Cystic Fibrosis Jennifer McDaniel, BS, RRT-NPS
Overview Cystic fibrosis is the most common fatal, inherited disease in the U. S. CF results from a defective autosomal recessive gene One copy of gene = carrier Codes for a protein responsible for salt transport by epithelial cells Defective gene found on chromosome #7 Several hundred mutations possible ~12 mutations identified, delta F508 most common (68%)
Overview Genetic defect expressed when two carriers produce progeny 25% chance of CF 50% chance of carriers 25% chance of normal Affects all racial and ethnic groups, but Caucasians of northern European ancestry most often affected
Statistics of CF Median age of survival 1960s: ~2-4 yrs Early 1990s: ~25 years 2000: ~30 years 2006: ~37 years Incidence 30,000 Americans, 20,000 Europeans, 3,000 Canadians In U. S., 12,000,000 carriers 2500 CF babies born annually in U. S.
Statistics of CF Incidence Caucasians: 1 in 1600 births African Americans: 1 in 13,000 births Asian Americans: 1 in 50,000 births 1 in 22 Caucasians are carriers
Genetics and Dysfunction Defective gene identified in 1989 Bichemical abnormality called cystic fibrosis transmembrane regulator (CFTR) Interferes with Cl - transport across epithelial membranes, primarily manifested in exocrine glands
Respiratory Related Conditions Repeated infections Chronic cough Recurrent bronchitis Recurrent pneumonia Bronchiectasis Pneumothorax Hemoptysis Digital clubbing Cor pulmonale Sinusitis Allergic bronchopulmonary asperigillosis Nasal polyps
Digital Clubbing
Chest X-Ray
Other Manifestations Gastrointestinal Failure to thrive Greasy, foul-smelling stools Meconium ileus Distal intestinal obstruction Hyperglycemia Abdominal discomfort Rectal prolapse Hepatobiliary System Liver disease Prolonged neonatal Jaundice Reproductive Tract Delayed puberty Infertility Sweat Glands High salt content
Diagnosis Genetic testing Sweat test Other Prenatal diagnosis Medical history Immunoreactive trypsinogen test Nasal potential difference measurement Pulmonary function testing
Pulmonary Infections Staphylococcus aureus (early) Pseudomonas aeruginosa Burkholderia cepacia
Sweat Chloride Test Use pilocarpine and a mild electrical current to promote sweat production Wrap with pad and plastic covering Collect and analyze sweat for chloride Positive test Cl - > 60 mmoles/l in children Cl - > 80 mmoles/l in adults
Treatment Antibiotics Improved nutrition Antiinflammatories Pancreatic enzyme supplements Bronchial hygiene Bronchodilators & mucolytics Physical therapy & exercise Lung transplantation
Airway Clearance Techniques Chest physical therapy Forced expiratory technique Active cycle breathing Positive expiratory pressure Autogenic drainage Flutter device Vest Exercise
Mucolytics Rh DNAse (Pulmozyme) Acetylcysteine (Mucomyst) Saline (nasal washes)
Lung Transplantation Limitations High cost Posttransplantation comlications Oliterative bronchiolitis (30% to 50% in 3-5 years) 1 year survival: ~72% 3 year survival: 55% 5 year survival: 49%
Lung Transplantation General criteria <60-65 years old No significant extrapulmonary complications No steroid regimen >20 mg prednisone daily No malignancy within past 5 years 20% of ideal body weight Ambulatory and capable of pretransplantation rehab program Motivated and likely to comply with regimen No smoking or drug/alcohol abuse No major psychiatric problems Adequate financial resources
Lung Transplantation Severity of disease criteria FEV 1 <30% PaO 2 < 55 mm Hg PaCO 2 > 50 mm Hg Suffering from an unacceptable quality of life
Lung Transplantation Potentially inadvisable situations Significant liver disease Severe malnourishment Extensive pleural scarring Ventilator dependent Colonized by Burkholderia cepacia Aspergilloma with extensive pleural reaction Severe osteoporosis with history of vertebral compression
Thoughts on Mechanical Ventilation Return to spontaneous ventilation is likely Not usually for end-stage condition