PubMed HealthSearch

Biomedical subjects

E F Wouters

Publications and source records attributed to E F Wouters.

At least 19 recordsLinked to original sources

Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema.

Chronic obstructive pulmonary disease (COPD) is often characterized by an impaired skeletal muscle energy metabolism, which is at least partly related to chronic hypoxia and a reduced diffusing capacity. We have found that muscle glutamate (Glu), which is negatively influenced by these conditions, was reduced in patients with severe COPD. The aim of this study was to investigate whether the reduced intracellular Glu level in patients with emphysema is associated with an increased muscle glycolytic metabolism. Since Glu is an important substrate in the synthesis of glutamine (Gln) and glutathione (GSH), the influence of Glu status on muscle GSH and Gln was also examined. In 13 patients with emphysema and 25 control patients, arterial blood and biopsies from the vastus lateralis muscle were obtained. Expressed as a percentage of the control values, the patients with emphysema had reduced values for muscle Glu (64 +/- 12%; p < 0.001), GSH (76 +/- 23%; p < 0.01), and Gln (93 +/- 5%; p < 0.01), and higher values for lactate (p < 0.01) and pyruvate (p < 0.05). No differences were found in plasma values. Muscle Glu was highly associated with GSH (R(2) = 0.61; p < 0.001), but not with Gln. This study illustrates that reduced Glu levels in skeletal muscle of patients with emphysema are possibly related to an enhanced glycolytic activity and associated with decreased GSH levels.

Biomarkers

Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation.

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25 mg x kg(-1) x day(-1) for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31 mg x kg(-1) x day(-1) for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P < 0.01), glycogen synthase [GS(i + d)] activity (P < 0.05) and glycogen content (P < 0.01) in the tibialis anterior muscle. The PR and ND caused no alterations in PFK or citrate synthase (CS) activity compared to FF. Compared to PR, TR induced an increase in PFK (P < 0.01), CS (P < 0.05) and GS(i + d) activity (P < 0.01). Both TR and PR caused an increased muscle glycogen content, being more pronounced in TR (P < 0.05). Compared to ND, TR induced an increased CS (P < 0.05) and GS(i + d) activity (P < 0.01) and glycogen content (P < 0.01). The ND resulted in a decreased glycogen content compared to FF (P < 0.05). None of the treatments affected the activity of glycogen phosphorylase, beta-hydroxyacyl coenzyme A dehydrogenase and lactate dehydrogenase. It was concluded that corticosteroids led to an increased muscle glycogen content; however, the changes in the enzymes of carbohydrate metabolism were corticosteroid type specific and did not relate to undernutrition, which accompanied the triamcinolone treatment.

Animals

Serum beta-glucuronidase activity in a population of ex-coalminers.

BACKGROUND: The aim of this study was to investigate whether BGD activity is of additional value in the assessment of pulmonary inflammation caused by coal dust exposure. DESIGN AND METHODS: Ex-coalminers were included in this study. Forty-eight healthy male subjects, without a relevant medical history, were used as controls. RESULTS: In ex-coalminers serum BGD activity was higher compared to the control group. Moreover, ex-coalminers with a normal chest radiograph and normal serum LDH demonstrated elevated serum BGD compared to the control group. However, no relation was found in the total group of ex-coalminers between serum BGD activity and pulmonary function parameters. CONCLUSIONS: Our study adds in vivo human evidence to the already existing animal data that BGD is a potential biomarker useful in monitoring pulmonary inflammation caused by coal dust exposure.

Aged

Usefulness of monitoring beta-glucuronidase in pleural effusions.

