Resting energy expenditure, pulmonary inflammation, and genotype in the early course of cystic fibrosis M. A. Thomson, MRCP, R. W. Wilmott, MD, C. Wainwright, FRACP, B. Masters, MB, FRACP, P. J. Francis, MD, FRACP, and R. W. Shepherd, MD, FRACP From the Children's Nutrition Research Centre, Royal Children's Hospital, Brisbane, Austra- lia, the Department of Pediatrics, Division of Pulmonary Medicine, Children's Hospital Med- ical Center, Cincinnati, Ohio, and the Cystic FibrosisClinics, Royal Children's and Mater Children's Hospitals, Brisbane, Australia To further investigate the early course of cystic fibrosis (CF), specifically to exam- ine factors contributing to energy imbalance, we examined resting energy expenditure (REE) (by indirect calorimetry) per unit body weight and metaboli- cally active body cell mass (by total body potassium), in relation to CF genotype (by genomic DNA analysis), CF pancreatic phenotype, and markers of pulmonary inflammation (from bronchoalveolar lavage fluid). Eighteen subjects with pres- ymptomatic CF who were less than 2 years of age (n = 1I, ±F508/~F508 genotype; n = 15, pancreatic insufficiency phenotype), identified by newborn screening, were compared with age-, sex-, and length-matched control subjects (n = 13). Those with the ~F508/~F508 genotype had significantly higher mean REE ex- pressed per unit body weight (125%) and body cell mass (I 15%; p <0.03). Those with other genotypes (n = 7) did not, as a group, have significantly different mean REEs, but individuals with known "severe" genotypes had REEsin the high range and those with a pancreatic-sufficient phenotype had significantly lower REEthan those with a pancreatic-insufficient phenotype (p <0.05), and REEswere in the normal range. Examination of bronchoalveolar lavage fluid revealed positive culture results (7/10) but variable colony counts, neutrophil percentages, and concentrations of interleukin-8 and interleukin-113 equally in both CF genotype groups. These markers of pulmonary inflammation were not correlated, individ- ually or collectively, with REEor genotype. We conclude that genotypic variations in energy balance are detectable early in CF unrelated to lung inflammation. Subclinical defects in body composition and pulmonary integrity occur early in CF and, in combination with increased cellular metabolic activity, have important clinical implications with respect to early diagnosis and management. (J Pediatr 1996; 129:367-73) Supported in part by the Cystic Fibrosis Association of Queensland and by the Royal Children's Hospital Foundation (Dr. Thomson, Research Fellow). Submitted for publication July 25, 1995; accepted April 23, 1996. Reprint requests: R. W. Shepherd, MD, FRACP, Associate Profes- sor, Children's Nutrition Research Centre, Royal Children's Hos- pital, Brisbane, Queensland 4029, Australia. Copyright © 1996 by Mosby-Year Book, Inc. 0022-3476/96/$5.00 + 0 9/21/74505 Malnutrition and nutritional growth retardation is a common complication of cystic fibrosis known to affect prognosis adversely.l' 2 The observation that raised energy expenditure contributes to energy imbalance is now well documented. 3-I3 In infants with presymptomatic CF, resting energy expendi- ture may be increased, 5' 6 and we suggested previously that total energy expenditure is increased] although this possi- bility is disputed. 13 In older subjects, it appears that there may be compensation for increased REE by reducing spon- 367