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  • 101.
    Gustafsson, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. FOI.
    Nanomaterials: respiratory and immunological effects following inhalation of engineered nanoparticles2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Nanotechnology is an important and promising field that can lead to improved environment and human health and contribute to a better social and economic development. Materials in nanoscale have unique physiochemical properties which allow for completely new technical applications. Enlarged surface area and properties due to quantum physics are among the properties that distinguish the nanoscale. Nano safety has evolved as a discipline to evaluate the adverse health effects from engineered nanomaterials (ENMs). The prevalence of allergic diseases is increasing in the society. An additional issue is the influence of inherited factors on the health responses to ENMs. The aim of this thesis was to investigate the respiratory, inflammatory, and immunological effects following inhalation of ENMs; both sensitive and genetically susceptible individuals were used. Sensitive individuals refer to individuals with pre-existing respiratory diseases, such as allergic asthma, and genetically susceptible individuals refer to individuals prone to autoimmune and allergic diseases.

    Methods In vivo models of mice and rats were used. In study I the inflammatory and immune responses following exposure to titanium dioxide nanoparticles (TiO2 NPs) were investigated. The effect of when the TiO2 NP exposure occurs during the development of allergic airway inflammation was investigated in study II, with regards to respiratory, inflammatory, and immune responses. In study III, the influence of the genetics on the respiratory, inflammatory, and immune responses, following TiO2 NP exposure to naïve and sensitive rats was evaluated. In study IV, the inflammatory and immune responses of naïve mice and mice with an allergic airway inflammation were studied in lung fluid and lymph nodes draining the airways following inhalation to hematite NPs (α-Fe2O2).

    Results Exposure to TiO2 NPs induced a long-lasting lymphocytic response in the airways, indicating a persistent immune stimulation. The dose and timing of TiO2 NP exposure affected the airway response in mice with allergic airway disease. When the mice were exposed to particles and an allergen during the same period, a decline in general health was observed. By comparing different inbred rat strains it was demonstrated that genetically determined factors influence the immune and respiratory responses to TiO2 NP exposure in both naïve and sensitive individuals. Exposure to hematite NPs resulted in different cellular responses: naïve mice had increased numbers of cells while mice with allergic airway inflammation had decreased cell numbers in BALF. Analogous cell responses were also observed in the lung draining lymph nodes.

    Conclusion Altogether, this thesis emphasises the complexity of assessing health risks associated with nanoparticle exposure and the importance of including sensitive populations when evaluating adverse health effects of ENMs.

  • 102.
    Gustafsson, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Swedish Def Res Agcy, Div CBRN Def & Secur, SE-90182 Umea, Sweden.
    Bergström, Ulrika
    Ågren, Lina
    Österlund, Lars
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Swedish Def Res Agcy, Div CBRN Def & Secur, SE-90182 Umea, Sweden.
    Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles2015In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 288, no 1, p. 1-11Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials.

  • 103.
    Gustafsson, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bergström, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. FOI.
    Ågren, Lina
    FOI.
    Österlund, Lars
    Ångström Laboratory, Uppsala University.
    Sandström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. FOI.
    Mice with established airway inflammation exert differential cellular responses to inhaled hematite nanoparticles than healthy miceManuscript (preprint) (Other academic)
    Abstract [en]

    The aim of this study was to investigate the inflammatory and immunological responses in the airways and the lung-draining lymph nodes, following lung exposure to hematite nanoparticles (NPs). The responses to hematite NPs were evaluated in both non-sensitized healthy mice, and allergen-sensitized mice, in which the latter represent a group of sensitive individuals with allergic airway disease. This allergic airway disease was induced by sensitization and aerosol challenge to a respiratory allergen resulting in an established eosinophilic and lymphocytic airway inflammation at the time of NP exposure. The mice received either hematite NPs or vehicle (PBS) intratracheally and the cellular responses were evaluated on day 1, 2, and 7, following exposure.

    Intratracheal instillation of hematite NPs induced an increase of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on day 1 and 2 following exposure. At these time-points the lymphocytes in the lymph nodes were also increased. In contrast, exposure to hematite NPs in sensitized mice induced a rapid and unspecific cellular reduction in the alveolar space on the first day after exposure. A similar decrease of lymphocytes was also observed in the mediastinal lymph nodes draining the airways. The study did not indicate a reduction of inflammatory cells in the lung tissue or a translocation of cells from alveolar space to lung tissue. Although, mucociliary cellular clearance could be a possible explanation, our finding of cellular decrease also in lung draining lymph nodes point at cell death as the most likely cause to this unspecific cellular reduction.

    The results indicate that cells in the airways and lymph nodes of individuals with established airway inflammation undergo cell death when exposed to iron oxide NPs. A possible reason to the toxic response is extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways, which is further catalyzed by Fe ions released by the hematite NPs, or by generation of ROS at the surface of the NPs. Such cell toxic response was not detected in healthy non-sensitized individuals. This study clearly demonstrates the different response of sensitized and non-sensitized mice, and highlights the importance of including individuals with respiratory disorders, such as allergic asthma, when evaluating health effects of inhaled nanomaterials.

  • 104.
    Gustafsson, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. FOI.
    Jonasson, Sofia
    FOI.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lorentzen, Johnny
    KI, IMM.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. FOI.
    Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles2014In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 326, p. 74-85Article in journal (Other academic)
    Abstract [en]

    This study examines the immunological responses in rats following inhalation to titanium dioxide nanoparticles (TiO2 NPs), in naïve rats and in rats with induced allergic airway disease. The responses of two different inbred rat strains were compared: the Dark Aguoti (DA), susceptible to chronic inflammatory disorders, and the Brown Norwegian (BN), susceptible to atopic allergic inflammation. Naïve rats were exposed to an aerosol of TiO2 NPs once daily for 10 days. Another subset of rats was sensitized to the allergen ovalbumin (OVA) in order to induce airway inflammation. These sensitized rats were exposed to TiO2 NPs before and during the allergen challenge. Naïve rats exposed to TiO2 NPs developed an increase of neutrophils and lymphocytes in both rat strains. Airway hyperreactivity and production of inflammatory mediators typical of a T helper 1 type immune response were significantly increased, only in DA rats. Sensitization of the rats induced a prominent OVA-specific-IgE and IgG response in the BN rat while DA rats only showed an increased IgG response. Sensitized rats of both strains developed airway eosinophilia following allergen challenge, which declined upon exposure to TiO2 NPs. The level of neutrophils and lymphocytes increased upon exposure to TiO2 NPs in the airways of DA rats but remained unchanged in the airways of BN rats. In conclusion, the responses to TiO2 NPs were strain-dependent, indicating that genetics play a role in both immune and airway reactivity. DA rats were found to be higher responder compared to BN rats, both when it comes to responses in naïve and sensitized rats. The impact of genetically determined factors influencing the inflammatory reactions pinpoints the complexity of assessing health risks associated with nanoparticle exposures.

