CYSTIC FIBROSIS Madhu Pendurthi MD MPH Staff Physician, Mercy Hospital Springfield, MO NO CONFLICT OF INTEREST TO DISCLOSE OBJECTIVES Epidemiology of Cystic Fibrosis (CF) Genetic basis and pathophysiology Overview of diagnosis Respiratory disease Extra-pulmonary disease Treatment
SOURCE CF FOUNDATION, WWW.CFF.ORG EPIDEMIOLOGY More than 30,000 people in the US 1000 new cases every year 75% are diagnosed by age 2 More than 50% of the population are 18 or above Most common genetic disease in Caucasians Changing demographics WHAT IS THE CURRENT LIFE EXPECTANCY IN CF IN YEARS? A. 55 B. 28 C. 37 D. 20 GENETICS Single gene mutation in long arm of chromosome 7 Most prevalent mutation is F508del Mutations that result in premature degradation or incomplete maturation About one in every 31 Americans is a symptomless carrier of the defective CFTR gene SCIENCE 01 SEP 1989:
AUTOSOMAL RECESSIVE DISEASE PATHOPHYSIOLOGY Mutation in the CFTR (Cystic fibrosis transmembrane conductance regulator) Protein OPENSOURCE: WIKIPEDIA
PATHOPHYSIOLOGY PATHOPHYSIOLOGY CFTR gene defect Abnormal CFTR Protein Defective ion transport Decreased mucous clearance Abnormal mucous Defective bacterial killin Repeated infections, inflammation, mucous obstruction, bronchiectasis End stage lung disease DIAGNOSTIC CRITERIA OF CF Phenotypic +++ Laboratory evidence
DIAGNOSTIC CRITERIA OF CF- PHENOTYPIC!Chronic sinopulmonary disease!chronic cough and sputum production!persistent infection with characteristic pathogens- Staph, Pseudomonas!Airflow obstruction!chronic chest radiographic abnormalities!sinus disease; nasal polyposis!clubbing!gastrointestinal and nutritional abnormalities!exocrine pancreatic insufficiency!recurrent pancreatitis!fat-soluble vitamin deficiency!distal intestinal obstruction!obstructive azoospermia in males DIAGNOSTIC CRITERIA OF CF- LABORATORY Elevated sweat chloride Disease causing mutation in CFTR gene Bioelectric abnormalities in nasal epithelium Ex vivo intestinal current measurement DIAGNOSIS IN NEWBORN- SCREENING
DIAGNOSTIC ALGORITHM-ADULTS ADAPTED FROM FARRELL PM, ROSENSTEIN BJ, WHITE TB, ET AL: GUIDELINES FOR DIAGNOSIS OF CYSTIC CLINICAL MANIFESTATIONS WIKIMEDIA COMMONS PULMONARY MANIFESTATIONS Cough with bronchitis Wheezing Phlegm Exacerbations Triggers
MICROBIOLOGY Chronic infection and colonization Staphylococcus aureus Hemophilus influenza MRSA Pseudomonas Achromobacter Stenotrophomonas MDR-Pseudomonas PFT- SPIROMETRY WAGENER JS, HEADLEY AA. CYSTIC FIBROSIS: CURRENT TRENDS IN RESPIRATORY CARE. RESPIR CARE. 2003;48(3):234-45. CHEST IMAGING MURRAY AND NADAL 6TH ED
COMPLICATIONS OF RESPIRATORY DISEASE Atelectasis Pneumothorax Hemoptysis ABPA Digital Clubbing Respiratory failure GASTROINTESTINAL MANIFESTATIONS Distal intestinal obstruction syndrome Gastroesophageal reflux disease Rectal prolapse Exocrine pancreatic insufficiency Malabsorption and nutritional failure Recurrent pancreatitis CF-associated liver disease Cholelithiasis CF-related diabetes GENITOURINARY TRACT ABNORMALITIES Vas deferens is congenitally absent in almost all males with CF Women-infertility in CF- 20%
TREATMENT WHICH OF THE FOLLOWING IS NOT INDICATED IN REGULAR THERAPY OF CF? 1. Inhaled Tobramycin 2. Prednisone 3. Human recombinant DNase 4. 7% hypertonic saline TREATMENT- RESPIRATORY Restoring airway hydration- Hypertonic saline Mucolytics- Dornase Alfa Anti-inflammatory- ibuprofen Inhaled antibiotics- Tobramycin, Aztreonam Systemic antibiotics Targeted therapies
AIRWAY CLEARANCE TECHNIQUES Huffing Air cycled breathing Autogenic drainage Chest physical therapy/ percussion High frequency oscillator/vest PEP AOD TREATMENT Gastrointestinal- Pancreatic enzymes ENT care- Nasal steroids, antihistamines, neti pot, sinus surgeries Diabetes Nutritional support Physical Therapy IN WHICH YEAR WAS FIRST CFTR MODULATOR APPROVED BY FDA? 1. 1997 2. 2003 3. 2012 4. 2017
KUK K, TAYLOR-COUSAR JL. LUMACAFTOR AND IVACAFTOR IN THE MANAGEMENT OF PATIENTS WITH CYSTIC FIBROSIS: CURRENT EVIDENCE AND FUTURE PROSPECTS. THER ADV NEW THERAPIES IN CF Ivacaftor (Kalydeco)-G551D mutation- increases the time the CFTR is open. 4-5% of CF patients Lumicaftor+Ivacaftor (Orkambi)- in patients with 2 copies of F508del, 3% improvement in lung function 34% reduction in hospital admission Tezacaftor+Ivacaftor (Symdeko)-in patients with 1 copy of F508del- Feb, 2018 Gene therapies RESPIR DIS. 2015;9(6):313-26. LUNG TRANSPLANT First transplant in 1983 CF accounted for approximately 16.4% of LT recipients Median survival for patients surviving at least 3 months was 10.0 years When to refer?! FEV1<30%, respiratory failure with ICU stay, pulmonary hypertension, hypercapnic failure LYNCH JP, SAYAH DM, BELPERIO JA, WEIGT SS. LUNG TRANSPLANTATION FOR CYSTIC FIBROSIS: RESULTS, INDICATIONS, COMPLICATIONS, AND CONTROVERSIES. SEMIN RESPIR CRIT CARE MED. 2015;36(2):299-320. ROLE OF PRIMARY CARE PROVIDERS Identification Timely referral to a CF center Reinforcing patient participation Early use of antibiotics and longer duration Use of CF cultures Convey hope
RECAP CF is a genetic disease Pulmonary and extrapulmonary involvement Multispecialty and multimodality approach Emerging therapies and improved life expectancy CF REFERRAL CENTERS IN MISSOURI Adult:! St. Louis University Medical Center, St. Louis! University of Missouri, Columbia! Washington University, St. Louis Pediatric! Cardinal Glennon, St. Louis! Children s Hospital, Columbia! University of Missouri, Kansas City! St. Louis Children Hospital! Outreach clinic- Springfield, MO THANK YOU