INCREASED ENERGY-EXPENDITURE IN CYSTIC-FIBROSIS IS ASSOCIATED WITH SPECIFIC MUTATIONS

1. Measurements of resting metabolic rate were made by open-circuit indirect calorimetry in 78 unrelated cystic fibrosis patients and 30 healthy control subjects. The aims of this study were: (i) to determine the range of variability in resting metabolic rate in cystic fibrosis, (ii) to relate this to pulmonary function and body size, and (iii) to investigate the hypothesis that, in cystic fibrosis, genotype exerts a significant influence on energy requirements. 2. There was no significant difference in age or body weight between patients with cystic fibrosis and control subjects. Resting metabolic rates for control subjects fell within +/- 10% of predicted values. Fifty-nine per cent of patients with cystic fibrosis had elevated resting metabolic rates (i.e. > 111% of predicted). Genotype analysis divided the patients with cystic fibrosis into three groups: DELTA-F508 homozygotes, DELTA-F508 heterozygotes and others. Patients homozygous for the DELTA-F508 allele had a significantly higher resting metabolic rate (121% of predicted, 95% confidence interval 116-126%), compared with other genotypes (P < 0.005). 3. There were significant differences in pulmonary function between the groups (P < 0.005). However, after adjustment of individual resting metabolic rates for differences in pulmonary function by using analysis of covariance, resting metabolic rates remained significantly higher for DELTA-F508 homozygotes than for other genotypes (P < 0.05). 4. We conclude that there is a significant contribution to resting metabolic rate in cystic fibrosis associated with specific mutations that is not explained by declining pulmonary function. The increase in resting metabolic rate in patients homozygous for mutations involving a nucleotide-binding fold, which may result from a disruptive effect on ATP binding, indicates a practical implication of genotype identification with the need for effective nutritional intervention and support in this patient subgroup.