  • 105.
    Gustafsson, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindstedt, Elsa
    Elfsmark Svensson, Linda
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lung exposure of titanium dioxide nanoparticles induces innate immune activation and long-lasting lymphocyte response in the Dark Agouti rat2011In: Journal of Immunotoxicology, ISSN 1547-691X, E-ISSN 1547-6901, Vol. 8, no 2, p. 111-121Article in journal (Refereed)
    Abstract [en]

    Nanomaterial of titanium dioxide (TiO(2)) is manufactured in large-scale production plants, resulting in risks for accidental high exposures of humans. Inhalation of metal oxide nanoparticles in high doses may lead to both acute and long-standing adverse effects. By using the Dark Agouti (DA) rat, a strain disposed to develop chronic inflammation following exposure to immunoactivating adjuvants, we investigated local and systemic inflammatory responses after lung exposure of nanosized TiO(2) particles up to 90 days after intratracheal instillation. TiO(2) induced a transient response of proinflammatory and T-cell-activating cytokines (interleukin [IL]-1α, IL-1β, IL-6, cytokine-induced neutrophil chemoattractant [CINC]-1, granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-2) in airways 1-2 days after exposure, accompanied by an influx of eosinophils and neutrophils. Neutrophil numbers remained elevated for 30 days, whereas the eosinophils declined to baseline levels at Day 8, simultaneously with an increase of dendritic cells and natural killer (NK) cells. The innate immune activation was followed by a lymphocyte expansion that persisted throughout the 90-day study. Lymphocytes recruited to the lungs were predominantly CD4(+) helper T-cells, but we also demonstrated presence of CD8(+) T-cells, B-cells, and CD25(+) T-cells. In serum, we detected both an early cytokine expression at Days 1-2 (IL-2, IL-4, IL-6, CINC-1, IL-10, and interferon-gamma [IFN-γ] and a second response at Day 16 of tumor necrosis factor-alpha (TNF-α), indicating systemic late-phase effects in addition to the local response in airways. In summary, these data demonstrate a dynamic response to TiO(2) nanoparticles in the lungs of DA rats, beginning with an innate immune activation of eosinophils, neutrophils, dendritic cells, and NK cells, followed by a long-lasting activation of lymphocytes involved in adaptive immunity. The results have implications for the assessment of risks for adverse and persistent immune stimulation following nanoparticle exposures in sensitive populations.

  • 106.
    Gustafsson, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Svensson-Elfsmark, Linda
    Lorentzen, Johnny C
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Strain differences influence timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in rats2014In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 34, no 3, p. 272-280Article in journal (Refereed)
    Abstract [en]

    The acute pulmonary responses after exposure to sulfur and nitrogen mustards are well documented whereas the late pulmonary effects are not. With a novel focus on the immune system this paper investigate whether late phase pulmonary effects developed in rats exposed to the nitrogen mustard melphalan are linked to the acute responses and whether the reactions are genetically regulated. The DA rat strain was used to establish a lung exposure model. Five other inbred rat strains (PVG, PVG.1AV1, LEW, WF and F344) were compared within the model at selected time points. All rat strains displayed a biphasic pattern of leukocyte infiltration in the lungs, dominated by neutrophils 2days after exposure and a second peak dominated by macrophages 29days after exposure. The number of macrophages was higher in the DA rat compared with the other strains. The infiltration of lymphocytes in the lungs varied in both time of appearance and magnitude between strains. The quantity of collagen deposition in the lungs varied between strains at day 90; LEW and WF displayed high collagen content which coincided with an increased level of cytotoxic T cells. LEW further displayed an increased number of T helper cells and natural killer (NK) T cells in the lungs. The results in this study suggest there is a link between the development of lung fibrosis and high cytotoxic cell responses and that there is a genetic influence, as there are variations in acute and late adverse reactions between rat strains in both timing and magnitude.

    Copyright (c) 2013 John Wiley & Sons, Ltd.

  • 107. Hagstad, Stig
    et al.
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease In Northern Sweden (OLIN) Studies, Norrbotten County Council, Luleå, Sweden.
    Bjerg, Anders
    Ekerljung, Linda
    Ye, Xiong
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease In Northern Sweden (OLIN) Studies, Norrbotten County Council, Luleå, Sweden.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Unit of Research , Education and Development - Luleå, Umeå University .
    Torén, Kjell
    Lötvall, Jan
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease In Northern Sweden (OLIN) Studies, Norrbotten County Council, Luleå, Sweden.
    Lundbäck, Bo
    Prevalence and risk factors of COPD among never-smokers in two areas of Sweden: Occupational exposure to gas, dust or fumes is an important risk factor2015In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, no 11, p. 1439-1445Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although active tobacco smoking is the main risk factor for COPD, COPD is not uncommon also among never-smokers. Different study locations along with different spirometric definitions of COPD have historically yielded different prevalence estimates of the disease.

    AIM: To study current prevalence and risk factors of COPD among never-smokers in two areas of Sweden.

    METHODS: Data collected in 2008-2012 within the West Sweden Asthma Study and Obstructive Lung Disease in Northern Sweden Studies was pooled. The study population consisted of 1839 subjects who participated in spirometry and interviews. COPD was defined as post-bronchodilator a) FEV1/(F)VC < 0.7, b) FEV1/FVC < 0.7 and c) FEV1/FVC < lower limit of normal.

    RESULTS: Of the 1839 subjects, 967 (52.6%) were never-smokers. Among the never-smoking subjects, the prevalence of COPD according to definitions a-c was 7.7%, 4.9% and 3.0%, respectively. The corresponding prevalence of GOLD grade ≥2 was 2.0%, 1.4% and 1.3%. No significant difference in prevalence between the two study areas was observed. In never-smokers, occupational exposure to gas, dust or fumes (GDF) was significantly associated with both COPD (OR 1.85, 95% CI 1.03-3.33), and GOLD ≥2 (OR 4.51, 1.72-11.9) according to definition a), after adjusting for age, educational level and exposure to passive smoking at work.

    CONCLUSION: Depending on definition, prevalence of COPD among never-smokers was 3.0-7.7%, whereas GOLD ≥2 was present in 1.3-2.0%. Occupational exposure to GDF remained independently and significantly associated with COPD regardless of spirometric definition of the disease.

