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  • 151.
    Larsson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundström, Susanna
    Pinto, Rui
    Rankin, Greg
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Karimpour, Masoumeh
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wheelock, Craig
    Nording, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 43, no 2, p. 453-463Article in journal (Refereed)
    Abstract [en]

    Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups ((RY)-Y-2[cum]=0.822 and Q(2)[cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.

  • 152.
    Larsson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rankin, Greg
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bicer, Melis
    Roos-Engstrand, Ester
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Vitamin C transporters in the airways of healthy and asthmatic humansManuscript (preprint) (Other academic)
  • 153.
    Larsson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rankin, Gregory D.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bicer, Elif M.
    Roos-Engstrand, Ester
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mudway, Ian S.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Identification of vitamin C transporters in the human airways: a cross-sectional in vivo study2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 4, article id e006979Article in journal (Refereed)
    Abstract [en]

    Objectives: Vitamin C is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role as a sacrificial antioxidant, little is known about its transport into the respiratory tract lining fluid (RTLF), or the underlying airway epithelial cells. While several vitamin C transporters have been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of their protein distribution within the human lung is limited, in the case of GLUTs or unknown for SVCTs.

    Setting and participants: Protein expression of vitamin C transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid, obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In addition, antioxidant concentrations were determined in RTLF. The study was performed at one Swedish centre.

    Primary and secondary outcome measures: The primary outcome measure was to establish the location of vitamin C transporters in the human airways. As secondary outcome measures, RTLF vitamin C concentration was measured and related to transporter expression, as well as bronchial epithelial inflammatory and goblet cells numbers.

    Results: Positive staining was identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were present in the apical bronchial epithelium, where SVCT2 staining was predominately localised to goblet cells and inversely related to RTLF vitamin C concentrations.

    Conclusions: This experimental study is the first to demonstrate protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A negative correlation between SVCT2-positive goblet cells and bronchial RTLF vitamin C concentrations suggests a possible role for goblet cells in regulating the extracellular vitamin C pool.

  • 154. Lefaudeux, Diane
    et al.
    De Meulder, Bertrand
    Loza, Matthew J
    Peffer, Nancy
    Rowe, Anthony
    Baribaud, Frédéric
    Bansal, Aruna T
    Lutter, Rene
    Sousa, Ana R
    Corfield, Julie
    Pandis, Ioannis
    Bakke, Per S
    Caruso, Massimo
    Chanez, Pascal
    Dahlén, Sven-Erik
    Fleming, Louise J
    Fowler, Stephen J
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shaw, Dominic E
    Singer, Florian
    Sterk, Peter J
    Roberts, Graham
    Adcock, Ian M
    Djukanovic, Ratko
    Auffray, Charles
    Chung, Kian Fan
    U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics2017In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 6, p. 1797-1807Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided.

    OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum.

    METHODS: Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data.

    RESULTS: Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels.

    CONCLUSION: Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.

  • 155.
    Lennelöv, Emma
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    The prevalence of airway symptoms and asthma among young adolescent cross-country skiers2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 156. Liaaen, Erik Dyb
    et al.
    Henriksen, Anne H
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    A Scandinavian audit of hospitalizations for chronic obstructive pulmonary disease2010In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 104, no 9, p. 1304-1309Article in journal (Refereed)
    Abstract [en]

    In Scandinavia no large audits of hospitalizations for chronic obstructive pulmonary disease (COPD) have been performed, and data on adherence to national guidelines are scarce. The aims of the present study were to audit hospitalizations for COPD exacerbations in three Scandinavian hospitals with respect to incidence, patient population and standards of hospital care. Retrospectively all hospitalizations in the Departments of Internal and Respiratory Medicine in Ostersund Hospital (Sweden), Aalesund Hospital (Norway) and Trondheim University Hospital (Norway) from Jan 1 to Dec 31, 2005, with discharge ICD-10 diagnoses J43-J44, J96 + J44 or J13-18 + j44 were registered. A total of 1144 admissions (731 patients) were identified from patient administrative systems and medical charts. Among the admitted patients 27% were >80 years old, >50% had COPD stage III or IV, and 14% had respiratory acidosis at admittance. Patients with 3 or more admissions (13%) during 2005 accounted for 36% of all hospitalizations. One third of the patients were current smokers. Non-invasive ventilation was used in 14% of the admissions, with large variation between centres. In-hospital mortality was 3.7%. In this first large Scandinavian audit of COPD-hospitalizations, all centres had low in-hospital mortality. We consider this as an indication of good clinical practice in the three studied centres and possibly due to the frequent use of non-invasive ventilation.

  • 157.
    Lindberg, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bjerg Bäcklund, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Larsson, Lars-Gunnar
    Lundbäck, Bo
    Prevalence and underdiagnosis of COPD by disease severity and the attributable fraction of smoking Report from the Obstructive Lung Disease in Northern Sweden Studies.2006In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 100, no 2, p. 264-272Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is a lack of epidemiological data on COPD by disease severity. We have estimated the prevalence and underdiagnosis of COPD by disease severity defined by the British Thoracic Society (BTS) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. The impact of smoking was evaluated by the population attributable fraction of smoking in COPD. METHODS: A random sample of 1500 responders of the third postal survey performed in 1996 of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies' first cohort (6610 subjects recruited in 1985) were invited to structured interview and spirometry. One thousand two hundred and thirty-seven subjects (82%) performed spirometry. RESULTS: The prevalence of mild BTS-COPD was 5.3%, moderate 2.2%, and severe 0.6% (GOLD-COPD: mild 8.2%, moderate 5.3%, severe 0.7%, and very severe 0.1%). All subjects with severe COPD were symptomatic, corresponding figures among mild COPD were 88% and 70% (BTS and GOLD), Subjects with severe BTS-COPD reported a physician-diagnosis consistent with COPD in 50% of cases, in mild BTS-COPD 19%, while in mild GOLD-COPD only 5% of cases. The major risk factors, age and smoking, had a synergistic effect on the COPD-prevalence. The Odds Ratio (OR) for having COPD among smokers aged 76-77 years was 59 and 34 (BTS and GOLD) when non-smokers aged 46-47 was used as reference population. CONCLUSIONS: Most subjects with COPD have a mild disease. The underdiagnosis is related to disease-severity. Though being symptomatic, only a half of the subjects with severe COPD are properly labelled. Smoking and increasing age were the major risk factors and acted synergistic.

