Vibeke Backer

Bispebjerg Hospital, Copenhagen University, København, Capital Region, Denmark

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Publications (280)972.85 Total impact

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    ABSTRACT: Asthma is one of the most frequent chronic diseases worldwide. For decades, asthma has been treated with bronchodilators and inhaled corticosteroids (ICS). However, adverse effects of ICS and disease heterogeneity necessitate improvements in the existing treatment regimes. Recently approved ICS show improved pharmocodynamic properties. Nevertheless, emerging drugs acting on the same receptor as the ICS, glucocorticoid receptor agonists (GRAs), are under current research. These drugs exhibit selective action on the glucocorticoid receptor (GR), which may improve their adverse effect profile, compared to the currently approved ICS that act unselectively on the GR. Areas covered: The present article reviews emerging GRAs for the treatment of asthma. Furthermore, the more recently approved ICS with improved safety profiles are reviewed. Expert opinion: Compared with drugs acting on other pathological pathways, research in GRAs for asthma is sparse. However, a few promising agents acting selectively on the GR are currently under investigation and may reach approval for asthma treatment. These drugs exhibit improved pharmacodynamic properties due to selectivity in the mechanism of action, including promotion of transrepression and reduction of transactivation. However, competition from already approved ICS and other emerging treatment options may lead to cessation of development of the new GRAs.
    Expert Opinion on Emerging Drugs 06/2015; DOI:10.1517/14728214.2015.1061503 · 3.28 Impact Factor
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    ABSTRACT: The present study investigated the influence of exercise and dehydration on the urine concentrations of salbutamol after inhalation of that maximal permitted (1600 µg) on the 2015 World Anti-Doping Agency (WADA) prohibited list. Thirteen healthy males participated in the study. Urine concentrations of salbutamol were measured during three conditions: exercise (EX), exercise+dehydration (EXD), and rest (R). Exercise consisted of 75 min cycling at 60% of VO2max and a 20-km time-trial. Fluid intake was 2300, 270, and 1100 mL during EX, EXD, and R, respectively. Urine samples of salbutamol were collected 0-24 h after drug administration. Adjustment of urine concentrations of salbutamol to a specific gravity (USG) of 1.020 g/mL was compared with no adjustment. The 2015 WADA decision limit (1200 ng/mL) for salbutamol was exceeded in 23, 31, and 10% of the urine samples during EX, EXD, and R, respectively, when unadjusted for USG. When adjusted for USG, the corresponding percentages fell to 21, 15, and 8%. During EXD, mean urine concentrations of salbutamol exceeded (1325±599 ng/mL) the decision limit 4 h after administration when unadjusted for USG. Serum salbutamol Cmax was lower (P<0.01) for R(3.0±0.7 ng/mL) than EX(3.8±0.8 ng/mL) and EXD(3.6±0.8 ng/mL). AUC was lower for R (14.1±2.8 ng/mL·∙h) than EX (16.9±2.9 ng/mL·∙h)(P<0.01) and EXD (16.1±3.2 ng/mL·∙h)(P<0.05). In conclusion, exercise and dehydration affect urine concentrations of salbutamol and increase the risk of Adverse Analytical Findings in samples collected after inhalation of that maximal permitted (1600 µg) for salbutamol. This should be taken into account when evaluating doping cases of salbutamol. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 06/2015; DOI:10.1002/dta.1828 · 2.82 Impact Factor
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    ABSTRACT: Preservation of lung health requires understanding the modifiable risk factors of airflow limitation. This study investigates the association between diet and lung function in a population of Greenland Inuit residing in the Arctic (Greenland) or Western Europe (Denmark). Two unselected Inuit populations were recruited, one living in Greenland (Urban (Nuuk) n=358; Rural (Uummannaq) n=207) and the other in Denmark (n=539). Lung function was measured using spirometry and diet by a food frequency questionnaire. Factors associated with airflow limitation were assessed using multiple linear regression models. The dietary composition differed significantly in the two regions, with higher whale, seal and wild meat intake and lower fruit and vegetable intake in the Arctic regions compared with Denmark. Consumption of vegetables (P=0.004) and whale and/or seal (P<0.0001) was significantly and positively associated with FEV1, as well as with FVC (vegetables: P=0.001, whale and/or seal: P=0.002). Regular fruit intake was included in the statistical models; however, it did not reach statistical significance (FEV1: P=0.053; FVC: P=0.055). High dietary intake of vegetables as well as intake of arctic marine mammals had independent positive associations with lung function in this cohort of Greenlandic Inuit. These findings suggest an additive role of dietary intake of antioxidants and unsaturated fatty acids in lung health, which warrants prospective evaluation.European Journal of Clinical Nutrition advance online publication, 27 May 2015; doi:10.1038/ejcn.2015.85.
