| 1. |
- Barath, Stefan, 1963-, et al.
(författare)
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Diesel exhaust but not ozone increases fraction of exhaled nitric oxide in a randomized controlled experimental exposure study of healthy human subjects
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12, s. 36-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airway inflammation that may be used to assess respiratory effects of air pollution. We evaluated FENO as a measure of airway inflammation after controlled exposure to diesel exhaust or ozone. Methods: Healthy volunteers were exposed to either diesel exhaust (particle concentration 300 mu g/m(3)) and filtered air for one hour, or ozone (300 ppb) and filtered air for 75 minutes. FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after each exposure. Results: Exposure to diesel exhaust increased FENO at 6 hours compared with air at expiratory flow rates of 10 mL/s (p = 0.01) and at 50 mL/s (p = 0.011), but FENO did not differ significantly at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours. Ozone did not affect FENO at any flow rate or time point. Conclusions: Exposure to diesel exhaust, but not ozone, increased FENO concentrations in healthy subjects. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone, with implications for the use of FENO as an index of exposure to air pollution.
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| 2. |
- Barath, Stefan, 1963-, et al.
(författare)
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Fraction of exhaled nitric oxide after experimental exposure to diesel exhaust and ozone in man
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airways inflammation that may be used to assess the respiratory effects of air pollution, and when sampled at multiple expiratory flow rates can measure inflammation at different levels of the airway tract. We evaluate FENO as a measure of airways inflammation after controlled exposure to dilute diesel exhaust and ozone. Methods: Using a double blind randomised cross-over design, healthy volunteers (26±5 years) were exposed to either diesel exhaust (particle concentration 300 µg/m3) and filtered air for one hour (n=10), or ozone(300 ppb) and filtered air for 75 minutes (n=36). FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after the end of each exposure. Results: Exposure to diesel exhaust increased FENO at 6 hours compared to filtered air at expiratory flow rates of 10 mL/s [mean±SEM 60.8 ± 6.0 ppb versus 50.2 ± 5.9 ppb; P=0.01] and at 50 mL/s [18.6 ± 1.6 ppb versus 15.9 ± 1.5 ppb; P=0.011], but concentrations did not differ at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours and exposure to ozone did not affect FENO at any flow rate or time point. Conclusion: Exposure to diesel exhaust, but not ozone, increases the concentration of FENO in healthy subjects consistent with an inflammatory effect in the central airways. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone with implications for the use of FENO as an index of exposure to air pollution.
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| 3. |
- Barath, Stefan, 1963-
(författare)
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Respiratory and cardiovascular effects of exposure to oxidative air pollutants
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The negative effects of air pollution on morbidity and mortality have been known since the mid 20th century. The two most well known examples are the Meuse Valley disaster in the 1930’ies and the London black fog in December 1952. Whilst there are numerous epidemiological studies, in which associations between morbidity and mortality and high levels of pollutants have been reported, the underlying mechanisms are not clear. Two of the main air pollutants are particulate matter (PM) mostly emanating from diesel exhaust (DE), and ozone, both of which are highly oxidative. Exposure to DE has resulted in adverse effects both in the respiratory tract and in the cardiovascular system. High ozone levels have also been shown to be associated with increased admissions to hospital for respiratory as well as cardiovascular conditions. The main aim of this thesis was to investigate the respiratory and cardiovascular effects of a combination of exposures to ozone and DE. DE generated during the urban part of the standardized European Transient Cycle (ETC) was compared to DE generated by an idling engine. It was also evaluated whether an acute exposure to ozone would have any effects on the cardiovascular system as assessed by venous occlusion forearm plethysmography and heart rate variability (HRV). In addition, fraction of exhaled nitric oxide (FENO) was evaluated as a potential marker for acute exposure to ozone or DE. Methods: Four double-blind randomized cross-over exposure studies were conducted to investigate the effects of ozone and DE on both the respiratory tract and the vascular function in healthy volunteers. All of the exposures were performed in purposely built “walk-in” chambers with strictly controlled exposures. In the first study, the volunteers were exposed to DE (300µg/m3) generated by an idling engine or to air, for one hour in the morning and to ozone (200 ppb) for two hours in the afternoon. A bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 24 hours after the initial exposure. In study II and III, an assessment of vascular function using venous occlusion forearm plethysmography was performed after an exposure to DE (250 µg/m3) generated under transient running conditions, compared to air exposure (study II) and ozone and air exposure (study III). HRV was assessed under a 24 hour period starting before each exposure (study III). In study IV, FENO measurements were conducted after DE and ozone exposures to investigate whether the previously established airway inflammation would be detectable by this non-invasive method. Results: DE exposure enhanced the established ozone-induced airway inflammation in terms of a pronounced neutrophilia in BW. DE generated under transient running conditions, impaired vascular function in healthy volunteers, whereas exposure to ozone did not. HRV were not altered by exposure to ozone. Exposure to DE caused a significant increase in FENO at the 10 (FENO10) and 50 (FENO50) mL/s flow rates at 6 hours post-exposure, but ozone exposure did not affect FENO at any flow rate or time point. Conclusion: We have tried to mimic real-life exposure to air pollutants. In the first study, an exposure to DE followed by an exposure to ozone in the afternoon resulted in an enhanced airway inflammation, suggesting an additive or synergistic