1. Cystic Fibrosis An Overview
Julie Mitchell, RRT

2. Definition Chronic obstructive pulmonary disease
Most common lethal inherited disease among Caucasians
Life expectancy – Male 37yrs, female 34 yrs
Mainly affects the respiratory and digestive systems

3. Incidence 1 in 2,500 live births (Caucasians)
1 in 25 persons carry the trait
Approximately 60,000 diagnosed cases worldwide
In Alberta – new cases/yr

4. Etiology Mendelian recessive trait residing on chromosome 7
Defective gene discovered 1989
Possession of a defective trait in both parents required
1 in 4 chance of cystic fibrosis manifesting
If both parents have the defective trait, then there is a 1 in 4 chance of their child having cystic fibrosis.

5. Carrier
Carrier
Cystic Fibrosis
Carrier
Carrier
Non-Carrier

6. Pathophysiology
The genetic defect found on chromosome 7 results in impaired transport of electrolytes across epithelial layers of various organs affected
CFTR is the dysfunctional protein (Cystic Fibrosis Transmembrane conductance Regulator)

7. Normal epithelia
Actively excrete Cl out of cells (In response to increased levels of cAMP and calcium ions)
Causing absorption of Na, and thus
The excretion of H2O to liquefy fluids providing digestive, lubricative, or protective function

8. Cystic fibrosis epithelia has impaired ion transport preventing chloride ions and water from leaving the cell to hydrate fluids in the extracellular space

9. Manifestations of CF COPD (Hypersecretion of mucus)
Pancreatic insufficiency (Malnutrition)
Elevated NaCl levels in sweat (Dehydration)
Infertility

10. Pathology of Lung Disease
At birth, the lungs are histologically normal
Soon after birth, hypertrophy of goblet cells occurs, with increased production of mucus
CFTR defect contributes to the mucus thickening
Copious thick secretion clogs airways and limits the mucociliary transport system

11. Static secretions gather infectious bacterium
Infection causes inflammation, and immune mediators increase the secretion of mucus
Repeated infections cause scarring or fibrosis of the lung

12. Bacteria commonly found in the CF population
Staphylococcus aureus
Haempohilus influenzae
Pseudomonas aeruginosa
Burkholderia cepacia

13. Predicted Pseudomonas Infection Rates
20% by 2 yrs of age
31% by 5 yrs of age
45% by 7 yrs of age

14. Pathology of Pancreatic Insufficiency
85% of CF persons have pancreatic insufficiency
At birth, 99% of pancreatic function is impaired for those who are diagnosed with insufficiencies

15. Pancreatic duct is blocked by thickened mucus
Digestive enzymes needed for fats and proteins are not delivered to the stomach
Nutrients are not absorbed. Failure to gain weight and height occurs – “Failure to thrive”

16. “Salty Sweat”
Sweat glands are described as having normal ion channel function
CF sweat glands produce up to four times the amount of Na+ and Cl- found in normal amounts of sweat
Therefore, there is a higher concentration of NaCl
Causes dehydration of the body

17. Pathology of Reproductive Organs
In 95% of men, the vas deferens is blocked with thickened mucus, rendering the male infertile
In women, the mucus lining of the cervix is thickened, making it difficult for sperm to penetrate
Also, poor weight gain makes ovulation less frequent

18. Diagnosis
1938 – Cystic fibrosis first described 1953 – Sweat chloride testing was widely used to test for the disease 2003 – Various genetic testing. However, sweat chloride testing remains the “gold standard”

19. Sweat Chloride Test
> 60 mEq/L of chloride in sweat indicates cystic fibrosis
This elevation must exist in two separate testing sessions to confirm diagnosis

20. Clinical Manifestations Affecting the Cardiopulmonary System
Increases in the following
Respiratory rate
Heart rate, cardiac output, and blood pressure
Anteroposterior chest diameter (barrel chest)
Accessory muscle use, pursed lip breathing
Cough and sputum production

21. Changes in PFTs
Hypoxemia – Digital clubbing, polycythemia
Hypercapnia
Cor pulmonale

22. Other Systems Affected
Liver disease
Diabetes mellitus
Meconium Ileus
Meconium Ileus equivalent

23. Therapeutic Interventions
Gene Therapy
Transplantation
Proteins Repair
Nutrition
GOALS
Prevention of respiratory damage
Ion Transport
Optimum nutrition
Control of Infection
Mucus Modification
Control of Inflammation
Mucus Clearance

24. Nutrition Pancreatic enzymes and supplemental vitamins
% increase in energy expenditure due to daily chest physio, coughing, and increased WOB at rest

25. Control of Infection Oral/inhaled antibiotics
Nebulized tobramycin – Used to prevent exacerbations
Treat first infection earlier to delay colonization of PA

26. Control of Inflammation
Corticosteriods
Ibuprofen
Under study – Oral mucomyst

27. Mucus Clearance Chest physiotherapy Postural drainage Bronchodilators
PEP
Flutter valve
VEST
Cof-flator

28. Mucus Modification VEST Pulmozyme Under study Aerosolized surfactant
Aerosolized hypertonic saline

29. Transplantation Cadaveric vs. Living donor Survival sates (Cadaveric)
80% – 1 year post tx
58% – 5 years post tx

30. Prognosis
Life expectancy has increased from 4 years of age in 1960 to 35 years of age in 2003
Since the discovery of the gene in 1989, life expectancy has almost doubled.

31. Prevention
Basically, selective breeding is the only way to prevent cystic fibrosis from arising in our offspring
With genetic screening and education, cystic fibrosis can be eradicated
Until then, advances in therapies used to combat the disease are our best hopes to allow those who suffer with cystic fibrosis a higher quality of life