umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
12 1 - 50 av 67
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Andersen, Grethe Neumann
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Nilsson, Kenneth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Hackett, Tillie-Louise
    Kazzam, Elsadig
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Warner, Jane
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Sandström, Thomas
    Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.2007Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, nr 10, s. 2199-2206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.

  • 2. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Scholz, Saskia
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smed-Sörensen, Anna
    Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry2017Ingår i: Jove-journal pf visualized experiments, ISSN 1940-087X, nr 119, artikel-id e55222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

  • 3. Baharom, Faezzah
    et al.
    Thomas, Saskia
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lepzien, Rico
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smed-Sorensen, Anna
    Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans2016Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, nr 11, s. 4498-4509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

  • 4.
    Behndig, A. F.
    et al.
    Umeå universitet.
    Linder, Robert
    Umeå universitet.
    Pourazar, Jamshid
    Umeå universitet.
    Lindberg, A.
    Umeå universitet.
    Blomberg, Anders
    Umeå universitet.
    Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies2016Ingår i: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, ISSN 1073-449X, Vol. 193Artikel i tidskrift (Refereegranskat)
  • 5.
    Behndig, Annelie F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Linder, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Inflammatory Markers In Different COPD Subgroups Compared To Smokers And Healthy Controls2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A2884Artikel i tidskrift (Övrigt vetenskapligt)
  • 6.
    Bosson, Jenny. A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Connolly-Andersen, Anne-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Langrish, J. P.
    Increased Soluble Thrombomodulin In Plasma Following Diesel Exhaust Exposure2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A3210Artikel i tidskrift (Övrigt vetenskapligt)
  • 7.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Barath, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans2008Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 31, nr 6, s. 1234-1240Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian
    Frew, Anthony
    Kelly, Frank
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Early suppression of NFκB and IL-8 bronchial epithelium after ozone exposure in healthy human subjects2009Ingår i: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, nr 11, s. 913-919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor κB (NFκB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-α, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFκB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  • 9.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian S
    Frew, Anthony J
    Kelly, Frank J
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects2009Ingår i: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, nr 11, s. 913-919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exposure to elevated concentrations of ozone, a common air pollutant, has been associated with numerous adverse health effects. We have previously reported the time-course of ozone-induced airway inflammation, demonstrating an early up-regulation of vascular endothelial adhesion molecules in bronchial mucosa at 1.5 hours, followed by a neutrophilic infiltration 6 hours after exposure to 0.2 ppm ozone. We hypothesized that the neutrophilic infiltration in the bronchial mucosa would reflect an early increase in bronchial epithelial expression of redox-sensitive transcription factors and kinases regulating neutrophil chemoattractant expression. To test this hypothesis, endobronchial biopsies were obtained from healthy human subjects (n = 11) 1.5 hours after 0.2 ppm of ozone and filtered air exposures (lasting for 2 hours) and stained for mitogen-activated protein kinases (MAPKs), transcription factors, and neutrophil chemoattractants. Total epithelial staining was quantified, as well as the extent of nuclear translocation. Contrary to expectation, ozone significantly suppressed total and nuclear expression of nuclear factor kappaB (NFkappaB) in bronchial epithelial cells (p = 0.02 and p = 0.003 respectively). Similarly, the total staining for phosphorylated C-jun was suppressed (p = 0.021). Expression of interleukin 8 (IL-8) in the bronchial epithelium was likewise decreased after ozone (p = 0.018), while GRO-alpha, ENA-78, C-fos, p-p38, p-JNK, and p-ERK stainings were unchanged. These data suggest that the redox-sensitive NFkappaB and activator protein 1 (AP-1) pathways within the human bronchial epithelium do not seem to be involved in the early inflammatory cell recruitment pathways in healthy subjects exposed to ozone.

  • 10.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ozone enhances the airway inflammation initiated by diesel exhaust.2007Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, nr 6, s. 1140-1146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 11.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bucht, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Holgate, Stephen
    Kelly, Frank
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wilson, Susan
    Frew, Anthony
    Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects2003Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, nr 6, s. 777-782Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 12. Brown, J L
    et al.
    Behndig, A F
    Sekerel, B E
    Pourazar, Jamshid
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, F J
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Frew, A J
    Wilson, S J
    Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls.2007Ingår i: Clin Exp Allergy, ISSN 0954-7894, Vol. 37, nr 5, s. 688-95Artikel i tidskrift (Refereegranskat)
  • 13.
    Dove, Rosamund E.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
    Leong-Smith, Pheneatia
    Roos-Engstrand, Ester
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Shah, Mittal
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian S.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD2015Ingår i: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 2, artikel-id 27837Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.