BACKGROUND: The objective of the study was to evaluate the additional value of beta-glucuronidase (BGD), a lysosomal enzyme in the analysis of transudative and exsudative pleural effusions, especially between malignant and non-malignant effusions. DESIGN AND METHODS: Pleural fluid samples obtained from four respective diagnostic groups: transudates parapneumonic effusions, malignant effusions or pleuritis carcinomatosa, and empyema were evaluated. RESULTS: Beta-glucuronidase was significantly different between transudative and exsudative effusions (p<0.001) as well as between parapneumonic and malignant effusions (p<0.03), parapneumonic effusions and empyema (p<0.002), and malignant and empyema (p<0.002), respectively. Logistic regression analysis yielded a weak discrimination between the parapneumonic and malignant groups. CONCLUSIONS: Beta-glucuronidase activity differed between pleural effusions of various origin. However, including BGD in the biochemical work-up of pleural effusions did not reveal discriminatory value in the assessment of the classification of these effusions.

Adult

Different patterns of chronic tissue wasting among patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: Nutritional depletion is frequently present in patients with chronic obstructive pulmonary disease, but it is unknown whether a difference exists between the two subtypes. The aim of this study was to determine whether patterns of tissue depletion were different between emphysema and chronic bronchitis patients and whether these were related to pulmonary function. METHODS: In 99 severe COPD patients and 28 healthy volunteers, body weight and composition were assessed by dual-energy X-ray absorptiometry. Patients were stratified into chronic bronchitis (n=50) and emphysema (n=49) by high-resolution computed tomography. RESULTS: Lean mass depletion was found in 37% of the emphysema patients and in 12% of the chronic bronchitis patients. The emphysema patients had lower values for body mass index than the other groups (P< 0.01), mainly due to a lower lean mass (P< 0.01) and bone mineral content (P< 0.01). Fat mass was also lower in the emphysema group compared to the chronic bronchitis group (P< 0.001). The chronic bronchitis patients had a higher fat mass (P< 0.05) and a lower bone mineral content (P< 0.01) than the healthy volunteers. CONCLUSIONS: Substantial differences in body composition were found not only between chronic obstructive pulmonary disease patients and healthy volunteers, but also between chronic bronchitis and emphysema patients.

Absorptiometry, Photon

Bioelectrical impedance analysis to assess changes in total body water in patients with cancer.

Predominantly based on studies in obese individuals, the applicability of single-frequency bioelectrical impedance analysis (BIA) to measure changes in total body water and fat-free mass has been questioned. To further clarify this issue, we compared changes in BIA-derived height(2)/resistance (ht(2)/R) with changes in total body water (deuterium dilution, delta-TBWdeu) in cancer patients participating in a clinical trial. Thirty-three patients (mean body mass index 23.2 +/- 3.5 kg/m(2)) were studied after an average follow-up of 11 weeks. Changes in TBWdeu occurred in both directions (mean +0.2 +/- 1.6 L, range -3.3 to +3.1 L). These changes were significantly predicted by changes in ht(2)/R (r(2)0.43, P < 0.0001, SEE 1.22 L), although precision was poor (residual SD 1. 2 L). There were in this regard no significant differences between patients with and without underweight. We conclude that in underweight and normal-weight cancer patients, BIA-derived changes in ht(2)/R significantly predict changes in total body water assessed by deuterium dilution.

Adipose Tissue

Impairment of quality of life: rheumatoid arthritis versus sarcoidosis.

BACKGROUND: Quality of life (QOL) has become an important item in health care. QOL should be a major target of treatment in chronic diseases such as rheumatoid arthritis (RA) and sarcoidosis. The aim of this study was to compare the impact of RA and sarcoidosis on patients' QOL. We expected more serious impairment of QOL in the RA group than in the sarcoidosis group. METHODS: QOL was studied in RA patients (n = 32), sarcoidosis patients (n = 37), and a healthy control group (n = 37) employing the World Health Organization Quality of Life assessment instrument (WHOQOL-100). RESULTS: In both patient groups QOL was impaired with respect to Physical Health, Level of Independence (P < 0.001), and Overall QOL and General Health (P < 0.01). Moreover, RA patients appeared to have a lower QOL with respect to Pain and Discomfort (P < 0.001) and Mobility (P < 0.001). CONCLUSIONS: In RA and sarcoidosis, fatigue and sleep were major problems. In contrast to our expectations, with respect to activities of daily living and working capacity, the two patient groups did not show any difference. Impairment of QOL was more serious and included more aspects of QOL in RA than in sarcoidosis.

