Am J Clin Nutr 1995;62:633-8. Printed in USA. © 1995 American Society for Clinical Nutrition 633 Reduced copper enzyme activities in blood cells of children with cystic fibrosis1 Susan S Percival, Ellen Bowser, and Mary Wagner ABSTRACT Cystic fibrosis patients are at risk for nutrient deficiencies from malabsorption related to exocnine pancreatic insufficiency. This research examined the copper homeostasis of children with cystic fibrosis. Our objective was to measure cyto- chrome oxidase and copper-zinc superoxide dismutase activities in mononuclear cells, neutrophils, and enythnocytes of adolescents with cystic fibrosis, as well as plasma copper and ceruloplasmin. Thirteen adolescents with pancreatic insufficiency caused by cys- tic fibrosis were compared with 10 age- and sex-matched control subjects. Serum copper concentrations and cenuloplasmin mea- surements were not significantly different between the two groups. Cytochrome oxidase activity was significantly lower in the mono- nuclear cells and copper-zinc superoxide dismutase activity was significantly lower in the neutrophils and erythrocytes of the cystic fibrosis group. Other measures of trace element status such as hemoglobin concentration, serum ferritin, serum zinc, glutathione peroxidase activity, and manganese superoxide dismutase activity were not different between the two groups. Reductions in the activity of two copper-dependent enzymes suggest abnormal cop- per homeostasis in this population. Am J Clin Nutr 1995;62; 633-8. KEY WORDS Copper, cystic fibrosis, copper-zinc super- oxide dismutase activity, cytochrome oxidase, copper status INTRODUCTION Cystic fibrosis (CF) is an autosomal recessive disorder of the exocnine glands. The disease is characterized by high concen- trations of sodium and chloride in the sweat, respiratory diffi- culties from acute and chronic infections, pancreatic insuffi- ciency with persistent malabsonption, and, in some patients, by liver disease and diabetes mellitus. Pancreatic exocrine insuf- ficiency is found in 85-95% of CF patients (1). Despite pan- creatic enzyme-replacement therapy, some fat and micronutri- ent malabsorption occurs. Maldigestion and malabsorption of protein, fat, and fat-soluble vitamins has been fairly well char- actenized but the impact of this disease on water-soluble vita- mm or mineral status has not been well-studied (2). Evidence suggests that the nutritional status of CF patients is directly correlated with survival (3). The functional integrity of the immune system, the course of pulmonary disease, and ulti- mately life span, may be adversely influenced by general or nutrient-specific malnutrition. One such essential nutrient, copper, functions as a cofactor in numerous enzymes that catalyze oxidation-reduction reactions. Serious or overt copper deficiency results in anemia and neu- tropenia (4, 5), heart disorders, muscle weakness, bleeding tendencies, skin and bone disorders related to connective tissue impairment (6, 7), possibly cellular damage from free radical toxicity (8-10), pancreatic atrophy (1 1, 12), and impairment of nearly all cellular functions of the immune system (13, 14). Copper may be particularly critical for neurological develop- ment in growing children because of its role in catecholamine and biopeptide synthesis (15). Although a child with CF may not exhibit any overt signs of copper deficiency, a marginal copper deficiency in addition to other aspects of the disease may complicate or intensify the progression. A reliable indicator of copper status for the general popula- tion does not exist. Serum or plasma copper values were used in the past to determine copper status; however, these values fluctuate in response to hormones and situations not related to copper nutriture (16). Ceruloplasmin (Cp), an acute-phase re- actant, is responsible for as much as a threefold rise in serum copper concentrations. A marginal copper deficiency would not be indicated by serum concentrations of copper if the subject was infected or had an inflammatory condition, as do many CF patients. A case study in 1961 presented an infant with CF who was persistently anemic and was subsequently found to be hypocu- premic (17). A comprehensive case-control study, performed in 1982 with CF children, found serum copper concentrations and Cp activities significantly higher in CF children compared with control subjects (18). Three other studies measured serum copper and found that it was slightly but not significantly higher (19-21). In each study, the only method used to deter- mine copper status was serum copper or Cp. All authors concluded that copper status was normal in CF patients, yet based these conclusions on indicators of copper status that may not be reliable. The objective of this study, then, was to examine copper homeostasis not only in the serum but also in the blood cells of 1 From the Food Science and Human Nutrition Department, and the Division of Pulmonary Diseases/Cystic Fibrosis, Department of Pediatrics, University of Florida, Gainesville. 2 Supported by NIH grants MCJ-129612 and DDK R29-43518. 3 This is Florida Agricultural Journal series number R-04318. 4 Address reprint requests to 55 Percival, Food Science and Human Nutrition Department, P0 Box 110370, University of Florida, Gainesville, FL 32611. Received January 6, 1995. Accepted for publication April 6, 1995.