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  • 1. Ahlroth Pind, C.
    et al.
    Gunnbjörnsdottír, M.
    Bjerg, A.
    Järvholm, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lundbäck, B.
    Malinovschi, A.
    Middelveld, R.
    Nilsson Sommar, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Norbäck, D.
    Janson, C.
    Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: a cross-sectional study2017Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, nr 11, s. 1383-1389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: An association between dampness at home and respiratory conditions has been convincingly demonstrated in children. Fewer studies have been performed in adults, and data are lacking for chronic rhinosinusitis (CRS). With a prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of life, as well as economy.

    OBJECTIVE: Our aim was to study CRS and other respiratory conditions in relation to dampness at home in a representative sample of adults.

    METHODS: The Swedish GA(2) LEN questionnaire was answered by 26 577 adults (16-75 years) and included questions on respiratory symptoms, smoking, education and environmental exposure. CRS was defined according to the EP(3) OS criteria. Dampness was defined as reporting water damage, floor dampness or visible moulds in the home during the last 12 months. The dampness score was ranked from 0 to 3, counting the number of signs of dampness reported.

    RESULTS: Dampness at home was reported by 11.3% and was independently related to respiratory conditions after adjustment for demographic and socio-economic factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR 1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other respiratory conditions was further elevated in subjects reporting multiple signs of dampness.

    CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an independent association between dampness at home and CRS in adults. The high burden of this and the other respiratory conditions studied is a strong argument in favour of countering indoor dampness by improving building standards.

  • 2. Alahmadi, Fahad
    et al.
    Simpson, Andrew
    Gomez, Christina
    Wheelock, Craig
    Shaw, Dominick
    Fleming, Louise
    Roberts, Graham
    Riley, John
    Bates, Stewart
    Sousa, Ana R.
    Knowles, Richard
    Bansal, Aruna
    Corfield, Julie
    Pandis, Ioannis
    Sun, Kai
    Bakke, Per
    Caruso, Massimo
    Chanez, Pascal
    Dahlen, Babro
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Singer, Florian
    Wagers, Scott
    Adcock, Ian
    Djukanovic, Ratko
    Chung, Kian
    Sterk, Peter J.
    Dahlen, Sven-Erik
    Fowler, Stephen J.
    Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

  • 3. 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 study2011Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 183, nr 2, s. 165-170Artikel i tidskrift (Refereegranskat)
    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.

  • 4. Andersson Kallin, Sandra
    et al.
    Lindberg, Eva
    Nilsson Sommar, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bossios, Apostolos
    Ekerljung, Linda
    Malinovschi, Andrei
    Middelveld, Roelinde
    Janson, Christer
    Excessive daytime sleepiness in asthma: what are the risk factors?2018Ingår i: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, Vol. 55, nr 18, s. 844-850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Previous studies have found that excessive daytime sleepiness (EDS) is a more common problem in asthmatic subjects than in the general population. The aim of this study was to investigate whether the prevalence of EDS is increased in asthmatic subjects and, if so, to analyse the occurrence of potential risk factors for EDS in asthmatics.

    METHODS: Cross-sectional epidemiological study. In 2008, a postal questionnaire was sent out to a random sample of 45,000 individuals aged 16-75 years in four Swedish cities.

    RESULTS: Of the 25,160 persons who participated, 7.3% were defined as having asthma. The prevalence of EDS was significantly higher in asthmatic subjects (42.1% vs 28.5%, p<0.001) compared with non-asthmatic subjects. Asthma was an independent risk factor for EDS (adjusted OR 1.29) and the risk of having EDS increased with asthma severity. Risk factors for EDS in subjects with asthma included insomnia (OR, 3.87; 95% CI, 3.10-4.84), chronic rhinosinusitis (OR, 2.00; 95% CI, 1.53-2.62), current smoking (OR, 1.60; 95% CI, 1.15-2.22) and obesity (OR, 1.53; 95% CI, 1.09-2.13).

    CONCLUSIONS: EDS is a common problem among subjects with asthma. Asthma is an independent risk factor for having EDS. Furthermore, subjects with asthma often have other risk factors for EDS, many of them potentially modifiable.

  • 5.
    Andersson, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bjerg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lundbäck, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    The clinical expression of asthma in schoolchildren has changed between 1996 and 20062010Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 21, nr 5, s. 859-866Artikel i tidskrift (Refereegranskat)
    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.

  • 6.
    Andersson, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedman, Linnéa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Bjerg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lundbäck, B
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Persistence and remission of asthma followed from 7 to 19 years of ageManuskript (preprint) (Övrigt vetenskapligt)
  • 7.
    Andersson, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Hedman, Linnéa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Nordberg, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eriksson, Kåre
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Norrbotten County Council, Luleå, Sweden.
    Swimming pool attendance is related to asthma among atopic school children: a population-based study2015Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 14, nr 14, artikel-id 37Artikel i tidskrift (Refereegranskat)
    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.

