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Sökning: WFRF:(Dahlen Sven Erik)

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  • James, Anna, et al. (författare)
  • The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma
  • 2013
  • Ingår i: International Archives of Allergy and Immunology. - 1018-2438. ; 162:2, s. 135-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The effect of aspirin on the release of key arachidonic acid metabolites in activated eosinophils from subjects with aspirin-intolerant asthma (AIA) has not been investigated previously, despite the characteristic eosinophilia in AIA. Methods: Peripheral blood eosinophils were isolated from four groups of subjects: healthy volunteers (HV; n = 8), mild asthma (MA; n = 8), severe asthma (SA; n = 9) and AIA (n = 7). In the absence or presence of lysine-aspirin, eosinophils were stimulated with arachidonic acid or calcium ionophore to trigger the 15-lipoxygenase-1 (15-LO) and 5-lipoxygenase (5-LO) pathways, respectively. 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and eoxin C4 (EXC4) were measured as 15-LO products and leukotriene (LT)C4 as a product of the 5-LO pathway. Results: Activated eosinophils from patients with SA and AIA produced approximately five times more 15-HETE than eosinophils from HV or MA patients. In the presence of lysine-aspirin, eosinophils from AIA, MA and SA patients generated higher levels of 15-HETE than in the absence of lysine-aspirin. Furthermore, in the presence of lysine-aspirin, formation of EXC4 was also significantly increased in eosinophils from AIA patients, and LTC4 synthesis was increased both in AIA and SA patients. Conclusions: Taken together, this study shows an increased release of the recently discovered lipid mediator EXC4, as well as the main indicator of 15-LO activity, 15-HETE, in activated eosinophils from severe and aspirin-intolerant asthmatics, and also elevated EXC4 and LTC4 formation in eosinophils from AIA patients after cellular activation in the presence of lysine-aspirin. The findings support a pathophysiological role of the 15-LO pathway in SA and AIA.
  • Protudjer, Jennifer L P, et al. (författare)
  • Household Costs Associated with Objectively Diagnosed Allergy to Staple Foods in Children and Adolescents
  • 2015
  • Ingår i: Journal of Allergy and Clinical Immunology-In Practice. - 2213-2198. ; 3:1, s. 68-75
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We previously reported that indirect and intangible costs burden households with a food allergic adult. We now extend our investigation to households with food allergic children and adolescents. OBJECTIVE: The objective of this study was to estimate direct, indirect, and intangible costs of food allergy in households with a child and/or adolescent with objectively diagnosed allergy to staple foods (cow's milk, hen's egg, and/or wheat), and to compare these costs with age-and sex-matched controls. METHODS: Direct and indirect cost parent-reported data collected via the Food Allergy Socio-Economic Questionnaire of 84 children (0-12 years) and 60 adolescents (13-17 years) with objectively diagnosed allergy to staple foods ("cases") and age- and sex-matched controls (n = 94 children; n = 56 adolescents) were compared. Annual household costs were calculated. Total household costs included direct plus indirect costs. Intangible costs included parent-reported health of their child and/or adolescent, standard of living, and perceptions of well-being. RESULTS: Amongst cases, total household costs were higher by (sic)3961 for children and (sic)4792 for adolescents versus controls (P < .05), and were driven by direct (eg, medications) and indirect (eg, time with health care professionals) costs. For children only, a history of anaphylaxis was associated with higher direct costs than no anaphylaxis ((sic)13,016 vs (sic)10,044, P < .05). Intangible costs (eg, parent-reported health of a child and/or adolescent) were significantly impacted amongst cases versus controls (P < .01). CONCLUSION: Households with a child and/or adolescent with objectively diagnosed allergy to staple foods have higher total household costs than controls. Direct and indirect costs were significantly higher for cases versus controls amongst children only. Amongst both age groups, such allergy adversely impacted intangible costs. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
  • Protudjer, Jennifer Lisa Penner, et al. (författare)
  • Impaired health-related quality of life in adolescents with allergy to staple foods
  • 2016
  • Ingår i: Clinical and Translational Allergy. - 2045-7022. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cow's milk, hen's egg and wheat are staple foods in a typical western diet. Despite the ubiquity of these foods, the impact of staple food allergy on health-related quality of life (HRQL) amongst adolescents is incompletely understood. The aims of this study were to make use of the Swedish version of EuroPrevall's disease-specific food allergy quality of life questionnaire-teenager form (FAQLQ-TF) and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents. Methods: In this cross-sectional study, 58 adolescents aged 13-17 years [n = 40 (69 %) boys] with objectively-diagnosed allergy to the staple foods cow's milk, hen's egg and/or wheat and living in Stockholm, Sweden were included. Adolescents completed the FAQLQ-TF, which has a corresponding scale of 1 = best HRQL, and 7 = worst HRQL. Overall HRQL and domain-specific HRQL were established. Adolescents also reported symptoms, adrenaline auto injector (AAI) prescription and presence of other food allergies. A history of anaphylaxis was defined among those reporting difficulty breathing, inability to stand/collapse, and/or loss of consciousness. Clinically different HRQL was set at a mean difference of >= 0.5. Results: Overall mean HRQL was poorer than average [mean: 4.70/7.00 (95 % CI 4.30-5.01)]. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions (mean difference = 0.76; p < 0.001). Girls had clinically worse, but not statistically significantly different mean HRQL than boys (mean difference = 0.71; p < 0.07). HRQL tended to be worse amongst those with allergies to more than three foods or an AAI prescription. The number and types of symptoms, including a history of anaphylaxis were not associated with worse HRQL. Conclusions: As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL.
