorbidity. These findings highlight the need for multipollutant control strategies and targeted prevention efforts among clinically vulnerable populations.

Introduction: Heated Tobacco Products (HTPs) are marketed as less harmful alternatives than cigarettes. While industry-funded studies suggest lower risks associated with HTP use compared with cigarettes, the health impacts of HTP use relative to non-use remain uncertain.

Methods: We reviewed tobacco industry-independent studies published between 2019 and 2024 investigating chemical composition of HTP sticks and emissions, and cardiovascular- and pulmonary health effects associated with their use in human subjects and relevant human in vitro models. Only original research articles were included. Studies on secondhand emissions, animal models and epidemiological studies were excluded.

Results: 74 studies met the inclusion criteria. HTP emissions contain lower levels of harmful tobacco-related chemicals (e.g. nicotine, Tobacco-Specific Nitrosamines and carbonyls) compared to cigarette smoke but higher concentrations of certain carcinogens. HTP-specific toxicants include formaldehyde cyanohydrin and plastic-derived compounds. Compared to smokers, HTP users show reduced levels of biomarkers of exposure (nicotine, exhaled CO, aromatic amines) and lower toxicity (oxidative stress, inflammation, DNA damage), although higher than in nonusers. Human studies reveal that HTP use adversely affects cardiovascular and pulmonary function. In vitro findings support these outcomes, showing cytotoxicity, oxidative stress, inflammation, and genotoxicity, often to a lesser extent compared to cigarette smoke.

Conclusions: HTP use exposes consumers to noxious chemicals and detrimentally impacts cardiovascular health and pulmonary function. Although the long-term harm of HTPs is unknown, current evidence suggests short-term toxicity comparable to cigarettes.

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.

Objective: Vaping's perception as a safe method of nicotine consumption has contributed to its widespread use among American youth. Research indicates that serious lung disease termed EVALI (E-cigarette or Vaping Product Use-Associated Lung Injury) can develop from vaping. However, the broader consequences on lung health remain less understood.

Methods: We evaluated the effects of vaping on college students' lungs using fractional exhaled nitric oxide (FeNO) scores, metal concentrations, and microbiota composition collected over three months.

Results and discussion: Mass spectrometry analysis of vape coils revealed that ceramic coils contained higher levels of metals Mg, Al, Cr, Mn, Fe, Ni, As, Sr, Ag, and Ti, while mesh coils had elevated concentrations of Cu, Cd, Pb, and Sn. Corresponding metals were detected in participants' exhaled breath, with vaping status and coil type significantly influencing heavy metal profiles, and FeNO contributing among vapers. FeNO levels positively correlated with vaping duration, indicating effects on airway inflammation. Analysis of exhaled microbiota showed that temporal variation (sampling month) and, among vapers, duration of vaping had stronger influences on microbial composition than vaping status or coil type, while FeNO had minimal impact. Specific metals, including Al, Fe, Co, Zn, and Zr, were modestly associated with microbial patterns, with Zn and Fe showing the strongest effects.

Conclusions: These findings identified three interconnected effects of vaping: lung inflammation, heavy metal exposure from heating coils, and changes in lung microbiota. This highlights the need for further research to clarify the mechanisms linking these outcomes.

Objective: Ammonia (NH₃) inhalation is a common occupational exposure, causing injuries similar to acute lung injury (ALI). Medical management is limited to supportive care, as no specific antidotes are currently available. This study aimed to evaluate the efficacy of potential therapeutic interventions to mitigate NH₃-induced damage using both in vivo (mouse) and in vitro (A549 alveolar epithelial cells) models.

Methods: BALB/c mice received 91.0 mg/kg NH₃ via intratracheal instillation, followed by intraperitoneal dexamethasone (100 mg/kg) at 1, 5, and 23 h post-exposure to assess therapeutic effects. Analyses were performed on days 1 and 7. The complementary studies in A549 cells examined whether therapeutic interventions could counteract NH₃-induced toxicity affecting cell viability and function.

Results: Dexamethasone-treatment did not counteract the lethal damage in mice or significantly reduce the severity of ALI that intensified over time, including increased lung inflammatory cell infiltration, lung hemorrhages, and coagulation abnormalities. However, treatment reduced methacholine-induced AHR, and MMP-9 and SP-D levels at 20h post-exposure. Most treatments in A549 cells failed to prevent apoptotic and necrotic cell death, oxidative stress, mitochondrial dysfunction, and membrane damage caused by NH₃ exposure however, the membrane stabilizer Poloxamer 188 (P188) highlighted the importance of stabilizing the cellular membrane damage to prevent further damages.

Conclusions: While standard treatment with corticosteroids offered limited protection in NH₃-exposed mice, the study's complementary in vitro investigations on new medical counter measures highlighted the complexity and severity of NH₃-induced lung injury. Together, the in vivo and in vitro findings emphasize the urgent need for effective medical countermeasures.

Objective: Phosgene is a highly toxic asphyxiating gas and also an important chemical raw material. Phosgene has been regarded as an environmental pollutant, and the accidental leakage of phosgene in the process of industrial production has posed a serious threat to related occupational groups. Phosgene exposure may lead to acute lung injury (ALI), marked by inflammation, heightened vascular permeability, and potentially life-threatening pulmonary edema. BML-111 is a lipid A4 receptor agonist which is compound with anti-inflammatory and antioxidant properties. The involvement of BML-111 in mitigating phosgene-induced ALI and the underlying mechanisms remain unclear.

Methods: In this study, we established a phosgene induced ALI rat model, examined the effects of phosgene exposure on lung tissue and bronchoalveolar lavage fluid (BALF) of rats, and evaluated the lung tissue pathology, lung wet weight, lung coefficient and respiratory function of phosgene exposed rats after intervention with BML-111. The levels of pro-inflammatory cytokines and oxidative stress markers were measured in BALF and lung tissue.