  • 8. Andersson, Mikael
    et al.
    Stridsman, Caroline
    Emtner, Margareta
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Physical activity and fatigue in chronic obstructive pulmonary disease - A population based study2015Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, nr 8, s. 1048-1057Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    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 COPD2014Ingår i: Clinical Respiratory Journal, ISSN 1752-6981, E-ISSN 1752-699X, Vol. 8, nr 1, s. 93-99Artikel i tidskrift (Refereegranskat)
    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.

  • 10. Antoniewicz, Lukasz
    et al.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Kuhl, Jeanette
    Abdel-Halim, Samy M.
    Kiessling, Anna
    Mobarrez, Fariborz
    Lundback, Magnus
    Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers2016Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 255, s. 179-185Artikel i tidskrift (Refereegranskat)
    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.

  • 11. Axelsson, Inge
    et al.
    Naumburg, Estelle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Prietsch, Silvio O. M.
    Zhang, Linjie
    Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth2019Ingår i: Cochrane Database of Systematic Reviews, ISSN 1469-493X, E-ISSN 1469-493X, nr 6, artikel-id CD010126Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians.

    Objectives: To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma.

    Search methods: We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019.

    Selection criteria: We selected parallel‐group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma.

    Data collection and analysis: At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta‐analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random‐effects model for meta‐analyses. We did not perform planned subgroup analyses due to there being too few included trials.

    Main results: We included six randomized trials involving 1199 children aged from 4 to 12 years (per‐protocol population: 1008), with mild‐to‐moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.

    One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI ‐0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).

    Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane‐metered dose inhaler (HFA‐MDI) and beclomethasone administered via chlorofluorocarbon‐metered dose inhaler (CFC‐MDI) at an equivalent dose (MD ‐0.44 cm/year, 95% CI ‐1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence).

    Authors' conclusions: This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head‐to‐head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real‐life observational studies seem more attractive and feasible.

  • 12.
    Aytekin, Cenk
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen Designhögskolan.
    Living an Active Life with Asthma2012Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    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.

  • 13.
    Backman, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lung function and prevalence trends in asthma and COPD: the Obstructive Lung Disease in Northern Sweden Thesis XVI2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

  • 14.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Ekerljung, Linda
    Eriksson, Berne
    Stridsman, Caroline
    Mincheva, Roxana
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hagstad, Stig
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ullman, Anders
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lundback, Bo
    Decrease in prevalence of COPD in Sweden after decades of decrease in smoking2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: The smoking prevalence in Sweden has steadily decreased during three decades. The prevalence of COPD in Sweden in the 1990s and around the millennium shift was similar to neighboring European countries, i.e. estimated at 11-17%, and of moderate to severe COPD to 7-11%, in ages over 40y.

    Aim: Has the prevalence of chronic airway obstruction (CAO) and of COPD in Sweden decreased after decades of decreasing smoking prevalence?

    Methods: Within two large scale population studies in progress, the West Sweden Asthma Study (WSAS) and the Obstructive Lung Disease in Northern Sweden Studies (OLIN), the prevalence of COPD in ages 41-72y was calculated among randomly selected subjects from the general population in 2009-2012. The following post-bronchodilator definitions were used; CAO: FEV1/FVC<LLN and FEV1/FVC<0.7; moderate to severe CAO: FEV1/FVC<LLN with FEV1<LLN, and FEV1/FVC<0.7 with FEV1<80% of predicted. In line with the GOLD 2017 guidelines, both CAO and respiratory symptoms were required for the diagnosis of COPD.

    Results: The prevalence of CAO based on the FEV1/FVC<LLN and FEV1/FVC<0.7 criteria, respectively, was 6.4% and 10.3%, while the corresponding prevalence of COPD was 5.6% and 8.4%. The prevalence of moderate to severe CAO was 4.0% (LLN-criterion) and 5.0% (fixed ratio-criterion) and of moderate to severe COPD 3.8% and 4.4%, respectively. Main risk factors for both CAO and COPD were smoking, male sex and increasing age.

    Conclusion: As prevalence of COPD defined as chronic airway obstruction before and around the millennium shift was estimated at 11-17% in ages >40 years, the prevalence of COPD has decreased in Sweden, and the decrease in smoking over decades is probably the main causal factor.

  • 15.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå.
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. The OLIN Studies, Department of Research and Development, Norrbotten County Council, Luleå,.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. 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 Sweden2014Ingår i: The World Allergy Organization journal, ISSN 1939-4551, Vol. 7, nr 1, s. 1-Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Department of Health Sciences, Luleå University, Luleå, Sweden.
    Stridsman, Caroline
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundbäck, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    A population-based cohort of adults with asthma: mortality and participation in a long-term follow-up2017Ingår i: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 4, artikel-id 1334508Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: Asthma is a major public health concern. The aim of this study was to characterize a large population-based cohort of adults with asthma, and to study factors associated with all-cause mortality and non-participation in a long-term follow-up. Design: Random and stratified samples from five population-based cohorts were clinically examined during 1986-2001, and all subjects with asthma were included in the study (n = 2055, age 19-72 years, 55% women). Independent associations between different risk factors and (i) mortality and (ii) non-participation in a clinical follow-up in 2012-2014 were estimated. Results: In 1986-2001, 95% reported any wheeze and/or attacks of shortness of breath in the past 12 months, and/or asthma medication use. Over the up to 28 years of follow-up time, the cumulative mortality was 22.7%. Male gender, current smoking, and lower forced expiratory volume in 1 sec of predicted (FEV1% of predicted) were independent risk factors for mortality, while obesity was associated with non-participation in the follow-up. Older ages, ischemic heart disease, and low socioeconomic status were associated with both mortality and non-participation. Conclusions: The risk factors associated with mortality in this adult population-based asthma cohort were similar to those commonly identified in general population samples, i.e. male gender, current smoking, and lower FEV1% of predicted, while obesity was associated with non-participation in a long-term follow-up. Ischemic heart disease, low socioeconomic status, and older ages were associated with both mortality and non-participation.

