| 1. |
- Muala, Ala, et al.
(författare)
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Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity
- 2015
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Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, < 0.05, < 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (< 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, < 0.05 and < 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, < 0.05, < 0.05 and < 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.
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| 2. |
- Al-Rekabi, Zeinab, et al.
(författare)
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Uncovering the cytotoxic effects of air pollution with multi-modal imaging of in vitro respiratory models
- 2023
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Ingår i: Royal Society Open Science. - : Royal Society Publishing. - 2054-5703. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell-pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.
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| 3. |
- Barath, Stefan, et al.
(författare)
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Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions
- 2010
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Ingår i: Particle and Fibre Toxicology. - : BioMed Central. - 1743-8977. ; 7:1, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.
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| 4. |
- Behndig, Annelie, 1963-
(författare)
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Airway antioxidant responses to oxidative air pollution and vitamin supplementation
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Air pollutants, such as ozone (O3) and diesel exhaust particles, elicit oxidative stress in the lung. Antioxidants within the respiratory tract lining fluid (RTLF) protect the underlying tissue from oxidative injury. Supplementation with vitamins has been shown to modulate the acute ozone-induced effects, but the mechanisms behind this have not been fully clarified. The aim of this thesis was to investigate the airway responses to diesel exhaust and ozone exposure in healthy humans, with the emphasis on inflammatory and antioxidant responses. Furthermore, to study whether oral supplementation with vitamin C could increase ascorbate concentration in the RTLF and whether vitamin supplementation could modulate the negative effects induced by ozone exposure. Diesel exhaust (100 µg/m3 PM10 for 2h), evaluated 18 hours post exposure (PE), induced a neutrophilic airway inflammation and an increase in bronchoalveolar (BAL) urate and reduced glutathione. During O3 exposure (0.2 ppm for 2h), significant losses of nasal RTLF urate and ascorbate concentrations were observed. Six hours PE, a neutrophilic inflammation was evident in the bronchial wash (BW), together with enhanced concentrations of urate and total glutathione. In the bronchoalveolar lavage (BAL), where vitamin C, urate and glutathione concentrations were augmented, no inflammatory response was seen. In alveolar lavage leukocytes, there was a significant loss of glutathione and cysteine, whereas an increase in ascorbate was found in bronchial tissue samples. Following supplementation with increasing doses of vitamin C (60-1,000 mg/day, for 14 days), evaluated 24 hours after the last dose, ascorbate concentrations were unchanged in the nasal RTLF, despite elevated concentrations in plasma and urine. In contrast, following a single dose of 1g of vitamin C, vitamin C concentrations increased significantly in both plasma and nasal lavage two hours post supplementation, before returning to baseline levels at 24 hours. Notably, dehydroascorbate (DHA) accounted for the largest part of RTLF vitamin C and a number of control experiments were performed to ensure the authenticity of this finding. Healthy O3 responders were exposed to O3 (0.2 ppm for 2 h) and air, following seven days of supplementation with vitamin C and E or placebo. No protective effect on lung function or airway inflammation was observed following supplementation. BW and BAL-DHA were enhanced after O3, with further increases following supplementation. In conclusion, oxidative air pollutants induce airway inflammation, as well as a broad spectrum of antioxidant adaptations, which could ultimately limit the airway inflammatory responses. Oral vitamin supplementation was shown to augment RTLF-vitamin C concentrations, but it did not provide protection from the ozone-induced airway responses following a single insult of ozone. The finding of high concentrations of DHA in the RTLF could indicate that DHA represents an important transport form of vitamin C onto the surface of the lung.
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| 5. |
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| 6. |
- Behndig, Annelie F, et al.
(författare)
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Antioxidant responses to acute ozone challenge in the healthy human airway
- 2009
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Ingår i: Inhalation Toxicology. - : Informa UK Limited. - 0895-8378 .- 1091-7691. ; 21:11, s. 933-942
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to characterize ozone-induced antioxidant responses in the human airway, including the resident leukocyte population, bronchial mucosa, and respiratory-tract lining fluids. Fifteen healthy subjects were exposed to 0.2 ppm ozone for 2 h, with bronchial wash, bronchoalveolar lavage, and biopsy sampling performed 6 h postexposure. Nasal lavage was also performed at multiple time points pre- and postexposure to evaluate responses during the actual exposure period. During the ozone challenge significant losses of nasal lining fluid urate and vitamin C were observed, which resolved 6 h postexposure. At this time point, increased numbers of neutrophils and enhanced concentrations of total glutathione, vitamin C, and urate were seen in bronchial airway lavages. In bronchoalveolar lavage, increased concentrations of total glutathione, vitamin C, urate, alpha-tocopherol, and extracellular superoxide dismutase occurred 6 h post ozone. In alveolar leukocytes significant losses of glutathione were observed, whereas ascorbate concentrations in endobronchial mucosal biopsies were elevated after ozone at this time. These data demonstrate that ozone elicits a broad spectrum of airway antioxidant responses, with initial losses of vitamin C and urate followed by a phase of augmentation of low-molecular-weight antioxidant concentrations at the air-lung interface. The temporal association between the increased RTLF glutathione following ozone and the loss of this thiol from macrophages implies a mobilization to the lung surface, despite the absence of a quantitative association. We propose this constitutes an acute protective adaptation to ozone.
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| 7. |
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| 8. |
- Behndig, Annelie F, et al.
(författare)
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Augmentation of respiratory tract lining fluid ascorbate concentrations through supplementation with vitamin C.
- 2009
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Ingår i: Inhalation toxicology. - : Informa UK Limited. - 1091-7691 .- 0895-8378. ; 21:3, s. 250-8
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Tidskriftsartikel (refereegranskat)abstract
- Low molecular weight antioxidants within human respiratory tract lining fluids (RTLFs) have been proposed to confer protection against the damaging action of inhaled oxidant gases. There is therefore considerable interest in augmenting the concentrations of these moieties at the air-lung interface to protect against injury to the airway epithelium, the induction of inflammation, and declines in lung function. To determine whether RTLF ascorbate concentrations could be augmented through vitamin C supplementation, 24 healthy subjects with low plasma ascorbate (< 50 microM) were recruited into a double-blinded study. Subjects were divided into two groups, one receiving 60 mg/day of vitamin C for 14 days, the other placebo. On days 8 and 15 of this protocol, plasma, urine, and nasal lavage were obtained for ascorbate determination. After a 7-14-day non-intervention period, subjects previously on placebo received supplements containing 125 mg ascorbate, whilst the group previously on supplements received the placebo compound. This "switching" protocol was repeated three more times utilizing 250, 500, and 1000 mg/day ascorbate dosage regimens. Plasma ascorbate increased incrementally with vitamin C dose, as did its urinary excretion. Despite this, nasal lavage concentrations remained unaltered 24 h after the final supplement at all doses. Closer examination of this issue demonstrated that nasal lavage ascorbate concentrations increased acutely after ingestion of a high dose (1000 mg) supplement, peaking at 2-4 h (p < 0.05) before returning to baseline concentrations 24 h post-supplement. In the absence of a quantitative association between plasma and lavage ascorbate concentrations we contend that this response does not simply reflect ascorbate transudation from the plasma and interstitial space into the lavage medium. We therefore conclude that RTLF ascorbate can be augmented, albeit transiently, by oral vitamin C supplementation, with the transient nature of this response likely reflecting oxidative losses within the RTLF or its sequestration into airway cells.
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| 9. |
- Behndig, Annelie F., et al.
(författare)
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Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium : an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects
- 2015
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Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms.Methods: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 μg/m 3 ) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis.Results: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge.Conclusion: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.
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| 10. |
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