Adult

Association of fatigue with an acute phase response in sarcoidosis.

The pathophysiological explanation for fatigue, one of the most common symptoms in sarcoidosis, still has to be elucidated. It was hypothesized that the presence of fatigue is associated with an acute phase response in sarcoidosis. A cross-sectional study was performed in 38 sarcoidosis patients. Resting energy expenditure (REE) was measured in the fasting state by indirect calorimetry using a ventilated hood and adjusted for fat-free mass (FFM). Patients with fatigue (n=25) also suffered more frequently from other symptoms, such as exercise intolerance (p=0.01), the need for sleep (p=0.02) and weight loss (p=0.01), compared to those without fatigue (n=13). However, no relationship was found between fatigue and serum angiotensin-converting enzyme (sACE) or lung function impairment. Patients with fatigue had higher levels of C-reactive protein (CRP) (11.4+/-6.8 microg x mL(-1), p<0.0001) and REE adjusted for FFM (33.0+/-3.7 kcal x kg FFM(-1), p<0.003) compared to those without fatigue (3.2+/-2.2 mg x mL(-1); 29.2+/-2.8 kcal x kg FF(-1)). Furthermore, REE/FFM was significantly related to CRP (r=0.54, p=0.001). This study confirms the presence of an acute phase response as indicated by metabolic derangements and a moderate increase in C-reactive protein levels in sarcoidosis, particularly in those patients with constitutional symptoms. Future studies should focus on the clinical relevance and therapeutic implications of these findings.

Acute-Phase Reaction

N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.

Administration, Oral

Intrapulmonary gas mixing and the sloping alveolar plateau in COPD patients with macroscopic emphysema.

Chronic obstructive pulmonary disease patients, especially those with emphysema, show steep slopes of the alveolar plateau (S). This study tested the hypothesis that continued gas exchange between poorly and well-ventilated lung units by means of collateral ventilation would contribute to S in these patients. Nine young volunteers, nine older volunteers and 11 patients with macroscopic emphysema performed wash-out tests with helium (He) and sulphur hexafluoride (SF6). S was determined for breaths 1-5 (range 1), and for breaths between 95% and 98% of complete wash-out (range 2). An unequal ventilation index (UVI) was defined as the ratio between the estimated mean alveolar pressure and the end tidal pressure (PET) of each tracer gas, calculated over range 2. Over the same range, a phase III ratio was calculated by dividing PET by the estimated pressure at Fowler dead space. In all groups of subjects, the S for He and SF6 were greater for range 2 than for range 1 (p< or =0.012). In the emphysema patients, the correlations between S and UVI were 0.72 for He (p=0.012) and 0.81 for SF6 (p=0.002), while the mean phase III ratios were 1.7 for He and 2.4 for SF6, much less than their theoretical maxima. It was concluded that in patients collateral ventilation may account for only a small part of the increase in the alveolar plateau slope between ranges 1 and 2, and that this increase was mainly caused by unequal ventilation in combination with sequential emptying of lung units. The degree of sequential emptying, however, was modest compared with its full potential.

Adult

Interval versus continuous training in patients with severe COPD: a randomized clinical trial.

