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  • 1. Aalbers, R
    et al.
    Backer, V
    Kava, T T K
    Omenaas, E R
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Jorup, C
    Welte, T
    Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma.2004Ingår i: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 20, nr 2, s. 225-40Artikel i tidskrift (Refereegranskat)
  • 2. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    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 cohort2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    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.

  • 3.
    Andersen, Grethe N.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Nilsson, Kenneth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Nagaeva, O
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Cytokine mRNA profile of alveolar T lymphocytes and macrophages in patients with systemic sclerosis suggests a local Tr1 response2011Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, nr 3, s. 272-81Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    Andersen, Grethe Neumann
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Nilsson, Kenneth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Hackett, Tillie-Louise
    Kazzam, Elsadig
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Warner, Jane
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Sandström, Thomas
    Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.2007Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, nr 10, s. 2199-2206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 5.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Stridsman, Caroline
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundback, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eosinophilic inflammation and lung function decline in a long-term follow-up of a large population-based asthma cohort2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    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.

  • 6.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Stridsman, Caroline
    Eriksson, Berne
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eklund, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundback, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Severe asthma among adults: Prevalence and clinical characteristics2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    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.

  • 7.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Stridsman, Caroline
    Eriksson, Berne
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Eklund, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lundbäck, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Severe asthma: A population study perspective2019Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, nr 6, s. 819-828Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Barath, Stefan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Langrish, Jeremy P.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Lundbäck, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Goudie, Colin
    Newby, David E.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men2013Ingår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 135, nr 2, s. 292-299Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Barath, Stefan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L
    Lundbäck, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Törnqvist, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lucking, Andrew J
    Langrish, Jeremy P
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik, Energiteknik och termisk processkemi.
    Westerholm, Roger
    Löndahl, Jakob
    Donaldson, Ken
    Mudway, Ian S
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions2010Ingår i: Particle and fibre toxicology, ISSN 1743-8977, Vol. 7, nr 1, s. 19-Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Behndig, Annelie F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Larsson, Nirina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Brown, Joanna L
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Duggan, Sean T
    Dove, Rosamund E
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wilson, Susan J
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, Frank J
    Mudway, Ian S
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma2011Ingår i: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 66, nr 1, s. 12-19Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Behndig, Annelie F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Shanmuganathan, Karthika
    Whitmarsh, Laura
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Östersund Research Unit, Umeå University. .
    Brown, Joanna L.
    Frew, Anthony J.
    Kelly, Frank J.
    Mudway, Ian S.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    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 subjects2015Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikel-id 99Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Behndig, Annelie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, IS
    Brown, JL
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Duggan, ST
    Wilson, SJ
    Boman, C
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik, Energiteknik och termisk processkemi.
    Cassee, FR
    Frew, AJ
    Kelly, FJ
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.2006Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, nr 2, s. 359-365Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Behndig, Annelie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, IS
    Brown, JL
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Duggan, ST
    Wilson, SJ
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik, Energiteknik och termisk processkemi.
    Cassee, FR
    Frew, AJ
    Kelly, FJ
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.2006Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, nr 2, s. 359-365Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Bjerg, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lundbäck, B
    Rönnmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. 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 sex2010Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 65, nr 1, s. 48-55Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Bjerg Bäcklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Perzanowski, M S
    Platts-Mills, T
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lundbäck, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Asthma during the primary school ages--prevalence, remission and the impact of allergic sensitization.2006Ingår i: Allergy, ISSN 0105-4538, Vol. 61, nr 5, s. 549-55Artikel i tidskrift (Refereegranskat)
  • 16. Bolling, Anette Kocbach
    et al.
    Totlandsdal, Annike Irene
    Sallsten, Gerd
    Braun, Artur
    Westerholm, Roger
    Bergvall, Christoffer
    Boman, Johan
    Dahlman, Hans Jorgen
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Cassee, Flemming
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    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 lines2012Ingår i: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 9, s. 45-Artikel i tidskrift (Refereegranskat)
    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.

  • 17. Boman, C
    et al.
    Forsberg, B
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Shedding new light on wood smoke: a risk factor for respiratory health.2006Ingår i: Eur Respir J, ISSN 0903-1936, Vol. 27, nr 3, s. 446-7Artikel i tidskrift (Refereegranskat)
  • 18.
    Boman, Christoffer
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Forsberg, B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Shedding new light on wood smoke: a risk factor for respiratory health.2006Ingår i: Eur Respir J, ISSN 0903-1936, Vol. 27, nr 3, s. 446-7Artikel i tidskrift (Refereegranskat)
  • 19.
    Bosson, Jenny A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian S.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Traffic-related Air Pollution, Health, and Allergy: The Role of Nitrogen Dioxide2019Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 200, nr 5, s. 523-524Artikel i tidskrift (Övrigt vetenskapligt)
  • 20.
    Bosson, Jenny. A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Connolly-Andersen, Anne-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Langrish, J. P.
    Increased Soluble Thrombomodulin In Plasma Following Diesel Exhaust Exposure2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A3210Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Barath, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Behndig, Annelie F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans2008Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 31, nr 6, s. 1234-1240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 22.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian
    Frew, Anthony
    Kelly, Frank
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Early suppression of NFκB and IL-8 bronchial epithelium after ozone exposure in healthy human subjects2009Ingår i: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, nr 11, s. 913-919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 23.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian S
    Frew, Anthony J
    Kelly, Frank J
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Early suppression of NFkappaB and IL-8 in bronchial epithelium after ozone exposure in healthy human subjects2009Ingår i: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, nr 11, s. 913-919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 24.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ozone enhances the airway inflammation initiated by diesel exhaust.2007Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, nr 6, s. 1140-1146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 25.
    Bosson, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bucht, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Holgate, Stephen
    Kelly, Frank
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wilson, Susan
    Frew, Anthony
    Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects2003Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, nr 6, s. 777-782Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

