Cystic Fibrosis Best Practices

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Cystic Fibrosis Best Practices. Diane Hanfelt-Goade MD Director, Adult CF Center. Case presentation. 28 year-old gentleman with cystic fibrosis, genotype Δ F508 homozygous Diagnosed as an infant with meconium ileus Followed every 3 months in CF clinic - PowerPoint PPT Presentation

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Cystic Fibrosis More than just mucus

Cystic FibrosisBest Practices

Diane Hanfelt-Goade MDDirector, Adult CF Center

128 year-old gentleman with cystic fibrosis, genotype F508 homozygousDiagnosed as an infant with meconium ileusFollowed every 3 months in CF clinicColonization with Pseudomonas aeruginosa and Staphylococcus aureusHistory of staph schleiferi and aspergillus tares. Called with increasing cough and SOB for three weeks

Case presentation

1. Moderate to severe lung dysfunction2.Pancreatic insufficiency.3.Chronic sinusitis, nasal polyps4.Allergic rhinitis.5.Impaired glucose tolerance. 6.Reactive airway disease.7.History of hiatal hernia.8.History of H. pylori9.Sleep apnea10.Low body mass index.

Problem list

1.Pulmozyme 2.5 milligrams inhaled once daily.2.7% hypertonic saline inhaled once per day.3.Oxygen 2 liters nocturnally.4.Vest once per day5.Acapella once or twice per day.6.Tobi 300 milligrams inhaled, 28 days on, 28 days off. This is an off cycle.7.Aztreonam 75 milligrams inhaled three times a day 28 days on, 28 days off. 8.Azithromycin 500 milligrams by mouth Monday, Wednesday, Friday.9.Ultrase MT18s, 8-9 with meals and 4-5 with snacks.10.Ensure three cans daily.11.Multivitamin one tablet by mouth once daily.12.Calcium 600 milligrams with 125 of D, once daily.13.Flonase 0.5 %, two sprays per nostril once or twice per day.14. AquADEK, 2 tablet by mouth daily15.Scan Dical as needed. 16.Vitamin D 50,000 international units reports he took for 8 to 10 days 17.Vitamin A, dosage unknown, one tablet by mouth every day. 18.Vitamin E 400 international units one by mouth every day. 19.Zyrtec 10 mg by mouth as needed for allergies.20. Spiriva 18 micrograms inhaled once daily. 21.Saline nasal washes as needed. 22.ProAir 90 micrograms inhaled two to three puffs prior to therapy and as needed.23.Advair HFA 2 puffs twice daily.

Medications and treatments:

Pulmonary function tests FVC of 2.27 (39%), FEV1 1.30 (27%), FEF 25-75% is 0.52 (11%), RV/TLC % of 46

A multisystem diseaseAutosomal recessive inheritanceCause: mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)chromosome 7 codes for a c-AMP regulated chloride channelWhat is cystic fibrosis (CF)?Rosenstein, BJ and Zeitlin, PL. Cystic fibrosis. The Lancet. 351: 277-82.

6Many functions still under investigation----CFTROne or more clinical features of CF PLUSTwo CF mutations on genetic testing ORTwo positive quantative pilocarpine iontophoresis sweat chloride values ORAn abnormal nasal transepithelial potential difference value

Diagnosis of cystic fibrosisCystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic fibrosis.1997.

1st Descriptions17th Century European folkloreA child that tastes salty when kissed will soon die.Thought to be hexed/bewitched

18th Century Case DescriptionsCases of children with severe malnourishment, steatorrhea, meconium ileus

Quinton PM. Phys Rev;1999;79:S3-S22. www.cysticfibrosismedicine.com

Clinical Description1943 Dr. Stanely FarberMucoviscidosisMultisystem diseaseMajor manifestationsChronic bronchopulmonary infectionsMalabsorption and steatorrheaGrowth Failure

Farber S. Arch Pathol 1944;37:283-250.

History1948 Dr. Paul di Sant AgneseHigh chloride/sodium in sweat CF patientsStandardization of sweat test by 1959

1954 1st comprehensive CF center

Cystic fibrosis transmembrane conductance regulator (CFTR) geneThe CFTR gene is located on the long arm of chromosome 7.There are 1522 mutations in CFTR listed on the mutation database (http://www.genet.sickkids.on.ca/cftr/)The most common mutation is F508-70% CF alleles in caucasians.1Causes loss of aa phenylalanine at position 508 in protein

http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/cftr.shtml1. Gibson, RL, Burns, JL, and Ramsey, BW. Pathophysiology and Management of PulmonaryInfections in Cystic Fibrosis. AJRCCM 168 (918-951);2003.

11Delta f508 causes loss of the amino acid phenylalanine located at position 508 in the protein CFTR

Gibson, RL, Burns, JL, and Ramsey, BW. Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis. AJRCCM 168 (918-951); 2003.CFTR functions as a regulated chloride channelAlso regulates the activity of other chloride and sodium channels at the cell surface

Cilia do not beat well when PCL volume is depletedMucins are not diluted and cannot be easily swept up the airway Mucus becomes concentratedResults in increased adhesion to airway surfacePromotes chronic infectionAirway surface liquid low volume hypothesis and consequencesDonaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.Current Opinion in Pulmonary Medicine. 9: 486-491; 2003.

