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ABSTRACT: Recently we developed a validated computer program based on polychotomous logistic regression analysis using bronchoalveolar avage fluid (BALF) results to distinguish between the three most common interstitial lung diseases (ILD): sarcoidosis, idiopathic pulmonary fibrosis (IPF) and extrinsic allergic alveolitis (EAA) or drug-induced pneumonitis. One of the limitations of this program was that it was not useful in discriminating between infectious disorders and non-infectious disorders. Therefore, we added BALF samples obtained from patients with a confirmed bacterial pulmonary infection based on culture results > or = 10(4) cfum l(-1) (group I: n=31) to the study population mentioned above (group II: n=272). Notably, just one variable, i.e. the percentage of polymorphonuclear neutrophils, allowed us to distinguish between infectious and non-infectious disorders. The agreement of predicted with the actual diagnostic group membership was 99.67% (groups I and II). Additionally, 91.2% of the cases with ILD were correctly classified. In conclusion, this updated Windows version 2000 of the validated computer program provides a very reliable prediction of the correct diagnosis for an arbitrary patient with suspected pneumonia or with ILD given information obtained from BALF analysis results, and is thought to improve the diagnostic power of BALF analysis.
Respiratory Medicine 10/2001; 95(10):781-6. · 2.47 Impact Factor
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ABSTRACT: Rapid activation of the IkappaB kinase (IKK) complex is considered an obligatory step in the activation of nuclear factor-kappaB (NF-kappaB) in response to diverse stimuli. Since oxidants have been implicated in the regulation of NF-kappaB, the focus of the present study was the activation of IKK by tumor necrosis factor alpha (TNFalpha) in the presence or absence of hydrogen peroxide (H(2)O(2)). Exposure of mouse alveolar epithelial cells to H(2)O(2) was not sufficient to activate IKK, degrade IkappaBalpha, or activate NF-kappaB. In contrast, TNFalpha induced IKK activity rapidly and transiently resulting in IkappaBalpha degradation and NF-kappaB activation. Importantly, in the presence of H(2)O(2), the ability of TNFalpha to induce IKK activity was markedly decreased and resulted in prevention of IkappaBalpha degradation and NF-kappaB activation. Neither tyrosine kinases nor phosphatidylinositol 3-kinases, known regulators of NF-kappaB by oxidants, were involved in IKK inhibition by H(2)O(2). Direct addition of H(2)O(2) to the immunoprecipitated IKK complex inhibited enzyme activity. Inhibition of IKK activity by H(2)O(2) was associated with direct oxidation of cysteine residues present in the IKK complex and occurred only in enzymatically active IKK. In contrast to previously published observations, our findings demonstrate that the oxidant H(2)O(2) reduces NF-kappaB activation by inhibiting activated IKK activity.
Journal of Biological Chemistry 10/2001; 276(38):35693-700. · 4.77 Impact Factor
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ABSTRACT: The aim of this study was to test the hypothesis that the chronic inflammatory process present in chronic obstructive pulmonary disease (COPD) is due to a defective endogenous anti-inflammatory mechanism.
Systemic levels of the anti-inflammatory mediators soluble interleukin 1 receptor II (sIL-1RII), soluble tumour necrosis factor receptor p55 (sTNF-R55) and sTNF-R75, and of C reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were analysed in 55 patients with stable COPD (median forced expiratory volume in one second (FEV(1)) 34% predicted (range 15-78)) and compared with levels in 23 control subjects. In addition, changes in these mediators were studied in 13 patients with COPD (median FEV(1) 34% predicted (range 19-51)) during the first 7 days in hospital with an exacerbation of the disease.
Patients with stable COPD were characterised by a systemic inflammatory process indicated by an increased leucocyte count (7.2 (4.7-16.4) v 4.8 (3.5-8.3) x 10(9)/l), raised levels of CRP (11.8 (1.1-75.0) v 4.1 (0.6-75.0) microg/ml) and LBP (45.6 (8.1-200.0) v 27.9 (14.1-71.5) microg/ml), and moderate increases in both sTNF-Rs. In contrast, the sIL-1RII level did not differ between patients and controls (4.53 (2.09-7.60) v 4.63 (3.80-5.93) ng/ml). During treatment of disease exacerbations, systemic levels of both CRP (at day 3) and LBP (at day 7) were significantly reduced compared with day 1, whereas sIL-1RII levels increased.