    METHODS: Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).

    RESULTS: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.

    CONCLUSIONS: We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

  • 14.
    Eriksson Ström, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Linder, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bucht, Anders
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking2018Ingår i: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, artikel-id 244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.

    Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

    Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.

    Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.

    Trial registration: Clinicaltrials.gov identifier NCT02729220.

  • 15.
    Gouveia-Figueira, Sandra C.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust2018Ingår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, s. 62-69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

  • 16.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure2017Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, nr 11, s. 2967-2980Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 mu g/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, Nacylethanolamines, and related lipid metabolites in the collected BWand BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

  • 17.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mass spectrometry profiling of oxylipins, endocannabinoids and N-acylethanolamines in human lung lavage fluids reveal responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposureManuskript (preprint) (Övrigt vetenskapligt)
  • 18.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Effect of controlled exposure to biodiesel exhaust on human plasma bioactive lipid profilesManuskript (preprint) (Övrigt vetenskapligt)
  • 19.
    Hunter, Amanda
    et al.
    University of Edinburgh.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bosson, Jenny A
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Langrish, Jeremy P
    University of Edinburgh.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Raftis, Jennifer B
    University of Edinburgh.
    Miller, Mark R
    University of Edinburgh.
    Lucking, Andrew J
    University of Edinburgh.
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Nyström, Robin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Donaldson, Kenneth
    University of Edinburgh.
    Flapan, Andrew D
    University of Edinburgh.
    Pung, Louis
    University of Edinburgh.
    Sadiktsis, Ioannis
    Stockholm University.
    Masala, Silvia
    Stockholm University.
    Westerholm, Roger
    Stockholm University.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    University of Edinburgh.
    Mills, Nicholas L
    University of Edinburgh.
    Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters2014Ingår i: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 11, artikel-id 62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.

  • 20. Langrish, J. P.
    et al.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stannett, C.
    Mills, N. L.
    Newby, D. E.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    The use of a highly-efficient facemask to protect against the acute cardiovascular effects of dilute diesel exhaust exposure2016Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, s. 550-551Artikel i tidskrift (Övrigt vetenskapligt)
  • 21. Langrish, Jeremy P
    et al.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Barath, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Muala, Ala
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blackwell, Scott
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Megson, Ian L
    Treweeke, Andrew
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L
    Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man2013Ingår 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)
    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.

  • 22.
    Larsson, Nirina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Brown, Joanna
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wilson, Susan
    Mudway, Ian S
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Airway inflammatory responses to diesel exhaust in allergic rhinitics2013Ingår i: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 25, nr 3, s. 160-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Proximity to traffic, particularly to diesel-powered vehicles, has been associated with inducing and enhancing allergies. To investigate the basis for this association, we performed controlled exposures of allergic rhinitics to diesel exhaust (DE) at a dose known to be pro-inflammatory in healthy individuals.

    Objective: We hypothesized that diesel-exhaust exposure would augment lower airway inflammation in allergic rhinitics.

    Materials and methods: Fourteen allergic rhinitics were exposed in a double-blinded, randomized trial to DE (100 mu g/m(3) PM10) and filtered air for 2 h on separate occasions. Bronchoscopy with endobronchial mucosal biopsies and airway lavage was performed 18 h post-exposure, and inflammatory markers were assessed.

    Results: No evidence of neutrophilic airway inflammation was observed post-diesel, however, a small increase in myeloperoxidase was found in bronchoalveolar lavage (p = 0.032). We found no increases in allergic inflammatory cells. Reduced mast cell immunoreactivity for tryptase was observed in the epithelium (p = 0.013) parallel to a small decrease in bronchial wash stem cell factor (p = 0.033). Discussion and conclusion: DE, at a dose previously shown to cause neutrophilic inflammation in healthy individuals, induced no neutrophilic inflammation in the lower airways of allergic rhinitics, consistent with previous reports in asthmatics. Although there was no increase in allergic inflammatory cell numbers, the reduction in tryptase in the epithelium may indicate mast cell degranulation. However, this occurred in the absence of allergic symptoms. These data do not provide a simplistic explanation of the sensitivity in rhinitics to traffic-related air pollution. The role of mast cells requires further investigation.

