Nutritional depletion in patients on long-term oxygen therapy and/or home mechanical ventilation.

The purpose of this study was to estimate the prevalence of malnutrition in outpatients on long-term oxygen therapy or home mechanical ventilation, to determine the relationships between malnutrition and impairment/disability and smoking and also to identify relevant tools for routine nutritional assessment. In 744 patients (M:F 1.68, aged 65+/-15 yrs) with chronic obstructive pulmonary disease (COPD, 40%), restrictive disorders (27%), mixed respiratory failure (15%), neuromuscular diseases (13%) and bronchiectasis (5%), body mass index (BMI), fat-free mass (FFM), serum albumin, transthyretin, 6-min walking test, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and blood gases were recorded. FFM was the most sensitive parameter for detecting malnutrition, being abnormal in 53.6% of patients, while BMI was <20 in 23.2%, serum albumin <35 g x L(-1) in 20.7%, and serum transthyretin <200 mg x L(-1) in 20%. FFM depletion predominated in neuromuscular, bronchiectasis and restrictive disorders. BMI and FFM were correlated with FEV1, FVC and 6-min walking test. In multivariate analysis a BMI<20 was related to FEV1 and smoking habits, and a low FFM to smoking, FEV1 and female sex. Malnutrition is highly prevalent in home-assisted respiratory patients and is related to causal disease, forced expiratory volume in one second, smoking and disability. Fat-free mass appeared to be the most sensitive and relevant nutritional parameter according to impairment and disability.

In vivo hypoxic exposure impairs metabolic adaptations to a 48 hour fast in rats.

Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p<0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.

Mechanism of gluconeogenesis inhibition in rat hepatocytes isolated after in vivo hypoxia.

Gluconeogenesis was studied in hepatocytes isolated from fasted rats submitted to 24 h of hypoxic exposure (inspired O2 fraction 0.1) or to room air. Hepatocytes from hypoxic rats compared with controls exhibited a lower gluconeogenic rate with lactate (5.1 +/- 0.3 vs. 7.2 +/- 0.3 mumol.min-1.g dry cells-1, P < 0.001) but not with dihydroxyacetone (9.1 +/- 0.3 vs. 9.4 +/- 0.4 mumol.min-1.g dry cells-1), suggesting involvement of the phosphoenolpyruvate-pyruvate cycle. Experiments with perifused hepatocytes from hypoxic and control rats showed a single relationship between phosphoenolpyruvate and glucose flux (JGlc) but two different curves when cytosolic oxalacetate was plotted against JGlc. The decreased phosphoenolpyruvate carboxykinase (PEPCK) activity in the hypoxic group (9.0 +/- 0.9 vs. 16.2 +/- 1.9 nmol.min-1.mg protein-1, P < 001) without change in the Michaelis constant further settled the involvement of this step. The significant decrease in PEPCK mRNA levels in livers from hypoxic rats led us to propose that in vivo hypoxic exposure inhibits gluconeogenesis at the PEPCK level by decreasing PEPCK gene transcription.

Changes in left ventricular ejection fraction during REM sleep and exercise in chronic obstructive pulmonary disease and sleep apnoea syndrome.

Nine patients, 4 with chronic obstructive pulmonary disease (COPD) and 5 with obstructive sleep apnoea syndrome (OSAS) were monitored during sleep, rest and exercise. Left ventricular ejection fraction (LVEF) was investigated using gated equilibrium 99mtechnetium ventricular scintigraphy during rapid eye movement (REM) sleep, during exercise, and during wakeful rest. Control wakeful rest periods used for comparison with a study state (either REM sleep or exercise) were always selected during the same circadian segment as that state. Myocardial stress thallium-201 scintigraphy was performed during, and 4 h after, exercise, and results were compared to a daytime rest period. Several patients had myocardial hypoperfusion despite a normal electrocardiographic (ECG) treadmill test. During REM sleep, all patients exhibited a significant change in LVEF (greater than 5%) compared to wakefulness. During exercise, 5 subjects increased their LVEF normally (greater than 5%) and 4 (1 COPD, 3 OSAS) decreased it. All patients had a similar change (increase or decrease) during REM and at maximal exercise. Our results suggest that REM sleep in COPD and in OSAS can produce a myocardial stress as great as that produced by exercise. We conclude that REM sleep, like exercise, is a state in which morbidity may become higher and that it may account for mortality in COPD and OSAS patients with compromised myocardial circulation.

Effects of captopril combined with oxygen therapy at rest and on exercise in patients with chronic bronchitis and pulmonary hypertension.

The aim of this study was to determine the effects of captopril combined with oxygen therapy on pulmonary hemodynamics and gas exchange in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension. Eleven subjects, with severe airflow obstruction (FEV1/FVC: 42 +/- 11%) and chronic respiratory failure (PaO2: 54 +/- 6 mm Hg, PaCO2: 46 +/- 8 mm Hg) treated with long-term oxygen, underwent two successive hemodynamic and arterial gas studies, at rest and during exercise. All the studies were performed whilst the patients were breathing oxygen, at rest and during exercise and 1 h after intake of 12.5 mg of captopril. The second study was performed in 9 out of the 11 patients after 8 weeks of treatment with 12.5 mg captopril 3 times daily. At rest, there was no significant effect of captopril. Mean pulmonary arterial pressure (PAP) showed a trend towards decrease after 8 weeks treatment. During exercise, there was a statistically significant decrease of mean PAP, pulmonary capillary wedge pressure and total pulmonary vascular resistance, without any deleterious effect on blood gases. However, the clinical significance of these variations during exercise is poor. We conclude that a low dose of captopril associated with oxygen therapy has no significant clinical effect on pulmonary hemodynamics at rest and during exercise in COPD.

Pulmonary histiocytosis X with mediastinal lymph node involvement.

In this report, we describe a patient with the classic histology of pulmonary histiocytosis X, who had bilateral reticulonodular densities and mediastinal lymph node involvement. The diagnosis was confirmed by the use of electron microscopy and immunohistochemical markers (PS100, HLA-DR, and CD1), which allowed us to recognize the lymph node infiltration of X histiocytes. An association of mediastinal lymph node enlargement with pulmonary histiocytosis X has been reported but it has never been histologically documented.