These data suggest an imbalance in systemic levels of pro- and anti-inflammatory mediators in patients with stable COPD. The increase in the anti-inflammatory mediator sIL-1RII during treatment of exacerbations may contribute to the clinical improvement.
Thorax 10/2001; 56(9):721-6. · 6.84 Impact Factor
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ABSTRACT: This study investigated apoptosis in lungs after local exposure to lipopolysaccharide (LPS). Mice were instilled intratracheally with 5 microg LPS, which corresponds to the amount acquired by smoking approximately 25 cigarettes, and killed at different time points after exposure. Our data demonstrate that local LPS exposure resulted in apoptosis in lungs from 2 h and peaked at 24 h, as detected by ligation-mediated polymerase chain reaction. Morphologic examination and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end label staining demonstrated apoptosis in bronchial epithelial cells early after intratracheal (IT) LPS challenge, whereas infiltrating neutrophils displayed positive staining at 24 and 72 h after exposure. Apoptosis in lungs clearly preceded pulmonary neutrophil infiltration, confirming that neutrophils did not contribute to pulmonary apoptosis at early time points. Further, using three experimental approaches--namely, anti-tumor necrosis factor (TNF)-alpha treatment, IT TNF-alpha instillation, and TNF/lymphotoxin-alpha knockout mice--we demonstrate that TNF-alpha, which was elevated in lungs at both messenger RNA and protein levels after IT LPS challenge, was no primary mediator in LPS-induced apoptosis at early time points. Thus, local LPS exposure in mice resulted in early apoptosis of bronchial epithelial cells independent of infiltrating neutrophils and TNF-alpha, which suggests that apoptosis of bronchial epithelium may be involved in airway injury during exposure to LPS.
American Journal of Respiratory Cell and Molecular Biology 06/2001; 24(5):569-76. · 5.13 Impact Factor
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ABSTRACT: Muscle wasting is often associated with chronic inflammation. Because tumor necrosis factor alpha (TNF-alpha) has been implicated as a major mediator of cachexia, its effects on C2C12 myocytes were examined. TNF-alpha activated nuclear factor-kappaB (NF-kappaB) and interfered with the expression of muscle proteins in differentiating myoblasts. Introduction of a mutant form of inhibitory protein kappaBalpha (IkappaBalpha) restored myogenic differentiation in myoblasts treated with TNF-alpha or interleukin 1beta. Conversely, activation of NF-kappaB by overexpression of IkappaB kinase was sufficient to block myogenesis, illustrating the causal link between NF-kappaB activation and inhibition of myogenic differentiation. The inhibitory effects of TNF-alpha on myogenic differentiation were reversible, indicating that the effects of the cytokine were not due to nonspecific toxicity. Treatment of differentiated myotubes with TNF-alpha did not result in a striking loss of muscle-specific proteins, which shows that myogenesis was selectively affected in the myoblast stage by TNF-alpha. An important finding was that NF-kappaB was activated to the same extent in differentiating and differentiated cells, illustrating that once myocytes have differentiated they become refractory to the effects of NF-kappaB activation. These results demonstrate that inflammatory cytokines may contribute to muscle wasting through the inhibition of myogenic differentiation via a NF-kappaB-dependent pathway.
The FASEB Journal 06/2001; 15(7):1169-80. · 5.71 Impact Factor
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ABSTRACT: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association between the level of symptom relief and objective tumor response, as well as with radiation-induced pulmonary changes, was investigated.
One hundred sixty-four patients were entered onto this prospective study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 were used to investigate changes in QOL: Assessments were performed before radiotherapy and 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after the completion of radiotherapy.