    European journal of clinical nutrition 05/2015; DOI:10.1038/ejcn.2015.85 · 2.95 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is associated with several systemic diseases, such as type 2 diabetes. It has been suggested that comorbidity between COPD and type 2 diabetes is due to shared genetic factors. To examine the relationship between type 2 diabetes and chronic bronchitis and COPD in adult twins, and to examine to what extent comorbidity between these diseases is explained by shared genetic or environmental factors. Questionnaire data on chronic bronchitis and hospital discharge data on diagnosed COPD in 13,649 twins, aged 50-71 years, from the Danish Twin Registry were cross-linked with hospital discharge diagnosis data on type 2 diabetes from the Danish National Patient Registry. The risk of type 2 diabetes was higher in persons with symptoms of chronic bronchitis than in those without symptoms (3.5 vs. 2.3%), OR = 1.57 (1.10-2.26), p = 0.014, and in individuals with diagnosed COPD than in those without the diagnosis (6.6 vs. 2.3%), OR = 2.62 (1.63-4.2), p < 0.001. The results were significant after adjusting for age, sex, smoking, and BMI. Correlations between genetic effects on chronic bronchitis and type 2 diabetes, and between genetic effects on diagnosed COPD and type 2 diabetes, respectively, were 0.33 (0.00-0.79), p = 0.103, and 0.43 (0.00-0.98), p = 0.154. Non-shared environmental correlations between chronic bronchitis and type 2 diabetes were -0.13 (-0.43 to 0), p = 0.498 and diagnosed COPD and type 2 diabetes -0.12 (-0.48 to 0), p = 0.665. Patients with chronic bronchitis or COPD have an increased risk of type 2 diabetes independent of sex, age, smoking and BMI. The genetic correlation between type 2 diabetes and chronic bronchitis was 33% and type 2 diabetes and COPD was 43%, however neither were statistically significant. The increased risk of type 2 diabetes should be accommodated in the management of patients with chronic bronchitis or COPD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Respiratory medicine 05/2015; DOI:10.1016/j.rmed.2015.05.015 · 2.92 Impact Factor
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    ABSTRACT: Allergic rhinitis triggered by grass pollen is a common disease, affecting millions of people worldwide. Treatment consists of symptom-alleviating drugs, such as topical corticosteroids or antihistamines. Another option is potentially curative immunotherapy, currently available as sublingual and subcutaneous treatment. We investigated the potential differences in the prevalence and severity of adverse events related to subcutaneous and sublingual immunotherapy against grass pollen-induced allergic rhinitis. A thorough literature search was performed using PubMed and EMBASE. The findings were compared with the available summaries of product characteristics and with commercial pharmacology databases (Micromedex). The majority of available safety data originates from registered products of standardized allergens. A surprisingly large percentage of drugs, especially those used in the United States, have no systematically collected safety data. No sufficiently powered randomized trials comparing sublingual and subcutaneous immunotherapy were available, but general safety assessments indicate that sublingual tablet treatment is safer than subcutaneous treatment. Not all commonly used immunotherapy drugs are officially registered and not all have systematically collected safety data. This is especially true for older drugs used in the United Stages. In contrast, newer drugs that have undergone extensive clinical testing have better documentation, but unified collection of safety data is still lacking. Considering the evidence available, most drugs elicit similar side effects from the same organ systems, and symptoms from the sublingual drug classes are probably less severe. However, a head-to-head comparison of safety and efficacy is lacking. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Basic & Clinical Pharmacology & Toxicology 05/2015; DOI:10.1111/bcpt.12416 · 2.29 Impact Factor
