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  • 51. Carlsten, Chris
    et al.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pui, Mandy
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wong, Sze Wing
    Alexis, Neil
    Hirota, Jeremy
    Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study2016In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 71, no 1, p. 35-44Article in journal (Refereed)
    Abstract [en]

    Rationale Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. Objective To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. Methods 18 blinded atopic volunteers were exposed to filtered air or 300 mg PM2.5/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. Results Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. Conclusion Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.

  • 52. Castro-Giner, F
    et al.
    Kogevinas, M
    Mächler, M
    de Cid, R
    Van Steen, K
    Imboden, M
    Schindler, C
    Berger, W
    Gonzalez, J R
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Janson, C
    Jarvis, D
    Omenaas, E
    Burney, P
    Rochat, T
    Estivill, X
    Antó, J M
    Wjst, M
    Probst-Hensch, N M
    TNFA -308G>A in two international population-based cohorts and risk of asthma2008In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 32, no 2, p. 350-361Article in journal (Refereed)
    Abstract [en]

    Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.

  • 53. Crüts, Björn
    et al.
    Driessen, Anique
    van Etten, Ludo
    Törnqvist, Håkan
    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.
    Mills, Nicholas L
    Borm, Paul Ja
    Reply to comment on Cruts et al. (2008), "Exposure to diesel exhaust induces changes in EEG in human volunteers" by Valberg et al.2008In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 5, p. 11-Article in journal (Other academic)
  • 54. Crüts, Björn
    et al.
    van Etten, Ludo
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Borm, Paul Ja
    Exposure to diesel exhaust induces changes in EEG in human volunteers.2008In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 5, p. 4-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: BACKGROUND: Ambient particulate matter and nanoparticles have been shown to translocate to the brain, and potentially influence the central nervous system. No data are available whether this may lead to functional changes in the brain. METHODS: We exposed 10 human volunteers to dilute diesel exhaust (DE, 300 mug/m3) as a model for ambient PM exposure and filtered air for one hour using a double blind randomized crossover design. Brain activity was monitored during and for one hour following each exposure using quantitative electroencephalography (QEEG) at 8 different sites on the scalp. The frequency spectrum of the EEG signals was used to calculate the median power frequency (MPF) and specific frequency bands of the QEEG. RESULTS: Our data demonstrate a significant increase in MPF in response to DE in the frontal cortex within 30 min into exposure. The increase in MPF is primarily caused by an increase in fast wave activity (beta2) and continues to rise during the 1 hour post-exposure interval. CONCLUSION: This study is the first to show a functional effect of DE exposure in the human brain, indicating a general cortical stress response. Further studies are required to determine whether this effect is mediated by the nanoparticles in DE and to define the precise pathways involved.

  • 55. Cullinan, Paul
    et al.
    Muñoz, Xavier
    Suojalehto, Hille
    Agius, Raymond
    Jindal, Surinder
    Sigsgaard, Torben
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Charpin, Denis
    Annesi-Maesano, Isabella
    Gulati, Mridu
    Kim, Yangho
    Frank, Arthur L
    Akgün, Metin
    Fishwick, David
    de la Hoz, Rafael E
    Moitra, Subhabrata
    Occupational lung diseases: from old and novel exposures to effective preventive strategies2017In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 5, no 5, p. 445-455Article in journal (Refereed)
    Abstract [en]

    Occupational exposure is an important, global cause of respiratory disease. Unlike many other non-communicable lung diseases, the proximal causes of many occupational lung diseases are well understood and they should be amenable to control with use of established and effective approaches. Therefore, the risks arising from exposure to silica and asbestos are well known, as are the means of their prevention. Although the incidence of occupational lung disease has decreased in many countries, in parts of the world undergoing rapid economic transition and population growth-often with large informal and unregulated workforces-occupational exposures continue to impose a heavy burden of disease. The incidence of interstitial and malignant lung diseases remains unacceptably high because control measures are not implemented or exposures arise in novel ways. With the advent of innovative technologies, new threats are continually introduced to the workplace (eg, indium compounds and vicinal diketones). In developed countries, work-related asthma is the commonest occupational lung disease of short latency. Although generic control measures to reduce the risk of developing or exacerbating asthma are well recognised, there is still uncertainty, for example, with regards to the management of workers who develop asthma but remain in the same job. In this Review, we provide recommendations for research, surveillance, and other action for reducing the burden of occupational lung diseases.

  • 56.
    Dahlqvist, Johanna
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Dahlqvist, Åke
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Marklund, Marie
    Umeå University, Faculty of Medicine, Odontology, Ortodontics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Physical findings in the upper airways related to obstructive sleep apnea in men and women2007In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 127, no 6, p. 623-630Article in journal (Refereed)
    Abstract [en]

    CONCLUSIONS:There are gender differences when it comes to the risk factors for sleep apnea. Large tonsils, a high tongue and a wide uvula are risk factors for sleep apnea in men, while large tonsils and a retrognathic mandible are risk factors in women. Upper airway abnormalities including mandibular retrognathia are, however, unable to predict sleep apnea among snorers being investigated for suspected sleep apnea.

    OBJECTIVES: To identify gender-specific risk factors for obstructive sleep apnea and the diagnostic performance from physical upper airway examinations among snoring men and women investigated because of suspected sleep apnea.

    PATIENTS AND METHODS: The dimensions of the uvula, tonsils, velopharynx and tongue, and nasal septal deviation, mandibular position, neck circumference, weight, and height were systematically scored in 801 consecutive snoring patients (596 men and 205 women), who had been referred for a primary sleep apnea recording.

    RESULTS: In men, large tonsils, a high tongue, and a wide uvula were independent factors associated with an apnea-hyopnea index of > 15. In women, large tonsils and mandibular retrognathia were independent factors associated with an apnea-hypopnea index of > 15. The positive predictive values for upper airway abnormalities ranged between 0.20 and 0.25 in men and between 0.09 and 0.15 in women.

  • 57. Dewilde, S
    et al.
    Turk, F
    Tambour, M
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients: adaptation of INNOVATE to Sweden.2006In: Curr Med Res Opin, ISSN 0300-7995, Vol. 22, no 9, p. 1765-76Article in journal (Refereed)
  • 58.
    Dove, Rosamund E.
    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. MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
    Leong-Smith, Pheneatia
    Roos-Engstrand, Ester
    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.
    Pourazar, Jamshid
    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.
    Shah, Mittal
    Behndig, Annelie F.
    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.
    Mudway, Ian S.
    Blomberg, Anders
    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.
    Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD2015In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 2, article id 27837Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 59. Duong, MyLinh
    et al.
    Subbarao, Padmaja
    Adelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Obminski, George
    Strinich, Tara
    Inman, Mark
    Pedersen, Soren
    O'Byrne, Paul M
    Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma.2008In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 133, no 2, p. 404-11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed. RESULTS: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time. CONCLUSIONS: These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs. Trial registration: clinicaltrial.gov; Identifier: NCT00525772.

  • 60. Ekstrand-Hammarström, B
    et al.
    Österlund, Camilla
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Lilliehöök, B
    Bucht, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Vitamin E down-modulates mitogen-activated protein kinases, nuclear factor-kappaB and inflammatory responses in lung epithelial cells.2007In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 147, no 2, p. 359-369Article in journal (Refereed)
  • 61. Ekstrand-Hammarström, Barbro
    et al.
    Akfur, Christine M
    Andersson, Per Ola
    Lejon, Christian
    Österlund, Lars
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Human primary bronchial epithelial cells respond differently to titanium dioxide nanoparticles than the lung epithelial cell lines A549 and BEAS-2B2012In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404, Vol. 6, no 6, p. 623-634Article in journal (Refereed)
    Abstract [en]

    We have compared the cellular uptake and responses of five preparations of nanocrystalline titanium dioxide (TiO(2)) between normal human bronchial epithelial (NHBE) cells and epithelial cell lines (A549 and BEAS-2B). The P25 nanoparticles, containing both anatase and rutile modifications, induced reactive oxygen species (ROS) and secretion of the neutrophil chemoattractant IL-8 in all three cell types used. Pure anatase and rutile particles provoked differential IL-8 response in A549 and no response in BEAS-2B cells despite similar formation of ROS. The pure TiO(2) modifications also provoked release of the inflammatory mediators: IL-6, G-CSF and VEGF, in NHBE cells but not in the two cell lines. We conclude that the responsiveness of lung epithelial cells is strongly dependent on both the physicochemical properties of TiO(2) nanoparticles and the type of responder cells. The differential pro-inflammatory responsiveness of primary lung epithelial cells compared with immortalized cell lines should be considered in the assessment of adverse reactions to inhaled nanoparticles.

  • 62. Ekstrand-Hammarström, Barbro
    et al.
    Hong, Jaan
    Davoodpour, Padideh
    Sandholm, Kerstin
    Ekdahl, Kristina N.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nilsson, Bo
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. 

  • 63. Ekstrand-Hammarström, Barbro
    et al.
    Magnusson, Roger
    Österlund, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Andersson, Britt M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wingfors, Håkan
    Oxidative stress and cytokine expression in respiratory epithelial cells exposed to well-characterized aerosols from Kabul, Afghanistan2013In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 27, no 2, p. 825-833Article in journal (Refereed)
    Abstract [en]

    In this study aerosol samples collected in an Asian mega-city (Kabul, Afghanistan) were compared to PM samples collected in a European location with traffic (Umea, Sweden) and a reference urban dust material (SRM 1649b). The toxicity of each sample towards normal human bronchial epithelial (NHBE) cells and a human bronchial epithelial cell line (BEAS-2B) was tested along with their ability to induce reactive oxygen species (ROS) formation and inflammatory responses. The extracts' morphology and elemental composition was studied by SEM-EDXRF, and filter samples were analyzed for metals and organic compounds. The PM from Kabul contained a larger fraction of fine particles, 19 times more polyaromatic hydrocarbons (PAH) and 37 times more oxygenated PAH (oxy-PAH) compared to samples from timed. The PM-samples from Kabul and the reference material (SRM 1649b) induced significantly stronger oxidative stress responses than the samples from Umea. Furthermore, samples collected in Kabul induced significantly higher secretion of the cytokines IL-6, IL-8 and GM-CSF while SRM1649b induced a cytokine pattern more similar to samples collected in Umea. Several properties of the particles could potentially explain these differences, including differences in their size distribution and contents of PAH and oxy-PAH, possibly in combination with their relative transition metal contents. 

  • 64.
    Ekstrand-Hammarström, Barbro
    et al.
    Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
    Wigenstam, Elisabeth
    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.
    Inhalation of alkylating mustard causes long-term T cell-dependent inflammation in airways and growth of connective tissue2011In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 280, no 3, p. 88-97Article in journal (Refereed)
    Abstract [en]

    Low-dose exposure of alkylating mustard gas causes long-term respiratory complications characterized by bronchitis and lung fibrosis. In this study, we utilized a mouse model for lung exposure of the nitrogen mustard melphalan, in order to define early and late events in the pathogenesis such as expression of pro-inflammatory cytokines, recruitment of inflammatory cells to airways and late-phase fibrosis. We investigated the roles of different T lymphocyte subsets on the inflammatory response by using knockout mice lacking either the genes expressing T cell receptor (TCR)αβ or TCRγδ, and compared the responsiveness with that of wild type mice and double knockout mice completely deficient in T cells. Exposure to melphalan induced an early burst of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-23 in airways, followed by extensive infiltration of neutrophils in the lung tissue and airways within 24h. The acute phase was followed by a sustained lymphocytic response that persisted for at least 14 days with resulting lung fibrosis. Engagement of T lymphocytes, particularly the γδ T cell subset, was crucial both for the acute cytokine and neutrophil response and for the late-phase lung fibrosis as indicated by the lack of response in γδ T cell deficient mice. Our data demonstrate that T lymphocytes play a prominent role in the pathogenesis of long-term lung injuries caused by strong alkylating agents.

  • 65. Ekstrom, Magnus
    et al.
    Gustafson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Kenneth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Tornling, Goran
    Murgia, Nicola
    Toren, Kjell
    Effects of smoking, gender and occupational exposure on the risk of severe pulmonary fibrosis: a population-based case-control study2014In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 4, no 1, p. e004018-Article in journal (Refereed)
    Abstract [en]

    Objectives: To estimate the effects of smoking, gender and occupational exposure on the risk of developing severe pulmonary fibrosis (PF), including dose-response and interaction effects. Methods: National case-control study of 171 patients (cases) who had started a long-term oxygen therapy for PF in Sweden between February 1997 and April 2000, and 719 random control participants from the general population. Of these cases, 137 had probable idiopathic PF (IPF). The ORs for smoking, gender and occupational exposure were estimated using Mantel-Haenszel analysis and conditional logistic regression, controlling for age and year of diagnosis. Results: The adverse effect of smoking was amplified by male gender and occupational exposure, OR 4.6 (95% CI 2.1 to 10.3) for PF, and OR 3.0 (1.3 to 6.5) for IPF, compared with in non-exposed women. Higher cumulative smoking exposure was linearly associated with increased risks. Compared with smoking less than 10 pack-years, smoking >= 20 pack-years was associated with increased risk of PF and IPF, OR 2.6 (1.4 to 4.9) and OR 2.5 (1.3 to 5.0), respectively. Conclusions: Smoking has a dose-related association with increased risk of severe PF. Men with a history of smoking and occupational exposure is a particular risk group for developing severe PF.

  • 66. Emilsson, O. I.
    et al.
    Bengtsson, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Toren, K.
    Benediktsdottir, B.
    Farkhooy, A.
    Weyler, J.
    Dom, S.
    De Backer, W.
    Gislason, T.
    Janson, C.
    Onset of symptoms of obstructive sleep apnoea and asthma in persistent nocturnal gastroesophageal reflux2012In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 21, no S1, p. 162-162Article in journal (Other academic)
  • 67.
    Emilsson, Ossur I.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bengtsson, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Toren, Kjell
    Benediktsdottir, Bryndis
    Farkhooy, Amir
    Weyler, Joost
    Dom, Sandra
    De Backer, Wilfried
    Gislason, Thorarinn
    Janson, Christer
    Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA: a longitudinal, general population study2013In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 41, no 6, p. 1347-1354Article in journal (Refereed)
    Abstract [en]

    Nocturnal gastro-oesophageal reflux (nGOR) is associated with asthma and obstructive sleep apnoea (OSA). Our aim was to investigate whether nGOR is a risk factor for onset of asthma and onset of respiratory and OSA symptoms in a prospective population-based study. We invited 2640 subjects from Iceland, Sweden and Belgium for two evaluations over a 9-year interval. They participated in structured interviews, answered questionnaires, and underwent spirometries and methacholine challenge testing. nGOR was defined by reported symptoms. Subjects with persistent nGOR (n=123) had an independent increased risk of new asthma at follow-up (OR 2.3, 95% CI 1.1-4.9). Persistent nGOR was independently related to onset of respiratory symptoms (OR 3.0, 95% CI 1.6-5.6). The risk of developing symptoms of OSA was increased in subjects with new and persistent nGOR (OR 2.2, 95% CI 1.3-1.6, and OR 2.0, 95% CI 1.0-3.7, respectively). No significant association was found between nGOR and lung function or bronchial responsiveness. Persistent symptoms of nGOR contribute to the development of asthma and respiratory symptoms. New onset of OSA symptoms is higher among subjects with symptoms of nGOR. These findings provide evidence that nGOR may play a role in the genesis of respiratory symptoms and diseases.

  • 68. Erlinge, D.
    et al.
    Omerovic, E.
    Frobert, O.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Danielewicz, M.
    Hamid, M.
    Swahn, E.
    Henareh, L.
    Wagner, H.
    Hårdhammar, P.
    Sjögren, I.
    Stewart, J.
    Grimfjärd, P.
    Jensen, J.
    Aasa, M.
    Robertsson, L.
    Lindroos, P.
    Haupt, J.
    Wikström, H.
    Ulvenstam, A.
    Bhiladvala, P.
    Lindvall, B.
    Lundin, A.
    Tödt, T.
    Ioanes, D.
    Råmunddal, T.
    Kellerth, T.
    Zagozdzon, L.
    Götberg, M.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Angerås, O.
    Östlund, O.
    Lagerqvist, B.
    Held, C.
    Wallentin, L.
    Scherstén, F.
    Eriksson, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Koul, S.
    James, S.
    Bivalirudin versus heparin monotherapy in myocardial infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors.

    METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up.

    RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76).

    CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART Clinical-TrialsRegister.eu number, 2012-005260-10; ClinicalTrials.gov number, NCT02311231.)

  • 69. Fajardo, Ignacio
    et al.
    Svensson, Linda
    Bucht, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Pejler, Gunnar
    Increased levels of hypoxia-sensitive proteins in allergic airway inflammation.2004In: Am J Respir Crit Care Med, ISSN 1073-449X, Vol. 170, no 5, p. 477-84Article in journal (Refereed)
  • 70.
    Farooqi, Nighat
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nutrition and energy expenditure in women with chronic obstructive pulmonary disease2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim

    The overall objective of this thesis was to increase the knowledge and validate methods for assessment of total daily energy expenditure (TEE), energy requirement and energy intake (EI) in women with COPD. We also investigated the relationship of BMI with clinical characteristics of COPD in a population-based study. Due to the substantial and increasing morbidity in women with COPD, special attention was given to this group.

    Methods

    Resting metabolic rate (RMR) was measured by indirect calorimetry (IC). TEE was measured by criterion method, doubly labeled water (DLW) (Paper I-III) during a 14-day period. TEE was simultaneously assessed by SenseWear Armband, software version 5.1 and 6.1 (SWA5 respectively SWA6), and ActiHeart (paper I). EI was assessed by diet history interview and 7-day food diary (paper II), and energy requirement was predicted using pedometer-determined physical activity level (paper III). Energy requirement data was also acquired from studies concerning TEE measured by DLW in patients with COPD (paper IV). BMI and other characteristics in subjects with COPD were compared with non-COPD subjects in a population-based study, Obstructive Lung disease in Norrbotten study (OLIN) (paper V).

    Results

    There was a large variation in RMR and TEE measured by DLW in this group of women with COPD. The results of energy expenditure study showed that the SWA5 assessed TEE with good accuracy over a 14-day period in free-living women with COPD. However, the SWA6 and ActiHeart methods tend to underestimate TEE. A higher proportion of women were within ± 5% of the TEE individually measured with the DLW method using SWA5 than SWA6 and AH (63%, 47%, 37% respectively). The agreement between the TEE measured by DLW and SWA5 was strong, and with SWA6 and ActiHeart it was lesser. Bland-Altman plots revealed no systematic bias for TEE. The reported EI was underestimated by 28% respectively 20 % when assessed by diet, and the 7-day food diary compared with the criterion method, DLW. More women were identified as valid-reporters based on their 7- day food diaries than on their diet histories (63% vs 32%). The accuracy of reported EI was only related to BMI. The agreement between the DLW and the EI methods was weak. The Bland-Altman plots revealed a slight systematic bias for both methods. The energy requirement predicted by pedometer-determined PAL multiplied by six different RMR equations was within a reasonable accuracy (±10%) of the measured TEE for all equations except one. The agreement between the DLW and four of six predicted TEE methods was strong. The Bland– Altman plots revealed no systematic bias for predicted energy requirement except for one. Estimated PAL from the pedometer was lower by 14 % than the measured criterion PAL. The energy requirement calculation based on available TEE data measured by DLW varied by BW and FFM. Compared to men, women had a lower RMR and TEE/kg BW/day, and higher RMR and TEE/kg FFM/day. The correlates of RMR/kg BW were gender and forced expiratory volume in 1st second (FEV1) % of predicted value, of TEE/ kg BW the correlates were age and gender, and of TEE/kg FFM were age and FEV1 % predicted. BMI decreased significantly with increase in disease severity and correlated significantly to forced expiratory volume in 1st second % predicted. In the population-based study (OLIN), subjects with COPD had lower BMI and a higher prevalence of underweight than in non-COPD, and its sub-groups namely, normal lung function and restrictive spirometry pattern subjects. There was an independent association between COPD and low BMI. Fewer COPD subjects were obese than in the non-COPD, normal lung function and restrictive spirometry pattern groups. Among the subjects with COPD, women had a lower mean BMI and a higher proportion were under-weight than men. In COPD women with under-weight, FEV1 % predicted values increased with an increase in BMI.

    Conclusion

    Compared with the gold standard DLW method, the total daily energy expenditure can be assessed reliably by SenseWear Armband 5 in women with COPD, while other devices underestimated TEE. The energy intake was underestimated by diet history and 7-day food diary methods, and energy requirement was predicted with reasonable accuracy using pedometer-determined PAL and common RMR equations, compared with DLW. Furthermore, the energy requirement was determined per kg BW/day and per kg FFM/day, using DLW based TEE data in patients with COPD. In the population-based study (OLIN), subjects with COPD had lower BMI and higher prevalence of under-weight than subjects without COPD. There was a gender difference, which was particularly significant in COPD, for women to have lower mean BMI and a higher prevalence of under-weight. The present findings indicate that low BMI is common in COPD and needs to be intervened. For a successful nutritional treatment, it is imperative to assess the patient’s ener

  • 71.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Carlsson, Maine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Social medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Slinde, Frode
    Energy expenditure in women and men with COPDArticle in journal (Refereed)
  • 72.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Carlsson, Maine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Slinde, Frode
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Sweden..
    Energy expenditure in women and men with COPD2018In: Clinical Nutrition ESPEN, ISSN 2405-4577, Vol. 28, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Background: Many patients with chronic obstructive pulmonary disease (COPD) lose weight. Successful nutritional intervention is vital, thus assessment of energy requirement is required. The aim of this study was to present an improved possibility to assess energy requirement in patients with COPD.

    Methods: Pub Med search was conducted for all the studies reporting total energy expenditure (TEE) measured by doubly labeled water (DLW) method in patients with COPD. Four studies were identified, whereof three were conducted in Sweden. The present analysis is based on these three studies of which the data was acquired.

    Results: There was a large variation in resting metabolic rate (RMR) and TEE. Body mass index decreased significantly with increase in disease severity (p < .001), and correlated significantly to forced expiratory volume in 1 s (FEV1) % predicted (r = .627, p < .001). FEV1% predicted had a significant correlation with RMR/kg body weight (BW)/day (r = -.503, p = .001), RMR/kg fat-free mass (FFM)/day (r = .338, p = .031), and TEE/kg FFM/day (r = .671, p < .001). Compared to men, women had a lower RMR and TEE/kg BW/day (p < .001 respectively p = .002), and higher RMR and TEE/kg FFM/day (p = .080 respectively p = .005). The correlates of: RMR/kg BW were gender and FEV1% predicted; of TEE/kg BW the correlates were age and gender, and of TEE/kg FFM the correlates were age and FEV1% predicted.

    Conclusion: In this study, we have presented a possibility to assess energy requirement per kg BW/day and per kg FFM/day in patients with COPD in clinical settings. However, gender, age, and disease severity must be considered. 

  • 73.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nordström, Lisbeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Lundgren, Rune
    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.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Changes in body weight and physical performance after receiving dietary advice in patients with chronic obstructive pulmonary disease (COPD): 1-year follow-up.2011In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 53, no 1, p. 70-75Article in journal (Refereed)
    Abstract [en]

    Nutritional studies in patients with chronic obstructive pulmonary disease (COPD) are often based on oral nutritional supplementation and are of short duration. Our aim was to study the changes in body weight and physical performance in COPD patients after receiving the dietary advice for 1 year. Thirty-six patients with COPD as a primary diagnosis (mean age: 68.5+/-7.8 years), referred to a pulmonary rehabilitation program were studied. Each patient received dietary advice individually. Body weight had increased significantly by 1.3kg (p=0.02) and walking distance by 83.2m (p=0.007) after 1 year. There was an increase in mean handgrip strength after 1 year (1.6kg, p=0.07). The mean intake of energy and protein expressed as percent of energy and protein requirement had increased after 1 year (15%, p<0.001, and 5.6%, p=0.09, respectively). Handgrip strength correlated significantly with energy (r=0.53, p=0.002), fat (r=0.50, p=0.02) and protein intake (r=0.41, p=0.002) after 1 year. In conclusion, positive effects on body weight, handgrip strength and walking distance in patients with COPD were seen after receiving dietary advice with a 1-year follow-up.

  • 74.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umea Univ Hosp, Dept Resp Med & Allergy, SE-90185 Umea, Sweden.
    Slinde, F.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Assessment of energy intake in women with chronic obstructive pulmonary disease: A doubly labeled water method study2015In: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 19, no 5, p. 518-524Article in journal (Refereed)
    Abstract [en]

    To maintain energy balance, reliable methods for assessing energy intake and expenditure should be used in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to validate the diet history and 7-day food diary methods of assessing energy intake (EI) using total energy expenditure (TEE) with the doubly labeled water (DLW) method (TEEDLW) as the criterion method in outpatient women with COPD. EI was assessed by diet history (EIDH) and a 7-day food diary (EIFD) in 19 women with COPD, using TEEDLW as the criterion method. The three methods were compared using intra-class correlation coefficients (ICC) and Bland-Altman analyses. The participants were classified according to their reporting status (EI/TEE) as valid-reporters 0.79-1.21, under-reporters < 0.79 or over-reporters > 1.21. Diet history underestimated reported EI by 28%, and 7-day food diary underestimated EI by approximately 20% compared with TEEDLW. The ICC analysis showed weak agreement between TEEDLW and EIDH (ICC=-0.01; 95%CI-0.10 to 0.17) and between TEEDLW and EIFD (ICC=0.11; 95%CI -0.16 to 0.44). The Bland-Altman plots revealed a slight systematic bias for both methods. For diet history, six women (32%) were identified as valid-reporters, and for the 7-day food diary, twelve women (63%) were identified as valid-reporters. The accuracy of reported EI was only related to BMI. The diet history and 7-day food diary methods underestimated energy intake in women with COPD compared with the DLW method. Individuals with higher BMIs are prone to underreporting. Seven-day food diaries should be used with caution in assessing EI in women with COPD.

  • 75.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Slinde, Frode
    Carlsson, Maine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Predicting energy requirement with pedometer-determined physical-activity level in women with chronic obstructive pulmonary disease2015In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 10, p. 1129-1137Article in journal (Refereed)
    Abstract [en]

    Background: In clinical practice, in the absence of objective measures, simple methods to predict energy requirement in patients with chronic obstructive pulmonary disease (COPD) needs to be evaluated. The aim of the present study was to evaluate predicted energy requirement in females with COPD using pedometer-determined physical activity level (PAL) multiplied by resting metabolic rate (RMR) equations. Methods: Energy requirement was predicted in 18 women with COPD using pedometer-determined PAL multiplied by six different RMR equations (Harris-Benedict; Schofield; World Health Organization; Moore; Nordic Nutrition Recommendations; Nordenson). Total energy expenditure (TEE) was measured by the criterion method: doubly labeled water. The predicted energy requirement was compared with measured TEE using intraclass correlation coefficient (ICC) and Bland-Altman analyses. Results: The energy requirement predicted by pedometer-determined PAL multiplied by six different RMR equations was within a reasonable accuracy (+/- 10%) of the measured TEE for all equations except one (Nordenson equation). The ICC values between the criterion method (TEE) and predicted energy requirement were: Harris-Benedict, ICC =0.70, 95% confidence interval (CI) 0.23-0.89; Schofield, ICC =0.71, 95% CI 0.21-0.89; World Health Organization, ICC =0.74, 95% CI 0.33-0.90; Moore, ICC =0.69, 95% CI 0.21-0.88; Nordic Nutrition Recommendations, ICC =0.70, 95% CI 0.17-0.89; and Nordenson, ICC =0.40, 95% CI -0.19 to 0.77. Bland-Altman plots revealed no systematic bias for predicted energy requirement except for Nordenson estimates. Conclusion: For clinical purposes, in absence of objective methods such as doubly labeled water method and motion sensors, energy requirement can be predicted using pedometer-determined PAL and common RMR equations. However, for assessment of nutritional status and for the purpose of giving nutritional treatment, a clinical judgment is important regarding when to accept a predicted energy requirement both at individual and group levels.

  • 76.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Slinde, Frode
    Hedman, Linnea
    Carlsson, Maine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Social medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nilsson, Ulf
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindberg, Anne
    The association between COPD and BMI: a population-based studyManuscript (preprint) (Other academic)
  • 77.
    Farooqi, Nighat
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Slinde, Frode
    Håglin, Lena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Validation of SenseWear Armband and ActiHeart monitors for assessments of daily energy expenditure in free-living women with chronic obstructive pulmonary disease2013In: Physiological Reports, E-ISSN 2051-817X, Vol. 1, no 6, article id e00150Article in journal (Refereed)
    Abstract [en]

    To provide individually adapted nutritional support to patients with chronic obstructive pulmonary disease (COPD), objective and reliable methods must be used to assess patient energy requirements. The aim of this study was to validate the use of SenseWear Armband (SWA) and ActiHeart (AH) monitors for assessing total daily energy expenditure (TEE) and activity energy expenditure (AEE) and compare these techniques with the doubly labeled water (DLW) method in free‐living women with COPD. TEE and AEE were measured in 19 women with COPD for 14 days using SWAs with software version 5.1 (TEESWA5, AEESWA5) or 6.1 (TEESWA6, AEESWA6) and AH monitors (TEEAH, AEEAH), using DLW (TEEDLW) as the criterion method. The three methods were compared using intraclass correlation coefficient (ICC) and Bland–Altman analyses. The mean TEE did not significantly differ between the DLW and SWA5.1 methods (−21 ± 726 kJ/day; P = 0.9), but it did significantly differ between the DLW and SWA6.1 (709 ± 667 kJ/day) (P < 0.001) and the DLW and AH methods (709 ± 786 kJ/day) (P < 0.001). Strong agreement was observed between the DLW and TEESWA5 methods (ICC = 0.76; 95% CI 0.47–0.90), with moderate agreements between the DLW and TEESWA6 (ICC = 0.66; 95% CI 0.02–0.88) and the DLW and TEEAH methods (ICC = 0.61; 95% CI 0.05–0.85). Compared with the DLW method, the SWA5.1 underestimated AEE by 12% (P = 0.03), whereas the SWA6.1 and AH monitors underestimated AEE by 35% (P < 0.001). Bland–Altman plots revealed no systematic bias for TEE or AEE. The SWA5.1 can reliably assess TEE in women with COPD. However, the SWA6.1 and AH monitors underestimate TEE. The SWA and AH monitors underestimate AEE.

  • 78.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    From the author2007In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 30, no 5, p. 1023-1024Article in journal (Other academic)
  • 79.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Obstruktiv sömnapné ökar risken för tidig död bland strokepatienter2008In: Läkartidningen, Vol. 22, p. 1647-Article in journal (Other academic)
  • 80.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Sleep apnea - Where are the physicians in respiratory medicine?2008In: Clinical Respiratory Journal, Vol. 2, p. 196-Article in journal (Refereed)
  • 81.
    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.
    Sleep apnoea screening in heart failure? Not until benefit is proven!2007In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 29, no 6, p. 1073-1074Article in journal (Refereed)
  • 82.
    Franklin, Karl A
    et al.
    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.
    Anttila, Heidi
    Axelsson, Susanna
    Gislason, Thorarinn
    Maasilta, Paula
    Myhre, Kurt I
    Rehnqvist, Nina
    Effects and side-effects of surgery for snoring and obstructive sleep apnea--a systematic review2009In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 32, no 1, p. 27-36Article in journal (Refereed)
    Abstract [en]

    Only a small number of randomized controlled trials with a limited number of patients assessing some surgical modalities for snoring or sleep apnea are available. These studies do not provide any evidence of effect from laser-assisted uvulopalatoplasty or radiofrequency ablation on daytime sleepiness, apnea reduction, quality of life or snoring. We call for research of randomized, controlled trials of surgery other than uvulopalatopharyngoplasty and uvulopalatoplasty, as they are related to a high risk of long-term side-effects, especially difficulty swallowing.

  • 83.
    Franklin, Karl A
    et al.
    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.
    Gi­slason, Thorarinn
    Omenaas, Ernst
    Jogi, Rain
    Jensen, Erik Juel
    Lindberg, Eva
    Gunnbjörnsdottir, Maria
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Laerum, Birger N
    Björnsson, Eythor
    Toren, Kjell
    Janson, Christer
    The influence of active and passive smoking on habitual snoring.2004In: Am J Respir Crit Care Med, ISSN 1073-449X, Vol. 170, no 7, p. 799-803Article in journal (Refereed)
  • 84.
    Franklin, Karl A
    et al.
    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.
    Haglund, Bengt
    Axelsson, Susanna
    Holmlund, Thorbjörn
    Rosén, Mans
    Risks with surgical interventions for obstructive sleep apnea in adults: A registry-based study in Sweden2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 14, p. 1012-1014Article in journal (Refereed)
  • 85.
    Franklin, Karl A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rehnqvist, Nina
    Freyschuss, Bo
    Axelsson, Susanna
    Obesity surgery in sleep apnea? The effect should be studied in RCTs.2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 37, p. 2499-2500Article in journal (Other (popular science, discussion, etc.))
  • 86.
    Franklin, Karl A.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    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.
    Lindberg, Eva
    Sleep apnoea is a common occurrence in females2013In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 41, no 3, p. 610-615Article in journal (Refereed)
    Abstract [en]

    Obstructive sleep apnoea (OSA) is primarily regarded as a male disorder, presenting with snoring, daytime sleepiness and cardiovascular disease. We aimed to determine the frequency of sleep apnoea among females in the general population. We investigated 400 females from a population-based random sample of 10,000 females aged 20-70 yrs. They answered a questionnaire and performed overnight polysomnography. OSA (apnoea/hypopnoea index (AHI) >= 5) was found in 50% (95% CI 45-55%) of females aged 20-70 yrs. Sleep apnoea was related to age, obesity and hypertension, but not to daytime sleepiness. Severe sleep apnoea (AHI >= 30) was present in 14% (95% CI 8.1-21%) of females aged 55-70 yrs and in 31% (95% CI 12-50%) of obese females with a body mass index of >= 30 kg.m(-2) aged 55-70 yrs. Sleep apnoea with daytime sleepiness and sleep apnoea with hypertension were observed as two different phenotypes of OSA. OSA occurs in 50% of females aged 20-70 yrs. 20% of females have moderate and 6% severe sleep apnoea. Sleep apnoea in females is related to age, obesity and hypertension, but not to daytime sleepiness. When searching for sleep apnoea in females, females with hypertension or obesity should be investigated.

  • 87.
    Franklin, Karl
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Axelsson, S
    Rehnquist, Nina
    Obstructive sleep apnoea syndrome. Report of a joint Nordic project.2007Report (Other academic)
  • 88.
    Franklin, Karl
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine. Lungmedicin.
    Gustafson, Torbjörn
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine. Lungmedicin.
    Ranstam, Jonas
    Ström, Kerstin
    Survival and future need of long-term oxygen therapy for chronic obstructive pulmonary disease--gender differences.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 7, p. 1506-1511Article in journal (Refereed)
  • 89.
    Franklin, Karl
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Janson, Christer
    Gíslason, Thórarinn
    Gulsvik, Amund
    Gunnbjörnsdottir, Maria
    Laerum, Birger N
    Lindberg, Eva
    Norrman, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Omenaas, Ernst
    Torén, Kjell
    Svanes, Cecilie
    Early life environment and snoring in adulthood.2008In: Respiratory research (Online), ISSN 1465-9921, E-ISSN 1465-993X, Vol. 9, no 63Article in journal (Refereed)
    Abstract [en]

    Background: To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life. 

    Methods: A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%). 

    Results: A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child (OR = 1.18; 95% CI 1.05-1.33), growing up in a large family (OR = 1.04; 95% CI 1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95% CI 1.12-1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined. 

    Conclusion: The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood.

  • 90.
    Franklin, Karl
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Rehnqvist, Nina
    Axelsson, S
    Obstruktiv sömnapné - Starkt vetenskapligt stöd för behandling med CPAP2007In: Tandläkartidningen, Vol. 8, p. 44-7Article in journal (Refereed)
  • 91.
    Franklin, Karl
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Rehnqvist, Nina
    Axelsson, Susanna
    [Obstructive sleep apnea syndrome--diagnosis and treatment. A systematic literature review from SBU]2007In: Lakartidningen, ISSN 0023-7205, Vol. 104, no 40, p. 2878-81Article in journal (Refereed)
  • 92.
    Franklin, Karl
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Bålfors, Eva
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hemodynamics, cerebral circulation, and oxygen saturation in Cheyne-Stokes respiration1997In: J Appl Physiol, Vol. 83, no 4, p. 1184-91Article in journal (Refereed)
    Abstract [en]

    Because cardiovascular disorders and stroke may induce Cheyne-Stokes respiration, our purpose was to study the interaction among cerebral activity, cerebral circulation, blood pressure, and blood gases during Cheyne-Stokes respiration. Ten patients with heart failure or a previous stroke were investigated during Cheyne-Stokes respiration with recordings of daytime polysomnography, cerebral blood flow velocity, intra-arterial blood pressure, and intra-arterial oxygen saturation with and without oxygen administration. There were simultaneous changes in wakefulness, cerebral blood flow velocity, and respiration with accompanying changes in blood pressure and heart rate approximately 10 s later. Cerebral blood flow velocity, blood pressure, and heart rate had a minimum occurrence in apnea and a maximum occurrence during hyperpnea. The apnea-induced oxygen desaturations were diminished during oxygen administration, but the hemodynamic alterations persisted. Oxygen desaturations were more severe and occurred earlier according to intra-arterial measurements than with finger oximetry. It is not possible to explain Cheyne-Stokes respiration by alterations in blood gases and circulatory time alone. Cheyne-Stokes respiration may be characterized as a state of phase-linked cyclic changes in cerebral, respiratory, and cardiovascular functions probably generated by variations in central nervous activity.

  • 93. Gerlofs-Nijland, Miriam E
    et al.
    Dormans, Jan A M A
    Bloemen, Henk J T
    Leseman, Daan L A C
    John, A
    Boere, F
    Kelly, Frank J
    Mudway, Ian S
    Jimenez, Al A
    Donaldson, Ken
    Guastadisegni, Cecilia
    Janssen, Nicole A H
    Brunekreef, Bert
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    van Bree, Leendert
    Cassee, Flemming R
    Toxicity of coarse and fine particulate matter from sites with contrasting traffic profiles.2007In: Inhal Toxicol, ISSN 1091-7691, Vol. 19, no 13, p. 1055-69Article in journal (Refereed)
  • 94.
    Gonzalez, Manuel Cruz
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Robinson, Simon
    Mills, Nicholas L
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyperleptinemia is associated with altered endothelial functionManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction The adipocyte-derived hormone leptin has been associated with increased risk of cardiovascular disease but the underlying mechanisms are unclear. Leptin effects on vascular endothelium may be a key mediator although contradictory results have been presented. We aimed to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary heart disease.

    Methods and Results The vascular effects of leptin were assessed using venous occlusion plethysmography in healthy volunteers (n=17) and in patients with stable coronary heart disease (CHD) (n=83). In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n=10) did not affect forearm blood flow or plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 (PAI-1) concentrations (all P>0.05).  However, during concomitant co-infusion with leptin (800 ng/min; n=10), induced vasodilatation was reduced (P=0.001), and tPA activity increased (P=0.002). In line with this, patients with coronary heart disease included in the highest tertile of plasma leptin concentrations had reduced substance P-induced vasodilatation (P<0.001), and increased tPA antigen and activity release (p<0.001 and p=0.03 respectively) compared to those in the lowest tertile.

    Conclusions Although leptin does not directly affect basal vascular function, acute local and chronic systemic hyperleptinemia are associated with altered endothelial function in healthy volunteers and patients with coronary heart disease respectively. These results support hyperleptinemia as a link between obesity and cardiovascular disease.

  • 95.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fowler, Christopher
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Relative and absolute reliability of measures of linoleic acid-derived oxylipins in human plasma2015In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 121, no Part B, p. 227-233Article in journal (Refereed)
    Abstract [en]

    Modern analytical techniques allow for the measurement of oxylipins derived from linoleic acid in biological samples. Most validatory work has concerned extraction techniques, repeated analysis of aliquots from the same biological sample, and the influence of external factors such as diet and heparin treatment upon their levels, whereas less is known about the relative and absolute reliability of measurements undertaken on different days. A cohort of nineteen healthy males were used, where samples were taken at the same time of day on two occasions, at least 7 days apart. Relative reliability was assessed using Lin's concordance correlation coefficients (CCC) and intraclass correlation coefficients (ICC). Absolute reliability was assessed by Bland-Altman analyses. Nine linoleic acid oxylipins were investigated. ICC and CCC values ranged from acceptable (0.56 [13-HODE]) to poor (near zero [9(10)- and 12(13)-EpOME]). Bland-Altman limits of agreement were in general quite wide, ranging from ±0.5 (12,13-DiHOME) to ±2 (9(10)-EpOME; log10 scale). It is concluded that relative reliability of linoleic acid-derived oxylipins varies between lipids with compounds such as the HODEs showing better relative reliability than compounds such as the EpOMEs. These differences should be kept in mind when designing and interpreting experiments correlating plasma levels of these lipids with factors such as age, body mass index, rating scales etc.

  • 96. Gruber, Jan
    et al.
    Tang, Soon Yew
    Jenner, Andrew M
    Mudway, Ian
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Kasiman, Katherine
    Lee, Chung-Yung J
    Seet, Raymond C S
    Zhang, Wenxia
    Chen, Christopher
    Kelly, Frank J
    Halliwell, Barry
    Allantoin in human plasma, serum, and nasal-lining fluids as a biomarker of oxidative stress: avoiding artifacts and establishing real in vivo concentrations.2009In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 11, no 8, p. 1767-1776Article in journal (Refereed)
    Abstract [en]

    Urate is the terminal product of purine metabolism in primates, including humans. Urate is also an efficient scavenger of oxidizing species and is thought to be an important antioxidant in human body fluids. Allantoin, the major oxidation product of urate, has been suggested as a candidate biomarker of oxidative stress because it is not produced metabolically. Although urate is converted to allantoin under strongly alkaline pH, such conditions have been used in the past to facilitate extraction of allantoin. We evolved a method for the determination of allantoin concentrations in human plasma and serum by gas chromatography-mass spectrometry without such artifact. With this method, we show that alkaline conditions do indeed cause breakdown of urate, leading to significant overestimation of allantoin concentration in human samples. By using our alternative method, serum samples from 98 volunteers were analyzed, and allantoin levels were found to be significantly lower than was previously reported. The in vivo utility and sensitivity of our method was further evaluated in human nasal-lining fluids. We were able to demonstrate an ozone-induced increase in allantoin, in the absence of increases in either ascorbate or glutathione oxidation products.

  • 97. Guastadisegni, Cecilia
    et al.
    Kelly, Frank J
    Cassee, Flemming R
    Gerlofs-Nijland, Miriam E
    Janssen, Nicole AH
    Pozzi, Roberta
    Brunekreef, Bert
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian
    Determinants of the proinflammatory action of ambient particulate matter in immortalized murine macrophages2010In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 118, no 12, p. 1728-1734Article in journal (Refereed)
    Abstract [en]

    We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells.

  • 98. Gulin-Sarfraz, Tina
    et al.
    Jonasson, Sofia
    Wigenstam, Elisabeth
    von Haartman, Eva
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
    Rosenholm, Jessica M.
    Feasibility Study of Mesoporous Silica Particles for Pulmonary Drug Delivery: Therapeutic Treatment with Dexamethasone in a Mouse Model of Airway Inflammation2019In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 11, no 4, article id 149Article in journal (Refereed)
    Abstract [en]

    Diseases in the respiratory tract rank among the leading causes of death in the world, and thus novel and optimized treatments are needed. The lungs offer a large surface for drug absorption, and the inhalation of aerosolized drugs are a well-established therapeutic modality for local treatment of lung conditions. Nanoparticle-based drug delivery platforms are gaining importance for use through the pulmonary route. By using porous carrier matrices, higher doses of especially poorly soluble drugs can be administered locally, reducing their side effects and improving their biodistribution. In this study, the feasibility of mesoporous silica particles (MSPs) as carriers for anti-inflammatory drugs in the treatment of airway inflammation was investigated. Two different sizes of particles on the micron and nanoscale (1 mu m and 200 nm) were produced, and were loaded with dexamethasone (DEX) to a loading degree of 1:1 DEX:MSP. These particles were further surface-functionalized with a polyethylene glycol-polyethylene imine (PEG-PEI) copolymer for optimal aqueous dispersibility. The drug-loaded particles were administered as an aerosol, through inhalation to two different mice models of neutrophil-induced (by melphalan or lipopolysaccharide) airway inflammation. The mice received treatment with either DEX-loaded MSPs or, as controls, empty MSPs or DEX only; and were evaluated for treatment effects 24 h after exposure. The results show that the MEL-induced airway inflammation could be treated by the DEX-loaded MSPs to the same extent as free DEX. Interestingly, in the case of LPS-induced inflammation, even the empty MSPs significantly down-modulated the inflammatory response. This study highlights the potential of MSPs as drug carriers for the treatment of diseases in the airways.

  • 99.
    Gulyas, Miklos
    et al.
    Uppsala, Sweden.
    Mattsson, Johanna S. M.
    Uppsala, Sweden.
    Lindgren, Andrea
    Linkoping, Sweden.
    Sederholm, Christer
    Linkoping, Sweden.
    Ek, Lars
    Lund, Sweden.
    Lamberg, Kristina
    Uppsala, Sweden.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Holmberg, Erik
    Gothenburg, Sweden.
    Micke, Patrick
    Uppsala, Sweden.
    Bergman, Bengt
    Gothenburg, Sweden.
    COX-2 Expression Does Not Predict Outcome of Celecoxib in Addition to Standard Chemotherapy in Advanced Non-Small Cell Lung Cancer2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S541-S542Article in journal (Other academic)
  • 100.
    Gustafson, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine. Lungmedicin.
    Dahlman-Höglund, Anna
    Nilsson, Kenneth
    Ström, Kerstin
    Tornling, Göran
    Torén, Kjell
    Occupational exposure and severe pulmonary fibrosis.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 10, p. 2207-2212Article in journal (Refereed)
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