  • 108.
    Hansson, Alva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    DNA damage effects of wood smoke in airway epithelial cell lines and human bronchoalveolar lavage cells2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 109.
    Hedman, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Stridsman, Caroline
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, Magnus
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ekerljung, Linda
    Association of Electronic Cigarette Use With Smoking Habits, Demographic Factors, and Respiratory Symptoms2018In: JAMA NETWORK OPEN, ISSN 2574-3805, Vol. 1, no 3, article id e180789Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE There is an ongoing debate about whether electronic cigarettes (e-cigarettes) are the solution to the tobacco epidemic or a new public health threat. Large representative studies are needed to study e-cigarette use in the general population, but hardly any have been published. OBJECTIVES To estimate the prevalence of e-cigarette use and to investigate the association of e-cigarette use with smoking habits, demographic factors, and respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, population-based study of random samples of the population, performed within the Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). The same validated questionnaire including identical questions was used in OLIN and WSAS. In 2016, OLIN and WSAS conducted postal questionnaire surveys in random samples of adults aged 20 to 75 years. In OLIN, 6519 participated (response rate, 56.4%); in WSAS, 23 753 participated (response rate, 50.1%). MAIN OUTCOMES AND MEASURES Electronic cigarette use, smoking habits, and respiratory symptoms. RESULTS Of 30 272 participants (16 325 women [53.9%]). 3897 (12.9%) were aged 20 to 29 years; 4242 (14.0%). 30 to 39 years; 5082 (16.8%). 40 to 49 years; 6052 (20.0%), 50 to 59 years; 6628 (21.9%), 60 to 69 years; and 4371(14.4%), 70 to 75 years. The number of current smokers was 3694 (12.3%), and 7305 (24.4%) were former smokers. The number of e-cigarette users was 529 (2.0%). and e-cigarette use was more common among men (275 of 12 347 [2.2%; 95% CI, 2.0%-2.5%]) than women (254 of 14 022 [1.8%; 95% CI, 1.6%-2.0%]). Among current smokers. 350 of 3566 (9.8%; 95% CI, 8.8%10.8%) used e-cigarettes compared with 79 of 6875 (1.1%; 95% CI, 0.9%-1.3%) in former smokers and 96 of 15 832 (0.6%; 95% CI, 0.5%-0.7%) in nonsmokers (P < .001). Among e-cigarette users who answered the survey question about cigarette-smoking habits (n = 525). 350 (66.7%; 95% CI, 62.7%-70.7%) were current smokers, 79 (15.0%; 95% CI, 11.9%-18.1%) were former smokers, and 96 (18.3%; 95% CI, 15.0%-21.6%) were nonsmokers (P < .001 for trend). In a regression analysis, e-cigarette use was associated with male sex (odds ratio [OR], 1.35; 95% CI. 1.12-1.62); age groups 20 to 29 years (OR. 2.77; 95% CI, 1.90-4.05), 30 to 39 years (OR, 2.27; 95% CI, 1.53-3.36), 40 to 49 years (OR, 1.65; 95% CI, 1.11-2.44). and 50 to 59 years (OR, 1.47; 95% CI, 1.01-2.12); educational level at primary school (OR, 1.99; 95% CI, 1.51-2.64) and upper secondary school (OR, 1.57; 95% CI, 1.25-1.96); former smoking (OR. 2.37; 95% CI, 1.73-3.24); and current smoking (OR. 18.10; 95% CI, 14.19-23.09). All respiratory symptoms were most common among dual users and former smokers and nonsmokers who used e-cigarettes. CONCLUSIONS AND RELEVANCE Use of e-cigarettes was most common among smokers, and dual users had the highest prevalence of respiratory symptoms. On a population level, this study indicates that the present use of e-cigarettes does not adequately serve as a smoking cessation tool.

  • 110.
    Hedman, Linnéa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bjerg Bäcklund, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Perzanowski, Matthew
    Sundberg, Sigrid
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Factors related to tobacco use among teenagers2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 3, p. 496-502Article in journal (Refereed)
    Abstract [en]

    AIM: To examine tobacco use among teenagers, identify factors related to tobacco use, as well as evaluate the outcome of a smoking prevention program.

    METHODS: From age 7/8 to 14/15, annual questionnaires about asthma and allergy have been completed in the OLIN paediatric study in Northern Sweden. From 12/13 years, questions about tobacco use, i.e. smoking and snuff, were added. A smoking prevention program was performed during 2 years.

    RESULTS: Any tobacco use increased from 5.0% at age 12/13 years, to 14.4% at age 14/15. At age 14/15 years, the prevalence of tobacco use was significantly higher among boys than girls (16.7 and 12.0%, respectively). More girls than boys smoked (8.9 and 2.8%, respectively), while use of snuff was more common among the boys (15.6 and 4.2%, respectively). Significant risk factors for smoking were any of the family members currently smoking, OR 6.1 (95% CI 4.0-9.3) and a physician-diagnosed asthma at the age of 14/15 years, OR 1.9 (95% CI 1.2-3.0). A protective factor against tobacco use was participation in sports, OR 0.3 (95% CI 0.2-0.4). The prevention program did not result in less tobacco use, although it may have delayed smoking initiation.

    CONCLUSION: The patterns of tobacco use differed significantly between boys and girls. Though any tobacco use was more common among boys, girls were more likely to smoke, and boys were more likely to use snuff. Having asthma did not prevent the teenagers from smoking. Since having a smoking family member was the major risk factor for tobacco use, prevention programs should be directed at smoking families in addition to the individuals.

  • 111.
    Helleday, Ragnberth
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Segerstedt, Bo
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Mudway, Ian
    Nordberg, Gunnar
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Bernard, Alfred
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Exploring the time dependence of serum clara cell protein as a biomarker of pulmonary injury in humans.2006In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 130, no 3, p. 672-675Article in journal (Refereed)
  • 112. Hellgren, Johan
    et al.
    Omenaas, Ernst
    Gíslason, Thórarinn
    Jögi, Rain
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindberg, Eva
    Janson, Christer
    Torén, Kjell
    Perennial non-infectious rhinitis--an independent risk factor for sleep disturbances in Asthma.2007In: Respir Med, ISSN 0954-6111, Vol. 101, no 5, p. 1015-20Article in journal (Refereed)
  • 113.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundqvist, Martin
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rohani, Morteza
    Al-Khalili, Faris
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rosenqvist, Mårten
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Atrial fibrillation in patients with sleep apneaManuscript (preprint) (Other academic)
  • 114.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundqvist, Martin
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rohani, Morteza
    Al-Khalili, Faris
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rosenqvist, Mårten
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Atrial fibrillation among patients under investigation for suspected obstructive sleep apnea2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0171575Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: Obstructive sleep apnea is common among patients with atrial fibrillation, but the prevalence and risk factors for atrial fibrillation among patients who are being investigated on suspicion of sleep apnea are not well known. The aim of the study was to estimate the prevalence of atrial fibrillation among patients investigated for suspected obstructive sleep apnea and to identify risk factors for atrial fibrillation among them.

    METHODS: The prevalence of atrial fibrillation was investigated among 201 patients referred for suspected obstructive sleep apnea. Patients without known atrial fibrillation were investigated with a standard 12-lead ECG at hospital and short intermittent handheld ECG recordings at home, during 14 days.

    RESULTS: Atrial fibrillation occurred in 13 of 201 subjects (6.5%), and in 12 of 61 men aged 60 years and older (20%). The prevalence of atrial fibrillation increased with sleep apnea severity (p = 0.038). All patients with atrial fibrillation were men and all had sleep apnea. Age 60 or older, the occurrence of central sleep apnea and diabetes mellitus were independent risk factors for atrial fibrillation after adjustments for body mass index, gender, sleep apnea and cardiovascular disease.

    CONCLUSIONS: Atrial fibrillation is common among subjects referred for sleep apnea investigation and the prevalence of atrial fibrillation increases with sleep apnea severity. Independent risk factors for atrial fibrillation among patients investigated for suspected obstructive sleep apnea include the occurrence of coexisting central sleep apnea, age 60 years or older and diabetes mellitus.

  • 115.
    Henein, Michael Y
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Ying
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sun, Lin
    Khir, Ashraf W
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The human heart: application of the golden ratio and angle2011In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 150, no 3, p. 239-242Article in journal (Refereed)
    Abstract [en]

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality.

  • 116. Hillerdal, Gunnar
    et al.
    Löfdahl, Claes-Göran
    Ström, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Skoogh, Bengt-Eric
    Jorfeldt, Lennart
    Nilsson, Folke
    Forslund-Stiby, Dycke
    Ranstam, Jonas
    Gyllstedt, Erik
    Comparison of lung volume reduction surgery and physical training on health status and physiologic outcomes: a randomized controlled clinical trial2005In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 128, no 5, p. 3489-3499Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements.

    DESIGN: After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year.

    SETTING: All seven thoracic surgery centers in Sweden.

    PATIENTS: All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS.