  • Bjerg, Anders, et al. (författare)
  • Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
  • 2013
  • Ingår i: Plos One. - 1932-6203. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods: In 2008 the Global Allergy and Asthma European Network (GA(2)LEN) questionnaire was mailed to 45.000 Swedes (age 16-75 years), and 26.851 (60%) participated. "Any wheeze'': any wheeze during the last 12 months. "Asthmatic wheeze'': wheeze with breathlessness apart from colds. Results: Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56-2.19) vs. 1.60 (1.30-1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age >= 53 years. Discussion: In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
  • Bjerg, Anders, et al. (författare)
  • The association between asthma and rhinitis is stable over time despite diverging trends in prevalence
  • 2015
  • Ingår i: Respiratory Medicine. - 0954-6111. ; 109:3, s. 312-319
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  • Ekerljung, Linda, et al. (författare)
  • No further increase of incidence of asthma: Incidence, remission and relapse of adult asthma in Sweden
  • 2008
  • Ingår i: Respiratory Medicine. - 0954-6111. ; 102:12, s. 1730-1736
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Knowledge about time trends of disease patterns in society is essential for planning and prioritizing health care resources. Longitudinal population-based studies on asthma are scarce but provide an opportunity to assess incidence, remission and relapse of asthma, and their determinants, which were the objectives of the present study.METHODS: A postal questionnaire was sent on two occasions, 1996 and 2006, to a randomly selected sample of subjects aged 20-69 years in 1996. The response rates were 72% and 83%, respectively, and in total 4479 subjects participated in both surveys. The questionnaire included questions on asthma, respiratory symptoms and possible determinants. Logistic regression was used to assess determinants.RESULTS: Cumulative incidence of asthma was 2.4% (men 1.9%; women 2.8%, p=0.06). Family histories of asthma (OR 2.31, CI 95% 1.42-3.76), rhinitis (OR 2.25, CI 95% 1.43-3.53) and being an ex-smoker (OR 2.17, CI 95% 1.27-3.71) were determinants for incident asthma. The 10-year remission of asthma was 14.6% and inversely associated with rhinitis. Relapse was found in 38% of eligible subjects.CONCLUSIONS: The current study with high participation rates concludes that the incidence of asthma among adults has been stable in Sweden for the past two decades. Remission was associated with mild disease at study start. Relapse in adults has rarely been reported previously and provide new insight in the course of asthma. Low remission and high relapse further support the view of asthma as a chronic disease; possibly representing fluctuations of the disease over time.
  • Gaber, Flora, et al. (författare)
  • Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma
  • 2008
  • Ingår i: Thorax. - 1468-3296. ; 63:12, s. 1076-82
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E(4) (LTE(4)) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B(4) (LTB(4)) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators. METHODS: Induced sputum, saliva, urine and blood were obtained at baseline from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB(4) and the prostaglandin D(2) metabolite 9alpha,11beta-prostaglandin F(2) were performed and the fraction of exhaled nitric oxide was measured. RESULTS: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB(4) levels between the groups. Levels of urinary LTE(4) and 9alpha,11beta-prostaglandin F(2) increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase. CONCLUSION: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.
  • Gyllfors, Pär, et al. (författare)
  • Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate
  • 2006
  • Ingår i: Journal of Allergy and Clinical Immunology. - 0091-6749. ; 118:1, s. 78-83
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved. OBJECTIVE: We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma. METHODS: In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis. RESULTS: Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations. CONCLUSION: These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids. CLINICAL IMPLICATIONS: The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.
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