1. Cystic Fibrosis "Woe to that child which when kissed on the forehead tastes salty. He is bewitched and soon must die." This European adage accurately describes the fate of an individual diagnosed with cystic fibrosis during ancient times. Part 2

2. Diagnosis Patients present with persistent pulmonary infections, pancreatic insufficiency, and elevated sweat chloride levels Adults are more likely to present with GI symptoms, diabetes, and infertility As of 2010 CF newborn screening is required in all states

3. Diagnostic Criteria BOTH of the following criteria must be met to diagnose CF: 1.Clinical symptoms consistent with CF in at least one organ system, AND 2.Evidence of CFTR dysfunction (any of the following): Elevated sweat chloride ≥60 mmol/L (on two occasions) Presence of two disease-causing mutations in CFTR from each parental allele Abnormal nasal potential difference

4. Sweat Chloride Test Remains the primary test for the diagnosis of CF. Intermediate results of sweat testing should be clarified by DNA analysis using a CFTR multi-mutation method, and sweat chloride testing should be repeated.

5. Treatment and Survival Although CF shortens lifespan, survival has dramatically increased from the 1950’s –Between 1985 and 2007 the median lifespan increased from 25 to 37 years 45% of CF patients are >18 years old 10% of CF patients are >40 years old In 2011 the median predicted survival for patient in the United States was 36.8 years

6. Cornerstones of Chronic Cystic Fibrosis Therapy Airway clearance –Manual percussion, oscillating vest, flutter valve Mucolytic dornase alfa Nebulized antibiotics –Tobramycin –Colistimethate, aztreonam Oral azithromycin Inhaled hypertonic saline Aggressive antibiotic therapy for exacerbations Nutritional support –High-caloric, high salt diet Replacement of fat- soluble vitamins ADEK Exercise

7. Pulmonary Treatments

8. Ivacaftor (Kalydeco®) Only for patients with G551D mutation 150 mg by mouth twice daily with high fat meal Improves chloride transport by potentiating CFTR Decreases sweat chloride, increases FEV1, increases weight, decreases exacerbations, increases quality of life

9. Dornase Alfa (Pulmozyme®) Reduces mucous viscosity Dosed at 2.5 mg daily or twice daily Administered via nebulizer and should not be mixed with other drugs Improves FEV1 and decreases exacerbations

10. Hypertonic Saline Improves airway clearance by hydrating the airway surface liquid 3% or 7% saline twice daily to four times daily Administered via nebulizer Improved FEV1 and decreased exacerbations

11. Inhaled Tobramycin (TOBI) Antipseudomonal aminogylcoside antibiotic Dosed at 300 mg inhaled every 12 hours for 28 days and then not taken for 28 days Must be used with PARI-LC PLUS handheld nebulizer Administer TOBI last and do not mix with other inhaled medications Improves FEV1 and decreases exacerbations

12. Aztreonam (Cayston®) Antipseudomonal antibiotic Dosed at 75 mg inhaled every 8 hours for 28 days and then off for 28 days Utilizes Alteral Nebulizer System. Do not mix with other inhaled medications Improves FEV1 and decreases exacerbations

13. Azithromycin (Zithromax®) Antibiotic that does not have anti- pseudomonal activity also exhibits some anti-inflammatory properties Dosed at 250 or 500 mg orally three times a week Decreases exacerbations