2. Objectives Review the causes of cystic fibrosis (CF) Describe the symptoms and laboratory findings in CF Review current and emerging CF treatments Review expectations of quality of life (QOL) for CF patients Look at current research in the area of CF

3. By The Numbers Most common life-shortening disease in the Caucasian population –Frequency of 1 in 2000-3000 live births In the 1970’s, patients only survived into their teens By 2006 advances in care extended survival to 36 years In 2011 the median predicted survival for patient in the United States was 36.8 years

4. The Genetics Of CF CF is caused by autosomal recessive inheritance

5. The Genetics Of CF CF is caused by a mutation of the cystic fibrosis transmembrane regulator (CFTR) gene on Chromosome 7 –Most common mutation is delta F508 –CFTR can function as a chloride channel Over 1500 mutations have been identified –Typical panels only screen for 30 of these mutations

6. CF Sweat Gland Pathophysiology

7. Cystic Fibrosis Pathophysiology Organ(s)AbnormalityResult PulmonaryThick secretions Infection Chronic obstruction, infection PancreasDeficiency of pancreatic enzymes, insulin Malabsorption, malnutrition, CF diabetes IntestinesThick secretionsObstruction DIOS LiverBiliary cirrhosis, fatty infiltration Portal hypertension, esophageal varices Sweat glandsUnable to reabsorb sodium Hyponatremia ReproductiveObstruction in male reproductive tract Azospermia, infertility

8. CF Lung Pathophysiology Diminished host defenses results in chronic bacterial infections of the lung which results in: –Inflammation –Infection –Obstruction Common bacterial pathogens: –Pseudomonas aeruginosa (most common) –Staphylococcus aureus –Haemophilus influenzae –Burkholderia cepacia Inflammation + Infection + Obstruction + Bacterial Toxins = Impaired Gas Exchange

9. CF Gastrointestinal Pathophysiology Exocrine Insufficiency –Due to obstruction of pancreatic ducts and intestinal tract and their inability to digest essential nutrients –Newborns may present with meconium ileus –Pancreatic enzyme insufficiency Trypsin, chymotrypsin, carboxypeptidase, amylase, and lipase –Fat soluble vitamin deficiency- A, D, E, K –Malnutrition due to fat malabsorption

10. CF Gastrointestinal Pathophysiology Endocrine Insufficiency –Typically onset occurs between 18-24 years –Pancreatic malfunction can lead to insulin deficiency Cystic Fibrosis Related Diabetes (CFRD) –Approximately 25 percent of patients develop CFRD by 20 years of age and up to 50 percent of adults with CF have CFRD –Typically presents with both type 1 and type 2 features –Pancreas cannot meet carbohydrate demands –High blood glucose following meals

11. Signs and Symptoms Sinus/Pulmonary Nasal polyps Cough Increased sputum production Recurrent pneumonia SOB Dyspnea Barrel chest Digital clubbing Gastrointestinal/ Endocrine Meconium ileus Abdominal pain and distension Nausea and vomiting Steatorrhea Malnutrition Hyperglycemia Salty skin