Limited information is available regarding the physiological responses to different types of exercise training in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was two fold: firstly, to investigate the physiological response to training at 60% of achieved peak load in patients with severe COPD; and secondly to study the effects of interval (I) versus continuous (C) training in these patients. Twenty-one patients with COPD (mean+/-SD forced expiratory volume in one second: 37+/-15% of predicted, normoxaemic at rest) were evaluated at baseline and after 8 weeks' training. Patients were randomly allocated to either I or C training. The training was performed on a cycle ergometer, 5 days a week, 30 min daily. The total work load was the same for both training programmes. C training resulted in a significant increase in oxygen consumption (V'O2) (17%, p<0.05) and a decrease in minute ventilation (V'E)/V'O2 (p<0.01) and V'E/carbon dioxide production (V'CO2) (p<0.05) at peak exercise capacity, while no changes in these measures were observed after interval training. During submaximal exercise a significant decrease was observed in lactic acid production, being most pronounced in the C-trained group (-31%, p<0.01 versus -20%, p<0.05). Only in the I-trained group did a significant increase in peak work load (17%, p<0.05) and a decrease in leg pain (p<0.05) occur. Training did not result in a significant improvement in lung function, but maximal inspiratory mouth pressure increased in both groups by 10% (C: p<0.05) and 23% (I: p<0.01). The present study shows a different physiological response pattern to interval or continuous training in chronic obstruction pulmonary disease, which might be a reflection of specific training effects in either oxidative or glycolytic muscle metabolic pathways. Further work is required to determine the role of the different exercise programmes and the particular category of patients for whom this might be beneficial.

Aged

Diagnostic value of BAL fluid cellular profile and enzymes in infectious pulmonary disorders.

Determination of the cellular profile of bronchoalveolar lavage fluid (BALF), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) appeared to be useful in monitoring pulmonary damage. The aim of this study was to investigate whether the cellular profile, LDH, its isoenzyme pattern and/or ALP in BALF are useful in the diagnostic work-up of patients with suspected pneumonia. The BALF specimens of 80 patients were studied. Group I consisted of patients with a pulmonary infection (n=33) and group II of patients without signs of a pulmonary infection (n=47). Differentiation between these two groups was based upon the results of microscopy and quantitative cultures. The absolute as well as relative numbers of polymorphonuclear neutrophils (PMNs) was significantly higher in group I compared to group II (p<0.0001). The absolute number of PMNs showed a sensitivity of predicting the correct group of 95.7% and a specificity of 84.8%. The LDH activity in BALF was significantly higher in group I than in group II (p<0.0001). The LDH4/LDH5 ratio in BALF was lower in group I compared to group II (p<0.0001) and appeared to be the best discriminator between the two groups with a sensitivity of 93.6% and a specificity of 93.9%. In conclusion, the number of polymorphonuclear neutrophils as well as the lactate dehydrogenase activity, particularly its isoenzymes, in bronchoalveolar lavage fluid appeared to be of potential practical value to distinguish between infectious and noninfectious pulmonary disorders.

Alkaline Phosphatase

Relationship between enzymatic markers of pulmonary cell damage and cellular profile: a study in bronchoalveolar lavage fluid.

It has been suggested that alterations in bronchoalveolar lavage fluid (BALF) reflect pathologic changes in the lung. Cytoplasmatic enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and LDH isoenzymes are recognized indicators of cell damage or death. The aim of this study was to determine whether there is a relation between the enzyme activity and the cell types present in BALF. Therefore, BALF samples obtained from patients with various pulmonary disorders were studied. Out of these samples a group with mainly polymorphonuclear neutrophils (PMNs; n = 15; Group I) and another with mainly alveolar macrophages (AMs; n = 10; Group II) were selected. Additionally, the value of analysis of lysed cells in BALF for assessment of LDH-isoenzyme patterns was examined. The cell-free fraction of BALF of Group II showed lower LDH and ALP activity compared to Group I. The LDH-isoenzyme pattern also differed, with the LDH3/LDH5 ratios being lower in all BALF samples with predominantly PMNs than in BALF samples with predominantly AMs. Lysis of the cells present in the BALF samples by sonication prior to LDH-isoenzyme analysis provided no additional information beyond that found by analysis of the cell-free BALF. In conclusion, determination of enzyme activity appears to be useful in monitoring pulmonary inflammation.

Alkaline Phosphatase

The DD genotype of the angiotensin converting enzyme gene is negatively associated with right ventricular hypertrophy in male patients with chronic obstructive pulmonary disease.