  • 158.
    Lindberg, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Jonsson, AC
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundgren, Rune
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ten-year cumulative incidence of COPD and risk factors for incident disease in a symptomatic cohort.2005In: Chest, Vol. 127, no 5, p. 1544-52Article in journal (Refereed)
  • 159. Lindberg, Anne
    et al.
    Jonsson, Ann-Christin
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundgren, Rune
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, Lars-Gunnar
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    10-year cumulative incidence of COPD and risk factors for incident disease in a symptomatic cohort2005In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 127, no 5, p. 1544-1552Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: To determine the 10-year cumulative incidence of COPD in a cohort of subjects with respiratory symptoms (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) using the British Thoracic Society (BTS) and GOLD spirometric criteria. Furthermore, we sought to evaluate risk and gender factors for incident COPD. DESIGN AND SETTING: A postal questionnaire was administered in 1986 to all 6,610 subjects in eight areas of northern Sweden who had been born in 1919 to 1920 (group 1), 1934 to 1935 (group 2), and 1949 to 1950 (group 3). The response rate was 86%. All of the subjects reporting respiratory symptoms were invited to participate in a structured interview and pulmonary function test (PFT), and 1,506 (91%) participated. In 1996, 90% could be traced for follow-up, of whom 1,165 (86%) of the invited subjects participated and 1,109 subjects (534 women) were able to perform technically adequate PFTs in both 1986 and 1996. RESULTS: The 10-year cumulative incidence of COPD was estimated at 8.2% (using BTS criteria) and 13.5% (using GOLD criteria). Significant risk factors for incident COPD (using BTS and GOLD criteria) in a multivariate analysis were higher age (group 1 odds ratio [OR]: BTS criteria, 3.49; GOLD criteria, 3.37; group 2 OR: BTS criteria, 4.50; GOLD criteria, 5.70) and smoking (OR: BTS criteria, 5.37; GOLD criteria, 4.56), but not gender or heredity. Respiratory symptoms were significantly associated with incident COPD when added to the same model. In analogous analyses that were conducted separately for men and women, smoking yielded an OR of 8.52 among women (95% confidence interval [CI], 3.43 to 21.2) compared with 3.14 among men (95% CI, 1.26 to 7.84). The symptoms cough, sputum production, and chronic productive cough reached statistical significance in women, while dyspnea and wheeze did so in men. CONCLUSION: In this cohort, the 10-year cumulative incidence of COPD was 8.2% (using BTS criteria) and 13.5% (using GOLD criteria). Increasing age, smoking, and bronchitic symptoms, but not gender, were risk factors for incident COPD. GOLD stage 0 therefore appears to identify subjects who are at risk of COPD, but men and women presented different risk profiles.

  • 160.
    Lindberg, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Jonsson, Ann-Christin
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundgren, Rune
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Larsson, Lars-Gunnar
    Lundbäck, Bo
    Prevalence of chronic obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor's diagnosis, symptoms, age, gender, and smoking habits.2005In: Respiration, ISSN 0025-7931, Vol. 72, no 5, p. 471-9Article in journal (Refereed)
  • 161.
    Lindberg, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. the OLIN unit, Umeå University, Umeå, Sweden .
    Niska, Benjamin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. the OLIN unit, Umeå University, Umeå, Sweden .
    Stridsman, Caroline
    Eklund, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eriksson, Berne
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Low nicotine dependence and high self-efficacy can predict smoking cessation independent of the presence of chronic obstructive pulmonary disease: a three year follow up of a population-based study2015In: Tobacco Induced Diseases, ISSN 1617-9625, E-ISSN 1617-9625, Vol. 13, article id 27Article in journal (Refereed)
    Abstract [en]

    Background: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), and smoking cessation is the only intervention that slows disease progression. It is important to know whether current factors related to smoking and smoking cessation are different among subjects with and without COPD in order to support smoking cessation. The aim of this study was to evaluate factors related to smoking cessation and to compare characteristics and nicotine dependence among smokers with and without COPD.

    Methods: In 2005, 1614 subjects in a population-based longitudinal study of subjects with COPD and controls were examined. The Fagerstrom Test for Nicotine Dependence (FTND) and motivation for smoking cessation were assessed for current smokers (n = 299 total, 194 with COPD). Data on smoking cessation were collected in a follow-up in 2008 (n = 240).

    Results: Smokers with COPD had more pack-years and respiratory symptoms than smokers without COPD, whereas higher FTND scores were associated with anxiety/depression and respiratory symptoms in both groups. Nineteen percent of the smokers had quit smoking by the follow-up 3 years later, and they had significantly lower FTND scores (2.54 vs. 3.75, p < 0.001) and higher self-efficacy scores (10.0 vs. 6.0, p = 0.020) at baseline than the sustained smokers. Smoking cessation was related to low FTND scores and high self-efficacy independent of the presence of COPD, respiratory symptoms, anxiety/depression, and heart disease.

    Conclusions: The FTND score and a simple visual analog scale for assessing self-efficacy seem to be valuable instruments for predicting smoking cessation over several years, independent of COPD, respiratory symptoms, presence of anxiety/depression, and heart disease.

  • 162.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Proteolytic imbalance in COPD: epidemiological and clinical aspects2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The complete pathologic mechanism behind the development of chronic obstructive pulmonary disease (COPD) remains unclear, but several risk factors have been identified, of which smoking is the most common. Proteolytic imbalance contributes to lung tissue degradation and is related to both smoking and COPD symptoms. Spirometry and symptomatic assessments are the standard diagnostics, but COPD has varying clinical features, that hamper clinical management and research assessment. Evaluating proteolytic markers' relationship to COPD and its clinical presentation could reveal proteolytic imbalance as an important disease mechanism.

    Aims: 1) To evaluate proteolytic markers in COPD and non-COPD. 2) To study the relationship between proteolytic markers and both lung function decline and prognosis. 3) To recruit subjects from a longitudinal study to a clinical study of disease mechanisms. 4) To study proteolytic markers in airways and serum and their relation to rate of decline in lung function.

    Methods: Spirometry, serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were evaluated in a population-based study comprising 993 COPD subjects and 993 age- and sex-matched non-COPD referents. In addition, data from 2005 to 2010 were surveyed comprising longitudinal spirometry data and mortality records. For a clinical study, we described the recruitment process of COPD subjects with a FEV1 decline of ≥60 or ≤30 mL/year, along with ever- and never-smoking controls with normal lung function. MMP-9, MMP-12, and TIMP-1 data from bronchial wash (BW), bronchoalveolar lavage (BAL) and serum (collected from 2012 to 2014) were assessed in the clinical study.

    Results: COPD subjects presented higher serum concentrations of MMP- 9 compared to non-COPD subjects (p = 0.017). MMP-9 and MMP- 9/TIMP-1 ratio had a negative linear association with the forced expiratory volume in one second (FEV1) percentage predicted in COPD. Associating the 2005 levels of MMP-9 and MMP-9/TIMP-1 ratio to decline in FEV1 and FEV1% predicted, revealed a similar negative association pattern in both non-COPD and COPD, however, this was only significant for non-COPD. A non-response analysis comparing proteolytic marker values from 2005 between participating and non-participating subjects at follow-up in 2010 (excluding deceased individuals) demonstrated significantly higher MMP-9 and MMP-9/TIMP-1 ratios in both non-COPD and COPD, and significantly lower TIMP-1 concentration in non-participants compared to participants. Among the deceased, MMP-9 levels and MMP-9/TIMP-1 ratios were higher in COPD compared to non-COPD. In the longitudinal study, all-cause mortality was higher in the COPD group (16%), than in the non-COPD (10%) (p = 0.008).

    For the clinical study, 15 subjects were recruited to the two normal lung function groups, while this goal was unachieved for the two COPD groups. The most prevalent reasons for exclusion in the COPD groups were comorbidities. BW- and BAL-MMP-12 concentrations were higher in the COPD group comprising current- and ex-smokers, compared to both ever-smokers (BW: p = 0.001, BAL: p = 0.001) and non-smokers with normal lung function (BW: p = 0.001, BAL: p = 0.001). To evaluate the impact of smoking, COPD ex-smokers were compared to COPD current smokers, with no significant difference in BW- and BAL-MMP- 12. In contrast COPD-ex smokers had higher BW- and BAL-MMP-12 compared to ex-smokers with normal lung function, thus suggesting increased BW- and BAL-MMP-12 as markers of COPD rather than of smoking. MMP-12 concentrations in serum were higher for COPD current smokers compared to COPD ex-smokers (p = 0.028), but there was no significant difference between COPD ex-smokers and ex-smokers with normal lung function. BAL-MMP-12 in COPD was associated with annual decline in FEV1 (r = 0.61, p = 0.005).

