Cystic FibrosisAn OverviewBridget Platania RN MSN CPNPAPP Grand Rou - PDF document

Cystic Fibrosis:An OverviewBridget Platania RN, MSN, CPNPAPP Grand Rounds/Enduring PresentationSpring 2019 ObjectivesUnderstand the genetic abnormality causing cystic fibrosis (CF) and the newborn screen processRecognize the multiple organ systems affected by CFIdentify common treatments /medications and management strategies

for CF (both inpatient and outpatientUnderstand the CFTR modulators available and a general overview of how they workUnderstand the unique infection control issues related to CFRecognize the psychosocial implications of What is Cystic Fibrosis? Cff.orglung infections and limits the ability to bre

athe over time. In people with CF, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the CFTR protein to become dysfunctional… Epidemiology/Demographics of Cystic FibrosisAutosomal recessive transmissionOver 1700 mutations on CFTR gene known to date per 31 Americans are symptom free

carriers of defective CFTR gene 1 in 29 CaucasianAmericans1 in 46 HispanicAmericans1 in 65 AfricanAmericans1 in 90 AsianAmericans Epidemiology of Cystic Fibrosis (cont’d)individuals worldwide)1 in 2,5003,500 CaucasianAmericans1 in 4,00010,000 HispanicAmericans (steady increase over the past 15 years reflecting national po

pulation trends)1 in 15,00020,000 AfricanAmericans1 in 100,000 AsianAmericans~ 1,000 new cases of CF are diagnosed each yearMore than 75% of new diagnoses are made by age 2 yearsMedian predicted age of survival has increased from 33.4 years in 2003 to 40.7 years in 2013 to 46.2 in 2017 CFTR: What is it?ystic ibrosis ransmembra

ne conductance egulatorA protein found in the cells that line various organs (like the lungs and pancreas)This protein is responsible for regulating the flow of salt and fluids in and out of the cells in different parts of the bodyPlays a key role in maintenance of airway surface liquid layer How CFTR works in healthy cells(Ad

apted from Orenstein, 2004) Lumenal Surface1. Production2. Folding3. Regulation4. Conduction Airway Cell signals Chloride CFTR Abnormalityefective proteinmalfunction or not be made at allthe protein is not working correctly, it’s unable to help move chloride a component of salt to the cell surface. Without the chloride to

attract water to the cell surface, the mucus in various organs becomes thick and stickysalt balance in the body is disturbed. Without CFTR:Airway surface liquid is depletedMucociliaryclearance is reducedMucus viscosity is increasedailure to resorb NaClpatients do not make more mucus than non Cystic Fibrosis Foundation: Cilia

(CFTR in Action) ��9&#x/BBo;&#xx [1;—.6;& ;W.9;( ;ԧ.;ࡱ&#x 85.;7 ;&#x]/Su;typ; /F;&#xoote;&#xr /T;&#xype ;&#x/Pag;&#xinat;&#xion ;&#x/BBo;&#xx [1;—.6;& ;W.9;( ;ԧ.;ࡱ&#x 85.;7 ;&#x]/Su;typ; /F;&#xoote;&#xr /T;&#xype ;&#x/Pag;&#xinat;&#xion

;(click on image to play video) 10 ��Cff.org and CFF Registry Report, 45.3% 2 copies of F508del40.9% 1 copy of F508del 4.6%G542x 4.5%G551D 2.9% Arrows indicate % of all people with CF in 2017 who have a specific mutation Newborn Screen (NBS) Process for Cystic FibrosisNY State started NBS in 2002 (nationwide sin

ce 2010)NYS revised screening protocol in 12/2017 to include DNA testing on eligible samplesBetter nutritional outcomes which ultimately leads to improved pulmonary healthNBS is a screening tool, not a diagnostic oneChloride Measurement **BEST METHODQuantitative pilocarpineiontophoresisLoss of CFTR function failure to reabsorb