The renin angiotensin system plays an important role in the development of pulmonary artery remodeling and right ventricular hypertrophy in hypoxia-induced pulmonary hypertension as may occur in patients with COPD. Several polymorphisms of genes encoding for components of the renin angiotensin system such as the M235T polymorphism in the angiotensinogen gene, the 287-base-pair insertion (I)/deletion (D) polymorphism at intron 16 of the ACE gene, and the A1166C polymorphism in the angiotensin II type 1 receptor gene have been associated with an increased risk of cardiovascular diseases. With respect to the pulmonary circulation, only limited data exist on possible associations between polymorphisms of these genes and pulmonary hypertension and/or right ventricular hypertrophy. The objective of the present study was to investigate a possible relationship between polymorphisms of the renin angiotensin system and electrocardiographic evidence of right ventricular hypertrophy in patients with COPD. We therefore determined the angiotensinogen (M235T), angiotensin converting enzyme (I/D), and angiotensin II type 1 receptor (A1166C) genotypes in 87 patients with severe COPD and correlated these data with electrocardiographic parameters of right ventricular hypertrophy. Thirty-one patients (36%) of 87 patients with COPD showed electrocardiographic evidence of right ventricular hypertrophy. In the male, but not in the female, subgroup, the angiotensin-converting enzyme DD genotype was negatively associated with electrocardiographic evidence of right ventricular hypertrophy (male: chi2 = 3.8, p = 0.05; female: chi2 = 0.05, p = 0.82). We found no associations between the investigated polymorphisms in the angiotensinogen and angiotensin II type 1 receptor genes and electrocardiographic evidence of right ventricular hypertrophy.

Aged

Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic wasting, in part associated with a chronic inflammatory response. The aim of this study was to investigate cross-sectionally and prospectively the potential role of leptin in relation to systemic inflammation in the regulation of the energy balance in COPD. Body composition by deuterium dilution, resting energy expenditure (REE) by indirect calorimetry, and plasma concentrations of leptin and soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75 by ELISA were measured in 27 male patients with emphysema and 15 male patients with chronic bronchitis (disease-subtype defined by high-resolution computed tomography [HRCT]). Emphysematous patients were characterized by a lower body mass index due to a lower fat mass (FM) (p = 0.001) and by lower mean (detectable) leptin concentrations (p = 0.020) compared with bronchitic patients. Leptin was exponentially related to FM in emphysema (r = 0.74, p < 0.001) and in chronic bronchitis (r = 0.80, p = 0.001). Furthermore, a significant partial correlation coefficient between leptin and sTNF-R55 adjusted for FM and oral corticosteroid use was seen in emphysema (r = 0.81, p < 0.001) but not in chronic bronchitis. In 17 predominantly emphysematous depleted male patients with COPD, baseline plasma leptin divided by FM was in addition logarithmically inversely related to baseline dietary intake (r = -0.50, p = 0.047) and to the degree of weight change after 8 wk of nutritional support (r = -0.60, p = 0.017). This proposed cytokine-leptin link in pulmonary cachexia may explain the poor response to nutritional support in some of the cachectic patients with COPD and may open a novel approach in combating this significant comorbidity in COPD. Schols AMWJ, Creutzberg EC, Buurman WA, Campfield LA, Saris WHM, Wouters EFM. Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.

Aged

Changes in levels of catalase and glutathione in erythrocytes of patients with stable asthma, treated with beclomethasone dipropionate.

In asthmatic patients, antioxidant defence is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little is known of their effect on cellular antioxidant levels. The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP; 1,000 microg x day(-1)) on erythrocyte antioxidant levels in stable asthmatic patients. Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. The results show that during treatment with BDP, erythrocyte catalase levels increased (at entry (mean +/-SEM) 41+/-4, after 6 weeks 54+/-4 micromol H2O2 x min(-1) x g haemoglobin (Hb)(-1), p = 0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1) (p = 0.04)). In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding ((mean +/-SEM) 340+/-39 and 153+/-52x10(6) cells x L(-1), respectively, p = 0.05). The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma.

