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Sökning: WFRF:(Langhammer Arnulf Professor)

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1.
  • Ellingsen, Jens, 1979- (författare)
  • Chronic obstructive pulmonary disease: exacerbations and mortality : Prognostic value of biomarkers and comorbidities
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. COPD is associated with systemic inflammation, and comorbidities are common. A characteristic feature is acute exacerbations (AECOPDs), i.e., episodes of worsening symptoms. AECOPDs are associated with increased mortality.Aim: To find prognostic risk factors for COPD mortality and AECOPDs, focusing on comorbidities and inflammatory biomarkers.Methods: In Paper I, associations between comorbidities, pharmacological treatment, and mortality were analysed in a real-world cohort of almost 18,000 primary care COPD patients. Data from medical records and national registers were analysed in Cox proportional hazards regressions.Papers II–IV were based on the Tools Identifying Exacerbations (TIE) cohort study of 572 COPD patients recruited from primary and secondary care in three Swedish regions. Participants were invited to three yearly visits, including phlebotomy, spirometry, and health questionnaires.In Paper II, the ability of blood neutrophil-to-lymphocyte ratio (NLR) and eosinophils (B-Eos) to predict AECOPDs was analysed with mixed-effects logistic regressions.In Paper III, the ability of C-reactive protein (CRP), fibrinogen, blood leukocytes (B-Leu), and four blood cell indices to predict AECOPDs was analysed with ordinal logistic regressions.In Paper IV, an algorithm for clinical phenotyping previously developed to predict mortality was studied. The algorithm’s ability to predict AECOPDs and mortality was analysed with Cox proportional hazards regressions; additionally, the identified phenotypes were analysed concerning differences in blood-based inflammatory biomarkers.Results: Several comorbidities, including heart diseases, were associated with increased mortality risk. Some pharmacological treatments were associated with increased or decreased mortality risk (Paper I). NLR, B-Eos, CRP, fibrinogen, and B-Leu (Papers II–III) predicted AECOPDs after adjustment for confounders, whereas other blood cell indices were of limited value (Paper III). The clinical phenotyping algorithm predicted AECOPDs and mortality, and the phenotypes had different patterns of inflammatory biomarkers (Paper IV).Conclusions: Comorbidities, particularly heart diseases, are substantial risk factors for mortality in COPD and should be an integral part of management of COPD patients. NLR, B-Eos, CRP, fibrinogen, and B-Leu are independent predictors of AECOPDs and should be further investigated as parts of, e.g., risk prediction tools. A previously developed algorithm for clinical phenotyping predicts mortality and AECOPDs.
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2.
  • Backman, Helena, 1979- (författare)
  • Lung function and prevalence trends in asthma and COPD
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Asthma and chronic obstructive pulmonary disease (COPD) are common obstructive airway diseases with a substantial burden in terms of morbidity, mortality and costs. Smoking is the single most important risk factor for COPD, and is associated with incident asthma. It is important to know if the prevalence of asthma and COPD is increasing or decreasing in the population in order to effectively allocate health care resources. The definitions of these diseases have varied over time which makes it difficult to measure changes in prevalence. The preferred method is to estimate the prevalence with the same procedures and definitions based on cross-sectional population samples with identical age distributions in the same geographical area at different time points. Measurements of lung function (spirometry) are required to diagnose COPD, and spirometry is used to evaluate disease severity and progress of both asthma and COPD, where observed values are compared to reference values. The most commonly used reference values in Sweden are published during the mid 1980s, and there are few evaluations of how appropriate they are today based on Swedish population samples. The aim of the thesis was to estimate trends in the prevalence of asthma and COPD in relation to smoking habits, and to evaluate and estimate reference values for spirometry.Methods: The project was based on population-based samples of adults from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Postal questionnaires were sent to large cohorts, recruited in 1992 (n=4851, 20-69 years), 1996 (n=7420, 20-74 years) and 2006 (n=6165, 20-69 years), respectively. The questionnaire included questions on respiratory symptoms and diseases, their comorbidities and several possible risk factors including smoking habits. Structured interviews and spirometry were performed in random samples of the responders to the 1992 and 2006 surveys, of which n=660 (in 1994) and n=623 (in 2009) were within identical age-spans (23-72 years). The trend in asthma prevalence was estimated by comparing the postal questionnaire surveys in 1996 and 2006, and the trend in COPD prevalence was estimated by comparing the samples participating in dynamic spirometry in 1994 and 2009, respectively. The prevalence of COPD was estimated based on two different definitions of COPD. Commonly used reference values for spirometry were evaluated based on randomly sampled healthy non-smokers defined in clinical examinations of participants in the 2006 postal questionnaire (n=501). The main focus of the evaluation was the global lung function initiative (GLI) reference values published in 2012, for which Z-scores and percent of predicted values were analysed. New sex-specific reference values for spirometry were estimated by linear regression, with age and height as predictors. These new OLIN reference values were also evaluated on a sample of healthy non-smokers identified in the population-based West Sweden Asthma Study.Results: Although the prevalence of smoking decreased from 27.4% to 19.1%, p<0.001, between 1996 and 2006, the prevalence of physician-diagnosed asthma increased from 9.4% to 11.6%, p<0.001. The prevalence of symptoms common in asthma such as recurrent wheeze did not change significantly between the surveys or tended to decrease, while bronchitis symptoms such as cough and sputum production decreased significantly. The evaluation of the GLI reference values showed that the predicted values were significantly lower compared to the observed values in Norrbotten, which makes the percent of predicted too high. This was especially true for FVC percent predicted with a mean of 106%. In general, the deviations were more pronounced among women. New OLIN reference values valid for the Norrbotten sample were modelled and showed a high external validity when applied on the sample from western Sweden. The prevalence of moderate to severe COPD decreased substantially over the 15-year period between 1994 and 2009, regardless of definition.Conclusions: In parallel with substantially decreased smoking habits in the population between 1996 and 2006, the prevalence of several airway symptoms decreased while the prevalence of physician-diagnosed asthma increased. These results suggest increased diagnostic activity for asthma, but may also suggest that the asthma prevalence has continued to increase. In contrast to asthma, the prevalence of COPD tended to decrease and moderate to severe COPD decreased substantially. The continuous decrease in smoking in Sweden during several decades prior to the study period is most likely contributing to these results. The evaluation of reference values showed that the GLI reference values were lower than the observed spirometric values in the population, especially for women, why the new up-to date reference values may be of importance for disease evaluation in epidemiology and in the health care as well.
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3.
  • Guida, Florence, et al. (författare)
  • The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
  • 2021
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLOS). - 1549-1277 .- 1549-1676. ; 18:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., −0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10−5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10−3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.Conclusions: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI - the principal modifiable risk factor of kidney cancer.
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4.
  • Gustafsson, Stefan, et al. (författare)
  • Markers of imminent myocardial infarction
  • 2024
  • Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590.
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.
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