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  • 1.
    Abrahamsson, Thomas R.
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Div Pediat, Linkoping, Sweden..
    Jakobsson, Hedvig E.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Andersson, Anders F.
    KTH Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden..
    Björksten, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Engstrand, Lars
    KTH Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden..
    Jenmalm, Maria C.
    Linkoping Univ, Dept Clin & Expt Med, Div Pediat, Linkoping, Sweden.;Linkoping Univ, Unit Autoimmun & Immune Regulat, Dept Clin & Expt Med, Div Clin Immunol, Linkoping, Sweden..
    Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, 248-249 p.Article in journal (Refereed)
  • 2. Adrian, L.
    et al.
    Svanes, C.
    Johannessen, A.
    Lodge, C.
    Bertelsen, R.
    Dratva, J.
    Forsberg, B.
    Gislason, T.
    Benedikstdottir, B.
    Holm, M.
    Jogi, R.
    Modig, L.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Omenaas, E.
    Real, F.
    Schlunssen, V
    Sigsgaard, T.
    Skorge, T.
    Timm, S.
    Wieslander, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dharmage, S.
    Early life parental exposure to cats and dogs reduces the risk of allergic disease in their children: possible intergenerational effect2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, 577-578 p.Article in journal (Other academic)
  • 3. Ahlgrim, C.
    et al.
    Gutermuth, J.
    Onell, A.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Schaeffner, I
    Darsow, U.
    Pfab, F.
    Brockow, K.
    Ring, J.
    Behrendt, H.
    Jakob, T.
    Huss-Marp, J.
    Comparison of Molecular Multiplex and Singleplex Analysis of IgE to Grass Pollen Allergens in Untreated German Grass Pollen-Allergic Patients2015In: Journal of investigational allergology & clinical immunology, ISSN 1018-9068, E-ISSN 1698-0808, Vol. 25, no 3, 190-195 p.Article in journal (Refereed)
    Abstract [en]

    Background: The ImmunoCAP ISAC 112 platform is the only commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with the molecular singleplex ImmunoCAP IgE platform are lacking. Objective:To compare the multiplex ISAC 112 platform and the singleplex ImmunoCAP platform in regard to IgE to grass pollen allergens in untreated grass pollen allergic patients in Germany. Methods: Serum samples from 101 adults with grass pollen allergy were analyzed for specific IgE (sIgE) to 8 allergenic molecules from timothy grass pollen and to the 112 allergenic molecules included in the ISAC panel. The results for the multiplex and singleplex tests were subsequently analyzed statistically. Results: Comparison of sIgE to grass pollen allergens detected by ISAC 112 and the singleplex ImmunoCAP assay revealed the following correlation coefficients: 0.88 (rPhl p1), 0.96 (rPhl p2), 0.70 (nPhl p4), 0.94 (rPhl p5b), 0.92 (rPhl p6), 0.85 (rPhl p11), and 0.78 (rPhl p12). Conclusion: Molecular testing with ISAC 112 correlates well with the ImmunoCAP platform for respective molecular timothy grass pollen allergens.

  • 4.
    Ahmadi, Z.
    et al.
    Lund Univ, Lund, Sweden..
    Sundh, J.
    Univ Orebro, Orebro, Sweden..
    Bornefalk Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ekström, M.
    Lund Univ, Lund, Sweden..
    Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 5. Ahmadi, Zainab
    et al.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Franklin, Karl A.
    Midgren, Bengt
    Ekstrom, Magnus P.
    Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study2014In: Respiratory research (Online), ISSN 1465-993X, Vol. 15, 30- p.Article in journal (Refereed)
    Abstract [en]

    Background: The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD. Methods: National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications. Results: Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO2 (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa. Conclusion: In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality.

  • 6.
    Ahmadi, Zainab
    et al.
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, Lund, Sweden.
    Sundh, Josefin
    Univ Orebro, Sch Med Sci, Dept Resp Med, Orebro, Sweden.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Ekström, Magnus
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, Lund, Sweden.
    Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, e0163293Article in journal (Refereed)
    Abstract [en]

    Long-term oxygen therapy (LTOT) >= 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease ( COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.

  • 7.
    Ahmadi, Zainab
    et al.
    Lund University, Lund, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences.
    Hermansson, Anna B.
    Uppsala University Hospital, Uppsala, Sweden.
    Ekström, Magnus
    Lund University, Lund, Sweden.
    Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 8. Akerstedt, T.
    et al.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Gruber, G.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Schwarz, J.
    What does good sleep mean in terms of macro and microstructure of sleep in women and how does age affect this relation?2014In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, 240-240 p.Article in journal (Other academic)
  • 9.
    Akner, Gunnar
    Örebro University, School of Health and Medical Sciences.
    Undernäringstillstånd vid KOL2006In: KOL: kroniskt obstruktiv lungsjukdom / [ed] Kjell Larsson, Stockholm: Studentlitteratur , 2006, 2, 227-237 p.Chapter in book (Other academic)
  • 10.
    Ali, Neserin
    et al.
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Mattsson, Karin
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Rissler, Jenny
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Karlsson, Helen Marg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Svensson, Christian R
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Gudmundsson, Anders
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Lindh, Christian H
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Jönsson, Bo A G
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Cedervall, Tommy
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Kåredal, Monica
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.2016In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404, Vol. 10, no 2, 226-234 p.Article in journal (Refereed)
    Abstract [en]

    Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.

  • 11.
    Almqvist, C
    et al.
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Egmar, Ann-Charlotte
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Hedlin, G
    Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm.
    Lundqvist, M
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Nordvall, S L
    Institute of Woman and Child Health, Uppsala University, Uppsala.
    Pershagen, G
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm.
    Svartengren, M
    Department of Public Health Sciences, Karolinska Institutet, Stockholm.
    van Hage-Hamsten, M
    Department of Medicine, Unit of Clinical Immunology and Allergy, Karolinska Institutet and Hospital, Stockholm.
    Wickman, M
    Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Direct and indirect exposure to pets: - risk of sensitization and asthma at 4 years in a birth cohort2003In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, no 9, 1190-1197 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results.

    OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study.

    METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders.

    RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38).

    CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.

  • 12.
    Almqvist, C
    et al.
    The Department of Environmental Health, Karolinska Hospital, Stockholm.
    Larsson, P H
    National Institute for Working Life, Stockholm.
    Egmar, Ann-Charlotte
    The Department of Environmental Health, Karolinska Hospital, Stockholm.
    Hedrén, M
    National Institute for Working Life, Stockholm.
    Malmberg, P
    National Institute for Working Life, Stockholm.
    Wickman, M
    The Department of Environmental Health, Karolinska Hospital, Stockholm.
    School as a risk environment for children allergic to cats and a site for transfer of cat allergen to homes1999In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 103, no 6, 1012-1017 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many children are allergic to furred pets and avoid direct pet contact. The school may be a site of indirect exposure to pet allergens, which may induce or maintain symptoms of allergic diseases.

    OBJECTIVE: We sought to investigate airborne levels of cat allergen (Fel d 1) at schools and in homes with or without cats and to study clothes as a route for dissemination of allergens between homes and school.

    METHODS: Airborne cat allergen was collected with personal samplers from (1) children attending classes with many (>25%) or few (<10%) cat owners and (2) homes with or without cats. A recently developed amplified ELISA assay, which detects low levels of airborne cat allergen in pet-free environments, was used. Dust samples were collected from clothes and mattresses.

    RESULTS: There was a 5-fold difference in the median levels of airborne cat allergen between classes with many and few cat owners (2.94 vs 0.59 ng/m3; P <.001). The median airborne cat allergen concentration in classes with many cat owners was significantly higher than that found in the homes of non-cat owners (P <.001) but lower than that found in homes with cats (P <.001). Allergen levels in non-cat owners' clothes increased after a school day (P <.001). Non-cat owners in classes with many cat owners had higher levels of mattress-bound cat allergen (P =.01).