  • 23.
    Larsson, Nirina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lundström, Susanna
    Pinto, Rui
    Rankin, Greg
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Karimpour, Masoumeh
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wheelock, Craig
    Nording, Malin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans2014Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 43, nr 2, s. 453-463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups ((RY)-Y-2[cum]=0.822 and Q(2)[cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.

  • 24.
    Larsson, Nirina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Rankin, Greg
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bicer, Melis
    Roos-Engstrand, Ester
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Vitamin C transporters in the airways of healthy and asthmatic humansManuskript (preprint) (Övrigt vetenskapligt)
  • 25.
    Larsson, Nirina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Rankin, Gregory D.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bicer, Elif M.
    Roos-Engstrand, Ester
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian S.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Identification of vitamin C transporters in the human airways: a cross-sectional in vivo study2015Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, nr 4, artikel-id e006979Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Vitamin C is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role as a sacrificial antioxidant, little is known about its transport into the respiratory tract lining fluid (RTLF), or the underlying airway epithelial cells. While several vitamin C transporters have been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of their protein distribution within the human lung is limited, in the case of GLUTs or unknown for SVCTs.

    Setting and participants: Protein expression of vitamin C transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid, obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In addition, antioxidant concentrations were determined in RTLF. The study was performed at one Swedish centre.

    Primary and secondary outcome measures: The primary outcome measure was to establish the location of vitamin C transporters in the human airways. As secondary outcome measures, RTLF vitamin C concentration was measured and related to transporter expression, as well as bronchial epithelial inflammatory and goblet cells numbers.

    Results: Positive staining was identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were present in the apical bronchial epithelium, where SVCT2 staining was predominately localised to goblet cells and inversely related to RTLF vitamin C concentrations.

    Conclusions: This experimental study is the first to demonstrate protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A negative correlation between SVCT2-positive goblet cells and bronchial RTLF vitamin C concentrations suggests a possible role for goblet cells in regulating the extracellular vitamin C pool.

  • 26. Lepzien, Rico
    et al.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Muala, Ala
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Eklund, Anders
    Grunewald, Johan
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Smed-Sorensen, Anna
    Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients2019Ingår i: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 105, nr 4, s. 797-807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sarcoidosis is a T-cell driven inflammatory disease characterized by granuloma formation. Mononuclear phagocytes (MNPs)-macrophages, monocytes, and dendritic cells (DCs)-are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by cytokine production. Granulomas manifest primarily in lungs and lung-draining lymph nodes (LLNs) but these compartments are less studied compared to blood and bronchoalveolar lavage (BAL). Sarcoidosis can present with an acute onset (usually Lofgren's syndrome (LS)) or a gradual onset (non-LS). LS patients typically recover within 2 years while 60% of non-LS patients maintain granulomas for up to 5 years. Here, four LS and seven non-LS patients underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). From each patient, blood, BAL, endobronchial biopsies (EBBs), and LLN samples obtained by EBUS-TBNA were collected and MNPs characterized using multicolor flow cytometry. Six MNP subsets were identified at varying frequencies in the anatomical compartments investigated. Importantly, monocytes and DCs were most mature with migratory potential in BAL and EBBs but not in the LLNs suggesting heterogeneity in MNPs in the compartments typically affected in sarcoidosis. Additionally, in LS patients, frequencies of DC subsets were lower or lacking in LLNs and EBBs, respectively, compared to non-LS patients that may be related to the disease outcome. Our work provides a foundation for future investigations of MNPs in sarcoidosis to identify immune profiles of patients at risk of developing severe disease with the aim to provide early treatment to slow down disease progression.

  • 27. Lepzien, Rico
    et al.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Muala, Ala
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eklund, Anders
    Grunewald, Johan
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sörensen, Anna Smed
    Mononuclear phagocytes in lungs, lymph nodes and blood of sarcoidosis patients2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Sarcoidosis is characterized by granuloma formation primarily in the lung and lung-draining lymph nodes (LN). The disease can present with an acute onset (usually Löfgren’s syndrome (LS)) or a gradual onset (non-LS). Mononuclear phagocytes (MNPs) - macrophages, monocytes and dendritic cells (DC) - are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by production of cytokines. MNPs in lung tissue and LN are poorly studied in both, non-LS and LS sarcoidosis patients.

