8.1 Cystic Fibrosis & Respiratory Support

Pathophysiology and Diagnosis of Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7. The defective CFTR protein impairs chloride and bicarbonate transport across epithelial membranes, producing thick, dehydrated secretions in the airways, pancreatic ducts, intestine, and biliary tree. Roughly 85-90% of patients develop exocrine pancreatic insufficiency (PI), usually in infancy, so fat and protein maldigestion is the default assumption unless proven otherwise.

Newborn screening is universal in the United States: an elevated immunoreactive trypsinogen (IRT) triggers repeat IRT and/or CFTR DNA analysis, with a diagnostic sweat chloride test as the confirmatory step (>=60 mmol/L diagnostic, 30-59 mmol/L intermediate). About 10-20% of newborns with CF present with meconium ileus, which is nearly pathognomonic and signals severe genotype and high risk for early PI.

Energy and Macronutrient Needs

Classic CF guidelines recommended energy intakes of 110-200% of age-related norms to overcome maldigestion, chronic infection, and the work of breathing; current practice individualizes the prescription to weight gain, growth velocity, and lung status, and energy needs often fall once a patient responds to a CFTR modulator. The diet is deliberately high in fat (35-40% of kcal) with no fat restriction — fat is the most energy-dense way to close the calorie gap. The Cystic Fibrosis Foundation (CFF) growth target is BMI-for-age at or above the 50th percentile for ages 2-20 (and weight-for-length >=50th percentile under age 2), because better nutritional status is strongly associated with better forced expiratory volume in 1 second (FEV1).

Pancreatic Enzyme Replacement Therapy (PERT)

Pancreatic enzyme replacement therapy replaces lipase, protease, and amylase. Standard starting doses are 500-2,500 lipase units/kg per meal and about half that dose per snack, titrated to symptoms and growth. Do not exceed 10,000 lipase units/kg/day or 4,000 lipase units/g of dietary fat, because very high doses are associated with fibrosing colonopathy. Products are enteric-coated microspheres that must be given with all fat-containing feeds, including breast milk and infant formula — capsules are opened and the beads are mixed into an acidic soft food (such as applesauce) for infants, without crushing or chewing, which destroys the coating.

• Signs of under-dosing: steatorrhea (oily, foul, floating stools), gas, abdominal distension and pain, and poor weight gain or growth faltering.
• Signs of over-dosing: constipation and hard stools; chronic overdose raises the risk of distal intestinal obstruction syndrome (DIOS) and, at extreme doses, fibrosing colonopathy.

Fat-Soluble Vitamins, Salt, and Bone Health

Pancreatic-insufficient patients malabsorb vitamins A, D, E, and K, so all are supplemented with a CF-specific multivitamin containing higher, water-miscible doses of the fat-soluble vitamins, taken with food and enzymes. Serum levels of A, D, and E (plus a marker of vitamin K status) are checked at least annually and doses are titrated. Vitamin D is managed aggressively — typically 400-2,000 IU/day titrated to a serum 25-hydroxyvitamin D of at least 30 ng/mL — because CF-related bone disease (low bone mineral density from malabsorption, chronic inflammation, corticosteroids, and reduced weight-bearing) is common; screening DXA is recommended from about age 8 in at-risk patients.

Because sweat chloride losses are extreme, infants are routinely supplemented with about 1/8 teaspoon of table salt per day (roughly 12.5 mmol sodium), and older children liberalize dietary salt, especially in hot weather and with exercise. Unsupplemented infants can present with hyponatremic, hypochloremic dehydration (a pseudo-Bartter picture), even without heat exposure.

Cystic Fibrosis-Related Diabetes (CFRD)

CFRD results from progressive pancreatic islet destruction and is primarily insulinopenic, not type 2 insulin resistance. Screening is an annual oral glucose tolerance test (OGTT) starting at age 10. Treatment is insulin, and a critical exam point: carbohydrate is never restricted — patients need high energy intake, so insulin is matched to the diet rather than the diet being cut. Untreated CFRD accelerates weight loss and lung decline.

Growth Failure, DIOS, Liver Disease, and Modulators

When oral intake plus PERT and behavioral strategies cannot sustain growth, enteral feeding (gastrostomy or jejunostomy) with overnight feeds is the standard escalation. Distal intestinal obstruction syndrome — partial or complete obstruction at the ileocecal junction from thickened stool — must be distinguished from simple constipation and is managed with osmotic laxatives and enzyme review. CF-related liver disease (focal biliary cirrhosis) is monitored with annual liver enzymes and ultrasound.

CFTR modulators — ivacaftor, lumacaftor/ivacaftor, and the triple combination elexacaftor/tezacaftor/ivacaftor — improve weight and BMI, sometimes enough that energy prescriptions and vitamin doses must be re-evaluated. They are taken with fat-containing food for absorption, are metabolized by CYP3A, and interact with grapefruit and Seville oranges, which must be avoided.

Nutrition During Respiratory Support

Children with bronchopulmonary dysplasia (BPD) or on mechanical ventilation have elevated energy needs — the work of breathing alone can raise requirements by roughly 25% or more. However, overfeeding carbohydrate increases carbon dioxide production; as the respiratory quotient (RQ) approaches or exceeds 1.0 (lipogenesis), the added ventilatory burden can delay weaning. Prescriptions therefore favor adequate energy with a higher proportion of fat, careful fluid management (BPD often requires fluid restriction that concentrates nutrients), and avoidance of both under- and overfeeding.