The state of the lungs determines the health and life span of the majority of patients with CF.
Cystic fibrosis (CF) was first recognized as a distinct disease in the late 1930s.1 Currently, there are approximately 30,000 people affected by CF in the United States.2 Although CF is seen in all races, it is the most common fatal genetic disorder among whites.2 CF is an autosomal recessive disorder; an individual must receive two copies of the defective gene, one from each parent, in order to have the disease. In the United States, one person in 31 is a symptomless carrier of CF.2
The defective gene causes an alteration in the CF transmembrane-conductance regulator (CFTR) protein. The CFTR protein, a chloride ion channel, is responsible for regulating ion transport in the epithelial cell membranes. Disruption of ion transport causes decreased water movement to the luminal surface of the airway epithelium, resulting in the presence of thick, viscous secretions.
The major clinical effects of the defective CFTR protein are seen in the exocrine organs of the body, which depend on the movement of secretions through ducts in order to function properly. The defective protein causes thickening of secretions, which do not then move freely through these ducts. The following table shows the major organs affected by this disease.
| Respiratory System • Sinusitis • Nasal polyps • Bronchiectasis |
| Digestive System • Pancreatic insufficiency • Malnutrition • Distal intestinal obstruction syndrome • Hepatobiliary disease |
| Reproductive System • Congenital absence or abnormal development of the vas deferens (males) • Thickened cervical mucosa (females) |
| Sweat Glands • Dehydration from salt loss |
| Other • Diabetes mellitus • Osteoporosis |
Diagnosis
Diagnosis is usually made within the first 3 years of life, although 8% of new diagnoses are made in patients 18 or more years old. Diagnosis is based on two positive sweat tests. This test is a simple, inexpensive, and painless procedure. It can be performed on any individual, although some newborns do not produce enough sweat to permit the acquisition of accurate results. In this instance the test would need to be repeated. The test involves placing a small amount of pilocarpine on the arm (or, in infants, on the leg). This is followed by the application of a weak electrical current to induce sweating; a pad with a plastic coil is applied to collect the sweat. This remains in place for 30 minutes and is then sent to a laboratory for analysis. A positive test result is indicated by the presence of more than 60 mEq/L of chloride. A negative test result shows less than 40 mEq/L.
There are several other methods used to test for CF. One of these involves checking the genotype of DNA purified from a blood sample or a buccal swab. Approximately 700 different mutations have been identified in the CFTR gene. Commercial laboratories screen for up to 72 of the most common mutations for a detection rate of 85% to 90%.3
Nasal potential difference is also used to make a CF diagnosis. This method measures the electrical charge in the nose (a person with CF has a higher electrical charge than one without the disorder). This test is very accurate for diagnosis, but it is difficult to perform correctly and is available at only a few centers.
Disease Management
Advances in nutritional management and improvements in antibiotics and aerosols, coupled with the development of CF care centers knowledgeable about this disease, have extended life expectancies for individuals with CF. In the 1940s, median survival was less than 1 year; currently, it is 31 years4 (see the following table.)
| Year | 1940 | 1950 | 1960 | 1970 | 1980 | 1990 | 1996 |
| Median Survival Age |
<1 yr | 1 | 10 | 16 | 18 | 29 | 31 |
The National Cystic Fibrosis Foundation, Bethesda, Md, has developed comprehensive patient-care guidelines. The goals of CF care are to control infection, promote mucus clearance, improve nutrition, maintain lung function, and improve quality of life. In order to meet these goals, airway clearance, exercise, oxygen supplementation, pharmacotherapy, and nutritional support are employed.
Airway Clearance
More than any other factor, the state of the lungs determines the health and life span of the majority of patients with CF. Respiratory disease accounts for 75% of their hospitalizations and 95% of deaths.5 Thick, viscous secretions in the airways lead to a vicious cycle of inflammation and infection; this cycle, in turn, leads to obstruction and bronchiectasis.
An effective way to reduce obstruction is to use airway-clearance techniques. Several methods work well, but the specific regimen used must be tailored for the individual.