effect, supporting the epidemiological findings of unfavorable effects of the combination of these two air pollutants. DE generated by an engine running at the urban part of the standardized European Transient Cycle impaired two important and complementary aspects of vascular function, the regulation of vascular tone and endogenous fibrinolysis. This has previously been shown with DE generated at idling conditions. This suggests that the mechanisms behind the adverse effects can be found in the properties of the particles and not in the gaseous components. In these studies, exposure to ozone did not impair vascular function in healthy subjects, or cause any alterations in HRV. This suggests that the epidemiological evidence for an increased risk of cardiovascular mortality following acute exposure to ozone might not be totally accurate. Previous controlled exposure studies with ozone have not shown an airway inflammation affecting the endothelium, at least not in the same time-frame as following DE exposure. FENO could possibly be a useful tool for assessing airway inflammation caused by DE, whereas the powerful oxidant ozone did not affect FENO. This suggests that the airway inflammatory effects caused by these two pollutants are regulated via different mechanisms.
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| 4. |
- Bosson, Jenny, et al.
(författare)
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Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans
- 2008
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 31:6, s. 1234-1240
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to particulate matter and ozone cause adverse airway reactions. Individual pollutant effects are often addressed separately, despite coexisting in ambient air. The present investigation was performed to study the effects of sequential exposures to diesel exhaust (DE) and ozone on airway inflammation in human subjects. Healthy subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial wash (BW) sampling on two occasions. Once following a DE exposure (with 300 mug.m(-3) particles with a 50% cut-off aerodynamic diameter of 10 mum) with subsequent exposure to O(3) (0.2 ppm) 5 h later. The other bronchoscopy was performed after a filtered air exposure followed by an ozone exposure, using an identical protocol. Bronchoscopy was performed 24 h after the start of the initial exposure. Significant increases in neutrophil and macrophage numbers were found in BW after DE followed by ozone exposure versus air followed by ozone exposure. DE pre-exposure also raised eosinophil protein X levels in BAL compared with air. The present study indicates additive effects of diesel exhaust on the ozone-induced airway inflammation. Together with similar results from a recent study with sequential diesel exhaust and ozone exposures, the present data stress a need to consider the interaction and cumulative effects of different air pollutants.
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| 5. |
- Bosson, Jenny, 1975-
(författare)
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Ozone and diesel exhaust : airway signaling, inflammation and pollutant interactions
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is well established that air pollution has detrimental effects on both human health as well as the environment. Exposure to ozone and particulate matter pollution, is associated with an increase in cardiopulmonary mortality and morbidity. Asthmatics, elderly and children have been indicated as especially sensitive groups. With a global increase in use of vehicles and industry, ambient air pollution represents a crucial health concern as well as a political, economical and environmental dilemma. Both ozone (O3) and diesel exhaust (DE) trigger oxidative stress and inflammation in the airways, causing symptoms such as wheezing, coughing and reduced lung function. The aim of this thesis was to further examine which pro-inflammatory signaling pathways that are initiated in the airways by ozone, as compared to diesel exhaust. Furthermore, to study the effects of these two ambient air pollutants in a sequential exposure, thus mimicking an urban profile. In order to investigate this in healthy as well as asthmatic subjects, walk-in exposure chambers were utilized and various airway compartments were studied by obtaining induced sputum, endobronchial biopsies, or airway lavage fluids. In asthmatic subjects, exposure to 0.2 ppm of O3 induced an increase in the cytokines IL 5, GM-CSF and ENA-78 in the bronchial epithelium six hours post-exposure. The healthy subjects, however, displayed no elevations of bronchial epithelial cytokine expression in response to the ozone exposure. The heightened levels of neutrophil chemoattractants and Th2 cytokines in the asthmatic airway epithelium may contribute to symptom exacerbations following air pollution exposure. When examining an earlier time point post O3 exposure (1½ hours), healthy subjects exhibited a suppression of IL-8 as well as of the transcription factors NFκB and c-jun in the bronchial epithelium, as opposed to after filtered air exposure. This inhibition of early signal transduction in the bronchial epithelium after O3 differs from the response detected after exposure to DE. Since both O3 and DE are associated with generating airway neutrophilia as well as causing direct oxidative damage, it raises the query of whether daily exposure to these two air pollutants creates a synergistic or additive effect. Induced sputum attained from healthy subjects exposed in sequence to 0.2 ppm of O3 five hours following DE at a PM concentration of 300 µg/m3, demonstrated significantly increased neutrophils, and elevated MPO levels, as compared to the sequential DE and filtered air exposure. O3 and DE interactions were further investigated by analyses of bronchoalveolar lavage and bronchial wash. It was demonstrated that pre-exposure to DE, as compared to filtered air, enhances the O3-induced airway inflammation, in terms of an increase in neutrophil and macrophage numbers in BW and higher EPX expression in BAL. In conclusion, this thesis has aspired to expand the knowledge of O3-induced inflammatory pathways in humans, observing a divergence to the previously described DE initiated responses. Moreover, a potentially adverse airway inflammation augmentation has been revealed after exposure to a relevant ambient combination of these air pollutants. This provides a foundation towards an understanding of the cumulative airway effects when exposed to a combination of ambient air pollutants and may have implications regarding future regulations of exposure limits.
