Pathogenesis of malnutrition in cystic fibrosis, and its treatment

Pathogenesis: We have developed a model of the pathogenesis of malnutrition in cystic fibrosis. It consists of the relationship between nutrient balan ce and nutrient requirement. The validation has been conducted with respect to energy, but the same general principals can be applied to any nutrient. A patient with CF either loses weight or fails to grow normally if their a bsorbed energy intake is less than their total daily energy expenditure. Mu ltiple factors have the potential to contribute to reduced energy intake in cluding, anorexia, gastroeosophageal (GE) reflux leading to vomiting and he nce food loss, as well as maldigestion. Another more recently recognized so urce of energy loss, is glucosuria as a result of CF related diabetes (CFRD ). Conversely, lung inflammation appears to be related to increases in rest ing metabolic rate (RMR). Acute exacerbations of the chronic lung disease i ncreases RMR which returns to a basal level some weeks after the inflammati on is treated. In clinically stable patients with CF, RMR rises in a quadra tic fashion as lung function falls. When FEV1 is > 85% predicted RMR is not different from controls, but it rises in a curvilinear fashion as FEV1 fal ls. Initially it appears that patients adapt to their increased RMR by redu cing their activity so their total daily energy expenditure (TDEE) is often no higher than controls. But this is by no means always the case. Furtherm ore good lung care requires CF patients to be involved in aerobic activitie s, hence their TDEE would rise. Although there has been considerable intere st as to whether the genetic defect has an energy wasting effect, it appear s genetic factors have little or no effect on RMR. Treatment: This starts with making an energy diagnosis. First, a 3 day faec al fat balance study is conducted. This provides information with regard to intake as well as to maldigestion. In addition a history of GE reflux is s ought, since it can readily be treated with Hp-blockers. If significant fat malabsorption exists, efforts are made to improve pancreatic enzyme dose a nd function. The possibility of CFRD also needs to be considered. We measur e the RMR of the patient using open circuit indirect calorimetry. Recommend ations for diet therapy are based on estimated TDEE, which is determined fr om RMR taking into account faecal losses. Diet therapy places the emphasis on increasing the fat content of the diet. We have conducted a study to det ermine whether or not oral supplements help increase TDEE and they did not; they merely replaced food energy. Conversely, nocturnal gastrostomy supple mental feeding, while reducing voluntary food energy intake by about 20%, d oes result in a significant increase in total daily energy intake. Our targ et is to achieve a completely normal nutritional status. Long term follow-u p of these patients has shown significantly better survival in patients who achieve normal nutritional status. The advent of lung transplantation has added another dimension. In our experience, following a successful lung tra nsplant, most patients no longer need their supplemental gastrostomy feedin g. Summary: Our clinic policy is to encourage a high fat diet (35-40% total en ergy) and our patients grow normally in height and weight until their lung disease deteriorates significantly. Patients who develop a negative energy balance seldom if ever respond to diet therapy and hence are candidates for supplemental nocturnal gastrostomy feeds. Gastrostomy fed patients constit ute 3 to 5% of our total CF population of approximately 590 patients. (C) 2 000 Harcourt Publishers Ltd.