Tiffany Rimmer

 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.

 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

 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

 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

 Sweat Test is the standard diagnosis for CF  Sweat is obtained by stimulating the skin on the forearm with pilocarpine iontophoresis  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

 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

 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

 Bacterial infections  Infection is caused by colonization of CF airways with various bacteria ( Staphylococcus aureus, Haemophilus influenzae, 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

 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 neutrophil elastase may be responsible for the airway destruction and inflammatory response

 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)

 Chronic hypoxemia and progressive lung disease lead to increased pulmonary vascular resistance, hypertension and cor pulmonale  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

 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

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

 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