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    ABSTRACT: Asthma is a common chronic disease among young adults, and several studies have reported increased mortality rates in patients with asthma. However, no study has described sudden unexpected death in a nationwide setting in patients with uncontrolled asthma. We defined uncontrolled asthma as a previous hospital admittance because of asthma (of any severity) or when asthma was considered to have influenced the death according to the death certificate. The purpose of this study is to increase the medical focus on young persons with uncontrolled asthma and thereby hopefully aid in preventing sudden unexpected deaths. We therefore aimed to describe clinical characteristics, symptoms, causes of death, and contact with the healthcare system prior to sudden unexpected death in young persons with uncontrolled asthma. Through the review of death certificates, we found 625 sudden unexpected death cases in individuals aged 1-35 years in Denmark from 2000 to 2006. Of those, 49 persons with uncontrolled asthma were identified. Previous contacts with the healthcare system were identified, and available records from general practitioners were retrieved. We identified 49 individuals who suffered from uncontrolled asthma. This corresponds to an incidence rate of 0.32 per 100,000 person-years. The cause of death in 31 cases (63%) was sudden cardiac death, and in 13 cases (27%), it was a fatal asthma attack. Symptoms (chest pain, dyspnea, seizures, general malaise, syncope, and palpitations) prior to death were reported in 41 (84%) of the cases. In 34 (69%) of the cases, antecedent symptoms (symptoms >24 hours before death) were present, and 28 (57%) patients had prodromal symptoms (symptoms <24 hours before death). The most common antecedent symptoms were dyspnea and chest pain, whereas the most common prodromal symptoms were dyspnea, general malaise, and/or fatigue. Twenty-eight patients (57%) sought medical advice from a general practitioner and/or emergency department due to these symptoms. The cause of death was predominantly sudden cardiac death followed by fatal asthma attack. We found that 41 (84%) of patients suffered from symptoms prior to death and that 28 (57%) sought medical advice from the emergency department and/or general practitioners.
    BMC Pulmonary Medicine 04/2015; 15(1):35. DOI:10.1186/s12890-015-0033-z · 2.49 Impact Factor
  • Revue Française d Allergologie 04/2015; 55(3):266. DOI:10.1016/j.reval.2015.02.162 · 0.22 Impact Factor
  • Revue Française d Allergologie 04/2015; 55(3):271-272. DOI:10.1016/j.reval.2015.02.177 · 0.22 Impact Factor
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    ABSTRACT: To examine the association between early menarche and risk of post-menarcheal asthma. Using data from two multidisciplinary questionnaire surveys, conducted eight years apart, we prospectively studied 10,648 female twins, 12-41 years of age, from the nationwide Danish Twin Registry. Early menarche was defined as menarche before 12 years of age. We performed a cohort analysis and a co-twin control analysis including twin pairs discordant for incident asthma. Early menarche was observed in 9.3% of the individuals. The eight-year cumulative incidence of asthma was higher in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31-2.22), p < 0.001; also after adjustment for BMI, current age, physical activity, education, and smoking, OR = 1.53 (1.15-2.04), p = 0.003. The unadjusted risk of asthma was increased by 8% (1-15%), p = 0.041 per year earlier menarche occurred. Among 167 twin pairs discordant for incident asthma, there was a non-significant tendency towards early menarche being more common in the asthmatic than the non-asthmatic co-twin (12.0 vs. 9.6%), OR = 1.57 (0.61-4.05), p = 0.350. The risk of asthma was not uniform in discordant monozygotic and dizygotic twins. Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non-genetic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Respiratory medicine 03/2015; 109(5). DOI:10.1016/j.rmed.2015.03.007 · 2.92 Impact Factor