    Aim: To characterise the distribution and phenotype of MNPs in BAL, endobronchial biopsies (EBB), LN sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and blood from the same non-LS or LS sarcoidosis patients.

    Results: We identified MNPs from all four anatomical compartments in non-LS (n=7) and LS (n=4) sarcoidosis patients. Blood, BAL and LN contained all MNP subsets while EBB only harboured one of three monocyte subsets. Frequencies, maturation and migratory status were different between the compartments as well as between non-LS and LS patients. Our results suggest heterogeneity in distribution and function of MNPs within organs typically affected in sarcoidosis and their potential involvement in the disease course.

    Conclusions: We show that cells from BAL fluid do not necessarily reflect cells from EBB, a tissue primarily affected by granuloma formation. Our work provides a foundation for future investigations of MNPs in non-LS and LS sarcoidosis patients, allowing improved stratification to identify patients at risk of developing severe disease and provide early treatment to slow down disease progression.

  • 28.
    Linder, Robert
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Increased Mmp-9/timp-1 Ratio Is Associated With Increased Mortality-Report From The Obstructive Lung Disease In Northern Sweden (olin) COPD Study2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A2312Artikel i tidskrift (Övrigt vetenskapligt)
  • 29.
    Linder, Robert
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Proteolytic imbalance is related to FEV1 decline in COPDManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background

    It is generally accepted that metalloproteinases contribute to lung tissue destruction. This study intends to examine how proteolytic imbalance impacts COPD in relation to phenotypes of non-rapid and rapid decline in lung function, by clinically assessing subjects recruited from a population-based cohort.

    Methods

    Subjects were recruited from the longitudinal OLIN COPD study providing spirometry data over time. In total 52 subjects were included: 12 with COPD and a rapid decline in FEV1 (≥60 mL/year), 10 with COPD and a non-rapid decline in FEV1 (≤30 mL/year), 15 current and ex-smokers with normal lung function, and 15 non-smokers with normal lung function. Proteolytic markers MMP-9, MMP-12 and TIMP-1 were assessed in serum and airway lavages.

    Results

    MMP-12 in BW and BAL was higher in COPD compared to both ever- smokers (BW: p = 0.001, BAL: p = 0.001) and non-smokers with normal lung function (BW: p = 0.001, BAL: p = 0.001). BAL-MMP-12 in COPD displayed a positive association to annual decline in FEV1

    (r = 0.61, p = 0.005). The lowest concentration of S-TIMP-1 (477 (295- 717) ng/mL) was found in COPD with a rapid decline in lung function, with a negative association between annual decline in FEV1 and s-TIMP- 1 (r = -0.42, p = 0.05).

    Conclusion

    Airway protease activity measured as MMP-12 concentration in BAL was increased in COPD, compared to both smokers with normal lung function and healthy. Individuals with the highest levels of airway MMP- 12 experienced the greatest decline in FEV1. Furthermore, a negative association was found between TIMP-1 in serum and FEV1 decline. Increased airway proteolytic activity may play an important role in the progress of COPD.

  • 30.
    Linder, Robert
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study2015Ingår i: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 16, artikel-id 28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population- based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.

    Methods: Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.

    Results: Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).

    Conclusion: Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.

  • 31.
    Linder, Robert
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN unit.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Proteolytic biomarkers are related to prognosis in COPD: report from a population-based cohort2018Ingår i: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, artikel-id 64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort.

    METHODS: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbent assay (ELISA). Mortality data were collected from the Swedish national mortality register from the date of examination in 2005 until 31st December 2010.

    RESULTS: The correlation between biomarkers and lung function decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP-9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs. 10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher among those who died during follow up, as well as among those alive but not participating in 2010, when compared to those participating in the 2010-examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP-9/TIMP-1 ratio were associated with increased risk for death, while increased TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP-9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death.

    CONCLUSIONS: The expected association between these biomarkers and lung function decline in COPD was not confirmed in this population-based study, probably due to a healthy survivor effect. Still, it is suggested that increased proteolytic imbalance may be of greater prognostic importance in COPD than in non-COPD.