NaCland therefore high Cl levels in patients with CF Symptoms at Diagnosisn individuals 1year if ageMeconium ileus or intestinal obstruction: 13.1Failure to Thrive: 5.1%Steatorrhea/abnormal stools/malabsorption: 2.8%Acute or persistent respiratory abnormalities: 1.3%In individuals &#x-1.3;&#x 000;1 year of ageAcute or persist

ent respiratory abnormalities: 45%Failure to Thrive: 11.2%Nasal polyps/sinus disease: 10.8%CBVAD or infertility/GU abnormalities: 7.4%Steatorrhea/abnormal stools/malabsorption: 6.7%Taken from Martinez, 2010 The Cystic Fibrosis Foundationcure and control cystic fibrosis and to improve the quality of life for those with the dise

aseGrants for care and researchQI TrainingCF Care GuidelinesEducation and advocacy resourcesPatient Registry (houses data from 29,887 CF patients) CFF Registry Report, 2017 15 ��•380 deaths total in 2017��•Of those 47.6 percent occurred in individuals with 2 copies of delF508��

0;CFF Registry Report, 2017 CFF Registry Report, 2017 Multiple organ systems affected CysticFibrosis Complications of CF, 2017 (taken from CFF Registry Report, 2017) Upper Respiratory Tract14 yearsstline treatment:Nasal irrigation (NeilMed sinus rinse) and topical steroidsNew rinse kit available by request for inpatient

; stocked in clean utility room w/ premixed packets; use w/ sterile waterENT referral for surgical management of persistent and symptomatic polyps may improve lung function If performed, typically at the end of an inpt tune Lower Respiratory Tract: Pathogenesis of Cystic FibrosisDefective CFTRAbnormal (Airway) Surface Environm

ent Bronchial ObstructionInfectionInflammationBronchiectasis Lower Respiratory Tract Lung disease begins within the first few months of life without symptomsCigarette smoke exposure a risk factorAirway clearance recommended for all patients with Airway Clearance Techniques“The Vest” which sputum mobilization

The Flutter or The Acapella (can be ordered by MD for inpts)PEP valve or AerobiKA Airway Clearance DevicesHigh Frequency Chest Wall Oscillation (“Vest”)Intraluminal Oscillation: The Acapella Huff Cough Technique5 huff coughs during and after airway clearance AerobiKA http://www.trudellmed.com/consumerhealth/aerobikao

scillatingpep increased expiratory resistance to thin, dislodge and move mucus to the upper airways where it can be coughed out.prevent infectionsair trappingof each exhalation and continue through the end for maximum effect AerobiKA http://www.trudellmed.com/consumerhealth/aerobikaoscillatingpep Can be used with nebulized me

dications like albuterol, Hypertonic Saline &/or Pulmozyme Medications that enhance airway clearance techniques hydrates thick, sticky mucus in the airwayshigh osmolality draws water from the airway to reestablish the aqueous surface layer that is deficient in CF (where salt goes, water goes)Albuterol before dose to limit bro

nchospasmTrial in PFT lab for first doseUpToDate and CFF.org Medications that enhance airway clearance techniques uniquely targets extracellular DNA, a cause of thick , sticky mucousacts like “scissors” in the mucusCuts up the DNA strands outside the cell that can make CF mucus thick and stickyDNA is from the white

blood cells that work to fight lung infections. (present even if no lung infection)Cff.org and pulmozyme.com Pulmozyme.com CF Pulmonary ExacerbationRespiratory infectionBuild up over timeDifficulty keeping up with prescribed respiratory plan of careIncreased cough and sputumSputum turns greenerFatigueWeight lossDecline in lung

function (FEV1) CFF Registry Report, 2017 Spirometry/lung function testing ��31&#x/BBo;&#xx [2;.0;ն ;x.5;ɸ ;Դ.;吗&#x 105;&#x.662;&#x ]/S;&#xubty;&#xpe /;oot;r /;&#xType;&#x /Pa;&#xgina;&#xtion;&#x 000;&#x/BBo;&#xx [2;.0;ն ;x.5;ɸ ;Դ.;吗&#x 105;&#x.662;&#x

]/S;&#xubty;&#xpe /;oot;r /;&#xType;&#x /Pa;&#xgina;&#xtion;&#x 000;(click on image to play video) CF Pulmonary Exacerbation: Treatmentway approachAirway Clearance to combat mucous obstructionAntibiotics to combat lung infectionAggressive nutrition to provide ample energy to fight infection and inflammationstringent /

stronger interventions when inpatient Pulmonary Exacerbation: Outpatient Antibiotics Look at last sputum culture (routinely obtained every 3 months)Often a 21day course with a 1 month followThose with pseudomonas aeruginosa on sputum/deep throat culture qualify for inhaled antibioticsTOBI via nebulized solution or Podhaler(B

