Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy.

Cystic fibrosis (CF) is a progressive, genetic, multi-organ disease affecting the respiratory, digestive, endocrine, and reproductive systems. CF can affect any aspect of the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, colon, pancreas, liver, and gall bladder. GI pathophysiology associated with CF results from CF membrane conductance regulator (CFTR) dysfunction. The majority of people with CF (pwCF) experience exocrine pancreatic insufficiency resulting in malabsorption of nutrients and malnutrition. Additionally, other factors can cause or worsen fat malabsorption, including the potential for short gut syndrome with a history of meconium ileus, hepatobiliary diseases, and disrupted intraluminal factors, such as inadequate bile salts, abnormal pH, intestinal microbiome changes, and small intestinal bacterial overgrowth. Signs and symptoms associated with fat malabsorption, such as abdominal pain, bloating, malodorous flatus, gastroesophageal reflux, nausea, anorexia, steatorrhea, constipation, and distal intestinal obstruction syndrome, are seen in pwCF despite the use of pancreatic enzyme replacement therapy. Given the association of poor nutrition status with lung function decline and increased mortality, aggressive nutrition support is essential in CF care to optimize growth in children and to achieve and maintain a healthy body mass index in adults. The introduction of highly effective CFTR modulator therapy and other advances in CF care have profoundly changed the course of CF management. However, GI symptoms in some pwCF may persist. The use of current knowledge of the pathophysiology of the CF GI tract as well as appropriate, individualized management of GI symptoms continue to be integral components of care for pwCF.

Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis.

While typically considered a pulmonary disease, cystic fibrosis patients develop significant nutritional complications and comorbidities, especially those who are pancreatic insufficient. Clinicians must have a high suspicion for cystic fibrosis among patients with clinical symptoms of pancreatic insufficiency, and pancreatic enzymatic replacement therapy (PERT) must be urgently initiated. PERT presents a myriad of considerations for patients and their supporting dieticians and clinicians, including types of administration, therapy failures, and complications.

Characteristics of Resting Metabolic Rate in Critically Ill, Mechanically Ventilated Adults With Cystic Fibrosis.

BACKGROUND: Critically ill patients with cystic fibrosis may be especially sensitive to the negative consequences of overfeeding and underfeeding, yet there is almost no information available about the energy needs of these patients. The purpose of this study was to characterize the metabolic rate of critically ill adult patients with cystic fibrosis requiring mechanical ventilation. METHODS: This was an observational study in which the resting metabolic rate, oxygen consumption, and carbon dioxide production of adult patients with cystic fibrosis requiring critical care, sedation, and mechanical ventilation were measured with indirect calorimetry. This group was compared with a cohort of adult critical care patients without cystic fibrosis. RESULTS: Twelve patients with cystic fibrosis were identified and measured. These were compared with a control group of 25 critically ill patients. Both groups were underweight (body mass index, 17.4 ± 4.0 kg/m2 in cystic fibrosis and 18.4 ± 2.3 kg/m2 in control). Adjusting for differences in age, sex, height, and weight, there was no difference in resting metabolic rate between the cystic fibrosis and control groups (1702 ± 193 vs 1642 ± 194 kcal/d, P = .388). Measured resting metabolic rate matched predicted values 58% of the time in cystic fibrosis and 60% of the time in control. CONCLUSIONS: The resting metabolic rate of sedated adult patients with cystic fibrosis being assisted with mechanical ventilation is not different from that of adult critical care patients without cystic fibrosis. In both these underweight groups, accurate prediction of resting metabolic rate is difficult to obtain.