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    ABSTRACT: Exacerbations are a key outcome in clinical research, providing patient-relevant information about symptomatic control, health state and disease progression. Generally considered as an episode of (sub)acute deterioration of respiratory symptoms, a precise, clinically useful definition is needed for use in clinical trials. Focussing on moderate exacerbations, this opinion piece reviews landmark trials and current guidelines to provide a practical definition of a moderate exacerbation. Specifically, we adapt the ATS/ERS consensus statement of terminology Reddel et al. (2009) [1] which provides a conceptual (or 'theoretical') definition for moderate exacerbations, to an operational (or 'practical') criterion suitable for use in clinical research. The proposed definition for a moderate exacerbation requires ≥1 of the following criteria combined with a change in treatment: a) nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights or an increase of ≥0.75 from baseline in daily symptom scores on 2 consecutive days; b) increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase: 4 puffs/day); c) ≥20% decrease in PEF from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline and/or d) visit to the emergency room/trial site for asthma treatment not requiring systemic corticosteroids. A clinically and patient-relevant, operational definition of moderate exacerbations is needed. The proposed definition has been endorsed by the EMA Scientific Advice Working Party in 2011and needs to be trialled in forthcoming clinical studies. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Respiratory Medicine 02/2015; 109(5). DOI:10.1016/j.rmed.2015.01.012 · 2.92 Impact Factor
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    ABSTRACT: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease and report the AR results. Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). In the subgroup, the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was -0.78 (95% confidence interval -1.47 to -0.07, relative difference 28.8%, P = .0357). Furthermore, a significant difference was found for the total score of the Rhinitis Quality of Life Questionnaire with Standardized Activities RQLQ(S) and for the individual domains: activities, sleep, non-nose and non-eye symptoms, and nasal symptoms. For the TCRS and Rhinitis Quality of Life Questionnaire score, a dose response was seen, with numerically lower, nonsignificant differences for 1 and 3 SQ-HDM. The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups. No safety concerns were observed. Efficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Questionnaire score in subjects with AR present at baseline. The treatment was well tolerated. EudraCT, no 2006-001795-20; ClinicalTrials.gov, identifier NCT00389363. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2015; 114(2):134-140.e1. DOI:10.1016/j.anai.2014.11.015 · 2.75 Impact Factor
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    ABSTRACT: Abstract Aim: To examine the relationship between body mass index (BMI) and different indicators of asthma severity in a large community-based sample of Danish adolescents and adults. Methods: A total of 1,186 subjects, 14-44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore height and weight, skin test reactivity, lung function, and airway responsiveness were measured. Results: A total of 516 individuals had asthma. The mean BMI was 24.9 kg/m(2) (SD=5.1). Asthma severity measured by GINA score increased with increasing BMI (p=0.009). The result remained significant after adjusting for age, sex, medication use for asthma and smoking (p=0.010). Severity of individual asthma symptoms; cough (p=0.002) and chest tightness (p=0.023) was also significantly related to BMI, whereas severity of wheezing and shortness of breath was not. Airway obstruction was more pronounced in subjects with increased BMI (p<0.001) but the effect disappeared after adjustment for covariates (p=0.233). Lung function, airway responsiveness, and atopy were not significantly related to BMI as were use of medication for asthma and adherence to treatment. Conclusions: In adults, increased body mass index predicts severity of asthma symptoms but not objective asthma traits.
    Journal of Asthma 01/2015; DOI:10.3109/02770903.2015.1005840 · 1.83 Impact Factor
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    ABSTRACT: It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls. We found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon.