Results: This study showed that BML-111 notably enhanced respiratory function, mitigated ALI severity, and reduced pulmonary edema in phosgene-exposed rats. Mechanistically, these protective effects were attributed to a reduction in pro-inflammatory cytokines and oxidative stress, alongside an enhancement of overall antioxidant capacity. Furthermore, it was found that the activation of ACE2 is a key mechanism through which BML-111 exerts its protection.

Conclusion: The findings suggest that BML-111 can alleviate phosgene-induced ALI in rats by activating ACE2, thereby inhibiting inflammatory responses and oxidative stress. BML-111 shows promise as a preventive candidate for treating phosgene-induced ALI.

Electronic nicotine delivery systems (ENDS) arrived on the U.S. market in 2007 and rapidly grew in popularity as a harm reduction tool for traditional cigarette users. While initially marketed as a healthier alternative to combustible cigarettes, the unique mixture of chemical constituents in ENDS products and their emissions have led to rising concern about their safety and the long-term health implications. Given the lack of long-term, epidemiological research on the health effects of these products, recent research has sought to understand the impacts on cellular components and gain understanding of acute effects to inform potential chronic health implications. Studies have demonstrated the deleterious effects the use of ENDS has on the oral cavity, respiratory, and cardiovascular systems. ENDS use has been linked to gingival inflammation and alterations in the oral microbiome contributing to periodontal disease. Further, the presence of heavy metals and other constituents in ENDS emissions contribute to aberrant oxidative stress and inflammation within the lung, contributing to alterations in functional lung capacity and respiratory symptoms in ENDS users. In addition, harmful components of ENDS emissions make their way to the circulatory system, leading to detrimental impacts in cardiovascular functioning such as a rise in blood pressure, impaired vascular functioning, and increased heart rate, all of which are known to underscore long-term cardiovascular ailments. This review will provide an in-depth discussion of the current literature available on the consequences of ENDS use on the oral cavity, respiratory, and cardiovascular systems as well as provide insight into long-term implications that may result.

The ever-changing popularity of electronic nicotine delivery systems (ENDS) among both youth and adults in the United States has been influential in shaping users' perceptions and behaviors. This behavior driven ENDS usage is described as puffing topography (PT) which includes user's puff duration, flow rate, intra puff interval, the volume of e-liquid used and total number of puffs per session. These metrics are not only useful for characterizing individual vaping behaviors but are also critical for assessing the extent of exposure to potentially harmful substances such as nicotine, volatile organic compounds (VOCs), and particulate matter emitted during use. Previous studies have indicated that puff volume and flow rate are distinct but related parameters that determine exposure to hazardous emissions among users and bystanders. However, current evidence suggests that vaping behavior is also influenced by the age at which users first encounter ENDS, the strength of the nicotine present, and whether users develop circadian patterns of ENDS usage. This review article, which is a part of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement summarizes the critical aspects of PT and explores how various factors including lifestyle, gender, e-liquid composition (such as flavor and nicotine concentration), and device parameters can influence exposure risks. The standardization of puffing topography as a tool to evaluate vaping behavior and exposure risks to toxic emissions could be instrumental in developing consensus standards for ENDS and protecting public health.

While electronic nicotine delivery systems or ENDS are often marketed as a safer alternative to traditional cigarettes, emissions generated during the operation of these devices contain a complex mixture of toxic substances. ENDS emissions are primarily composed of fine particulate matter (PM_2.5, smaller than 2.5 µm in size) and ultrafine particles/nanoparticles (PM_0.1, smaller than 100 nm in size), metals (nickel, copper, zinc, tin, lead, and their oxides), carbonyls (formaldehyde, acetaldehyde (a carcinogen), and acrolein), volatile organic compounds (VOCs) (benzene, toluene, and over 70 other VOCs), nicotine, and many unknown chemicals. The levels and composition of these toxic emissions can vary based on factors like device design, e-liquid formulation, device power and temperature levels, and vaping behavior of the user. Within this section of the Special Issue 'Science Education and Research on Vaping and Interventions for Community Engagement', important parameters in defining and characterizing ENDS aerosols will be discussed. Hazardous components of ENDS aerosols including particulate matter, heavy metals, and volatile organic compounds will be delineated and appropriate analytical methods to accurately determine physicochemical properties will be highlighted. Definitions and comparisons of first-hand, second-hand, and third-hand emissions will also be explored alongside pertinent device parameters that influence each type of ENDS emission.

The widespread use of electronic nicotine delivery systems (ENDS) among youth and adults has become a significant public health concern. Approximately 19.6% of middle and high school students in the United States have reported using ENDS containing nicotine. Factors contributing to their popularity include social and recreational appeal, sensory satisfaction, ease of accessibility, and aggressive marketing strategies including influencer-driven promotions and youth-targeted campaigns through social media platforms. The variety of available flavors and modifiable features of ENDS devices further enhances their acceptance, often overshadowing their potential health risks. Despite their perceived advantages, misconceptions about ENDS persist, including beliefs that emissions are harmless, vaping is safer than smoking, and secondhand exposure is inconsequential. These misunderstandings contribute to the normalization of ENDS use, hindering public awareness of the associated health and environmental hazards. This manuscript addresses seven prevalent misconceptions about ENDS ranging from their safety during pregnancy to their environmental impact, highlighting the need for comprehensive education and community engagement to mitigate the risks of ENDS usage and promote informed decision-making. In the following section of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement (SERVICE), we will explore how these misconceptions not only encourage the societal acceptance and use of ENDS but also contribute to potential health risks.