    CONCLUSION: The results indicate significant exposure to cat allergen at school. Allergen is spread through clothing from homes with cats to classrooms. There the allergen is dispersed in air and contaminates the clothes of children without cats. The allergen levels in non-cat owners' homes correlate with exposure to cat allergen at school.

  • 13.
    Almqvist, Catarina
    et al.
    The Department of Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Egmar, Ann-Charlotte
    The Department of Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    van Hage-Hamsten, Marianne
    The Department of Medicine, Unit of Clinical Immunology and Allergy, Karolinska Institutet, Stockholm.
    Berglind, Niklas
    The Department of Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Pershagen, Göran
    The Institute of Environmental Medicine, Karolinska Institutet.
    Nordvall, S Lennart
    The Institute of Woman and Child Health, Uppsala University, Uppsala.
    Svartengren, Magnus
    The Department of Public Health Sciences, Karolinska Institutet.
    Hedlin, Gunilla
    The Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm.
    Wickman, Magnus
    The Department of Occupational and Environmental Health, Karolinska Hospital, Stockholm.
    Heredity, pet ownership, and confounding control in a population-based birth cohort2003In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 111, no 4, 800-806 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The association between pet ownership in childhood and subsequent allergic disease is controversial. Bias related to selection of pet exposure has been suggested as a reason for contradictory study results.

    OBJECTIVE: The purpose of this investigation was to elucidate how pet exposure depends on family history of allergic disease, smoking, and socioeconomic factors in a prospective birth cohort.

    METHODS: Parents of 4089 two-month-old children answered a questionnaire that included detailed questions about family history of asthma (maternal, paternal, and sibling), rhinoconjunctivitis, atopic eczema/dermatitis syndrome, pollen and pet allergy, smoking habits, parental occupation, and family pet ownership (cat and dog). Dust samples collected from the mothers' beds were analyzed for Fel d 1 and Can f 1 in a subgroup of the cohort.

    RESULTS: Cats were less frequently kept in families with parental asthma, rhinoconjunctivitis, or pet or pollen allergy (3.5% to 5.8%) than in families without parental allergic disease (10.8% to 11.8%). Dogs were less common in families with (3.3%) than in families without (5.9%) parental atopic eczema/dermatitis syndrome. Families with smoking mothers and those with low socioeconomic index kept cats and dogs more frequently. Cat allergen levels were lower in homes with than in homes without maternal pet allergy, and this tended to hold true even for homes without a cat. Cat ownership decreased from birth to 2 years of age, especially in families with parental history of allergic diseases.

    CONCLUSION: There seems to be a selection of pet exposure based on parental history of allergy, maternal smoking, and socioeconomic factors. This has to be taken into consideration in evaluations of risk associations between pet exposure and allergic disease in childhood.

  • 14.
    Almqvist, Catarina
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Lung & Allergy Unit, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Olsson, Henrik
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundholm, Cecilia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Sibship and risk of asthma in a total population: A disease comparative approach2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 138, no 4, 1219-1222 p.Article in journal (Refereed)
  • 15.
    Alpkvist, Helena
    et al.
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden..
    Athlin, Simon
    Univ Orebro, Dept Infect Dis, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Naucler, Pontus
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Stockholm, Sweden..
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Abdeldaim, Guma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Benghazi Univ, Dept Med Microbiol & Parasitol, Fac Med, Benghazi, Libya..
    Slotved, Hans-Christian
    Statens Serum Inst, Dept Microbiol & Infect Control, DK-2300 Copenhagen, Denmark..
    Hedlund, Jonas
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Stockholm, Sweden..
    Stralin, Kristoffer
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden.;Univ Orebro, Dept Infect Dis, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, e0140112Article in journal (Refereed)
    Abstract [en]

    Background We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia. Methods Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test. Results Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance. Conclusions Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

  • 16.
    Al-Shamkhi, Nasrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Dahlen, S. E.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Hedlin, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Middelveld, R.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Bjerg, A.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Ekerljung, L.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Olin, A. C.
    Univ Gothenburg, Sect Occupat & Environm Med, Dept Publ Hlth & Community Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Sommar, J.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Forsberg, B.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, 1185-1193 p.Article in journal (Refereed)
    Abstract [en]

    Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2)LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

  • 17.
    Amaral, Andre F. S.
    et al.
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Coton, Sonia
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Kato, Bernet
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Tan, Wan C.
    Univ British Columbia, Heart Lung Innovat Ctr, Vancouver, BC V5Z 1M9, Canada..
    Studnicka, Michael
    Paracelsus Med Univ, Dept Pulm Med, Salzburg, Austria..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gislason, Thorarinn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Reykjavik, Iceland..
    Mannino, David
    Univ Kentucky, Div Pulm Crit Care & Sleep Med, Lexington, KY USA..
    Bateman, Eric D.
    Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa..
    Buist, Sonia
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Burney, Peter G. J.
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Tuberculosis associates with both airflow obstruction and low lung function: BOLD results2015In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 46, no 4, 1104-1112 p.Article in journal (Refereed)
    Abstract [en]

    In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income. A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19). A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common.

