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Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
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2008 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 31, no 6, 1234-1240 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2008. Vol. 31, no 6, 1234-1240 p.
Keyword [en]
Air pollution, bronchoscopy, neutrophils, particulate matter, sequential exposure
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:umu:diva-19127DOI: 10.1183/09031936.00078407PubMedID: 18321939OAI: oai:DiVA.org:umu-19127DiVA: diva2:201432
Available from: 2009-03-04 Created: 2009-03-04 Last updated: 2012-03-01Bibliographically approved
In thesis
1. Ozone and diesel exhaust: airway signaling, inflammation and pollutant interactions
Open this publication in new window or tab >>Ozone and diesel exhaust: airway signaling, inflammation and pollutant interactions
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2007. 83 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1097
Keyword
air pollution, ozone, diesel exhaust, airway inflammation, asthma, immunohistochemistry
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
urn:nbn:se:umu:diva-1071 (URN)978-91-7264-266-9 (ISBN)
Public defence
2007-04-21, Sal B, 9 trappor, Tandläkarhuset, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2007-04-02 Created: 2007-04-02 Last updated: 2012-03-01Bibliographically approved
2. Respiratory and cardiovascular effects of exposure to oxidative air pollutants
Open this publication in new window or tab >>Respiratory and cardiovascular effects of exposure to oxidative air pollutants
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2011. 45 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1443
Keyword
Air Pollution, Particulate Matter, Diesel Exhaust, Ozone, Experimental Exposure studies, Luftföroreningar, Partiklar, Disel avgaser, ozon, Experimentella exponerings studier
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Cardiology; biology, Environmental Science
Identifiers
urn:nbn:se:umu:diva-46533 (URN)978-91-7459-279-5 (ISBN)
Public defence
2011-10-05, Sal B, Målpunkt T9, Norrlands Universitetssjukhus, 901 85 Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2011-09-09 Created: 2011-09-05 Last updated: 2011-09-12Bibliographically approved

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Bosson, JennyBarath, StefanPourazar, JamshidBehndig, Annelie FSandström, ThomasBlomberg, AndersÄdelroth, Ellinor

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