  • 32. Lucking, Andrew J
    et al.
    Lundbäck, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Barath, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L
    Sidhu, Manjit K
    Langrish, Jeremy P
    Boon, Nicholas A
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Badimon, Juan J
    Gerlofs-Nijland, Miriam E
    Cassee, Flemming R
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik, Energiteknik och termisk processkemi.
    Donaldson, Kenneth
    Sandstrom, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men2011Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 123, nr 16, s. 1721-1728Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men.

    METHODS AND RESULTS: Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release.

    CONCLUSIONS: Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

  • 33. Lucking, Andrew J
    et al.
    Lundbäck, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L
    Faratian, Dana
    Barath, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Cassee, Flemming R
    Donaldson, Kenneth
    Boon, Nicholas A
    Badimon, Juan J
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Diesel exhaust inhalation increases thrombus formation in man2008Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 29, nr 24, s. 3043-3051Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men.

    METHODS AND RESULTS: In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust inhalation increased thrombus formation under low- and high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels. Diesel exhaust also increased platelet-neutrophil and platelet-monocyte aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air.

    CONCLUSION: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.

  • 34.
    Lundbäck, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lucking, Andrew
    Barath, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas
    Sidhu, Manjit
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Badimon, Juan
    Cassee, Flemming
    Donaldson, Kenneth
    Boon, Nicholas
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Exhaust particle traps reduce the adverse vascular and prothrombotic effects associated with diesel exhaust exposure in manManuskript (preprint) (Övrigt vetenskapligt)
  • 35. Löfdahl, Magnus J
    et al.
    Roos-Engstrand, Ester
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bucht, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Dahlen, Barbro
    Elmberger, Göran
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sköld, C Magnus
    Increased intraepithelial T-cells in stable COPD2008Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 102, nr 12, s. 1812-1818Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The airway epithelium is the first line of defence in the response to inhaled particles and irritants. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by an irreversible loss of lung function, with cigarette smoking as a major risk factor. Here, we address intraepithelial T-cells in COPD, as these cells are a distinct T-cell subtype thought to have important regulatory functions. We hypothesised that intraepithelial T-cells play a role in the response to lung irritants and that the T-cell populations would be altered and associated with signs of inflammation in COPD.

    METHODS: Bronchoscopy with endobronchial mucosal biopsy sampling was performed in 22 patients (mean age; 57) with stable COPD (median FEV(1)% predicted: 51). Age- and smoking- matched smokers (S) with normal lung function (n=14) and age-matched non-smokers (NS) (n=15) served as controls. Airway inflammation was recorded visually using bronchitis index (BI). Biopsy specimens were processed into glycol methacrylate resin and inflammatory cells were stained immunohistochemically.

    RESULTS: The number of intraepithelial CD4+ T-cells were significantly higher in COPD patients compared to smokers as well as trend towards significance in non-smokers (p=0.005 and p=0.036, respectively), whereas intraepithelial CD8+ T-cells number were increased in patients with COPD compared to non-smokers (p=0.017). Both patients with COPD and smokers had a higher BI than non-smokers (p<0.001 for both).

    CONCLUSIONS: The present data suggest a role for intraepithelial CD4+ and CD8+ T-cells in stable COPD and indicate that T-cells are of importance in the long-term inflammatory response in COPD or, alternatively, play a regulatory role.

  • 36.
    Muala, Ala
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Nyström, Robin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Pettersson, Esbjörn
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Bergvall, Christoffer
    Westerholm, Roger
    Jalava, Pasi I.
    Happo, Mikko S.
    Uski, Oskari
    Hirvonen, Maija-Riitta
    Kelly, Frank J.
    Mudway, Ian S.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity2015Ingår i: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 12, artikel-id 33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, < 0.05, < 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (< 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, < 0.05 and < 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, < 0.05, < 0.05 and < 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.

  • 37.
    Muala, Ala
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Nyström, Robin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Pettersson, Esbjörn
    Bergvall, Christoffer
    Westerholm, Roger
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, Frank
    Mudway, Ian
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bronchial mucosal inflammation in healthy subjects after exposure to wood smoke from incomplete combustionManuskript (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.

  • 38.
    Muala, Ala
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bion, Anne
    Renault Technocentre, Guyancourt, France.
    Österlund, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bucht, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Mudway, Ian S.
    MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King’s College London, London, UK.
    Langrish, Jeremy P.
    BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK .
    Couderc, Stephane
    Renault Technocentre, Guyancourt, France.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers2014Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, nr 1, artikel-id 16Artikel i tidskrift (Refereegranskat)
    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.