Coughing is the natural way to protect the lungs and clear them of foreign substances. Ineffective or frequent involuntary coughing can induce early airway compression. Huffing is a gentle way of coughing. By using an open glottis, patients are able to avoid airway collapse and maximize airflow. When patients perform a huff cough, they inhale slowly using diaphragmatic breathing; they then hold the breath for 3 seconds and exhale slowly, whispering the word huff. Huffing helps to move mucus from the lower airways.
Chest physiotherapy (CPT) is the traditional means of airway clearance in CF. It uses postural drainage in various positions, percussion, vibration, deep breathing, and coughing to loosen and move secretions out of the lungs. A caregiver is usually required to administer CPT.
An inflatable vest used to supply a form of CPT incorporates an air-pulse generator that delivers high-frequency vibrations, which then oscillate the chest wall. These vibrations, along with increased airflow, help loosen mucus from the lungs. This therapy is self-administered in a sitting position and can be effective for patients unable to tolerate postural-drainage positioning. The vest is equipped with a usage meter that allows monitoring patient compliance.
Positive expiratory pressure (PEP) is a technique that uses a mask or a mouthpiece to create pressure in the lungs in order to promote collateral air movement. The patient takes in a normal breath, exhales against a fixed resistance, and then performs a series of 10 to 15 breaths followed by huffing; this is repeated four to six times. This cycle helps loosen airway obstructions by moving the mucus from behind, so that coughing becomes more productive. The PEP device is relatively inexpensive, it can be administered without a caregiver, and its small size allows portability. The patient must have proper instruction and practice good technique for PEP to be effective.
One PEP device is a plastic pipe-shaped instrument that contains a stainless-steel ball resting in a cone. As the patient exhales into the mouthpiece, the ball sends vibrations to the airways. These vibrations help loosen mucus from the airway walls. The accelerated expiratory airflow facilitates movement of the mucus up the airway. The mucus is then expectorated more easily.
The active cycle of breathing technique uses a combination of deep breathing, controlled breathing, and huff coughing. The cycle lasts between 15 and 20 minutes. This form of airway clearance is popular in the United Kingdom.
Autogenic drainage uses expiratory airflow to move mucus from the smaller airways to the central airways. The patient performs controlled breathing exercises and breath holding at different lung volumes, combined with huff coughing, to expectorate the mucus. Using varying lung volumes allows the equal pressure point to move up the airway, transporting mucus from the smaller airways to the larger airways. Application of this intensive technique requires several teaching sessions given by an RCP who has been trained in its use if it is to be performed properly.
Patient participation, controlled coughing, and proper instruction are key elements in making airway clearance successful. The patient’s psychosocial situation, the demands of school or work, and caregiver involvement should all be considered in choosing the proper regimen for the individual.
Exercise
Exercise is vital to the maintenance of optimal health. Regular exercise increases maximal oxygen consumption and tolerance for shortness of breath, and assists patients with airway clearance by helping mucus to move out of the lungs. To be effective, exercise should consist of a minimum of 20 to 30 minutes of continuous aerobic activity.6 Patients exercising a minimum of three times per week receive the pulmonary benefits of exercise as well as the psychological benefits associated with stronger feelings of independence and well-being.
Oxygen Supplementation
Some patients with CF require supplemental oxygen in order to maintain adequate oxygen-saturation levels. Patients with severe disease may require continuous oxygen, while others may need supplemental oxygen only during exercise or sleep. Continuous positive airway pressure therapy may be beneficial in preventing nocturnal desaturations and respiratory disturbances in patients with severe CF who already require supplemental oxygen.7
Drug Therapy
Pharmacological treatment of CF is aimed at controlling infection, facilitating mucus clearance, and maintaining lung function. This is accomplished through the coordination of antibiotic treatment, airway clearance, and aerosolized medication.
The airways of CF patients are chronically infected with bacteria; some of the most common bacteria colonizing the airways are Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. These infections flare up on occasion and require more aggressive treatment, which usually entails increasing the frequency of airway clearance and using antibiotics to treat the infection. Some exacerbations can be treated using an oral antibiotic and more aggressive pulmonary toilet at home. More severe exacerbations may require treatment using parenteral antibiotics.
