| 1. |
- Kraen, Morten, et al.
(author)
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Brain natriuretic peptide levels in middle aged subjects with normal left ventricular function in relation to mild-moderate COPD
- 2018
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In: Clinical Respiratory Journal. - : Wiley. - 1752-6981. ; 12:3, s. 1061-1067
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Journal article (peer-reviewed)abstract
- Background: Levels of plasma brain natriuretic peptide (BNP) have been shown to be elevated in chronic obstructive pulmonary disease (COPD) especially in connection with cor pulmonale (CP) and the late stages of the disease. BNP is also raised in left sided heart failure which sometimes coincides with COPD. Whether BNP is elevated in subjects with mild-moderate stable COPD and normal left ventricular function is not clear. Objective: To investigate BNP levels in subjects with mild-moderate COPD and normal left ventricular function. Methods: This was a cross sectional study of 450 subjects from a population-based respiratory questionnaire survey. All subjects were examined with echocardiography and spirometry and blood samples were drawn for BNP measurements. Subjects with left sided heart disease (n=26) or echocardiographic signs of elevated filling pressure (n=75), COPD stages III and IV (n=5) or missing data (n=13) were excluded. Results: In the final study population (n=331) spirometry identified 86 subjects with COPD (GOLD stage I, n=65 and GOLD stage II, n=21). In comparison with the rest of the study population subjects with COPD were significantly older, longer and with a male predominance. In a multivariate linear regression analysis with log-normalized (lnBNP) as the dependent variable a significant correlation was found with age, left atrial volume, body surface area and haemoglobin, but not with any pulmonary variables. Even when comparing groups no significant difference could be found between the plasma levels of lnBNP in normal subjects (1.8±0.7 mean±SD, pmol/L) subjects and in COPD subjects (1.9±0.7, P=0.47). Conclusions: In a population with normal left ventricular function no significant differences in BNP levels between stable mild-moderate COPD subjects and normal individuals could be found.
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| 2. |
- Kraen, Morten
(author)
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Chronic obstructive pulmonary disease. Aspects of smoking, biomarkers and cardiovascular disease.
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Chronic obstructive pulmonary disease (COPD) is a common and preventable disease characterized by airflow obstruction and emphysema development. COPD often coexist with cardiovascular disease (CVD) and both diseases have common risk factors i.e. age and smoking and shared features i.e. chronic inflammation. Smoking is of particular interest as it substantially increases the risk of developing COPD and CVD and is known to elicit systemic inflammatory responses. COPD (and CVD as well) often go unnoticed for years in the preclinical or early stage of disease so arguably, early disease detection is of great importantance and vital to improve prognosis. Plasma biomarkers of inflammation could be instrumental in this task and in recent years many new biomarkers have been described, but very few make it into clinical use.This thesis deals with COPD and its comorbidity (CVD) and their common risk factor smoking, with focus on the role of new and established biomarkers of COPD and atherosclerosis.All papers in this thesis are cross sectional studies based on the ROLLS study population. ROLLS was an invitational study including 450 subjects on the basis of self-reported smoking habits and pulmonary symptoms. All participants underwent a one day study protocol consisting of transthoracic echocardiography, lung function tests, carotid ultrasound examination, resting blood pressure measurement, blood sample analysis and a questionnaire.In paper I the aim was to study the impact of smoking status on echocardiographic variables of cardiac function in a population without clinically evident cardiopulmonary disease. Here, no convincing effect of current or prior smoking on echocardiographic variables of systolic and diastolic function could be detected, even if smokers had significantly higher cardiac index due to a slightly increased heart rate. In paper II the aim was to examine whether brain natriuretic peptide (BNP), an established marker of cardiac dysfunction, could be used as a biomarker of COPD in a population with normal cardiac function. The results showed no significant differences in BNP levels between subjects with COPD and controls. Thus, the clinical value of BNP in this setting is limited. Paper III evaluated matrix metalloproteinases (MMP´s) as biomarkers of COPD and atherosclerosis and the impact of smoking. The results showed that MMP´s are influenced by smoking status and that MMP-1 and MMP-12 are independent predictors of concomitant COPD and carotid plaque even when adjusting for traditional risk factors.In paper IV the aim was to explore whether a novel inflammatory biomarker, fibroblast growth factor 23 (FGF23), was influenced by COPD status and impaired pulmonary function. The findings showed that FGF23 was associated with the presence of COPD even after adjusting for traditional risk factors, and that FGF23 was associated with impaired pulmonary function and gas exchange.In conclusion, this thesis evaluated the impact of smoking on cardiac function and MMP´s and explored the current (BNP) and future (MMP and FGF23) value of biomarkers in COPD and CVD
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| 3. |
- Kraen, Morten, et al.
(author)
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Echocardiographic consequences of smoking status in middle-aged subjects
- 2017
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In: Echocardiography. - : Wiley. - 0742-2822. ; 34:1, s. 14-19
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Journal article (peer-reviewed)abstract
- Background: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy population. Methods: Subjects (n=355) from a previous population-based respiratory questionnaire survey (never smokers, ex-smokers, and current smokers without significant chronic obstructive lung disease) were examined with echocardiography, and CI (L/min/m2) was calculated. Results: Current smokers had a higher CI than never smokers 2.61±0.52 L/min/m2 vs. 2.42±0.49 L/min/m2 (P<.01). Ex-smokers had a nonsignificant, numerically higher value for CI than never smokers 2.54±0.54 L/min/m2 vs. 2.42±0.49 L/min/m2 (P>.05). Smoking status had no significant effect on other echocardiographic variables. Conclusion: We conclude that currents smokers without known cardiac disease or significant chronic obstructive lung disease show signs of slightly altered hemodynamics.
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| 4. |
- Kraen, Morten, et al.
(author)
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Incremental Value of Exercise ECG to Myocardial Perfusion Single-Photon Emission Computed Tomography for Prediction of Cardiac Events
- 2023
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In: Journal of the American Heart Association. - 2047-9980. ; 12:9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Both myocardial perfusion single-photon emission computed tomography (MPS) and exercise ECG (Ex-ECG) carry prognostic information in patients with stable chest pain. However, it is not fully understood if combining the findings of MPS and Ex-ECG improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of chronic coronary syndrome, but Ex-ECG could still be of incremental prognostic importance. METHODS AND RESULTS: This study comprised 908 consecutive patients (age 63.3±9.4 years, 49% male) who performed MPS with Ex-ECG. Subjects were followed for 5 years. The end point was a composite of cardiovascular death, acute myocardial infarction, unstable angina, and unplanned percutaneous coronary intervention. National registry data and medical charts were used for end point allocation. Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients or absence of ischemia in 634 patients. Discordant results were found in 202 patients (MPS−/Ex-ECG+, n=126 and MPS+/Ex-ECG−, n=76). During follow-up, 95 events occurred. Annualized event rates significantly increased across groups (MPS−/Ex-ECG− =1.3%, MPS−/Ex-ECG+ =3.0%, MPS+/Ex-ECG− =5.1% and MPS+/Ex-ECG+ =8.0%). In multivariable analy-ses MPS was the strongest predictor regardless of Ex-ECG findings (MPS+/Ex-ECG−, hazard ratio [HR], 3.0, P=0.001 or MPS+/Ex-ECG+, HR,4.0, P<0.001). However, an abnormal Ex-ECG almost doubled the risk in subjects with normal MPS (MPS−/Ex-ECG+, HR, 1.9, P=0.04). CONCLUSIONS: In patients with chronic coronary syndrome, combining the results from MPS and Ex-ECG led to improved risk prediction. Even though MPS is the stronger predictor, there is an incremental value of adding data from Ex-ECG to MPS, especially in patients with normal MPS.
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| 7. |
- Nielsen, Kraen Vodder, et al.
(author)
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Marine diesel engine control to meet emission requirements and maintain maneuverability
- 2018
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In: Control Engineering Practice. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0967-0661 .- 1873-6939. ; 76, s. 12-21
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Journal article (peer-reviewed)abstract
- International shipping has been reported to account for 13% of global NOx emissions and 2.1% of global green house gas emissions. Recent restrictions of NOx emissions from marine vessels have led to the development of exhaust gas recirculation (EGR) for large two-stroke diesel engines. Meanwhile, the same engines have been downsized and derated to optimize fuel efficiency. The smaller engines reduce the possible vessel acceleration, and to counteract this, the engine controller must be improved to fully utilize the physical potential of the engine. A fuel index limiter based on air/fuel ratio was recently developed (Turbo, 2016), but as it does not account for EGR, accelerations lead to excessive exhaust smoke formation which could damage the engine when recirculated. This paper presents two methods for extending a fuel index limiter function to EGR engines. The methods are validated through simulations with a mean-value engine model and on a vessel operating at sea. Validation tests compare combinations of the two index limiter methods, using either traditional PI control for the EGR loop or the recently developed fast adaptive feedforward EGR control (Nielsen et al., 2017a). The experiments show that the extended limiters reduce exhaust smoke formation during acceleration to a minimum, and that the suggested limiter, combined with adaptive feedforward EGR control, is able to maintain full engine acceleration capability. Sea tests with engine speed steps from 35 to 50 RPM, made peak exhaust opacity increase by only 5% points when using the proposed limiter, whereas it increased 70% points without the limiter.
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| 8. |
- Vodder Nielsen, Kraen, et al.
(author)
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Adaptive feedforward control of exhaust recirculation in large diesel engines
- 2017
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In: Control Engineering Practice. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0967-0661 .- 1873-6939. ; 65, s. 26-35
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Journal article (peer-reviewed)abstract
- Environmental concern has led the International Maritime Organization to restrict NOx emissions from marine diesel engines. Exhaust gas recirculation (EGR) systems have been introduced in order to comply to the new standards. Traditional fixed-gain feedback methods are not able to control the EGR system adequately in engine loading transients so alternative methods are needed. This paper presents the design, convergence proofs and experimental validation of an adaptive feedforward controller that significantly improves the performance in loading transients. First the control concept is generalized to a class of first order Hammerstein systems with sensor delay and exponentially converging bounds of the control error are proven analytically. It is then shown how to apply the method to the EGR system of a two-stroke crosshead diesel engine. The controller is validated by closed loop simulation with a mean-value engine model, on an engine test bed and on a vessel operating at sea. A significant reduction of smoke formation during loading transients is observed both visually and with an opacity sensor. (C) 2017 Elsevier Ltd. All rights reserved.
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| 9. |
- Vodder Nielsen, Kraen, et al.
(author)
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Control-Oriented Model of Molar Scavenge Oxygen Fraction for Exhaust Recirculation in Large Diesel Engines
- 2017
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In: Journal of Dynamic Systems Measurement, and Control. - : ASME. - 0022-0434 .- 1528-9028. ; 139:2
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Journal article (peer-reviewed)abstract
- Exhaust gas recirculation (EGR) systems have been introduced to large marine engines in order to reduce NOx formation. Adequate modeling for control design is one of the bottlenecks to design EGR control that also meets emission requirements during transient loading conditions. This paper therefore focuses on deriving and validating a mean-value model of a large two-stroke crosshead diesel engine with EGR. The model introduces a number of amendments and extensions to previous, complex models and shows in theory and practice that a simplified nonlinear model captures all essential dynamics that is needed for EGR control. Our approach is to isolate and reduce the gas composition part of the more complex models using nonlinear model reduction techniques. The result is a control-oriented model (COM) of the oxygen fraction in the scavenge manifold with three molar flows being inputs to the COM, and it is shown how these flows are estimated from signals that are commonly available. The COM is validated by first comparing the output to a simulation of the full model, then by comparing with measurement series from two engines. The control-oriented nonlinear model is shown to be able to replicate the behavior of the scavenge oxygen fraction well over the entire envelope of load and blower speed range that are relevant for EGR. The simplicity of the new model makes it suitable for observer and control design, which are essential steps to meet the emission requirements for marine diesel engines that take effect from 2016.
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