Early non-elective readmission for chronic obstructive pulmonary disease is associated with weight loss.

AIM: To identify risk factors for early nonelective readmission in patients with chronic obstructive pulmonary disease, previously admitted for an exacerbation of their disease. Clinical characteristics were analysed with special emphasis on body weight on admission and weight changes during hospitalization. METHODS: The computerized hospital database was used to select all hospital admissions in 1994 and 1995 with exacerbation of chronic obstructive pulmonary disease as main discharge diagnosis. Cases were retained if they were nonselectively readmitted within 14 days after prior discharge, and if they had no oedema. Controls were randomly selected from the discharge listing and were not readmitted within 3 months. Cases and controls were matched on several parameters including FEV(1)% predicted obtained during a stable phase of the disease. Hospital charts were reviewed for clinical parameters on admission, discharge and readmission. RESULTS: Fourteen cases were retained in the study. On admission, lung function, blood gases and parameters describing morbidity and social factors, were not different in cases and controls. The discharge procedure was adequate. During hospitalization the cases lost weight (mean+/-SD) (-1.6+/-1.9 kg, P= 0.01), while controls remained weight stable. Using a matched pairs logistic regression analysis, weight loss during hospitalization (P= 0.011) and low BMI on admission (P= 0. 046) were related to the increased risk of unplanned readmission. CONCLUSION: These findings provide further support for the concept that nutritional status is related to morbidity in COPD.

Oral UFT, etoposide and leucovorin in recurrent non-small cell lung cancer: a non-randomized phase II study.

BACKGROUND: Oral treatment regimens with few side effects are appealing in the 2nd or 3rd line treatment of non-small cell lung cancer (NSCLC) patients. PURPOSE: The aim was to investigate the efficacy and toxicity of the oral combination etoposide, Uracil-Tegafur (UFT) and leucovorin in 2nd or 3rd line in Caucasian patients with advanced NSCLC. METHODS: Etoposide 50 mg/m(2), UFT 250 mg/m(2) and leucovorin 90 mg (fixed dose) were dosed in 3 gifts approximately 8h apart for 14 days followed by 1 week rest every 3 weeks until progressive disease (PD). Primary endpoint was response rate (RR), secondary endpoints toxicity and time to progression (TTP). RESULTS: The median number of cycles was 3.5 (95% CI 2-5); 9 patients received > or =6 cycles, 4>10 cycles. The median dose intensities for etoposide and UFT were 223 mg/m(2)/week (95% CI 213-232) and 1092 mg/m(2)/week (95% CI 1032-1167), the relative dose intensities 92% and 90%, respectively. Grade 3/4 neutropenia was observed in 12% (4/32), grade 3/4 thrombocytopenia in 15% (5/32), without febrile neutropenia. Non-hematological toxicity grade 3 included hepatic toxicity (6%), lethargy (15%), diarrhea (3%) and nausea (3%). One patient developed grade 4 arterial ischemia. Fourteen percent (95% CI 4-33%) (4/28) had a confirmed partial response, 57% (95% CI 44-81%) (16/28) stable disease and 28% (95% CI 19-56%) (8/28) progressive disease. The median TTP was 3 months (95% CI 1.3-4.4), the median overall survival 6.7 months (95% CI 4.0-9.3). CONCLUSION: The combination of UFT, etoposide and leucovorin is active in 2nd or 3rd line therapy of Caucasian NSCLC patients and because of its favourable toxicity profile this treatment warrants further investigation.

Elevated inosine monophosphate levels in resting muscle of patients with stable chronic obstructive pulmonary disease.

In order to investigate disturbances in energy metabolism in resting muscle of patients with stable chronic obstructive pulmonary disease (COPD), concentrations of adenine nucleotides and related compounds were examined comparing 34 COPD patients with eight age-matched healthy control subjects. Biopsies were taken from the anterior tibialis muscle. Special attention was paid to the muscle content of inosine monophosphate (IMP), a deamination product of adenosine monophosphate (AMP), because IMP formation is thought to reflect an imbalance between resynthesis and utilization of adenosine triphosphate (ATP). The absolute concentrations of high-energy phosphate compounds did not differ between patients and control subjects, but the ATP/ADP and the phosphocreatine/creatine ratio were significantly lower in the patients. IMP (detection level = 0.06 mmol/kg dry weight) was detected in 25 of 34 patients versus one of eight control subjects (p = 0.001). Mean (SD) IMP level in these patients was 0.18 (0.14) versus 0.06 mmol/kg dry weight in the one control subject. Based on the presence of detectable levels of muscle IMP, the patient group was divided into two subgroups. In IMP-positive patients, ATP/ADP and phosphocreatine/creatine ratios were significantly lower than in IMP-negative patients. IMP-positive patients were furthermore characterized by a significantly lower DL(CO). The results of this study indicate an imbalance between the utilization and resynthesis of ATP in resting muscle of patients with stable COPD.