    INTERVENTIONS: Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively.

    MEASUREMENTS AND RESULTS: Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months.

    CONCLUSIONS: In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.

  • 117. Hogberg, Sofie M.
    et al.
    Akerstedt, Hans O.
    Holmstedt, Elise
    Lundstrom, T. Staffan
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Time-Dependent Deposition of Micro- and Nanofibers in Straight Model Airways2012In: Journal of Fluids Engineering - Trancactions of The ASME, ISSN 0098-2202, E-ISSN 1528-901X, Vol. 134, no 5, p. 051208-Article in journal (Refereed)
    Abstract [en]

    In this paper, we increase the understanding of the influence of the breathing pattern on the fate of inhaled non-spherical micro and nanoparticles and examine the accuracy of replacing the cyclic flow field with a quasi-steady flow. This is done with new analysis and numerical simulations on straight model airways using a previously developed discrete model for fiber motion. For the conditions studied, maximum deposition is obtained when fibers are released at the start of the inspiratory cycle, and minimum is received at the peak of inhalation. A quasi-steady solution generally provides a relatively good approximation to cyclic flow if an average velocity over one residence time of the particles moving with the mean fluid velocity is used. For a batch type, supply of particles deposition is favored in light activity breathing as compared to heavy breathing and the inclusion of a short pause after the inhalation results in an increased deposition in the terminal bronchiole. During zero-flow over the time of a breathing pause, spherical 10 nm particles experience considerable deposition in the distal airways, whereas only a few percent of larger and/or fibrous nanoparticles were deposited. Hence, size and shape are crucial variables for deposition for no flow conditions. Common for all breathing parameters examined was that minimum deposition was obtained for the spherical 1 mu m-particles and the fibrous 100 nm-particles. The former is expected from studies on spherical particles, and the latter is in agreement with results from a recent publication on steady inspiration.

  • 118. Holgate, Stephen T
    et al.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Frew, Anthony J
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nördenhall, Charlotta
    Salvi, Sundeep
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Söderberg, Margaretha
    Health effects of acute exposure to air pollution. Part I: Healthy and asthmatic subjects exposed to diesel exhaust2003In: Research report (Health Effects Institute), ISSN 1041-5505, no 112, p. 1-30; discussion 51Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to assess the impact of short-term exposure to diluted diesel exhaust on inflammatory parameters in human airways. We previously exposed control subjects for 1 hour to a high ambient concentration of diesel exhaust (particle concentration 300 pg/m3--a level comparable with that found in North Sea ferries, highway underpasses, etc). Although these exposures did not have any measurable effect on standard indices of lung function, there was a marked neutrophilic inflammatory response in the airways accompanied by increases in blood neutrophil and platelet counts. Endothelial adhesion molecules were upregulated, and the expression of interleukin 8 messenger RNA (IL-8 mRNA*) was increased in a pattern consistent with neutrophilia. Individuals with asthma have inflamed airways and are clinically more sensitive to air pollutants than are control subjects. The present study was designed to assess whether this clinical sensitivity can be explained by acute neutrophilic inflammation or an increase in allergic airway inflammation resulting from diesel exhaust exposure. For this study, we used a lower concentration of diesel exhaust (100 microg/m3 PM10) for a 2-hour exposure. At this concentration, both the control subjects and those with asthma demonstrated a modest but statistically significant increase in airway resistance following exposure to diesel exhaust. This increase in airway resistance was associated with an increased number of neutrophils in the bronchial wash (BW) fluid obtained from control subjects (median after diesel exhaust 22.0 vs median after air 17.2; P = 0.015), as well as an increase in lymphocytes obtained through bronchoalveolar lavage (BAL) (15.0% after diesel exhaust vs 12.3% after air; P = 0.017). Upregulation of the endothelial adhesion molecule P-selectin was noted in bronchial biopsy tissues from control subjects (65.4% of vessels after diesel exhaust vs 52.5% after air). There was also a significant increase in IL-8 protein concentrations in BAL fluid and IL-8 mRNA gene expression in the bronchial biopsy tissues obtained from control subjects after diesel exhaust exposure (median IL-8 expression 65.7% of adenine phosphoribosyl transferase [APRT] gene expression value after diesel exhaust vs 51.0% after air; P = 0.007). There were no significant changes in total protein, albumin, or other soluble inflammatory markers in the BW or BAL fluids. Red and white blood cell counts in peripheral blood were unaffected by diesel exhaust exposure. Airway mucosal biopsy tissues from subjects with mild asthma (defined as forced expiratory volume in 1 second [FEV1] greater than or equal to 70% of the predicted value) showed eosinophilic airway inflammation after air exposure compared with the airways of the corresponding control subjects. However, among the subjects with mild asthma, diesel exhaust did not induce any significant change in airway neutrophils, eosinophils, or other inflammatory cells; cytokines; or mediators of inflammation. The only clear effect of diesel exhaust on the airways of subjects with asthma was a significant increase in IL-10 staining in the biopsy tissues. This study demonstrated that modest concentrations of diesel exhaust have clear-cut inflammatory effects on the airways of nonasthmatic (or control) subjects. The data suggest a direct effect of diesel exhaust on IL-8 production leading to upregulation of endothelial adhesion molecules and neutrophil recruitment. Despite clinical reports of increased susceptibility of patients with asthma to diesel exhaust and other forms of air pollution, it does not appear that this susceptibility is caused either directly by induction of neutrophilic inflammation or indirectly by worsening of preexisting asthmatic airway inflammation. The increased level of IL-10 after diesel exhaust exposure in airways of subjects with asthma suggests that this pollutant may induce subtle changes in airway immunobiology. This is an important topic for further investigation. Other possible explanations for the apparent lack of response to diesel exhaust among subjects with asthma include (1) the time course of the response to diesel may differ from the response to allergens, which peaks 6 to 8 hours after exposure; (2) a different type of inflammation may occur that was not detectable by the standard methods used in this study; and (3) the increased sensitivity of patients with asthma to particulate air pollution may reflect the underlying bronchial hyperresponsiveness found in asthma rather than any specific increase in inflammatory responses.

  • 119. Holm, B C
    et al.
    Lorentzen, J C
    Bucht, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Adjuvant oil induces waves of arthritogenic lymph node cells prior to arthritis onset.2004In: Clin Exp Immunol, ISSN 0009-9104, Vol. 137, no 1, p. 59-64Article in journal (Refereed)
  • 120. Holm, M
    et al.
    Omenaas, E
    Gíslason, T
    Svanes, C
    Jögi, R
    Norrman, Eva
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Janson, C
    Torén, K
    Remission of asthma: a prospective longitudinal study from northern Europe (RHINE study).2007In: Eur Respir J, ISSN 0903-1936, Vol. 30, no 1, p. 62-5Article in journal (Refereed)
  • 121.
    Huber, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henriksson, Robin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jakobsson, Stina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Implementation of a telephone-based secondary preventive intervention after acute coronary syndrome (ACS): participation rate, reasons for non-participation and 1-year survival2016In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 17, article id 85Article in journal (Refereed)
    Abstract [en]

    Background: Acute coronary syndrome (ACS) is a major cause of death from a non-communicable disease. Secondary prevention is effective for reducing morbidity and mortality, but evidence-based targets are seldom reached and new interventional methods are needed. The present study is a feasibility study of a telephone-based secondary preventive programme in an unselected ACS cohort. Methods: The NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) ACS trial is a prospective randomized controlled trial. All eligible patients admitted for ACS were randomized to usual follow-up by a general practitioner or telephone follow-up by study nurses. The intervention was made by continuous telephone contact, with counseling on healthy living and titration of medicines to reach target values for blood pressure and blood lipids. Exclusion criteria were limited to physical inability to follow the study design or participation in another study. Results: A total of 907 patients were assessed for inclusion. Of these, 661 (72.9 %) were included and randomized, 100 (11 %) declined participation, and 146 (16.1 %) were excluded. The main reasons for exclusion were participation in another trial, dementia, and advanced disease. "Excluded" and "declining" patients were significantly older with more co-morbidity, decreased functional status, and had more seldom received education above compulsory school level than "included" patients. Non-participants had a higher 1-year mortality than participants. Conclusions: Nurse-led telephone-based follow-up after ACS can be applied to a large proportion in an unselected clinical setting. Reasons for non-participation, which were associated with increased mortality, include older age, multiple co-morbidities, decreased functional status and low level of education.

  • 122.
    Hunter, Amanda
    et al.
    University of Edinburgh.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Langrish, Jeremy P
    University of Edinburgh.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Raftis, Jennifer B
    University of Edinburgh.
    Miller, Mark R
    University of Edinburgh.
    Lucking, Andrew J
    University of Edinburgh.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Nyström, Robin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    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 fighters2014In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 11, article id 62Article in journal (Refereed)
    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.

  • 123. Janson, C
    et al.
    Norbäck, D
    Omenaas, E
    Gislason, T
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Jögi, R
    Lindberg, E
    Gunnbjörnsdottir, M
    Norrman, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wentzel-Larsen, T
    Svanes, C
    Jensen, E J
    Torén, K
    Insomnia is more common among subjects living in damp buildings.2005In: Occup Environ Med, ISSN 1470-7926, Vol. 62, no 2, p. 113-8Article in journal (Refereed)
  • 124. Janssen, Nicole
    et al.
    Meliefste, Kees
    Fuchs, Oliver
    Weiland, Stephan K
    Cassee, Flemming
    Brunekreef, Bert
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    High and low volume sampling of paticulate matter at sites with different traffic profiles in the Netherlands and Germany: Results from the HEPMEAP study2008In: Atmospheric Environment, ISSN 1352-2310, E-ISSN 1873-2844, Vol. 42, no 6, p. 1110-1120Article in journal (Refereed)
  • 125.
    Jansson, Sven-Arne
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ericsson, Asa
    Borg, Sixten
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Andersson, Fredrik
    Lundbäck, Bo
    Cost differences for COPD with and without physician-diagnosis.2005In: COPD, ISSN 1541-2555, Vol. 2, no 4, p. 427-34Article in journal (Refereed)
    Abstract [en]

    Previous studies have presented divergent estimates of the cost of illness of COPD due to differences in methodology. The objective of this study was to examine differences between register-based estimates versus population-based estimates on the burden of COPD. This study therefore examined differences in costs of COPD among physician-diagnosed and un-diagnosed subjects. During a one-year period, four telephone interviews were made with 212 randomly selected subjects with COPD derived from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Health care resource utilization and productivity losses were measured, and the costs were also transformed with the estimated COPD prevalence in Sweden. Average annual costs were SEK 18,252 (USD 2,207, EUR 2,072), and SEK 9,327 (USD 1,128, EUR 1,059) for subjects with and without a physician-diagnosis, respectively. Although lower per individual, the costs of undiagnosed subjects accounted for approximately 40% of the total costs in Sweden, since the majority of subjects with COPD in Sweden lack a physician-diagnosed disease. In conclusion, we found that the costs due to COPD differed considerably between those with and without physician-diagnosed disease. This study indicates that register-based studies result in underestimated costs of COPD.

  • 126. Jerning, Camilla
    et al.
    Martinander, Emma
    Bjerg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ekerljung, Linda
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Larsson, Kjell
    Malinovschi, Andrei
    Middelveld, Roelinde
    Emtner, Margareta
    Janson, Christer
    Asthma and physical activity: a population based study results from the Swedish GA(2)LEN survey2013In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 107, no 11, p. 1651-1658Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Having asthma has in previous reports been related to a lower physical activity level. At the same time the prevalence of asthma among elite athletes is high. The aim of this study was to investigate the association between physical activity level and asthma.

    METHODS: A postal questionnaire was completed by 25,610 individuals in Sweden. Current asthma was defined as having had an asthma attack during the last 12 months or current use of asthma medication. The participants were asked how often and for how many hours a week they were physically active.

    RESULTS: In the population 1830 subjects (7.1%) had current asthma. There was no significant difference in the proportion of subjects that reported being inactive or slightly physically active between asthmatic and non-asthmatics (57 vs. 58%) while the proportion of subjects that were vigorously physically active (≥2 times a week and ≥7 h per week) was higher among the subjects with asthma (6.7 vs. 4.8%, p < 0.0001). Being vigorously physically active was independently related to current asthma (OR (95% CI)) 1.40 (1.11-1.77)), wheeze (1.39 (1.17-1.65)), wheeze and breathlessness (1.68 (1.38-2.04)), and wheezing without having a cold (1.39 (1.13-1.71)). The association between being vigorously physically active and wheeze was significantly stronger in women compared to men.

    CONCLUSIONS: There was no difference in the proportion of subjects with a reported low level of physical activity between asthmatics and non-asthmatics. Health care professionals should, however, be aware of the increased prevalence of asthma and asthma-related symptoms in vigorously physically active subjects.

  • 127. Jonasson, S.
    et al.
    Koch, B.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Inhalation of chlorine causes long-standing lung inflammation and airway hyperresponsiveness in a murine model of chemical-induced lung injury2013In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 303, p. 34-42Article in journal (Refereed)
    Abstract [en]

    Chlorine is highly irritating when inhaled, and is a common toxic industrial gas causing tissue damage in the airways followed by an acute inflammatory response. In this study, we investigated mechanisms by which chlorine exposure may cause reactive airways dysfunction syndrome (RADS) and we examined the dose-dependency of the development of symptoms. Mice were exposed to 50 or 200ppm Cl2 during a single 15min exposure in a nose-only container. The experiment terminated 2, 6, 12, 24, 48, 72h and 7, 14, 28 and 90 days post exposure. Inflammatory cell counts in bronchoalveolar lavage (BAL), secretion of inflammatory mediators in BAL, occurrence of lung edema and histopathological changes in lung tissue was analyzed at each time-point. Airway hyperresponsiveness (AHR) was studied after 24 and 48h and 7, 14, 28 and 90 days. The results showed a marked acute response at 6h (50ppm) and 12h (200ppm) post exposure as indicated by induced lung edema, increased airway reactivity in both central and peripheral airways, and an airway inflammation dominated by macrophages and neutrophils. The inflammatory response declined rapidly in airways, being normalized after 48h, but inflammatory cells were sustained in lung tissue for at least seven days. In addition, a sustained AHR was observed for at least 28 days. In summary, this mouse model of chlorine exposure shows delayed symptoms of hyperreactive airways similar to human RADS. We conclude that the model can be used for studies aimed at improved understanding of adverse long-term responses following inhalation of chlorine.

  • 128. Jonasson, Sofia
    et al.
    Gustafsson, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Koch, Bo
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Inhalation exposure of nano-scaled titanium dioxide (TiO2) particles alters the inflammatory responses in asthmatic mice2013In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 25, no 4, p. 179-191Article in journal (Refereed)
    Abstract [en]

    Context: Titanium dioxide (TiO2) nanoparticles (NPs) are regarded as relatively non-toxic in concentrations occurring in occupational environments. Nevertheless, it is conceivable that adverse health effects may develop in sensitive populations such as individuals with respiratory diseases.

    Objective: We investigated whether single or repeated exposure to TiO2 could aggravate inflammatory responses in naive mice and mice with ovalbumin (OVA)-induced airway inflammation.

    Methods: Exposure to aerosolized TiO2 was performed during OVA sensitization, before, or during the OVA challenge period. The effects on respiratory physiology, inflammatory cells in bronchoalveolar lavage (BAL) and inflammatory mediators in BAL and serum were assessed 24 h after the last OVA challenge or TiO2 exposure.

    Results: A single exposure of TiO2 had a marked effect on responses in peripheral airways and increasing infiltration of neutrophils in airways of naive animals. Marked aggravation of airway responses was also observed in animals with allergic disease provided that the single dose TiO2 was given before allergen challenge. Repeated exposures to TiO2 during sensitization diminished the OVA-induced airway eosinophilia and airway hyperresponsiveness but concomitant exposure to TiO2 during the OVA challenge period resulted in neutrophilic airway inflammation and a decline in general health condition as indicated by the loss of body weight.

    Conclusion: We conclude that inhalation of TiO2 may aggravate respiratory diseases and that the adverse health effects are highly dependent on dose and timing of exposure. Our data imply that inhalation of NPs may increase the risk for individuals with allergic airway disease to develop symptoms of severe asthma.

  • 129. Jonasson, Sofia
    et al.
    Wigenstam, Elisabeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Koch, Bo
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. FOI.
    Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids2013In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 271, no 2, p. 168-174Article in journal (Refereed)
  • 130. Jäger, Linda
    et al.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Midgren, Bengt
    Löfdahl, Kerstin
    Ström, Kerstin
    Increased survival with mechanical ventilation in post-tuberculosis patients with the combination of respiratory failure and chest wall deformity.2007In: Chest, ISSN 0012-3692Article in journal (Refereed)
  • 131.
    Karl, Franklin
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    S, Axelsson
    N, Rehnqvist
    M, Rosén
    Adekvata studier möjliga men sällsynta2007In: Läkartidningen, Vol. 23, p. 1835-Article in journal (Other academic)
  • 132. Kelly, F J
    et al.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Air pollution, oxidative stress, and allergic response2004In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 363, no 9403, p. 95-96Article in journal (Refereed)
  • 133.
    Kesek, Milos
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindberg, Eva
    Heart rate variability during sleep and sleep apnoea in a population based study of 387 women2009In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 29, no 4, p. 309-315Article in journal (Refereed)
    Abstract [en]

    Increased sympathetic activity during sleep has been suggested as a link between obstructive sleep apnoea syndrome and cardiovascular disease. Heart rate variability (HRV) is a measure of autonomic effect on the heart. Different parameters have been associated with sympathetic and parasympathetic activity. We have studied HRV in different sleep stages and related the HRV-pattern to sleep apnoea in a population-based sample of 387 women. We investigated the HRV-parameters standard deviation of all R-R intervals (SDNN), root of the averaged square of successive differences (RMSSD), low frequency component (LF), high frequency component (HF), ratio of low frequency component to high frequency component LF/HF and VSAI [variation in sympathetic activity between rapid eye movement (REM) and slow wave sleep, defined as LF(REM)-LF(SWS)]. The HRV-parameters were compared with the results of a full-night polysomnography. Hourly incidence of obstructive episodes was used for classifying the subjects into four apnoea-hypopnoea index (AHI)-groups (<5, > or =5 and <15, 15-30 and >30 events). Individual sleep stages were analysed by pooling all recordings. Women with high AHI had higher heart rate and LF/HF ratio. In subjects with AHI >30, LF/HF ratio however dropped to same level as with AHI <5. Subjects with high AHI had low VSAI. Levels of SDNN, LF and LF/HF ratio during REM and light sleep were similar to wakefulness. In slow wave sleep the parameters decreased. In conclusion, moderately increased prevalence of obstructive apnoeas was associated with signs of higher sympathetic activity. High AHI was however associated with a HRV-pattern suggestive of depressed sympathetic drive and lowered ability to increase it during REM.

  • 134. Kilinç, E
    et al.
    Van Oerle, R
    Borissoff, J I
    Oschatz, C
    Gerlofs-Nijland, M E
    Janssen, N A
    Cassee, F R
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Renné, T
    Ten Cate, H
    Spronk, H M H
    Factor XII activation is essential to sustain the procoagulant effects of particulate matter2011In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 9, no 7, p. 1359-1367Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Particulate matter (PM) is a key component of ambient air pollution and has been associated with an increased risk of thrombotic events and mortality. The underlying mechanisms remain unclear.

    OBJECTIVES:  To study the mechanisms of PM-driven procoagulant activity in human plasma and to investigate mainly, the coagulation driven by ultrafine particles (UFPs; < 0.1 μm) in genetically modified mice.

    METHODS: Thrombin generation in response to PM of different sizes was assessed in normal human platelet-poor plasma, as well as in plasmas deficient in the intrinsic pathway proteases factors XII (FXII) or XI (FXI). In addition, UFPs were intratracheally instilled in wild-type (WT) and FXII-deficient (FXII(-/-) ) mice and plasma thrombin generation was analyzed in plasma from treated mice at 4 and 20 h post-exposure.

    RESULTS: In normal human plasma, thrombin generation was enhanced in the presence of PM, whereas PM-driven thrombin formation was completely abolished in FXII- and FXI-deficient plasma. UFPs induced a transient increase in tissue factor (TF)-driven thrombin formation at 4 h post-instillation in WT mice compared with saline instillation. Intratracheal instillation of UFPs resulted in a procoagulant response in WT mice plasma at 20 h, whereas it was entirely suppressed in FXII(-/-) mice.

    CONCLUSIONS:  Overall, the data suggest that PM promotes its early procoagulant actions mostly through the TF-driven extrinsic pathway of coagulation, whereas PM-driven long lasting thrombogenic effects are predominantly mediated via formation of activated FXII. Hence, FXII-driven thrombin formation may be relevant to an enhanced thrombotic susceptibility upon chronic exposure to PM in humans.

  • 135. Kumar, Abhinav
    et al.
    Bicer, Elif Melis
    Pfeffer, Paul
    Monopoli, Marco P.
    Dawson, Kenneth A.
    Eriksson, Jonny
    Edwards, Katarina
    Lynham, Steven
    Arno, Matthew
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Somers, Graham
    Hassall, Dave
    Dailey, Lea Ann
    Forbes, Ben
    Mudway, Ian
    Differences in the coronal proteome acquired by particles depositing in the lungs of asthmatic versus healthy humans2017In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 13, no 8, p. 2517-2521Article in journal (Refereed)
    Abstract [en]

    Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLFs). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines. The asthmatic coronal proteome displayed a reduced contribution of surfactant proteins (SP-A and B) and a higher contribution of alpha 1-antitrypsin. Pathway analysis suggested that asthmatic RTLFs may also be deficient in proteins related to metal handling (e.g. lactoferrin). This study demonstrates how the composition of the corona acquired by inhaled nanoparticles is modified in asthma and suggests depressed mucosal immunity even in mild airway disease.