Administration, Inhalation

Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis?

The aim of this study was to assess whether the cellular bronchoalveolar lavage fluid (BALF) profile, particularly the number of polymorphonuclear neutrophils (PMNs), is associated with disease severity of sarcoidosis and its usefulness in determining remission. Twenty-six nonsmoking outpatients with sarcoidosis were included in this study. The patients were divided into two subgroups according to the absolute number of PMNs in BALF: < or =0.2x10(4) cells x mL(-1) (group 1; n = 15) and >0.2x10(4) cells x mL(-1) (group 2; n = 11). The radiographic stage, high-resolution computed tomography (HRCT) findings, 67Ga lung uptake as well as lung function tests differed significantly between group 1 and 2. Follow-up revealed that 14 (93.3%) patients of group 1 compared to four (36.4%) of group 2 recovered spontaneously without the help of corticosteroids. In contrast, no differences were found in the number of lymphocytes in BALF nor in the serum angiotensin converting enzyme (sACE) level between both groups. The number of PMNs, the transfer factor of the lungs for carbon monoxide (TL,CO), the forced expiratory volume in one second (FEV1) and one of the HRCT subscores discriminated between patients with different disease progression. Of these parameters the PMNs appeared to be the only one which differentiated patients who demonstrated remission and those who deteriorated. In conclusion, these results indicate that the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid distinguish between sarcoidosis patients who demonstrated remission and those having a more severe course of the disease. Whether polymorphonuclear neutrophils may be considered as markers of disease activity and/or prognosis in sarcoidosis needs further investigation.

Adult

Weight loss and low body cell mass in males with lung cancer: relationship with systemic inflammation, acute-phase response, resting energy expenditure, and catabolic and anabolic hormones.

The aim of the present study was to investigate, in human lung cancer, the relationship between weight loss and the existence of a low body cell mass (BCM) on the one hand, and the putative presence of systemic inflammation, an increased acute-phase response, anorexia, hypermetabolism and changes in circulating levels of several anabolic and catabolic hormones on the other. In 20 male lung cancer patients, pre-stratified by weight loss of >/=10% (n=10) or of <10% (n=10), the following measurements were performed: BCM (by dual-energy X-ray absorptiometry/bromide dilution), circulating levels of sTNF-R55 and sTNF-R75 (soluble tumour necrosis factor receptors of molecular masses 55 and 75 kDa respectively), interleukin-6, lipopolysaccharide-binding protein, albumin, appetite (scale of 0-10), resting energy expenditure (by indirect calorimetry) and circulating levels of catabolic (cortisol) and anabolic [testosterone, insulin-like growth factor-I (IGF-I)] hormones. Compared with the patients with a weight loss of <10%, those with a weight loss of >/=10% were characterized by higher levels of sTNF-R55 (trend towards significance; P=0.06), and lower levels of albumin (27.4 compared with 34.4 mmol/l; P=0.02), testosterone (13.2 compared with 21.5 nmol/l; P=0.01) and IGF-I (119 compared with 184 ng/ml; P=0.004). In the patient group as a whole, the percentage weight loss was significantly correlated with sTNF-R55 (r=0.59, P=0.02), albumin (r=-0.63, P=0.006) and IGF-I (r=-0.50, P=0.02) levels. Height-adjusted BCM was significantly correlated with sTNF-R55 (r=-0.57, P=0.03), sTNF-R75 (r=-0.50, P=0. 04), lipopolysaccharide-binding protein (r=-0.50, P=0.04), albumin (r=0.56, P=0.02) and resting energy expenditure/BCM (r=-0.54, P=0. 03), and there was a trend towards a correlation with IGF-I concentration (r=0.44, P=0.06). We conclude that, in human lung cancer, weight loss and the presence of a low BCM are associated with systemic inflammation, an increased acute-phase response and decreased levels of IGF-I. In addition, a decreased BCM is associated with hypermetabolism.

Acute-Phase Proteins