Snapshot A 3-year-old boy with a history of recurrent pneumonia and chronic diarrhea. His mother states that he has 6-8 four smelling stools per day. PE reveals a low grade fever, scattered rhonchi over both lung fields, crepitant rales at the left lung base and dullness to percussion. Introduction Cystic fibrosis is a genetic disorder leading to excessive, viscous secretions that plug exocrine glands autosomal recessive disorder caused by mutations in CFTR gene (chloride channel) on chromosome 7 CFTR is a transmembrane cAMP-activated ion channel its normal function is to reabsorb chloride ions (lumen → cell) in sweat glands and to secrete chloride ions (cell → lumen) in other exocrine glands (e.g., pancreas and lungs) movement of chloride creates a charge gradient that induces movement of sodium ions in the same direction as chloride to mitigate the gradient movement of these ions drags solvent (water) with them 3 nucleotide deletion most common mutation is 508 Phe del result is instability of CFTR protein and premature degradation by Golgi apparatus inability to alter ionic gradients of Cl- results in mucus dehydration Affects multiple organ systems with widespread exocrine gland dysfunction pancreatic exocrine insufficiency is responsible for most of them Epidemiology most common genetic disease in the United States mostly affects Caucasians Newborn screening now routine in all states Presentation Symptoms respiratory symptoms are more prominent in adulthood recurrent pulmonary infections Pseudomonal spp and S. aureus are most common chronic sinusitis chronic, productive cough dyspnea on exertion hemoptysis gastrointestinal symptoms are more prominent in infancy chronic, frequent diarrhea greasy stool with flatulence from malabsorption secondary to pancreatic insufficiency steatorrhea can cause deficiency in fat soluble vitamins can lead to rectal prolapse meconium ileus in infants (15%) pancreatitis other symptoms calcium oxalate kidney stones secondary to fat malabosorption Physical exam failure to thrive (50%) respiratory compromise (50%) "salty taste" cyanosis digital clubbing ronchi rales hyperresonance of chest to percussion nasal polyposis Evaluation CXR hyperinflation prominent bronchovascular markings bronchiectasis with "tram tracks" and peribronchial cuffing diffuse bronciectactic changes Sweat chloride test historical diagnostic gold standard >60 mEq/L in patients <20 years old >80 mEq/L in adults Genetic testing confirms disease by identification of specific genetic mutation Immunoreactive trypsinogen assay Nasal transepithelial potential difference Pulmonary function testing often abnormal before first birthday obstructive pattern with increased lung volumes (TLC and RV) over time from air trapping and hyperinflation reduced diffusing capacity (DLCO) reduced or normal FEV1:FVC ratio given obstructive pattern with possible late restrictive features (e.g., fibrosis, tissue destruction, and/or hyperinflation) Differential Inherited immunodeficiency (SCID, CVID) Primary ciliary dyskinesia Treatment Lifestyle health maintenance nutritional counseling psychiatric/psychologic support indicated in most patients with or without mental instability up-to-date immunizations indicated in all patients Pharmacologic respiratory therapy indicated in all patients includes several components including chest physiotherapy (percussion, positive pressure, nebulizers) bronchodilators inhaled corticosteriods if asthmatic component or ABPA DNA-ase and hypertonic saline antibiotics chronic macrolide therapy common IV antibiotics for acute exacerbations anti-inflammatory agents (ibuprofen) pancreatic enzymes and fat-soluble vitamins indicated for malabsorption Operative lung and pancreas transplantation indicated for most severe, but only if patient can tolerate surgery Prognosis, Prevention, and Complications Prognosis while patients are living longer and more complete lives with modern medicine, rarely do CF patients live beyond 40 years of age without transplantation Prevention immunization for influenza and pneumococcus can prevent infections embryonic selection, although controversial, has been used by known carriers or affected couples to prevent transmission of the disease to their children Complications chronic hypoxemia and hypercapnia lead to pulmonary hypertension patients often develop cor pulmonale (RHF) Recurrent, drug-resistent bacterial or fungal pneumonias classically Pseudomonas idiopathic hyponatremia CF-related diabetes mellitus fat-soluble vitamin deficiency (low vitamin A, D, K, and E) esophageal varices biliary cirrhosis and cholelithiasis infertility (95%) absence/obliteration of the vas deferens heat exhaustion (poor sweating)