The QoL response rates were excellent for hemoptysis (83%); good for chest pain (68%), arm/shoulder pain (63%), and appetite loss (60%); and poor for dyspnea (37%), cough (31%), and fatigue (28%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for physical and role functioning to 55% for social and cognitive functioning. The response rate for global QoL was 36%. A significant association was found between tumor response and palliation of chest pain, arm/shoulder pain, and physical functioning. During radiotherapy, a significant increase for most general symptoms and a deterioration in functioning and QoL were noted.
This study is the first to describe palliation and changes in QoL in radically irradiated patients with NSCLC. Radical radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with NSCLC who have relatively good prognostic features. Although tumor reduction is associated with palliation of respiratory symptoms, it cannot serve as a surrogate for palliation.
Journal of Clinical Oncology 05/2001; 19(8):2123-33. · 18.37 Impact Factor
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ABSTRACT: Sarcoidosis is an inflammatory disorder of unknown origin. The nuclear regulatory factor-kappaB (NF-kappaB) appears to play a key role in immune and inflammatory processes such as asthma, rheumatoid arthritis and inflammatory bowel disease. We hypothesized that NF-kappaB activation might be involved in the pathological process of sarcoidosis.
Twelve sarcoidosis patients, biopsy proven, and five healthy control subjects, all nonsmokers, were studied. Blood samples were taken and routinely analysed for several parameters including the serum angiotensin converting enzyme (sACE) level. Mononuclear cells were isolated from these patients in order to quantify the NF-kappaB contents in the nuclear extract of the mononuclear cells.
Mononuclear cells NF-kappaB expressed per mg protein were twice as high in both untreated (n = 5) and treated (n = 7) patients with sarcoidosis compared to the control subjects (p < 0.001). In contrast, the sACE level appeared to be low in the treated patients compared to the untreated patients (p < 0.01).
These results indicate that the inflammation in sarcoidosis is associated with NF-kappaB activation. Moreover, the suppression of the activated NF-kappaB response by glucocorticoids seems less successful than the suppression of the sACE activity. Future studies should focus on the clinical relevance of this observation and establish the possible therapeutic consequences of the increased NF-kappaB activation in sarcoidosis.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 04/2001; 18(1):50-6. · 1.27 Impact Factor
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ABSTRACT: Systemic corticosteroids are often administered in COPD patients. The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was retrospectively analysed. Baseline characteristics of the patients, in stable clinical condition, were collected on admission to a pulmonary rehabilitation centre. Overall mortality was asessed at the end of follow-up. The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use, distinguishing administration route (oral/inhalation) and oral dose, and overall mortality, adjusted for the influence of age, sex, smoking, lung function, resting arterial blood gases and body mass index. On multivariate analysis, oral glucocorticoid use at a (prednisone equivalent) dose of 10 mg x day(-1) without inhaled glucocorticoids, was associated with an increased risk (RR=2.34, 95% confidence interval (CI) 1.24-4.44) while 15 mg x day(-1) carried a relative risk of 4.03, CI = 1.99-8.15). A significant interaction was observed between inhaled and oral glucocorticoid use. Combined with inhaled glucocorticoids, the relative risk of oral glucocorticoid use appeared to be significantly smaller. It is concluded that in severe chronic obstructive pulmonary disease, maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner. Since the present study design cannot exclude the possibility of bias by indication, further prospective studies are indicated using a broader patient characterization.
European Respiratory Journal 04/2001; 17(3):337-42. · 5.89 Impact Factor
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ABSTRACT: In the present study, the diagnostic yield of high resolution computed tomography (HRCT) is evaluated in patients with thoracoscopically-verified idiopathic spontaneous pneumothorax (SP). Visual assessment as well as densitometry of lung parenchyma was performed. In eight of the 20 prospectively-evaluated SP patients, emphysema-like (EL) changes such as blebs and bullae could be detected. The SP patients with EL changes were significantly older and were more heavy smokers. Spirometrically-controlled CT lung densitometry showed no differences between the patient group with or without these EL changes. Comparing the densitometric measurements of the patient group with a healthy control group no significant differences in densitometry between both groups were found. In conclusion, this study confirms that HRCT is a reliable method of detecting blebs and bullae in patients with spontaneous pneumothorax. Furthermore CT lung densitometry revealed no parenchymal abnormalities or signs of air trapping in patients with spontaneous pneumothorax.
