Overview and Risk Factors
Cystic fibrosis (CF) is a systemic disease of the exocrine glands characterized by a progressive obstructive lung disease (bronchiectasis) and exocrine pancreatic insufficiency. The sweat glands, vas deferens, and other organs are also affected to varying degrees.
CF is the most common inherited genetic disorder in North America. In the United States, approximately 30,000 individuals have the condition and about 12 million people are carriers. Cystic fibrosis is also the most common cause of pancreatic insufficiency in children. Because normal absorption and digestion of nutrients, especially fat, are altered by pancreatic insufficiency, failure to thrive, malnutrition, and growth retardation are common clinical features in the absence of treatment. The median age of survival is approximately 35 years.
CF is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which controls the concentration of sodium and chloride across certain epithelial cell membranes. Its disruption causes abnormal sodium resorption and chloride secretion. This in turn produces thick mucus, which renders lungs susceptible to bacterial infections. Destruction of the pancreas is typically present at birth, resulting in the absence of digestive enzymes released into the digestive tract. Over 1,000 mutations of this gene have been identified; the most common is the DF508 mutation.
Risk Factors
Genetics. CF is an autosomal recessive condition. If both parents are carriers, a child has a 25% chance of having the disease and a 50% chance of also being a carrier. One in 25 Caucasians is a carrier. A family history of cystic fibrosis and unexplained infant death are also risk factors.
Race. The prevalence of CF is approximately 1 in 2,500 for Caucasians, 1 in 15,000 for African Americans, and 1 in 30,000 for Asian Americans.
Diagnosis
Signs and symptoms of cystic fibrosis primarily reflect respiratory and intestinal involvement.
Respiratory problems include:
Frequent cough, which is dry at first, subsequently becoming productive, and may contain blood due to bronchiectasis.
Infections of the bronchi, which can occasionally evolve into secondary bronchopneumonia associated with increased risk of pulmonary abscess or pleurisy.
Recurrent respiratory infections, which are associated with Staphylococcus aureus and Pseudomonas aeruginosa infections in particular.
Other respiratory problems such as wheezing, dyspnea, pneumothorax, sinusitis and/or nasal polyposis, and mild cyanosis, which may be generalized or of the lips and extremities.
Intestinal involvement may lead to:
Bowel obstruction, with meconium ileus and intussusception are particularly common at birth. Other digestive symptoms are steatorrhea, frequent vomiting, rectal prolapse, liver disease, and cystic fibrosis-related diabetes.
Malabsorption, which causes failure to thrive, retarded growth, and fatigue.
Male infertility is also a symptom. Men nearly always have azoospermia due to congenital bilateral absence of the vas deferens.
Women may have some abnormalities of the cervical mucus, but fertility does not appear to be significantly reduced in the absence of severe malnutrition.
Cystic fibrosis is diagnosed by a sweat test (which can be done as early as 48 hours of age). A positive sweat test (see below), combined with pulmonary and/or gastrointestinal symptoms, establishes the classic diagnosis in nearly all cases. CF mutations, identified through genetic testing, can also confirm diagnosis, or they can be used to make the diagnosis in patients with mild forms of the disease.
A patient with the symptoms and/or signs presented above may require the following tests:
- Sweat test: Most patients with CF have chloride values between 60 and 110 mEq/L.
- Genetic testing: Patients with a family history of CF, and those who exhibit signs and symptoms, but do not have a positive sweat test, should have a genetic test. Prenatal testing and newborn screening may be used. Early detection renders a better clinical course.
- Stool tests: Fecal fat analysis can be used to confirm pancreatic insufficiency.
Treatment
The cornerstones of treatment for CF patients are antibiotics, airway clearance, and nutritional support. A standard treatment regimen includes airway clearance and exercise, mucolytic agents, bronchodilators, anti-inflammatory agents, supplemental oxygen, and nutritional support. CF patients should be cared for at a comprehensive cystic fibrosis care center by a multidisciplinary health care team that includes a physician, nurse, respiratory therapist, dietitian, and social worker. A consensus statement detailing the current evidence-based approach to the care of these patients has recently been published.1
Pulmonary
The pulmonary status of patients should be regularly monitored by an assessment of symptoms, a physical examination, and spirometry. Percent predicted forced expiratory volume in 1 second (FEV1) is accepted as the single most useful objective measure of pulmonary status. Oxygen saturation at rest, during exercise, and/or during sleep should be measured routinely in patients with moderate-to-severe pulmonary disease to assess the need for supplemental oxygen.
Antibiotics are used both for pulmonary exacerbations and chronic suppressive therapy. Azithromycin and inhaled tobramycin are both beneficial as part of a maintenance strategy. During exacerbations of infections, the choice of antibiotics depends on sputum culture and sensitivity. A complete microbiologic assessment of expectorated sputum, including antibiotic susceptibility testing, should be performed at least once a year. Over 80% of CF patients are chronically infected by P. aeruginosa by adulthood, and this represents the most significant cause of infection over the life of the patient.