Mucus---helps clear airway of bacteriaClearance of mucus depends on Ciliary functionMucin secretion Volume of airway surface liquid (ASL) Forms periciliary liquid layerDilutes mucus---facilates entrapment of bacteria and clearanceOptimal volume of ASL regulated by Na+ absorption and Cl- secretionAirway surface liquid low volume hypothesisDonaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.Current Opinion in Pulmonary Medicine. 9: 486-491; 2003.

CFTR and Airway Surface Liquid

Donaldson,SH and Boucher,RC. Update on the pathogenesis of cystic fibrosis lung disease.Current Opinion in Pulmonary Medicine. 9: 486-491; 2003.

Most common life-shortening recessive genetic disease in Caucasians 1:3,500 newborns in the US

1 in 10,500 Native Americans

1 in 11,500 Hispanics

1 in 14,000 to 17,000 African Americans

1 in 25,500 Asians http://www.cff.orgBurden of CF

About 30,000 people affected in United States

>10,000,000 people carriers of mutant CFTR

80% cases diagnosed by age 3

Almost 10% diagnosed 18 yearsatypical disease

UNM Adult care center has approx 66 patientsBurden of CF (continued)http://www.cff.org

Overall trend is improved survival

Female survival worse than male between 2-20 years of age1

35% of patients are older than 18 years of age2

Median survival 36.8 years31930s life expectancy was about 6 months2

The impact of usual adult diseases in CF is virtually unknown

CF Survival1.Goss, CH and Rosenfeld, M. Update on cystic fibrosis epidemiology. Current Opinion in Pulmonary Medicine. 10:510-514; 2004.2. Davis, P. Cystic Fibrosis Since 1938. AJRCCMss. Doi: 10.1164/rccm.200505-840OE; 2005. 3.www.cff.org/news/general_news

Chronic SinusitisChronic pulmonary infectionsEndobronchial diseaseGI diseaseNutritional deficienciesLiver diseaseCFRD, pancreatic dysfunctionObstructive azospermia

CF clinical manifestations

Chronic infection with CF pathogens Endobronchial diseaseCough/sputum productionAir obstruction---wheezing; evidence of obstruction on PFTsChest x-ray anomaliesDigital ClubbingSinus diseaseNasal PolypsCT or x-ray findings of sinus diseaseChronic Sino-Pulmonary DiseaseCystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic fibrosis.1997.

Endobronchial disease

HyperinflationPeribronchial cuffingBronchiectasisDiffuse fibrosis AtelectasisFrom: http://www.meddean.luc.edu/lumen/meded/elective/pulmonary/cf/cf_f.htm

Nasal Polyps

Benign lesions in nasal airwayIf large enough, can be associated with significant nasal obstruction, drainage, headaches, snoringLikely associated with chronic inflammationMay need surgical interventionHigh recurrence rateFrom: http://www.emedicine.com/ped/topic1550.htm

Intestinal abnormalityMeconium ileusDistal intestinal obstruction syndrome (DIOS)Rectal prolapseHepatobiliary diseaseFocal biliary cirrhosisMultilobular cirrhosisPancreatic endocrine dysfunctionCystic fibrosis related diabetes

GI disease

Pancreatic insufficiencyAutopsy of malnourished infants--1938--- cystic fibrosis of the pancreas---mucus plugging of glandular ducts1Nutritional deficiencyDavis, P. Cystic Fibrosis Since 1938. AJRCCM Articles in Press. Doi: 10.1164/rccm.200505-840OE; 2005.

Chloride impermeability affects HCO3- secretion and fluid secretion in pancreatic ducts2Pancreatic enzymes stay in ducts and are activated intraductallyAutolysis of pancreasInflammation, calcification, plugging of ducts, fibrosis

MalabsorptionFailure to thriveFat soluble vitamin deficiencyNutritional deficiencyDavis, P. Cystic Fibrosis Since 1938. AJRCCM Articles in Press. Doi: 10.1164/rccm.200505-840OE; 2005.2. Quinton, P. Physiologic Basis of Cystic Fibrosis. Physiol Rev 79:3-22, 1999.

ComplicationsEndocrineGlucose intolerance/CFRDReduction in insulin secretion due to pancreatic damageInsulin resistance related to infection and CF exacerbationsAssociated with accelerated pulmonary decline and increased mortalityArthropathy (2-9%)Osteopenia/osteoporosis

Focal inspissation of bileObstructs biliary ductulesSecond leading cause of death in CF1Prevalence 9-37%1Spectrum of disease increased liver enzymes biliary cirrhosis portal hypertension

Cystic fibrosis related liver disease1. Efrati, O et al., Liver Cirrhosis and portal hypertension in CF. European Journal of Gastroenterology and Hepatology. 15(10): 1073-1078; 2003.

27Ursodiol increases bile flow {02} . In chronic cholestatic liver disease, ursodiol appears to reduce the detergent properties of the bile salts, thus reducing their cytotoxicity. Also, ursodiol may protect liver