  • 18.
    Amaral, Andre F. S.
    et al.
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Coton, Sonia
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Kato, Bernet
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Tan, Wan C.
    Univ British Columbia, Heart Lung Innovat Ctr, Vancouver, BC V5Z 1M9, Canada..
    Studnicka, Michael
    Paracelsus Med Univ, Dept Pulm Med, Salzburg, Austria..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gislason, Thorarinn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Reykjavik, Iceland..
    Mannino, David
    Univ Kentucky, Div Pulm Crit Care & Sleep Med, Lexington, KY USA..
    Bateman, Eric D.
    Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa..
    Buist, Sonia
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Burney, Peter G. J.
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol Occupat Med & Publ Hlth, London SW3 6LR, England..
    Lung function defects in treated pulmonary tuberculosis patients2016In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 47, no 1, 352-353 p.Article in journal (Refereed)
  • 19.
    Amaral, Andre F. S.
    et al.
    Univ London Imperial Coll Sci Technol & Med, Resp Epidemiol Occupat Med & Publ Hlth, Natl Heart & Lung Inst, Emmanuel Kaye Bldg,1B Manresa Rd, London SW3 6LR, England..
    Newson, Roger B.
    Univ London Imperial Coll Sci Technol & Med, Resp Epidemiol Occupat Med & Publ Hlth, Natl Heart & Lung Inst, Emmanuel Kaye Bldg,1B Manresa Rd, London SW3 6LR, England.;Univ London Imperial Coll Sci Technol & Med, Dept Primary Care & Publ Hlth, Sch Publ Hlth, London, England..
    Abramson, Michael J.
    Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic 3004, Australia..
    Anto, Josep M.
    Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.;IMIM Hosp del Mar, Med Res Inst, Barcelona, Spain.;UPF, Barcelona, Spain.;CIBERESP, Madrid, Spain..
    Bono, Roberto
    Univ Turin, Dept Publ Hlth & Pediat, Turin, Italy..
    Corsico, Angelo G.
    Univ Pavia, Div Resp Dis, IRCCS Policlin San Matteo Fdn, Via Palestro 3, I-27100 Pavia, Italy..
    de Marco, Roberto
    Univ Verona, Unit Epidemiol & Med Stat, Dept Publ Hlth & Community Med, I-37100 Verona, Italy..
    Demoly, Pascal
    CHU Montpellier, Dept Pulmonol, Div Allergy, Arnaud de Villeneuve Hosp, Paris, France.;INSERM, EPAR Team, UMR S 1136, Paris, France..
    Forsberg, Bertil
    Umea Univ, Div Occupat & Environm Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Gislason, Thorarinn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Natl Univ Hosp Iceland, Landspitali, Dept Resp Med & Sleep, Reykjavik, Iceland..
    Heinrich, Joachim
    Helmholtz Zentrum, Inst Epidemiol 1, Munich, Germany.;Univ Munich, Inst & Outpatient Clin Occupat Social & Environm, Inner City Clin, Univ Hosp Munich, Munich, Germany..
    Huerta, Ismael
    Dept Hlth Asturias, Directorate Gen Publ Hlth, Epidemiol Surveillance Sect, Oviedo, Spain..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Jogi, Rain
    Tartu Univ Hosp, Lung Clin, Tartu, Estonia..
    Kim, Jeong-Lim
    Univ Gothenburg, Dept Publich Hlth & Community Med, Sahlgrenska Acad, Gothenburg, Sweden..
    Maldonado, Jose
    Univ Hosp Huelva, Unit Clin Management Pneumol & Allergy, Huelva, Spain..
    Rovira, Jesus Martinez-Moratalla
    Univ Hosp Albacete, Unit Pneumol, Albacete, Spain..
    Neukirch, Catherine
    INSERM, UMR1152, Paris, France.;Univ Paris 07, UMR1152, Paris, France..
    Nowak, Dennis
    Univ Munich, Inst & Outpatient Clin Occupat Social & Environm, Inner City Clin, Univ Hosp Munich, Munich, Germany.;German Ctr Lung Res, Munich, Germany..
    Pin, Isabelle
    CHU Grenoble, Pole Couple Enfants, Pediat, F-38043 Grenoble, France.;Inst Albert Bonniot, INSERM, U823, Grenoble, France.;Univ Grenoble 1, Grenoble, France..
    Probst-Hensch, Nicole
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Raherison-Semjen, Chantal
    Bordeaux Univ, Inst Publ Hlth & Epidemiol, INSERM, U897, Bordeaux, France..
    Svanes, Cecilie
    Univ Bergen, Ctr Int Hlth, Bergen, Norway.;Haukeland Hosp, Dept Occupat Med, N-5021 Bergen, Norway..
    Landa, Isabel Urrutia
    Galdakao Hosp, Dept Pneumol, Bizkaia, Spain..
    van Ree, Ronald
    Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands..
    Versteeg, Serge A.
    Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands..
    Weyler, Joost
    Univ Antwerp, Epidemiol & Social Med, B-2020 Antwerp, Belgium.;Univ Antwerp, StatUA Stat Ctr, B-2020 Antwerp, Belgium..
    Zock, Jan-Paul
    Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.;UPF, Barcelona, Spain.;CIBERESP, Madrid, Spain..
    Burney, Peter G. J.
    Univ London Imperial Coll Sci Technol & Med, Resp Epidemiol Occupat Med & Publ Hlth, Natl Heart & Lung Inst, Emmanuel Kaye Bldg,1B Manresa Rd, London SW3 6LR, England..
    Jarvis, Deborah L.
    Univ London Imperial Coll Sci Technol & Med, Resp Epidemiol Occupat Med & Publ Hlth, Natl Heart & Lung Inst, Emmanuel Kaye Bldg,1B Manresa Rd, London SW3 6LR, England..
    Changes in IgE sensitization and total IgE levels over 20 years of follow-up2016In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 137, no 6, 1788-+ p.Article in journal (Refereed)
    Abstract [en]

    Background: Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect. Objective: We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period. Methods: Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse. Results: Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (-4.6%; 95% CI, -7.0% to -2.1%). The prevalence of sensitization to house dust mite (-4.3%; 95% CI, -6.0% to -2.6%) and cat (-2.1%; 95% CI, -3.6% to -0.7%) decreased more than sensitization to grass (-0.6%; 95% CI, -2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts. Conclusion: Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years.

  • 20. Amaral, Andre F. S.
    et al.
    Ramasamy, Adaikalavan
    Castro-Giner, Francesc
    Minelli, Cosetta
    Accordini, Simone
    Sorheim, Inga-Cecilie
    Pin, Isabelle
    Kogevinas, Manolis
    Jõgi, Rain
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Balding, David J.
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Verlato, Giuseppe
    Olivieri, Mario
    Probst-Hensch, Nicole
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Zock, Jan-Paul
    Heinrich, Joachim
    Jarvis, Deborah L.
    Interaction between gas cooking and GSTM1 null genotype in bronchial responsiveness: results from the European Community Respiratory Health Survey2014In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 69, no 6, 558-564 p.Article in journal (Refereed)
    Abstract [en]

    Background Increased bronchial responsiveness is characteristic of asthma. Gas cooking, which is a major indoor source of the highly oxidant nitrogen dioxide, has been associated with respiratory symptoms and reduced lung function. However, little is known about the effect of gas cooking on bronchial responsiveness and on how this relationship may be modified by variants in the genes GSTM1, GSTT1 and GSTP1, which influence antioxidant defences. Methods The study was performed in subjects with forced expiratory volume in one second at least 70% of predicted who took part in the multicentre European Community Respiratory Health Survey, had bronchial responsiveness assessed by methacholine challenge and had been genotyped for GSTM1, GSTT1 and GSTP1-rs1695. Information on the use of gas for cooking was obtained from interviewer-led questionnaires. Effect modification by genotype on the association between the use of gas for cooking and bronchial responsiveness was assessed within each participating country, and estimates combined using meta-analysis. Results Overall, gas cooking, as compared with cooking with electricity, was not associated with bronchial responsiveness (beta=-0.08, 95% CI -0.40 to 0.25, p=0.648). However, GSTM1 significantly modified this effect (beta for interaction=-0.75, 95% CI - 1.16 to -0.33, p=4x10(-4)), with GSTM1 null subjects showing more responsiveness if they cooked with gas. No effect modification by GSTT1 or GSTP1-rs1695 genotypes was observed. Conclusions Increased bronchial responsiveness was associated with gas cooking among subjects with the GSTM1 null genotype. This may reflect the oxidant effects on the bronchi of exposure to nitrogen dioxide.

  • 21. Amberbir, Alemayehu
    et al.
    Medhin, Girmay
    Alem, Atalay
    Department of Psychiatry, Addis Ababa University, Addis Ababa, Ethiopia.
    Britton, John
    Davey, Gail
    Venn, Andrea
    The role of acetaminophen and geohelminth infection on the incidence of wheeze and eczema: a longitudinal birth-cohort study2011In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 183, no 2, 165-170 p.Article in journal (Refereed)
    Abstract [en]

    These findings suggest frequent acetaminophen use early in life increases the risk of new-onset wheeze, whereas the role of geohelminth infection on allergic disease incidence remains to be seen as the cohort matures.

  • 22.
    Amin, Kawa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Dept. of Microbiology/Immunology, University of Sulaimani, Sulaimani, Iraq.
    Hurst, David S
    Roomans, Godfried M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Sveus, Lahja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Eosinophils and neutrophils in biopsies from the middle ear of atopic children with otitis media with effusion1999In: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 48, no 12, 626-631 p., 10669113Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE AND DESIGN:

    The majority of patients with otitis media with effusion (OME) and atopy have been shown to have elevated levels of eosinophil cationic protein (ECP) in their middle ear fluid. The mechanism underlying these elevated levels of ECP is not clear. The purpose of this study was to investigate the feasibility of a quantitative determination of eosinophils and neutrophils in the middle ear lining by specific immunocytochemical markers, in order to study the extent of the involvement of these cells in patients with OME.

    METHODS:

    Bilateral middle ear biopsies from five children with persistent OME and atopy confirmed by in vitro testing were evaluated for the presence of eosinophils and neutrophils with monoclonal antibodies against specific granule proteins. Five subjects who had no signs of effusion or infection but were undergoing routine tympanoplasty for dry perforations served as controls. The biopsies were embedded in a plastic resin to improve the structural preservation of the target cells and to increase the resolution in the light microscope. Dual markers were used to determine which marker was better for eosinophils and neutrophils, respectively. The following markers were used: eosinophil cationic protein (EG2), and eosinophil peroxidase (EPO) for eosinophils and myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) for neutrophils.