    Conclusion: Extrapolating the data on MMP-9 and MMP-9/TIMP-1 ratio suggests increased proteolytic activity is related to airflow limitation and consequently to COPD severity. Considering the population-based nature of the study, the association of both MMP-9 and MMP-9/TIMP-1-ratio in COPD to mortality risk could be translated to the general population. Identifying COPD subjects with specific phenotypes proved difficult despite the large number of available individuals. Increased airway levels of MMP-12 indicated a state of increased proteolytic activity and were associated with rapid lung function decline in COPD. These findings imply that proteolytic imbalance is related to symptoms, lung function decline and prognosis, suggesting it represents a relevant disease mechanism in COPD.

  • 163.
    Linder, Robert
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Increased Mmp-9/timp-1 Ratio Is Associated With Increased Mortality-Report From The Obstructive Lung Disease In Northern Sweden (olin) COPD Study2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A2312Article in journal (Other academic)
  • 164.
    Linder, Robert
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Proteolytic imbalance is related to FEV1 decline in COPDManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    It is generally accepted that metalloproteinases contribute to lung tissue destruction. This study intends to examine how proteolytic imbalance impacts COPD in relation to phenotypes of non-rapid and rapid decline in lung function, by clinically assessing subjects recruited from a population-based cohort.

    Methods

    Subjects were recruited from the longitudinal OLIN COPD study providing spirometry data over time. In total 52 subjects were included: 12 with COPD and a rapid decline in FEV1 (≥60 mL/year), 10 with COPD and a non-rapid decline in FEV1 (≤30 mL/year), 15 current and ex-smokers with normal lung function, and 15 non-smokers with normal lung function. Proteolytic markers MMP-9, MMP-12 and TIMP-1 were assessed in serum and airway lavages.

    Results

    MMP-12 in BW and BAL was higher in COPD compared to both ever- smokers (BW: p = 0.001, BAL: p = 0.001) and non-smokers with normal lung function (BW: p = 0.001, BAL: p = 0.001). BAL-MMP-12 in COPD displayed a positive association to annual decline in FEV1

    (r = 0.61, p = 0.005). The lowest concentration of S-TIMP-1 (477 (295- 717) ng/mL) was found in COPD with a rapid decline in lung function, with a negative association between annual decline in FEV1 and s-TIMP- 1 (r = -0.42, p = 0.05).

    Conclusion

    Airway protease activity measured as MMP-12 concentration in BAL was increased in COPD, compared to both smokers with normal lung function and healthy. Individuals with the highest levels of airway MMP- 12 experienced the greatest decline in FEV1. Furthermore, a negative association was found between TIMP-1 in serum and FEV1 decline. Increased airway proteolytic activity may play an important role in the progress of COPD.

  • 165.
    Lott, Alexander
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Exercise-induced laryngeal obstruction in elite cross-country skiers2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 166. Lucking, Andrew J
    et al.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan L
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Sidhu, Manjit K
    Langrish, Jeremy P
    Boon, Nicholas A
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Badimon, Juan J
    Gerlofs-Nijland, Miriam E
    Cassee, Flemming R
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Donaldson, Kenneth
    Sandstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men2011In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 123, no 16, p. 1721-1728Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men.

    METHODS AND RESULTS: Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release.

    CONCLUSIONS: Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

  • 167. Lucking, Andrew J
    et al.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Faratian, Dana
    Barath, Stefan L
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cassee, Flemming R
    Donaldson, Kenneth
    Boon, Nicholas A
    Badimon, Juan J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Diesel exhaust inhalation increases thrombus formation in man2008In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 29, no 24, p. 3043-3051Article in journal (Refereed)
    Abstract [en]

    AIMS: Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men.

    METHODS AND RESULTS: In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust inhalation increased thrombus formation under low- and high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels. Diesel exhaust also increased platelet-neutrophil and platelet-monocyte aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air.

    CONCLUSION: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.

  • 168.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Lung Medicine, Central Hospital, Boden.
    Asthma, chronic bronchitis and respiratory symptoms: prevalence and important determinants1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The Obstructive Lung Disease in Northern Sweden study's (OLIN) overall aim is prevention of obstructive airways diseases; asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD). The first part of the OLIN study was a cross- sectional study in three phases, which aimed to estimate the prevalence obstructive lung diseases and to collect data on possible determinants of diseases. This thesis is based on the first part of the OLIN study, and on a postal survey mainly performed in order to evaluate the external validity of the first part of the project Aims:

    * To assess the prevalences of asthma, chronic bronchitis and respiratory symptoms in adults.

    * To compare the influence of various diagnostic criteria on prevalence.

    * To identify subjects with obstructive lung diseases, in particular asthma, for case-referent

    and prospective longitudinal studies.

    * To examine whether the trend towards an increase in the prevalence of asthma persists.

    * Study factors that may influence the development of obstructive lung diseases; age,

    gender, smoking habit, occupation, socio-economic group, population density and area of domicile.

    The first part of the OLIN study consisted of three phases. A postal questionnaire regarding respiratory symptoms and diseases, smoking habit and profession was sent to all subjects aged 35-36 y, 50-51 y and 65-66 y (n=6,610) living in eight representative areas of Sweden's northernmost province; 86% completed the questionnaire. Those reporting symptoms suspicious of asthma or chronic bronchitis (n=l,340), together with a stratified sample (n=315) of those not suspected of having the diseases according to the postal questionnaire, were invited to structured interviews and lung function tests. The prevalence of asthma, 5- 6% according to both the postal questionnaire and to the structured interview, prompted a validity study, which included bronchial provocation tests. While the prevalence remained unchanged, the validity study better identified the subjects with asthma and chronic bronchitis, thus improving the representativeness of the subjects with the diseases. In 1992, the study base was expanded by a postal questionnaire study which included 20/489 subjects 20-69 y in order to assess whether the prevalence had changed, to create possibilities to estimate the incidence, and to be better able to detect determinants of diseases.

    The results show that the prevalence of asthma in adults in 1992 was 7-8% according to postal questionnaire and was considerably higher, approximately 10%, in young adults. Further, the prevalence of asthma in 1986-1987 in subjects aged 35-36 y, 50-51 y and 65-66 y was 5% by using a combination of epidemiological and clinical methods. Various operational criteria yielded a prevalence of 4-7%. Between 1986 and 1992 the prevalence of asthma in these age groups increased with 1% according to the postal questionnaire. Chronic bronchitis in subjects aged 35-36 y was 3% in 1986-1987. The prevalence of chronic bronchitis increased with age, particularly in men. The mean prevalence in the three age groups 35-36 y, 50-51 y and 65-66 y was 12% in men and 8% in women. Chronic bronchitis was strongly associated with smoking, age and a family history of obstructive airways disease. Regarding socioeconomic group chronic bronchitis was related to manual workers in industry and to self- employed other than professionals, and it was particularly common in miners and in those employed in agriculture. The strongest risk factor for asthma was a family history of asthma, and asthma was more common in manual workers in service, in non-manual assistant employees as well as in farmers. The results also indicate the presence of an urban factor in asthma in northern Sweden, in spite of the fact that respiratory symptoms in general tended to be more common in the colder interior of the province compared with the coastal area.