  • 17.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Stridsman, Caroline
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundback, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eosinophilic inflammation and lung function decline in a long-term follow-up of a large population-based asthma cohort2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

  • 18.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Stridsman, Caroline
    Eriksson, Berne
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eklund, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundback, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Severe asthma among adults: Prevalence and clinical characteristics2018Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

  • 19.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Stridsman, Caroline
    Eriksson, Berne
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Eklund, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lundbäck, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Severe asthma: A population study perspective2019Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, nr 6, s. 819-828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

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

  • 20.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jansson, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Stridsman, Caroline
    Department of Health Sciences, Luleå University, Luleå, Sweden.
    Muellerova, Hana
    Real-World Evidence&Epidemiology, GSK R&D, Uxbridge, UK.
    Wurst, Keele
    Real-World Evidence&Epidemiology, GSK R&D, Uxbridge, UK.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Department of Health Sciences, Luleå University, Luleå, Sweden.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Chronic airway obstruction in a population-based adult asthma cohort: Prevalence, incidence and prognostic factors2018Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 138, s. 115-122Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Asthma and COPD may overlap (ACO) but information about incidence and risk factors are lacking. This study aimed to estimate prevalence, incidence and risk factors of chronic airway obstruction (CAO) in a population-based adult asthma cohort.

    METHODS: /FVC<0.7.

    RESULTS: decline and higher levels of neutrophils than asthma only. Smoking, older age and male sex were independently associated with increased risk for both prevalent and incident CAO, while obesity had a protective effect.

    CONCLUSIONS: In this prospective adult asthma cohort, the majority did not develop CAO. Smoking, older age and male sex were risk factors for prevalent and incident CAO, similar to risk factors described for COPD in the general population.

  • 21.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sovijarvi, Anssi
    Larsson, Kjell
    Lundbäck, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Evaluation of the global lung function initiative 2012 reference values for spirometry in a Swedish population sample2015Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikel-id 26Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    Backman, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Räisänen, Petri
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Department of Health Sciences, Luleå University, Luleå, Sweden.
    Stridsman, Caroline
    Department of Health Sciences, Luleå University, Luleå, Sweden.
    Andersson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundbäck, Bo
    Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016: results from three population surveys2017Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, nr 11, s. 1426-1435Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: During the latter half of the 20th century, the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends among adults after 2010, especially regarding studies separating allergic asthma from non-allergic asthma, is lacking.

    Objective: The aim was to estimate prevalence trends of current asthma among adults, both allergic and non-allergic, from 1996 to 2016.

    Methods: Three cross-sectional samples from the same area of Sweden, 20-69 years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis (ARC) was used as a marker for allergic sensitization to define allergic asthma.

    Results: The prevalence of current asthma increased from 8.4% (95% CI: 7.8-9.0) in 1996 to 9.9% (95% CI: 9.2-10.6) in 2006 and 10.9% (95% CI: 10.1-11.7) in 2016 (P<.001). Allergic asthma increased from 5.0% (95% CI: 4.5-5.5) in 1996 to 6.0% (95% CI: 5.4-6.6) in 2006 and further to 7.3% (95% CI: 6.6-8.0) in 2016 (P<.001), while the prevalence of non-allergic asthma remained stable around 3.4%-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use and ARC also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016.

    Conclusions and clinical relevance: The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.

  • 23. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Scholz, Saskia
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smed-Sörensen, Anna
    Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry2017Ingår i: Jove-journal pf visualized experiments, ISSN 1940-087X, nr 119, artikel-id e55222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

  • 24. Baharom, Faezzah
    et al.
    Thomas, Saskia
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lepzien, Rico
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smed-Sorensen, Anna
    Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans2016Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, nr 11, s. 4498-4509Artikel i tidskrift (Refereegranskat)
    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.

  • 25. Bakke, PS
    et al.
    Rönnmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    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 COPD2011Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 38, nr 6, s. 1261-1277Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Barath, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Respiratory and cardiovascular effects of exposure to oxidative air pollutants2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

  • 27.
    Barath, Stefan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Olin, Anna-Carin
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Diesel exhaust but not ozone increases fraction of exhaled nitric oxide in a randomized controlled experimental exposure study of healthy human subjects2013Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 12, s. 36-Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Barath, Stefan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas, L
    Centre for Cardiovascular Science, Edinburgh University, Edinburgh, United Kingdom.
    Ädelroth, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Olin, Anna-Carin
    Dept. of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Fraction of exhaled nitric oxide after experimental exposure to diesel exhaust and ozone in manManuskript (preprint) (Övrigt vetenskapligt)
    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.

  • 29. Barman, M.
    et al.
    Nilsson, S.
    Naluai, Torinsson A.
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Wold, A.
    Sandberg, A-S
    Single nucleotide polymorphisms in fatty acid desaturases is associated with cord blood long chain PUFA proportions and development of allergy2015Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 70, s. 402-402Artikel i tidskrift (Övrigt vetenskapligt)
  • 30. Barman, Malin
    et al.
    Johansson, Sara
    Hesselmar, Bill
    Wold, Agnes E.
    Sandberg, Ann-Sofie
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 7, s. e67920-Artikel i tidskrift (Refereegranskat)
    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.

  • 31.
    Behndig, A. F.
    et al.
    Umeå universitet.
    Linder, Robert
    Umeå universitet.
    Pourazar, Jamshid
    Umeå universitet.
    Lindberg, A.
    Umeå universitet.
    Blomberg, Anders
    Umeå universitet.
    Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies2016Ingår i: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, ISSN 1073-449X, Vol. 193Artikel i tidskrift (Refereegranskat)
  • 32.
    Behndig, Annelie F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Duggan, Sean T
    Kelly, Frank J
    Mudway, Ian S
    Antioxidant responses to acute ozone challenge in the healthy human airway2009Ingår i: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 21, nr 11, s. 933-942Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the study was to characterize ozone-induced antioxidant responses in the human airway, including the resident leukocyte population, bronchial mucosa, and respiratory-tract lining fluids. Fifteen healthy subjects were exposed to 0.2 ppm ozone for 2 h, with bronchial wash, bronchoalveolar lavage, and biopsy sampling performed 6 h postexposure. Nasal lavage was also performed at multiple time points pre- and postexposure to evaluate responses during the actual exposure period. During the ozone challenge significant losses of nasal lining fluid urate and vitamin C were observed, which resolved 6 h postexposure. At this time point, increased numbers of neutrophils and enhanced concentrations of total glutathione, vitamin C, and urate were seen in bronchial airway lavages. In bronchoalveolar lavage, increased concentrations of total glutathione, vitamin C, urate, alpha-tocopherol, and extracellular superoxide dismutase occurred 6 h post ozone. In alveolar leukocytes significant losses of glutathione were observed, whereas ascorbate concentrations in endobronchial mucosal biopsies were elevated after ozone at this time. These data demonstrate that ozone elicits a broad spectrum of airway antioxidant responses, with initial losses of vitamin C and urate followed by a phase of augmentation of low-molecular-weight antioxidant concentrations at the air-lung interface. The temporal association between the increased RTLF glutathione following ozone and the loss of this thiol from macrophages implies a mobilization to the lung surface, despite the absence of a quantitative association. We propose this constitutes an acute protective adaptation to ozone.

  • 33.
    Behndig, Annelie F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Larsson, Nirina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Brown, Joanna L
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Helleday, Ragnberth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Duggan, Sean T
    Dove, Rosamund E
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wilson, Susan J
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Kelly, Frank J
    Mudway, Ian S
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma2011Ingår i: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 66, nr 1, s. 12-19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 34.
    Behndig, Annelie F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Linder, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Inflammatory Markers In Different COPD Subgroups Compared To Smokers And Healthy Controls2015Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, artikel-id A2884Artikel i tidskrift (Övrigt vetenskapligt)
  • 35.
    Behndig, Annelie F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Shanmuganathan, Karthika
    Whitmarsh, Laura
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Östersund Research Unit, Umeå University. .
    Brown, Joanna L.
    Frew, Anthony J.
    Kelly, Frank J.
    Mudway, Ian S.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wilson, Susan J.
    Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium: an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects2015Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, artikel-id 99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 36.
    Bergdahl, Ingvar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Torén, K
    Nilsson, Tohr
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eriksson, Kåre
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hedlund, U
    Flodin, R
    Järvholm, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Increased mortality in COPD among construction workers exposed to inorganic dust: from the authors2004Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 24, nr 3, s. 512-512Artikel i tidskrift (Refereegranskat)
  • 37.
    Bergqvist, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Christensen, H. Nordahl
    Wiklund, F.
    Bergström, S.
    Characteristics and Long-Term OS of Non-Small Cell Lung Cancer Patients Receiving EGFR Tyrosine Kinase Inhibitor Treatment2018Ingår i: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, nr 10, s. S419-S419Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are important therapeutic agents in treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. However, long-term follow-up and knowledge of clinical factors and TKI treatment patterns, which may be associated with longer OS, remains unclear. Using nationwide registry data, the aim was to investigate survival, prognostic factors for OS, and first line TKI treatment pattern of stage IIIB/IV NSCLC patients in Sweden.