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| 6. |
- Bosson, Jenny, et al.
(författare)
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Ozone enhances the airway inflammation initiated by diesel exhaust.
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:6, s. 1140-1146
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to air pollution is associated with adverse health effects, with particulate matter (PM) and ozone (O(3)) both indicated to be of considerable importance. Diesel engine exhaust (DE) and O(3) generate substantial inflammatory effects in the airways. However, as yet it has not been determined whether a subsequent O(3) exposure would add to the diesel-induced airway inflammatory effects. Healthy subjects underwent two separate exposure series: A 1-h DE exposure at a PM-concentration of 300 microg/m(3), followed after 5h by a 2-h exposure to filtered air and 0.2 ppm O(3), respectively. Induced sputum was collected 18 h after the second exposure. A significant increase in the percentage of neutrophils (PMN) and concentration of myeloperoxidase (MPO) was seen in sputum post DE+O(3) vs. DE+air (p<0.05 and <0.05, respectively). Significant associations were observed between the responses in MPO concentration and total PMN cells (p=0.001), and also between MPO and matrix metalloproteinase-9 (MMP-9) (p<0.001). The significant increase of PMN and MPO after the DE+O(3) exposures, compared to DE+air, denotes an O(3)-induced magnification of the DE-induced inflammation. Furthermore, the correlation between responses in MPO and number of PMNs and MMP-9 illustrate that the PMNs are activated, resulting in a more potent inflammatory response. The present study indicates that O(3) exposure adds significantly to the inflammatory response that is established by diesel exhaust. This interaction between exposure to particulate pollution and O(3) in sequence should be taken into consideration when health effects of air pollution are considered.
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| 7. |
- Nordenhäll, Charlotta, 1972-
(författare)
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Airway effects of diesel exhaust in healthy and asthmatic subjects
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several epidemiological studies have revealed an association between particulate matter (PM) pollution and various health effects. Importantly, there is evidence to suggest that individuals with pre-existing respiratory disease, such as asthma, are more sensitive to elevated ground levels of particulate matter as compared to healthy subjects. Among the various sources of PM pollution, diesel powered vehicles have been identified as important contributors.The aim of this thesis was to investigate the airway effects of experimental chamber exposure to diesel exhaust (DE) in healthy and asthmatic subjects, focusing on airway responsiveness, airway inflammation and lung function. To achieve a comprehensive picture of the airway responses to DE, a number of different methods were used, including lung function measurements, methacholine inhalation tests, induced sputum and bronchoscopy. Each subject acted as his/her own control by being exposed both to filtered air and DE in a crossover design.Short term exposure to DE, at a particle concentration (PMi0) of 300 ug/m3, was associated with a clinically significant increase in bronchial hyperresponsiveness in asthmatic subjects. In accordance with the epidemiological data suggesting a 1-4 day lag effect for most health outcomes to PM pollution, the increase was detected one day after DE exposure, indicating a long lasting response to DE in asthmatic airways.Diesel exhaust induced a range of airway inflammatory changes as reflected in induced sputum, bronchoalveolar lavage and bronchial mucosal biopsies. In healthy subjects, DE exposure was associated with an increase in neutrophils and IL-6 in sputum, elevated levels of IL-8 and IL-6 in bronchial wash (BW), enhanced expression of IL-8 and GRO-a in the bronchial epithelium and with increases in P-selectin and VCAM-1 in the airway mucosa. In contrast, asthmatics responded with an increase in IL-6 in sputum and an enhanced expression of IL-10 in the bronchial epithelium following exposure DE. Thus, clear differences were identified between healthy and asthmatic subjects in the inflammatory response to DE.Airway epithelial cells constitute the first line of cellular defence towards inhaled air pollutants and increasing evidence suggests that these cells contribute markedly to the initiation of airway inflammatory responses. The bronchial epithelium was identified to have an important regulatory role in response to diesel exhaust, including the capacity to produce chemoattractant and immunoregulatory proteins associated with development of airway inflammation and bronchial hyperresponsiveness.Lung function measurements revealed that short-term exposure to DE induces an immediate bronchoconstrictive response in both healthy and asthmatic individuals, with significant increases in airway resistance (Raw) following DE exposure.This thesis also investigated the effects of a lower concentration of DE (PMio 100 ug/m3) than previously studied. It was shown that exposure to DE at a concentration corresponding to a PM level that may be encountered in busy traffic situations, was still associated with potentially adverse airway responses in healthy and asthmatic subjects.In summary, the results presented here indicate that short term exposure to diesel exhaust, at high ambient concentrations, has the potential to induce a range of biological events in the airways of healthy and asthmatic subjects.