  • 169. Lundbäck, Bo
    et al.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Jonsson, Ann-Christin
    Larsson, Lars-Gunnar
    James, Mark
    Asthma control over 3 years in a real-life study2009In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 103, no 3, p. 348-355Article in journal (Refereed)
    Abstract [en]

    This was a 3-year "real-life" study, during which patients' medication was increased and decreased to achieve sustained asthma control. Patients (282) were randomised to receive treatment with SAL 50microg, FP 250microg, or SFC 50/250microg via a Diskustrade mark inhaler, bid. A 12-month double-blind period was followed by a 2-year open phase. The physician increased or decreased patients' medication to achieve and maintain asthma control at regular clinical assessments using criteria based on the asthma treatment guidelines. On completion 73% (168/229) of the subjects were receiving SFC to maintain control of their asthma, compared with 21% (49/229) receiving FP and 5% (12/229) receiving SAL. Odds ratio for requiring increased treatment were 2.66 (p=0.002) for patients initially randomised to FP and 9.38 (p<0.0001) SAL, compared with SFC. Time until 25% of patients first required an increase in study medication was 6months for patients initially treated with SAL compared to 12months for FP and 21months for SFC. Symptoms and use of rescue medication improved first, followed rapidly by PEF with the greatest improvements occurring over the first year. Airway hyperresponsiveness continued to improve throughout the study. The majority of patients achieved and maintained control of asthma over a 3-year period with physician-driven medication changes. Patients treated with SFC were more likely to achieve control than patients treated with FP or SAL alone. Continuing improvements in airway hyperresponsiveness indicate the importance of maintaining treatment after clinical control of symptoms and lung function are achieved.

  • 170. Lundbäck, Bo
    et al.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Jonsson, Ann-Christin
    Larsson, Lars-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pétavy, Frank
    James, Mark
    Control of mild to moderate asthma over 1-year with the combination of salmeterol and fluticasone propionate.2006In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 100, no 1, p. 2-10Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to assess asthma control using salmeterol plus fluticasone propionate (FP) in combination (SFC) versus salmeterol or FP as monotherapy in patients with mild to moderate asthma. METHODS: In this randomised, double-blind, parallel-group study, 322 symptomatic patients were recruited, of which 282 were randomised to receive either salmeterol (50 microg), FP (250 microg), or SFC (50 microg/250 microg), via a single Diskus inhaler twice daily for 12 months. Outcome variables included the number of patients requiring an increase in study medication and the number experiencing 2 exacerbations during the 12-month treatment period. Airway hyper-responsiveness (AHR) and lung function tests were performed at clinic visits. Peak expiratory flow, rescue medication use, symptom scores and adverse events were recorded in diary cards. RESULTS: Fewer patients required an increase in study medication with SFC (10.5%) than with either FP (34.8%) or salmeterol (61.1%) (P<0.001). Significantly fewer patients experienced 2 exacerbations with SFC (4.2%), compared with FP (17.4%; P<0.01) or salmeterol (40%; P<0.001). SFC improved AHR to a significantly greater extent than FP (methacholine PC20=1.8 mg/ml vs. 1.1 mg/ml; P<0.05) or salmeterol (methacholine PC20=1.8 mg/ml vs. 0.7 mg/ml; P<0.001). CONCLUSIONS: The protection against exacerbations may be attributed to better control of inflammation, AHR and lung function parameters achieved with salmeterol and FP in combination, compared with either treatment alone.

  • 171.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Cardiovascular effects of diesel exhaust: mechanistic and interventional studies2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air pollution has been related to increased incidence of cardiovascular and respiratory morbidity and mortality, specifically in susceptible populations. Ambient particles, with a diameter of less than 2.5 mm, have been suggested to be the strongest contributor to these health effects. Diesel exhaust (DE) is a major source of small combustion-derived PM air pollution world wide. 

    In healthy volunteers, exposure to DE, has been associated with airway inflammation and impaired vasomotor function and endogenous fibrinolysis.

    The aims of this thesis were to further elucidate the underlying mechanisms to the reported cardiovascular effects following exposure to DE, with specific focus on endothelin-1 (ET-1). Additionally, the vascular effects of the major gaseous component of DE, nitrogen dioxide (NO2), were assessed together with the impact of an exhaust particle trap to reduce the observed negative vascular effects after DE exposure.

    Methods: In all studies healthy, non-smoking male volunteers were included and exposed for one hour during intermittent exercise in a randomised double-blind crossover fashion. In studies I-III, subjects were exposed to DE at a particulate matter concentration of approximately 300 μg/m3 and filtered air, on two different occasions. In study V an additional exposure was employed, during which DE was filtered through an exhaust particle trap. In study IV subjects were exposed to nitrogen dioxide (NO2) at 4 ppm or filtered air.

    In study I, thrombus formation and platelet activation were assessed using the Badimon ex vivo perfusion chamber and flow cytometry. Study II comprised the determination of arterial stiffness including pulse wave analysis and velocity.

    In studies III-V, vascular assessment was performed using venous occlusion plethysmography. In studies IV and V, the vascular responses to intra-arterially infused endothelial-dependent and endothelial-independent vasodilatators were registered. In study III, vascular responses to intra-arterial infusion of Endothelin-1 (ET-1) and ET-1-receptor antagonists were assessed. Venous occlusion phlethysmography was in all cases performed 4-6 hours following exposures. Blood samples for markers of inflammation, coagulation and platelet activation were collected before and throughout the study periods in studies III and V.

    Results: Exposure to DE increased ex vivo thrombus formation and arterial stiffness, in terms of augmentation index. DE inhalation impaired vasomotor function and endogenous fibrinolysis. The exhaust particle trap reduced the particle concentration by 98% and abolished the effects on vasomotor function, endogenous fibrinolysis and ex vivo thrombus formation. Plasma concentrations of ET-1 and its precursor big-ET-1 were unchanged following exposure. Dual endothelial receptor antagonism caused similar vasodilatation after both exposures, although vasodilatation to the endothelin-A receptor alone was blunted after DE exposure. ET-1 infusion induced vasoconstriction only following DE exposure. Exposure to nitrogen dioxide did not affect vascular function.

    Conclusion: Inhalation of diesel exhaust in young healthy men impaired important and complementary aspects of vascular function in humans; regulation of vascular tone and endogenous fibrinolysis as well as increased ex vivo thrombus formation. The use of an exhaust particle trap significantly reduced particle emissions and abolished the DE-induced vascular and prothrombotic effects. The adverse vascular effects following DE exposure do not appear to be directly mediated through the endothelin system. Neither is NO2 suggested to be a major arbiter of the DE-induced cardiovascular responses. Arterial stiffness is a non-invasive and easily accessible method and could thus be employed to address vascular function in larger field studies. Taken together, this thesis has given further knowledge about the mechanisms underlying the DE-induced vascular effects.

  • 172.
    Lundbäck, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lucking, Andrew
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas
    Sidhu, Manjit
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Badimon, Juan
    Cassee, Flemming
    Donaldson, Kenneth
    Boon, Nicholas
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Exhaust particle traps reduce the adverse vascular and prothrombotic effects associated with diesel exhaust exposure in manManuscript (preprint) (Other academic)
  • 173.
    Lundbäck, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Lucking, Andrew
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Donaldson, Ken
    Newby, David E
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Experimental exposure to diesel exhaust increases arterial stiffness in man2009In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 6, no 13, p. 7-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: INTRODUCTION: Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness. METHODS: In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 mug/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated. RESULTS: Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure. CONCLUSION: Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution.