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

  • 26. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    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 volunteers2018Ingår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 14, nr 10, artikel-id 123Artikel i tidskrift (Refereegranskat)
    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.

  • 27. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    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 asthma2019Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, nr 5, s. 1811-1820.e7Artikel i tidskrift (Refereegranskat)
    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.

  • 28. Brown, J L
    et al.
    Behndig, A F
    Sekerel, B E
    Pourazar, Jamshid
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, F J
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    Frew, A J
    Wilson, S J
    Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls.2007Ingår i: Clin Exp Allergy, ISSN 0954-7894, Vol. 37, nr 5, s. 688-95Artikel i tidskrift (Refereegranskat)
  • 29. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    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 Proteome2018Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 17, nr 6, s. 2072-2091Artikel i tidskrift (Refereegranskat)
    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.

  • 30. Carlsten, Chris
    et al.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pui, Mandy
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wong, Sze Wing
    Alexis, Neil
    Hirota, Jeremy
    Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study2016Ingår i: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 71, nr 1, s. 35-44Artikel i tidskrift (Refereegranskat)
    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.

  • 31. Crüts, Björn
    et al.
    Driessen, Anique
    van Etten, Ludo
    Törnqvist, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    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.2008Ingår i: Particle and fibre toxicology, ISSN 1743-8977, Vol. 5, s. 11-Artikel i tidskrift (Övrigt vetenskapligt)
  • 32. Dewilde, S
    et al.
    Turk, F
    Tambour, M
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients: adaptation of INNOVATE to Sweden.2006Ingår i: Curr Med Res Opin, ISSN 0300-7995, Vol. 22, nr 9, s. 1765-76Artikel i tidskrift (Refereegranskat)
  • 33. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    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 cohort2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 9, artikel-id e0203874Artikel i tidskrift (Refereegranskat)
    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.

  • 34.
    Eriksson, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Schagatay, Filip
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sjöström, Rita
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Soderstrom, Lars
    Hanstock, Helen
    Sandström, Thomas
    Department of Medicine, Respiratory & allergy unit, Umeå university hospital, Umeå, Sweden.
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Symptoms of moderate exercise in subzero temperatures - An experimental exposure study2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    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.

  • 35.
    Farooqi, Nighat
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Carlsson, Maine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Håglin, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Slinde, Frode
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Sweden..
    Energy expenditure in women and men with COPD2018Ingår i: Clinical Nutrition ESPEN, ISSN 2405-4577, Vol. 28, s. 171-178Artikel i tidskrift (Refereegranskat)
    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. 

  • 36.
    Farooqi, Nighat
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Nordström, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Lundgren, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Håglin, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Changes in body weight and physical performance after receiving dietary advice in patients with chronic obstructive pulmonary disease (COPD): 1-year follow-up.2011Ingår i: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 53, nr 1, s. 70-75Artikel i tidskrift (Refereegranskat)
    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.

  • 37.
    Farooqi, Nighat
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. Umea Univ Hosp, Dept Resp Med & Allergy, SE-90185 Umea, Sweden.
    Slinde, F.
    Håglin, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Assessment of energy intake in women with chronic obstructive pulmonary disease: A doubly labeled water method study2015Ingår i: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 19, nr 5, s. 518-524Artikel i tidskrift (Refereegranskat)
    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.

  • 38.
    Farooqi, Nighat
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Slinde, Frode
    Carlsson, Maine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Håglin, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Predicting energy requirement with pedometer-determined physical-activity level in women with chronic obstructive pulmonary disease2015Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 10, s. 1129-1137Artikel i tidskrift (Refereegranskat)
    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.

  • 39.
    Farooqi, Nighat
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Slinde, Frode
    Håglin, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Validation of SenseWear Armband and ActiHeart monitors for assessments of daily energy expenditure in free-living women with chronic obstructive pulmonary disease2013Ingår i: Physiological Reports, E-ISSN 2051-817X, Vol. 1, nr 6, artikel-id e00150Artikel i tidskrift (Refereegranskat)
    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.

  • 40.
    Frykholm, Erik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Klijn, Peter
    Saey, Didier
    van Hees, Hieronymus W. H.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sörlin, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Maltais, François
    Nyberg, Andre
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial2019Ingår i: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 20, nr 1, artikel-id 6Artikel i tidskrift (Refereegranskat)
    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.