    RESULTS:

    Antibodies against EPO gave a more localized and intense staining than antibodies against EG2. Antibodies against HNL appear more specific to neutrophils than antibodies against MPO that also recognize monocytes. The number of cells was determined both in the tissue and in the mucus covering the epithelium. Eosinophils and neutrophils were present in the subepithelial connective tissue and in the mucus blanket in the middle ear of patients with OME in significantly higher number than in the control group. In general, there were more inflammatory cells in the mucus than in the tissue itself, but the number of inflammatory cells in the mucus showed a significant positive correlation with the number of inflammatory cells in the tissue. There was a significant positive correlation between the number of neutrophils and the number of eosinophils in the tissue as well as in the mucus, irrespective of which marker was used.

    CONCLUSION:

    The results of this study show the feasibility of using specific antibodies to identify eosinophils and neutrophils in the middle ear. The initial data suggest that atopic children with OME have higher numbers of such cells as compared to non-OME controls.

  • 23.
    Andersson, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bjerg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lundbäck, Bo
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    The clinical expression of asthma in schoolchildren has changed between 1996 and 20062010In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 21, no 5, 859-866 p.Article in journal (Refereed)
    Abstract [en]

    Several studies have reported diverging trends in the prevalence of asthma and wheeze. The aim of this study was to investigate the clinical expression of childhood asthma in 1996 and 2006 by studying asthma morbidity, treatment, and environmental exposures in school children with physician-diagnosed asthma and wheeze, respectively. All children enrolled in first or second grade (7-8 yr-old) in three municipalities in northern Sweden were invited to a questionnaire study in 1996 and 2006, respectively. In 1996, 3430 (97%) participated; and in 2006, 2585 (96%) participated. The same parental completed questionnaire, including the ISAAC questions, was used in both surveys. Physician-diagnosed asthma was reported at 5.7% in 1996 and 7.4% in 2006. A significantly greater proportion of children with asthma were using inhaled corticosteroids (ICS) in 2006, 67% vs. 55% in 1996. This increase was parallel to a major decrease in severe asthma symptoms such as disturbed sleep because of wheeze (49% vs. 38%) and troublesome asthma (21% vs. 11%). The prevalence of current wheeze among the asthmatics decreased significantly; however, this was seen only among children not using ICS. Parental smoking decreased significantly as did the proportion living in damp buildings. In conclusion, although asthma remains a major public health issue in school age children, children with asthma had less respiratory symptoms and a better asthma control in 2006 compared to 1996. This parallels with an increase in treatment with ICS, more beneficial environmental conditions, and an increased diagnostic intensity resulting in a larger proportion of children with mild symptoms being diagnosed as having asthma.

  • 24.
    Andersson, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bjerg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, B
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Persistence and remission of asthma followed from 7 to 19 years of ageManuscript (preprint) (Other academic)
  • 25.
    Andersson, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Hedman, Linnéa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Nordberg, Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Swimming pool attendance is related to asthma among atopic school children: a population-based study2015In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 14, no 14, 37Article in journal (Refereed)
    Abstract [en]

    Background: By-products of water disinfectants have been suggested to cause asthma, especially in atopic children. However, studies on indoor swimming pool attendance and asthma in children have presented conflicting results. The present study examined the relationship between indoor swimming pool attendance and asthma among sensitized and non-sensitized children aged 11-12 years.

    Methods: An extended ISAAC questionnaire was sent to the families of all children attending fifth or sixth grade, aged 11-12 years, in two municipalities in Northern Sweden in 2010. A total of 1866 participated (96% of those invited) in the questionnaire study and 1652 (89%) also participated in skin prick testing for 10 standard airborne allergens. Asthma was defined as physician-diagnosed asthma in combination with wheeze or use of asthma medication in the last 12 months. Current swimming pool attendance was reported as >= 1/week or <1/week. Logistic regression models were used for data analysis.

    Results: The prevalence of current asthma was 8.9% (10.0% of boys; 7.9% of girls) and 14% had attended indoor pools >= 1/week. Children currently attending swimming pools >= 1/week had an increased risk of current asthma. Stratified analyses for allergic sensitization adjusted for sex, parental smoking, parental asthma, and damp housing, showed a statistically significant association for current asthma only among sensitized subjects (OR 95% CI 1.90 1.09-3.32). No association was found between current pool attendance and wheeze, sensitization, rhinitis or eczema.

    Conclusions: The present study supports the proposed link between indoor swimming pool attendance and asthma in sensitized children.

  • 26.
    Andersson, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Accuracy of three activity monitors in patients with chronic obstructive pulmonary disease: A comparison with video recordings2014In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, Vol. 11, no 5, 560-567 p.Article in journal (Refereed)
    Abstract [en]

    Low physical activity and sedentary behaviour characterise the lives of patients with chronic obstructive pulmonary disease (COPD). Using activity monitors, assessment of both aspects are possible, but many outcomes are not well validated. The aim of this study was to assess the accuracy and equivalency of three activity monitors regarding steps, body position and their ability to differentiate between periods of physical activity and inactivity.

    Fifteen patients with COPD (8 females; median (interquartile range, IQR) age, 64 (59-69) years; forced expiratory volume in one second, 37 (28-48) % predicted; six-minute walk distance, 444 (410-519) m) were enrolled. The DynaPort ADL-monitor, the DynaPort MiniMod monitor and the SenseWear Armband Pro 3 monitor were assessed. Subjects performed a structured protocol alternating physical activity and inactivity while simultaneously wearing all three monitors and being video recorded.

    The mean difference (limits of agreement) in step count from monitors compared to manual step count was -69 (-443 to 305) for the ADL-monitor, -19 (-141 to 103) for the MiniMod and -479 (-855 to -103) for the SenseWear Armband. Compared to the video, the sitting time was 97 (94-100) % when measured by the ADL-monitor and 121 (110-139) % by the MiniMod. Standing time was 114 (107-122) % when measured by the ADL-monitor and 68 (47-106) % by the MiniMod.

    Activity monitors are not equivalent in their abilities to detect steps or body positions. The choice of monitor should be based on the particular outcome of interest. 

  • 27. Andersson, Mikael
    et al.
    Stridsman, Caroline
    Emtner, Margareta
    Lindberg, Anne
    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.
    Physical activity and fatigue in chronic obstructive pulmonary disease - A population based study2015In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, no 8, 1048-1057 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In subjects with chronic obstructive pulmonary disease (COPD), symptoms of fatigue, concomitant heart disease and low physical activity levels are more frequently described than in subjects without COPD. However, there are no population-based studies addressing the relationship between physical activity, fatigue and heart disease in COPD. The aim was to compare physical activity levels among subjects with and without COPD in a population based study, and to evaluate if concomitant heart disease and fatigue was associated to physical activity.

    METHODS: In this, 470 subjects with COPD and 659 subjects without COPD (non-COPD) participated in examinations including structured interview and spirometry. A ratio of the forced expiratory volume in one second (FEV1)/best of forced vital capacity (FVC) and vital capacity (VC) < 0.7 was used to define COPD. Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ), and fatigue with the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F).

    RESULTS: The prevalence of low physical activity was higher among subjects with FEV1 < 80% predicted compared to non-COPD subjects (22.4% vs. 14.6%, p = 0.041). The factors most strongly associated with low physical activity in subjects with COPD were older age, OR 1.52, (95% CI 1.12-2.06), a history of heart disease, OR 2.11 (1.10-4.08), and clinically significant fatigue, OR 2.33 (1.31-4.13); while obesity was the only significant factor among non-COPD subjects, OR 2.26 (1.17-4.35).

    CONCLUSION: Physical activity levels are reduced when lung function is decreased below 80% of predicted, and the factors associated with low physical activity are different among subject with and without COPD. We propose that the presence of fatigue and heart disease are useful to evaluate when identifying subjects for pulmonary rehabilitation.

  • 28.
    Andersson, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Stridsman, Caroline
    Ronmark, Eva
    Lindberg, Anne
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Physical activity and fatigue in chronic obstructive pulmonary disease - A population based study2015In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, no 8, 1048-1057 p.Article in journal (Refereed)
    Abstract [en]

    Background: In subjects with chronic obstructive pulmonary disease (COPD), symptoms of fatigue, concomitant heart disease and low physical activity levels are more frequently described than in subjects without COPD. However, there are no population-based studies addressing the relationship between physical activity, fatigue and heart disease in COPD. The aim was to compare physical activity levels among subjects with and without COPD in a population based study, and to evaluate if concomitant heart disease and fatigue was associated to physical activity. Methods: In this, 470 subjects with COPD and 659 subjects without COPD (non-COPD) participated in examinations including structured interview and spirometry. A ratio of the forced expiratory volume in one second (FEV1)/best of forced vital capacity (FVC) and vital capacity (VC) <0.7 was used to define COPD. Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ), and fatigue with the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). Results: The prevalence of low physical activity was higher among subjects with FEV1 <80% predicted compared to non-COPD subjects (22.4% vs. 14.6%, p = 0.041). The factors most strongly associated with low physical activity in subjects with COPD were older age, OR 1.52, (95% CI 1.12-2.06), a history of heart disease, OR 2.11 (1.10-4.08), and clinically significant fatigue, OR 2.33 (1.31-4.13); while obesity was the only significant factor among non-COPD subjects, OR 2.26 (1.17-4.35). Conclusion: Physical activity levels are reduced when lung function is decreased below 80% of predicted, and the factors associated with low physical activity are different among subject with and without COPD. We propose that the presence of fatigue and heart disease are useful to evaluate when identifying subjects for pulmonary rehabilitation.

  • 29.
    Andreassen, Siw Lillevik
    et al.
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
    Liaaen, Erik Dyb
    Department of Internal Medicine, Aalesund Hospital, Aalesund, Norway.
    Stenfors, Nikolai
    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.
    Henriksen, Anne H
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Thoracic- and Occupational Medicine, Trondheim University Hospital, Trondheim, Norway.
    Impact of pneumonia on hospitalizations due to acute exacerbations of COPD2014In: Clinical Respiratory Journal, ISSN 1752-6981, Vol. 8, no 1, 93-99 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Pneumonia is often diagnosed among patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aims of this study were to find the proportion of patients with pneumonia among admissions due to AECOPD and whether pneumonia has impact on the length of stay (LOS), usage of non-invasive ventilation (NIV) or the in-hospital mortality.

    METHODS: Retrospectively, all hospitalizations in 2005 due to AECOPD in the Departments of Internal and Respiratory Medicine in one Swedish and two Norwegian hospitals were analyzed. A total of 1144 admittances (731 patients) were identified from patient administrative systems. Pneumonic AECOPD (pAECOPD) was defined as pneumonic infiltrates on chest X-ray and C-reactive protein (CRP) value of ≥40 mg/L, and non-pneumonic AECOPD (npAECOPD) was defined as no pneumonic infiltrate on X-ray and CRP value of <40 at admittance.

    RESULTS: In admissions with pAECOPD (n = 237), LOS was increased (median 9 days vs 5 days, P < 0.001) and usage of NIV was more frequent (18.1% vs 12.5%, P = 0.04), but no significant increase in the in-hospital mortality (3.8% vs 3.6%) was found compared to admissions with npAECOPD. A higher proportion of those with COPD GOLD stage I-II had pAECOPD compared to those with COPD GOLD stage III-IV (28.2% vs 18.7%, P = 0.001).

    CONCLUSIONS: In-hospital morbidity, but not mortality, was increased among admissions with pAECOPD compared to npAECOPD. This may, in part, be explained by the extensive treatment with antibiotics and NIV in patients with pAECOPD.

  • 30. Annema, Jouke T
    et al.
    Vogiatzis, Ioannis
    Grgic, Aleksander
    Antoniou, Katerina
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Herth, Felix F
    Clinical highlights from Amsterdam.2016In: ERJ open research, Vol. 2, no 3, 00031-2016Article in journal (Refereed)
    Abstract [en]

    This article contains highlights and a selection of the scientific advances from the Clinical Assembly that were presented at the 2015 European Respiratory Society International Congress in Amsterdam, the Netherlands. The most relevant topics for clinicians will be discussed, covering a wide range of areas including interventional pulmonology, rehabilitation and chronic care, thoracic imaging, diffuse and parenchymal lung diseases, and general practice and primary care. In this comprehensive review, exciting novel data will be discussed and put into perspective.

  • 31. Antoniewicz, Lukasz
    et al.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kuhl, Jeanette
    Abdel-Halim, Samy M.
    Kiessling, Anna
    Mobarrez, Fariborz
    Lundback, Magnus
    Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 255, 179-185 p.Article in journal (Refereed)
    Abstract [en]

    Background and aims: The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes.

    Methods: Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear content (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h.

    Results: EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p < 0.038). FeNO was unaffected by exposure to ECV. Conclusions: In healthy volunteers, ten puffs of e-cigarette vapor inhalation caused an increase in EPCs. This increase was of the same magnitude as following smoking of one traditional cigarette, as we previously demonstrated. Taken together, these results may represent signs of possible vascular changes after short e-cigarette inhalation. Further studies analyzing potential cardiovascular health effects are critical as the e-cigarette market continues to burgeon.

  • 32.
    Arne, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Chronic Obstructive Pulmonary Disease: Patients´ Perspectives, Impact of the Disease and Utilization of Spirometry2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of this thesis was to describe subjects with chronic obstructive pulmonary disease (COPD) from different perspectives. Focus was on patients at the time of diagnosis, impact of the disease in comparison to other chronic diseases, factors associated with good health and quality of life (QoL), and diagnostic spirometry in clinical practice.

    Methods: Qualitative method, grounded theory, was used to analyse patients´ perspectives at the time of diagnosis in a primary care setting (n=10). Public health surveys in the general population were used to compare chronic diseases (n=10,755) and analyse factors associated with health outcomes in COPD (n=1,475). Medical records and spirometry reports, from primary and secondary care, were analysed to assess diagnosis of COPD in clinical practice (n=533).

    Results: In clinical practice, 70% of patients at the time of diagnosis of COPD lacked spirometry results confirming the diagnosis. Factors related to consequences of smoking, shame and restrictions in physical activity (PA) in particular, were described by patients at the time of diagnosis of COPD. In general subjects with COPD (84%), rheumatoid arthritis (74%) and diabetes mellitus (72%) had an activity level considered too low to maintain good health. In COPD, the most important factor associated with good health and quality of life was a high level of PA. Odds ratios (OR (95%CI)) varied from 1.90 (1.47-2.44) to 7.57 (4.57-12.55) depending on the degree of PA, where subjects with the highest PA level had the best health and QoL.

    Conclusions: Subjects with COPD need to be diagnosed at an early stage, and health professionals should be aware that feelings of shame could delay patients from seeking care and thus obtaining a diagnosis. The use of spirometry and the diagnostic quality should be emphasised. In patients with COPD greater attention should be directed on increasing the physical activity level, as patients with a low level of physical activity display worse health and quality of life.