    PLoS ONE 01/2015; 10(7):e0127228. DOI:10.1371/journal.pone.0127228 · 3.53 Impact Factor
  • European Respiratory Journal 12/2014; 45(2). DOI:10.1183/09031936.00187514 · 7.13 Impact Factor
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    ABSTRACT: We read with interest the report by Fang and colleagues of the relationship between psoriasis and asthma in a large retrospective case-control study from Taiwan [1]. The study found a 1.38-fold increased risk of asthma among patients with psoriasis, and with an increasing risk according to higher age of the patients. However, although adjustment for age, sex, and selected comorbidities was performed the study lacked important confounder control, particularly for smoking and body mass index.This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 12/2014; 172(6). DOI:10.1111/bjd.13637 · 4.10 Impact Factor
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    ABSTRACT: Asthma is the most frequent chronic disease among young adults, not least in the western societies, with an even higher frequency among elite athletes. Asthma consists of airway inflammation and smooth muscle contraction, normally treated with antiasthma therapy, some of which have side effects. n-3 LCPUFA in fish oil (FO) has antiinflammatory effects, and some studies have shown clinical effects of FO on asthma. We aimed to study if FO has an anti-asthma effect in elite athletes with asthma. The study was a randomized, double-blinded clinical trial. Ten elite athletes with a medical certificate allowing the use of asthma medication, age 15-46 years, were recruited among elite athletes supported by the Team Denmark Organization. All subjects had a positive mannitol test prior to enrollment. Depending on whether they used inhaled corticosteroids or not, the subjects were randomly assigned in pairs to either FO (2 g EPA and 1.3 g DHA) or soy oil capsules (SO) for 8 weeks. Change in forced expiratory volume (FEV1) after exercise, NO excretion, sputum cell count and use of medication were measured before and after intervention. There was a slight trend towards increased exercise-induced decrease in lung function, use of asthma medication and respiratory inflammation in the FO-group, but the changes were neither significant nor clinically relevant.
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    ABSTRACT: Background: Chronic rhinosinusitis (CRS) is a common health problem that is subclassified as CRS with nasal polyps (CRSwNPs) or CRS without NPs (CRSsNP). In accordance with the united airways concept, CRSwNPs frequently coexists with asthma but to date, this association remains unexplained and its strength is uncertain. Here, we aimed to examine the association between CRSwNPs and asthma in collaboration between the neighboring specialities: otorhinolaryngology and respiratory medicine. Methods: A prospective clinical study was performed comprising 40 CRS patients scheduled for functional endoscopic sinus surgery and 21 control persons. We performed nasal endoscopy, peak expiratory flow, spirometry, and bronchodilation tests. In selected cases, additional pulmonary tests were performed. Atopy was assessed by skin-prick test or by measuring specific IgE in serum. Results: Asthma was diagnosed in 26 patients with CRSwNPs (65%; odds ratio = 5.9 [1.79, 19.65]; p = 0.003), and 5 control persons (24%). Twenty-five percent of the CRSwNP patients had undiagnosed asthma. Atopy was not significantly associated with CRSwNPs (p = 0.39) or with coexisting asthma within the CRSwNP group (p = 0.50). Conclusion: Compared with previous studies, we found a very high prevalence of asthma and, frequently, asthma was undiagnosed. Furthermore, CRSwNPs was associated with chronic bronchitis and, in those with asthma, lower airway obstruction. These results call for a closer collaboration between otorhinolaryngology and respiratory medicine in relation to patients with CRSwNPs, in research as well as in clinical practice.
    American journal of rhinology & allergy 10/2014; 28(5). DOI:10.2500/ajra.2014.28.4076 · 2.18 Impact Factor
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    ABSTRACT: Background Late onset asthma is associated with more severe disease and higher morbidity than in younger asthma patients. This may in part relate to under recognition of asthma in older adults, but evidence on the impact of patient age on diagnostic assessment of asthma in a specialist setting is sparse. Aim To examine the impact of patient age on the type and proportion of diagnostic tests performed in patients undergoing specialist assessment for asthma. Methods Data from a clinical population consisting of all patients consecutively referred over a 12 months period to a specialist clinic for assessment of asthma were analysed. Results A total of 224 patients with asthma or suspected asthma were referred during the 12 month period; 86 adults aged < 35 years, 95 aged 35-55 years and 43 aged > 55 years. Symptom characteristics were similar, but adults > 35 years had a lower lung function than younger adults, and were more frequently smokers. However, a regression analysis showed that older age was associated with a lower likelihood of diagnostic assessment with a reversibility test, a bronchial challenge test, or measurement of exhaled NO, independently of a known diagnosis of asthma, smoking habits and lung function at referral. Conclusion A lower level of diagnostic assessment was observed already after the age of 35 years, indicating a risk for under diagnosis of asthma at an earlier patient age than previously thought.
