1. Cystic Fibrosis Fred Hill, MA, RRT

2. Overview Cystic fibrosis is the most common fatal, inherited disease in the U. S. Cystic fibrosis is the most common fatal, inherited disease in the U. S. CF results from a defective autosomal recessive gene 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%)

3. Overview Genetic defect expressed when two carriers produce progeny 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 Affects all racial and ethnic groups, but Caucasians of northern European ancestry most often affected

4. Statistics of CF Median age of survival Median age of survival –1960s: ~2-4 yrs –Early 1990s: ~25 years –2000: ~30 years –2006: ~37 years Incidence 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.

5. Statistics of CF Incidence 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

6. Genetics and Dysfunction Defective gene identified in 1989 Defective gene identified in 1989 Bichemical abnormality called cystic fibrosis transmembrane regulator (CFTR) Bichemical abnormality called cystic fibrosis transmembrane regulator (CFTR) Interferes with Cl - transport across epithelial membranes, primarily manifested in exocrine glands Interferes with Cl - transport across epithelial membranes, primarily manifested in exocrine glands

7. Respiratory Related Conditions Repeated infections Repeated infections Chronic cough Chronic cough Recurrent bronchitis Recurrent bronchitis Recurrent pneumonia Recurrent pneumonia Bronchiectasis Bronchiectasis Pneumothorax Pneumothorax Hemoptysis Hemoptysis Digital clubbing Digital clubbing Cor pulmonale Cor pulmonale Sinusitis Sinusitis Allergic bronchopulmonary asperigillosis Allergic bronchopulmonary asperigillosis Nasal polyps Nasal polyps

8. Digital Clubbing

9. Chest X-Ray

10. Other Manifestations Gastrointestinal Failure to thrive Failure to thrive Greasy, foul-smelling stools Greasy, foul-smelling stools Meconium ileus Meconium ileus Distal intestinal obstruction Distal intestinal obstruction Hyperglycemia Hyperglycemia Abdominal discomfort Abdominal discomfort Rectal prolapse Rectal prolapse Hepatobiliary System Liver disease Liver disease Prolonged neonatal Jaundice Prolonged neonatal Jaundice Reproductive Tract Delayed puberty Delayed puberty Infertility Infertility Sweat Glands High salt content High salt content

11. Diagnosis Genetic testing Genetic testing Sweat test Sweat test Other Other – Prenatal diagnosis – Medical history – Immunoreactive trypsinogen test – Nasal potential difference measurement – Pulmonary function testing

12. Pulmonary Infections Staphylococcus aureus (early) Staphylococcus aureus (early) Pseudomonas aeruginosa Pseudomonas aeruginosa Burkholderia cepacia Burkholderia cepacia

13. Sweat Chloride Test Use pilocarpine and a mild electrical current to promote sweat production Use pilocarpine and a mild electrical current to promote sweat production Wrap with pad and plastic covering Wrap with pad and plastic covering Collect and analyze sweat for chloride Collect and analyze sweat for chloride Positive test Positive test –Cl - > 60 mmoles/L in children –Cl - > 80 mmoles/L in adults

14. Treatment Antibiotics Antibiotics Improved nutrition Improved nutrition Antiinflammatories Antiinflammatories Pancreatic enzyme supplements Pancreatic enzyme supplements Bronchial hygiene Bronchial hygiene Bronchodilators & mucolytics Bronchodilators & mucolytics Physical therapy & exercise Physical therapy & exercise Lung transplantation Lung transplantation

15. Airway Clearance Techniques Chest physical therapy Chest physical therapy Forced expiratory technique Forced expiratory technique Active cycle breathing Active cycle breathing Positive expiratory pressure Positive expiratory pressure Autogenic drainage Autogenic drainage Flutter device Flutter device Vest Vest Exercise Exercise

16. Mucolytics Rh DNAse (Pulmozyme) Rh DNAse (Pulmozyme) Acetylcysteine (Mucomyst) Acetylcysteine (Mucomyst) Saline (nasal washes) Saline (nasal washes)

17. Lung Transplantation Limitations Limitations – High cost – Posttransplantation comlications Oliterative bronchiolitis (30% to 50% in 3-5 years) Oliterative bronchiolitis (30% to 50% in 3-5 years) 1 year survival: ~72% 1 year survival: ~72% 3 year survival: 55% 3 year survival: 55% 5 year survival: 49% 5 year survival: 49%

18. Lung Transplantation General criteria 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

19. Lung Transplantation Severity of disease criteria Severity of disease criteria – FEV 1 <30% – PaO 2 < 55 mm Hg – PaCO 2 > 50 mm Hg – Suffering from an unacceptable quality of life

20. Lung Transplantation Potentially inadvisable situations 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

21. Thoughts on Mechanical Ventilation Return to spontaneous ventilation is likely Return to spontaneous ventilation is likely Not usually for end-stage condition Not usually for end-stage condition