Respiratory Medicine 04/2001; 95(4):292-6. · 2.47 Impact Factor
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ABSTRACT: Depletion of fat-free mass (FFM) significantly contributes to decreased skeletal muscle weakness and impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). FFM wasting suggests disturbances in intermediary metabolism, confirmed by data showing profound alterations in the skeletal muscle amino acid (AA) status in COPD at rest. To unravel whether there is a role for AAs in the mechanisms for skeletal muscle dysfunction in COPD, basic knowledge of AA metabolism in the muscle during exercise is important. We examined the effects of 20 min of exercise on AA metabolism in 14 patients with COPD and eight control subjects. Arterialized venous blood and a quadriceps femoris muscle biopsy were obtained before and immediately after exercise. FFM was not significantly different between the groups. In COPD, a significant reduction of most muscle AAs was present postexercise, whereas several plasma AAs were increased (p < 0.05). Consequently, sum AAs was reduced in muscle (20%; p < 0.01) and increased in plasma (16%, p < 0.05), suggesting an enhanced AA release from muscle in COPD during exercise. In the COPD group, the increase in plasma alanine and glutamine was even higher postexercise (61%, p < 0.01 and 21%, p < 0.01, respectively), suggesting enhanced nitrogen efflux. This study shows that exercise alters amino acid (intermediary) metabolism in patients with COPD and independent of the presence of FFM wasting.
American Journal of Respiratory and Critical Care Medicine 03/2001; 163(4):859-64. · 11.08 Impact Factor
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ABSTRACT: Use of nutritional supplements in depleted patients with chronic obstructive pulmonary disease (COPD) requires optimization between positive effects on outcome and potential acute adverse effects on metabolism and exercise performance.
The aim of this study was to investigate the acute effects of nutritional supplements on metabolism and exercise capacity in stable COPD patients.
In part 1, the effects of 3 different energy loads (placebo, 1046 kJ, and 2092 kJ) with a normal distribution of macronutrients were investigated in 14 COPD patients. In part 2, the effects of a fat-rich compared with a carbohydrate-rich supplement (both 1046 kJ) were studied in 11 COPD patients. The study was performed in a randomized, double-blind, crossover fashion. Metabolic and ventilatory variables were measured postprandially and during a submaximal cycle endurance exercise test.
Overall, no immediate negative effects of the supplements were found in part 1. A slight but significant postprandial increase in respiratory quotient was found after the 1046-kJ and 2092-kJ supplements compared with placebo. There was no significant difference in metabolism or exercise capacity after a fat-rich or carbohydrate-rich supplement. Surprisingly, the change in shortness of breath (postprandial compared with preprandial) was significantly greater after the fat-rich supplement.
An energy load up to 2092 kJ had no adverse immediate effect in COPD patients compared with placebo. The subjects who consumed the fat-rich supplement experienced more shortness of breath than did the subjects who consumed the carbohydrate-rich supplement.
American Journal of Clinical Nutrition 03/2001; 73(2):295-301. · 6.67 Impact Factor
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E F Wouters
Pediatric Pulmonology 02/2001; Suppl 23:22-4. · 2.53 Impact Factor
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ABSTRACT: The present study investigated whether development or maintenance of a relatively increased fat mass in normal-weight patients with chronic obstructive pulmonary disease (COPD), despite periods of weight loss, may be related to impaired beta-adrenoceptor-mediated responses in lipid utilization and thermogenesis. Nine COPD patients and nine healthy controls (body mass index: 23.0 +/- 1.3 vs. 23.8 +/- 0.6 kg/m2, not significant; fat mass: 19.0 +/- 2.1 vs. 11.9 +/- 1.5 kg, P < 0.01) received consecutive 30-min infusions of 6, 12, and 24 ng x kg fat free mass(-1) x min(-1) isoproterenol. During beta-adrenergic stimulation, nonesterified fatty acid levels increased significantly less in COPD patients (P < 0.001). Respiratory exchange ratio decreased similarly in both groups, indicating a similar change in the rate of lipid to carbohydrate oxidation. Energy expenditure increased similarly in both groups during beta-adrenergic stimulation. However, because plasma isoproterenol concentrations were significantly higher in COPD patients, thermogenesis related to isoproterenol concentration was significantly reduced in this group (P < 0.05). In conclusion, beta-adrenoceptor-mediated lipolysis and thermogenesis are impaired in COPD patients. This may play a role in the development or maintenance of their relatively increased fat mass.
AJP Endocrinology and Metabolism 02/2001; 280(2):E357-64. · 4.75 Impact Factor
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ABSTRACT: In this prospective open study of 14 children with cystic fibrosis (CF), we evaluated the effect of 1 year adjuvant therapy with lansoprazole, a proton pump inhibitor (PPI), on growth, fecal fat loss, body composition and lung function. Only stable patients with pancreatic insufficiency were included, and their data were compared to those of a large Dutch pediatric normal reference population. During the use of the PPI, mean weight and height did not change significantly, while body mass index improved (P < 0.05). An immediate significant and persistent reduction of fecal acid steatocrit (P < 0.05) was demonstrated. Compared to normal Dutch children, the CF patients showed significantly decreased standard deviation scores (SDS) for total body fat (TBF, -0.966) and fat-free mass (FFM, -1.826). Under lansoprazole, TBF improved significantly (P < 0.05), while mean FFM remained unchanged. A significant improvement in total lung capacity (P < 0.05), residual volume (P = 0.055), and maximal inspiratory mouth pressure (P = 0.002) was also demonstrated. Hyperinflation tended to decrease during the use of a PPI. Daily recordings of peak expiratory flow (PEF) showed a maximal diurnal variability of 28% of recent best PEF and minimal morning PEF of 72% of recent best PEF, confirming that bronchial hyperresponsiveness is increased in CF. We conclude that adjuvant therapy with lansoprazole in young CF patients with persistent fat malabsorption, decreased fat losses and improved total body fat. Lung hyperinflation decreased, which may partly explain the improvement in inspiratory muscle performance. The simultaneous improvements in body composition and lung hyperinflation suggest a relationship between these two parameters. Further research is necessary to confirm such a relationship and to elucidate the mechanisms involved.
Pediatric Pulmonology 02/2001; 31(1):59-66. · 2.53 Impact Factor
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ABSTRACT: There is increasing evidence of abnormal protein metabolism in patients with chronic obstructive pulmonary disease (COPD), as reflected by lower plasma branched-chain amino acid (BCAA) concentrations and different muscle amino acid (AA) patterns than in age-matched control subjects.
We examined whether the low plasma BCAA concentrations in COPD reflect an imbalance between anabolic and catabolic processes as evidenced by a low fat-free mass (FFM) and alterations in the anabolic hormone insulin and whether discrepancies in muscle AA concentrations between studies are related to different patient characteristics.
AA profiles in arterial plasma and quadriceps femoris muscle and insulin concentrations in venous plasma were analyzed in 28 postabsorptive COPD patients (14 with and 14 without macroscopic emphysema) and in 28 control subjects. FFM was measured by dual-energy X-ray absorptiometry.
The lower sum of plasma BCAAs in the COPD group than in the control subjects was the result of a lower leucine concentration (P: < 0.001); no significant difference in valine and isoleucine was found between the groups. In the COPD group, the lower leucine concentrations were associated with low FFM (P: < 0.01). Compared with the control group, the muscle-to-plasma leucine gradient was higher in the COPD group (P: < 0.001) and was associated with a higher insulin concentration (P: < 0.01). Several muscle AA concentrations were higher or tended to be higher in the group without emphysema than in the control group, whereas nearly all AA concentrations were lower in the group with emphysema.
Leucine metabolism is altered in COPD patients and is associated with low FFM and high insulin concentrations. There were striking differences in the skeletal muscle AA profile between the COPD subtypes.
American Journal of Clinical Nutrition 01/2001; 72(6):1480-7. · 6.67 Impact Factor
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ABSTRACT: Weight loss and muscle wasting commonly occur in patients with chronic obstructive pulmonary disease (COPD). A decreased dietary intake and elevated energy requirements underlie weight loss in these patients. Disturbances in intermediary metabolism caused by altered anabolic and catabolic mediators such as hormones, cytokines, and growth factors, and resulting in disproportionate muscle wasting have been described. Nutritional supplementation in combination with an anabolic stimulus (e.g. exercise) has been shown effective in improving functional capacity, health status, and mortality in most depleted patients. Nutritional or pharmacologic modulation of the catabolic response may further enhance the response in the near future.
Clinics in Chest Medicine 01/2001; 21(4):753-62. · 3.28 Impact Factor
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ABSTRACT: Early lactic acidosis has been suggested as negatively influencing the exercise capacity of patients with chronic obstructive pulmonary disease (COPD). We conducted a study to investigate whether the early lactate (La) response to exercise in COPD is related to alterations in exercise-related substrate levels in resting muscle, associated with physical inactivity. Twenty-seven COPD patients and 22 controls (physically inactive [PI] subjects, n = 15; and physically active [PA] subjects, n = 7) performed an incremental cycle test. Venous blood was sampled for La analyses, and the oxygen uptake at which the La level began to rise (La threshold) was calculated. Vastus lateralis biopsy specimens were obtained at rest. In the PA group, muscle glutamate (GLU) and glycogen were higher, but muscle La, pyruvate, and glucose were not different than in the PI group. Moreover, the La threshold was higher in the PA group. The COPD group had lower values for La threshold and muscle GLU, and higher values for muscle La and pyruvate levels than did the PI group. Stratification of patients into those with and without macroscopic emphysema (EMPH+, EMPH-, respectively), with comparable physical activity levels on the basis of previous observations, revealed lower values for La threshold and GLU in EMPH+ patients. Diffusing capacity for carbon monoxide (DL(CO)) and arterial oxygen tension (Pa(O(2))) in the four study groups were positively related to GLU and La threshold. Moreover, La threshold was positively related to GLU. This study illustrates that the early lactic acidosis during exercise in patients with COPD is associated with the physical inactivity-related reduction in these patient's muscle GLU. However, factors other than physical inactivity, such as Pa(O(2)) or DL(CO), play a role in the different La responses during exercise in subjects with different subtypes of COPD.
American Journal of Respiratory and Critical Care Medicine 12/2000; 162(5):1697-704. · 11.08 Impact Factor
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ABSTRACT: A substantial number of patients with chronic obstructive pulmonary disease (COPD) are characterized by fat-free mass wasting and altered muscle and plasma amino acid levels, suggesting changes in protein metabolism. In the present study, we examined whether whole-body protein breakdown (PB) and synthesis (PS) differ between 14 stable patients with COPD and 8 healthy controls. Whole-body PB, PS, and net PB (= PB-PS) were measured by the combined infusion of the stable isotopes L-[ring-(2)H(5)]phenylalanine (Phe) and L-[ring-(2)H(2)]tyrosine. Because there is evidence for specific disturbances in leucine (Leu) metabolism, the PB values were compared with those obtained when infusing L-[1-(13)C]Leu tracer. In arterialized-venous plasma and in vastus lateralis muscle, the isotope enrichment values and amino acid concentrations were measured. Whole-body PS and PB, assessed by Phe and Tyr tracer, were higher in the COPD group than in the control group (p < 0.05), indicating an elevated protein turnover. Net PB was increased in both groups, indicating a comparable degree of protein catabolism in the postabsorptive state. In contrast, whole-body PB determined by Leu tracer was not different between the groups. As a consequence, the ratio of Leu to Phe breakdown was reduced in the COPD group (p < 0.001). Moreover, in the COPD group a higher muscle-to-plasma gradient was found for Leu (p < 0.001) but not for Phe. The present study reveals elevated levels for protein turnover in patients with COPD, and indicates that infusion of the Leu tracer gives a reflection of Leu metabolism but not of whole-body protein metabolism in these patients.