Plasma and muscle amino acid levels in relation to resting energy expenditure and inflammation in stable chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD), muscle wasting can occur independently of fat loss, suggesting disturbances in protein metabolism. In order to provide more insight in amino-acid (AA) metabolism in patients with stable COPD, we examined arterial plasma and anterior tibialis muscle AA levels, comparing 12 COPD patients with eight age-matched healthy control subjects. We also studied relationships between AA levels, the acute phase response as measured by lipopolysaccharide-binding protein (LBP), and resting energy expenditure (REE). In contrast to findings in acute diseases associated with muscle wasting, we found increased muscle glutamine (GLN) levels in our patient group (mean +/- SEM = 10,782 +/- 770 versus 7,844 +/- 293 micromol/kg wet weight, p < 0. 01). Furthermore, muscle arginine, ornithine, and citrulline were significantly increased in the patient group, whereas glutamic acid was decreased. In plasma, the sum of all AA (SumAA) was decreased in the patient group (2,595 +/- 65 versus 2,894 +/- 66 micromol/L, p < 0.01), largely because of decreased levels of alanine (254 +/- 10 versus 375 +/- 25 micromol/L, p < 0.0001), GLN (580 +/- 17 versus 641 +/- 17 micromol/L, p < 0.05), and glutamic acid (91 +/- 5 versus 130 +/- 10 micromol/L, p < 0.01). LBP levels were increased in COPD patients as compared with controls (11.7 +/- 4.5 versus 8.6 +/- 1.0 mg/L, p < 0.05), and showed a positive correlation with REE (r = 0. 49, p = 0.03), a negative correlation with the SumAA in plasma (r = -0.76, p < 0.0001), and no correlation with muscle AA levels. In conclusion, various disturbances in plasma and muscle AA levels were found in COPD patients. A relationship between the observed decreased plasma AA levels and inflammation was suggested.

Clinical assessment after a life-threatening attack of asthma; the role of bronchial hyperreactivity.

Between 1973 and 1986, 19 patients were treated on 21 occasions for life-threatening attacks of asthma. Twelve times mechanical ventilation was needed. None of the patients died. Most of the patients had been recognized as severely asthmatic before the life-threatening attack. Thirteen out of the 19 patients had previously been admitted with a severe asthmatic attack. All patients, except one, were already using maintenance treatment, and 17 had previously been referred to a pulmonologist. During follow-up the bronchial obstruction was, in most cases, fully reversible while using a rather extensive maintenance treatment (maximum forced expiratory volume in one second (FEV1), 69-138% of predicted). Recently, 17 of the 19 patients were reinvestigated, while in stable phase. The patients who had been mechanically ventilated were significantly more sensitive to inhaled histamine than the patients who had not been mechanically ventilated. This was not explained by any difference in basal FEV1 % pred or dosage of corticosteroids. A very low provocation concentration of histamine producing a 20% fall in FEV1 (PC20) may indicate the risk of a severe, life-threatening attack of asthma.

Muscle metabolic status in patients with severe COPD with and without long-term prednisolone.

Both abnormalities in high energy phosphate metabolism and a decreased oxidative enzyme capacity have been reported in skeletal muscle of stable chronic obstructive pulmonary disease (COPD) patients. The first aim of this study was to investigate whether these findings are present in anterior tibialis muscle and whether or not they are associated. Abnormalities in mitochondrial structure and function as well as signs of myopathy have been found during corticosteroid treatment. The second aim of this study, therefore, was to investigate whether in COPD patients prolonged use of low dose prednisolone has effects on muscle energy metabolism and qualitative morphology. In a cross-sectional study 15 COPD patients (forced expiratory volume in one second (FEV1) 33+/-9 (mean+/-SD) % predicted) who were steroid-naive (CORT-) were compared with 10 healthy control subjects (HC) and with 14 COPD patients (FEV1 30+/-11 % pred), who had been using oral prednisolone for at least 1 yr (CORT+). It was found that adenosine triphosphate (ATP)/adenosine diphosphate was lower in CORT- compared to HC (5.7 versus 6.2, p=0.03). Inosine monophosphate was detected in 13 of 15 CORT- compared to 3 of 10 HC (p=0.004). However, although indications were found for an imbalance in production and utilization of ATP, comparing CORT- and HC, no differences in oxidative (citrate synthase and 3-hydroxy-acyl-coenzyme A dehydrogenase) and glycolytic (hexokinase, lactate dehydrogenase and phosphofructokinase) enzyme capacities were found. When, comparing steroid-treated and steroid-naive patient subgroups, no differences in the above mentioned parameters of muscle energy metabolism and of muscle qualitative morphology were found.