Photocatalytic Decomposition of Formic Acid on Mo2C-Containing Catalyst

Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to filtered air and wood smoke. Samples were collected before (pre), at 24 h and 44 h after exposure, to air and wood smoke. Data are given as medians with interquartile range. (DOCX 62 kb

Diesel exhaust and wood smoke : mechanisms, inflammation and intervention

Background Particulate matter (PM) air pollution is associated with increased respiratory and cardiovascular morbidity and mortality. Diesel engine exhaust (DE) and wood combustion are major contributors to ambient air pollution and adverse health effects. The aim of this thesis was to investigate the fate of inhaled combustion-derived PM, the subsequent effects on pulmonary inflammation and symptomatology and to explore the potential for particle filters to improve public health. Additionally, it aimed at increasing the understanding of the pathophysiological mechanisms underlying the adverse vascular effects of PM inhalation in man. Methods In study I, lung deposition of wood smoke-derived particulates from incomplete combustion was determined in healthy and COPD subjects. In study II, airway inflammation was assessed in healthy subjects exposed to wood smoke and filtered air. In study III, vehicle cabin air inlet filters were evaluated regarding filtering capacity for DE and whether they affected the toxicological potential of the filtered PM. Healthy subjects were then exposed to filtered air and unfiltered DE, as well as DE filtered through two selected filters. In study IV, healthy subjects were exposed to filtered air and DE. Nitric oxide bioavailability was assessed by plethysmography in the presence of an NO clamp (NO synthase inhibitor NG-monomethyl locally and systemically administered) with measurements of arterial stiffness, cardiac output and blood pressure (BP). Results Study I: The total PM number deposition fraction of the wood smoke was 0.32 and 0.35 for healthy and COPD subjects respectively. Study II: Inhalation of wood smoke caused CD3+ and mast cell infiltration in the bronchial submucosa along with CD8+ cell recruitment to the epithelium. In bronchial wash, inflammatory cells, myeloperoxidase and matrix metalloproteinase 9 levels decreased. Study III: An efficient cabin air filter with an active charcoal component was most favourable in in-vitro tests and reduced symptoms in the human exposure study. Study IV: Local NO synthase inhibition caused similar vasoconstriction after exposure to DE and filtered air, along with an increase in plasma nitrate concentrations, suggesting an increase in the basal NO release due to oxidative stress. Systemic NO synthase inhibition increased arterial stiffness and blood pressure after DE exposure along with an increase in systemic vascular resistance and reduced cardiac output, implying that the increased basal NO release could not compensate for the reduced NO bioavailability in the conduit vessels. Conclusion Wood smoke particles from incomplete combustion tend to have a greater airway deposition than particles from better combustion. The airway inflammatory responses to the former particles differ from what have been shown for other PM pollutants, which may be of importance for subsequent health effects. The vasomotor dysfunction shown after DE exposure may largely be explained by reduced NO bioavailability. A vehicle cabin air inlet particle filter with active charcoal was effective to reduce DE exposure and subsequent symptoms. This may conceptually be of benefit when it comes to decreasing engine exhaust-related adverse health effects

Comparable Response Following Exposure to Biodiesel and Diesel Exhaust Particles in Advanced Multicellular Human Lung Models

