| 1. |
- Porsbjerg, C., et al.
(författare)
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Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults
- 2018
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Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma ('difficult asthma') should undergo systematic assessment, in order to differentiate between true severe asthma, and 'difficult-to-treat' patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care.
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| 2. |
- Backman, Helena, et al.
(författare)
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Decreased prevalence of moderate to severe COPD over 15 years in northern Sweden
- 2016
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 114, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: The burden of COPD in terms of mortality, morbidity, costs and prevalence has increased worldwide. Recent results on prevalence in Western Europe are conflicting. In Sweden smoking prevalence has steadily decreased over the past 30 years. Aim: The aim was to study changes in prevalence and risk factor patterns of COPD in the same area and within the same age-span 15 years apart. Material and methods: Two population-based cross-sectional samples in ages 23-72 years participating at examinations in 1994 and 2009, respectively, were compared in terms of COPD prevalence, severity and risk factor patterns. Two different definitions of COPD were used; FEV1/FVC < LLN and FEV1/FVC < 0.7. The severity of COPD was assessed by FEV1, both as % of predicted and in relation to the LLN. Results: The prevalence of COPD decreased significantly from 9.5% to 6.3% (p = 0.030) according to the FEV1/FVC < LLN criterion, while the decrease based on the FEV1/FVC < 0.7 criterion from 10.5% to 8.5% was non-significant. The prevalence of moderate to severe COPD decreased substantially and significantly, and the risk factor pattern was altered in 2009 when, beside age and smoking, also socioeconomic status based on occupation was significantly associated with COPD. Conclusions: Changes in both prevalence and risk factor patterns of COPD were observed between surveys. Following a continuing decrease in smoking habits over several decades, a decrease in the prevalence of moderate to severe COPD was observed from 1994 to 2009 in northern Sweden.
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| 3. |
- Franssen, F. M. E., et al.
(författare)
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Lung Function Abnormalities in Smokers with Ischemic Heart Disease
- 2016
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 194:5, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The aim of the ALICE (Airflow Limitation in Cardiac Diseases in Europe) study was to investigate the prevalence of airflow limitation in patients with ischemic heart disease and the effects on quality of life, healthcare use, and future health risk. Objectives: To examine prebronchodilator and post-bronchodilator spirometry in outpatients aged greater than or equal to 40 years with clinically documented ischemic heart disease who were current or former smokers. Methods: This multicenter, cross-sectional study was conducted in 15 cardiovascular outpatient clinics in nine European countries. Airflow limitation was defined as post-bronchodilator FEV1/FVC less than 0.70. Measurements and Main Results: Among the 3,103 patients with ischemic heart disease who were recruited, lung function was defined for 2,730 patients. Airflow limitation was observed in 30.5% of patients with ischemic heart disease: 11.3% had mild airflow limitation, 15.8% moderate airflow limitation, 3.3% severe airflow limitation, and 0.1% very severe airflow limitation. Most patients with airflow limitation (70.6%) had no previous spirometry testing or diagnosed pulmonary disease. Airflow limitation was associated with greater respiratory symptomatology, impaired health status, and more frequent emergency room visits (P < 0.05). Conclusions: Airflow limitation compatible with chronic obstructive pulmonary disease affects almost one-third of patients with ischemic heart disease. Although airflow limitation is associated with additional morbidity and societal burden, it is largely undiagnosed and untreated.
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| 4. |
- Herold, Nikolas, et al.
(författare)
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Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:2, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults'. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP)(2-5), which causes DNA damage through perturbation of DNA synthesis(6). Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment(7-9). Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.
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| 5. |
- Jansson, Sven-Arne, et al.