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| 8. |
- Nordenhäll, C, et al.
(författare)
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Airway inflammation following exposure to diesel exhaust : a study of time kinetics using induced sputum
- 2000
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 15:6, s. 1046-1051
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Tidskriftsartikel (refereegranskat)abstract
- The adverse health effects of particulate matter pollution are of increasing concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway inflammation was detected following exposure to diesel exhaust (DE). The present study was conducted in order to evaluate the time kinetics of the inflammatory response following exposure to DE using induced sputum from healthy volunteers. Fifteen healthy nonsmoking volunteers were exposed to DE particles with a 50% cut-off aerodynamic diameter of 10 microm 300 microg x m(-3) and air for 1 h on two separate occasions. Sputum induction with hypertonic saline was performed 6 and 24 h after each exposure. Analyses of sputum differential cell counts and soluble protein concentrations were performed. Six hours after exposure to DE, a significant increase was found in the percentage of sputum neutrophils (37.7 versus 26.2% p=0.002) together with increases in the concentrations of interleukin-6 (12.0 versus 6.3 pg x mL(-1), p=0.006) and methylhistamine (0.11 versus 0.12 microg x L(-1), p=0.024). Irrespective of exposure, a significant increase was found in the percentage of sputum neutrophils at 24 as compared to 6 h, indicating that the procedure of sputum induction itself may change the composition of sputum. This study demonstrates that exposure to diesel exhaust induces inflammatory response in healthy human airways, represented by an early increase in interleukin-6 and methylhistamine concentration and the percentage of neutrophils. Induced sputum provides a safe tool for the investigation of the inflammatory effects of diesel exhaust, but care must be taken when interpreting results from repeated sputum inductions.
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| 9. |
- Nordenhäll, C, et al.
(författare)
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Diesel exhaust enhances airway responsiveness in asthmatic subjects
- 2001
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 17:5, s. 909-915
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Tidskriftsartikel (refereegranskat)abstract
- Particulate matter (PM) pollution has been associated with negative health effects, including exacerbations of asthma following exposure to PM peaks. The aim of the present study was to investigate the effects of short-term exposure to diesel exhaust (DE) in asthmatics, by specifically addressing the effects on airway hyperresponsiveness, lung function and airway inflammation. Fourteen nonsmoking, atopic asthmatics with stable disease, on continuous treatment with inhaled corticosteroids, were included. All were hyperresponsive to methacholine. Each subject was exposed to DE (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) 300 microg x m(-3)) and air during 1 h on two separate occasions. Lung function was measured before and immediately after the exposures. Sputum induction was performed 6 h, and methacholine inhalation test 24 h, after each exposure. Exposure to DE was associated with a significant increase in the degree of hyperresponsiveness, as compared to after air, of 0.97 doubling concentrations at 24 h after exposure (p < 0.001). DE also induced a significant increase in airway resistance (p=0.004) and in sputum levels of interleukin (IL)-6 (p=0.048). No changes were detected in sputum levels of methyl-histamine, eosinophil cationic protein, myeloperoxidase and IL-8. This study indicated that short-term exposure to diesel exhaust, equal to high ambient levels of particulate matter, is associated with adverse effects in asthmatic airways, even in the presence of inhaled corticosteroid therapy. The increase in airway responsiveness may provide an important link to epidemiological findings of exacerbations of asthma following exposure to particulate matter.
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| 10. |
- O'Byrne, Paul M, et al.
(författare)
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Beta2 deja vu.
- 2006
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Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 129:1, s. 3-5
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Tidskriftsartikel (refereegranskat)
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