| 1. |
- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)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.
(author)
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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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In: Respiratory Medicine. - 1532-3064. ; 93:8, s. 563-570
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Journal article (peer-reviewed)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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| 7. |
- Ekberg-Jansson, Ann, et al.
(author)
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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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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 95:5, s. 363-373
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Journal article (peer-reviewed)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.
(author)
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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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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:1, s. 40-47
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Journal article (peer-reviewed)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.
(author)
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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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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 94:3, s. 264-272
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Journal article (peer-reviewed)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.
(author)
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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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In: Clinical Epidemiology. - 1179-1349. ; 12, s. 783-796
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Journal article (peer-reviewed)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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| 11. |
- Plymoth, A., et al.
(author)
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Human bronchoalveolar lavage: biofluid analysis with special emphasis on sample preparation
- 2003
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In: Proteomics. ; 3:6
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Journal article (peer-reviewed)abstract
- Respiratory diseases are an important health problem throughout the world. Whether caused by industrial pollutants, infections, smoking, cancer or metabolic diseases, damage to the lungs and airways often lead to morbidity or death. Bronchoalveolar lavage (BAL) obtained by fiber-optic bronchoscopy is a biofluid mirroring the expression of normally secreted pulmonary proteins and the products of activated cells and destructive processes. The characterization of the proteome within this compartment provides an opportunity to establish temporal and prognostic indicators of airway disease. The objective of this study was to develop methods of analysis of BAL samples, which achieved the highest level of annotation of the expression map of this proteome. We have optimized the process of sample preparation after investigating a variety of techniques including dialysis, ultramembrane filtration, precipitation and gel filtration. We have further studied methods to remove albumin from BAL in order to unmask proteins hidden on two-dimensional gels. In a pilot application of the method, BAL protein profiles obtained from healthy nonsmokers and smokers at risk for developing chronic obstructive pulmonary disease showed distinct differences.
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| 13. |
- Strang, Susann, 1953, et al.
(author)
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Experience of Guilt and Strategies for Coping with Guilt in Patients with Severe COPD: A qualitative interview study
- 2014
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In: Journal of Palliative Care. - : SAGE Publications. - 0825-8597 .- 2369-5293. ; 30:2, s. 108-115
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Journal article (peer-reviewed)abstract
- Guilt is associated with an increased level of mood disturbance and a poorer quality of life. The aim of this study was to explore how patients with severe COPD view and experience guilt and the ways in which they cope with this guilt. A total of 31 COPD patients were interviewed about their perceptions and experiences of guilt. Qualitative content analysis was used to examine the interviews. In the descriptive (manifest) analysis, the categories "not feeling personal guilt" and "experiencing guilt" emerged; in the interpretative (latent) analysis, various strategies for dealing with guilt were identified for example, acceptance or blaming others. Relatively few patients reported that they felt guilt on a conscious level, but those who did expressed anguish, and remorse before God; some felt blamed by others. It is important that healthcare providers acknowledge the guilt that their patients express, since guilt may have adverse effects on the patients' overall health.
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| 14. |
- Stridsman, Caroline, et al.
(author)
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The Swedish National Airway Register (SNAR): development, design and utility to date
- 2020
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In: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 7:1
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Journal article (peer-reviewed)abstract
- Background: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. Aim: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. Methods: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. Results: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children <12 yr, 6545 adolescents 12-17 yr, and 57,344 adults >17 yr) and 38,117 with COPD. Depending on age and disease group, 43-77% had performed spirometry, 36-65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. Conclusion: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide.
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| 15. |
- Sundqvist, Martina, et al.
(author)
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Systemic Galectin-3 in Smokers with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis: The Impact of Exacerbations
- 2021
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In: International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 16, s. 367-377
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Journal article (peer-reviewed)abstract
- Purpose: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations. Patients and Methods: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth. Results: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with FINS or LTS. Nor did this level of Galectin3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations. Conclusion: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.
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| 16. |
- Tylen, U, et al.
(author)
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Emphysematous lesions and lung function in healthy smokers 60 years of age
- 2000
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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 94:1, s. 38-43
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Journal article (peer-reviewed)abstract
- We aimed to study the occurrence of emphysematous lesions in symptom free smoking men of about 60 years of age and in a matching group of never-smoking men and the relationship between pulmonary changes at high resolution computed tomography (HRCT) and lung function tests. Our investigation included 57 smoking and 32 never-smoking healthy men from a randomized epidemiological study. HRCT was performed at full inspiration with a 1.5 mm slice thickness and a 3 cm inter-slice distance. Evaluation was made by two radiologists unaware of smoking history. Emphysematous lesions were scored visually. Pulmonary function tests were performed including spirometry and diffusion capacity test (DLCO). Emphysematous changes were demonstrated in 25 of 57 smokers but in only one never-smoker. DLCO/VA was the most sensitive test for early emphysematous lesions. It also correlated with radiographical scoring. Emphysematous lesions were evident in 44% of the healthy symptom free smokers. HRCT may reveal early emphysematous lesions in smokers before clinical symptoms have developed.
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