| 1. |
- Larsson, Kjell
(författare)
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Tätare uppdateringar behövs av riktlinjer vid astma och KOL
- 2020
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 117
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Rekommendationer för omhändertagande vid astma och kroniskt obstruktiv lungsjukdom (KOL) uppdateras av Läkemedelsverket cirka vart sjunde år och ligger till grund för diagnostik och behandling framför allt i primärvården. Internationella riktlinjer för omhändertagande av astma (Global initiative for asthma, GINA) och KOL (Global initiative for chronic obstructive lung disease, GOLD) uppdateras årligen för att ny kunskap om behandling snabbt ska nå patienterna.De långa intervallen mellan uppdateringarna innebär att rekommendationerna hinner bli inaktuella innan nästa version publiceras, och Sverige hamnar i otakt med internationella riktlinjer. Farmakologisk behandling uppdateras av regionala läkemedelskommittéer, men rekommendationerna skiljer sig i olika delar av landet och stäms ofta inte av mot internationella riktlinjer, vilket leder till ojämlik behandling över landet. Läkemedelsverkets kunskapsstöd Läkemedelsboken innehöll ett kapitel om astma och KOL där man vid behov kunde uppdatera riktlinjer för primärvården, men detta stöd har lagts ned.Vid astma rekommenderar riktlinjerna kortverkande beta-2-agonister vid behov som enda behandling vid lindrig astma (steg 1) samt som tillägg till underhållsbehandling vid svårare sjukdom vid symtomgenombrott [1]. Som alternativ vid svårare astma (steg 3–5) rekommenderas inhalationssteroider i fast kombination med formoterol (steroid + formoterol) vid behov i stället för kortverkande b2-agonister [1]. Vid lindrig astma ger steroid + formoterol vid behov som enda behandling bättre resultat än endast kortverkande beta-2-agonister vid behov [2-5]. Vidare har steroid + formoterol (inhalerat vid behov) lika god exacerbationsförebyggande effekt som regelbunden behandling med inhalationssteroider och kortverkande beta-2-agonister vid behov trots en betydligt lägre kortisonbelastning [3, 5].I juni 2019 uppdaterades GINA:s astmarekommendationer genomgripande [6]. Här rekommenderas steroid + formoterol vid behov vid alla svårighetsgrader av astma. Kortverkande beta-2-agonister (salbutamol, terbutalin) vid behov är struket som förstahandsalternativ. Data indikerar att endast kortverkande beta-2-agonister vid behov faktiskt ökar risken för svåra exacerbationer och astmarelaterad mortalitet. Genom tillägg av inhalationssteroid till en snabb- och långverkande beta-2-agonist reduceras risken signifikant [6]. Vidare rekommenderas steroid + formoterol vid behov som alternativ till regelbunden behandling med inhalationssteroider på steg 2. Riktlinjerna har redan godkänts i flera länder.Vid KOL-behandling är två viktiga mål att lindra symtom och förebygga exacerbationer. Basbehandlingen för att uppnå detta är långverkande antikolinergika. Tillägg av långverkande beta-2-agonist till långverkande antikolinergika ger ytterligare god effekt på symtom, men en mer blygsam tilläggseffekt på exacerbationer [8]. Vid KOL ges inhalationssteroid i syfte att förebygga exacerbation. Hög nivå av eosinofiler i blod förekommer ofta vid KOL. Nyare forskning visar att blodeosinofili varierar hos patienter med KOL. Inhalationssteroider förebygger exacerbationer mer effektivt hos KOL-patienter med eosinofili, och blodeosinofili kan vägleda den förebyggande behandlingen [9-12]. Kontroll av eosinofiler i blod förespråkas i det senaste GOLD-dokumentet inför val av terapi och nydiagnostiserad KOL. Vid KOL och samtidig eosinofili anges inhalationssteroid + långverkande beta-2-agonist som tänkbart förstahandsalternativ i förebyggande syfte [13].Vi anser att behandling av patienter med astma och/eller KOL i Sverige ska baseras på rekommendationer från Läkemedelverket och att de senaste landvinningarna inom området måste återfinnas i riktlinjerna. Läkemedelsverket bör uppdatera riktlinjerna kontinuerligt, helst årligen. Detta kan göras av en mindre grupp experter genom en begränsad arbetsinsats till låg kostnad. Potentiella bindningar eller jävsförhållanden: Samtliga författare har deltagit i expertgrupp och/eller föreläst/haft utbildningsuppdrag hos företag som verkar inom området.