  • 33.
    Arne, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lisspers, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Boman, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    How often is diagnosis of COPD confirmed with spirometry?2010In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 104, no 4, 550-556 p.Article in journal (Refereed)
    Abstract [en]

    Background: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. Diagnosis is customarily confirmed with spirometry, but there are few studies on documented spirometry use in everyday clinical practice. Methods: In a cross-sectional survey and study of the medical records of primary and secondary care COPD patients aged 18-75 in a Swedish region, patients with COPD were randomly selected from the registers of 56 primary care centres and 14 hospital outpatient clinics. Spirometry data at diagnosis ±6 months were analyzed. Results: From 1,114 patients with COPD, 533 with a new diagnosis of COPD during the four-year study period were identified. In 59% (n=316), spirometry data in connection with diagnosis were found in the medical records. Spirometry data with post-bronchodilator forced expiratory volume in one second (FEV1)/ vital capacity (VC) ratios were available in 45% (n=241). FEV1/VC ratio <0.70 were found in 160 patients, which corresponds to 30% of the patients with a new diagnosis. Lower age, female gender, current smoking, higher body mass index (BMI) and shorter forced exhalation time were related to COPD diagnosis despite an FEV1/VC ratio of ≥0.70. The most common problem in the quality assessment was an insufficient exhalation time. Conclusions: Only a third of Swedish patients with COPD had their diagnosis confirmed with spirometry. Our data indicate that female gender, current smoking, higher BMI and short exhalation time increase the risk of being diagnosed with COPD without fulfilling the spirometric criteria for the disease.

  • 34.
    Arne, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lundin, Fredrik
    Boman, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Staffan
    Emtner, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Factors associated with good self-rated health and quality of life in subjects with self-reported COPD2011In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 6, 511-519 p.Article in journal (Refereed)
    Abstract [en]

    Background: Recent guidelines for chronic obstructive pulmonary disease (COPD) state that COPD is both preventable and treatable. To gain a more positive outlook on the disease it is interesting to investigate factors associated with good, self-rated health and quality of life in subjects with self-reported COPD in the population.

    Methods: In a cross-sectional study design, postal survey questionnaires were sent to a stratified, random population in Sweden in 2004 and 2008. The prevalence of subjects (40–84 years) who reported having COPD was 2.1% in 2004 and 2.7% in 2008. Data were analyzed for 1475 subjects. Regression models were used to analyze the associations between health measures (general health status, the General Health Questionnaire, the EuroQol five-dimension questionnaire) and influencing factors.

    Results: The most important factor associated with good, self-rated health and quality of life was level of physical activity. Odds ratios for general health varied from 2.4 to 7.7 depending on degree of physical activity, where subjects with the highest physical activity level reported the best health and also highest quality of life. Social support and absence of economic problems almost doubled the odds ratios for better health and quality of life.

    Conclusions: In this population-based public health survey, better self-rated health status and quality of life in subjects with self-reported COPD was associated with higher levels of physical activity, social support, and absence of economic problems. The findings indicated that of possible factors that could be influenced, promoting physical activity and strengthening social support are important in maintaining or improving the health and quality of life in subjects with COPD. Severity of the disease as a possible confounding effect should be investigated in future population studies.

  • 35. Artigas, Antonio
    et al.
    Noël, Julie-Lyn
    Brochard, Laurent
    Busari, Jamiu O
    Dellweg, Dominic
    Ferrer, Miguel
    Geiseler, Jens
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Nava, Stefano
    Navalesi, Paolo
    Orfanos, Stylianos
    Palange, Paolo
    Pelosi, Paolo
    Rohde, Gernot
    Schoenhofer, Bernd
    Vassilakopoulos, Theodoros
    Simonds, Anita K
    Defining a training framework for clinicians in respiratory critical care2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 3, 572-577 p.Article in journal (Refereed)
  • 36.
    Aytekin, Cenk
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Living an Active Life with Asthma2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In 2019 a striking 400 million people worldwide will be living with asthma. Environment, genetics and lifestyle are all factors that are assumed to cause this chronic disease. The current treatment of asthma is focused on medication, and wellness through exercise is not promoted. The benefits of an active lifestyle for asthmatics are many and include a reduced medication dose, increased tolerance to triggers and less asthma symptoms. Regular exercise can therefore dramatically decrease the effects of asthma and the mental and physical limitations that may follow. However, many asthmatics experience difficulties maintaining an active lifestyle due to the fear of having an exercise-induced asthma attack. There is also reluctance to the necessary intake of the high dosage of preventive medication.

  • 37.
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lung function and prevalence trends in asthma and COPD: the Obstructive Lung Disease in Northern Sweden Thesis XVI2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Asthma and chronic obstructive pulmonary disease (COPD) are common obstructive airway diseases with a substantial burden in terms of morbidity, mortality and costs. Smoking is the single most important risk factor for COPD, and is associated with incident asthma. It is important to know if the prevalence of asthma and COPD is increasing or decreasing in the population in order to effectively allocate health care resources. The definitions of these diseases have varied over time which makes it difficult to measure changes in prevalence. The preferred method is to estimate the prevalence with the same procedures and definitions based on cross-sectional population samples with identical age distributions in the same geographical area at different time points. Measurements of lung function (spirometry) are required to diagnose COPD, and spirometry is used to evaluate disease severity and progress of both asthma and COPD, where observed values are compared to reference values. The most commonly used reference values in Sweden are published during the mid 1980s, and there are few evaluations of how appropriate they are today based on Swedish population samples. The aim of the thesis was to estimate trends in the prevalence of asthma and COPD in relation to smoking habits, and to evaluate and estimate reference values for spirometry.

    Methods

    The project was based on population-based samples of adults from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Postal questionnaires were sent to large cohorts, recruited in 1992 (n=4851, 20-69 years), 1996 (n=7420, 20-74 years) and 2006 (n=6165, 20-69 years), respectively. The questionnaire included questions on respiratory symptoms and diseases, their comorbidities and several possible risk factors including smoking habits. Structured interviews and spirometry were performed in random samples of the responders to the 1992 and 2006 surveys, of which n=660 (in 1994) and n=623 (in 2009) were within identical age-spans (23-72 years). The trend in asthma prevalence was estimated by comparing the postal questionnaire surveys in 1996 and 2006, and the trend in COPD prevalence was estimated by comparing the samples participating in dynamic spirometry in 1994 and 2009, respectively. The prevalence of COPD was estimated based on two different definitions of COPD. Commonly used reference values for spirometry were evaluated based on randomly sampled healthy non-smokers defined in clinical examinations of participants in the 2006 postal questionnaire (n=501). The main focus of the evaluation was the global lung function initiative (GLI) reference values published in 2012, for which Z-scores and percent of predicted values were analysed. New sex-specific reference values for spirometry were estimated by linear regression, with age and height as predictors. These new OLIN reference values were also evaluated on a sample of healthy non-smokers identified in the population-based West Sweden Asthma Study.

    Results

    Although the prevalence of smoking decreased from 27.4% to 19.1%, p<0.001, between 1996 and 2006, the prevalence of physician-diagnosed asthma increased from 9.4% to 11.6%, p<0.001. The prevalence of symptoms common in asthma such as recurrent wheeze did not change significantly between the surveys or tended to decrease, while bronchitis symptoms such as cough and sputum production decreased significantly. The evaluation of the GLI reference values showed that the predicted values were significantly lower compared to the observed values in Norrbotten, which makes the percent of predicted too high. This was especially true for FVC percent predicted with a mean of 106%. In general, the deviations were more pronounced among women. New OLIN reference values valid for the Norrbotten sample were modelled and showed a high external validity when applied on the sample from western Sweden. The prevalence of moderate to severe COPD decreased substantially over the 15-year period between 1994 and 2009, regardless of definition.

    Conclusions

    In parallel with substantially decreased smoking habits in the population between 1996 and 2006, the prevalence of several airway symptoms decreased while the prevalence of physician-diagnosed asthma increased. These results suggest increased diagnostic activity for asthma, but may also suggest that the asthma prevalence has continued to increase. In contrast to asthma, the prevalence of COPD tended to decrease and moderate to severe COPD decreased substantially. The continuous decrease in smoking in Sweden during several decades prior to the study period is most likely contributing to these results. The evaluation of reference values showed that the GLI reference values were lower than the observed spirometric values in the population, especially for women, why the new up-to date reference values may be of importance for disease evaluation in epidemiology and in the health care as well.

