Cystic fibrosis

1. Cystic fibrosis Tiffany Rimmer

2. Cystic Fibrosis • CF is the most common lethal autosomal recessive genetic disease in Caucasians. • It affects over 30,000 individuals in the United States. • The median survival age is 35 years old.

3. Cystic Fibrosis • CF is a chronic disease with primary manifestations in the Respiratory, Digestive, and Reproductive systems. • Characterized primarily by: • Chronic obstruction and infection of airways • Exocrine pancreatic insufficiency with its consequences of maldigestion and small bowel obstruction • Elevated sweat chloride levels

4. Genetics • Defect in a single gene on chromosome 7 • Autosomal recessive disease with mutations in the CFTR gene • Both parents of a child with CF are carriers of the gene, which means there is a 1 in 4 chance these parents will have a child with CF • There is family history in only 17% of newly diagnosed patients • It is estimated that 4% of Caucasians in the US are carriers with no recognizable clinical symptoms

5. Diagnosis • Diagnosis is made at the median age of 6 months • Diagnosis requires positive lab testing along with history or clinical conditions consistent with CF • One item from each of the following categories must be present • Lab Testing • Sweat Chloride Level >60 mEq/L • Two CFTR mutations identified • Abnormal ion transport across nasal epithelia • History or Condition • Clinical evidence of CF • Sibling with CF • Positive newborn screening for CF

6. Diagnosis • Sweat Test is the standard diagnosis for CF • Sweat is obtained by stimulating the skin on the forearm with pilocarpineiontophoresis • Normal secretion and resorption of chloride in the sweat gland are dependent on CFTR • In CF, there is a production of hypertonic sweat containing high concentrations of sodium and chloride • Must have a level >60 mEq/L

7. Pulmonary Disease • Accounts for much of CF morbidity and causes death in more than 90% of cases • Abnormal water and electrolyte transport across the respiratory epithelium • Leads to thick tenacious sputum, impaired secretion clearance, mucus plugging of the airways, chronic bacterial infection, and airway inflammation • Usually begins with an onset of NPC that evolves into a loose, productive cough with purulent secretions

8. Pulmonary Disease • Mucus production & Airway Obstruction • Lungs are normal at birth; airway dysfunction begins during first year of life • Thickened mucus and plugging of the submucosal gland ducts in the large airways • Increased goblet cells and hypertrophy of submucosal glands; leads to increased secretions and sputum production • Secretions are relatively dehydrated • Disease was once referred to as mucoviscidosis • Mucociliary clearance is variable; reduction in clearance is believed to be caused by increased volume of secretions and abnormally thick mucus

9. Pulmonary Disease • Bacterial infections • Infection is caused by colonization of CF airways with various bacteria (Staphylococcus aureus, Haemophilusinfluenzae, Pseudomonas) • May result in acute necrotizing pneumonia • Results in progressive damage to the airway wall and accumulation of thicker sputum within the scarred airways; severe obstruction of the airway results and the pt develops bronchiectasis and respiratory failure

10. Pulmonary Disease • Airway inflammation • Major component of CF and occurs early in disease process • Present in those as young as 4 weeks, likely occurring before infection • Abundance of neutrophils and the enzyme neutrophilelastase may be responsible for the airway destruction and inflammatory response

11. Clinical Manifestations • Bronchitis • Bronchiectasis • Pneumonia • Refractory asthma • Chronic cough • Sputum is mucopurulent and difficult to expectorate • Tachypnea • Dyspnea • Use of accessory muscles • Retractions • Wheezes, crackles, rhonchi, and decreased air exchange on auscultation • Digital clubbing (advanced CF)

12. Clinical Manifestations • Chronic hypoxemia and progressive lung disease lead to increased pulmonary vascular resistance, hypertension and corpulmonale • Chest Xray (Pg 603) • Initially shows hyperinflation with flattened diaphragm secondary to air trapping • Mucus plugging and bronchial wall thickening • Diffuse fibrosis and bronchiectasis in upper lobes at beginning but eventually involves all fields • Pneumothorax occurs in older pts as result of a rupture of subpleural blebs

13. Clinical Manifestations • PFT • Initially shows airflow obstruction but as it progresses, shows both restrictive and obstructive patterns as well as decrease in air flow • 50% of pts have positive methalcholine challenge tests which indicates hyperreactivity

14. Clinical Manifestations • Upper airway disorders-sinusitis, nasal polyps • Pancreatic insufficiency • Steatorrhea • Failure to thrive • Failure to gain weight in spite of good appetites • Diabetes Mellitus • MeconiumIleus & Distal Intestinal Obstruction • Rectal prolapse • GERD • Sterility in males • Hepatobilliary disorders-cirrohsis, gallbladder abnormalities

15. Treatment • Focus on routine therapy aimed at physically removing thickened mucus from the airways and pharmacologic control of infection with the aggressive use of antibiotics • Medications (CFF Handout) • Airway and Secretion Clearance • Antibiotic Therapy • Oxygen Therapy • Lung transplant