Biodiesel is considered to be a sustainable alternative for fossil fuels such as petroleum-based diesel. However, we still lack knowledge about the impact of biodiesel emissions on humans, as airways and lungs are the primary target organs of inhaled toxicants. This study investigated the effect of exhaust particles from well-characterized rapeseed methyl ester (RME) biodiesel exhaust particles (BDEP) and petro-diesel exhaust particles (DEP) on primary bronchial epithelial cells (PBEC) and macrophages (MQ). The advanced multicellular physiologically relevant bronchial mucosa models were developed using human primary bronchial epithelial cells (PBEC) cultured at air–liquid interface (ALI) in the presence or absence of THP-1 cell-derived macrophages (MQ). The experimental set-up used for BDEP and DEP exposures (18 µg/cm2 and 36 µg/cm2) as well as the corresponding control exposures were PBEC-ALI, MQ-ALI, and PBEC co-cultured with MQ (PBEC-ALI/MQ). Following exposure to both BDEP and DEP, reactive oxygen species as well as the stress protein heat shock protein 60 were upregulated in PBEC-ALI and MQ-ALI. Expression of both pro-inflammatory (M1: CD86) and repair (M2: CD206) macrophage polarization markers was increased in MQ-ALI after both BDEP and DEP exposures. Phagocytosis activity of MQ and the phagocytosis receptors CD35 and CD64 were downregulated, whereas CD36 was upregulated in MQ-ALI. Increased transcript and secreted protein levels of CXCL8, as well as IL-6 and TNF-α, were detected following both BDEP and DEP exposure at both doses in PBEC-ALI. Furthermore, the cyclooxygenase-2 (COX-2) pathway, COX-2-mediated histone phosphorylation and DNA damage were all increased in PBEC-ALI following exposure to both doses of BDEP and DEP. Valdecoxib, a COX-2 inhibitor, reduced the level of prostaglandin E2, histone phosphorylation, and DNA damage in PBEC-ALI following exposure to both concentrations of BDEP and DEP. Using physiologically relevant multicellular human lung mucosa models with human primary bronchial epithelial cells and macrophages, we found BDEP and DEP to induce comparable levels of oxidative stress, inflammatory response, and impairment of phagocytosis. The use of a renewable carbon-neutral biodiesel fuel does not appear to be more favorable than conventional petroleum-based alternative, as regards of its potential for adverse health effects

In vitro toxicity evaluation in A549 cells of diesel particulate matter from two different particle sampling systems and several resuspension media

In urban areas, inhalation of fine particles from combustion sources such as diesel engines causes adverse health effects. For toxicity testing, a substantial amount of particulate matter (PM) is needed. Conventional sampling involves collection of PM onto substrates by filtration or inertial impaction. A major drawback to those methodologies is that the extraction process can modify the collected particles and alter their chemical composition. Moreover, prior to toxicity testing, PM samples need to be resuspended, which can alter the PM sample even further. Lastly, the choice of the resuspension medium may also impact the detected toxicological responses. In this study, we compared the toxicity profile of PM obtained from two alternative sampling systems, using in vitro toxicity assays. One system makes use of condensational growth before collection in water in an impinger – BioSampler (CG-BioSampler), and the other, a Dekati® Gravimetric Impactor (DGI), is based on inertial impaction. In addition, various methods for resuspension of DGI collected PM were compared. Tested endpoints included cytotoxicity, formation of cellular reactive oxygen species, and genotoxicity. The alternative collection and suspension methods affected different toxicological endpoints. The water/dimethyl sulfoxide mixture and cell culture medium resuspended particles, along with the CG-BioSampler sample, produced the strongest responses. The water resuspended sample from the DGI appeared least toxic. CG-BioSampler collected PM caused a clear increased response in apoptotic cell death. We conclude that the CG-BioSampler PM sampler is a promising alternative to inertial impaction sampling

Respiratory tract deposition of inhaled wood smoke particles in healthy volunteers

Background: Respiratory tract deposition of air pollution particles is a key to their adverse health effects. This study was aimed to determine the size-resolved deposition fraction (DF) of sooty wood smoke particles in the lungs of healthy subjects. The type of wood smoke investigated is typical for household air pollution from solid fuels, which is among the largest environmental health problems globally. Methods: Twelve healthy volunteers inhaled diluted wood smoke from incomplete soot-rich combustion in a common wood stove. The DF of smoke particles (10–500 nm) was measured during three 15-min exposures in each subject during spontaneous breathing. Lung function was measured using standard spirometry. Results: The total DFs by particle number concentration were 0.34±0.08. This can be compared with DFs of 0.21–0.23 in healthy subjects during previous experiments with wood pellet combustion. For particle mass, the total DFs found in this study were 0.22±0.06. DF and breathing frequency were negatively correlated as expected from model calculations (p<0.01). Conclusions: The DF of the investigated sooty wood smoke particles was higher than for previously investigated particles generated during more efficient combustion of biomass. Together with toxicological studies, which have indicated that incomplete biomass combustion particles rich in soot and polycyclic aromatic hydrocarbons (PAHs) are especially harmful, these data highlight the health risks of inadequate wood combustion