  • 38.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå,.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå, Sweden.
    Lundbäck, Bo
    The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå, Sweden ; Krefting Research Centre/Department of Internal Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå.
    Prevalence trends in respiratory symptoms and asthma in relation to smoking: two cross-sectional studies ten years apart among adults in northern Sweden2014In: The World Allergy Organization journal, ISSN 1939-4551, Vol. 7, no 1, 1- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Smoking is considered to be the single most important preventable risk factor for respiratory symptoms. Estimating prevalence of respiratory symptoms is important since they most often precede a diagnosis of an obstructive airway disease, which places a major burden on the society. The aim of this study was to estimate prevalence trends of respiratory symptoms and asthma among Swedish adults, in relation to smoking habits. A further aim was to estimate the proportion of respiratory symptom and asthma prevalence attributable to smoking.

    METHODS: Data from two large-scale cross-sectional surveys among adults performed in northern Sweden in 1996 and 2006 were analysed. Identical methods and the same questionnaire were used in both surveys. The association between smoking, respiratory symptoms and asthma was analysed with multiple logistic regression analyses. Changes in prevalence of respiratory symptoms and asthma from 1996 to 2006 were expressed as odds ratios. Additionally, the population attributable risks of smoking were estimated.

    RESULTS: The prevalence of most respiratory symptoms decreased significantly from 1996 to 2006. Longstanding cough decreased from 12.4 to 10.1%, sputum production from 19.0 to 15.0%, chronic productive cough from 7.3 to 6.2%, and recurrent wheeze from 13.4 to 12.0%. Any wheeze and asthmatic wheeze remained unchanged. This parallels to a decrease in smoking from 27.4 to 19.1%. In contrast, physician-diagnosed asthma increased from 9.4 to 11.6%. The patterns were similar after correction for confounders. All respiratory symptoms were highly associated with smoking, and the proportion of respiratory symptoms in the population attributed to smoking (PAR) ranged from 9.8 to 25.5%. In 2006, PAR of smoking was highest for recurrent wheeze (20.6%).

    CONCLUSIONS: In conclusion, we found that respiratory symptoms, in particular symptoms common in bronchitis, decreased among adults in northern Sweden, parallel to a decrease in smoking from 1996 to 2006. In contrast, the prevalence of physician-diagnosed asthma increased during the same time-period. Up to one fourth of the respiratory symptom prevalence in the population was attributable to smoking.

  • 39.
    Backman, Helena
    et al.
    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, Medicine.
    Sovijarvi, Anssi
    Larsson, Kjell
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Evaluation of the global lung function initiative 2012 reference values for spirometry in a Swedish population sample2015In: BMC Pulmonary Medicine, ISSN 1471-2466, Vol. 15, 26Article in journal (Refereed)
    Abstract [en]

    Background: The Global Lung Function Initiative 2012 (GLI) reference values are currently endorsed by several respiratory societies but evaluations of applicability for adults resident in European countries are lacking. The aim of this study was to evaluate if the GLI reference values are appropriate for an adult Caucasian Swedish population.

    Methods: During 2008-2013, clinical examinations including spirometry were performed on general population samples in northern Sweden, in which 501 healthy Caucasian non-smokers were identified. Predicted GLI reference values and Z-scores were calculated for each healthy non-smoking subject and the distributions and mean values for FEV1, FVC and the FEV1/FVC ratio were examined. The prevalence of airway obstruction among these healthy non-smokers was calculated based on the Lower Limit of normal (LLN) criterion (lower fifth percentile) for the FEV1/FVC ratio. Thus, by definition, a prevalence of 5% was expected.

    Results: The Z-scores for FEV1, FVC and FEV1/FVC were reasonably, although not perfectly, normally distributed, but not centred on zero. Both predicted FEV1 and, in particular, FVC were lower compared to the observed values in the sample. The deviations were greater among women compared to men. The prevalence of airway obstruction based on the LLN criterion for the FEV1/FVC ratio was 9.4% among women and 2.7% among men.

    Conclusions: The use of the GLI reference values may produce biased prevalence estimates of airway obstruction in Sweden, especially among women. These results demonstrate the importance of validating the GLI reference values in different countries.

  • 40. Baharom, Faezzah
    et al.
    Thomas, Saskia
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lepzien, Rico
    Pourazar, Jamshid
    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.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sorensen, Anna
    Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans2016In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 11, 4498-4509 p.Article in journal (Refereed)
    Abstract [en]

    Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

  • 41. Bakke, PS
    et al.
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eagan, T
    Pistelli, F
    Annesi-Maesano, I
    Maly, M
    Meren, M
    Vermeire, P
    Vestbo, J
    Viegi, G
    Zielinski, J
    Lundbäck, B
    Recommendations for epidemiological studies on COPD2011In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 38, no 6, 1261-1277 p.Article in journal (Refereed)
    Abstract [en]

    The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.

  • 42. Bakolis, I
    et al.
    Doekes, G
    Heinrich, J
    Zock, J P
    Heederik, D
    Kogevinas, M
    Guerra, S
    Norbäck, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Ramasamy, A
    Nevalainen, A
    Svanes, C
    Chen, C M
    Verlato, G
    Olivieri, M
    Castro-Giner, F
    Jarvis, D
    Respiratory health and endotoxin: associations and modification by CD14/-260 genotype2012In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 39, no 3, 573-581 p.Article in journal (Refereed)
    Abstract [en]

    Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about health effects of domestic exposure in adults. We describe the association of respiratory disease, IgE sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults and determine whether these associations are modified by polymorphisms in CD14.Endotoxin levels in mattress dust from a population based sample of 972 adults were measured. Associations were examined using generalized linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed.Mattress endotoxin levels varied from 0.1 to 402.6&emsp14;EU·mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of FEV1 and FVC with endotoxin was modified by CD14/-260 genotype (p for interaction 0.005 and 0.013 respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity was associated with mattress endotoxin levels.In this large epidemiological study of adults there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14-genotype.

  • 43.
    Balbi, Bruno
    et al.
    IRCCS, Ist Clin Sci Maugeri, Pulm Rehabil, Veruno, Italy..
    Vallese, Davide
    IRCCS, Ist Clin Sci Maugeri, Pulm Rehabil, Veruno, Italy..
    Chavannes, Niels
    Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Baiardi, Paola
    IRCCS, Ist Clin Sci Maugeri, Sci Direct, Pavia, Italy..
    General practitioners and rare lung diseases: a task force for the development of rare lung diseases educational material2016In: Breathe, ISSN 1810-6838, E-ISSN 2073-4735, Vol. 12, no 4, 341-350 p.Article, review/survey (Refereed)
  • 44.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Respiratory and cardiovascular effects of exposure to oxidative air pollutants2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The negative effects of air pollution on morbidity and mortality have been known since the mid 20th century. The two most well known examples are the Meuse Valley disaster in the 1930’ies and the London black fog in December 1952. Whilst there are numerous epidemiological studies, in which associations between morbidity and mortality and high levels of pollutants have been reported, the underlying mechanisms are not clear. Two of the main air pollutants are particulate matter (PM) mostly emanating from diesel exhaust (DE), and ozone, both of which are highly oxidative. Exposure to DE has resulted in adverse effects both in the respiratory tract and in the cardiovascular system. High ozone levels have also been shown to be associated with increased admissions to hospital for respiratory as well as cardiovascular conditions.