  • 174.
    Lundbäck, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas
    Lucking, Andrew
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Donaldson, Kenneth
    Newby, David
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Exposure to diesel exhaust increases arterial stiffness in man2009In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 6, no 7Article in journal (Refereed)
    Abstract [en]

    Introduction Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness.

    Methods In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 μg/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated.

    Results Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure.

    Conclusion Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution.

  • 175.
    Lundström, Susanna L.
    et al.
    Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
    Levanen, Bettina
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nording, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Klepczynska-Nystrom, Anna
    Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Sköld, Magnus
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Haeggström, Jesper Z.
    Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
    Grunewald, Johan
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svartengren, Magnus
    Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Hammock, Bruce D.
    Department of Entomology and Cancer Research Center, University of California Davis, Davis, California, United States of America.
    Larsson, Britt-Marie
    Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Eklund, Anders
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Åsa M.
    Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wheelock, Craig E.
    Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
    Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 8, p. e23864-Article in journal (Refereed)
    Abstract [en]

    Background: Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.

    Objectives: This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.

    Methods: Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPAR gamma). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.

    Results: Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and alpha-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.

    Conclusions: Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

  • 176. Löfdahl, Kerstin
    et al.
    Gustafson, Torbjörn
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Ström, Kerstin
    [Need of integrated guidelines for home oxygen therapy]2007In: Lakartidningen, ISSN 0023-7205, Vol. 104, no 24-25, p. 1902-4Article in journal (Refereed)
  • 177. Löfdahl, Magnus J
    et al.
    Roos-Engstrand, Ester
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Dahlen, Barbro
    Elmberger, Göran
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sköld, C Magnus
    Increased intraepithelial T-cells in stable COPD2008In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 102, no 12, p. 1812-1818Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The airway epithelium is the first line of defence in the response to inhaled particles and irritants. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by an irreversible loss of lung function, with cigarette smoking as a major risk factor. Here, we address intraepithelial T-cells in COPD, as these cells are a distinct T-cell subtype thought to have important regulatory functions. We hypothesised that intraepithelial T-cells play a role in the response to lung irritants and that the T-cell populations would be altered and associated with signs of inflammation in COPD.

    METHODS: Bronchoscopy with endobronchial mucosal biopsy sampling was performed in 22 patients (mean age; 57) with stable COPD (median FEV(1)% predicted: 51). Age- and smoking- matched smokers (S) with normal lung function (n=14) and age-matched non-smokers (NS) (n=15) served as controls. Airway inflammation was recorded visually using bronchitis index (BI). Biopsy specimens were processed into glycol methacrylate resin and inflammatory cells were stained immunohistochemically.

    RESULTS: The number of intraepithelial CD4+ T-cells were significantly higher in COPD patients compared to smokers as well as trend towards significance in non-smokers (p=0.005 and p=0.036, respectively), whereas intraepithelial CD8+ T-cells number were increased in patients with COPD compared to non-smokers (p=0.017). Both patients with COPD and smokers had a higher BI than non-smokers (p<0.001 for both).

    CONCLUSIONS: The present data suggest a role for intraepithelial CD4+ and CD8+ T-cells in stable COPD and indicate that T-cells are of importance in the long-term inflammatory response in COPD or, alternatively, play a regulatory role.

  • 178.
    Löfdahl, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Andersson, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bennett, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nitrogen narcosis and emotional processing during compressed air breathing2013In: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 84, no 1, p. 17-21Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies on nitrogen narcosis have focused on how it affects behavior, performance, and cognitive function. However, little is known about the effects of nitrogen narcosis on the emotional processing of external stimuli. Method: We presented 20 volunteers with images from the International Affective Picture System (IAPS) and categorized as unpleasant, neutral, or pleasant, while sitting in a hyperbaric chamber at the surface (101,3kPa) and at 39 m equivalent depth (496.4 kPa). The participants rated the images along three affective dimensions: valence (intrinsic attractiveness or aversiveness of a stimuli), arousal, and dominance. Results: In the valence dimension there was no signifi cant effect of increased pressure or interaction between increased pressure and image category. There was a signifi cant interaction between image category and the pressure at which the images were viewed in the arousal dimension. The mean arousal rating score for unpleasant stimuli was 0.5 point (on a 9-point scale) lower at hyperbaric conditions and equal arousal rating score for neutral stimuli in general. Discussion: The absence of any effect of pressure in the valence dimension suggests that divers have no impairment in their ability to determine the pleasantness or unpleasantness of different stimuli. Furthermore, this study suggests that the effects of nitrogen narcosis on the emotional processing of external stimuli are primarily evident in the arousal dimension. Although differences in arousal ratings were relatively small in magnitude, even a small alteration in emotional response to external stimuli might be important in the context of deep diving. © Aerospace Medical Association, Alexandria, VA.

  • 179. Löndahl, Jakob
    et al.
    Pagels, Joakim
    Boman, Christoffer
    Swietlicki, Erik
    Massling, Andreas
    Rissler, Jenny
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Bohgard, Mats
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Deposition of biomass combustion aerosol particles in the human respiratory tract.2008In: Inhalation toxicology, ISSN 1091-7691, Vol. 20, no 10, p. 923-33Article in journal (Refereed)
    Abstract [en]

    Smoke from biomass combustion has been identified as a major environmental risk factor associated with adverse health effects globally. Deposition of the smoke particles in the lungs is a crucial factor for toxicological effects, but has not previously been studied experimentally. We investigated the size-dependent respiratory-tract deposition of aerosol particles from wood combustion in humans. Two combustion conditions were studied in a wood pellet burner: efficient ("complete") combustion and low-temperature (incomplete) combustion simulating "wood smoke." The size-dependent deposition fraction of 15-to 680-nm particles was measured for 10 healthy subjects with a novel setup. Both aerosols were extensively characterized with regard to chemical and physical particle properties. The deposition was additionally estimated with the ICRP model, modified for the determined aerosol properties, in order to validate the experiments and allow a generalization of the results. The measured total deposited fraction of particles from both efficient combustion and low-temperature combustion was 0.21-0.24 by number, surface, and mass. The deposition behavior can be explained by the size distributions of the particles and by their ability to grow by water uptake in the lungs, where the relative humidity is close to saturation. The experiments were in basic agreement with the model calculations. Our findings illustrate: (1) that particles from biomass combustion obtain a size in the respiratory tract at which the deposition probability is close to its minimum, (2) that particle water absorption has substantial impact on deposition, and (3) that deposition is markedly influenced by individual factors.

  • 180.
    Löndahl, Jakob
    et al.
    Department of Physics, Division of Nuclear Physics, Lund University, Lund, Sweden.
    Swietlicki, Erik
    Department of Physics, Division of Nuclear Physics, Lund University, Lund, Sweden.
    Rissler, Jenny
    Department of Design Sciences, Division of Ergonomics and Aerosol Technology (EAT), Lund University, Lund, Sweden.
    Bengtsson, Agneta
    Department of Physics, Division of Nuclear Physics, Lund University, Lund, Sweden.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Experimental determination of the respiratory tract deposition of diesel combustion particles in patients with chronic obstructive pulmonary disease2012In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 9, p. 30-Article in journal (Refereed)
    Abstract [en]

    Background: Air pollution, mainly from combustion, is one of the leading global health risk factors. A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD). There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles. Objectives: To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing. Methods: Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber. The respiratory tract deposition of the particles was measured in the size range 10-500 nm during spontaneous breathing. Results: The deposited dose rate increased with increasing severity of the disease. However, the deposition probability of the ultrafine combustion particles (< 100 nm) was decreased in COPD patients. The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function. Conclusions: The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability. The strong correlations between lung function and particle deposition, especially in the size range of 20-30 nm, suggest that altered particle deposition could be used as an indicator respiratory disease.