    Respiratory Medicine 10/2014; 108(10). DOI:10.1016/j.rmed.2014.07.005 · 2.92 Impact Factor
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    ABSTRACT: The aim of the present study was to examine the effect of beta2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca2+ release and uptake, and Na+/K+-ATPase-activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 M, EXP2, n = 20 M), where beta2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction of m.quadriceps (MVC) was measured, followed by exercise to fatigue at 120% of Vo2max. A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m.quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45-s sprints. Non-fatigued MVC was 6±3 and 6±2% higher (P < 0.05) for terbutaline than placebo in EXP1 and EXP2. Furthermore, peak twitch force was 11±7% higher (P < 0.01) for terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to same levels for terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half relaxation time prolonged (P < 0.05) with terbutaline. Rates of SR Ca2+ release and uptake at 400 nM [Ca2+] were 15±5 and 14±5% (P < 0.05) higher for terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na+/K+-ATPase-activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in Vmax at time of fatigue. In conclusion, increased contractile force induced by beta2-adrenergic stimulation is associated with enhanced rate of Ca2+ release in humans. While beta2-adrenergic stimulation elicits positive inotropic and lusitropic effects of non-fatigued m.quadriceps, these effects are blunted when muscles fatigue.This article is protected by copyright. All rights reserved
    The Journal of Physiology 10/2014; 592(24). DOI:10.1113/jphysiol.2014.277095 · 4.54 Impact Factor
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    ABSTRACT: Background Eosinophil cationic protein (ECP) is one of four basic proteins of the secretory granules of eosinophils. It has a variety of functions associated with inflammatory responses. Little is known about the causes for variation in serum ECP levels.AimTo identify factors associated with variation in serum ECP and to determine the relative proportion of the variation in ECP due to genetic and non-genetic factors, in an adult twin sample.MethodsA sample of 575 twins, selected through a proband with self-reported asthma, had serum ECP, lung function, airway responsiveness to methacholine, exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels.ResultsSex (regression coefficient =-0.107, p<0.001), BMI (0.007, p=0.028) and airway responsiveness to methacholine (0.074, p=0.001) were significantly associated with ECP. Adjusted for these factors, ECP correlated 0.53 (p<0.001) and 0.27 (p=0.001) in monozygotic and dizygotic twins, respectively (p-value for difference=0.05). According to the most parsimonious variance component model, genetic factors accounted for 57% (CI: 42-72%, p<0.001) of the variance in ECP levels, whereas the remainder (43%) was ascribable to non-shared environmental factors. The genetic correlation between ECP and airway responsiveness to methacholine was statistically non-significant (r=-0.11, p=0.50).Conclusion Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance.This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 10/2014; DOI:10.1111/cea.12445 · 4.32 Impact Factor

Publication Stats

4k Citations
972.85 Total Impact Points

Institutions

  • 1995–2015
    • Bispebjerg Hospital, Copenhagen University
      • • Department of Dermatology
      • • Institute for Sports Medicine
      • • Department of Pulmonary Medicine
      København, Capital Region, Denmark
  • 2013–2014
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1990–2011
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1990–2006
    • Copenhagen University Hospital Hvidovre
      • • Department of Clinical Biochemistry
      • • Department of Infectious Diseases
      Hvidovre, Capital Region, Denmark
  • 2005
    • Statens Serum Institut
      • Department of Epidemiology Research
      København, Capital Region, Denmark
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 2004
    • University of Copenhagen
      København, Capital Region, Denmark
  • 2003
    • National Institute of Public Health, Denmark
      København, Capital Region, Denmark
    • National Institute of Public Health
      København, Capital Region, Denmark
  • 1996
    • Rigshospitalet
      København, Capital Region, Denmark
  • 1994
    • National University (California)
      San Diego, California, United States
    • Glostrup Hospital
      • Department of Paediatrics
      København, Capital Region, Denmark