  • 136. Laerum, B N
    et al.
    Svanes, C
    Gulsvik, A
    Iversen, M
    Thorarinsdottir, H R
    Gislason, T
    Jogi, R
    Norrman, Eva
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Gunnbjörnsdottir, M
    Wentzel-Larsen, T
    Janson, C
    Omenaas, E
    Is birth weight related to lung function and asthma symptoms in Nordic-Baltic adults?2004In: Respiratory medicine, ISSN 0954-6111, Vol. 98, no 7, p. 611-8Article in journal (Refereed)
  • 137. Laerum, B N
    et al.
    Svanes, C
    Wentzel-Larsen, T
    Gulsvik, A
    Iversen, M
    Gislason, T
    Jogi, R
    Norrman, Eva
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Janson, C
    Omenaas, E
    The association between birth size and atopy in young North-European adults.2005In: Clin Exp Allergy, ISSN 0954-7894, Vol. 35, no 8, p. 1022-7Article in journal (Refereed)
  • 138. Laerum, Birger N
    et al.
    Svanes, Cecilie
    Wentzel-Larsen, Tore
    Gulsvik, Amund
    Torén, Kjell
    Norrman, Eva
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Gíslason, Thorarinn
    Janson, Christer
    Omenaas, Ernst
    Young maternal age at delivery is associated with asthma in adult offspring.2007In: Respir Med, ISSN 0954-6111, Vol. 101, no 7, p. 1431-8Article in journal (Refereed)
  • 139.
    Lagerkvist, Birgitta Json
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Bernard, Alfred
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Bergström, Erik
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Holmstrom, Karin
    Karp, Kjell
    Lundstrom, Nils-Goran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Segerstedt, Bo
    Svensson, Mona
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Nordberg, Gunnar
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Pulmonary epithelial integrity in children: relationship to ambient ozone exposure and swimming pool attendance.2004In: Environ Health Perspect, ISSN 0091-6765, Vol. 112, no 17, p. 1768-71Article in journal (Refereed)
  • 140. Langrish, J. P.
    et al.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Muala, Ala
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, D. E.
    Mills, N. L.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 3, p. 224-239Article, review/survey (Refereed)
    Abstract [en]

    Objective Air pollution is now recognized as an important independent risk factor for cardiovascular morbidity and mortality and may be responsible for up to 3 similar to million premature deaths each year worldwide. The mechanisms underlying the observed effects are poorly understood but are likely to be multifactorial. Here, we review the acute and chronic effects of air pollution exposure on the cardiovascular system and discuss how these effects may explain the observed increases in cardiovascular morbidity and mortality.

  • 141.
    Langrish, Jeremy
    et al.
    Centre for Cardiovascular Sciences, University of Edinburgh, United Kingdom.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mills, Nicholas L
    Centre for Cardiovascular Sciences, University of Edinburgh, United Kingdom.
    Newby, David
    Centre for Cardiovascular Sciences, University of Edinburgh, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Exposure to nitrogen dioxide is not associated with vascular dysfunction in man2010In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 3, p. 192-198Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to air pollution is associated with increased cardiorespiratory morbidity and mortality. It is unclear whether these effects are mediated through combustion-derived particulate matter or gaseous components, such as nitrogen dioxide.

    Objectives: To investigate the effect of nitrogen dioxide exposure on vascular vasomotor and six fibrinolytic functions.

    Methods: Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered air for 1 h during intermittent exercise in a randomized double-blind crossover study. Bilateral forearm blood flow and fibrinolytic markers were measured before and during unilateral intrabrachial infusion of bradykinin (100–1000 pmol/min), acetylcholine (5–20 μg/min), sodium nitroprusside (2–8 μg/min), and verapamil (10–100 μg/min) 4 h after the exposure. Lung function was determined before and after the exposure, and exhaled nitric oxide at baseline and 1 and 4 h after the exposure.

    Results: There were no differences in resting forearm blood flow after either exposure. There was a dose-dependent increase in forearm blood flow with all vasodilators but this was similar after either exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose-dependent increase in plasma tissue-plasminogen activator, but again there was no difference between the exposures. There were no changes in lung function or exhaled nitric oxide following either exposure.

    Conclusion: Inhalation of nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function. Nitrogen dioxide does not appear to be a major arbiter of the adverse cardiovascular effects of air pollution.

  • 142. Langrish, Jeremy
    et al.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas
    Johnston, Neil
    Webb, David
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Contribution of endothelin-1 to the vascular effects of diesel exhaust inhalation in humans2009In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 54, no 4, p. 910-915Article in journal (Refereed)
    Abstract [en]

    Diesel exhaust inhalation impairs vascular function, and, althoughthe underlying mechanism remains unclear, endothelin (ET) 1and NO are potential mediators. The aim of this study was toidentify whether diesel exhaust inhalation affects the vascularactions of ET-1 in humans. In a randomized, double-blind crossoverstudy, 13 healthy male volunteers were exposed to either filteredair or dilute diesel exhaust (331±13 µg/m3). Plasmaconcentrations of ET-1 and big-ET-1 were determined at baselineand throughout the 24-hour study period. Bilateral forearm bloodflow was measured 2 hours after the exposure during infusionof either ET-1 (5 pmol/min) or the ETA receptor antagonist,BQ-123 (10 nmol/min) alone and in combination with the ETB receptorantagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure hadno effect on plasma ET-1 and big-ET-1 concentrations (P>0.05for both) or 24-hour mean blood pressure or heart rate (P>0.05for all). ET-1 infusion increased plasma ET-1 concentrationsby 58% (P<0.01) but caused vasoconstriction only after dieselexhaust exposure (–17% versus 2% after air; P<0.001).In contrast, diesel exhaust exposure reduced vasodilatationto isolated BQ-123 infusion (20% versus 59% after air; P<0.001)but had no effect on vasodilatation to combined BQ-123 and BQ-788administration (P>0.05). Diesel exhaust inhalation increasesvascular sensitivity to ET-1 and reduces vasodilatation to ETAreceptor antagonism despite unchanged plasma ET-1 concentrations.Given the tonic interaction between the ET and NO systems, weconclude that diesel exhaust inhalation alters vascular reactivityto ET-1 probably through its effects on NO bioavailability.

  • 143. Langrish, Jeremy P.
    et al.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E.
    Mills, Nicholas L.
    Atmospheric Interactions and Cardiac Arrhythmias: Langrish et al. espond2015In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 123, no 6, p. A144-A145Article in journal (Refereed)
  • 144. Langrish, Jeremy P
    et al.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Muala, Ala
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blackwell, Scott
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Megson, Ian L
    Treweeke, Andrew
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man2013In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, no 1, p. e004309-Article in journal (Refereed)
    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.

  • 145.
    Langrish, Jeremy P.
    et al.
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Watts, Simon J.
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Hunter, Amanda J.
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Shah, Anoop S. V.
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Bosson, Jenny A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cassee, Flemming R.
    National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands .
    Donaldson, Ken
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E.
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Mills, Nicholas L.
    University of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom.
    Controlled exposures to air pollutants and risk of cardiac arrhythmia2014In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, no 7, p. 747-753Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups. OBJECTIVES: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease. METHODS: We analyzed data from 13 double-blind randomized crossover studies including 282 participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was recorded for each exposure and study population. RESULTS: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles, or high ambient levels of air pollution in either healthy volunteers or patients with coronary heart disease. CONCLUSIONS: Acute controlled exposure to air pollutants did not increase the short-term risk of arrhythmia in participants. Research employing these techniques remains crucial in identifying the important pathophysiological pathways involved in the adverse effects of air pollution, and is vital to inform environmental and public health policy decisions.

