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  • 1.
    Behndig, Annelie F.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Mirgorodskaya, Ekaterina
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Olin, Anna-Carin
    Surfactant Protein A in particles in exhaled air (PExA), bronchial lavage and bronchial wash - a methodological comparison2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, no 1, article id 214Article in journal (Refereed)
    Abstract [en]

    Introduction: At present, there are few methods available for monitoring respiratory diseases affecting distal airways. Bronchoscopy is the golden standard for sampling the lower airways. The recently developed method for collecting non-volatile material from exhaled air – PExA (Particles in Exhaled air) is a promising new tool, but no direct comparison between the two methods has yet been performed. The aim of the present study was to compare sampling using PExA with bronchial wash (BW) representing the larger more proximal airways and broncho-alveolar lavage (BAL) representing the distal airways.

    Methods: 15 healthy non-smoking subjects (7 female/8 male), age 28 ± 4 years, with normal lung function were included in the study. PExA-sampling (2 × 250 ng particles) and bronchoscopy with BW (2 × 20 ml) and BAL (3 × 60 ml sterile saline) was performed. Albumin and Surfactant Protein A (SP-A) were analyzed with ELISA, and analyses of correlation were performed.

    Results: A significant association was found between BAL-fluid albumin and PExA-albumin (rs:0.65 p = 0.01). There was also an association between SP-A in PExA and BAL, when corrected for albumin concentration (rs:0.61, p = 0.015). When correlating concentrations of albumin and SP-A in bronchial wash and PExA respectively, no associations were found.

    Conclusions: This is the first direct comparison between the bronchoscopy-based BW/BAL-fluids and material collected using the PExA methodology. Both albumin and albumin-corrected SP-A concentrations were significantly associated between BAL and PExA, however, no such association was found in either marker between BW and PExA. These results indicate that the PExA method samples the distal airways. PExA is thus considered a new promising non-invasive assessment for monitoring of the distal airways.

  • 2.
    Eriksson Ström, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bucht, Anders
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking2018In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, article id 244Article in journal (Refereed)
    Abstract [en]

    Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.

    Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

    Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.

    Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.

    Trial registration: Clinicaltrials.gov identifier NCT02729220.

  • 3. Flexeder, Claudia
    et al.
    Zock, Jan-Paul
    Jarvis, Deborah
    Verlato, Giuseppe
    Olivieri, Mario
    Benke, Geza
    Abramson, Michael J.
    Sigsgaard, Torben
    Svanes, Cecilie
    Toren, Kjell
    Nowak, Dennis
    Jogi, Rain
    Martinez-Moratalla, Jesus
    Demoly, Pascal
    Janson, Christer
    Gislason, Thorarinn
    Bono, Roberto
    Holm, Mathias
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Garcia-Aymerich, Judith
    Siroux, Valerie
    Leynaert, Benedicte
    Dorado Arenas, Sandra
    Corsico, Angelo Guido
    Pereira-Vega, Antonio
    Probst-Hensch, Nicole
    Urrutia Landa, Isabel
    Schulz, Holger
    Heinrich, Joachim
    Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, article id 33Article in journal (Refereed)
    Abstract [en]

    Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (beta: - 49 ml; 95%-CI: -132, 35 for FEV1 and beta: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.

  • 4.
    Linder, Robert
    et al.
    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.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Behndig, Annelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study2015In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 16, article id 28Article in journal (Refereed)
    Abstract [en]

    Background: Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population- based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.

    Methods: Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.

    Results: Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).

    Conclusion: Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.

  • 5.
    Linder, Robert
    et al.
    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. The OLIN unit.
    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.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Proteolytic biomarkers are related to prognosis in COPD: report from a population-based cohort2018In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, article id 64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort.

    METHODS: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbent assay (ELISA). Mortality data were collected from the Swedish national mortality register from the date of examination in 2005 until 31st December 2010.

    RESULTS: The correlation between biomarkers and lung function decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP-9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs. 10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher among those who died during follow up, as well as among those alive but not participating in 2010, when compared to those participating in the 2010-examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP-9/TIMP-1 ratio were associated with increased risk for death, while increased TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP-9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death.

    CONCLUSIONS: The expected association between these biomarkers and lung function decline in COPD was not confirmed in this population-based study, probably due to a healthy survivor effect. Still, it is suggested that increased proteolytic imbalance may be of greater prognostic importance in COPD than in non-COPD.

  • 6. Pindus, Mihkel
    et al.
    Orru, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Institute of Family Medicine and Public Health, University of Tartu, Ravila 19, 50411, Tartu, Estonia..
    Jõgi, Rain
    Change in the symptom profile treated as asthma - two cross-sectional studies twenty years apart2020In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 21, no 1, article id 41Article in journal (Refereed)
    Abstract [en]

    AIMS: The aims of the study were to investigate prevalence trends of respiratory symptoms, asthma and asthma treatment among young adults in Estonia and to estimate changes in symptom profile among subjects who self-report asthma attacks or use asthma medications.

    METHODS: Two similar questionnaires on respiratory health were sent to subjects in Tartu, Estonia, aged between 20 and 44 years; first in 1993/94, and then in 2014/15. To study the impact of different respiratory symptoms on asthma diagnosis and treatment, the log-binomial regression was used to estimate the association between 'attack of asthma' (as a proxy for current asthma) and respiratory symptoms as well as asthma treatment and respiratory symptoms, adjusted for age, sex and smoking history.

    RESULTS: Self-reported prevalence of asthma attack, asthma medication use and nasal allergies increased over the twenty years between studies, whereas there was no change in prevalence of asthma-related symptoms, and the prevalence of most respiratory symptoms either decreased, or remained unchanged. For women experiencing asthma attacks, the prevalence of nasal allergies increased and waking with chest tightness decreased. For men using asthma medication, the prevalence of a wheeze without a cold decreased. Women using asthma medication reported decreased prevalence of waking with chest tightness.

    CONCLUSION: Self-reported asthma attacks and asthma medication use has increased in last 20 years, while the prevalence of most respiratory symptoms either decreased or did not change. It is likely that changes in asthma symptom profile have had an impact on the prevalence of asthma and asthma treatment.

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