(författare)
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Health care consumption and HRQOL in severe asthma in Sweden
- 2017
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Ingår i: Value in Health. - : ELSEVIER SCIENCE INC. - 1098-3015 .- 1524-4733. ; 20:9, s. A513-A513
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Severe asthma is a disabling and costly disease, often poorly controlled despite high-dosage controller medications. The objectives of this analysis were to estimate health care consumption and to investigate health-related quality of life (HRQOL) in a severe asthma cohort, derived from a large-scale population survey in northern Sweden. Methods: Severe asthma was defined by US SARP criteria; high-dosage inhaled corticosteroids (ICS) by GINA 2014 criteria. In total, 32 patients with severe asthma were invited to a clinical examination and structured interview. Retrospective data of all asthma-related direct and indirect resource consumption during the last year were collected following a defined protocol. HRQOL was assessed by four patient-reported outcome measures: two general measures (SF-36; EQ-5D) and two disease-specific measures (SGRQ; ACT). The cohort was divided into two groups —patients with (OCS) or without maintenance oral corticosteroid (non-OCS) treatment. Results: Health care resource utilization was greater in the OCS-group compared with the non-OCS group. Mean annual number of visits to specialist care was 2.0 in the OCS group vs. 0.5 visits in the non-OCS group. Four patients in the OCS group had early retirement vs. none in the non-OCS group. HRQOL was worse in the OCS group, both when measured with general and disease-specific instruments. The Mental and Physical Component Summary scores of the SF-36 in the OCS vs. non-OCS group were 50.1 vs. 40.7 and 55.8 vs. 44.4, respectively. Similarly, the total SGRQ scores indicated worse HRQOL for the OCS-group compared with the non-OCS group (37.0 vs. 27.0). Conclusions: In this severe asthma population, patients treated with maintenance OCS consumed more health care resources, were more frequently early retired, and had worse HRQOL compared with those not receiving maintenance OCS. The results indicate a need for improved treatment for patients with severe asthma on maintenance OCS. Sponsor: AstraZeneca.
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| 6. |
- Lundbäck, Peter, et al.
(författare)
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A novel high mobility group box 1 neutralizing chimeric antibody attenuates drug-induced liver injury and postinjury inflammation in mice
- 2016
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 64:5, s. 1699-1710
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (APAP) overdoses are of major clinical concern. Growing evidence underlines a pathogenic contribution of sterile postinjury inflammation in APAP-induced acute liver injury (APAP-ALI) and justifies development of anti-inflammatory therapies with therapeutic efficacy beyond the therapeutic window of the only current treatment option, N-acetylcysteine (NAC). The inflammatory mediator, high mobility group box 1 (HMGB1), is a key regulator of a range of liver injury conditions and is elevated in clinical and preclinical APAP-ALI. The anti-HMGB1 antibody (m2G7) is therapeutically beneficial in multiple inflammatory conditions, and anti-HMGB1 polyclonal antibody treatment improves survival in a model of APAP-ALI. Herein, we developed and investigated the therapeutic efficacy of a partly humanized anti-HMGB1 monoclonal antibody (mAb; h2G7) and identified its mechanism of action in preclinical APAP-ALI. The mouse anti-HMGB1 mAb (m2G7) was partly humanized (h2G7) by merging variable domains of m2G7 with human antibody-Fc backbones. Effector function-deficient variants of h2G7 were assessed in comparison with h2G7 in vitro and in preclinical APAP-ALI. h2G7 retained identical antigen specificity and comparable affinity as m2G7. 2G7 treatments significantly attenuated APAP-induced serum elevations of alanine aminotransferase and microRNA-122 and completely abrogated markers of APAP-induced inflammation (tumor necrosis factor, monocyte chemoattractant protein 1, and chemokine [C-X-C motif] ligand 1) with prolonged therapeutic efficacy as compared to NAC. Removal of complement and/or Fc receptor binding did not affect h2G7 efficacy. Conclusion: This is the first report describing the generation of a partly humanized HMGB1-neutralizing antibody with validated therapeutic efficacy and with a prolonged therapeutic window, as compared to NAC, in APAP-ALI. The therapeutic effect was mediated by HMGB1 neutralization and attenuation of postinjury inflammation. These results represent important progress toward clinical implementation of HMGB1-specific therapy as a means to treat APAP-ALI and other inflammatory conditions. (Hepatology 2016;64:1699-1710).
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| 7. |
- Makowska, J. S., et al.
(författare)
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Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA(2)LEN) survey
- 2016
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 71:11, s. 1603-1611
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. MethodsThe GA(2)LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. ResultsThe mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. ConclusionOur study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.
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