  • 39. Mudway, Ian S
    et al.
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Frew, Anthony J
    Kelly, Frank J
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Vitamin supplementation does not protect against symptoms in ozone-responsive subjects2006Ingår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 40, nr 10, s. 1702-1712Artikel i tidskrift (Refereegranskat)
  • 40.
    Nordenhäll, C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Levin, Jan-Olof
    Dept of Occupational Chemistry, Institute for Working Life, Umeå.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Airway inflammation following exposure to diesel exhaust: a study of time kinetics using induced sputum2000Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 15, nr 6, s. 1046-1051Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 41.
    Nordenhäll, C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ledin, M-C
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Levin, Jan-Olof
    Institute for Working Life, Dept of Occupational Chemistry, Umeå.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Diesel exhaust enhances airway responsiveness in asthmatic subjects2001Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 17, nr 5, s. 909-915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 42. Pfeffer, Paul E.
    et al.
    Ho, Tzer R.
    Mann, Elizabeth H.
    Kelly, Frank J.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dove, Rosamund E.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mudway, Ian S.
    Hawrylowicz, Catherine M.
    Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes2018Ingår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 153, nr 4, s. 502-512Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

  • 43.
    Pourazar, Jamshid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Muala, Ala
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Langrish, J. P.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Airway Inflammatory Response In Healthy Subjects Following Chamber Exposure To 100% Rme Biodiesel2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A5252Artikel i tidskrift (Övrigt vetenskapligt)
  • 44.
    Pourazar, Jamshid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, Frank J
    Davies, Donna E
    Wilson, Susan J
    Holgate, Stephen T
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium2008Ingår i: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 5, artikel-id 8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is a major contributor to particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, together with an enhanced epithelial expression of cytokines such as IL-8, Gro-alpha, IL-13 and activation of redox sensitive transcription factors (NFkappaB, AP-1), and MAP kinases (p38, JNK). The aim of the present investigation was to elucidate the involvement of the epidermal growth factor receptor (EGFR) signalling pathway in the epithelial response to DE in-vivo.

    RESULTS: Immunohistochemical staining was used to quantify the expression of the EGFR, phosphorylated Tyrosine residues, MEK and ERK in the bronchial epithelium of archived biopsies from 15 healthy subjects following exposure to DE (PM10, 300 mug/m3) and air. DE induced a significant increases in the expression of EGFR (p = 0.004) and phosphorylated C-terminal Tyr 1173 (p = 0.02). Other investigated EGFR tyrosine residues, Src related tyrosine (Tyr 416), MEK and ERK pathway were not changed significantly by DE.

    CONCLUSION: Exposure to DE (PM10, 300 mug/m3) caused enhanced EGFR expression and phosphorylation of the tyrosine residue (Tyr 1173) which is in accordance with the previously demonstrated activation of the JNK, AP-1, p38 MAPK and NFkB pathways and associated downstream signalling and cytokine production. No effects were seen on the MEK and ERK pathway suggesting that at the investigated time point (6 hours post exposure) there was no proliferative/differentiation signalling in the bronchial epithelium. The present findings suggest a key role for EGFR in the bronchial response to diesel exhaust.

  • 45.
    Pourazar, Jamshid
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Frew, Anthony J
    Blomberg, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, Frank J
    Wilson, Susan
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Diesel exhaust exposure enhances the expression of IL-13 in the bronchial epithelium of healthy subjects.2004Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 98, nr 9, s. 821-825Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is an important contributor to ambient particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, with an enhanced epithelial expression of IL-8, and Gro-α in healthy subjects. The present investigation was aimed to further characterise the epithelial response to DE in vivo, with particular reference to possible TH2 response, in non-atopic healthy subjects. To determine this response, 15 healthy, non-atopic non-smoking subjects with normal lung function were exposed to DE (PM10 300 μg/m3) and filtered air during 1 h on two separate randomised occasions. Bronchoscopy sampling of bronchial mucosal biopsies was performed 6 h after exposure. Immunohistochemical staining were performed using mAb for IL-10, IL-13 and IL-18 expression. DE exposure induced a significant increase in the expression of IL-13 in the bronchial epithelium cells, 2.1 (1.35–4.88) Md (Q1–Q3) vs. air 0.94 (0.53–1.23); P=0.009. No significant changes were seen in IL-10 and IL-18 expression. This finding suggests an TH2-inflammatory response in the airways of non-atopic healthy individuals.

