Repeatability and methodology of resting energy expenditure in patients with cystic fibrosis.

In this study, intra-individual variation of resting energy expenditure (REE) in adults with cystic fibrosis (CF) and the effect of measurement duration were determined. Twelve adults with CF and chronic Pseudomonas aeruginosa (Ps. aeruginosa) infection and 12 healthy volunteers, matched for age and sex were studied whilst clinically stable on days 1.2, and 15. Respiratory gas exchange was monitored by continuous measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) using a ventilated hood indirect calorimeter. Coefficients of variation (CVs) were 4.3% in patients and 2.4% in controls comparing days 1 and 2. The CV for patients was 5.0% and for controls 2.9% comparing days 1 and 15. The effect of measurement duration on REE was assessed in eight of the CF patients. REE remained stable for 40 min but tended to rise by 80 min. Plasma catecholamine concentrations were stable between study days in patients but fell with time in controls suggesting some adaptation to experimental procedure. The greater variability of REE in patients was related to change in serum CRP over 2 weeks. REE is a repeatable measurement in clinically stable patients with CF, though variability was greater in patients than healthy subjects. This has implications for the design and interpretation of longitudinal studies of REE in patients with chronic lung disease.

Resting energy expenditure and oxygen cost of breathing in patients with cystic fibrosis.

BACKGROUND: Resting energy expenditure (REE) is often increased and may contribute towards energy imbalance in patients with cystic fibrosis. Several mechanisms may lead to increased REE including the gene defect, the effect of chronic infection, and abnormal pulmonary mechanics. Increased oxygen cost of breathing (OCB) has been demonstrated in patients with chronic obstructive pulmonary disease (COPD), but has not been the subject of extensive study in cystic fibrosis. METHODS: Ten clinically stable patients with cystic fibrosis and 10 healthy control subjects were studied. OCB was estimated using the dead space hyperventilation method. Mixed expired gas fractions were measured by online gas analysers and ventilation by a pneumotachograph. After measurement of resting ventilation and gas exchange, minute ventilation (VE) was stimulated by 6-10 1/min by the addition of a dead space and OCB calculated from the slope of the differences in oxygen uptake (VO2) and VE. REE and the non-respiratory component of REE were calculated from gas exchange data. To assess the repeatability of OCB all subjects had a further study performed one week later. RESULTS: The patients had lower weight, fat free mass (FFM), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (TLCO) than controls. Resting respiratory rate, VE, and oxygen uptake per kilogram of FFM (VO2/kg FFM) were higher in patients (20 (7), 10.4 (1.4) 1/min and 5.5 (0.8) ml/kg FFM/min) than in controls (13 (4), 7.0 (1.2), and 4.2 (0.5), respectively.) The error standard deviation for replicated measures of OCB was 0.5 ml O2/l VE in controls and 0.8 ml O2/l VE in patients with coefficients of variation of 24% in controls and 28% in patients. The mean OCB in patients was 2.9 (1.4) ml O2/l VE and 2.1 (0.7) ml O2/l VE in controls. OCB, expressed as ml/min (VO2resp) was 28.5 (11.7) in patients and 14.0 (3.6) in controls. REE was higher in patients (125.9 (14.0)% predicted) than in controls (99.0 (9.4)%). The estimated non-respiratory component of REE was 112.1 (14.9)% for patients and 93.0 (10.0)% for controls. CONCLUSIONS: In clinically stable patients with cystic fibrosis the OCB at rest is increased but is not the sole explanation for increased metabolic rate. This contrasts with the finding in COPD where the increase in REE is largely explained by increased OCB. This study also showed poor repeatability and OCB measurements similar to earlier studies, which indicates that the technique is not suitable for longitudinal studies.

Tumour necrosis factor-alpha, resting energy expenditure and cachexia in cystic fibrosis.

1. We investigated the relationship between circulating tumour necrosis factor-alpha concentrations, resting energy expenditure, cachexia and altered intermediary metabolism in patients with cystic fibrosis and chronic pulmonary infection. 2. Twenty adult patients with cystic fibrosis and chronic bronchial sepsis covering a spectrum of severity of lung disease (forced expiratory volume in 1 s 30-100% of predicted) were compared with 10 age matched, healthy, non-cystic fibrosis subjects. 3. Circulating tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex concentrations were determined simultaneously with glycerol, non-esterified fatty acids, catecholamines, anthropometric indices and resting energy expenditure (ventilated hood method). 4. Weight, body mass index and arm muscle mass were reduced in patients with cystic fibrosis compared with healthy control subjects (P < 0.01), whereas mean resting energy expenditure was increased [121 versus 101% predicted, mean difference 19.2% (95% confidence interval 11.0-27.4%), P < 0.001]. Circulating concentrations of glycerol (P < 0.01), non-esterified fatty acids (P < 0.01), adrenaline (P < 0.05), tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex (P < 0.01) were increased in patients compared with control subjects [tumour necrosis factor-alpha 96.9 versus 24.7 pg/ml, mean difference 72.2 pg/ml [95% confidence interval 27.7-116.7 pg/ml), P < 0.001]. Resting energy expenditure was significantly related to tumour necrosis factor-alpha levels and forced expiratory volume in 1 s. 5. In patients with cystic fibrosis and chronic pulmonary sepsis changes in resting energy expenditure, body composition and intermediary metabolism are consistent with the systemic effects of the host inflammatory response, which may be responsible for cachexia in adult patients. In particular these changes are consistent with the action of tumour necrosis factor-alpha, which was detected in the circulation during a period of apparent clinical stability.

An assessment of a double-isotope method for the detection of transferrin accumulation in the lungs of patients with widespread pulmonary infiltrates.

1. The accumulation in the lung of the plasma protein transferrin was determined in 44 patients with widespread pulmonary infiltrates of various causes and in 11 healthy volunteers using a double-isotope method based on labelling in vivo of circulating transferrin with indium and erythrocytes with technetium. 2. In 22 patients meeting criteria for the adult respiratory distress syndrome (ARDS) the mean transferrin accumulation rate was threefold greater (P less than 0.005) than in 22 patients not meeting these criteria, although most possessed an appropriate risk factor for ARDS, in addition to extensive radiographic changes. 3. The double-isotope method did not completely separate patients with ARDS from those not meeting the criteria or from control subjects and cannot be considered a diagnostic test for the condition. Statistically significant rates of transferrin accumulation, however, occurred more frequently in patients with ARDS (82%) than in controls (64%) or in those without ARDS (59%).