  • 146.
    Larsson, B-M
    et al.
    Dept of Public Health Sciences, Division of Occupational Medicine, Karolinska institutet, Stockholm.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Grunewald, J
    Dept of Medicine, Division of Respiratory Medicine, Karolinska Institutet, Stockholm.
    Sköld, C M
    Dept of Medicine, Division of Respiratory Medicine, Karolinska Institutet, Stockholm.
    Lundin, A
    Dept of Occupational and Environmental Health, Stockholm Centre for Public Health, Stockholm County Council, Stockholm.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Eklund, A
    Dept of Medicine, Division of Respiratory Medicine, Karolinska Institutet, Stockholm.
    Svartengren, M
    Dept of Public Health Sciences, Division of Occupational Medicine, Karolinska institutet, Stockholm.
    Road tunnel air pollution induces bronchoalveolar inflammation in healthy subjects2007In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 29, no 4, p. 699-705Article in journal (Refereed)
    Abstract [en]

    Traffic-related air pollution is associated with adverse respiratory effects. The aim of the present study was to investigate whether exposure to air pollution in a road tunnel causes airway inflammatory and blood coagulation responses.

    A total of 16 healthy subjects underwent bronchoscopy with bronchial mucosal biopsies and bronchoalveolar lavage (BAL) on two occasions, in random order: once at 14 h after a 2-h exposure to air pollution in a busy road tunnel, and once after a control day with subjects exposed to urban air during normal activities. Peripheral blood was sampled prior to bronchoscopy.

    The road tunnel exposures included particulate matter with a 50% cut-off aerodynamic diameter of 2.5 μm, particulate matter with a 50% cut-off aerodynamic diameter of 10 μm and nitrogen dioxide which had median concentrations of 64, 176 and 230 µg·m−3, respectively. Significantly higher numbers of BAL fluid total cell number, lymphocytes and alveolar macrophages were present after road tunnel exposure versus control. Significantly higher nuclear expression of the transcription factor component c-Jun was found in the bronchial epithelium after exposure. No upregulation of adhesion molecules or cellular infiltration was present and blood coagulation factors were unaffected.

    In conclusion, exposure of healthy subjects to traffic-related air pollution resulted in a lower airway inflammatory response with cell migration, together with signs of an initiated signal transduction in the bronchial epithelium.

  • 147. Larsson, Britt-Marie
    et al.
    Grunewald, Johan
    Sköld, C Magnus
    Lundin, Anders
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Eklund, Anders
    Svartengren, Magnus
    Limited airway effects in mild asthmatics after exposure to air pollution in a road tunnel2010In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 104, no 12, p. 1912-1918Article in journal (Refereed)
    Abstract [en]

    Ambient air pollution is a contributing factor to respiratory morbidity and mortality and asthmatics are a particularly vulnerable population. The aim of the study was to investigate whether acute exposure to traffic related air pollution in a road tunnel would increase bronchial responsiveness in mild asthmatics, and if this would be accompanied by increased measures of inflammatory markers in the airways assessed by nasal lavage (NAL) and induced sputum. Fourteen mild asthmatics (7 treated with inhaled corticosteroids) were exposed for 2 h in a road tunnel and a control environment, respectively, separated by at least 3 weeks. Symptoms and peak expiratory flow (PEF) were recorded. Seven hours following exposure sessions, subjects underwent measurements of fraction of exhaled nitric oxide (FENO), spirometry, and a bronchial provocation test. NAL, induced sputum and blood samples were collected. The median PM(2.5) and PM(10) levels during the exposure occasions in the road tunnel were 80 (range 41-93) μg/m(3) and 183 (72-213) μg/m(3) respectively. Irritative symptoms from the airways increased and PEF decreased after road tunnel exposure. Increased levels of IL-10, IL-12 and TNF-α were observed in NAL fluid from subjects without ongoing inhaled corticosteroid treatment. Forced expiratory volume in 1 s (FEV(1)) and the degree of bronchial responsiveness in asthmatics did not change significantly after tunnel exposure. We conclude that asthmatics exhibit increased symptoms, decreased PEF and signs of inflammatory response in the upper airways, after a 2 h road tunnel exposure. Our findings may further emphasize asthmatics as a vulnerable group to common air pollutants.

  • 148. Larsson, Kjell
    et al.
    Löfdahl, Claes-Göran
    Lindén, Anders
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Johansson, Gunnar S
    Så blir KOL-vården bättre2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 35, p. 1604-1605Article in journal (Refereed)
  • 149.
    Larsson, Nirina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Allergic airway disease: studies on diesel exhaust exposures, oxylipins and antioxidants2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Allergic airway disease, i.e. allergic rhinitis (AR) and asthma, is a common health problem. The prevalence is increasing in most countries of the world. Traffic-related air pollution has been found to induce and enhance allergic airway disease, but the underlying mechanisms are not known.

    Oxylipins are fatty acid metabolites, of which several have been linked to asthmatic airway inflammation. Oxylipin profiles have previously been investigated in bronchoalveolar lavage (BAL), mainly reflecting the peripheral lung, but not in bronchial wash (BW), which better reflect the proximal airways.

    The airway epithelium is covered by a respiratory tract lining fluid (RTLF) The RTLF contains antioxidants to protect from oxidative stress, which may be caused by exposure to air pollution. Previous studies have reported diminished levels of the antioxidant ascorbate (vitamin C) in the RTLF of patients with asthma. Little is known about the regulation of vitamin C in the lung.

    The aim of this thesis was to investigate airway inflammatory responses to diesel exhaust exposure in patients with AR and allergic asthma; to evaluate oxylipin profiles in different regions of the lung in patients with allergic asthma; and to study the distribution of vitamin C transporters in the airways of patients with allergic asthma.

    Diesel exhaust (PM10 100 μg/m3 for 2 h) induced a neutrophilic airway inflammation in healthy individuals evaluated 18 h after exposure. Patients with AR and asthma did not respond with an enhanced airway inflammation. However, a small increase in myeloperoxidase was found in BAL from patients with AR, as well as decreases in epithelial tryptase and BW stem cell factor. This indicates that other mechanisms than classical inflammation are responsible for the increased sensitivity to traffic-related air pollution in patients with allergic airway disease.

    Oxylipin baseline profiles differed between peripheral and proximal airways in both allergic asthmatics and healthy individuals. Total oxylipin concentrations, and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway, were elevated in BW from asthmatics compared to healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. This suggests that lung compartment-specific sampling should be considered in future studies.

    Sodium dependent vitamin C transporter 2 (SVCT2) was, for the first time, found present in the human lung epithelium, localised mainly within goblet cells. A negative correlation between SVCT2+ goblet cells and vitamin C suggests that these cells may play a hitherto unknown function in ascorbate re-uptake and recycling at the air-lung interface.

  • 150.
    Larsson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brown, Joanna
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan
    Mudway, Ian S
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Airway inflammatory responses to diesel exhaust in allergic rhinitics2013In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 25, no 3, p. 160-167Article in journal (Refereed)
    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.

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