  • 41. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bjermer, Leif
    Bossios, Apostolos
    Dahlén, Barbro
    Janson, Christer
    Kankaanranta, Hannu
    Kauppi, Paula
    Kilpelainen, Maritta
    Lehtimäki, Lauri
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ulrik, Charlotte Suppli
    Viinanen, Arja
    Porsbjerg, Celeste
    Late Breaking Abstract - NORdic Database for aSThmA Research (NORDSTAR): Swedish and Finnish patients2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    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.

  • 42. Gerlofs-Nijland, ME
    et al.
    Boere, AJ
    Leseman, DL
    Dormans, JA
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Salonen, RO
    van Bree, L
    Cassee, FR
    Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats.2005Ingår i: Part Fibre Toxicol, Vol. 24, nr 2, s. 2-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study was performed within the scope of two multi-center European Commission-funded projects (HEPMEAP and PAMCHAR) concerning source-composition-toxicity relationship for particulate matter (PM) sampled in Europe. The present study aimed to optimize the design for PM in vivo toxicity screening studies in terms of dose and time between a single exposure and the determination of the biological responses in a rat model mimicking human disease resulting in susceptibility to ambient PM. Dust in thoracic PM size-range (aerodynamic diameter <10 μm) was sampled nearby a road tunnel (RTD) using a high volume cascade impactor. Spontaneously hypertensive rats were exposed to urban dust collected in Ottawa, Canada (EHC-93 10 mg/kg of body weight; reference PM) or different RTD doses (0.3, 1, 3, 10 mg/kg of body weight) by intratracheal instillation. Necropsy was performed at 4, 24, or 48 hr after exposure.

    Results

    The neutrophil numbers in bronchoalveolar lavage fluid increased tremendously after exposure to the highest RTD doses or EHC-93. Furthermore, PM exposure slightly affected blood coagulation since there was a small but significant increase in the plasma fibrinogen levels (factor 1.2). Pulmonary inflammation and oxidative stress as well as changes in blood coagulation factors and circulating blood cell populations were observed within the range of 3 to 10 mg PM/kg of body weight without significant pulmonary injury.

    Conclusion

    The optimal dose for determining the toxicity ranking of ambient derived PM samples in spontaneously hypertensive rats is suggested to be between 3 and 10 mg PM/kg of body weight under the conditions used in the present study. At a lower dose only some inflammatory effects were detected, which will probably be too few to be able to discriminate between PM samples while a completely different response pattern was observed with the highest dose. In addition to the dose, a 24-hr interval from exposure to sacrifice seemed appropriate to assess the relative toxic potency of PM since the majority of the health effects were observed one day after PM exposure compared to the other times examined. The aforementioned considerations provide a good basis for conducting PM toxicity screening studies in spontaneously hypertensive rats.

  • 43. Gerlofs-Nijland, Miriam E
    et al.
    Dormans, Jan A M A
    Bloemen, Henk J T
    Leseman, Daan L A C
    John, A
    Boere, F
    Kelly, Frank J
    Mudway, Ian S
    Jimenez, Al A
    Donaldson, Ken
    Guastadisegni, Cecilia
    Janssen, Nicole A H
    Brunekreef, Bert
    Sandström, Thomas
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Lungmedicin.
    van Bree, Leendert
    Cassee, Flemming R
    Toxicity of coarse and fine particulate matter from sites with contrasting traffic profiles.2007Ingår i: Inhal Toxicol, ISSN 1091-7691, Vol. 19, nr 13, s. 1055-69Artikel i tidskrift (Refereegranskat)
  • 44.
    Gonzalez, Manuel Cruz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Robinson, Simon
    Mills, Nicholas L
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hyperleptinemia is associated with altered endothelial functionManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

  • 45.
    Gouveia-Figueira, Sandra C.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust2018Ingår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, s. 62-69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 46.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure2017Ingår i: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, nr 11, s. 2967-2980Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 47.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mass spectrometry profiling of oxylipins, endocannabinoids and N-acylethanolamines in human lung lavage fluids reveal responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposureManuskript (preprint) (Övrigt vetenskapligt)
  • 48.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karimpour, Masoumeh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bosson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Unosson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Effect of controlled exposure to biodiesel exhaust on human plasma bioactive lipid profilesManuskript (preprint) (Övrigt vetenskapligt)
  • 49. Guastadisegni, Cecilia
    et al.
    Kelly, Frank J
    Cassee, Flemming R
    Gerlofs-Nijland, Miriam E
    Janssen, Nicole AH
    Pozzi, Roberta
    Brunekreef, Bert
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mudway, Ian
    Determinants of the proinflammatory action of ambient particulate matter in immortalized murine macrophages2010Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 118, nr 12, s. 1728-1734Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 50.
    Gustafsson, Åsa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. Swedish Def Res Agcy, Div CBRN Def & Secur, SE-90182 Umea, Sweden.
    Bergström, Ulrika
    Ågren, Lina
    Österlund, Lars
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Bucht, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. Swedish Def Res Agcy, Div CBRN Def & Secur, SE-90182 Umea, Sweden.
    Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles2015Ingår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 288, nr 1, s. 1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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