Corticosteroids may reduce airway inflammation. They can be administered orally for short periods or as inhalations for long-term therapy.
Chest physiotherapy by manual percussion or a vibrating vest should be performed daily to assist with clearing mucus from the patient's airways. Recombinant human DNase (Pulmozyme) decreases the viscosity of CF sputum by degrading extracellular DNA into smaller pieces.
Nearly all CF patients will have a component of reactive airways disease, and bronchodilator strategies similar to those used in treating asthma are appropriate in CF as well (see Asthma Chapter).
Participation in regular exercise may help preserve pulmonary function. A review of exercise benefits indicated that over 3 years of physical training, the mean annual rate of decline in forced vital capacity was significantly greater in the control group, compared with the exercise group.2 Both aerobic exercise and resistance exercise appear to benefit CF patients. Children who received aerobic training had significantly better peak aerobic capacity, whereas those who received resistance training had better weight gain, lung function, and leg strength than children who received aerobic training.3
In advanced disease, bilateral lung transplant is a viable option and should be considered in patients who are no longer responding to conventional therapies.
Pancreatic
Exogenous pancreatic enzyme replacement therapy allows for the digestion of lipids and prevents symptoms of steatorrhea.
A significant percentage of adults with the disease will develop CF-related diabetes mellitus (CFRD), which requires insulin treatment and individualized dietary advice.
Gastrointestinal
In the absence of steatorrhea, constipation can occur. This can be avoided and/or treated with an osmotic laxative, such as MiraLax or Golytely.
Cirrhosis due to biliary obstruction can be treated with ursodeoxycholic acid, which improves biliary excretion and bile acid composition.
Nutritional Considerations
Nutritional management has a dramatic effect on growth and survival in patients with CF, but is often challenging due to malabsorption. Survival is markedly poorer in patients who are underweight for their height. Thus, a high-energy diet is commonly recommended, along with nutritional supplements.4
Energy Intake
Maintenance of a high-calorie diet is a cornerstone of therapy. A study of adults with CF found that 60% failed to meet recommended calorie needs, and 72% failed to meet recommendations for both protein and energy.5 Patients with CF are susceptible to weight loss for several reasons, including ongoing steatorrhea and azotorrhea (despite enzyme therapy); a 10% to 30% increase in elevated resting energy expenditure (REE), particularly during pulmonary exacerbations; treatment with bronchodilators (which cause an 8% to20% increase in REE)6; infection-related anorexia; gastrointestinal disturbances; and clinical depression.4
With proper nutrition therapy, including an energy intake of 120% to 150% of the Recommended Dietary Allowance (RDA), patients with CF may grow normally. Although nutritional supplements have been used in an attempt to attain this goal, research does not support their efficacy.7 Instead, high-fat diets have typically been used,4 although this approach may increase the susceptibility of CF patients to oxidative stress.8 The kind of fat that should be given is also under debate (see below).
Provision of a diet high in essential fatty acids helps with weight and prevention of deficiency symptoms. Biochemical evidence of deficiency of both the essential omega-6 fatty acid linoleic acid and a derivative of the essential omega-3 essential fatty acid alpha-linolenic acid (docosahexanoic acid) is common in patients with CF, although clinical signs and symptoms are rare.9
Although a diet high in fat (including animal fat) is often recommended, it has disadvantages for patients with CF. The omega-6 fatty acid arachidonic acid found in these foods may adversely affect CF patients by contributing to oxidative stress and a pro-inflammatory effect in lung tissue through an increase in leukotriene B4.8 Omega-3 fats, however, appear to be of clinical benefit in patients with CF. Reduction of sputum volume, improved lung function, and a decrease in leukotriene B4 and in use of antibiotics have been observed in EPA/DHA-supplemented patients.4,10 Increasing the intake of plant sources of omega-3 fats (alpha-linolenic acid) and monounsaturated fats has been suggested as an alternative approach to improving fatty acid nutrition in CF patients.4 The Cystic Fibrosis Foundation consensus panel has made similar recommendations, suggesting that oils rich in both omega-3 and monounsaturated fats (eg, flax, canola, soy) benefit CF patient.9
Nutritional Adequacy
Patients should be monitored for evidence of vitamin deficiency and treated accordingly. Patients with CF require supplemental nutrients for various reasons. The fat-soluble vitamins A, D, E, and K are a priority, mainly because pancreatic enzyme insufficiency often results in malabsorption of these nutrients. Oxidative stress occurs to a greater degree in patients with CF than in healthy controls.8 Consequently, deficiencies of antioxidants (eg, vitamin C) and low concentrations of antioxidant enzymes (eg, glutathione peroxidase) have been found in patients with CF, along with poor selenium and zinc status.4 Patients with CF are also often iron deficient, may not take in recommended amounts of calcium, and are at risk for hyponatremia due to salt loss through the skin.9 The amounts of vitamins required in supplements follow.
Vitamin A and carotenoids. Deficiency of vitamin A occurs in 15% to 40% of CF patients,9 in spite of enzyme replacement and use of low-dose vitamin A supplements (2500-4000 IU/day). Supplementation of up to 12000 IU of vitamin A per day may become necessary to normalize plasma levels.4 Carotenoids are also malabsorbed in CF patients, and lycopene, alpha-carotene, and beta-carotene concentrations appear significantly lower than in age-matched controls.11 Supplemental beta-carotene decreases markers of oxidative stress in CF patients.4
Vitamin D. Deficiency of vitamin D occurs in 10% to 40% of children with CF, and in more than 81% of adults with this condition, especially at northern latitudes.12 Lack of vitamin D aggravates the already greater risk for osteoporosis and fractures seen in CF patients.9 Low concentrations of vitamin D have been found in patients with CF taking 1000 IU of vitamin D per day,4 and the deficiency appears not to be corrected even with megadoses of the vitamin.12 For increasing calcium absorption and bone density and decreasing markers of bone resorption, the active hormone (D3) form of vitamin D and vitamin D analogues appear more effective.13
Vitamin E. Deficiency of vitamin E occurs in 87% of unsupplemented patients with CF, prompting supplementation of 200 mg/day.4 Low serum levels are common despite supplementation.4,9
Vitamin K. Deficiency of vitamin K has been found in 81% of patients with CF. While vitamin K supplements (0.1-0.3 mg/day) reduced a sensitive indicator of vitamin K status, the number of persons found to be deficient decreased by only 50%.14 Increasing the dose to 1 mg/day resulted in normalization of vitamin K status.15
Orders
Nutrition consultation to assess nutrient status, advise patient in dietary change, and arrange follow-up. The diet should be individualized based on clinical status.
Exercise prescription: Patient-specific aerobic and resistance training.
What to Tell the Family
Cystic fibrosis is an inherited lung disease that frequently causes respiratory tract infection, resulting in poor appetite and weight loss. Poor absorption of nutrients is common, requiring pancreatic enzyme replacement and supplements of fat-soluble (and possibly water-soluble) vitamins. Patients with CF should follow a high-calorie, high-fat, nutrient-dense diet to help meet needs for energy, growth, and vitamins and minerals. Additional supplementation with fatty acids and minerals may be required if clinical examination or laboratory studies indicate a state of deficiency or insufficiency. Long-term complications of CF that may be delayed through proper diet, exercise, and medical care include osteoporosis, diabetes, and accelerated loss of pulmonary capacity.
References
1. Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D. Cystic fibrosis adult care: consensus conference report. Chest. 2004;125 (suppl 1):1S-39S.
2. Bradley J, Moran F. Physical training for cystic fibrosis. Cochrane Database Syst Rev. 2002;(2):CD002768.
3. Selvadurai HC, Blimkie CJ, Meyers N, et al. Randomized controlled study of in-hospital exercise training programs in children with cystic fibrosis. Pediatr Pulmonol. 2002;33:194-200.
4. Wood LG, Gibson PG, Garg ML. Circulating markers to assess nutritional therapy in cystic fibrosis. Clin Chim Acta. 2005;353:13-29.
5. White H, Morton AM, Peckham DG, Conway SP. Dietary intakes in adult patients with cystic fibrosis--do they achieve guidelines? J Cyst Fibros. 2004;3:1-7.
6. Schols A. Nutritional modulation as part of the integrated management of chronic obstructive pulmonary disease. Proc Nutr Soc. 2003;62:783-791.
7. Poustie VJ, Watling RM, Smyth RL. Oral protein-energy supplements for children with chronic disease: systematic review. Proc Nutr Soc. 2003;62:801-806.
8. Wood LG, Fitzgerald DA, Lee AK, et al. Improved antioxidant and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function. Am J Clin Nutr. 2003;77:150-159.
9. Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002;35:246-259.
10. Cawood AL, Carroll MP, Wootton SA, et al. Is there a case for n-3 fatty acid supplementation in cystic fibrosis? Curr Opin Clin Nutr Metab Care. 2005;8:153-159.
11. Rust P, Eichler I, Renner S, Elmadfa I. Effects of long-term oral beta-carotene supplementation on lipid peroxidation in patients with cystic fibrosis. Int J Vitam Nutr Res. 1998;68:83-87.
12. Boyle MP, Noschese ML, Watts SL, et al. Failure of high-dose ergocalciferol to correct vitamin D deficiency in adults with cystic fibrosis. Am J Respir Crit Care Med. 2005;172:212-217.
13. Aris R, Lester G, Ontjes D. Treatment of bone disease in cystic fibrosis. Curr Opin Pulm Med. 2004;10:524-530.
14. Wilson DC, Rashid M, Durie PR, et al. Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination. J Pediatr. 2001;138:851-855.
15. van Hoorn JH, Hendriks JJ, Vermeer C, Forget PP. Vitamin K supplementation in cystic fibrosis. Arch Dis Child. 2003;88:974-975.