Reduced bronchoalveolar macrophage phagocytosis and cytotoxic effects after controlled short-term exposure to wood smoke in healthy humans

Abstract Background Exposure to wood smoke has been shown to contribute to adverse respiratory health effects including airway infections, but the underlying mechanisms are unclear. A preceding study failed to confirm any acute inflammation or cell influx in bronchial wash (BW) or bronchoalveolar lavage (BAL) 24 h after wood smoke exposure but showed unexpected reductions in leukocyte numbers. The present study was performed to investigate responses at an earlier phase, regarding potential development of acute inflammation, as well as indications of cytotoxicity. Methods In a double-blind, randomised crossover study, 14 healthy participants were exposed for 2 h to filtered air and diluted wood smoke from incomplete wood log combustion in a common wood stove with a mean particulate matter concentration of 409 µg/m3. Bronchoscopy with BW and BAL was performed 6 h after exposure. Differential cell counts, assessment of DNA-damage and ex vivo analysis of phagocytic function of phagocytosing BAL cells were performed. Wood smoke particles were also collected for in vitro toxicological analyses using bronchial epithelial cells (BEAS-2B) and alveolar type II-like cells (A549). Results Exposure to wood smoke increased BAL lactate dehydrogenase (LDH) (p = 0.04) and reduced the ex vivo alveolar macrophage phagocytic capacity (p = 0.03) and viability (p = 0.02) vs. filtered air. BAL eosinophil numbers were increased after wood smoke (p = 0.02), while other cell types were unaffected in BW and BAL. In vitro exposure to wood smoke particles confirmed increased DNA-damage, decreased metabolic activity and cell cycle disturbances. Conclusions Exposure to wood smoke from incomplete combustion did not induce any acute airway inflammatory cell influx at 6 h, apart from eosinophils. However, there were indications of a cytotoxic reaction with increased LDH, reduced cell viability and impaired alveolar macrophage phagocytic capacity. These findings are in accordance with earlier bronchoscopy findings at 24 h and may provide evidence for the increased susceptibility to infections by biomass smoke exposure, reported in population-based studies

Exposure to wood smoke increases arterial stiffness and decreases heart rate variability in humans

Background: Emissions from biomass combustion are a major source of indoor and outdoor air pollution, and are estimated to cause millions of premature deaths worldwide annually. Whilst adverse respiratory health effects of biomass exposure are well established, less is known about its effects on the cardiovascular system. In this study we assessed the effect of exposure to wood smoke on heart rate, blood pressure, central arterial stiffness and heart rate variability in otherwise healthy persons. Methods: Fourteen healthy non-smoking subjects participated in a randomized, double-blind crossover study. Subjects were exposed to dilute wood smoke (mean particle concentration of 314 +/- 38 mu g/m(3)) or filtered air for three hours during intermittent exercise. Heart rate, blood pressure, central arterial stiffness and heart rate variability were measured at baseline and for one hour post-exposure. Results: Central arterial stiffness, measured as augmentation index, augmentation pressure and pulse wave velocity, was higher after wood smoke exposure as compared to filtered air (p &lt; 0.01 for all), and heart rate was increased (p &lt; 0.01) although there was no effect on blood pressure. Heart rate variability (SDNN, RMSSD and pNN50; p = 0.003, p &lt; 0.001 and p &lt; 0.001 respectively) was decreased one hour following exposure to wood smoke compared to filtered air. Conclusions: Acute exposure to wood smoke as a model of exposure to biomass combustion is associated with an immediate increase in central arterial stiffness and a simultaneous reduction in heart rate variability. As biomass is used for cooking and heating by a large fraction of the global population and is currently advocated as a sustainable alternative energy source, further studies are required to establish its likely impact on cardiovascular disease

Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response

Abstract Background Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. Methods Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo–keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed. Results DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = −0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo–keto reductases, or epoxide hydrolase protein expression. Conclusion These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways