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  • 251.
    Sahlin, Carin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Svanborg, Eva
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cheyne-Stokes respiration and supine dependency2005In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 25, no 5, p. 829-33Article in journal (Refereed)
  • 252. Salomonsson, A.
    et al.
    Patthey, Annika
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Reuterswärd, C.
    Jönsson, M.
    Botling, J.
    Brunnström, H.
    Hussein, A.
    Monsef, N.
    Ortiz-Villalon, C.
    Bergman, B.
    De Petris, L.
    Lamberg, K.
    Vikström, A.
    Wagenius, G.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brandén, E.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koyi, H.
    Staaf, J.
    Planck, M.
    A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 10, p. S431-S432Article in journal (Other academic)
    Abstract [en]

    Background: Smoking is by far the most important cause of lung cancer. However, lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. Therefore, as 1st project within the Swedish Molecular Initiative against Lung cancer (SMIL) we aim to characterize never-smoking lung cancer for etiological, diagnostic and therapeutic purposes.

    Method: Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site (n=6), clinical data were reviewed by a thoracic oncologist/pulmonologist through patients' medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As a first pre-planned analysis, we performed fusion gene mapping using an RNA-based NanoString nCounter Elements assay, as previously described [4].

    Result: In the first 212 (out of 540) analyzed samples, we detected 17 fusions involving ALK, 8 involving RET, and 2 involving NRG1. In addition, MET exon 14 skipping was found in 17 samples. In total, these findings involved 21% of analyzed cases. Additional results from further studies on the cohort will be presented.

    Conclusion: SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently collect one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, druggable oncogenic fusions are frequent.

  • 253. Salvi, Sundeep S.
    et al.
    Nordenhäll, Charlotta
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rudell, Bertil
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J.
    Wilson, Susan
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Holgate, Stephen T.
    Frew, Anthony J.
    Acute exposure to diesel exhaust increases IL-8 and Gro-alpha production in healthy human airways2000In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 161, no 2, p. 550-557Article in journal (Refereed)
  • 254.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Effects of pharmacological and non-pharmacological interventions.2010In: The clinical respiratory journal, ISSN 1752-699X, Vol. 4 Suppl 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma is recognised as a condition with variable airway obstruction with pathophysiological features that include activation of a wide range of inflammatory and structural cells. Additionally, structural changes in the airways have been demonstrated. This includes increased thickening of components in the basement membrane region, increased smooth muscle mass, increased vascularisation and many other events that is often referred to as remodelling of the airways. These processes and the underlying mechanisms have attracted considerable attention. METHODS AND RESULTS: This review describes the different interventive approaches that have been tried in order to improve asthma control and affect the underlying pathophysiological pathways. These include elimination of harmful environmental and occupational exposures, a wide range of pharmacological agents as well as bronchial thermoplasty. The existing evidence for effects on airway inflammation and airway remodelling is discussed in relationship to mechanistic aspects and short- and long-term outcome. CONCLUSION: It is expected that modulation of the asthmatic airway remodelling will become an even more important endpoint in the near future.

  • 255.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Omalizumab in the management of patients with allergic (IgE-mediated) asthma2009In: Journal of asthma and allergy, ISSN 1178-6965, Vol. 2, p. 49-62Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin E (IgE) is central to the pathophysiology of allergic asthma. Omalizumab, an anti-IgE monoclonal antibody, binds to the FcɛRI binding site on free IgE. As a result, circulating free IgE is reduced, IgE is prevented from attaching to mast cells and basophils, and FcɛRI receptor expression is down-regulated. The inflammatory response to allergens and the acute and chronic effector phases of allergic inflammation are thereby attenuated. In clinical trials in adults and adolescents, omalizumab reduced asthma exacerbations, severe asthma exacerbations, inhaled corticosteroid requirements, and emergency visits, as well as significantly improving asthma-related quality of life, morning peak expiratory flow and asthma symptom scores in patients with severe allergic (IgE-mediated) asthma. Results from clinical trials in children (<12 years) are consistent with those in the adult population. It is difficult to predict which patients will respond to omalizumab. Responders to omalizumab should be identified after a 16-week trial of therapy using the physician's overall assessment. When treatment is targeted to these responders, omalizumab provides a cost-effective therapy for inadequately controlled severe allergic (IgE-mediated) asthma. Long-term therapy with omalizumab shows the potential for disease-modification in asthma. Ongoing studies are also evaluating the use of omalizumab in other non-asthma IgE-mediated conditions.

  • 256.
    Sandström, Thomas
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Brunekreef, Bert
    Traffic-related pollution and lung development in children.2007In: Lancet, ISSN 1474-547X, Vol. 369, no 9561, p. 535-7Article in journal (Refereed)
  • 257.
    Sandström, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Desert dust: an unrecognized source of dangerous air pollution?2008In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 19, no 6, p. 808-809Article in journal (Refereed)
    Abstract [en]

    ABSTRACT:: Particulate matter (PM10) air pollution is associated with respiratory and cardiovascular morbidity, and mortality. A recent systematic review pointed toward the fine particle fraction (PM2.5) rather than the coarse fraction (PM2.5-10) 2.5 and PM2.5-10as being responsible for increased death rates. With this background, the report by Perez et al that windblown Saharan desert dust causes increased mortality in Barcelona, raises concern over possible underestimation of toxicity from coarse particles coming from desert sources. This may be of concern for large areas of the globe that periodically encounter high levels of windblown desert dust and warrants further attention.

  • 258.
    Sandström, Thomas
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Hedlin, Gunilla
    [Anti-IgE blocks central asthmatic mechanism]2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 26-27, p. 1933-4Article in journal (Refereed)
  • 259.
    Sandström, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J
    Traffic-related air pollution, genetics and asthma development in children.2009Other (Other (popular science, discussion, etc.))
  • 260.
    Sandström, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, B
    Tobacco smoke: old foe more important for asthma than commonly appreciated?2004In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 24, no 5, p. 720-721Article in journal (Refereed)
  • 261. Schaufelberger, C
    et al.
    Möllby, H
    Uddhammar, Agneta
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Bratt, J
    Nordborg, E
    No additional steroid-sparing effect of cyclosporine A in giant cell arteritis.2006In: Scand J Rheumatol, ISSN 0300-9742, Vol. 35, no 4, p. 327-9Article in journal (Refereed)
  • 262.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Respiratory effects of particulate matter air pollution: studies on diesel exhaust, road tunnel, subway and wood smoke exposure in human subjects2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background:

    Ambient air pollution is associated with adverse health effects, but the sources and components, which cause these effects is still incompletely understood. The aim of this thesis was to investigate the pulmonary effects of a variety of common air pollutants, including diesel exhaust, biomass smoke, and road tunnel and subway station environments. Healthy non-smoking volunteers were exposed in random order to the specific air pollutants and air/control, during intermittent exercise, followed by bronchoscopy.

    Methods and results:

    In study I, exposures were performed with diesel exhaust (DE) generated at transient engine load and air for 1 hour with bronchoscopy at 6 hours post-exposure. Immunohistochemical analyses of bronchial mucosal biopsies showed that DE exposure significantly increased the endothelial adhesion molecule expression of p-selectin and VCAM-1, together with increased bronchoalveolar lavage (BAL) eosinophils.

    In study II, the subjects were exposed for 1 hour to DE generated during idling with bronchoscopy at 6 hours. The bronchial mucosal biopsies showed significant increases in neutrophils, mast cells and lymphocytes together with bronchial wash neutrophils. Additionally, DE exposure significantly increased the nuclear translocation of the aryl hydrocarbon receptor (AhR) and phosphorylated c-jun in the bronchial epithelium. In contrast, the phase II enzyme NAD(P)H-quinone oxidoreductase 1 (NQO1) decreased after DE.

    In study III, the 2-hour exposures took place in a road tunnel with bronchoscopy 14 hours later. The road tunnel exposure significantly increased the total numbers of lymphocytes and alveolar macrophages in BAL, whereas NK cell and CD56+/T cell numbers significantly decreased. Additionally, the nuclear expression of phosphorylated c-jun in the bronchial epithelium was significantly increased after road tunnel exposure.

    In study IV, the subjects were exposed to metal-rich particulate aerosol for 2 hours at a subway station with bronchial biopsy and BAL sampling at 14 hours. The subway exposure significantly increased the concentration of glutathione disulphide (GSSG) in BAL, with no airway inflammatory responses. In contrast, the number of neutrophils in the bronchial mucosa and the nuclear expression of phosphorylated c-jun in the bronchial epithelium tended to decrease after the subway exposure.

    In study V, the exposure to biomass smoke lasted 3 hours. Bronchoscopy was conducted 24 hours post exposure. The investigated biomass combustion emissions resulted in a significant increase in total glutathione and reduced glutathione in BAL, without any evident acute airway inflammatory responses.

     

     

    Conclusion:

    The present thesis presents data from exposures of healthy subjects to a variety of common air pollutants, as compared with an air reference. Oxidative as well as bronchial mucosal and bronchoalveolar responses differed between these air pollutants, with the most pronounced airway effects seen after exposure to diesel exhaust. This may be due to differences in pulmonary deposition, physicochemical characteristics, toxicological pathways and potency. Additional studies will assist in addressing dose-response and time kinetic aspects of the airway responses.

  • 263.
    Sehlstedt, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Andersen, Grethe Neumann
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Nilsson, Kenneth
    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.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Suppressed signal transduction in the bronchial epithelium of patients with systemic sclerosis2009In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 103, no 2, p. 301-308Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder, which frequently affects the lungs, with manifestations of interstitial lung disease (ILD) with lung fibrosis and of pulmonary hypertension. The pathogenesis remains largely unrecognised.

    OBJECTIVE: The aim of this study was to elucidate the inflammation in the bronchial mucosa in patients with SSc.

    SUBJECTS AND METHODS: Twenty-three subjects diagnosed with SSc participated. Twelve of the SSc patients showed signs of ILD, four were smokers and seven were treated with oral corticosteroids. Seventeen non-smoking, age- and sex-matched healthy subjects served as controls. Bronchoscopy was performed to sample endobronchial mucosal biopsies, which were immunohistochemically stained using a panel of antibodies against inflammatory markers.

    RESULTS: The number of neutrophils was significantly elevated in the submucosa of SSc patients, regardless of ILD, or whether the subject was smoking or using oral corticosteroids. No up-regulation of neutrophil chemoattractants or cytokines was seen in the bronchial epithelium. The signal transduction pathways and adhesion molecule expression tended to be suppressed or unchanged in SSc patients compared with controls.

    CONCLUSION: It is concluded that SSc is associated with a chronic neutrophilic inflammation in the bronchial mucosal, with signs of suppressed signal transduction, regardless of the presence of interstitial lung disease.

  • 264.
    Sehlstedt, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Airway inflammatory response to diesel exhaust generated at urban cycle running conditions2010In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 14, p. 1144-1150Article in journal (Refereed)
    Abstract [en]

    DE generated under urban running conditions increased bronchial adhesion molecule expressions, together with the novel finding of bronchoalveolar eosinophilia, which has not been shown after exposure to DE at idling. Variations in airway inflammatory response to DE generated under diverse running condition may be related to differences in exhaust composition.

  • 265.
    Sehlstedt, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie
    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.
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Diesel exhaust exposure increases nuclear translocation of AhR and supresses the detoxification enzyme NQO1 in human airwaysManuscript (preprint) (Other academic)
  • 266.
    Sehlstedt, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Dove, Rosamund
    Kings College London, MRC-HPA Centre for Environment and Health, School of Biomedical and Healthy Studies, King's College London, London, UK .
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Pagels, Joakim
    Division of Aerosol Technology, Lund University, Lund, Sweden .
    Swietlicki, Erik
    Department of Physics, Lund University, Lund, Sweden .
    Löndahl, Jakob
    Department of Physics, Lund University, Lund, Sweden .
    Westerholm, Roger
    Department of Analytical Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden .
    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.
    Behndig, Annelie F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    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.
    Mudway, Ian S
    Kings College London, MRC-HPA Centre for Environment and Health, School of Biomedical and Healthy Studies, King's College London, London, UK.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Antioxidant airway responses following experimental exposure to wood smoke in man2010In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 7, p. 21-Article in journal (Refereed)
    Abstract [en]

    Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure.

  • 267.
    Sehlstedt, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Klepczynska-Nyström, Anna
    Larsson, Britt-Marie
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Dove, Rosamund
    Eklund, Anders
    Grunewald, Johan
    Pourazar, Jamshid
    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.
    Mudway, Ian
    Svartengren, Magnus
    Short-term exposure to a train-derived metal rich particulate aerosol in a subway microenvironment induces oxidative stress in the distal airwaysManuscript (preprint) (Other academic)
  • 268. Shaw, Dominick E.
    et al.
    Sousa, Ana R.
    Fowler, Stephen J.
    Fleming, Louise J.
    Roberts, Graham
    Corfield, Julie
    Pandis, Ioannis
    Bansal, Aruna T.
    Bel, Elisabeth H.
    Auffray, Charles
    Compton, Chris H.
    Bisgaard, Hans
    Bucchioni, Enrica
    Caruso, Massimo
    Chanez, Pascal
    Dahlen, Barbro
    Dahlen, Sven-Erik
    Dyson, Kerry
    Frey, Urs
    Geiser, Thomas
    de Verdier, Maria Gerhardsson
    Gibeon, David
    Guo, Yi-ke
    Hashimoto, Simone
    Hedlin, Gunilla
    Jeyasingham, Elizabeth
    Hekking, Pieter-Paul W.
    Higenbottam, Tim
    Horvath, Ildiko
    Knox, Alan J.
    Krug, Norbert
    Erpenbeck, Veit J.
    Larsson, Lars X.
    Lazarinis, Nikos
    Matthews, John G.
    Middelveld, Roelinde
    Montuschi, Paolo
    Musial, Jacek
    Myles, David
    Pahus, Laurie
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Seibold, Wolfgang
    Singer, Florian
    Strandberg, Karin
    Vestbo, Jorgen
    Vissing, Nadja
    von Garnier, Christophe
    Adcock, Ian M.
    Wagers, Scott
    Rowe, Anthony
    Howarth, Peter
    Wagener, Ariane H.
    Djukanovic, Ratko
    Sterk, Peter J.
    Chung, Kian Fan
    Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort2015In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 46, no 5, p. 1308-1321Article in journal (Refereed)
    Abstract [en]

    U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach. This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements. Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids. Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach.

  • 269. Sigsgaard, Torben
    et al.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Annesi-Maesano, Isabella
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bølling, Anette
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Bønløkke, Jakob
    Brauer, Michael
    Bruce, Nigel
    Héroux, Marie-Eve
    Hirvonen, Maija-Riitta
    Kelly, Frank
    Künzli, Nino
    Lundbäck, Bo
    Moshammer, Hanns
    Noonan, Curtis
    Pagels, Joachim
    Sallsten, Gerd
    Sculier, Jean-Paul
    Brunekreef, Bert
    Health impacts of anthropogenic biomass burning in the developed world2015In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 46, no 6, p. 1577-1588Article in journal (Refereed)
    Abstract [en]

    Climate change policies have stimulated a shift towards renewable energy sources such as biomass. The economic crisis of 2008 has also increased the practice of household biomass burning as it is often cheaper than using oil, gas or electricity for heating. As a result, household biomass combustion is becoming an important source of air pollutants in the European Union. This position paper discusses the contribution of biomass combustion to pollution levels in Europe, and the emerging evidence on the adverse health effects of biomass combustion products. Epidemiological studies in the developed world have documented associations between indoor and outdoor exposure to biomass combustion products and a range of adverse health effects. A conservative estimate of the current contribution of biomass smoke to premature mortality in Europe amounts to at least 40 000 deaths per year. We conclude that emissions from current biomass combustion products negatively affect respiratory and, possibly, cardiovascular health in Europe. Biomass combustion emissions, in contrast to emissions from most other sources of air pollution, are increasing. More needs to be done to further document the health effects of biomass combustion in Europe, and to reduce emissions of harmful biomass combustion products to protect public health.

  • 270.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Self-reported symptoms and bronchial hyperresponsiveness in elite cross-country skiers.2010In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 104, no 11, p. 1760-1763Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Respiratory symptoms in relationship to exercise, bronchial hyperresponsiveness (BHR), and exercise-induced asthma (EIA) are very common in elite winter athletes. Symptom-based screening for BHR would facilitate selection of athletes with possible EIA. OBJECTIVES: The aim of the present study was to evaluate the diagnostic accuracy of self-reported symptoms as predictors of BHR in an unselected population of adult elite cross-country skiers. METHODS: Forty-six Swedish adult skiers competing at national or international level were included. They had a mean (SD) training volume in the past 12 months of 593 (122) hours. Twenty-four subjects had previous physician-diagnosed asthma. The European Community Respiratory Health Survey questionnaire was used to evaluate the presence of respiratory symptoms. BHR was defined as bronchoconstriction to either eucapnic voluntary hyperventilation, dry powder mannitol or methacholine provocation. RESULTS: The "classical" EIA symptom of shortness of breath post-exercise was reported by 17% of all skiers. Eight subjects (17%) had BHR. None of the self-reported respiratory symptoms had high positive predictive values. However, symptoms caused by grass or pollen had high negative predictive values. DISCUSSION: EIA in elite winter athletes cannot accurately be based only on self-reported symptoms but requires verification with objective testing of BHR. Bronchoprovocation of elite winter athletes reporting respiratory symptoms in rest or because of exercise will probably reveal a high proportion of athletes without BHR. CLINICAL TRIAL: EUDRA-CT number 2006-005822-21.

  • 271.
    Stenfors, Nikolai
    et al.
    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.
    Helleday, Ragnberth
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, F J
    Frew, A J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, I S
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ozone exposure enhances mast-cell inflammation in asthmatic airways despite inhaled corticosteroid therapy.2010In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 2, p. 133-139Article in journal (Refereed)
    Abstract [en]

    Asthmatics are recognised to be more susceptible than healthy individuals to adverse health effects caused by exposure to the common air pollutant ozone. Ozone has been reported to induce airway neutrophilia in mild asthmatics, but little is known about how it affects the airways of asthmatic subjects on inhaled corticosteroids. We hypothesised that ozone exposure would exacerbate the pre-existent asthmatic airway inflammation despite regular inhaled corticosteroid treatment. Therefore, we exposed subjects with persistent asthma on inhaled corticosteroid therapy to 0.2 ppm ozone or filtered air for 2 h, on 2 separate occasions. Lung function was evaluated before and immediately after exposure, while bronchoscopy was performed 18 h post exposure. Compared to filtered air, ozone exposure increased airway resistance. Ozone significantly enhanced neutrophil numbers and myeloperoxidase levels in airway lavages, and induced a fourfold increase in bronchial mucosal mast cell numbers. The present findings indicate that ozone worsened asthmatic airway inflammation and offer a possible biological explanation for the epidemiological findings of increased need for rescue medication and hospitalisation in asthmatic people following exposure to ambient ozone.

  • 272.
    Stenfors, Nikolai
    et al.
    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.
    The Prevalence of COPD in Individuals with Acute Coronary Syndrome: A Spirometry-Based Screening Study2015In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563, Vol. 12, no 4, p. 453-461Article in journal (Refereed)
    Abstract [en]

    Background: The prevalence of COPD among individuals with acute coronary syndrome (ACS) is estimated at 5% to 18%, and COPD appears to be a predictor of poor outcome. Diagnosis of COPD has mostly been based on medical records without spirometry. As COPD is largely undiagnosed and misdiagnosed, the prevalence and clinical significance of COPD in the ACS population has not been reliably assessed. The present study aimed to estimate the prevalence of COPD in patients with ACS and evaluate the accuracy of medical record-based COPD diagnoses. Methods: This was a single-centre spirometry screening study for COPD in patients admitted for ACS in the county of Jämtland, Sweden. Patient medical records were reviewed to register previous medical history. Spirometry was performed prior to discharge or at the first follow-up outpatient visit after discharge. COPD was defined as a post-bronchodilator FEV1/FVC of <0.7 or below lower limit of normal. Results: Of 743 eligible patients, 407 performed spirometry. Five percent had COPD according to medical records; 11% and 5% fulfilled spirometric criteria of COPD according to FEV1/FVC of < 0.7 (p = 0.002) and below lower limit of normal definitions, respectively. “COPD according to medical history” had a sensitivity of 23%, specificity of 98%, positive predictive value of 53%, and negative predictive value of 91% compared with spirometric COPD FEV1/FVC of < 0.7 Conclusions: In patients with ACS, COPD is underdiagnosed and misdiagnosed. We raise concerns regarding the validity of medical record-based COPD in evaluating the biological and clinical association between COPD and coronary disease. ­Clinical Trial Registration: ISRCTN number 05697808 (www.controlled-trials.com)

  • 273.
    Stenfors, Nikolai
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nordenhäll, Charlotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Salvi, S S
    Mudway, I
    Söderberg, Margareta
    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.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Levin, Jan-Olof
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holgate, S T
    Kelly, F J
    Frew, A J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel.2004In: Eur Respir J, ISSN 0903-1936, Vol. 23, no 1, p. 82-6Article in journal (Refereed)
  • 274.
    Stenfors, Nikolai
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Krishna, M T
    Mudway, I
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Kelly, F J
    Frew, A J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Effect of ozone on bronchial mucosal inflammation in asthmatic and healthy subjects2002In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no 5, p. 352-358Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies suggestthat asthmatics are more affected by ozone than healthy people. This study tested three hypotheses (1) that short-term exposure to ozone induces inflammatory cell increases and up-regulation of vascular adhesion molecules in airway lavages and bronchial tissue 6 h after ozone exposure in healthy subjects; (2) these responses are exaggerated in subjects with mild allergic asthma; (3) ozone exacerbates pre-existent allergic airways inflammation. We exposed 15 mild asthmatic and 15 healthy subjects to 0.2 ppm of ozone or filtered air for 2 h on two separate occasions. Airway lavages and bronchial biopsies were obtained 6 h post-challenge. We found that ozone induced similar increases in bronchial wash neutrophils in both groups, although the neutrophil increase in the asthmatic group was on top of an elevated baseline. In healthy subjects, ozone exposure increased the expression of the vascular endothelial adhesion molecules P-selectin and ICAM- 1, as well as increasing tissue neutrophil and mast cell numbers. The asthmatics showed allergic airways inflammation at baseline but ozone did not aggravate this at the investigated time point. At 6 h post-ozone-exposure, we found no evidence that mild asthmatics were more responsive than healthy to ozone in terms of exaggerated neutrophil recruitment or exacerbation of pre-existing allergic inflammation. Further work is needed to assess the possibility of a difference in time kinetics between healthy and asthmatic subjects in their response to ozone.

  • 275. Ståhl, Elisabeth
    et al.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Svensson, Klas
    Andersson, Fredrik
    Löfdahl, Claes-Göran
    Lundbäck, Bo
    Health-related quality of life is related to COPD disease severity.2005In: Health and quality of life outcomes, ISSN 1477-7525, Vol. 3, p. 56-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures. METHODS: A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D. The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS. Age, gender, smoking status and socio-economic group were regarded as confounders. RESULTS: The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023). The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032). No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity. Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007). The SGRQ Total score was significant between age groups (p = 0.0047). No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed. CONCLUSION: The results show that HRQL in COPD deteriorates with disease severity and with age. These data show a relationship between HRQL and disease severity obtained by lung function.

  • 276. Subbarao, Padmaja
    et al.
    Duong, Mylinh
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Otis, Joceline
    Obminski, George
    Inman, Mark
    Pedersen, Soren
    O'byrne, Paul M
    Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma.2006In: J Allergy Clin Immunol, ISSN 0091-6749, Vol. 117, no 5, p. 1008-13Article in journal (Refereed)
  • 277. Sundberg, Rosita
    et al.
    Torén, Kjell
    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.
    Gislason, Thorarinn
    Omenaas, Ernst
    Svanes, Cecilie
    Janson, Christer
    Asthma in men and women: Treatment adherence, anxiety, and quality of sleep2010In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 104, no 3, p. 337-344Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare female and male asthmatics with special emphasis on reported adherence, anxiety, and quality of sleep. The study included 470 subjects with current asthma from the Nordic countries, who took part in the European Community Respiratory Health Survey (ECRHS) II. Subjects were investigated with a structured clinical interview, including questions on the presence of respiratory symptoms and therapy. They were also asked to fill in the self-reported Hospital Anxiety Depression scale and the Basic Nordic Sleep Questionnaire. Inhaled corticosteroids (OR=0.55) and a doctor's appointment in the last 12 months (OR=0.54) implied a significantly reduced risk for non-adherence in normal situations. At exacerbation in asthma, women had a significantly decreased risk for non-adherence (OR=0.46). Female gender and anxiety were independent risk factors for both insomnia (OR=3.67 and 2.53, respectively) and daytime sleepiness (OR=2.53 and 2.04, respectively). Women with asthma have a more positive attitude towards their medication, have a higher reported adherence, and use inhaled corticosteroids more often than men. At the same time women report more often anxiety and insomnia than men. Awareness of sex differences in the manifestations and attitudes towards treatment of asthma is important in order to improve asthma management.

  • 278. Sundbom, F
    et al.
    Lindberg, E
    Bjerg, A
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    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.
    Gunnbjörnsdottir, M
    Middelveld, R
    Torén, K
    Janson, C
    Asthma symptoms and nasal congestion as independent risk factors for insomnia in a general population: results from the GA (2) LEN survey2013In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 68, no 2, p. 213-219Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma and rhinitis have been related to insomnia. The aim of this study was to further analyse the association between asthma, nasal symptoms and insomnia and to identify risk factors for sleep disturbance among patients with asthma, in a large population-based set of material.

    METHOD: In 2008, a postal questionnaire was sent to a random sample of 45 000 adults in four Swedish cities. The questionnaire included questions on insomnia, asthma, rhinitis, weight, height, tobacco use and physical activity.

    RESULTS: Twenty-five thousand six hundred and ten subjects participated. Asthma was defined as either current medication for asthma or at least one attack of asthma during the last 12 months, and 1830 subjects (7.15%) were defined as asthmatics. The prevalence of insomnia symptoms was significantly higher among asthmatics than non-asthmatics (47.3% vs 37.2%, <0.0001). In the subgroup reporting both asthma and nasal congestion, 55.8% had insomnia symptoms compared with 35.3% in subjects without both asthma and nasal congestion. The risk of insomnia increased with the severity of asthma, and the adjusted OR for insomnia was 2.65 in asthmatics with three symptoms compared with asthmatics without symptoms. Nasal congestion (OR 1.50), obesity (OR 1.54) and smoking (OR 1.71) also increased the risk of insomnia.

    CONCLUSION: Insomnia remains a common problem among asthmatics. Uncontrolled asthma and nasal congestion are important, treatable risk factors for insomnia. Lifestyle factors, such as smoking and obesity, are also risk factors for insomnia among asthmatics.

  • 279. Sundh, Josefin
    et al.
    Bornefalk-Hermansson, Anna
    Ahmadi, Zainab
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Janson, Christer
    Currow, David C.
    McDonald, Christine F.
    McCaffrey, Nikki
    Ekström, Magnus
    REgistry-based randomized controlled trial of treatment and Duration and mortality in long-term OXygen therapy (REDOX) study protocol2019In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 19, article id 50Article in journal (Refereed)
    Abstract [en]

    Objective: Long-term oxygen therapy (LTOT) during 15h/day or more prolongs survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. No randomized controlled trial has evaluated the net effects (benefits or harms) from LTOT 24h/day compared with 15h/day or the effect in conditions other than COPD. We describe a multicenter, national, phase IV, non-superiority, registry-based, randomized controlled trial (R-RCT) of LTOT prescribed 24h/day compared with 15h/day. The primary endpoint is all-cause-mortality at 1year. Secondary endpoints include cause-specific mortality, hospitalizations, health-related quality of life, symptoms, and outcomes in interstitial lung disease. Methods/design: Patients qualifying for LTOT are randomized to LTOT 24h/day versus 15h/day during 12months using the Swedish Register for Respiratory Failure (Swedevox). Planned sample size in this pragmatic study is 2126 randomized patients. Clinical follow-up and concurrent treatments are according to routine clinical practice. Mortality, hospitalizations, and incident diseases are assessed using national Swedish registries with expected complete follow-up. Patient-reported outcomes are assessed using postal questionnaire at 3 and 12months. Discussion: The R-RCT approach combines the advantages of a prospective randomized trial and large clinical national registries for enrollment, allocation, and data collection, with the aim of improving the evidence-based use of LTOT. Trial registration: Clinical Trial registered with www.clinicaltrials.gov, Title: REgistry-based Treatment Duration and Mortality in Long-term OXygen Therapy (REDOX); ID: NCT03441204.

  • 280. Sundh, Josefin
    et al.
    Johansson, Gunnar
    Larsson, Kjell
    Linden, Anders
    Lofdahl, Claes-Goran
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Janson, Christer
    The phenotype of concurrent chronic bronchitis and frequent exacerbations in patients with severe COPD attending Swedish secondary care units2015In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 10, p. 2327-2334Article in journal (Refereed)
    Abstract [en]

    Background: Chronic bronchitis and previous exacerbations are both well-known risk factors for new exacerbations, impaired health-related quality of life, and increased mortality in COPD. The aim of the study was to characterize the phenotype of concurrent chronic bronchitis and frequent exacerbation in severe COPD. Methods: Information on patient characteristics, comorbidity, and exacerbations from the previous year (total number and number requiring hospitalization) was collected from 373 patients with stage III and IV COPD attending 27 secondary care respiratory units in Sweden. Logistic regression used chronic bronchitis and frequent exacerbations (. 2 exacerbations or. 1 hospitalized exacerbations in the previous year) as response variables. Stratification and interaction analyses examined effect modification by sex. Results: Chronic bronchitis was associated with current smoking (adjusted odds ratio [OR] [95% CI], 2.75 [1.54-4.91]; P=0.001), frequent exacerbations (OR [95% CI], 1.93 [1.24-3.01]; P=0.004), and musculoskeletal symptoms (OR [95% CI], 1.74 [1.05-2.86]; P=0.031), while frequent exacerbations were associated with lung function (forced expiratory volume in 1 second as a percentage of predicted value [FEV1% pred]) (OR [95% CI] 0.96 [0.94-0.98]; P=0.001) and chronic bronchitis (OR [95% CI] 1.73 [1.11-2.68]; P=0.015). The phenotype with both chronic bronchitis and frequent exacerbations was associated with FEV1% pred (OR [95% CI] 0.95 [0.92-0.98]; P=0.002) and musculoskeletal symptoms (OR [95% CI] 2.55 [1.31-4.99]; P=0.006). The association of smoking with the phenotype of chronic bronchitis and exacerbations was stronger in women than in men (interaction, P=0.040). Conclusion: Musculoskeletal symptoms and low lung function are associated with the phenotype of combined chronic bronchitis and frequent exacerbations in severe COPD. In women, current smoking is of specific importance for this phenotype. This should be considered in clinical COPD care.

  • 281. Sundh, Josefin
    et al.
    Johansson, Gunnar
    Larsson, Kjell
    Linden, Anders
    Löfdahl, Claes-Göran
    Janson, Christer
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Comorbidity and health-related quality of life in patients with severe chronic obstructive pulmonary disease attending Swedish secondary care units2015In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 10, no 1, p. 173-183Article in journal (Refereed)
    Abstract [en]

    Introduction: Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement. The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT). Methods: Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1) <50% of predicted value from 27 secondary care respiratory units in Sweden. Correlation analyses and multiple linear regression models were performed using EQ-5D index, EQ-5D visual analog scale (VAS), and CAT scores as response variables. Results: Having more comorbid conditions was associated with a worse HRQL as assessed by all instruments. Chronic bronchitis was significantly associated with a worse HRQL as assessed by EQ-5D index (adjusted regression coefficient [95% confidence interval] -0.07 [-0.13 to -0.02]), EQ-5D VAS (-5.17 [-9.42 to -0.92]), and CAT (3.78 [2.35 to 5.20]). Musculoskeletal symptoms were significantly associated with worse EQ-5D index (-0.08 [-0.14 to -0.02]), osteoporosis with worse EQ-5D VAS (-4.65 [-9.27 to -0.03]), and depression with worse EQ-5D index (-0.10 [-0.17 to -0.04]). In stratification analyses, the associations of musculoskeletal symptoms, osteoporosis, and depression with HRQL were limited to female patients. Conclusion: The instruments EQ-5D and CAT complement each other and emerge as useful for assessing HRQL in patients with COPD. Chronic bronchitis, musculoskeletal symptoms, osteoporosis, and depression were associated with worse HRQL. We conclude that comorbid conditions, in particular chronic bronchitis, depression, osteoporosis, and musculoskeletal symptoms, should be taken into account in the clinical management of patients with severe COPD.

  • 282. Svelander, Lena
    et al.
    Erlandsson Harris, Helena
    Lorentzen, Johnny C
    Trollmo, Christina
    Klareskog, Lars
    Bucht, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Oligodeoxynucleotides containing CpG motifs can induce T cell-dependent arthritis in rats.2004In: Arthritis Rheum, ISSN 0004-3591, Vol. 50, no 1, p. 297-304Article in journal (Refereed)
  • 283. Svensson, Malin
    et al.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Theorell-Haglöw, Jenny
    Lindberg, Eva
    Daytime sleepiness relates to snoring independent of the apnea-hypopnea index in women from the general population.2008In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 134, no 5, p. 919-24Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim was to investigate the significance of snoring and sleep apnea on daytime symptoms in a population-based sample of women. METHOD: From the general population, 400 women aged 20 to 70 years were randomly selected, with oversampling of habitually snoring women. The women were investigated using full-night polysomnography and a questionnaire. The apnea-hypopnea index (AHI) was calculated, and women who acknowledged snoring loudly and disturbingly often or very often were considered habitual snorers. RESULTS: Habitual snoring was independently related to excessive daytime sleepiness (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.31 to 3.99), to falling asleep involuntarily during the day (OR, 2.11; 95% CI, 1.06 to 4.21), to waking up unrefreshed (OR, 2.14; 95% CI, 1.30 to 3.52), to daytime fatigue (OR, 2.77; 95% CI, 1.54 to 4.99), and to a dry mouth on awakening (OR, 2.00; 95% CI, 1.22 to 3.27) after adjustment for AHI, age, body mass index (BMI), smoking, total sleep time, percentage of slow-wave sleep, and percentage of rapid eye movement (REM) sleep. An AHI > or = 15/h was only related to a dry mouth on awakening after adjustment for snoring, age, BMI, smoking, total sleep time, percentage of slow-wave sleep, and percentage of REM sleep (OR, 2.24; 95% CI, 1.14 to 4.40). An AHI of 5 to 15/h was not related to any daytime symptom. CONCLUSIONS: Excessive daytime sleepiness and daytime fatigue are related to habitual snoring independent of the apnea-hypopnea frequency, age, obesity, smoking, and sleep parameters in a population-based sample of women, but not to the AHI. This indicates that snoring is an independent cause of excess daytime sleepiness and not merely a proxy for sleep apnea.

  • 284. Svensson-Elfsmark, Linda
    et al.
    Koch, Bo L
    Gustafsson, Åsa
    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.
    Rats repeatedly exposed to toluene diisocyanate exhibit immune reactivity against methyl isocyanate-protein conjugates.2009In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 150, no 3, p. 229-236Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Volatile monoisocyanates are formed through thermal degradation when products containing polyurethane are heated. Repeated exposure to diisocyanates, such as toluene diisocyanate (TDI) are a well-known cause of occupational asthma. However, although monoisocyanates are abundant in occupational settings, there are few data concerning their ability to provoke immune reactions and asthma. We compared immune reactivity and respiratory disease following single or repeated inhalation exposures to the monoisocyanates methyl isocyanate (MIC) and isocyanic acid (ICA) with the effects of TDI. METHODS: Isocyanates were administrated either as single vapor exposures or as repeated intranasal instillations in rats. Adverse health effects were monitored by analyzing airway inflammation, respiratory function and weight gain. Immune reactivity caused by repeated exposures was studied by analysis of isocyanate-specific antibodies and airway infiltration of immune competent cells. RESULTS: Repeated exposures to TDI induced airway infiltration of neutrophils and lymphocytes, while neither MIC nor ICA provoked a detectable inflammatory response. Antibodies against isocyanate-albumin conjugates were detected in serum after both exposures to TDI and MIC, but not to ICA. TDI-exposed rats also displayed IgG antibodies against MIC-albumin conjugates. Even though MIC did not induce airway inflammation, single exposure provoked an increase in airway resistance and repeated exposures caused weight loss similar to that of TDI. CONCLUSIONS: Airway exposure to TDI produces an antibody response not only against TDI but also against MIC-protein conjugates. This indicates that immune reactivity against abundant monoisocyanates in occupational environments can occur in individuals pre-sensitized with low abundance but highly sensitizing diisocyanates.

  • 285. Sydbom, A
    et al.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Dept of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Parnia, S
    Dept of Respiratory Medicine and Allergy, University Hospital, Umeå and Respiratory Cell and Molecular Biology Research Division, Southampton General Hospital, Tremona Road, Southampton, UK.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Dept of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Dept of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Dahlén, S E
    Health effects of diesel exhaust emissions2001In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 17, no 4, p. 733-746Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components. Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function. There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response. Much of the research on adverse effects of diesel exhaust, both in vivo and in vitro, has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.

  • 286. Takahashi, Kentaro
    et al.
    Pavlidis, Stelios
    Kwong, Francois Ng Kee
    Hoda, Uruj
    Rossios, Christos
    Sun, Kai
    Loza, Matthew
    Baribaud, Fred
    Chanez, Pascal
    Fowler, Steve J.
    Horvath, Ildiko
    Montuschi, Paolo
    Singer, Florian
    Musial, Jacek
    Dahlen, Barbro
    Dahlen, Sven-Eric
    Krug, Norbert
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shaw, Dominic E.
    Lutter, Rene
    Bakke, Per
    Fleming, Louise J.
    Howarth, Peter H.
    Caruso, Massimo
    Sousa, Ana R.
    Corfield, Julie
    Auffray, Charles
    De Meulder, Bertrand
    Lefaudeux, Diane
    Djukanovic, Ratko
    Sterk, Peter J.
    Guo, Yike
    Adcock, Ian M.
    Chung, Kian Fan
    Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 51, no 5, article id 1702173Article in journal (Refereed)
    Abstract [en]

    Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed. Colony-stimulating factor (CSF) 2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated. Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

  • 287. Thors, L.
    et al.
    Koch, B.
    Koch, M.
    Hägglund, L.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden b Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University.
    In vitro human skin penetration model for organophosphorus compounds with different physicochemical properties2016In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 32, p. 198-204Article in journal (Refereed)
    Abstract [en]

    A flow-through diffusion cell was validated for in vitro human epidermal penetration studies of organophosphorus compounds (OPCs) applied by infinite dosing. By testing OPCs with similar molecular weight but different physicochemical properties, it was shown that hydrophilic and lipophilic properties are major determinants for the penetration rate. Lipophilic OPCs displayed maximum cumulative penetration in the 20-75% agent concentration range whereas the hydrophilic OPCs displayed maximum cumulative penetration at 10 or 20% agent concentration. Low penetration was observed for all agents at 1% agent concentration or when applied as neat agents. The impact of the receptor solution composition was evaluated by comparing the penetration using receptor solutions of different ratios of ethanol and water. For diluted OPCs, a high concentration of ethanol in the receptor solution significantly increased the penetration compared to lower concentrations. When OPCs were applied as neat agents, the composition of the receptor solution only affected the penetration for one of four tested compounds. In conclusion, the flow-through diffusion cell was useful for examining the penetration of OPCs through the epidermal membrane. It was also demonstrated that the penetration rates of OPCs are strongly influenced by dilution in water and the receptor fluid composition.

  • 288. Toren, K.
    et al.
    Bake, B.
    Olin, A-C
    Engstrom, G.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Vikgren, J.
    Hedner, J.
    Brandberg, J.
    Persson, H. L.
    Skold, C. M.
    Rosengren, A.
    Bergstrom, G.
    Janson, C.
    Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study2017In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 12, p. 973-980Article in journal (Refereed)
    Abstract [en]

    Background: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). Materials and methods: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 mu g of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to " Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. Results: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. Conclusion: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is 9%, 4% and 5%, respectively.

  • 289. Toren, Kjell
    et al.
    Olin, Anna-Carin
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Vikgren, Jenny
    Schioler, Linus
    Brandberg, John
    Johnsson, Ase
    Engstrom, Gunnar
    Persson, H. Lennart
    Skold, Magnus
    Hedner, Jan
    Lindberg, Eva
    Malinovschi, Andrei
    Piitulainen, Eeva
    Wollmer, Per
    Rosengren, Annika
    Janson, Christer
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergstrom, Goran
    Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS)2016In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 11, p. 927-933Article in journal (Refereed)
    Abstract [en]

    Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPD(VC) as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.

  • 290.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Respiratory and cardiovascular responses to diesel exhaust exposure2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

  • 291.
    Törnqvist, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Gonzalez, Manuel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Miller, Mark R
    Robinson, Simon D
    Megson, Ian L
    Macnee, William
    Donaldson, Ken
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Newby, David E
    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.
    Persistent endothelial dysfunction in humans after diesel exhaust inhalation.2007In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 176, no 4, p. 395-400Article in journal (Refereed)
  • 292.
    Törnqvist, Håkan
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, NL
    Gonzalez, M
    Robinson, SD
    Boon, NA
    MacNee, W
    Donaldson, K
    Newby, DE
    Sandström, T
    Blomberg, A
    Prolonged endothelial dysfunction following diesel exhaust inhalation2007In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 176, no 4, p. 395-400Article in journal (Refereed)
  • 293.
    Törnqvist, Håkan
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, J
    Ädelroth, E
    Sandström, T
    Blomberg, A
    Diesel exhaust exposure in subjects with chronic obstructive pulmonary diseaseManuscript (Other academic)
  • 294.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Acute cardiovascular effects of biofuel exhaust exposure2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Anthropogenic air pollution is a global health problem estimated to contribute to millions of premature deaths. Exposure to biomass smoke is common due to varying sources, such as wildfires, indoor cooking over open fires, and residential heating from wood stoves. In urban environments transportation and industry rely heavily on the combustion of fossil fuels yet environmental policies increasingly support a shift to renewable fuels such as biodiesel. It has not been investigated how either wood smoke or biodiesel exhaust affect human health in general or the cardiovascular system in particular. We hypothesized that wood smoke exposure would induce acute cardiovascular impairment via similar underlying mechanisms as have been established for petrodiesel exhaust exposure. We also hypothesized that replacing petrodiesel with biodiesel, as a blend or pure biodiesel, would generate an exhaust profile with a less harmful effect on the cardiovascular system than petrodiesel exhaust.

    Methods

    In four separate studies healthy non-smoking subjects were exposed to different air pollutants in controlled exposure chambers followed by clinical investigations of the cardiovascular system. All studies were performed as randomized controlled trials in a crossover fashion with each individual acting as her own control. In study I healthy volunteers were exposed to wood smoke at a target concentration of particulate matter (PM) 300 µg/mfor three hours followed by measures of blood pressure, heart rate variability and central arterial stiffness. In study II subjects were exposed to wood smoke at a target concentration of PM 1000 µg/mfor one hour followed by measures of thrombus formation using the Badimon technique and vasomotor function using forearm venous occlusion plethysmography. In study III subjects were exposed to petrodiesel exhaust and a 30% rapeseed methyl ester (RME30) biodiesel blend for one hour at a target concentration of PM 300 µg/m3. Following exposure, thrombus formation and vasomotor function were assessed as in study II. In study IV subjects were exposed to petrodiesel exhaust at a target concentration of PM 300 μg/m3for one hour and pure rapeseed methyl ester (RME100) exhaust generated at identical running conditions of the engine. Following exposure, thrombus formation and vasomotor function were assessed as in study II and III.

    Results

    In study I fourteen subjects (8 males) were exposed to wood smoke at P M 294±36 μg/m3. Compared to filtered air exposure, measures of central arterial stiffness were increased and heart rate variability was decreased following wood smoke exposure. No effect was seen on blood pressure. In study II sixteen males were exposed to wood smoke at PM 899±100 μg/m3. We found no evidence of increased thrombus formation or impaired vasomotor function following wood smoke exposure. In study III sixteen subjects (14 males) were exposed to petrodiesel exhaust (PM 314±27 µg/m3) and RME30 exhaust (PM 309±30 µg/m3). Thrombus formation and vasomotor function were equal following either exposure. In study IV nineteen males were exposed to petrodiesel exhaust (PM 310±34 µg/m3, 1.7±0.3 x105 particles/cm3) and RME100 exhaust (PM 165±16 µg/m3, 2.2±0.1 x10particles/cm3). As in study III, thrombus formation and vasomotor function were identical following both exposures.

    Conclusions

    We have for the first time demonstrated that wood smoke exposure can increase central arterial stiffness and decrease heart rate variability in healthy subjects. We did not, however find evidence of increased thrombus formation and impaired vasomotor function following wood smoke exposure at a higher concentration for a shorter time period. We have, for the first time, demonstrated that exhaust from RME biodiesel induced acute adverse cardiovascular effects of increased thrombus formation and impaired vasomotor function in man. These effects are on par with those seen following exposure to petrodiesel exhaust, despite marked physicochemical differences of the exhaust characteristics.

  • 295.
    Unosson, Jon
    et al.
    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.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    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.
    Kabele, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sadiktsis, Ioannis
    Stockholm University.
    Westerholm, Roger
    Stockholm University.
    Mudway, Ian
    King's College London.
    Purdie, Esme
    King's College London.
    Raftis, Jennifer
    University of Edinburgh.
    Mills, Nicholas L
    University of Edinburgh.
    Newby, David E
    University of Edinburgh.
    Langrish, Jeremy P
    University of Edinburgh.
    Bosson, Jenny A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rapeseed Methyl Ester Biodiesel Exhaust Exposure Causes Vascular Dysfunction in ManManuscript (preprint) (Other academic)
  • 296.
    Unosson, Jon
    et al.
    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.
    Sandström, Thomas
    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.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Nyström, Robin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Westerholm, Roger
    Mills, Nicholas L.
    Newby, David E.
    Langrish, Jeremy P.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Exposure to wood smoke increases arterial stiffness and decreases heart rate variability in humans2013In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 10, p. 20-Article in journal (Refereed)
    Abstract [en]

    Background: Emissions from biomass combustion are a major source of indoor and outdoor air pollution, and are estimated to cause millions of premature deaths worldwide annually. Whilst adverse respiratory health effects of biomass exposure are well established, less is known about its effects on the cardiovascular system. In this study we assessed the effect of exposure to wood smoke on heart rate, blood pressure, central arterial stiffness and heart rate variability in otherwise healthy persons. Methods: Fourteen healthy non-smoking subjects participated in a randomized, double-blind crossover study. Subjects were exposed to dilute wood smoke (mean particle concentration of 314 +/- 38 mu g/m(3)) or filtered air for three hours during intermittent exercise. Heart rate, blood pressure, central arterial stiffness and heart rate variability were measured at baseline and for one hour post-exposure. Results: Central arterial stiffness, measured as augmentation index, augmentation pressure and pulse wave velocity, was higher after wood smoke exposure as compared to filtered air (p < 0.01 for all), and heart rate was increased (p < 0.01) although there was no effect on blood pressure. Heart rate variability (SDNN, RMSSD and pNN50; p = 0.003, p < 0.001 and p < 0.001 respectively) was decreased one hour following exposure to wood smoke compared to filtered air. Conclusions: Acute exposure to wood smoke as a model of exposure to biomass combustion is associated with an immediate increase in central arterial stiffness and a simultaneous reduction in heart rate variability. As biomass is used for cooking and heating by a large fraction of the global population and is currently advocated as a sustainable alternative energy source, further studies are required to establish its likely impact on cardiovascular disease.

  • 297.
    Valham, Fredrik
    et al.
    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, Pulmonary Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Snoring men with daytime sleepiness drive more than others: a population-based study2009In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 10, no 9, p. 1012-1015Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate whether subjects with daytime sleepiness who snore or report witnessed sleep apneas drive more than others.

    Methods

    Questions on snoring, witnessed sleep apnea, excessive daytime sleepiness and driving distance per year were included in the Northern Sweden component of the WHO, MONICA study. Invited were 10756 subjects aged 25–79 years, randomly selected from the population register.

    Results

    There were 7905 (73%) subjects, 3858 men and 4047 women who responded to the questionnaire and attended a visit for a physical examination. Habitually snoring men with daytime sleepiness drove a mean of 22566 (95% CI 18550–26582) km a year, which was significantly more than non-snoring men without excessive daytime sleepiness who drove 17751 (95% CI 17076–18427) km a year, p = 0.02, after adjustments for age, body mass index, smoking and physical activity. Men reporting witnessed sleep apnea and excessive daytime sleepiness also drove more than their counterparts in adjusted analysis, p = 0.01. Women reporting daytime sleepiness and witnessed apnea tended to drive more, while snoring women with daytime sleepiness did not.

    Conclusions

    Men suffering from excessive daytime sleepiness who snore habitually or report witnessed sleep apneas drive significantly more than others.

  • 298.
    Valham, Fredrik
    et al.
    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.
    Rabben, Terje
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Wiklund, Urban
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year follow-up2008In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 118, no 9, p. 955-960Article in journal (Refereed)
    Abstract [en]

    Background The effect of sleep apnea on mortality and cardiovascular morbidity is mainly unknown. We aimed to study whether sleep apnea is related to stroke, death, or myocardial infarction in patients with symptomatic coronary artery disease.

    Methods and Results A total of 392 men and women with coronary artery disease referred for coronary angiography were examined by use of overnight sleep apnea recordings. Sleep apnea, defined as an apnea-hypopnea index ≥5, was recorded in 54% of the patients. All patients were followed up prospectively for 10 years, and no one was lost to follow-up. Stroke occurred in 47 (12%) of 392 patients during follow-up. Sleep apnea was associated with an increased risk of stroke, with an adjusted hazard ratio of 2.89 (95% confidence interval 1.37 to 6.09, P=0.005), independent of age, body mass index, left ventricular function, diabetes mellitus, gender, intervention, hypertension, atrial fibrillation, a previous stroke or transient ischemic attack, and smoking. Patients with an apnea-hypopnea index of 5 to 15 and patients with an apnea-hypopnea index ≥15 had a 2.44 (95% confidence interval 1.08 to 5.52) and 3.56 (95% confidence interval 1.56 to 8.16) times increased risk of stroke, respectively, than patients without sleep apnea, independent of confounders (P for trend=0.011). Death and myocardial infarction were not related to sleep apnea. Intervention in the form of coronary artery bypass grafting or percutaneous coronary intervention was related to a longer survival but did not affect the incidence of stroke.

    Conclusions Sleep apnea is significantly associated with the risk of stroke among patients with coronary artery disease who are being evaluated for coronary intervention.

  • 299.
    Valham, Fredrik
    et al.
    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.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ambient temperature and obstructive sleep apnea: effects on sleep, sleep apnea and morning alertness2012In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 35, no 4, p. 513-517Article in journal (Refereed)
    Abstract [en]

    Study Objectives: The aim of the study was to investigate the effect of ambient temperature on sleep, sleep apnea, and morning alertness in patients with obstructive sleep apnea. Design: Randomized controlled trial. Setting: In-hospital investigations. Participants: Forty patients with obstructive sleep apnea naive to treatment, with an apnea-hypopnea index of 10-30. Interventions: Three different nights in room temperatures of 16 degrees C, 20 degrees C, and 24 degrees C. Measurements: Overnight polysomnography and Karolinska Sleepiness Scale. Results: The obstructive apnea-hypopnea index was 30 +/- 17 at 16 degrees C room temperature, 28 +/- 17 at 20 degrees C, and 24 +/- 18 at 24 degrees C. The obstructive apnea-hypopnea index was higher at 16 degrees C room temperature versus 24 degrees C (P = 0.001) and at 20 degrees C room temperature versus 24 degrees C (P = 0.033). Total sleep time was a mean of 30 min longer (P = 0.009), mean sleep efficiency was higher (77 +/- 11% versus 71 +/- 13% respectively, P = 0.012), and the patients were significantly more alert according to the Karolinska Sleepiness Scale (P < 0.028) in the morning at 16 degrees C room temperature versus 24 degrees C. The amount of sleep in different sleep stages was not affected by room temperature. Conclusions: Untreated patients with obstructive sleep apnea sleep longer, have better sleep efficiency, and are more alert in the morning after a night's sleep at 16 degrees C room temperature compared with 24 degrees C, but obstructive sleep apnea is more severe at 16 degrees C and 20 degrees C compared with 24 degrees C.

  • 300.
    Valham, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Eva
    Department of Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Snoring and witnessed sleep apnea is related to diabetes mellitus in women2009In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 10, no 1, p. 112-117Article in journal (Refereed)
    Abstract [en]

    Background

    Gender differences in the relationship of snoring and diabetes mellitus are mainly unknown. We aimed to analyze the relationship between snoring, witnessed sleep apnea and diabetes mellitus and to analyze possible gender related differences in an unselected population.

    Methods

    Questions on snoring and witnessed sleep apneas were included in the Northern Sweden component of the WHO, MONICA study. Invited were 10,756 men and women aged 25–79 years, randomly selected from the population register.

    Results

    There were 7905 (73%) subjects, 4047 women and 3858 men who responded to the questionnaire and attended a visit for a physical examination. Habitual snoring was related to diabetes mellitus in women, with an adjusted odds ratio (OR) = 1.58 (95% confidence interval (CI) 1.02–2.44, p = 0.041) independent of smoking, age, body mass index and waist circumference. Witnessed sleep apnea was also independently related to diabetes mellitus in women, with an adjusted OR = 3.29 (95% CI 1.20–8.32, p = 0.012). Neither snoring, nor witnessed sleep apneas were associated with diabetes mellitus among men, except for witnessed sleep apnea in men aged 25–54 years old. They had an adjusted OR = 3.84 (95% CI 1.36–10.9, p = 0.011) for diabetes mellitus.

    Conclusions

    Snoring and witnessed sleep apneas are related to diabetes mellitus in women. Witnessed sleep apnea is related to diabetes mellitus in men younger than 55 years old.

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