The choice of antibiotic coverage is based on the most recent sputum-culture sensitivities. Therapy for infection by Pr. aeruginosa, the pathogen most commonly found in the airways in CF patients, usually involves dual antibiotic coverage from these drug categories: aminoglycosides, b-lactams, and fluoroquinolones. A traditional parenteral antibiotic course lasts 10 to 21 days. Patients with more severe lung disease may require a longer treatment course. The goal of treatment is to return patients to their baseline levels of symptoms and pulmonary function.
Aerosolized bronchodilators are used, in conjunction with airway clearance, to move mucus. Bronchodilator treatments are typically taken twice daily. Increases in bronchospasm or infection can necessitate the use of bronchodilation treatments up to four times per day.
Dornase alfa, an inhaled mucolytic, helps decrease the viscosity of CF sputum. Neutrophils accumulate in the lung to fight chronic infection. These neutrophils break open and release large quantities of extracellular DNA. The presence of abundant DNA makes CF sputum more viscous. Dornase alfa decreases the viscosity of the sputum by hydrolyzing the DNA; therefore, the mucus is easier to expectorate. A large clinical trial8 showed that patients using dornase alfa had modest increases in pulmonary function and decreases in respiratory-tract infection.
The US Food and Drug Administration has approved the first inhaled antibiotic for long-term suppression of P aeruginosa. Tobramycin, an aminoglycoside, is given twice per day in repeated cycles of 28 days of using the medication, then 28 days without it. Patients participating in clinical studies of inhaled tobramycin demonstrated improvements in lung function, fewer days of requiring antipseudomonal antibiotics, and decreased colonies of Pr. aeruginosa in their sputum.9,10
Nutritional Support
Many of the gastrointestinal complications associated with CF are due to the inability to digest food. The pancreatic ducts become clogged with viscous secretions. These secretions inhibit the ability of pancreatic enzymes to reach the stomach and small intestine, making it difficult for patients to digest food. Patients who have pancreatic insufficiency require enzymes for digestion. These patients frequently have deficiencies in the fat-soluble vitamins A, D, E, and K, and will require supplements. These supplements are best absorbed in a water-soluble preparation.
Good nutrition promotes growth and development and is an important aspect of care. The best way to achieve good nutrition is through the use of a high-calorie, high-protein diet and, for patients with pancreatic insufficiency, pancreatic enzyme replacement. Without proper nutrition, the body lacks the ability to fight infection. Poor nutritional status has been shown to have an impact on lung function.11
CF patients have a greater resting energy expenditure than their healthy counterparts.12 Often, this makes it difficult for them to consume adequate calories in meals and snacks. A good rule of thumb for determining caloric need is the use of up to two times the recommended daily allowance for an individual of the same age, sex, and height. At times, patients will require supplements to increase their caloric intake. There are a number of ways for a CF patient to increase calorie consumption. Usually, patients first opt for noninvasive measures, such as drinking a high-calorie beverage. A CF dietitian will help determine the additional calories needed and how best to achieve the necessary intake.
Patients are considered severely malnourished when their weight falls below 75% of ideal body weight (as determined using the Metropolitan Life small-frame adult body index). When a patient cannot gain weight using meals and supplements, more aggressive intervention is needed. Through placement of a nasogastric tube or a percutaneous endoscopic gastrostomy (PEG) tube, a malnourished patient can receive additional calories throughout the night. Patients can use nasogastric feedings during times of illness or stress to help maintain weight. Patients who are moderately to severely malnourished may use a nasogastric tube every night to receive additional calories. For some patients, placing an NG may be painful or they may have a deviated septum, in which case a PEG tube may be more appropriate. The PEG tube allows the patient to receive supplemental feedings via a catheter extending from the skin to the stomach. The catheter may be converted to a less intrusive button after the site has healed. Patients often experience discomfort during the healing phase because the catheter is placed through the abdominal wall. This causes pain during coughing, and a more aggressive pulmonary toilet may be indicated to move secretions out of the lungs. Aggressive nutritional intervention has been shown to improve the course of a malnourished CF patient.13
End-of-Life Issues
As lung disease progresses, CF patients are faced with end-of-life decisions. These often entail applying for disability benefits, writing a living will, and communicating with family and friends concerning code status. Another decision that the patient must consider is the option of lung transplantation. This is not for every CF patient; severity of disease, sputum antibiotic sensitivities, nutritional status, patient compliance, and comorbidities are all considered in determining eligibility for lung transplantation. The patient, family, CF care team, and lung-transplant team will decide whether this is an appropriate option. Although lung transplantation trades one medical condition for another, successful transplantation can extend, and improve the quality of, the recipient’s life.14 Living lobar lung transplants are an alternative to cadaveric transplants. This type of transplantation has been performed on a small number of patients who have more severe disease, and who would be unlikely to survive the waiting period for a cadaveric donor. A preliminary study15 showed outcomes comparable to those for procedures using cadaveric lungs.
