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- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 6. |
- Ekberg-Jansson, A, et al.
(författare)
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A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space
- 1999
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Ingår i: Respiratory Medicine. - 1532-3064. ; 93:8, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- In this study healthy never-smoking subjects (n = 18) were recruited from a population study. Bronchoalveolar lavage (BAL), blood lymphocytes and bronchial biopsies, analysed both in the epithelium and lamina propria, were stained for T and B lymphocytes, natural killer (NK) cells and different subpopulations of T lymphocytes. In BAL, significantly higher proportions of T lymphocytes (CD3), T lymphocyte activation markers; HLA-DR, CD26+, CD49a+, CD54+ and CD69+, helper T (CD3+4+) and memory helper T lymphocytes (CD4+45RO+29+) and memory T lymphocytes (CD3+45RO+) were found, compared to blood. However, the proportion of IL-2 receptor-positive T lymphocytes (CD25+) was lower in BAL than in blood. A previously described higher ratio of CD3+4+/CD3+8+ in BAL than in blood (3.4 vs 1.7; P = 0.001) was confirmed. In bronchial biopsies, we found significantly higher numbers of CD8+ cell profiles per mm2 in the epithelial compared to the lamina propria compartment. We conclude that healthy never-smoking men have higher levels of activated memory T lymphocytes in BAL than in blood, and that the T-cell subpopulations differ in the epithelial compared to the lamina propria compartment in the bronchial mucosa and these compartments should be analysed separately. It is reasonable to think that there is a gradient from blood to the airway lumen where T cells are recruited from blood to take part in the defense towards damaging agents.
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- Ekberg-Jansson, Ann, et al.
(författare)
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Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT
- 2001
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 95:5, s. 363-373
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a risk factor for developing chronic obstructive pulmonary disease (COPD), but there are no good indicators for early identification of subjects who will develop symptomatic COPD. The aim of this study was to investigate inflammatory mechanisms related to changes in lung function and emphysematous changes on high resolution computed tomography (HRCT) in 'healthy' smokers. Subjects were 60-year-old men from a population study. Bronchoscopy was performed in 30 smokers and 18 who had never smoked. Blood tests, lung function measurements and HRCT were carried out in 58 and 34 subjects, respectively. In comparison with never-smokers, smokers had higher levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and lysozyme in blood, higher levels of MPO, interleukin-8 (IL-8) and HNL in bronchial lavage (BL), and of IL-8, HNL and interleukin-lbeta (IL-1beta) in bronchoalveolar lavage (BAL). Smokers also had lower levels of Clara cell protein 16 (CC-16) in blood. HNL in BL and BAL showed strong correlations to other inflammatory markers (MPO, IL-8, IL-1beta). The variations in MPO in BL were explained by variations in HNL (R2 =0.69), while these variations in BAL were explained by variations in HNL and IL-1beta (R2 = 0.76). DL(CO) was the lung function variable most closely related to MPO and IL-8 in BL and BAL and to IL-1beta in BAL. In a multiple regression analysis, MPO, IL-1beta, IL-8 and CC-16 in BL and MPO in BAL contributed to the explanation of variations in DL(CO) to 41% and 22%. respectively, independent of smoking habits. In smokers with emphysematous lesions on HRCT, HNL in BAL correlated to emphysema score (r(s) = 0.71). We conclude that 'healthy' smoking men with a near normal FEV1 show signs of inflammation in the lower airways that are related to a decrease in DL(CO) and to emphysematous lesions on HRCT. This inflammation seems to be the result of both monocyte/macrophage and neutrophil activation.
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| 8. |
- Ekberg-Jansson, A, et al.
(författare)
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Respiratory symptoms relate to physiological changes and inflammatory markers reflecting central but not peripheral airways. A study in 60-year-old 'healthy' smokers and never-smokers
- 2001
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in 'healthy' smokers. The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests--spirometry, carbon monoxide transfer (DLco) and the single-breath N2 method (N2 test)--together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken. Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DLCO and the N2 test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms. It is concluded that even when smokers consider themselves 'healthy' they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways.
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| 9. |
- Ekberg-Jansson, A, et al.
(författare)
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The expression of lymphocyte surface antigens in bronchial biopsies, bronchoalveolar lavage cells and blood cells in healthy smoking and never-smoking men, 60 years old
- 2000
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 94:3, s. 264-272
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Tidskriftsartikel (refereegranskat)abstract
- In this study we investigated if smoking subjects with a normal or slightly decreased lung function differ in the lymphocyte pattern compared to never-smokers. In a group of 'healthy' smokers (n = 58) and never-smokers (n = 34) 60 years old, we investigated the lymphocyte pattern in both BAL (n = 30 and n = 18 respectively), bronchial epithelium and lamina propria (n = 14 and n = 10 respectively) and blood. We found that all subjects, despite smoking history, had a higher number of CD8+ cells per mm2 in the epithelium compared to the lamina propria in the bronchial biopsies. In smokers, these CD8+ cells were significantly negatively correlated to FEV1 (r = -0.56, P = 0.04). In smokers, the number of CD8+ lymphocytes was higher and the T cell activation markers (CD57+ and CD28+) were lower in BAL, than in never-smokers. This last finding was also seen in blood for CD3+ 57+. We conclude, that in 'healthy' smokers the lymphocyte patterns are different compared to never-smokers, to some extent in BAL. There is also a relation between lymphocytes in the bronchial mucosa and lung function. This has previously been shown in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis but not in asymptomatic smokers.
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| 10. |
- Khalaf, K., et al.
(författare)
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Geographical and sociodemographic differences in discontinuation of medication for Chronic Obstructive Pulmonary Disease - A Cross-Classified Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA)
- 2020
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 12, s. 783-796
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Tidskriftsartikel (refereegranskat)abstract
- Background: While discontinuation of COPD maintenance medication is a known problem, the proportion of patients with discontinuation and its geographical and sociodemographic distribution are so far unknown in Sweden. Therefore, we analyse this question by applying an innovative approach called multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). Patients and Methods: We analysed 49,019 patients categorized into 18 sociodemographic contexts and 21 counties of residence. All patients had a hospital COPD diagnosis and had been on inhaled maintenance medication during the 5 years before the study baseline in 2010. We defined "discontinuation" as the absolute lack of retrieval from a pharmacy of any inhaled maintenance medication during 2011. We performed a cross-classified MAIHDA and obtained the average proportion of discontinuation, as well as county and sociodemographic absolute risks, and compared them with a proposed benchmark value of 10%. We calculated the variance partition coefficient (VPC) and the area under the receiver operating characteristics curve (AUC) to quantify county and sociodemographic differences. To summarize the results, we used a framework with 15 scenarios defined by the size of the differences and the level of achievement in relation to the benchmark value. Results: Around 18% of COPD patients in Sweden discontinued maintenance medication, so the benchmark value was not achieved. There were very small county differences (VPC=0.35%, AUC=0.54). The sociodemographic differences were small (VPC=4.98%, AUC=0.57). Conclusion: Continuity of maintenance medication among COPD patients in Sweden could be improved by reducing the unjustifiably high prevalence of discontinuation. The very small county and small sociodemographic differences should motivate universal interventions across all counties and sociodemographic groups. Geographical analyses should be combined with sociodemographic analyses, and the cross-classified MAIHDA is an appropriate tool to assess health-care quality.
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