Nutrition and survival in cystic fibrosis.

The principal clinical manifestations of cystic fibrosis are bronchiectasis with chronic pulmonary infection and pancreatic malabsorption due to destruction of the exocrine pancreas.' The interactions between the lung disease and nutrition are important because nutritional state usually parallels declining lung function and is a predictor of survival.2 A better understanding of how these two factors relate to each other and influence survival may lead to further gains in outcome for patients. A number of factors work together to cause most older patients with cystic fibrosis to be underweight.3 Malabsorption of fat is the major primary abnormality with nutritional consequences. This often presents in infancy with failure to thrive and steatorrhoea and is the clinical presentation resulting in a diagnosis of cystic fibrosis in 50% of patients in the absence of neonatal screening.3 Although malabsorption can be clinically corrected by pancreatic enzyme replacement, many patients with cystic fibrosis continue to have evidence of maldigestion and consequent malabsorption. Despite apparently adequate enzyme replacement which controls bowel movements, patients with cystic fibrosis lose about 15% of energy taken orally.4 Most adults with cystic fibrosis have a resting energy expenditure (REE) which is on average 20% higher than healthy age and sex matched volunteers.5` There have been suggestions that, at the cellular level, the consequences of abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are energy requiring. Epithelial cells from cystic fibrosis cell lines have increased oxygen consumption and this may be a consequence of abnormal function of the energy requiring CFTR protein which has a large number of ATP binding sites on the nucleotide binding folds of the CFTR molecule.89 This, however, is not likely to be clinically important as infants with cystic fibrosis have similar resting energy expenditure to healthy controls,'0 and in older patients with cystic fibrosis the main determinant of energy expenditure is abnormal lung function.56 As pulmonary disease progresses during the second and third decades, energy demands increase due to the effects of airflow obstruction on lung mechanics. Overinflation of the lungs increases the oxygen cost of ventilation, which may account for up to 10% of REE.5 In patients with chronic obstructive pulmonary disease the increase of oxygen cost of breathing accounted for all of the increase in REE," while in patients with cystic fibrosis increased oxygen cost of ventilation only accounted for about 50% of the elevation in REE.6 An explanation for this is that chronic infection and inflammation may have energy requiring consequences, probably mediated by the effects of cytokines such as tumour necrosis factor alpha, interleukin 1, and interleukin 6 which have been noted to be raised in patients with cystic fibrosis.7' 12 Increased sympathetic