New Therapies
When the gene responsible for CF was discovered in 1989, it was hoped that a cure for the genetic defect would soon follow. Despite advances in understanding the molecular determinants of the disease, research has been complicated by the many different mutations that cause CF. Phase I clinical trials are exploring how to correct the different types of defects: null production, trafficking, regulation, and partial reduction. The abundance of new compounds directed at the trafficking mutation F508 is encouraging and is likely to benefit the majority of patients with CF.16
Conclusion
Adherence to prescribed airway-clearance therapies, careful monitoring of nutritional and pulmonary status, and treatment of exacerbations are indicated for optimal management of CF. Efforts to find a cure and to improve treatment of symptoms continue, in the hope that the majority of patients will live well into adulthood with an acceptable quality of life.
Acknowledgements
The author gratefully acknowledges the assistance of Bruce Marshall, MD, and Cathy Loring in critical review of the manuscript and Teresa Clark, RRT, in supplying knowledge of airway-clearance techniques and prescribed therapies.
Kristin M. Bleyl, RN, is the adult cystic fibrosis clinic coordinator, Intermountain Cystic Fibrosis Center, University of Utah HSC, Salt Lake City.
References
1. Anderson DH. Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study. Am J Dis Child. 1938;56:344-349.
2. Clinical Practice Guidelines for Cystic Fibrosis. Bethesda, Md: National Cystic Fibrosis Foundation; 1997:1.
3. Consensus Conference. Bethesda, Md: National Cystic Fibrosis Foundation; 1996;VII:2-3.
4. Annual Data Report. Bethesda, Md: Cystic Fibrosis Foundation Patient Registry; 1998:9-99.
5. Orenstein DM. Cystic Fibrosis: A Guide for Patient and Family. 2nd ed. Philadelphia, Pa: Lippincott-Raven; 1997:19-29.
6. Nixon P. Cystic Fibrosis. In: American College Sports Medicine Exercise Management for Persons with Chronic Diseases and Disabilities. 1st ed. Champaign, Ill: Human Kinetics; 1997:86.
7. Regnis JA. Benefits of nocturnal nasal CPAP in patients with cystic fibrosis. Chest. 1994;106:1717-1724.
8. Fuchs HJ. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med. 1996;331:637-642.
9. Ramsey BW. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993;328:1740-1745.
10. Ramsey B, Burns J, Smith A. Safety and efficacy of tobramycin solution for inhalation in patients with cystic fibrosis: the results of two phase III placebo controlled clinical trial. Pediatr Pulmonol Suppl. 1997;14:137-138.
11. Corey M. Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis. J Pediatr. 1997;131:809-814.
12. Vaisman N, Clarke R, Pencharz PB. Nutritional rehabilitation increases resting energy expenditure without affecting protein turnover in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 1991;13:383-390.
13. Steinkamp G, von der Hardt H. Improvement of nutritional status and lung function after long-term nocturnal gastrostomy feedings in cystic fibrosis. J Pediatr. 1994;124:244-249.
14. Hosenpud JD. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet. 1998;351:24-27.
15. Starnes VA. Living-donar lobar lung transplantation experience: intermediate results. J Thorac Cardiovasc Surg. 1996;112:1284-1291.
16. Zeitlin PL. Novel pharmacologic therapies for cystic fibrosis. J Clin Invest. 1999;103:447-452.