    The main aim of this thesis was to investigate the respiratory and cardiovascular effects of a combination of exposures to ozone and DE. DE generated during the urban part of the standardized European Transient Cycle (ETC) was compared to DE generated by an idling engine. It was also evaluated whether an acute exposure to ozone would have any effects on the cardiovascular system as assessed by venous occlusion forearm plethysmography and heart rate variability (HRV). In addition, fraction of exhaled nitric oxide (FENO) was evaluated as a potential marker for acute exposure to ozone or DE.

    Methods: Four double-blind randomized cross-over exposure studies were conducted to investigate the effects of ozone and DE on both the respiratory tract and the vascular function in healthy volunteers. All of the exposures were performed in purposely built “walk-in” chambers with strictly controlled exposures. In the first study, the volunteers were exposed to DE (300µg/m3) generated by an idling engine or to air, for one hour in the morning and to ozone (200 ppb) for two hours in the afternoon. A bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 24 hours after the initial exposure. In study II and III, an assessment of vascular function using venous occlusion forearm plethysmography was performed after an exposure to DE (250 µg/m3) generated under transient running conditions, compared to air exposure (study II) and ozone and air exposure (study III). HRV was assessed under a 24 hour period starting before each exposure (study III). In study IV, FENO measurements were conducted after DE and ozone exposures to investigate whether the previously established airway inflammation would be detectable by this non-invasive method.

    Results: DE exposure enhanced the established ozone-induced airway inflammation in terms of a pronounced neutrophilia in BW. DE generated under transient running conditions, impaired vascular function in healthy volunteers, whereas exposure to ozone did not. HRV were not altered by exposure to ozone. Exposure to DE caused a significant increase in FENO at the 10  (FENO10) and 50 (FENO50) mL/s flow rates at 6 hours post-exposure, but ozone exposure did not affect FENO at any flow rate or time point.

    Conclusion: We have tried to mimic real-life exposure to air pollutants. In the first study, an exposure to DE followed by an exposure to ozone in the afternoon resulted in an enhanced airway inflammation, suggesting an additive or synergistic effect, supporting the epidemiological findings of unfavorable effects of the combination of these two air pollutants. DE generated by an engine running at the urban part of the standardized European Transient Cycle impaired two important and complementary aspects of vascular function, the regulation of vascular tone and endogenous fibrinolysis. This has previously been shown with DE generated at idling conditions. This suggests that the mechanisms behind the adverse effects can be found in the properties of the particles and not in the gaseous components. In these studies, exposure to ozone did not impair vascular function in healthy subjects, or cause any alterations in HRV. This suggests that the epidemiological evidence for an increased risk of cardiovascular mortality following acute exposure to ozone might not be totally accurate. Previous controlled exposure studies with ozone have not shown an airway inflammation affecting the endothelium, at least not in the same time-frame as following DE exposure. FENO could possibly be a useful tool for assessing airway inflammation caused by DE, whereas the powerful oxidant ozone did not affect FENO. This suggests that the airway inflammatory effects caused by these two pollutants are regulated via different mechanisms.

  • 45.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas, L
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Olin, Anna-Carin
    Dept. of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Fraction of exhaled nitric oxide after experimental exposure to diesel exhaust and ozone in manManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airways inflammation that may be used to assess the respiratory effects of air pollution, and when sampled at multiple expiratory flow rates can measure inflammation at different levels of the airway tract. We evaluate FENO as a measure of airways inflammation after controlled exposure to dilute diesel exhaust and ozone.

    Methods: Using a double blind randomised cross-over design, healthy volunteers (26±5 years) were exposed to either diesel exhaust (particle concentration 300 µg/m3) and filtered air for one hour (n=10), or ozone(300 ppb) and filtered air for 75 minutes (n=36). FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after the end of each exposure.

    Results: Exposure to diesel exhaust increased FENO at 6 hours compared to filtered air at expiratory flow rates of 10 mL/s [mean±SEM 60.8 ± 6.0 ppb versus 50.2 ± 5.9 ppb; P=0.01] and at 50 mL/s [18.6 ± 1.6 ppb versus 15.9 ± 1.5 ppb; P=0.011], but concentrations did not differ at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours and exposure to ozone did not affect FENO at any flow rate or time point.

    Conclusion: Exposure to diesel exhaust, but not ozone, increases the concentration of FENO in healthy subjects consistent with an inflammatory effect in the central airways. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone with implications for the use of FENO as an index of exposure to air pollution.

  • 46.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L.
    Ädelroth, Ellinor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Olin, Anna-Carin
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Diesel exhaust but not ozone increases fraction of exhaled nitric oxide in a randomized controlled experimental exposure study of healthy human subjects2013In: Environmental health, ISSN 1476-069X, Vol. 12, 36- p.Article in journal (Refereed)
    Abstract [en]

    Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airway inflammation that may be used to assess respiratory effects of air pollution. We evaluated FENO as a measure of airway inflammation after controlled exposure to diesel exhaust or ozone. Methods: Healthy volunteers were exposed to either diesel exhaust (particle concentration 300 mu g/m(3)) and filtered air for one hour, or ozone (300 ppb) and filtered air for 75 minutes. FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after each exposure. Results: Exposure to diesel exhaust increased FENO at 6 hours compared with air at expiratory flow rates of 10 mL/s (p = 0.01) and at 50 mL/s (p = 0.011), but FENO did not differ significantly at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours. Ozone did not affect FENO at any flow rate or time point. Conclusions: Exposure to diesel exhaust, but not ozone, increased FENO concentrations in healthy subjects. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone, with implications for the use of FENO as an index of exposure to air pollution.

  • 47. Barman, M.
    et al.
    Nilsson, S.
    Naluai, Torinsson A.
    Sandin, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Wold, A.
    Sandberg, A-S
    Single nucleotide polymorphisms in fatty acid desaturases is associated with cord blood long chain PUFA proportions and development of allergy2015In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 70, 402-402 p.Article in journal (Other academic)
  • 48. Barman, Malin
    et al.
    Johansson, Sara
    Hesselmar, Bill
    Wold, Agnes E.
    Sandberg, Ann-Sofie
    Sandin, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development2013In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 7, e67920- p.Article in journal (Refereed)
    Abstract [en]

    Background: Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods: From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results: The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P < 0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18:1n-9 as well as total MUFA (p < 0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (P-trend < 0.001), n-6 LCPUFA (P-trend = 0.001), and total LCPUFA (P-trend < 0.001) and decreased linearly with the proportions of total MUFA (P-trend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion: A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant's immune system.

  • 49.
    Baverel, P.
    et al.
    MedImmune, Clin Pharmacol, Cambridge, England..
    Karlsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Agoram, B.
    MedImmune, Clin Pharmacol, Cambridge, England..
    Kantaria, R.
    AstraZeneca, Global Med Affairs, London, England..
    Characterization of dose-FEV1 response of tralokinumab, an investigational anti-IL13 monoclonal antibody in patients with uncontrolled asthma: a population pharmacokinetic/pharmacodynamic modeling analysis2015In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 70, no S101, 35-35 p., 70Article in journal (Other academic)
  • 50. Beeh, Kai M
    et al.
    Burgel, Pierre-Regis
    Franssen, Frits M E
    Lopez-Campos, Jose Luis
    Loukides, Stelios
    Hurst, John R
    Fležar, Matjaž
    Ulrik, Charlotte Suppli
    Di Marco, Fabiano
    Stolz, Daiana
    Valipour, Arschang
    Casserly, Brian
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Kostikas, Konstantinos
    Wedzicha, Jadwiga A
    How Do Dual Long-acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970Article in journal (Refereed)
    Abstract [en]

    Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease (COPD). Several studies have documented that long-acting bronchodilators (LABDs) can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroids (LABA/ICS) combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single LABDs or LABA/ICS in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. While preclinical studies suggest LABAs and LAMAs have anti-inflammatory effects, such effects have not been demonstrated yet in patients with COPD.

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