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| 2. |
- Kentson, Magnus, et al.
(författare)
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Factors associated with experience of fatigue, and functional limitations due to fatigue in patients with stable COPD
- 2016
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Ingår i: Therapeutic Advances in Respiratory Disease. - : Sage Publications. - 1753-4658 .- 1753-4666. ; 10:5, s. 410-424
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to determine the influence of selected physiological, psychological and situational factors on experience of fatigue, and functional limitations due to fatigue in patients with stable chronic obstructive pulmonary disease (COPD). Methods: In total 101 patients with COPD and 34 control patients were assessed for experience of fatigue, functional limitation due to fatigue (Fatigue Impact Scale), physiological [lung function, 6-minute walk distance (6MWD), body mass index (BMI), dyspnoea, interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hs-CRP), surfactant protein D], psychological (anxiety, depression, insomnia), situational variables (age, sex, smoking, living alone, education), and quality of life. Results: Fatigue was more common in patients with COPD than in control patients (72% versus 56%, p < 0.001). Patients with COPD and fatigue had lower lung function, shorter 6MWD, more dyspnoea, anxiety and depressive symptoms, and worse health status compared with patients without fatigue (all p < 0.01). No differences were found for markers of systemic inflammation. In logistic regression, experience of fatigue was associated with depression [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.28-2.25) and insomnia (OR 1.75, 95% CI 1.19-2.54). In linear regression models, depression, surfactant protein D and dyspnoea explained 35% (R-2) of the variation in physical impact of fatigue. Current smoking and depression explained 33% (R-2) of the cognitive impact of fatigue. Depression and surfactant protein D explained 48% (R-2) of the psychosocial impact of fatigue. Conclusions: Experiences of fatigue and functional limitation due to fatigue seem to be related mainly to psychological but also to physiological influencing factors, with depressive symptoms, insomnia problems and dyspnoea as the most prominent factors. Systemic inflammation was not associated with perception of fatigue but surfactant protein D was connected to some dimensions of the impact of fatigue
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| 3. |
- Kentson, Magnus
(författare)
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Fatigue and Peripheral Muscle Dysfunction: Studies on Vitamin D Status, Muscle Metabolism and Systemic Inflammation in Patients with COPD : Aspects of COPD severity beyond FEV1 and exacerbations
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe severity of Chronic Obstructive Pulmonary Disease (COPD) is usually described in terms of forced expiratory volume in one second (FEV1) and number of exacerbations. However, COPD is a complex disease with different ways of expression, involving pulmonary symptoms, extra pulmonal manifestations and comorbidities, which altogether affect the patient by contributing to reduced functional capacity, increased shortness of breath, reduced health-related quality of life and increased mortality. Systemic inflammation is common in COPD and can potentially constitute a link between the lungs and other organs. The aim of this thesis was to broaden the aspects of COPD severity beyond FEV1 and exacerbations by studying fatigue, the role of vitamin D, nutritional factors, systemic inflammation and peripheral muscle function in patients with COPD. Methods and ResultsIn paper I, we included 101 patients with COPD, and 34 control subjects. Assessment of experience of fatigue, functional limitation due to fatigue, and the relationships to physiological, psychological and situational variables and quality of life (QoL) were evaluated. We found that experience of fatigue was highly prevalent (72% versus 56% in control subjects) and a troublesome symptom in COPD. Patients with COPD and fatigue had lower lung function, shorter walking distance, more dyspnoea, anxiety and depressive symptoms and poorer health status compared to patients without fatigue (all p < 0.01). Several contributing factors were identified to experience of fatigue and functional limitations of fatigue with dyspnoea, depressive symptoms and insomnia as the most prominent factors. No clear association with systemic inflammation was found. Paper II evaluated vitamin D status in 66 patients with advanced COPD (28 with long-term oxygen therapy (LTOT)) and 47 control subjects. 