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Diesel exhaust and wood smoke: mechanisms, inflammation and intervention
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
2014 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet , 2014. , s. 85
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1641
Nyckelord [en]
Air pollution, deposition, bronchoscopy, Immunohistochemstry, filter, NO bioavailability
Nationell ämneskategori
Lungmedicin och allergi
Forskningsämne
lungmedicin
Identifikatorer
URN: urn:nbn:se:umu:diva-88614ISBN: 978-91-7601-028-0 (tryckt)OAI: oai:DiVA.org:umu-88614DiVA, id: diva2:716558
Disputation
2014-06-05, Hörsal Betula, byggnad 6M, Norrlands Universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2014-05-13 Skapad: 2014-05-11 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
Delarbeten
1. Respiratory Tract Deposition of Inhaled Wood Smoke Particles in Healthy Volunteers
Öppna denna publikation i ny flik eller fönster >>Respiratory Tract Deposition of Inhaled Wood Smoke Particles in Healthy Volunteers
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2015 (Engelska)Ingår i: Journal of Aerosol Medicine, ISSN 1941-2711, E-ISSN 1941-2703, Vol. 28, nr 4, s. 237-246Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Nyckelord
aerosol, biomass combustion, effective density, lung deposition, nanoparticles, toxicity
Nationell ämneskategori
Lungmedicin och allergi
Identifikatorer
urn:nbn:se:umu:diva-88608 (URN)10.1089/jamp.2014.1122 (DOI)000359795000001 ()
Anmärkning

Originally included in thesis in submitted form with the title "Respiratory tract deposition of inhaled wood smoke particles in healthy volunteers and subjects with COPD"

Tillgänglig från: 2014-05-11 Skapad: 2014-05-11 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
2. Bronchial mucosal inflammation in healthy subjects after exposure to wood smoke from incomplete combustion
Öppna denna publikation i ny flik eller fönster >>Bronchial mucosal inflammation in healthy subjects after exposure to wood smoke from incomplete combustion
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease worldwide. The mechanisms by which wood smoke exhibits its effects on human health are not well understood. The aim of this study was to determine whether exposure to wood smoke produced from incomplete combustion would elicit an airway inflammatory response.

Methods Fourteen healthy subjects underwent controlled chamber exposure on two occasions to filtered air and to sooty wood smoke (PM1 ~ 314 μg/m3), generated by a common Nordic wood stove firing birch logs. The study was performed with a double-blind randomized cross-over design and the subjects alternated between exercise (VE=20 L/min/m2) and rest at 15-minute intervals for 3 hours. Bronchoscopies were performed 24 hours after each exposure where bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial biopsies were taken. Differential cell counts and soluble components were analyzed in BW and BAL. Bronchial mucosal biopsies were analyzed using immunohistochemistry. Blood tests for inflammatory markers were sampled pre-exposure as well as at 24 and 44-hour time points post-exposure. Spirometry and Fraction of exhaled nitric oxide (FENO) were performed before, immediately after and 24 hours after each exposure.

Results There was a significant increase in submucosal and epithelial CD3+ lymphocytes (p<0.01 and <0.05 respectively), together with CD8+ cells in the epithelium (p<0.05) after exposure to wood smoke compared to filtered air. Mast cells were also significantly increased in the submucosa (p<0.01) after wood smoke exposure.

There were significant reductions in macrophages, neutrophils and lymphocytes in BW after exposure to wood smoke compared to filtered air, accompanied by decreased levels of soluble Intercellular Adhesion Molecule-1 (sICAM-1), myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). No significant effects on cell numbers or acute inflammatory markers were demonstrated in BAL fluid or peripheral blood. Lung function and FENO were not affected by exposure to wood smoke.

Conclusions Wood smoke exposure caused a significant increase in bronchial epithelial and submucosal CD3+ lymphocytes together with an increase in mucosal mast cells. Further examination revealed a significant increase in CD8+ lymphocytes within the epithelium. Unexpectedly there were no indications of any neutrophilic airway response or recruitment of alveolar macrophages. BW cell numbers, MPO and MMP-9 levels were also significantly reduced after wood smoke exposure. Further research is needed to determine the precise role of these events in relationship to the adverse health effects attributed to wood smoke exposure.

Nationell ämneskategori
Lungmedicin och allergi
Identifikatorer
urn:nbn:se:umu:diva-88609 (URN)
Tillgänglig från: 2014-05-11 Skapad: 2014-05-11 Senast uppdaterad: 2018-06-07
3. Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers
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2014 (Engelska)Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, nr 1, artikel-id 16Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.

METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.

RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.

CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2014
Nationell ämneskategori
Lungmedicin och allergi
Identifikatorer
urn:nbn:se:umu:diva-88557 (URN)10.1186/1476-069X-13-16 (DOI)000334547200001 ()24621126 (PubMedID)
Tillgänglig från: 2014-05-08 Skapad: 2014-05-08 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
4. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man
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2013 (Engelska)Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, nr 1, s. e004309-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects.

Methods and Results In 2 randomized double-blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1: Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 mu g/min) and sodium nitroprusside (SNP; 2 to 8 mu g/min) in the presence of the NO clamp (NO synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) 8 mu g/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2: Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous L-NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68 +/- 48 versus 41 +/- 32 nmol/L; P=0.006) despite similar L-NMMA-induced reductions in basal blood flow (-20.6 +/- 14.7% versus -21.1 +/- 14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose-dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, L-NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air.

Conclusions Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability.

Ort, förlag, år, upplaga, sidor
American stroke association, 2013
Nyckelord
air pollution, endothelial function, nitric oxide, nitric oxide synthase, vascular biology
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:umu:diva-83653 (URN)10.1161/JAHA.112.004309 (DOI)000326336800023 ()
Forskningsfinansiär
Hjärt-Lungfonden
Tillgänglig från: 2013-12-03 Skapad: 2013-12-03 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

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