    Method: In this cohort study, data on all patients diagnosed with stage IIIB-IV NSCLC during 2010—2015 from the nationwide Cancer Registry of Sweden were linked with data on dispensed EGFR-TKI drugs, comorbidity, and mortality data from Swedish national health registries. OS was defined as the interval from date of diagnosis until date of death. Survival rates were estimated using the Kaplan-Meier method. Assessment of predictive factors for OS was performed in multivariable Cox regression.

    Result: Of 9,992 stage IIIB/IV NSCLC patients (mean age 70 years, female 49%), 1419 (14%) received first-line TKI treatment. Overall, 59% of TKI treated patients (median age 68 years) were female, 44% had at least one comorbidity, 85% had adenocarcinoma, and 89% were stage IV. Median follow-up time was 15 months and median OS was 16 months; 1- and 3-years survival rates were 62% and 15%, respectively. Predictors of longer OS were younger age at diagnosis, adenocarcinoma, less advanced clinical stage, and less comorbid disease. Furthermore, patients included in the end of the period had a longer OS compared to earlier. TKI treatment switching/re-challenging, as well as prolonged TKI treatment, also predicted longer OS.

    Conclusion: This is the first nationwide study on NSCLC patients receiving first-line EGFR TKIs in routine clinical practice in Sweden. In addition to the reported prolonged TKI treatment length and TKI switching/re-challenging during the observation period, improvements and extension of EGFR testing targeting the appropriate NSCLC patient population may further have contributed to the observed relatively long overall survival.

  • 38. Bertelsen, R. J.
    et al.
    Rava, M.
    Carsin, A. E.
    Accordini, S.
    Benediktsdottir, B.
    Dratva, J.
    Franklin, Karl A.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Heinrich, J.
    Holm, M.
    Janson, C.
    Johannessen, A.
    Jarvis, D. L.
    Jogi, R.
    Leynaert, B.
    Norback, D.
    Omenaas, E. R.
    Raherison, C.
    Sanchez-Ramos, J. L.
    Schlunssen, V.
    Sigsgaard, T.
    Dharmage, S. C.
    Svanes, C.
    Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring2017Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, nr 5, s. 627-638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans.

    Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever.

    Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions.

    Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth.

    Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

  • 39. Berthold, Malin
    et al.
    Bjerg, Anders
    Winberg, Anna
    Mattsson, Lars
    Borres, Magnus
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Obstructive Lung Disease in Northern Sweden (OLIN) studies, Norrbotten county council, Luleå, Sweden.
    Association of Sensitization to Specific Pet Allergen Components with Asthma Symptoms in School Children2015Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, nr 2, s. AB22-AB22Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Animal sensitization is a known determinant of asthma in children. The objective was to study the association of asthma with sensitization to pet allergen components in schoolchildren. Methods: A random sample of 696 children (11-12 y) from a Swedish population-based cohort was analyzed for sensitization (≥0.1 kUA/L) to cat, dog and horse dander extracts using ImmunoCAP. Sensitized children were further analyzed for IgE antibodies to animal allergen components using ImmunoCAP ISAC112. An expanded ISAAC questionnaire was completed by the parents. Results: Of 259 animal-sensitized children (37%) the majority (75%) were sensitized to more than one species. Among the 11 % (n=77) with current asthma 69 % were sensitized to at least one animal extract, as compared to one third of children without current asthma (p<0.001). Current asthma and asthma symptoms upon contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. Already at moderate levels of IgE antibodies to Fel d 4 (1-15 ISU), at which level most children were sensitized also to Fel d 1, the prevalence of asthma symptoms upon contact with cats was significantly increased. Dog-sensitized children were commonly sensitized to several dog components, and the greatest risk for asthma was seen in children co-sensitized to Can f 5 and Can f 1/f 2. Conclusions: Among Northern Swedish schoolchildren furry animals were the main perennial sensitizers. Asthma symptoms were associated with sensitizations to multiple components within an animal species. In particular, cat Fel d 4 sensitization was strongly related to asthma symptoms.

  • 40. Bjerg, A.
    et al.
    Winberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Johansson, R.
    Berthold, M.
    Borres, M.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Norrbotten City Council, OLIN Studies, Luleå, Sweden.
    Backman, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Norrbotten City Council, OLIN Studies, Luleå, Sweden.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Norrbotten City Council, OLIN Studies, Luleå, Sweden.
    Sensitization to animal allergen components in relation to asthma among young adults in Northern Sweden2019Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, s. 291-291Artikel i tidskrift (Övrigt vetenskapligt)
  • 41. Bjerg, Anders
    et al.
    Ekerljung, Linda
    Eriksson, Jonas
    Näslund, Jonas
    Sjölander, Sigrid
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Gothenburg University, Göteborg.
    Dahl, Åslög
    Holmberg, Kenneth
    Wennergren, Göran
    Torén, Kjell
    Borres, Magnus P
    Lötvall, Jan
    Lundbäck, Bo
    Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood2016Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, nr 10, s. 1328-1336Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To date, most studies of the "allergy epidemic" have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults.

    OBJECTIVE: To study allergic sensitization, its risk factors, and time trends in prevalence.

    METHODS: Within West Sweden Asthma Study (WSAS) a population-based sample of 788 adults (17-60y) underwent skin prick tests (SPT) for 11 aeroallergens 2009-2012. Specific IgE was analyzed in 750 of the participants. Those aged 20-46y (n=379) were compared with the European Community Respiratory Health Survey sample aged 20-46y from the same area (n=591) in 1991-1992.

    RESULTS: Among those aged 20-46y the prevalence of positive SPT to pollen increased; timothy from 17.1% to 29.0% (p<0.001) and birch from 15.6% to 23.7% (p=0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60y any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98) respectively.

    CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990's, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.

  • 42.
    Bjerg, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Ekerljung, Linda
    Middelveld, Roelinde
    Dahlén, Sven-Erik
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Franklin, Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Larsson, Kjell
    Lötvall, Jan
    Ólafsdóttir, Inga Sif
    Torén, Kjell
    Lundbäck, Bo
    Janson, Christer
    Increased prevalence of symptoms of rhinitis but not of asthma between 1990 and 2008 in Swedish adults: comparisons of the ECRHS and GA2LEN surveys2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 2, s. e16082-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The increase in asthma prevalence until 1990 has been well described. Thereafter, time trends are poorly known, due to the low number of high quality studies. The preferred method for studying time trends in prevalence is repeated surveys of similar populations. This study aimed to compare the prevalence of asthma symptoms and their major determinants, rhinitis and smoking, in Swedish young adults in 1990 and 2008.

    Methods

    In 1990 the European Community Respiratory Health Survey (ECRHS) studied respiratory symptoms, asthma, rhinitis and smoking in a population-based sample (86% participation) in Sweden. In 2008 the same symptom questions were included in the Global Allergy and Asthma European Network (GA2LEN) survey (60% participation). Smoking questions were however differently worded. The regions (Gothenburg, Uppsala, Umeå) and age interval (20–44 years) surveyed both in 1990 (n = 8,982) and 2008 (n = 9,156) were analysed.

    Results

    The prevalence of any wheeze last 12 months decreased from 20% to 16% (p<0.001), and the prevalence of “asthma-related symptoms” was unchanged at 7%. However, either having asthma attacks or using asthma medications increased from 6% to 8% (p<0.001), and their major risk factor, rhinitis, increased from 22% to 31%. Past and present smoking decreased.

    Conclusion

    From 1990 to 2008 the prevalence of obstructive airway symptoms common in asthma did not increase in Swedish young adults. This supports the few available international findings suggesting the previous upward trend in asthma has recently reached a plateau. The fact that wheeze did not increase despite the significant increment in rhinitis, may at least in part be due to the decrease in smoking.

  • 43. Bjerg, Anders
    et al.
    Eriksson, Jonas
    Ólafsdóttir, Inga Sif
    Middelveld, Roelinde
    Franklin, Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Larsson, Kjell
    Torén, Kjell
    Dahlén, Sven-Erik
    Janson, Christer
    The association between asthma and rhinitis is stable over time despite diverging trends in prevalence2015Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, nr 3, s. 312-319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Despite the well-known association between asthma and rhinitis, in Swedish adults the prevalence of rhinitis rose from 22% to 31% between 1990 and 2008 while asthma prevalence was unchanged. We tested whether the association of rhinitis with asthma was stable over time using the same population-based databases.

    METHODS: Two surveys of adults (20-44 years) living in three regions of Sweden, carried out in 1990 (n = 8982) and 2008 (n = 9156) were compared. Identical questions regarding respiratory symptoms, asthma and rhinitis were used. Asthmatic wheeze: Wheeze with breathlessness apart from colds. Current asthma: Asthma attacks and/or asthma medication use.

    RESULTS: Subjects with rhinitis had level time trends in asthmatic wheeze, current asthma and most nocturnal respiratory symptoms between 1990 and 2008, adjusted for age, sex, area and smoking. Any wheeze however decreased slightly. In never-smokers asthma symptoms were similarly associated with rhinitis in 1990 and 2008: any wheeze OR 4.0 vs. 4.4 (p = 0.339); asthmatic wheeze OR 6.0 vs. 5.9 (p = 0.937); and current asthma OR 9.6 vs. 7.7 (p = 0.213). In the whole population there were decreases in the asthma symptoms most closely associated to smoking, which decreased by half 1990-2008. Conversely current asthma, which was strongly associated with rhinitis and not with smoking, increased (p < 0.001).

    CONCLUSIONS: The association of rhinitis with asthma was stable between 1990 and 2008. The pattern in the time trends of asthma outcomes strongly suggests that decreased smoking counterbalanced the driving effect of increased rhinitis on asthma prevalence. The findings illustrate the public health benefits of decreased smoking.

  • 44. Bjerg, Anders
    et al.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Perzanowski, Matthew
    Lundback, Bo
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    A Strong Synergism of Low Birth Weight and Prenatal Smoking on Asthma in Schoolchildren2011Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 127, nr 4, s. E905-E912Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Prenatal smoke exposure is associated with airway inflammation and asthma in children. It also increases the risk of low birth weight (LBW). LBW is associated with decreased lung function independently of smoking.

    OBJECTIVE: To study the independent and joint effects of prenatal smoking and LBW on childhood asthma.

    METHODS: In 1996, all children aged 7 to 8 years in 3 cities in northern Sweden were invited to an International Study of Asthma and Allergy in Childhood questionnaire survey. This study focused on the follow-up of children aged 11 to 12 years, in which 3389 children (96%) participated. A subset of 2121 children underwent skin-prick testing. Self-reported physician-diagnosed asthma has been clinically validated.

    RESULTS: Mean birth weight was 3360 g in children exposed to prenatal smoking and 3571 g in nonexposed children (P < .001). The association of prenatal smoking with physician-diagnosed asthma was stronger in LBW children (risk ratio: 8.8 [95% confidence interval: 2.1-38]) than in normal birth weight children (risk ratio: 1.3 [95% confidence interval: 1.0-1.8]). LBW alone was not an independent predictor of asthma. These associations were similar in multivariate analysis, and the interaction term LBW x smoking was highly statistically significant.

    CONCLUSIONS: There was a strong interaction of LBW and prenatal-smoking on the risk of physician-diagnosed asthma, which has not been demonstrated previously. This was consistently seen with adjustment for known risk factors, including allergic sensitization. Plausibly, airway inflammation from prenatal smoke exposure induces obstructive symptoms more easily in the underdeveloped airways of LBW children.

  • 45.
    Bjerg, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin. The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå.
    Asthma in school age: prevalence and risk factors by time and by age2008Ingår i: Clinical Respiratory Journal, ISSN 1752-6981, E-ISSN 1752-699X, Vol. 2, nr Suppl 1, s. 123-126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Childhood is the most important age for asthma development. Recent reports indicate that the prevalence of asthma. in children has plateaued after having increased for decades.

    Aims: To study prevalence and risk factor patterns of asthma by age and by time.

    Methods: In 1996, all children in grade 1-2 (age 7-8) in three cities ill Northern Sweden were invited to an expanded International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. A total of 3430 children (97%) participated yearly until 2000 (age 11-12). A subset (n = 2454) was invited to skill-prick testing in 1996 and 2000 with 88% and 90% participation. In 2006, another cohort (n = 2704) was identified and studied by identical methods with 96% participation. A total of 1700 children (90% of invited) were skin-prick tested.

    Results and comments: From age 7-8 to 11-12, the prevalence of physician-diagnosed asthma increased, 5.7%-7.7% (P<0.01) while current wheeze decreased, 11.7%-9.4% (P < 0.01), indicating a less diverse spectrum of symptoms with age. The yearly remission from asthma was 10% (lasting remission 5%), largely determined by allergic sensitisation. Allergic sensitisation (OR 5) and a family history of asthma (OR 3) were important risk factors for asthma at age 7-8 and 11-12. However, several other significant risk factors at age 7-8 (low birth weight, respiratory infections and house dampness) lost importance until age 11-12. Maternal and paternal asthma were equally important risk factors (OR 3-4) at age 7-8. Sibling asthma was only a marker of parental disease.

    Future perspectives: Through comparison with the 2006 cohort, trends in prevalence and in risk factors from 1996 to 2006 will be studied.

  • 46.
    Bjerg Bäcklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Epidemiology of asthma in primary school children: the Obstructive Lung Disease in Northern Sweden (OLIN) studies thesis VIII2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Childhood asthma has increased worldwide, although recent studies report a prevalence plateau in some western countries.

    Aims: To investigate the prevalence of asthma and the associated risk factor patterns from ages 7-8 to 11-12 with special emphasis on the hereditary component, and further to study prevalence trends at age 7-8 from 1996 to 2006 and the possible determinants of these trends.

    Methods: The studies involved two cohorts from Kiruna, Luleå and Piteå: one previously identified cohort of 3430 children age 7-8 followed by yearly questionnaires until age 11-12 with 97% yearly participation. Skin-prick tests for allergic sensitisation were performed at ages 7-8 and 11-12 in subsets of 2148 and 2155 children respectively (88% of invited). In 2006 a new cohort of 7-8-year-olds was identified and examined identically. 2585 (96% of invited) and 1700 (90% of invited) participated in the questionnaire and skin-prick tests, respectively. The questionnaire included questions about symptoms of asthma, allergic rhinitis and eczema, and possible risk factors.

    Results: In the 1996 cohort, from age 7-8 to 11-12 the prevalence of physician-diagnosed asthma increased (5.7%-7.7%, P<0.01) while current wheeze decreased (11.7%-9.4%, P<0.01), and 34.7% reported ever wheee at ≥one occasion. Remission was 10% of which half relapsed during the study. Remission was significantly lower among sensitised children. The strongest risk factors for current asthma at ages 7-8 and 11-12 were allergic sensitisation (OR 5) and family history of asthma (OR 3). Several other significant risk factors, e.g. respiratory infections, damp house and low birth weight, had lost importance at age 11-12. At age 7-8, parental asthma was a stronger risk factor (OR 3-4) than parental rhinitis or eczema (OR 1.5-2). Sibling asthma had no independent effect. Biparental asthma had a multiplicative effect (OR 10). Maternal and paternal asthma was equally important, regardless of the child’s sex and sensitisation status.

    From 1996 to 2006 the prevalence of current wheeze and asthma at age 7-8 did not increase (P=0.13, P=0.18), while lifetime prevalence of ever wheeze and physician-diagnosed asthma increased (P<0.01, P=0.01). Symptoms of rhinitis and eczema were unchanged, despite 45% increase (P<0.01) in allergic sensitisation. For current asthma the adjusted population attributable fractions of sensitisation and parental asthma increased (35%-41%, 27%-45%). This was however balanced by decreased exposure to infections, maternal smoking and home dampness, resulting in stable asthma prevalence. Stratification by sex revealed that current wheeze increased in boys (P<0.01) but tended to decrease in girls (P=0.37), seemingly due to symptom persistence in males. Several asthma indices followed this pattern. The boy-to-girl ratio in exposure to all studied risk factors increased, which may explain the sex-specific prevalence trends in wheeze.

    Conclusions: The prevalence of current asthma and wheeze did not increase statistically significantly. However, the risk factor pattern has changed considerably since 1996, which will presumably affect the clinical features of childhood wheeze in this region. Sex-specific trends in wheeze can be explained by changes in exposure, and trends in risk factors should be explored parallel to prevalence trends.

  • 47.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Update in environmental and occupational medicine 20112012Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 185, nr 11, s. 1166-1170Artikel i tidskrift (Refereegranskat)
  • 48.
    Blomberg, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sköld, M
    Linden, A
    Patofysiologi vid KOL2009Ingår i: Lungmedicin / [ed] Thomas Sandström, Anders Eklund, Lund, Sweden: Studentlitteratur , 2009, s. 371-385Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 49. Bolger, Claire
    et al.
    Tufvesson, Ellen
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Devereux, Graham
    Ayres, John
    Holmberg, Hans-Christer
    Bjermer, Leif
    Sue-Chu, Malcolm
    Kippelen, Pascale
    Urinary cc16 levels in winter versus summer sport athletes after eucapnic voluntary hyperpnoea2009Konferensbidrag (Refereegranskat)
    Abstract [en]

    Exercise induced bronchoconstriction (EIB) is highly prevalent in elite athletes, especially in those training in cold dry environments. Dehydration of the airways plays a key role in this process. EIB has recently been linked to airway epithelial injury in asthmatic individuals. The aim of the study is to determine whether a short period of hyperpnoea of dry air causes airway epithelial disruption in winter and/or summer sport athletes. We hypothesise that urinary level of the Clara cell protein (CC16) – an indirect marker of permeability/cellular integrity of the lung epithelial barrier – will be increased after a eucapnic voluntary hyperpnoea (EVH) test and that this increase will be larger in winter compared to summer athletes. Forty two female athletes – 28 summer athletes (age 31.1+/-1.7yr (SEM), training volume 9+/-1.1h/wk) and 14 winter athletes (age 21.4+/-0.8yr, training volume 12.0 ± 1.10h/wk) – took part in this study. They all performed an 8-min EVH test at a target ventilation rate of 30 times their baseline forced expiratory volume in one second (FEV1). After the challenge, FEV1 was measured in duplicate at 2, 5, 10, 15, 20, 30, 60 and 90min. A sustained decrease in FEV1 of at least 10% from baseline was considered positive. Urine samples were collected at baseline and at 30, 60 and 90min recovery. CC16 concentration was measured by enzyme immunoassay. Ten summer athletes had a positive test (max FEV1 fall = 19.6+/-2.4%), whilst eighteen of the summer athletes and all the winter athletes were negative (max FEV1 fall = 5.7+/-0.7% and 5.3+/-0.7%, respectively). CC16 increased significantly after the challenge in all three groups (P<0.01) with no difference between groups: delta CC16 (max post-EVH minus baseline) in summer EVH negative athletes was 0.241+/-0.1 ng/&#956;mol creatinine, 0.292+/-0.085 ng/&#956;mol creatinine in summer EVH positive athletes, and 0.123+/-0.047ng/&#956;mol creatinine in winter EVH negative athletes (P=0.415)In conclusion, a short period of hyperpnoea of dry air is associated with an increased rate of CC16 excretion in urine in both winter and summer athletes. This suggests that the integrity of the airway epithelium might be compromised by loss of airway surface lining fluid when athletes inhale dry air at high flow rates. This appears to occur irrespective of the degree of bronchoconstriction or regular training environment.

  • 50. Bolling, Anette Kocbach
    et al.
    Totlandsdal, Annike Irene
    Sallsten, Gerd
    Braun, Artur
    Westerholm, Roger
    Bergvall, Christoffer
    Boman, Johan
    Dahlman, Hans Jorgen
    Sehlstedt, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Cassee, Flemming
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Schwarze, Per E.
    Herseth, Jan Inge
    Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines2012Ingår i: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 9, s. 45-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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