25-hydroxyvitamin 25(OH)D were deter-mined in early fall in a short period of seven weeks. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were answered. Lung function tests and blood sampling including systemic inflammatory markers, carotenoids and protein carbonylation (PC) were assessed. The peak annual 25(OH)D of COPD patients was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Among vitamin D-deficient COPD patients, 25(OH)D correlated positively with lung function, blood oxygenation, food portion size, Mediterranean Diet Score and Ultra-violet Score and negatively with dyspnoea and DOSE-index, a composite index for COPD se-verity. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels <50 nmol/L. In paper III, we evaluated in the same cohort as paper II oxidative damage and levels of carotenoids. Patients with COPD (±LTOT) did not demonstrate increased oxidative damage. Com-pared with the control group, levels of several carotenoids were significantly lower in COPD, and the diet contained significantly less fruit and vegetables. Lycopene correlated positively with saturation and lutein correlated positively with some inflammatory markers but negatively with IL-6, an important marker for systemic inflammation. The study highlights the importance of dietary factors in COPD. In paper IV, 32 patients with COPD answered questionnaires, and were subjected to lung function tests and blood analysis including systemic inflammatory markers. Magnetic resonance imaging (MRI) for analysis of whole-body and thigh muscle composition was performed. Bioenergetics in the resting thigh muscle, (PCr/Pi ratio), were analysed using 31phosphorus magnetic resonance spectroscopy (31P-MRS). We found that adverse muscle composition was common in the COPD group. Clinical characteristics reflecting COPD severity were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa correlated positively to systemic inflammatory markers, negative to physical activity and PCr/Pi ratio. We compared the COPD group with a virtual control group from UK Biobank (n= 3200). ConclusionsSevere COPD is much more than airway obstruction and exacerbations. The presence of fatigue is associated, as well as vitamin D status and nutritional factors, with important clinical out-comes reflecting COPD severity. Adverse muscle composition is common in COPD and there seems to be a link between systemic inflammation, muscle fat infiltration and bioenergetics.
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| 4. |
- Kentson, Magnus, 1982-, et al.
(författare)
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Oxidant status, iron homeostasis, and carotenoid levels of COPD patients with advanced disease and LTOT
- 2018
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Ingår i: European Clinical Respiratory Journal. - : Taylor & Francis. - 2001-8525. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with oxidative stress. Both iron (Fe) and oxygen are involved in the chemical reactions that lead to increased formation of reactive oxygen species. Oxidative reactions are prevented by antioxidants such as carotenoids. Objective: To study the differences in Fe status, carotenoid levels, healthy eating habits, and markers of inflammation and oxidative damage on proteins in subjects with severe COPD ± long-term oxygen therapy (LTOT) and lung-healthy control subjects. Methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included. Questionnaires about general health, lifestyle, and dietary habits were answered. Lung function tests and blood sampling were performed. Results: COPD subjects (±LTOT) did not demonstrate increased oxidative damage, assessed by protein carbonylation (PC), while levels of soluble transferrin receptors (sTfRs) were slightly elevated. Soluble TfRs, which is inversely related to Fe status, was negatively associated with PC. Levels of carotenoids, total and ß-cryptoxanthin, a- and ß-carotenes, were significantly lower in COPD subjects, and their diet contained significantly less fruits and vegetables. Lutein correlated inversely with IL-6, lycopene correlated inversely with SAT, while ß-carotene was positively associated with a Mediterranean-like diet. Conclusions: Fe could favor oxidative stress in COPD patients, suggesting a cautious use of Fe prescription to these patients. COPD subjects ate a less healthy diet than control subjects did and would, therefore, benefit by dietary counseling. COPD patients with hypoxemia are probably in particular need of a lycopene-enriched diet.
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| 5. |
- Kentson, Magnus, et al.
(författare)
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The influence of disease severity and lifestyle factors on the peak annual 25(OH)D value of COPD patients
- 2018
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 13, s. 1389-1398
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of individuals deficient in vitamin D (defined as a serum level of the stable metabolite 25(OH)D amp;lt; 50 nmol/L) is increasing in countries with low annual ultraviolet (UV) radiation and among individuals unable to perform outdoor activities, for example, COPD patients. Objective: To assess the role of vitamin D deficiency, independently of seasonal variation, the peak annual value of 25(OH)D was measured in subjects with advanced COPD +/- long-term oxygen therapy (LTOT) and lung healthy control subjects. A method to grade the individual annual UV light exposure was designed and tested. Subjects and methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included, and the levels of 25(OH)D were determined in late summer/ early fall when the annual peak was assumed. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were used to collect data. Lung function tests and blood sampling were performed. Results: The peak annual 25(OH)D of COPD subjects was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels amp;gt;= 50 nmol/L. Among vitamin D-deficient COPD subjects, 25(OH)D correlated positively with forced expiratory volume in 1 second as % predicted, Modified British Medical Research Council score, blood oxygenation, food portion size, Mediterranean Diet Score and Ultraviolet Score. Conclusion: Vitamin D deficiency was common among healthy individuals and COPD subjects. Peak annual 25(OH)D levels of COPD subjects correlated with clinically important outcomes. The present study emphasizes the need to routinely monitor vitamin D status among patients with advanced COPD and to consider to medicate those with vitamin D deficiency with vitamin D supplementation.
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| 6. |
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| 7. |
- Norberg, Pernilla, et al.
(författare)
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Quantitative lung SPECT applied on simulated early COPD and humans with advanced COPD
- 2013
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Ingår i: EJNMMI Research. - Germany : SpringerOpen. - 2191-219X. ; 3:28
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers.METHODS:In the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers.RESULTS:A significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the five healthy volunteers and five patients with advanced COPD (p < 0.05).CONCLUSIONS:While our results are promising, the potential of the AUC(CVT) method to detect less advanced COPD in patients needs further clinical studies.
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| 8. |
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| 9. |
- Persson, Lennart, et al.
(författare)
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Skeletal Myosteatosis is Associated with Systemic Inflammation and a Loss of Muscle Bioenergetics in Stable COPD
- 2022
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Ingår i: Journal of Inflammation Research. - : DOVE MEDICAL PRESS LTD. - 1178-7031. ; 15, s. 4367-4384
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Tidskriftsartikel (refereegranskat)abstract
- Background: Common features among patients with more advanced chronic obstructive pulmonary disease (COPD) are systemic inflammation and a loss of both muscle mass and normal muscle composition. In the present study, we investigated COPD subjects to better understand how thigh muscle fat infiltration (MFI) and energy metabolism relate to each other and to clinical features of COPD with emphasis on systemic inflammation. Methods: Thirty-two Caucasians with stable COPD were investigated using questionnaires, lung function tests, blood analysis and magnetic resonance imaging (MRI) for analysis of body-and thigh muscle composition. Bioenergetics in the resting thigh muscle, expressed as the PCr/Pi ratio, were analysed using (31)phosphorus magnetic resonance spectroscopy (P-31-MRS). Results: Based on the combination of the MFI adjusted for sex (MFIa) and the thigh fat-tissue free muscle volume, expressed as the deviation from the expected muscle volume of a matched virtual control group (FFMVvcg), all COPD subjects displayed abnormally composed thigh muscles. Clinical features of increased COPD severity, including a decrease of blood oxygenation (r = -0.44, p < 0.05) and FEV1/FVC ratio, reflecting airway obstruction (r = -0.53, p < 0.01) and an increase of COPD symptoms (r = 0.37, p < 0.05) and breathing frequency at rest (r = 0.41, p < 0.05), were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa of the thigh muscle correlated positively with markers of systemic inflammation (white blood cell count, r = 0.41, p < 0.05; fibrinogen, r = 0.44, p < 0.05), and negatively with weekly physical activity (r = -0.40, p < 0.05) and the PCr/Pi ratio in the resting thigh muscle (r = -0.41, p < 0.05). Conclusion: The present study implies a link between systemic inflammation, excessive MFI and a loss of bioenergetics in subjects with stable COPD.
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| 10. |
- Sioutas, Apostolos, et al.
(författare)
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Oxidant-induced autophagy and ferritin degradation contribute to epithelial-mesenchymal transition through lysosomal iron
- 2017
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Ingår i: Journal of Inflammation Research. - : Dove Medical Press. - 1178-7031. ; 10, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor (TGF)-ß1 triggers epithelial-mesenchymal transition (EMT) through autophagy, which is partly driven by reactive oxygen species (ROS). The aim of this study was to determine whether leaking lysosomes and enhanced degradation of H-ferritin could be involved in EMT and whether it could be possible to prevent EMT by iron chelation targeting of the lysosome.
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| 11. |
- Svedberg, Anna, et al.
(författare)
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Erlotinib treatment induces cytochrome P450 3A activity in non-small cell lung cancer patients
- 2019
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 85:8, s. 1704-1709
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Tidskriftsartikel (refereegranskat)abstract
- Aims Erlotinib is a tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer highly metabolized by the cytochrome P450 (CYP) 3A. Hence, CYP3A4 activity might be a useful predictor of erlotinib pharmacokinetics in personalized medicine. The effect of erlotinib on CYP3A activity was therefore studied in non-small cell lung cancer patients. Methods The study included 32 patients scheduled for erlotinib monotherapy. CYP3A activity was assessed using quinine as a probe before and during erlotinib treatment. Plasma from blood samples drawn 16 hours post quinine administration were analysed using HPLC with fluorescence detection to determine the quinine/3-OH-quinine ratio. Results Matched samples, available from 13 patients, showed an induction of CYP3A activity (P = 0.003, Wilcoxon's signed rank test) after 2 months of treatment. The quinine/3-OH-quinine ratio decreased from 20.2 (+/- 13.4) at baseline to 11.0 (+/- 4.34). Single-point samples, available from 19 patients, supported the decrease in ratio (P = 0.007, Mann-Whitney U-test). Generally, females had a higher CYP3A activity both at baseline and after two months of treatment. Statistical analysis by gender also showed significant increase in CYP3A activity (males, n = 10, P = 0.001, and females, n = 22, P = 0.001). Conclusions An induction of CYP3A activity was observed after 2 months of erlotinib treatment which was also seen when subdividing based on gender. It could be important to take this into consideration for patients co-administering other CYP3A-metabolizing drugs during erlotinib treatment and also makes it difficult to use baseline CYP3A activity to predict erlotinib pharmacokinetics.
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| 12. |
- Tödt, Kristina, et al.
(författare)
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Experience of fatigue, and its relationship to physical capacity and disease severity in men and women with COPD
- 2014
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove medical Press. - 1176-9106 .- 1178-2005. ; 9, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several differences have been reported in the clinical characteristics of chronic obstructive pulmonary disease (COPD) between men and women. Differences have been found in the association between respiratory symptoms and lung function, and in the factors associated with dyspnea. This raises the question of whether there are differences between the sexes in the relationship between fatigue, the second most prevalent symptom, and the variables of physical capacity and disease severity. Objectives: To examine the experience of fatigue and its relationship to physical capacity and disease severity in men and women with COPD. Methods: In a cross-sectional study 121 patients with COPD (54 men and 67 women), the experience of fatigue (frequency, duration, and severity) and physical capacity (lung function, 6-minute walk distance [6MWD], grip strength, and timed-stand test) were assessed. Disease severity was graded according to the Body mass index, airway Obstruction, Dyspnoea and Exercise capacity (BODE) index. Two multiple logistic regression models were tested, both of which were performed separately in men and women, to examine the association between the experience of fatigue and variables of physical capacity and the BODE index. Results: Eighty-nine (73.6%) patients experienced fatigue, with similar proportions in men and women. The men with fatigue had worse physical capacity and more severe disease than did the men without fatigue: for men with and without fatigue, respectively, the percent of predicted forced expiratory volume in 1 second (FEV1) (mean [standard deviation]) was 47 (14) vs 64 (17); the 6MWD (mean [standard deviation]) was 398 (138) vs 539 (105) m; and the BODE index (median [quartile 1-3]) was 3 (2-5) vs 1 (0-1) (P<0.01). In women, only higher leg fatigue post-6MWD was seen among those experiencing fatigue compared with women without fatigue: for women with and without fatigue, respectively, leg fatigue (median [quartile 1-3]) was 4 (3-5) vs 2 (0-3) (P<0.001). The regression models showed that the 6MWD and the BODE index were associated with fatigue in both men and women, but in women, leg fatigue remained an independent associate in both models. Conclusion: Exercise capacity and disease severity were associated with fatigue in both men and women. In women, leg fatigue was strongly associated with fatigue, which warrants further investigation.
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| 13. |
- Tödt, Kristina, et al.
(författare)
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Fatigue is associated with reduced physical capacity and disease severity in men but not in women with COPD
- 2011
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Konferensbidrag (refereegranskat)abstract
- Purpose: The purpose was to examine the association between perception of fatigue, and physical capacity and disease severity in men and women with chronic obstructive pulmonary disease (COPD). Relevance: Fatigue is the second most common symptom among patients with COPD. Fatigue is shown to be associated with reduced functional status and perceived health. To optimize rehabilitation program in patients with COPD, knowledge about the association between fatigue and physical capacity in men and women is needed. Participants: In total 121 patients (67 women) with stable COPD, consecutively selected through the patient administrative system at two hospitals, were included. Mean age was 67 (± 7) years and FEV1% of predicted was 49 (± 16) with no differences between genders. Methods: Fatigue was assessed with structured questions covering frequency, duration and severity. The patients were classified into no, mild and severe fatigue. Physical capacity included lung function (FEV1 and FVC), 6-minute walk distance (6MWD), timed stands test and grip strength. Disease severity was classified with BODE-index including the body mass index, the degree of airway obstruction (FEV1% predicted), the degree of dyspnoea measured with the MRC-dyspnoea scale and exercise capacity measured as 6MWD. Analysis: Differences between patients with no, mild and severe fatigue were tested using the Kruskal-Wallis test with Bonferroni correction. Results: The proportion of patients with no, mild and severe fatigue was 26%, 52% and 22% respectively. This proportion was similar in men and women. Association between fatigue and physical capacity were seen in lung function (FVC) and 6MWD. FVC was more deteriorated (p=0.02) and the 6MWD was shorter (p=0.008) in patients with mild and severe fatigue than in those with no fatigue. The patients with mild and severe fatigue had a more severe disease compared with those with no fatigue (p<0.001). These differences in physical capacity and disease severity were only evident in men (FVC p= 0.02, FEV1 p=0.008, 6MWD p=0.003 and BODE-index p<0.001) and not in women (p=0.648, p=0.462, p=0.442 and p=0.285). Conclusions: The association between fatigue and physical capacity and disease severity seems to be evident in men only. Implications: The gender differences suggest different rehabilitation approaches in reducing fatigue in men and women with COPD. The results need to be confirmed in larger studies. :Funding acknowledgements: The study was supported by the Swedish Hearth Lung Foundation, Medical Research Council of Southeast Sweden and the Swedish Heart and Lung Association. Ethics approval: The study was approved by the Regional Ethical Review Board, Linköping, Sweden.
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