American Journal of Respiratory and Critical Care Medicine 11/2000; 162(4 Pt 1):1488-92. · 11.08 Impact Factor
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ABSTRACT: Previously we reported an impaired energy balance in patients with chronic obstructive pulmonary disease (COPD) during an acute disease exacerbation, but limited data are available on the underlying mechanisms. Experimental and clinical research supports the hypothesis of involvement of the hormone leptin in body weight and energy balance homeostasis. The aim of this study was to investigate the course of the energy balance in relation to leptin and the soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75, plasma glucose, and serum insulin in patients with severe COPD during the first 7 d of hospitalization for an acute exacerbation (n = 17, 11 men, age mean [SD] 66 [10] yr, FEV(1) 36 [12] %pred). For reference values of the laboratory parameters, blood was collected from 23 (16 men) healthy, elderly subjects. On admission, the dietary intake/resting energy expenditure (REE) ratio was severely depressed (1.28 [0.57]), but gradually restored until Day 7 (1.65 [0. 45], p = 0.005 versus Day 1). Glucose and insulin concentrations were elevated on admission, but on Day 7 only plasma glucose was decreased. The sTNF-Rs were not different from healthy subjects and did not change. Plasma leptin, adjusted for fat mass expressed as percentage of body weight (%FM), was elevated on Day 1 compared with healthy subjects (1.82 [3.85] versus 0.32 [0.72] ng%/ml, p = 0.008), but decreased significantly until Day 7 (1.46 [3.77] ng%/ml, p = 0. 015 versus Day 1). On Day 7, sTNF-R55 was, independently of %FM, correlated with the natural logarithm (LN) of leptin (r = 0.65, p = 0.041) and with plasma glucose (r = 0.81, p = 0.015). In addition, the dietary intake/REE ratio was not only inversely related with LN leptin (-0.74, p = 0.037), but also with sTNF-R55 (r = -0.93, p = 0. 001) on day seven. In conclusion, temporary disturbances in the energy balance were seen during an acute exacerbation of COPD, related to increased leptin concentrations as well as to the systemic inflammatory response. Evidence was found that the elevated leptin concentrations were in turn under control of the systemic inflammatory response, and, presumably, the high-dose systemic glucocorticosteroid treatment.
American Journal of Respiratory and Critical Care Medicine 11/2000; 162(4 Pt 1):1239-45. · 11.08 Impact Factor
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ABSTRACT: The relationship between tissue depletion and decreased exercise performance has been well established in patients with COPD. In this study we investigated the influence of the pattern of tissue depletion on health related quality of life (HRQL) and their mutual relationship with exercise capacity and dyspnoea. Patients with low body weight and/or low fat-free mass (FFM; using bioelectrical impedance) were categorized in three groups according to type of tissue depletion: loss of both FFM and fat mass (FM), and loss of FFM or FM only. Handgrip strength (HGS) was used as a functional outcome measure of tissue depletion. Exercise performance was assessed by 12 min walking distance (12MWD) and dyspnoea by visual analogue scale (VAS). HRQL was measured with the St George's Respiratory Questionnaire (SGRQ) and the Medical Psychological Questionnaire for Lung diseases (MPQL). Patients with depletion of FFM irrespective of body weight showed greater impairment in 12MWD, HGS, the 'activity' and 'impact' scores of the SGRQ and the domain 'invalidity' of the MPQL, in comparison with depleted patients with relative preservation of FFM. Exercise performance and dyspnoea were also significantly related to these subscores of HRQL. In addition, dyspnoea related significantly to the domain 'symptoms' of the SGRQ. Tissue depletion pattern remained significantly related to SGRQ-scores and the domain 'invalidity' of the MPQL when dyspnoea and walking distance were added to the model as a covariates. Tissue depletion is an important determinant of HRQL independent of exercise capacity and dyspnoea.
Respiratory Medicine 10/2000; 94(9):859-67. · 2.47 Impact Factor
