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| 2. |
- Bosson, Jenny, et al.
(författare)
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Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects
- 2003
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 33:6, s. 777-782
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Tidskriftsartikel (refereegranskat)abstract
- Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group. Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility. Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78. Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects. Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.
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| 3. |
- Fritioff, Karin, et al.
(författare)
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Observation of an excited C2-4 ion
- 2004
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 37:11, s. 2241-2246
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports an experimental investigation of the electron impact detachment of C−4. We observe structure in the electron impact cross section for detaching a single electron from a C−4 cluster anion, which we attribute to the formation and decay of the C2−4 dianion. The system is energetically unstable and very rapidly decays via double autodetachment. The energy and width of the resonance were determined to be 8.8(5) eV and 1.4(5) eV, respectively, and the resonance lies 1.5(5) eV above the ground state of the neutral system. The experiment was conducted by merging monoenergetic electron and ion beams in the heavy ion storage ring CRYRING. The detachment channel was monitored by detecting neutral C4 fragments.
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| 4. |
- Fritioff, K, et al.
(författare)
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Single and double detachment from H-
- 2004
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622 .- 2469-9926 .- 2469-9934. ; 69:4, s. 042707-
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Tidskriftsartikel (refereegranskat)abstract
- Absolute cross sections for single and double detachment from H- following electron impact have been measured over a range of collision energies from the thresholds to 170 eV. The measurements were made using a magnetic storage ring. The ions in the ring were merged with a monoenergetic electron beam and neutral and positively charged fragments were detected. We cover larger energy ranges than in many of the previous experiments, and this is the first time both single and double detachment have been measured simultaneously. This allows us to present accurate ratios between the single and double detachment cross sections. On the basis of these ratio measurements we discuss possible mechanisms leading to double detachment.
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| 5. |
- Holgate, Stephen T, et al.
(författare)
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Health effects of acute exposure to air pollution. Part I : Healthy and asthmatic subjects exposed to diesel exhaust
- 2003
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Ingår i: Research report (Health Effects Institute). - 1041-5505. ; :112, s. 1-30; discussion 51
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to assess the impact of short-term exposure to diluted diesel exhaust on inflammatory parameters in human airways. We previously exposed control subjects for 1 hour to a high ambient concentration of diesel exhaust (particle concentration 300 pg/m3--a level comparable with that found in North Sea ferries, highway underpasses, etc). Although these exposures did not have any measurable effect on standard indices of lung function, there was a marked neutrophilic inflammatory response in the airways accompanied by increases in blood neutrophil and platelet counts. Endothelial adhesion molecules were upregulated, and the expression of interleukin 8 messenger RNA (IL-8 mRNA*) was increased in a pattern consistent with neutrophilia. Individuals with asthma have inflamed airways and are clinically more sensitive to air pollutants than are control subjects. The present study was designed to assess whether this clinical sensitivity can be explained by acute neutrophilic inflammation or an increase in allergic airway inflammation resulting from diesel exhaust exposure. For this study, we used a lower concentration of diesel exhaust (100 microg/m3 PM10) for a 2-hour exposure. At this concentration, both the control subjects and those with asthma demonstrated a modest but statistically significant increase in airway resistance following exposure to diesel exhaust. This increase in airway resistance was associated with an increased number of neutrophils in the bronchial wash (BW) fluid obtained from control subjects (median after diesel exhaust 22.0 vs median after air 17.2; P = 0.015), as well as an increase in lymphocytes obtained through bronchoalveolar lavage (BAL) (15.0% after diesel exhaust vs 12.3% after air; P = 0.017). Upregulation of the endothelial adhesion molecule P-selectin was noted in bronchial biopsy tissues from control subjects (65.4% of vessels after diesel exhaust vs 52.5% after air). There was also a significant increase in IL-8 protein concentrations in BAL fluid and IL-8 mRNA gene expression in the bronchial biopsy tissues obtained from control subjects after diesel exhaust exposure (median IL-8 expression 65.7% of adenine phosphoribosyl transferase [APRT] gene expression value after diesel exhaust vs 51.0% after air; P = 0.007). There were no significant changes in total protein, albumin, or other soluble inflammatory markers in the BW or BAL fluids. Red and white blood cell counts in peripheral blood were unaffected by diesel exhaust exposure. Airway mucosal biopsy tissues from subjects with mild asthma (defined as forced expiratory volume in 1 second [FEV1] greater than or equal to 70% of the predicted value) showed eosinophilic airway inflammation after air exposure compared with the airways of the corresponding control subjects. However, among the subjects with mild asthma, diesel exhaust did not induce any significant change in airway neutrophils, eosinophils, or other inflammatory cells; cytokines; or mediators of inflammation. The only clear effect of diesel exhaust on the airways of subjects with asthma was a significant increase in IL-10 staining in the biopsy tissues. This study demonstrated that modest concentrations of diesel exhaust have clear-cut inflammatory effects on the airways of nonasthmatic (or control) subjects. The data suggest a direct effect of diesel exhaust on IL-8 production leading to upregulation of endothelial adhesion molecules and neutrophil recruitment. Despite clinical reports of increased susceptibility of patients with asthma to diesel exhaust and other forms of air pollution, it does not appear that this susceptibility is caused either directly by induction of neutrophilic inflammation or indirectly by worsening of preexisting asthmatic airway inflammation. The increased level of IL-10 after diesel exhaust exposure in airways of subjects with asthma suggests that this pollutant may induce subtle changes in airway immunobiology. This is an important topic for further investigation. Other possible explanations for the apparent lack of response to diesel exhaust among subjects with asthma include (1) the time course of the response to diesel may differ from the response to allergens, which peaks 6 to 8 hours after exposure; (2) a different type of inflammation may occur that was not detectable by the standard methods used in this study; and (3) the increased sensitivity of patients with asthma to particulate air pollution may reflect the underlying bronchial hyperresponsiveness found in asthma rather than any specific increase in inflammatory responses.
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| 7. |
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| 8. |
- Mudway, I S, et al.
(författare)
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Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone : a comparison of healthy and mild asthmatic subjects
- 2001
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Ingår i: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 31:8, s. 962-974
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Tidskriftsartikel (refereegranskat)abstract
- The air pollutant ozone induces both airway inflammation and restrictions in lung function. These responses have been proposed to arise as a consequence of the oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses present at the surface of the lung in two groups known to have profound differences in their antioxidant defense network: healthy control (HC) and mild asthmatic (MA) subjects. We hypothesized that baseline differences in antioxidant concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsiveness. We observed a significant loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%, p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in these compartments (p =.01 and p <.05). Corresponding responses were not seen in asthmatics, where basal ASC concentrations were significantly lower (p <.01) and associated with elevated concentrations of GSSG (p <.05). In neither group was any evidence of lipid oxidation seen following ozone. Despite differences in antioxidant levels and response, the magnitude of ozone-induced neutrophilia (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These data demonstrate significant differences between the interaction of ozone with RTLF antioxidants in MA and HC subjects. These responses and variations in basal antioxidant defense were not, however, useful predictive markers of group or individual responsiveness to ozone.
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| 9. |
- 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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| 10. |
- 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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