  • 181. Macsali, Ferenc
    et al.
    Real, Francisco Gómez
    Omenaas, Ernst Reidar
    Bjorge, Line
    Janson, Christer
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Svanes, Cecilie
    Oral contraception, body mass index, and asthma: a cross-sectional Nordic-Baltic population survey2009In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 123, no 2, p. 391-397Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emerging evidence suggests that sex steroid hormones may influence airways obstruction, and that metabolic status may modify potential effects.

    OBJECTIVE: This study investigated the association between use of oral contraceptive pills (OCPs) and asthma in a Nordic-Baltic population-based study, while taking into account possible interplay with body mass index (BMI).

    METHODS: Postal questionnaires were sent to subjects in Denmark, Estonia, Iceland, Norway, and Sweden from 1999 to 2001 (response rate in women, 77%). Pregnant women, women using hormone replacement therapy, and women >45 years were excluded. Analyses included 5791 women 25 to 44 years old, of whom 961 (17%) used OCP. Logistic regression analyses included adjustment for smoking, irregular menstruation, BMI, age, type of dwelling, and center.

    RESULTS: Oral contraceptive pills were associated with increased risk for asthma (odds ratio, 1.42; 95% CI, 1.09-1.86), asthma with hay fever (1.48; 1.08-2.03), wheeze with shortness of breath (1.27; 1.02-1.60), hay fever (1.25; 1.06-1.48), and >/=3 asthma symptoms (1.29; 1.05-1.58). The findings were consistent between centers. The associations were present only among normal weight women (BMI 20-25 kg/m(2), asthma: 1.45; 1.02-2.05) and overweight women (BMI >25kg/m(2): 1.91; 1.20-3.02), but not among lean women (BMI <20 kg/m(2): 0.41; 0.12-1.40). Interaction between BMI and OCP in association with asthma was significant (P(interaction) < .05).

    CONCLUSIONS: Women using oral contraceptive pills had more asthma. This was found only in normal weight and overweight women, indicating interplay between sex hormones and metabolic status in effect on the airways. The findings originate from a cross-sectional postal survey and should be interpreted with caution; it is recommended that asthma symptoms are included in clinical trials of oral contraception.

  • 182.
    Marklund, Marie
    et al.
    Umeå University, Faculty of Medicine, Odontology, Ortodontics.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Long-term effects of mandibular repositioning appliances on symptoms of sleep apnoea2007In: J Sleep Res, Vol. 16, no 4, p. 414-20Article in journal (Refereed)
    Abstract [en]

    Mandibular repositioning appliances (MRAs) reduce symptoms of obstructive sleep apnoea in the short term, but the long-term effects are unknown. Our objective was to evaluate the long-term symptomatic effects of custom-made MRAs and to identify the patients who will experience subjective benefits from treatment. A cohort of 260 consecutive patients treated with appliances for non-apnoeic snoring or sleep apnoea was followed up by a questionnaire and examination after an average of 5.4 years. The subjective effect was defined as good when complaints of daytime sleepiness occurred less than once a week. A total of 185 patients (71%) responded to the questionnaires. Of the respondents, 96 reported frequent use, 33 reported infrequent use, 26 reported discontinued treatment and 30 reported modified treatment. Mild cases (apnoea-hypopnoea index [AHI] < 15) were likelier than more severe cases to continue treatment. Patients who had used MRAs reported fewer complaints of sleepiness, headaches and daytime naps. Frequent use (P = 0.001), few night-time awakenings before start of treatment (P = 0.02) and effective apnoea reduction during treatment of more severe cases (P = 0.02) correlated with a good subjective effect at long-term follow-up. Our conclusion is that custom-made MRAs reduce sleep apnoea symptoms in the long term. The mildest cases will experience the greatest long-term benefit.The reason is that non-apnoeic snorers and patients with a mild disease are more likely to continue treatment and that their long-term results with regard to excessive sleepiness are similar to patients with a more severe disease.

  • 183.
    Marklund, Marie
    et al.
    Umeå University, Faculty of Medicine, Odontology, Ortodontics.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundgren, Rune
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    The effect of mandibular advancement device on apneas and sleep in patients with obstructive sleep apnea1998In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 113, p. 707-713Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the effects of a mandibular advancement device on apneas and sleep in, mild, moderate and severe obstructive sleep apnea.

    Design: Prospective study.

    Subjects: Forty-four of 47 patients included.

    Intervention: Individually adjusted mandibular advancement devices.

    Measurements: Polysomnographic sleep recordings for 1 night without the device and 1 night with it, with a median of 1 day and no changes in weight, medication, or sleep position between the recordings.

    Results: The device reduced the median apnea-hypopnea index from 11 (range, 7 to 19) to 5 (range, 0 to 17) (p<0.001) in 21 patients with mild sleep apnea, from 27 (range, 20 to 38) to 7 (range 1 to 19) (p<0.001) in 15 patients with moderate sleep apnea, and from 53 (range 44 to 66) to 14 (range, 2 to 32) (p=<0.05) in 8 patients with severe sleep apnea. The arousal index decreased and the sleep stage patterns improved in all severity groups. Twenty-eight of 44 patients were successfully treated with an obstructive apnea-hypopnea index of below 10 and a subjective reduction in snoring. Nine of 16 patients with treatment failure still reported a reduction in snoring. The success rate correlated inversely to the disease severity (r=-0.41; p<0.01).

    Conclusions: A mandibular advancement device reduces apnea and improves sleep quality in patients with obstructive sleep apnea, especially in those with mild and moderate disease. A follow-up sleep recording during treatment is necessary because of the risk of silent obstructive apneas without subjective snoring with the device.

  • 184. Midgren, Bengt
    et al.
    Mared, Lena
    Franklin, Karl Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Berg, Søren
    Erhardt, Leif
    Cline, Charles
    Cheyne-Stokes respiration is not related to quality of life or sleepiness in heart failure2010In: Clinical Respiratory Journal, ISSN 1752-6981, E-ISSN 1752-699X, Vol. 4, no 1, p. 30-36Article in journal (Refereed)
    Abstract [en]

    Background and aims:  The effects of central sleep apnea in Cheyne-Stokes respiration on sleep-related symptoms and quality of life are not very well established. We aimed to investigate whether Cheyne-Stokes respiration is related to health-related quality of life. We also studied the impact on daytime sleepiness and nocturnal dyspnea.

    Methods:  Included were 203 consecutive patients, stabilized following in-hospital treatment for decompensated congestive heart failure. They underwent overnight cardiorespiratory sleep apnea recordings in hospital and answered a set of questions on symptoms and health-related quality of life questionnaires in the form of the Nottingham Health Profile and the Minnesota Living with Heart Failure Questionnaire. After excluding seven patients with predominantly obstructive apneas and 14 with insufficient recordings, 182 patients were included in the final analysis.

