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Respiratory and cardiovascular responses to diesel exhaust exposure
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Exposure to traffic-derived air pollution is associated to high incidence of respiratory and cardio-vascular morbidity and mortality. Diesel engines and fossil fuel contribute to a great amount to the ambient particulate matter pollution. Exposure to diesel exhaust in healthy volunteers is known to cause inflammatory and oxidative responses in the airways. In contrast, very little is known about the air pollution-related mechanisms behind the adverse cardiovascular effects and why patients with cardiorespiratory disease are more susceptible to the adverse effect of particulate matter air pollution.

Methods: Volunteers were exposed to diesel exhaust at a particulate matter concentration of 300 μg/m3 and filtered air for one hour in random order. In studies I-II, patients with moderately severe, stable COPD were examined with lung function, induced sputum and peripheral blood samples. In studies III-V, vascular assessment was performed using venous occlusion plethysmography. Vascular responses to intra-arterially infused endothelial dependent and independent vasodilators were determined, together with endogenous fibrinolysis, systemic inflammation and long-term ECG registration. These vascular studies were carried out in healthy volunteers and patients with stable coronary heart disease.

Results: In healthy subjects, diesel exhaust exposure induced an acute vasomotor dysfunction, which was partly sustained at 24 hours. Endogenous fibrinolysis reflected by tissue plasminogen activator (t-Pa) levels and activity were reduced at 6 hours post exposure both in healthy subjects and patients with stable PCI-treated coronary heart disease. During diesel exhaust exposure, ECG analyses demonstrated significant exerciseinduced ST-T segment depression in patients with coronary heart disease. These findings occurred at a moderately increased heart rate of approximately 90 beats per minute during both diesel and air exposures. The investigated group of stable COPD patients did not demonstrate any further deterioration of lung function, induced sputum or systemic inflammatory parameters within the investigated time frame.

Conclusion: Inhalation of diesel exhaust impaired two important and complementary aspects of vascular function in healthy subjects; regulation of vascular tone and endogenous fibrinolysis. In men with stable coronary heart disease, exposure to diesel exhaust induced signs of myocardial ischemia, along with impaired endogenous fibrinolytic capacity, despite full secondary preventive medication. These exposure studies support the epidemiological evidence of an association between particulate matter air pollution and adverse cardiovascular effects and demonstrate important underlying mechanisms.

Place, publisher, year, edition, pages
Umeå: Lungmedicin , 2008. , p. 81
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1190
Research subject
Lung Medicine
Identifiers
URN: urn:nbn:se:umu:diva-1670ISBN: 978-91-7264-582-0 (print)OAI: oai:DiVA.org:umu-1670DiVA, id: diva2:141778
Public defence
2008-06-05, Sal E04, 6E, trappa R, NUS, Umeå, 13:00 (English)
Opponent
Available from: 2008-05-20 Created: 2008-05-20 Last updated: 2010-01-18Bibliographically approved
List of papers
1. Diesel exhaust exposure in subjects with chronic obstructive pulmonary disease
Open this publication in new window or tab >>Diesel exhaust exposure in subjects with chronic obstructive pulmonary disease
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Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-3251 (URN)
Available from: 2008-05-20 Created: 2008-05-20 Last updated: 2010-01-13Bibliographically approved
2. Exposure to diesel exhaust nanoparticles does not induce blood hypercoagulability in an at-risk population.
Open this publication in new window or tab >>Exposure to diesel exhaust nanoparticles does not induce blood hypercoagulability in an at-risk population.
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2005 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 3, no 9, p. 2103-2105Article in journal (Refereed) Published
Keywords
Aged, Biological Markers/blood, Environmental Exposure, Humans, Inflammation/chemically induced, Middle Aged, Nanostructures, Pulmonary Disease; Chronic Obstructive, Single-Blind Method, Thrombophilia/*chemically induced, Vehicle Emissions/*adverse effects/toxicity
Identifiers
urn:nbn:se:umu:diva-13382 (URN)doi:10.1111/j.1538-7836.2005.01559.x (DOI)16102120 (PubMedID)
Available from: 2007-05-08 Created: 2007-05-08 Last updated: 2018-06-09Bibliographically approved
3. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.
Open this publication in new window or tab >>Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.
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2005 (Swedish)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 112, no 25, p. 3930-3936Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-16084 (URN)doi:10.1161/CIRCULATIONAHA.105.588962 (DOI)16365212 (PubMedID)
Available from: 2007-08-17 Created: 2007-08-17 Last updated: 2018-06-09Bibliographically approved
4. Prolonged endothelial dysfunction following diesel exhaust inhalation
Open this publication in new window or tab >>Prolonged endothelial dysfunction following diesel exhaust inhalation
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2007 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 176, no 4, p. 395-400Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-3254 (URN)10.1164/rccm.200606-872OC (DOI)
Available from: 2008-05-20 Created: 2008-05-20 Last updated: 2017-12-14Bibliographically approved
5. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease
Open this publication in new window or tab >>Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease
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2007 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 357, no 11, p. 1075-1082Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function.

METHODS: In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions.

RESULTS: During both exposure sessions, the heart rate increased with exercise (P<0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P=0.67). Exercise-induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22+/-4 vs. -8+/-6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve).

CONCLUSIONS: Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events.

Keywords
Air Pollution/*adverse effects, Cardiovascular System/*drug effects/physiopathology, Coronary Disease/*physiopathology, Cross-Over Studies, Double-Blind Method, Environmental Exposure/adverse effects, Exercise/physiology, Fibrinolysis/drug effects, Humans, Inhalation, Male, Middle Aged, Myocardial Infarction, Myocardial Ischemia/*etiology, Particulate Matter/*adverse effects, Thrombosis/etiology, Vasodilator Agents/pharmacology, Vehicle Emissions/*toxicity
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-18156 (URN)10.1056/NEJMoa066314 (DOI)17855668 (PubMedID)
Available from: 2007-11-28 Created: 2007-11-28 Last updated: 2018-06-09Bibliographically approved

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