Cystic Fibrosis An Overview Julie Mitchell, RRT

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

Incidence 1 in 2,500 live births (Caucasians) 1 in 25 persons carry the trait Approximately 60,000 diagnosed cases worldwide In Alberta – 12 - 14 new cases/yr

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.

Carrier Carrier Cystic Fibrosis Carrier Carrier Non-Carrier

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)

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

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

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

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

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

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

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

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

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”

“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

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

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”

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

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

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

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

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

Nutrition Pancreatic enzymes and supplemental vitamins 30 - 50% increase in energy expenditure due to daily chest physio, coughing, and increased WOB at rest

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

Control of Inflammation Corticosteriods Ibuprofen Under study – Oral mucomyst

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

Mucus Modification VEST Pulmozyme Under study Aerosolized surfactant Aerosolized hypertonic saline

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

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.

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