RESTING ENERGY-EXPENDITURE, PULMONARY INFLAMMATION, AND GENOTYPE IN THE EARLY COURSE OF CYSTIC-FIBROSIS

To further investigate the early course of cystic fibrosis (CF), speci fically to examine factors contributing to energy imbalance, we examin ed resting energy expenditure (REE) (by indirect calorimetry) per unit body weight and metabolically active body cell mass (by total body po tassium), in relation to CF genotype (by genomic DNA analysis), CF pan creatic phenotype, and markers of pulmonary inflammation (from broncho alveolar ravage fluid). Eighteen subjects with presymptomatic CF who w ere less than 2 years of age (n=11, Delta F508/Delta F508 genotype; n= 15, pancreatic insufficiency phenotype), identified by newborn screeni ng, were compared with age-, sex-, and length-matched control subjects (n=13). Those with the Delta F508/Delta F508 genotype had significant ly higher mean REE expressed per unit body weight (125%) and body cell mass (115%; p <0.03). Those with other genotypes (n=7) did not, as a group, have significantly different mean REEs, but individuals with kn own ''severe'' genotypes had REEs in the high range and those with a p ancreatic-sufficient phenotype had significantly lower REE than those with a pancreatic-insufficient phenotype (p <0.05), and REEs were in t he 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-1 be ta equally in both CF genotype groups. These markers of pulmonary infl ammation were not correlated, individually or collectively, with REE o r genotype. We conclude that genotypic variations in energy balance ar e detectable early in CF unrelated to lung inflammation. Subclinical d efects in body composition and pulmonary integrity occur early in CF a nd, in combination with increased cellular metabolic activity, have im portant clinical implications with respect to early diagnosis and mana gement.