    Results:  One third of the patients had an apnea–hypopnea index (AHI) of >30. Falling asleep in front of the television was the only symptom related to (AHI). Nocturnal dyspnea, daytime sleepiness, generic quality of life or disease-specific quality of life were not related to AHI.

    Conclusions:  Cheyne–Stokes respiration was not associated with health-related quality of life, daytime sleepiness or nocturnal dyspnea among patients stabilized following treatment for congestive heart failure.

  • 185. Mills, Nicholas L
    et al.
    Donaldson, Ken
    Hadoke, Paddy W
    Boon, Nicholas A
    MacNee, William
    Cassee, Flemming R
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Adverse cardiovascular effects of air pollution2009In: Nature Clinical Practice Cardiovascular Medicine, ISSN 1743-4297, E-ISSN 1743-4300, Vol. 6, no 1, p. 36-44Article in journal (Refereed)
    Abstract [en]

    Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular disease in urban communities. Acute exposure has been linked to a range of adverse cardiovascular events including hospital admissions with angina, myocardial infarction, and heart failure. Long-term exposure increases an individual's lifetime risk of death from coronary heart disease. The main arbiter of these adverse health effects seems to be combustion-derived nanoparticles that incorporate reactive organic and transition metal components. Inhalation of this particulate matter leads to pulmonary inflammation with secondary systemic effects or, after translocation from the lung into the circulation, to direct toxic cardiovascular effects. Through the induction of cellular oxidative stress and proinflammatory pathways, particulate matter augments the development and progression of atherosclerosis via detrimental effects on platelets, vascular tissue, and the myocardium. These effects seem to underpin the atherothrombotic consequences of acute and chronic exposure to air pollution. An increased understanding of the mediators and mechanisms of these processes is necessary if we are to develop strategies to protect individuals at risk and reduce the effect of air pollution on cardiovascular disease.

  • 186.
    Mills, Nicholas L
    et al.
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Finlayson, Alexander E
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Gonzalez, Manuel C
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Vink, Elen
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Goudie, Colin
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Langrish, Jeremy P
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Boon, Nicholas A
    ntre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Fox, Keith A A
    ntre for Cardiovascular Science, Edinburgh University, Edinburgh, UK .
    Donaldson, Ken
    ELEGI Colt Laboratory, Centre for Inflammation Research, Edinburgh University, Edinburgh, UK .
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, UK.
    Diesel exhaust inhalation does not affect heart rhythm or heart rate variability2011In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 97, no 7, p. 544-550Article in journal (Refereed)
    Abstract [en]

    Objective Exposure to air pollution is associated with increases in cardiovascular morbidity and mortality. This study was undertaken to determine the effect of diesel exhaust inhalation on heart rhythm and heart rate variability in healthy volunteers and patients with coronary heart disease.

    Design and setting Double-blind randomised crossover studies in a university teaching hospital.

    Patients 32 healthy non-smoking volunteers and 20 patients with prior myocardial infarction.

    Interventions All 52 subjects were exposed for 1&emsp14;h to dilute diesel exhaust (particle concentration 300&emsp14;μg/m(3)) or filtered air.

    Main outcome measures Heart rhythm and heart rate variability were monitored during and for 24&emsp14;h after the exposure using continuous ambulatory electrocardiography and assessed using standard time and frequency domain analysis.

    Results No significant arrhythmias occurred during or following exposures. Patients with coronary heart disease had reduced autonomic function in comparison to healthy volunteers, with reduced standard deviations of the NN interval (SDNN, p<0.001) and triangular index (p<0.001). Diesel exhaust did not affect heart rate variability compared with filtered air (p>0.05 for all) in healthy volunteers (SDNN 101±6 vs 91±6, triangular index 20±1 vs 21±1) or patients with coronary heart disease (SDNN 47±5 vs 38±4, triangular index 8±1 vs 7±1).

    Conclusions Brief exposure to dilute diesel exhaust does not alter heart rhythm or heart rate variability in healthy volunteers or well-treated patients with stable coronary heart disease. Autonomic dysfunction does not appear to be a dominant mechanism that can explain the observed excess in cardiovascular events following exposure to combustion-derived air pollution.

  • 187. Mills, Nicholas L.
    et al.
    Miller, Mark R.
    Lucking, Andrew J.
    Beveridge, Jon
    Flint, Laura
    Boere, A. John F.
    Fokkens, Paul H.
    Boon, Nicholas A.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duffin, Rodger
    Donaldson, Ken
    Hadoke, Patrick W. F.
    Cassee, Flemming R.
    Newby, David E.
    Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 21, p. 2660-2671Article in journal (Refereed)
    Abstract [en]

    Aim: Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution.

    Methods and results: To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 +/- 4 vs. 133 +/- 3 mmHg, P < 0.05) and attenuated vasodilatation to bradykinin (P = 0.005), acetylcholine (P = 0.008), and sodium nitroprusside (P < 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n = 6-9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P < 0.001) and sodium-nitroprusside (P = 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate.

    Conclusion: Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions.

  • 188. Mills, Nicholas L
    et al.
    Robinson, Simon D
    Boon, Nicholas A
    Newby, David E
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Gonzalez, Manuel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Darnley, Kareen
    MacNee, William
    Donaldson, Ken
    Response to letter regarding article "Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis"2006In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 113, no 24, article id e872Article in journal (Other academic)
  • 189. Mills, Nicholas L
    et al.
    Robinson, Simon D
    Fokkens, Paul HB
    Leseman, Daan LAC
    Miller, Mark R
    Anderson, David
    Freney, Evelyn J
    Heal, Mathew R
    Donovan, Robert J
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    MacNee, William
    Boon, Nicholas A
    Donaldson, Ken
    Newby, David E
    Cassee, Flemming R
    Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease2008In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 116, no 6, p. 709-715Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.

    OBJECTIVES: We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. METHODS: Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables-including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine-6-8 hr after both exposures.

    RESULTS: Particulate concentrations (mean +/- SE) in the exposure chamber (190+/-37 microg/m(3)) were higher than ambient levels (31+/-8 microg/m(3)) and levels in filtered air (0.5+/-0.4 microg/m(3); p<0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9+/-8.5 vs. 4.9+/-1.2 pg/mL, p<0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p<0.001 for all), CAPs exposure had no effect on vascular function in either group.

    CONCLUSIONS: Despite achieving marked increases in particulate matter, exposure to CAPs--low in combustion-derived particles--did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.

  • 190. Mills, Nicholas L
    et al.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Gonzalez, Manuel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Vink, Elen
    Robinson, Simon D
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Boon, Nicholas A
    Donaldson, Ken
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease2007In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 357, no 11, p. 1075-1082Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function.

    METHODS: In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions.

    RESULTS: During both exposure sessions, the heart rate increased with exercise (P<0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P=0.67). Exercise-induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22+/-4 vs. -8+/-6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve).

    CONCLUSIONS: Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events.

  • 191. Mills, Nicholas L
    et al.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Robinson, Simon D
    Gonzalez, Manuel
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Donaldson, Ken
    Air pollution and atherothrombosis.2007In: Inhal Toxicol, ISSN 1091-7691, Vol. 19 Suppl 1, p. 81-9Article in journal (Refereed)
  • 192. Mills, NL
    et al.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Robinson, SD
    Gonzalez, M
    Darnley, K
    MacNee, W
    Boon, NA
    Donaldson, K
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, DE
    Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.2005In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 112, no 25, p. 3930-3936Article in journal (Refereed)
  • 193. Mobarrez, Fariborz
    et al.
    Antoniewicz, Lukasz
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kuhl, Jeanette
    Pisetsky, David S.
    Lundback, Magnus
    The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, p. e90314-Article in journal (Refereed)
    Abstract [en]

    Background: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. Materials and Methods: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. Results: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial-and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet-and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. Conclusion: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.

  • 194.
    Muala, Ala
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nicklasson, Hanna
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Swietlicki, Erik
    Nyström, Robin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Pettersson, Esbjörn
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rissler, Jenny
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Löndahl, Jakob
    Respiratory Tract Deposition of Inhaled Wood Smoke Particles in Healthy Volunteers2015In: Journal of Aerosol Medicine, ISSN 1941-2711, E-ISSN 1941-2703, Vol. 28, no 4, p. 237-246Article in journal (Refereed)
    Abstract [en]

    Background: Respiratory tract deposition of air pollution particles is a key to their adverse health effects. This study was aimed to determine the size-resolved deposition fraction (DF) of sooty wood smoke particles in the lungs of healthy subjects. The type of wood smoke investigated is typical for household air pollution from solid fuels, which is among the largest environmental health problems globally.

    Methods: Twelve healthy volunteers inhaled diluted wood smoke from incomplete soot-rich combustion in a common wood stove. The DF of smoke particles (10–500 nm) was measured during three 15-min exposures in each subject during spontaneous breathing. Lung function was measured using standard spirometry.

    Results: The total DFs by particle number concentration were 0.34±0.08. This can be compared with DFs of 0.21–0.23 in healthy subjects during previous experiments with wood pellet combustion. For particle mass, the total DFs found in this study were 0.22±0.06. DF and breathing frequency were negatively correlated as expected from model calculations (p<0.01).

    Conclusions: The DF of the investigated sooty wood smoke particles was higher than for previously investigated particles generated during more efficient combustion of biomass. Together with toxicological studies, which have indicated that incomplete biomass combustion particles rich in soot and polycyclic aromatic hydrocarbons (PAHs) are especially harmful, these data highlight the health risks of inadequate wood combustion.

  • 195.
    Muala, Ala
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nyström, Robin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Pettersson, Esbjörn
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Bergvall, Christoffer
    Westerholm, Roger
    Jalava, Pasi I.
    Happo, Mikko S.
    Uski, Oskari
    Hirvonen, Maija-Riitta
    Kelly, Frank J.
    Mudway, Ian S.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity2015In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 12, article id 33Article in journal (Refereed)
    Abstract [en]

    Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, < 0.05, < 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (< 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, < 0.05 and < 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, < 0.05, < 0.05 and < 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.

  • 196.
    Muala, Ala
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nyström, Robin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Pettersson, Esbjörn
    Bergvall, Christoffer
    Westerholm, Roger
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank
    Mudway, Ian
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bronchial mucosal inflammation in healthy subjects after exposure to wood smoke from incomplete combustionManuscript (preprint) (Other academic)
    Abstract [en]

    Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease worldwide. The mechanisms by which wood smoke exhibits its effects on human health are not well understood. The aim of this study was to determine whether exposure to wood smoke produced from incomplete combustion would elicit an airway inflammatory response.

    Methods Fourteen healthy subjects underwent controlled chamber exposure on two occasions to filtered air and to sooty wood smoke (PM1 ~ 314 μg/m3), generated by a common Nordic wood stove firing birch logs. The study was performed with a double-blind randomized cross-over design and the subjects alternated between exercise (VE=20 L/min/m2) and rest at 15-minute intervals for 3 hours. Bronchoscopies were performed 24 hours after each exposure where bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial biopsies were taken. Differential cell counts and soluble components were analyzed in BW and BAL. Bronchial mucosal biopsies were analyzed using immunohistochemistry. Blood tests for inflammatory markers were sampled pre-exposure as well as at 24 and 44-hour time points post-exposure. Spirometry and Fraction of exhaled nitric oxide (FENO) were performed before, immediately after and 24 hours after each exposure.

    Results There was a significant increase in submucosal and epithelial CD3+ lymphocytes (p<0.01 and <0.05 respectively), together with CD8+ cells in the epithelium (p<0.05) after exposure to wood smoke compared to filtered air. Mast cells were also significantly increased in the submucosa (p<0.01) after wood smoke exposure.

    There were significant reductions in macrophages, neutrophils and lymphocytes in BW after exposure to wood smoke compared to filtered air, accompanied by decreased levels of soluble Intercellular Adhesion Molecule-1 (sICAM-1), myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). No significant effects on cell numbers or acute inflammatory markers were demonstrated in BAL fluid or peripheral blood. Lung function and FENO were not affected by exposure to wood smoke.

    Conclusions Wood smoke exposure caused a significant increase in bronchial epithelial and submucosal CD3+ lymphocytes together with an increase in mucosal mast cells. Further examination revealed a significant increase in CD8+ lymphocytes within the epithelium. Unexpectedly there were no indications of any neutrophilic airway response or recruitment of alveolar macrophages. BW cell numbers, MPO and MMP-9 levels were also significantly reduced after wood smoke exposure. Further research is needed to determine the precise role of these events in relationship to the adverse health effects attributed to wood smoke exposure.

  • 197.
    Muala, Ala
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sehlstedt, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bion, Anne
    Renault Technocentre, Guyancourt, France.
    Österlund, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Swedish Defence Research Agency, FOI, Umeå, Sweden.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Mudway, Ian S.
    MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, King’s College London, London, UK.
    Langrish, Jeremy P.
    BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK .
    Couderc, Stephane
    Renault Technocentre, Guyancourt, France.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers2014In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, no 1, article id 16Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.

    METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.

    RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.

    CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

  • 198. Mudway, I S
    et al.
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Dunster, C
    Marklund, S L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Frew, A J
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
    Kelly, F J
    Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects2001In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 31, no 8, p. 962-974Article in journal (Refereed)
    Abstract [en]

    The air pollutant ozone induces both airway inflammation and restrictions in lung function. These responses have been proposed to arise as a consequence of the oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses present at the surface of the lung in two groups known to have profound differences in their antioxidant defense network: healthy control (HC) and mild asthmatic (MA) subjects. We hypothesized that baseline differences in antioxidant concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsiveness. We observed a significant loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%, p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in these compartments (p =.01 and p <.05). Corresponding responses were not seen in asthmatics, where basal ASC concentrations were significantly lower (p <.01) and associated with elevated concentrations of GSSG (p <.05). In neither group was any evidence of lipid oxidation seen following ozone. Despite differences in antioxidant levels and response, the magnitude of ozone-induced neutrophilia (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These data demonstrate significant differences between the interaction of ozone with RTLF antioxidants in MA and HC subjects. These responses and variations in basal antioxidant defense were not, however, useful predictive markers of group or individual responsiveness to ozone.

  • 199. Mudway, Ian S
    et al.
    Behndig, Annelie F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Duggan, Sean T
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kelly, Frank J
    Identification of dehydroascorbate in human nasal secretionsManuscript (preprint) (Other academic)
  • 200. Mudway, Ian S
    et al.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Helleday, Ragnberth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Frew, Anthony J
    Kelly, Frank J
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Vitamin supplementation does not protect against symptoms in ozone-responsive subjects2006In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 40, no 10, p. 1702-1712Article in journal (Refereed)
1234567 151 - 200 of 326
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