Cystic Fibrosis

Fred Hill, MA, RRT

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– FEV1 <30%

– PaO2 < 55 mm Hg

– PaCO2 > 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