  • 46.
    Pourazar, Jamshid
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Mudway, IS
    Samet, JM
    Helleday, Ragnberth
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Blomberg, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Wilson, SJ
    Frew, AJ
    Kelly, FJ
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Diesel exhaust activates redox-sensitive transcription factors and kinases in human airways2005Ingår i: American Journal of Physiology - Lung cellular and Molecular Physiology, ISSN 1040-0605, E-ISSN 1522-1504, Vol. 289, nr 5, s. L724-L730Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Diesel exhaust (DE) is a major component of airborne particulate matter. In previous studies we have described the acute inflammatory response of the human airway to inhaled DE. This was characterized by neutrophil, mast cell, and lymphocyte infiltration into the bronchial mucosa with enhanced epithelial expression of IL-8, Gro-alpha, and IL-13. In the present study, we investigated whether redox-sensitive transcription factors were activated as a consequence of DE exposure, consistent with oxidative stress triggering airway inflammation. In archived biopsies from 15 healthy subjects exposed to DE [particulates with a mass median diameter of <10 mum, 300 microg/m3] and air, immunohistochemical staining was used to quantify the expression of the transcription factors NF-kappaB (p65) and AP-1 (c-jun and c-fos), as well their upstream MAPKs, p38 and JNK, in the bronchial epithelium. In addition, phosphorylation of tyrosine residues was examined. DE induced a significant increase in the nuclear translocation of NF-kappaB (P = 0.02), AP-1 (P = 0.02), phosphorylated JNK (P = 0.04), and phosphorylated p38 (P = 0.01), as well as an increase in total (cytoplasmic + nuclear) immunostaining of phosphorylated p38 (P = 0.03). A significant increase in nuclear phosphorylated tyrosine was also observed (P < 0.05). These observations demonstrate that DE activates redox-sensitive transcription factors in vivo consistent with oxidative stress triggering the increased synthesis of proinflammatory cytokines.

  • 47.
    Pourazar, Jamshid
    et al.
    Umeå universitet.
    Rankin, Gregory Dominique
    Umeå universitet.
    Muala, Ala
    Umeå universitet.
    Unosson, Jon
    Umeå universitet.
    Sehlstedt, M.
    Umeå universitet.
    Behndig, A. F.
    Umeå universitet.
    Boman, C.
    Umeå universitet.
    Blomberg, A.
    Umeå universitet.
    Bosson, J.
    Umeå universitet.
    Sandstrom, T.
    Umeå universitet.
    Bronchoalveolar Eosinophilia In Human Subjects After Exposure To Biomass Smoke From Wood Pellet Combustion2016Konferensbidrag (Refereegranskat)
  • 48.
    Rankin, Gregory D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Rasmuson, Johan
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Immunolocalisation Of Puumala Hantavirus In Human Endobronchial Biopsies2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A3793Artikel i tidskrift (Övrigt vetenskapligt)
  • 49.
    Rankin, Gregory D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Thomas, S.
    Baharom, F.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Smed-Sorensen, A.
    Distribution Of Human Respiratory Dendritic Cell Subsets At Steady State Differs In Specific Compartments Of The Airways2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A1300Artikel i tidskrift (Övrigt vetenskapligt)
  • 50.
    Rasmuson, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Linderholm, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Presence of activated airway T lymphocytes in human puumala hantavirus disease2011Ingår i: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 140, nr 3, s. 715-722Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Hantaviruses cause two clinical syndromes; hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information of the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways.

    METHODS: In 15 hospitalized HFRS patients, bronchoscopy was performed with sampling of endobronchial mucosal biopsies and bronchoalveolar lavage (BAL) fluid. Biopsies were stained for leukocytes, lymphocyte subsets and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as control group.

    RESULTS: Compared to controls, endobronchial mucosal biopsies from HFRS patients revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (p≤0.001), along with an increase in submucosal CD4(+) T cells (p=0.001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (p<0.001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in HFRS patients (p<0.001). In HFRS patients, analyses of T cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (p=0.011 and p=0.025), NK cells (p<0.001) together with an increased expression of activation markers HLA-DR and CD25 on T cells (p<0.001 and p<0.001).

    CONCLUSIONS: The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.

12 1 - 50 av 67
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf