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  • 1. Aalbers, R
    et al.
    Backer, V
    Kava, T T K
    Omenaas, E R
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Jorup, C
    Welte, T
    Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.2004In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 20, no 2, p. 225-40Article in journal (Refereed)
  • 2.
    Abdel-Aziz, Mahmoud I.
    et al.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Dept of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
    Vijverberg, Susanne J.H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Neerincx, Anne H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Brinkman, Paul
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Wagener, Ariane H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Riley, John H.
    Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom.
    Sousa, Ana R.
    Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom.
    Bates, Stewart
    Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom.
    Wagers, Scott S.
    BioSci Consulting, Maasmechelen, Belgium.
    De Meulder, Bertrand
    European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBLINSERM, Lyon, France.
    Auffray, Charles
    European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBLINSERM, Lyon, France.
    Wheelock, Åsa M.
    Respiratory Medicine Unit, Dept of Medicine and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
    Bansal, Aruna T.
    Acclarogen Ltd, St John’s Innovation Centre, Cambridge, United Kingdom.
    Caruso, Massimo
    Dept of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
    Chanez, Pascal
    Département des Maladies Respiratoires APHM, U1067 INSERM, Aix Marseille Université Marseille, Marseille, France.
    Uddin, Mohib
    AstraZeneca BioPharmaceuticals R&D, Gothenburg, Sweden.
    Corfield, Julie
    AstraZeneca R&D, Molndal, Sweden; Areteva R&D, Nottingham, United Kingdom.
    Horvath, Ildiko
    Dept of Public Health, Semmelweis University, National Koranyi Institute for Pulmonology, Budapest, Hungary.
    Krug, Norbert
    Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany.
    Musial, Jacek
    Dept of Medicine, Jagiellonian University Medical College, Krakow, Poland.
    Sun, Kai
    Data Science Institute, South Kensington Campus, Imperial College London, London, United Kingdom.
    Shaw, Dominick E.
    Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Montuschi, Paolo
    Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
    Fowler, Stephen J.
    Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre and NIHR Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
    Lutter, René
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Dept of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Djukanovic, Ratko
    NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, and Human Development and Health, University of Southampton, Southampton, United Kingdom.
    Howarth, Peter
    NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, and Human Development and Health, University of Southampton, Southampton, United Kingdom.
    Skipp, Paul
    Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom.
    Sanak, Marek
    Dept of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
    Adcock, Ian M.
    National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield NHS Trust, London, United Kingdom.
    Chung, Kian Fan
    National Heart and Lung Institute, Imperial College London, Royal Brompton and Harefield NHS Trust, London, United Kingdom.
    Sterk, Peter J.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
    Kraneveld, Aletta D.
    Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
    Maitland-Van der Zee, Anke H.
    Dept of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Dept of Pediatric Respiratory Medicine, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, Netherlands.
    A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes2022In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 59, no 1, article id 2102603Article in journal (Refereed)
    Abstract [en]

    A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.

  • 3. Alahmadi, Fahad
    et al.
    Simpson, Andrew
    Gomez, Christina
    Wheelock, Craig
    Shaw, Dominick
    Fleming, Louise
    Roberts, Graham
    Riley, John
    Bates, Stewart
    Sousa, Ana R.
    Knowles, Richard
    Bansal, Aruna
    Corfield, Julie
    Pandis, Ioannis
    Sun, Kai
    Bakke, Per
    Caruso, Massimo
    Chanez, Pascal
    Dahlen, Babro
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Singer, Florian
    Wagers, Scott
    Adcock, Ian
    Djukanovic, Ratko
    Chung, Kian
    Sterk, Peter J.
    Dahlen, Sven-Erik
    Fowler, Stephen J.
    Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
    Abstract [en]

    Introduction: Rates of sub-optimal adherence to medications in asthma range up to 70%; the impact in severe asthma is likely to be particularly high. We measured self-reported adherence in participants in the U-BIOPRED cohort prescribed daily prednisolone using the Medication Adherence Response Scale (MARS), and compared to measured urinary prednisolone and metabolites in order to determine: 1. the prevalence of suboptimal adherence by each method; 2. the ability of MARS to predict urinary steroid detection.

    Methods: Participants completed the MARS, and/or provided urine samples (analysed for prednisolone and metabolites by LCMS). The performance characteristics of the MARS predicting undetected urinary steroid were calculated in the subgroup having both tests.

    Results: 181 participants currently taking regular oral corticosteroids were included, 59% female, mean (SD) age 54(12)yrs, FEV1 64.7(20.4)% predicted. Sub-optimal adherence (MARS score < 4.5) was reported in 62 participants, and 76 did not have detectable urinary prednisolone or metabolites. Good adherence by both methods was detected in only 52 participants (34%, see table). There was no difference in daily prednisolone dose between detectable and undetectable metabolites groups (p=0.848).

    Conclusion: Low levels of adherence to treatment in severe asthma is a common problem, when measured either directly or self-reported. There was very poor agreement (48% concordance) between these two methods, and we suggest that, for now both approaches should be used.

  • 4.
    Andersen, Grethe N.
    et al.
    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.
    Nagaeva, O
    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.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Cytokine mRNA profile of alveolar T lymphocytes and macrophages in patients with systemic sclerosis suggests a local Tr1 response2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, no 3, p. 272-81Article in journal (Refereed)
    Abstract [en]

    The development of an autoimmune disease like systemic sclerosis (SSc) is suspected to be driven by an activated T lymphocyte subset, expressing a cytokine profile specific to the disease. To further characterize the type of immune reaction in SSc, we searched for a broad panel of cytokine messenger ribonucleic acids (mRNAs) in T lymphocytes and monocytes/macrophages from paired samples of bronchoalveolar lavage fluid and peripheral blood in 18 patients and 16 age- and sex-matched controls. RNA from CD3(+) T lymphocytes and CD14(+) monocytes/macrophages was examined by means of the reverse transcriptase polymerase chain reaction. SSc alveolar T lymphocytes expressed a cytokine profile suggestive of a mixed Th1/Th2 reaction, showing an increased frequency of mRNA for interleukin (IL)-10, IL-6 and interferon (IFN)γ, while IL-1β, IFNγ and tumour necrosis factor β were expressed in blood T lymphocytes in a higher percentage of patients with SSc than controls. SSc alveolar T cells expressed IL-10 mRNA more often than peripheral T cells, a phenomenon not found in controls and which may point at local IL-10 activation/response in SSc lung. Transforming growth factor β mRNA was present in all alveolar as well as peripheral blood T cell samples in patients and controls. The cytokine mRNA profile in SSc with interstitial lung disease (ILD) was similar to the profile found in SSc without ILD. Our findings point at a mixed Th1/Th2 reaction in SSc and may indicate regulatory T 1 cell activation/response in the lungs of patients with SSc.

  • 5.
    Andersen, Grethe Neumann
    et al.
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Hackett, Tillie-Louise
    Kazzam, Elsadig
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Warner, Jane
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Sandström, Thomas
    Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 10, p. 2199-2206Article in journal (Refereed)
    Abstract [en]

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

  • 6.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Stridsman, Caroline
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundback, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eosinophilic inflammation and lung function decline in a long-term follow-up of a large population-based asthma cohort2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
    Abstract [en]

    The relationship between lung function decline and airway inflammation among asthmatics has important therapeutic implications, but has rarely been studied in large samples or in population-based asthma cohorts.

    A population-based adult asthma cohort (n=2055) was recruited during 1986-2001 and clinically examined including spirometry. In 2012-2014, all still eligible subjects (n=1425) were invited to a clinical follow-up including spirometry, blood sampling, and a structured interview, and n=1006 participated (55% women, mean age 59y, 32-92y). Linear regression was performed with age, sex, smoking habits, year of first examination, family history of asthma, socioeconomic status, eosinophils (EOS)>=0.3x109/L, and neutrophils (NEUT)>=5.0x109/L as independent variables and pre-bronchodilator FEV1 decline/year (ml and % of predicted [pp], respectively) as dependent. In secondary models, both ICS use at baseline and ICS use at follow-up were also included.

    The mean annual FEV1 decline in ml (pp) among asthmatics with EOS<0.3, 0.4>EOS>=0.3 and EOS>=0.4x109/L, respectively, was 26ml (0.03pp), 29ml (0.10pp) and 34ml (0.27pp) (p<0.001). In adjusted analyses, EOS>=0.3 was significantly associated with FEV1 decline, both in terms of ml (4ml excess annual decline vs EOS<0.3) and pp. The association between EOS and FEV1 decline in pp, but not ml, remained when additionally adjusted for ICS use. The association with NEUT>=5.0x109/L was less clear.

    On group level, adult asthmatics with higher levels of eosinophils in blood have a history of excess FEV1 decline compared to asthmatics with lower levels of eosinophil inflammation, independent of other factors such as ICS use.

  • 7.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Stridsman, Caroline
    Eriksson, Berne
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eklund, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundback, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Severe asthma among adults: Prevalence and clinical characteristics2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
    Abstract [en]

    Background: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.

    Methods: We estimated the prevalence and studied characteristics of severe asthma in a large adult population-based asthma cohort followed for 10-28 years in northern Sweden: 1006 subjects participated in a follow-up during 2012-14, when 830 (82.5%) still had current asthma (mean age 59y, 32-92y, 56% women). Severe asthma was defined according to three internationally well-known criteria: the US SARP, ATS/ERS and GINA. All subjects with severe asthma were undergoing respiratory specialist care, and were also contacted by telephone to verify adherence to treatment.

    Results: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma and <10% had controlled asthma according to the ACT. Severe asthma was related to age >50 years, nasal polyposis, decreased FEV1, not fully reversible airway obstruction, sensitization to aspergillus, elevated neutrophils and partly to eosinophils, and tended to be more common in women.

    Conclusion: The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the population in northern Sweden. A substantial proportion of those with severe asthma had uncontrolled disease, and severe asthma differed significantly from other asthma in terms of both clinical and inflammatory characteristics.

  • 8.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stridsman, Caroline
    Department of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Eriksson, Berne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eklund, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Severe asthma: A population study perspective2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 819-828Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.

    OBJECTIVE: To describe characteristics and estimate the prevalence of severe asthma in a large adult population-based asthma cohort followed for 10-28 years.

    METHODS: N=1006 subjects with asthma participated in a follow-up during 2012-14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well-known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.

    RESULTS: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.

    CONCLUSIONS AND CLINICAL RELEVANCE: Severe asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the general population.

  • 9.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Dept of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Dept of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Stridsman, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Dept of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort2020In: World Allergy Organization Journal, E-ISSN 1939-4551, Vol. 13, no 3, article id 100110Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.

    Objective: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.

    Methods: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.

    Results: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.

    Conclusions and clinical relevance: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.

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  • 10.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stridsman, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Rönnebjerg, Lina
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Nwaru, Bright I.
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Kankaanranta, Hannu
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Determinants of severe asthma: a long-term cohort study in northern Sweden2022In: Journal of Asthma and Allergy, ISSN 1178-6965, Vol. 15, p. 1429-1439Article in journal (Refereed)
    Abstract [en]

    Background: Risk factors for severe asthma are not well described. The aim was to identify clinical characteristics and risk factors at study entry that are associated with severe asthma at follow-up in a long-term prospective population-based cohort study of adults with asthma.

    Methods: Between 1986 and 2001, 2055 adults with asthma were identified by clinical examinations of population-based samples in northern Sweden. During 2012–2014, n = 1006 (71% of invited) were still alive, residing in the study area and participated in a follow-up, of which 40 were identified as having severe asthma according to ERS/ATS, 131 according to GINA, while 875 had other asthma. The mean follow-up time was 18.7 years.

    Results: Obesity at study entry and adult-onset asthma were associated with severe asthma at follow-up. While severe asthma was more common in those with adult-onset asthma in both men and women, the association with obesity was observed in women only. Sensitization to mites and moulds, but not to other allergens, as well as NSAID-related respiratory symptoms was more common in severe asthma than in other asthma. Participants with severe asthma at follow-up had lower FEV1, more pronounced FEV1 reversibility, and more wheeze, dyspnea and nighttime awakenings already at study entry than those with other asthma.

    Conclusion: Adult-onset asthma is an important risk factor for development of severe asthma in adults, and obesity increased the risk among women. The high burden of respiratory symptoms already at study entry also indicate long-term associations with development of severe asthma.

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  • 11.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Langrish, Jeremy P.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Goudie, Colin
    Newby, David E.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men2013In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 135, no 2, p. 292-299Article in journal (Refereed)
    Abstract [en]

    Air pollution exposure is associated with cardiovascular morbidity and mortality, yet the role of individual pollutants remains unclear. In particular, there is uncertainty regarding the acute effect of ozone exposure on cardiovascular disease. In these studies, we aimed to determine the effect of ozone exposure on vascular function, fibrinolysis, and the autonomic regulation of the heart. Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min on two occasions in randomized double-blind crossover studies. Bilateral forearm blood flow (FBF) was measured using forearm venous occlusion plethysmography before and during intra-arterial infusions of vasodilators 2–4 and 6–8h after each exposure. Heart rhythm and heart rate variability (HRV) were monitored during and 24h after exposure. Compared with filtered air, ozone exposure did not alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a dose-dependent increase in FBF with all vasodilators that was similar after both exposures at 2–4h. Ozone exposure did not impair vasomotor or fibrinolytic function at 6–8h but rather increased vasodilatation to acetylcholine (p = .015) and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during or after the exposure. Our findings do not support a direct rapid effect of ozone on vascular function or cardiac autonomic control although we cannot exclude an effect of chronic exposure or an interaction between ozone and alternative air pollutants that may be responsible for the adverse cardiovascular health effects attributed to ozone.

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  • 12.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Lundbäck, Magnus
    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.
    Lucking, Andrew J
    Langrish, Jeremy P
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Westerholm, Roger
    Löndahl, Jakob
    Donaldson, Ken
    Mudway, Ian S
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions2010In: Particle and Fibre Toxicology, E-ISSN 1743-8977, Vol. 7, no 1, p. 19-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.

    OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.

    METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.

    MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).

    CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.

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  • 13.
    Behndig, Annelie F
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Larsson, Nirina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brown, Joanna L
    Stenfors, Nikolai
    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.
    Duggan, Sean T
    Dove, Rosamund E
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J
    Mudway, Ian S
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma2011In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 66, no 1, p. 12-19Article in journal (Refereed)
    Abstract [en]

    Exposure to diesel exhaust at concentrations consistent with roadside levels elicited an acute and active neutrophilic inflammation in the airways of healthy subjects. This response was absent in subjects with asthma, as was evidence supporting a worsening of allergic airway inflammation.

  • 14.
    Behndig, Annelie F.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shanmuganathan, Karthika
    Whitmarsh, Laura
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Östersund Research Unit, Umeå University. .
    Brown, Joanna L.
    Frew, Anthony J.
    Kelly, Frank J.
    Mudway, Ian S.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan J.
    Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium: an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects2015In: BMC Pulmonary Medicine, E-ISSN 1471-2466, Vol. 15, article id 99Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms.

    Methods: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 μg/m 3 ) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis.

    Results: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge.

    Conclusion: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.

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  • 15.
    Behndig, Annelie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, IS
    Brown, JL
    Stenfors, Nikolai
    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.
    Duggan, ST
    Wilson, SJ
    Boman, C
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Cassee, FR
    Frew, AJ
    Kelly, FJ
    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.
    Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 2, p. 359-365Article in journal (Refereed)
    Abstract [sv]

    Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.

  • 16.
    Behndig, Annelie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, IS
    Brown, JL
    Stenfors, Nikolai
    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.
    Duggan, ST
    Wilson, SJ
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Cassee, FR
    Frew, AJ
    Kelly, FJ
    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.
    Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 2, p. 359-365Article in journal (Refereed)
    Abstract [sv]

    Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.

  • 17.
    Bjerg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, B
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå.
    Time trends in asthma and wheeze in Swedish children 1996-2006: prevalence and risk factors by sex2010In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 65, no 1, p. 48-55Article in journal (Refereed)
    Abstract [en]

    Background: Recent data suggest that the previously rising trend in childhood wheezing symptoms has plateaued in some regions. We sought to investigate sex-specific trends in wheeze, asthma, allergic conditions, allergic sensitization and risk factors for wheeze.

    Methods: We compared two population-based cohorts of 7 to 8-year olds from the same Swedish towns in 1996 and 2006 using parental expanded ISAAC questionnaires. In 1996, 3430 (97%) and in 2006, 2585 (96%) questionnaires were completed. A subset was skin prick tested: in 1996, 2148 (88%) and in 2006, 1700 (90%) children participated.

    Results: No significant change in the prevalence of current wheeze (P = 0.13), allergic rhinitis (P = 0.18) or eczema (P = 0.22) was found despite an increase in allergic sensitization (20.6-29.9%, P < 0.01). In boys, however, the prevalence of current wheeze (12.9-16.4%, P < 0.01), physician-diagnosed asthma (7.1-9.3%, P = 0.03) and asthma medication use increased. In girls the prevalence of current symptoms and conditions tended to decrease. The prevalence of all studied risk factors for wheeze and asthma increased in boys relative to girls from 1996 to 2006, thus increasing the boy-to-girl prevalence ratio in risk factors.

    Conclusions: The previously reported increase in current wheezing indices has plateaued in Sweden. Due to increased diagnostic activity, physician diagnoses continue to increase. Time trends in wheezing symptoms differed between boys and girls, and current wheeze increased in boys. This was seemingly explained by the observed increases in the prevalence of risk factors for asthma in boys compared with girls. In contrast to the current symptoms of wheeze, rhinitis or eczema, the prevalence of allergic sensitization increased considerably.

  • 18.
    Bjerg Bäcklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Perzanowski, M S
    Platts-Mills, T
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Asthma during the primary school ages--prevalence, remission and the impact of allergic sensitization.2006In: Allergy, ISSN 0105-4538, Vol. 61, no 5, p. 549-55Article in journal (Refereed)
  • 19. Bolling, Anette Kocbach
    et al.
    Totlandsdal, Annike Irene
    Sallsten, Gerd
    Braun, Artur
    Westerholm, Roger
    Bergvall, Christoffer
    Boman, Johan
    Dahlman, Hans Jorgen
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cassee, Flemming
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Schwarze, Per E.
    Herseth, Jan Inge
    Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines2012In: Particle and Fibre Toxicology, E-ISSN 1743-8977, Vol. 9, p. 45-Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to particulate matter (PM) has been linked to several adverse cardiopulmonary effects, probably via biological mechanisms involving inflammation. The pro-inflammatory potential of PM depends on the particles' physical and chemical characteristics, which again depend on the emitting source. Wood combustion is a major source of ambient air pollution in Northern countries during the winter season. The overall aim of this study was therefore to investigate cellular responses to wood smoke particles (WSPs) collected from different phases of the combustion cycle, and from combustion at different temperatures. Results: WSPs from different phases of the combustion cycle induced very similar effects on pro-inflammatory mediator release, cytotoxicity and cell number, whereas WSPs from medium-temperature combustion were more cytotoxic than WSPs from high-temperature incomplete combustion. Furthermore, comparisons of effects induced by native WSPs with the corresponding organic extracts and washed particles revealed that the organic fraction was the most important determinant for the WSP-induced effects. However, the responses induced by the organic fraction could generally not be linked to the content of the measured polycyclic aromatic hydrocarbons (PAHs), suggesting that also other organic compounds were involved. Conclusion: The toxicity of WSPs seems to a large extent to be determined by stove type and combustion conditions, rather than the phase of the combustion cycle. Notably, this toxicity seems to strongly depend on the organic fraction, and it is probably associated with organic components other than the commonly measured unsubstituted PAHs.

  • 20. Boman, C
    et al.
    Forsberg, B
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Enviromental Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Shedding new light on wood smoke: a risk factor for respiratory health.2006In: Eur Respir J, ISSN 0903-1936, Vol. 27, no 3, p. 446-7Article in journal (Refereed)
  • 21.
    Boman, Christoffer
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Forsberg, B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shedding new light on wood smoke: a risk factor for respiratory health.2006In: Eur Respir J, ISSN 0903-1936, Vol. 27, no 3, p. 446-7Article in journal (Refereed)
  • 22.
    Bosson, Jenny A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Traffic-related Air Pollution, Health, and Allergy: The Role of Nitrogen Dioxide2019In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 200, no 5, p. 523-524Article in journal (Other academic)
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  • 23.
    Bosson, Jenny. A.
    et al.
    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.
    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.
    Connolly-Andersen, Anne-Marie
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Langrish, J. P.
    Increased Soluble Thrombomodulin In Plasma Following Diesel Exhaust Exposure2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A3210Article in journal (Other academic)
  • 24.
    Bosson, Jenny
    et al.
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    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.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans2008In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 31, no 6, p. 1234-1240Article in journal (Refereed)
    Abstract [en]

    Exposure to particulate matter and ozone cause adverse airway reactions. Individual pollutant effects are often addressed separately, despite coexisting in ambient air. The present investigation was performed to study the effects of sequential exposures to diesel exhaust (DE) and ozone on airway inflammation in human subjects. Healthy subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial wash (BW) sampling on two occasions. Once following a DE exposure (with 300 mug.m(-3) particles with a 50% cut-off aerodynamic diameter of 10 mum) with subsequent exposure to O(3) (0.2 ppm) 5 h later. The other bronchoscopy was performed after a filtered air exposure followed by an ozone exposure, using an identical protocol. Bronchoscopy was performed 24 h after the start of the initial exposure. Significant increases in neutrophil and macrophage numbers were found in BW after DE followed by ozone exposure versus air followed by ozone exposure. DE pre-exposure also raised eosinophil protein X levels in BAL compared with air. The present study indicates additive effects of diesel exhaust on the ozone-induced airway inflammation. Together with similar results from a recent study with sequential diesel exhaust and ozone exposures, the present data stress a need to consider the interaction and cumulative effects of different air pollutants.

  • 25.
    Bosson, Jenny
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian
    Frew, Anthony
    Kelly, Frank
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Early suppression of NFκB and IL-8 bronchial epithelium after ozone exposure in healthy human subjects2009In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, no 11, p. 913-919Article in journal (Refereed)
    Abstract [en]

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

  • 26.
    Bosson, Jenny
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S
    Frew, Anthony J
    Kelly, Frank J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects2009In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, no 11, p. 913-919Article in journal (Refereed)
    Abstract [en]

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

  • 27.
    Bosson, Jenny
    et al.
    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.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ozone enhances the airway inflammation initiated by diesel exhaust.2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 6, p. 1140-1146Article in journal (Refereed)
    Abstract [en]

    Exposure to air pollution is associated with adverse health effects, with particulate matter (PM) and ozone (O(3)) both indicated to be of considerable importance. Diesel engine exhaust (DE) and O(3) generate substantial inflammatory effects in the airways. However, as yet it has not been determined whether a subsequent O(3) exposure would add to the diesel-induced airway inflammatory effects. Healthy subjects underwent two separate exposure series: A 1-h DE exposure at a PM-concentration of 300 microg/m(3), followed after 5h by a 2-h exposure to filtered air and 0.2 ppm O(3), respectively. Induced sputum was collected 18 h after the second exposure. A significant increase in the percentage of neutrophils (PMN) and concentration of myeloperoxidase (MPO) was seen in sputum post DE+O(3) vs. DE+air (p<0.05 and <0.05, respectively). Significant associations were observed between the responses in MPO concentration and total PMN cells (p=0.001), and also between MPO and matrix metalloproteinase-9 (MMP-9) (p<0.001). The significant increase of PMN and MPO after the DE+O(3) exposures, compared to DE+air, denotes an O(3)-induced magnification of the DE-induced inflammation. Furthermore, the correlation between responses in MPO and number of PMNs and MMP-9 illustrate that the PMNs are activated, resulting in a more potent inflammatory response. The present study indicates that O(3) exposure adds significantly to the inflammatory response that is established by diesel exhaust. This interaction between exposure to particulate pollution and O(3) in sequence should be taken into consideration when health effects of air pollution are considered.

  • 28.
    Bosson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Stenfors, Nikolai
    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.
    Bucht, 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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Holgate, Stephen
    Kelly, Frank
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan
    Frew, Anthony
    Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 6, p. 777-782Article in journal (Refereed)
    Abstract [en]

    Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group.

    Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility.

    Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78.

    Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects.

    Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.

  • 29. Brandsma, Joost
    et al.
    Goss, Victoria M.
    Yang, Xian
    Bakke, Per S.
    Caruso, Massimo
    Chanez, Pascal
    Dahlén, Sven-Erik
    Fowler, Stephen J.
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Shaw, Dominick E.
    Chung, Kian Fan
    Singer, Florian
    Fleming, Louise J.
    Sousa, Ana R.
    Pandis, Ioannis
    Bansal, Aruna T.
    Sterk, Peter J.
    Djukanovic, Ratko
    Postle, Anthony D.
    Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers2018In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 14, no 10, article id 123Article in journal (Refereed)
    Abstract [en]

    Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood.

    Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.

    Methods: Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.

    Results: The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.

    Conclusions: We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism.

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  • 30.
    Brandsma, Joost
    et al.
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Schofield, James P.R.
    National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom; Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom.
    Yang, Xian
    Data Science Institute, Imperial College, London, United Kingdom.
    Strazzeri, Fabio
    Mathematical Sciences, University of Southampton, Southampton, United Kingdom.
    Barber, Clair
    National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Goss, Victoria M.
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Koster, Grielof
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Bakke, Per S.
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Caruso, Massimo
    Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
    Chanez, Pascal
    Department of Respiratory Diseases, Aix-Marseille University, Marseille, France.
    Dahlén, Sven-Erik
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Fowler, Stephen J.
    Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, United Kingdom; Manchester Academic Health Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
    Horváth, Ildikó
    Department of Pulmonology, Semmelweis University, Budapest, Hungary.
    Krug, Norbert
    Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
    Montuschi, Paolo
    Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy; National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Sanak, Marek
    Department of Medicine, Jagiellonian University, Krakow, Poland.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Shaw, Dominick E.
    National Institute for Health Research Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom.
    Chung, Kian Fan
    National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Singer, Florian
    Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Paediatrics and Adolescent Medicine, Division of Paediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria.
    Fleming, Louise J.
    National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Adcock, Ian M.
    National Heart and Lung Institute, Imperial College, London, United Kingdom.
    Pandis, Ioannis
    Data Science Institute, Imperial College, London, United Kingdom.
    Bansal, Aruna T.
    Acclarogen Ltd, St John's Innovation Centre, Cambridge, United Kingdom.
    Corfield, Julie
    Areteva Ltd, Nottingham, United Kingdom.
    Sousa, Ana R.
    Respiratory Therapy Unit, GlaxoSmithKline, London, United Kingdom.
    Sterk, Peter J.
    Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
    Sánchez-García, Rubén J.
    Mathematical Sciences, University of Southampton, Southampton, United Kingdom.
    Skipp, Paul J.
    Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, United Kingdom.
    Postle, Anthony D.
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
    Djukanović, Ratko
    Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, Southampton, United Kingdom.
    Stratification of asthma by lipidomic profiling of induced sputum supernatant2023In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 152, no 1, p. 117-125Article in journal (Refereed)
    Abstract [en]

    Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.

    Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.

    Methods: Induced sputum supernatant was collected from 211 adults with asthma and 41 healthy individuals enrolled onto the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study. Sputum lipidomes were characterized by semiquantitative shotgun mass spectrometry and clustered using topologic data analysis to identify lipid phenotypes.

    Results: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of 9 molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthma patients and healthy controls, but also within the asthma patient population. Matching clinical, pathobiologic, proteomic, and transcriptomic data helped inform the underlying disease processes. Sputum lipid phenotypes with higher levels of nonendogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts.

    Conclusion: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthma patients resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator.

  • 31. Brinkman, Paul
    et al.
    Wagener, Ariane H.
    Hekking, Pieter-Paul
    Bansal, Aruna T.
    Maitland-van der Zee, Anke-Hilse
    Wang, Yuanyue
    Weda, Hans
    Knobel, Hugo H.
    Vink, Teunis J.
    Rattray, Nicholas J.
    D'Amico, Arnaldo
    Pennazza, Giorgio
    Santonico, Marco
    Lefaudeux, Diane
    De Meulder, Bertrand
    Auffray, Charles
    Bakke, Per S.
    Caruso, Massimo
    Chanez, Pascal
    Chung, Kian F.
    Corfield, Julie
    Dahlen, Sven-Erik
    Djukanovic, Ratko
    Geiser, Thomas
    Horvath, Ildiko
    Krug, Nobert
    Musial, Jacek
    Sun, Kai
    Riley, John H.
    Shaw, Dominic E.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sousa, Ana R.
    Montuschi, Paolo
    Fowler, Stephen J.
    Sterk, Peter J.
    Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 5, p. 1811-1820.e7Article in journal (Refereed)
    Abstract [en]

    Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes.

    Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to withinpatient clinical and inflammatory changes.

    Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability.

    Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNosedriven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045).

    Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.

  • 32. Brown, J L
    et al.
    Behndig, A F
    Sekerel, B E
    Pourazar, Jamshid
    Blomberg, Anders
    Kelly, F J
    Sandström, Thomas
    Frew, A J
    Wilson, S J
    Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls2007In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 37, no 5, p. 688-695Article in journal (Refereed)
    Abstract [en]

    Background: Allergic rhinitis (AR) and asthma represent a continuum of atopic disease. AR is believed to pre‐dispose an individual to asthma. Compared with asthmatics and normal controls, the inflammatory response in the lower airways of rhinitics is not fully elucidated. To test the hypothesis that the inflammatory response in the airways of subjects with AR is at a level intermediate between that in normal controls and asthmatics, we have characterized bronchial inflammation and cytokine mRNA levels in non‐asthmatic allergic rhinitics and compared it with subjects with allergic asthma and with normal controls.

    Methods: Endobronchial mucosal biopsies were obtained at bronchoscopy from 14 allergic rhinitics, 16 asthmatics and 21 normal controls. Biopsies were embedded into glycol methacrylate resin for immunohistochemical analysis of cellular inflammation and snap frozen for semi‐quantitative PCR analysis of cytokine mRNA levels.

    Results: Airway inflammation in rhinitic subjects was characterized by an increase in submucosal eosinophils, mast cells and the mRNA expression of TNF‐α, at an intermediate level between healthy and asthmatics. In addition, CD3+ and CD8+ lymphocytes in the epithelium, the endothelial expression of vascular adhesion molecule‐1 and IL‐1β mRNA were higher in the allergic rhinitics compared with both normal controls and asthmatics, whereas growth‐related oncogene α‐mRNA was decreased in AR compared with both healthy and asthmatics. Airway inflammation in the asthmatic group was characterized by higher numbers of eosinophils and mast cells, together with an increase in TNF‐α‐mRNA compared with both healthy and rhinitics. IFN‐γ mRNA was the highest in normal controls and lowest in the asthmatics.

    Conclusions: In individuals with AR the present data suggest an intermediate state of airway inflammation between that observed in normal individuals and subjects with clinical asthma. It is also indicated that IFN‐γ production by CD8+ T lymphocytes could be protective against the development of airway hyperresponsiveness. Further work is needed to evaluate this hypothesis.

  • 33. Burg, Dominic
    et al.
    Schofield, James P. R.
    Brandsma, Joost
    Staykova, Doroteya
    Folisi, Caterina
    Bansal, Aruna
    Nicholas, Ben
    Xian, Yang
    Rowe, Anthony
    Corfield, Julie
    Wilson, Susan
    Ward, Jonathan
    Lutter, Rene
    Fleming, Louise
    Shaw, Dominick E.
    Bakke, Per S.
    Caruso, Massimo
    Dahlen, Sven-Erik
    Fowler, Stephen J.
    Hashimoto, Simone
    Horvath, Ildiko
    Howarth, Peter
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Singer, Florian
    Sun, Kai
    Pandis, Ioannis
    Auffray, Charles
    Sousa, Ana R.
    Adcock, Ian M.
    Chung, Kian Fan
    Sterk, Peter J.
    Djukanovic, Ratko
    Skipp, Paul J.
    Large-Scale Label-Free Quantitative Mapping of the Sputum Proteome2018In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 17, no 6, p. 2072-2091Article in journal (Refereed)
    Abstract [en]

    Analysis of induced sputum supematant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in >= 40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in >= 3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.

  • 34. 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.

  • 35. 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, E-ISSN 1743-8977, Vol. 5, p. 11-Article in journal (Other academic)
  • 36. 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)
  • 37.
    Eklund, Linda M.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Anesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Sköndal, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Tufvesson, Ellen
    Department of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
    Sjöström, Rita
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Söderström, Lars
    Unit of Research, Education and Development, Östersund Hospital, Östersund, Sweden.
    Hanstock, Helen G.
    Department of Health Sciences, Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Cold air exposure at -15 °C induces more airway symptoms and epithelial stress during heavy exercise than rest without aggravated airway constriction2022In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 122, no 12, p. 2533-2544Article in journal (Refereed)
    Abstract [en]

    Purpose: Exposure to cold air may harm the airways. It is unclear to what extent heavy exercise adds to the cold-induced effects on peripheral airways, airway epithelium, and systemic immunity among healthy individuals. We investigated acute effects of heavy exercise in sub-zero temperatures on the healthy airways.

    Methods: Twenty-nine healthy individuals underwent whole body exposures to cold air in an environmental chamber at − 15 °C for 50 min on two occasions; a 35-min exercise protocol consisting of a 5-min warm-up followed by 2 × 15 min of running at 85% of VO2max vs. 50 min at rest. Lung function was measured by impulse oscillometry (IOS) and spirometry before and immediately after exposures. CC16 in plasma and urine, and cytokines in plasma were measured before and 60 min after exposures. Symptoms were surveyed pre-, during and post-trials.

    Results: FEV1 decreased after rest (− 0.10 ± 0.03 L, p < 0.001) and after exercise (− 0.06 ± 0.02 L, p = 0.012), with no difference between trials. Exercise in − 15 °C induced greater increases in lung reactance (X5; p = 0.023), plasma CC16 (p < 0.001) as well as plasma IL-8 (p < 0.001), compared to rest. Exercise induced more intense symptoms from the lower airways, whereas rest gave rise to more general symptoms.

    Conclusion: Heavy exercise during cold air exposure at − 15 °C induced signs of an airway constriction to a similar extent as rest in the same environment. However, biochemical signs of airway epithelial stress, cytokine responses, and symptoms from the lower airways were more pronounced after the exercise trial.

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  • 38.
    Eklund, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Schagatay, Filip
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Tufvesson, Ellen
    Sjöström, Rita
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Söderström, Lars
    Unit of Research, Education and Development, Östersund Hospital, Östersund, Sweden.
    Hanstock, Helen G.
    Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    An experimental exposure study revealing composite airway effects of physical exercise in a subzero environment2021In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 80, no 1, article id 1897213Article in journal (Refereed)
    Abstract [en]

    Exposure to a cold climate is associated with an increased morbidity and mortality, but the specific mechanisms are largely unknown. People with cardiopulmonary disease and winter endurance athletes are particularly vulnerable. This study aimed to map multiple domains of airway responses to exercise in subzero temperature in healthy individuals.

    Thirty-one healthy subjects underwent whole-body exposures for 50 minutes on two occasions in an environmental chamber with intermittent moderate-intensity exercise in +10 °C and -10 °C. Lung function, plasma/urine CC16 , and symptoms were investigated before and after exposures.

    Compared to baseline, exercise in -10 °C decreased FEV1 (p=0.002), FEV1/FVC (p<0.001), and increased R20Hz (p=0.016), with no differences between exposures. Reactance increased after +10 °C (p=0.005), which differed (p=0.042) from a blunted response after exercise in -10 °C. Plasma CC16 increased significantly within exposures, without differences between exposures. Exercise in -10 °C elicited more intense symptoms from the upper airways, compared to +10 °C. Symptoms from the lower airways were few and mild. 

    Short-duration moderate-intensity exercise in -10 °C induces mild symptoms from the lower airways, no lung function decrements or enhanced leakage of biomarkers of airway epithelial injury, and no peripheral bronchodilatation, compared to exercise in +10 °C. 

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  • 39.
    Eliasson, Gabriella
    et al.
    Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Janson, Christer
    Department of Medical Sciences, Respiratory; Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Johansson, Gunnar
    Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Larsson, Kjell
    Division for Lung and Airway Research, Institute of Environmental Medicine, Stockholm, Sweden.
    Lindén, Anders
    Division for Lung and Airway Research, Institute of Environmental Medicine, Stockholm, Sweden; Karolinska Severe COPD Center, Department of Respiratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Löfdahl, Claes-Göran
    Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sundh, Josefin
    Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Comorbid conditions as predictors of mortality in severe COPD: an eight-year follow-up cohort study2023In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 10, no 1, article id 2181291Article in journal (Refereed)
    Abstract [en]

    Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality.

    Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables.

    Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age ≥70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality.

    Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.

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  • 40. Emma, Rosalia
    et al.
    Bansal, Aruna T.
    Kolmert, Johan
    Wheelock, Craig E.
    Dahlen, Swen-Erik
    Loza, Matthew J.
    De Meulder, Bertrand
    Lefaudeux, Diane
    Auffray, Charles
    Dahlen, Barbro
    Bakke, Per S.
    Chanez, Pascal
    Fowler, Stephen J.
    Horvath, Ildiko
    Montuschi, Paolo
    Krug, Norbert
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shaw, Dominick E.
    Fleming, Louise J.
    Djukanovic, Ratko
    Howarth, Peter H.
    Singer, Florian
    Sousa, Ana R.
    Sterk, Peter J.
    Cortield, Julie
    Pandis, Ioannis
    Chung, Kian F.
    Adcock, Ian M.
    Lutter, Rene
    Fabbella, Lorena
    Caruso, Massimo
    Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 9, article id e0203874Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is believed to be a major driver of inflammation in smoking asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex-smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker information enabling characterization of these subjects. We investigated oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF(2 alpha) and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma U-BIOPRED subjects were further divided into current smokers with severe asthma (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial biopsy and brushing was performed in a subset of subjects. The main clinical data were analysed for each subset of subjects (urine-8-iso-PGF(2 alpha); IS-transcriptomics; BB-transcriptomics; BBrtranscriptomics). Urinary 8-iso-PGF(2 alpha) was quantified using mass spectrometry. Sputum, bronchial biopsy and bronchial brushing were processed for mRNA expression microarray analysis. Urinary 8-iso-PGF(2 alpha) was increased in SAs/ex, median (IQR) = 31.7 (24.5 +/- 44.7) ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6 +/- 36.6) ng/mmol creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4 +/- 47.7), vs. ESA, median (IQR) = 29.4 (22.3 +/- 40.5), and NSA, median (IQR) = 26.5 (19.6 +/- 16.6) ng/mmol creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006; 203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06, p = 0.014). The mRNA expression of antioxidant enzymes were similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in bronchial brushing of SAs/ex compared to SAn (fold-change = -1.10; p = 0.029). NOS2 mRNA expression in bronchial brushing correlated with FeNO (Kendal's Tau = 0.535; p< 0.001). From clinical and inflammatory analysis, FeNO was lower in CSA than in ESA in all the analysed subject subsets (p< 0.01) indicating an effect of active smoking. Results about FeNO suggest its clinical limitation, as inflammation biomarker, in severe asthma active smokers. These data provide evidence of greater systemic oxidative stress in severe asthma smokers as reflected by a significant changes of NOX2 mRNA expression in the airways, together with elevated urinary 8-iso-PGF(2 alpha) in the smokers/ex-smokers group.

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  • 41.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Schagatay, Filip
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sjöström, Rita
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Soderstrom, Lars
    Hanstock, Helen
    Sandström, Thomas
    Department of Medicine, Respiratory & allergy unit, Umeå university hospital, Umeå, Sweden.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Symptoms of moderate exercise in subzero temperatures - An experimental exposure study2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
    Abstract [en]

    Humans react to cold with various symptoms. Previous studies enquiring about symptoms during cold exposure have for the most part been population based studies using questionnaries and have focused on a narrow spectrum of symptoms. The purpose of this study was to study the effect of cold air and physical exercise on a wide range of symptoms in healthy individuals.

    A total of 31 healthy subjects were experimentally exposed to +10 °C and -10 °C in an environmental chamber for one hour, on two separate occasions. During each exposure, subjects performed an intermittent moderate-intensity running protocol between 62-78% of maximal oxygen consumption (VO2 max). At five timepoints, before, during and after the exposures, subjects were asked about 18 symptoms and their intensity. The Borg CR10 scale was used to rate the intensity from 0 to 11, where 0 meant "none" and 11 meant "maximal". The sum of all five Borg CR10-scores were added together to form a single score for each exposure. Paired Wilcoxon signed-rank test was used for analysis. Data are presented as medians.

    Symptoms of cough, eye irritation, physical discomfort, and cold extremities were present only at -10 °C. Compared to exercise in +10 °C, exercise in -10 °C induced significantly higher summed symptom scores for eye irritation 2.0 vs 0.5 (p=0.011), rhinitis 12.0 vs 8.0 (p=0.000), nasal irritation 3.5 vs 0.5 (p=0.001), cold face 7.0 vs 1.0 (p=0.000), physical discomfort 6.5 vs 0.0 (p=0.000), and cold extremities 10.0 vs 0.5 (p=0.000).

    In healthy subjects, moderate-intensity exercise in -10 °C can induce and enhance the intensity of a wide range of symptoms. Symptoms of the lower airways were infrequent and mild.

  • 42.
    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, E-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. 

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  • 43.
    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.

  • 44.
    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.

  • 45.
    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.

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  • 46.
    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.

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  • 47.
    Friberg, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bosson, J.A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Muala, Ala
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Barath, S.
    Department of Respiratory Medicine and Allergy, Lund University Hospital, Lund, Sweden.
    Dove, R.
    Wolfson Institute for Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
    Glencross, D.
    MRC Centre for Environment and Health, Imperial College London, London, United Kingdom; NIHR Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, United Kingdom.
    Kelly, F.J.
    MRC Centre for Environment and Health, Imperial College London, London, United Kingdom; NIHR Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, United Kingdom.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mudway, I.S.
    MRC Centre for Environment and Health, Imperial College London, London, United Kingdom; NIHR Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, United Kingdom.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response2023In: Particle and Fibre Toxicology, E-ISSN 1743-8977, Vol. 20, no 1, article id 47Article in journal (Refereed)
    Abstract [en]

    Background: Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE.

    Methods: Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo–keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed.

    Results: DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = −0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo–keto reductases, or epoxide hydrolase protein expression.

    Conclusion: These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.

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  • 48.
    Frykholm, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Klijn, Peter
    Saey, Didier
    van Hees, Hieronymus W. H.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Maltais, François
    Nyberg, Andre
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial2019In: Trials, E-ISSN 1745-6215, Vol. 20, no 1, article id 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In people with chronic obstructive pulmonary disease (COPD), limb-muscle dysfunction is one of the most troublesome systemic manifestations of the disease, which at the functional level is evidenced by reduced strength and endurance of limb muscles. Improving limb-muscle function is an important therapeutic goal of COPD management, for which resistance training is recommended. However, current guidelines for resistance training in COPD mainly focus on improving muscle strength which only reflects one aspect of limb-muscle function and does not address the issue of reduced muscle endurance. The latter is of importance considering that the reduction in limb-muscle endurance often is greater than that of muscle weakness, and also, limb-muscle endurance seems to be closer related to walking capacity as well as arm function than to limb-muscle strength within this group of people. Thus, strategies targeting multiple aspects of the decreased muscle function are warranted to increase the possibility for an optimal effect for the individual patient. Periodized resistance training, which represents a planned variation of resistance training variables (i.e., volume, intensity, frequency, etc.), is one strategy that could be used to target limb-muscle strength as well as limb-muscle endurance within the same exercise regimen.

    METHODS: This is an international, multicenter, randomized controlled trial comparing the effect and feasibility of non-linear periodized resistance training to traditional non-periodized resistance training in people with COPD. Primary outcomes are dynamic limb-muscle strength and endurance. Secondary outcomes include static limb-muscle strength and endurance, functional performance, quality of life, dyspnea, intramuscular adaptations as well as the proportion of responders. Feasibility of the training programs will be assessed and compared on attendance rate, duration, satisfaction, drop-outs as well as occurrence and severity of any adverse events.

    DISCUSSION: The proposed trial will provide new knowledge to this research area by investigating and comparing the feasibility and effects of non-linear periodized resistance training compared to traditional non-periodized resistance training. If the former strategy produces larger physiological adaptations than non-periodized resistance training, this project may influence the prescription of resistance training in people with COPD.

    TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03518723 . Registered on 13 April 2018.

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  • 49. Geale, Kirk
    et al.
    Darabi, Hatef
    Eklund, Oskar
    Lindh, Maria
    Wahl, Hanna Fues
    Ström, Oskar
    Cao, Hui
    Alvares, Luisa
    Dodge, Rikke
    Loefroth, Emil
    Altraja, Alan
    Backer, Vibecke
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bjermer, Leif
    Bossios, Apostolos
    Dahlén, Barbro
    Janson, Christer
    Kankaanranta, Hannu
    Kauppi, Paula
    Kilpelainen, Maritta
    Lehtimäki, Lauri
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ulrik, Charlotte Suppli
    Viinanen, Arja
    Porsbjerg, Celeste
    Late Breaking Abstract - NORdic Database for aSThmA Research (NORDSTAR): Swedish and Finnish patients2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
    Abstract [en]

    Background: A cross-border research collaboration was recently initiated across the Nordic countries. These countries maintain population-based registers containing a variety of patient-level health and socioeconomic variables, providing a basis for nation-wide, longitudinal research.

    Aims and objectives: Describe key characteristics of Swedish and Finnish asthma populations in 2014.

    Methods: NORDSTAR is a research platform with ethical approval based on Nordic register data. Patients with an asthma diagnosis (ICD-10: J45/46) at any age in specialist care, or ≥2 dispensed respiratory prescriptions (ATC: R03) while aged 6-44, during 2004-2014 were included. Those with diagnosis and treatment pairs unlikely to be asthma were excluded. Demographics (age, sex, income, education level, and urban residence), treatment, comorbidities, and asthma specialist visits in 2014 were described using summary statistics.

    Results: Finnish comorbidity levels appeared higher than in Sweden. More Finnish patients filled OCS prescriptions (24%) than Swedish patients (20%). Most Swedish patients lived in an urban setting, and the distribution of education level was similar to the general population. Mean family income was 49,960 and 42,840 EUR in Sweden and Finland respectively, while 31% and 44% of patients visited an asthma specialist. Prevalence of asthma was highest among women in both countries, and age distributions were similar.

    Conclusions: NORDSTAR is a platform for conducting asthma outcomes research in the Nordics. Swedish and Finnish patients appear to be similar in many dimensions except for prevalence of asthma specialist care contacts.

  • 50.
    Geale, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Quantify Research, Stockholm, Sweden.
    Darabi, Hatef
    Lindh, Maria
    Wahl, Hanna Fues
    Strom, Oskar
    Cao, Hui
    Alvares, Luisa
    Dodge, Rikke
    Loefroth, Emil
    Altraja, Alan
    Backer, Vibeke
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Bjermer, Leif
    Bossios, Apostolos
    Aarli, Bernt Bogvald
    Dahlen, Barbro
    Hilberg, Ole
    Janson, Christer
    Kankaanranta, Hannu
    Karjalainen, Jussi
    Kauppi, Paula
    Kilpelainen, Maritta
    Lehmann, Sverre
    Lehtimaki, Lauri
    Lundback, Bo
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ulrik, Charlotte Suppli
    Sverrild, Asger
    Viinanen, Arja
    von Bulow, Anna
    Yasinska, Valentyna
    Porsbjerg, Celeste
    NORDSTAR: paving the way for a new era in asthma research2020In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 55, no 4, article id 1902476Article in journal (Other academic)
    Abstract [en]

    NORDSTAR is a longitudinal dataset for the study of asthma comprising 3.3 million individuals and over 50 million person-years in 4 Nordic countries. The data include diagnoses, medication dispensing, use of resources and costs, socio-demographics, and mortality.

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