Cystic fibrosis is the most common cause of severe chronic lung disease in young adults and the most common fatal hereditary disorder of whites in the United States. It is an autosomal-recessive disorder affecting about 1 in 3000 whites; 1 in 25 is a carrier. Cystic fibrosis is caused by abnormalities in a membrane chloride channel (the cystic fibrosis transmembrane conductance regulator [CFTR] protein) that results in altered chloride transport and water flux across the apical surface of epithelial cells.
Cystic fibrosis affects the cells that produce mucus, sweat and digestive juices. These secreted fluids are normally thin and slippery. But in people with CF, a defective gene causes the secretions to become sticky and thick. Instead of acting as lubricants, the secretions plug up tubes, ducts and passageways, especially in the lungs and pancreas.
Over one-third of the nearly 30,000 cystic fibrosis patients in the United States are adults. Patients with cystic fibrosis have an increased risk of osteopenia, arthropathies, and malignancies of the gastrointestinal tract.
Symptoms and Signs
Cystic fibrosis should be suspected in an adult with a history of chronic lung disease (especially bronchiectasis), pancreatitis, or infertility.
Cough, sputum production, decreased exercise tolerance, and recurrent hemoptysis are typical complaints.
Patients also often complain of chronic rhinosinusitis symptoms, steatorrhea, diarrhea, and abdominal pain.
Patients with cystic fibrosis are often malnourished with low body mass index.
Digital clubbing, increased anteroposterior chest diameter, hyperresonance to percussion, and apical crackles are noted on physical examination.
Sinus tenderness, purulent nasal secretions, and nasal polyps may also be seen.
Nearly all men with cystic fibrosis have congenital bilateral absence of the vas deferens with azoospermia.
Biliary cirrhosis and gallstones may occur.
Arterial blood gas studies often reveal hypoxemia and, in advanced disease, a chronic, compensated respiratory acidosis. Pulmonary function studies show a mixed obstructive and restrictive pattern. There is a reduction in FVC, airflow rates, and TLC. Air trapping (high ratio of RV to TLC) and reduction in pulmonary diffusing capacity are common.
Hyperinflation is seen early in the disease process. Peribronchial cuffing, mucus plugging, bronchiectasis (ring shadows and cysts), increased interstitial markings, small rounded peripheral opacities, and focal atelectasis are common findings. Pneumothorax can also be seen. Thin-section CT scanning often confirms the presence of bronchiectasis.
Early recognition and comprehensive multidisciplinary therapy improve symptom control and the chances of survival. Referral to a regional cystic fibrosis center is strongly recommended. Conventional treatment programs focus on the following areas: clearance and reduction of lower airway secretions, reversal of bronchoconstriction, treatment of respiratory tract infections and airway bacterial burden, pancreatic enzyme replacement, and nutritional and psychosocial support (including genetic and occupational counseling).
Oral CFTR modulator drugs, alone or in combination, are available for patients with specific genetic mutations. The Pulmonary Therapies Committee, established by the Cystic Fibrosis Foundation, has issued evidenced-based recommendations regarding long-term use of medications for maintenance of lung function and reduction of exacerbations in patients with cystic fibrosis.
Clearance of lower airway secretions can be promoted by postural drainage, chest percussion or vibration techniques, positive expiratory pressure (PEP) or flutter valve breathing devices, directed cough, and other breathing techniques; these approaches require detailed patient instruction by experienced personnel.
Inhaled recombinant human deoxyribonuclease (rhDNase, dornase alpha) cleaves extracellular DNA in sputum, decreasing sputum viscosity; when administered long-term at a daily nebulized dose of 2.5 mg, this therapy leads to improved FEV1 and reduces the risk of cystic fibrosis–related respiratory exacerbations and the need for intravenous antibiotics.
Inhalation of hypertonic (7%) saline twice daily has been associated with small improvements in pulmonary function and fewer pulmonary exacerbations. The beneficial effects of hypertonic saline may derive from improved airway mucous clearance.
Short-term antibiotics are used to treat active airway infections based on results of culture and susceptibility testing of sputum. S aureus (including methicillin-resistant strains) and a mucoid variant of P aeruginosa are commonly present.
H influenzae, Stenotrophomonas maltophilia, and B cepacia (a highly drug-resistant organism) are occasionally isolated. Long-term antibiotic therapy is helpful in slowing disease progression and reducing exacerbations in patients with sputum cultures positive for P aeruginosa.
These antibiotics include azithromycin 500 mg orally three times a week, which has immunomodulatory properties, and various inhaled antibiotics (eg, tobramycin, aztreonam, colistin, and levofloxacin) taken two to three times a day.
The length of therapy depends on the persistent presence of P aeruginosa
Inhaled bronchodilators (eg, albuterol, two puffs every 4 hours as needed) should be considered in patients who demonstrate an increase of at least 12% in FEV1 after an inhaled bronchodilator. An inhaled corticosteroid should be added to the treatment regimen for patients who have cystic fibrosis with persistent asthma or allergic bronchopulmonary mycosis.
Lung transplantation is the only definitive treatment for advanced cystic fibrosis. Double-lung or heart-lung transplantation is required. A few transplant centers offer living lobar lung transplantation to selected patients. The median survival following transplantation for cystic fibrosis is 7.8 years.
Vaccination against pneumococcal infection and annual influenza vaccination are advised. Screening of family members and genetic counseling are suggested.