ID x 28 days)AND/ORCaystonvia nebulized solution (TID x 28 days)ength depends on frequency of colonizationi.efor one cycle or ongoing alternate month therapy Pulmonary Exacerbation: Inpatient Antibiotics Prefer peripheral access if “good veins”PICC risk factors: clot development, infectionNeed tobramycin levels dra

wn to determine therapeutic range; will also check kidney functionRequires audiology exam prior to discharge due to Tobramycinup started inpatient and completed at home The finer details of Inpatient Airway ClearanceEZ Pap or Aerobikaor DR Burton VPAP can be ordered with neb treatments based on status/ability; ordered by physi

cian as an RT order; RT does the 1st treatment to set the flow A separate neb cup is used for each med; after each treatment, wash the cup with soap & water; rinse with sterile water; turn upside down on a paper towel to air dry until the next treatmentHypertonic saline and pulmozymeare typically ordered BID during hospitaliza

tion; suggested order is hypertonic saline, pulmozymehypertonic saline, pulmozymethroughout the day so that the pulmozymewill “dwell” in lungs overnight 35 Inpatient Tuneawake; goal 45 times daily), nutritional support (dietician consult including calorie count, every other day weight, management of nutritional suppl

ements)participation vs passive while laying in bed)improvement in FEV1dischargeup is work and not a respite CFF Registry Report, 2017 CFF Registry Report, 2017 As of 1/2019 at URMC, 1 pt with CF with this bacteria; requires strict implementation of infection control measures in an effort to prevent transmission to other

CF pts URMC Data (both Pediatric and Adult) from 2017 CF Registry Center Specific Full Report CF Pulmonary ComplicationsAllergic hypersensitivity caused by Aspergillus fumigatus; screened for and diagnosed by labsTreatment: prolonged oral corticosteroids +/antifungalErosion of blood vesselsScant (ml), Mildmoderate (5240 ml),

massive (S.2;&#x 000;240 ml)Notify pulmonary team if patient becomes symptomatic8 % of all CF pts will have (risk age/severity)Symptoms include sudden onset chest pain, SOB Other Pulmonary Treatments: Antiinflammatory Therapy Helps delay progression of lung diseaseAssociated with significant side effect (check BGs)Used pri

marily for shortterm effects or severe lung diseaseWidely used if airway reactivity or wheezing presentMany patients with CF have a comorbidity of asthma The Gastrointestinal Systempresent at birth in 60% of infants dx by NBS~90% have at 1 year of ageLeads to malabsorption and fat soluble vitamin loss (ADEK) may lead to FTT an

d low vitamin levelsfecal elastase The Gastrointestinal System(PERT)start in infancy if 2 known mutations or objective evidence of pancreatic insufficiency (weight loss/GI Should be given prior to all meals/snacksIn infancy, this includes all formula/breast feedsDose is weight based Teach signs of malabsorption (greasy/shiny s

tools, foul odor, cramping, fatty floaters, frequent bulky stools) Pancreatic Enzyme Replacement TherapySwallow whole oropen capsule and mix beadswith an acidic food; make no beads left in mouth Pancreatic Enzyme Replacement Therapy • Singleuse, pointofcare digestive enzyme cartridge Connects inline with enteral feeding

pump tubing and patient extension sets (DO NOT connect to any IV line, setup or system)Designed to digest fats contained in enteral formulas, mimicking the function of the digestive lipase that is normally secreted by the pancreasUsed with continuous or overnight feeds (DO NOT use with bolus feeds)Used for patients� a

ge 5 yearsInfusion rates need to be � 24 ml/hr and less than 120 ml/hrDo not reuseDo not administer meds through thisContinue to give PO enzymes before oral meals/snacks 45 https://www.relizorb.com/patient/howuse CF and GI ComplicationsMeconium IleusPresenting sign of CF in 1020% of pts / 99% of MI due to CFintestinal o

bstruction from thick meconium present acutelyBroad range of clinical severity; typically requires surgeryDistal ilealobstruction syndrome (DIOS)Thick intestinal mucous and dehydrated stool contentsClinical Presentation: BMs, abdominal pain/cramps, emesisMay be able to palpate massWorkup includes abdfilms & labs: LFTs, amylas

e/lipaseEarly and aggressive treatment with bowel cleanoutMore severe cases require inptstay, NG tube, enemas &surgical consult risk of recurrence CF and GI ComplicationsIncreased index of suspicionMore extensive workMore aggressive therapyOther complicationsPancreatitisAppendicitisIntussusceptionGallstonesRectal prolapse CF a

nd Other GI Diseaseiver disease incidence: ~11%bile sludgingleads to biliary cirrhosisScreen with annual LFTs; if elevated, referred to GITreat with Actigall; end state disease liver transplant Cystic Fibrosis Related Diabetes (CFRD) Occurs in ~20% of the adolescent populationImbalance of insulin needs:Insulin requirement �

000; Insulin productionThe best therapy for CFRD is insulinAnnual OGTT recommended starting at age 10On initial inpt admission, typically check 2 days of postprandial and fasting BGs; stop if normalIf on prednisone burst inpatient, check BGs postprandial and fasting for the first 23 days of therapy & stop if WNLManagement refe

rred to Endocrine GroupPsychological burden a 2nd chronic disease Nutrition in Cystic Fibrosiscalorie/ nutritional absorptioncalorie useInadequate knowledge, maladaptive feeding behaviors, financial barriers to obtaining food, maladaptive family functioningConstipation, reflux, chronic ingestion of sputumNewborn to 6 months: 1

/8 tsp /day divided among feedsAge 6 months until on regular diet: ¼ tsp/day Nutrition in Cystic Fibrosisweigh daily)A higher BMI%ile at age 2 years is associated with better lung function later in childhoodTube a strong considerationParental involvement and consistency are keys CFF Registry Report, 2017 CFF Registry Report,

2017 CF Related Bone Health and DiseaseMalabsorption / malnutrition affects vitamin D levels and calcium absorption and low bone mineralsDelayed puberty contributes to less bone being madeInflammation related to lung infection leads to bone lossat age 8 years for those eligible for DEXA scan to assessassociated with airway cl

earance Female Reproductive System in CFrisk of clots if have a PICC or port; do antibiotics change effectiveness?Nutritional status and lung health contributePhysical and psychologic health affectedHowever, able to give birth to a healthy infant Male Reproductive System in CF Males Without CFMales With CFNormal sexual perform

ance YesYesMake spermYesYesAmount of ejaculateNormalPossibly slightly less than normalAt risk for sexually transmitted infectionsYesYesAbility to father a child Typically YesYes, but usually only with a special procedureor blockednot transported to the penis98% of males with CF do not have sperm in their ejaculatepleasure / pe

rformance Lung Transplantdiseasecenter should be considered when FEV1 ~30%people with CF have received lung transplants per yearover 80 percent are alive 1 year after transplantand over 50 percent are alive after 5 years. Cystic Fibrosis Foundation Therapeutics Pipeline page documentthe following topics (https://www.cff.org/

trials/pipeline):Restore CFTR FunctionMucociliaryClearanceAntiInflammatoryAntiInfectiveNutritionalGIOtherAll studies classified as:clinicalPhase OnePhase TwoPhase ThreeTo Patients Research Highlights1993: Pulmozyme thins mucous in the lungs1996: TOBI (nebulized medication) is FDA approved 2002: azithromycin improves lung healt

h2004: hypertonic saline helps clear lung mucous2010: Cayston is FDA approved2012 Kalydeco™ (ivacaftor) for G551D mutation (ages 6 and older) is FDA approved2012: FDA approval of TOBI Podhaler2014: FDA approval of Kalydeco™ for R117H mutation (ages 6 and older) plus 8 other gating mutations (covers 10 mutations tot

al)2015: FDA approval of Orkambi (ivacaftor/lumacaftor) for ages 12yrs+ for homozygous delF5082015: FDA approval of Kalydeco for ages 2 5 yrs (total of 10 mutations)2016: FDA approval of Orkambi for ages 6 years 11 years2017 (May): FDA approval to increase Kalydeco mutation coverage to 332017 (Aug): FDA approval to increase Ka

lydeco mutation coverage to 382017: FDA approval of Relizorb (digestive enzyme cartridge) for �/= 5 years on enteral feeds2018: FDA approval of Orkambi for ages 2 years 5 years2018: FDA approval of Kalydeco for ages 12 months 24 months2018: FDA approval of Symdeko (ivacaftor/tezacaftor) for homozygous delF508 ages 12yr

+ CFTR Modulationto correct function of defective CFTR proteinoal is for Cl and Na (salt) to move properly in and out of cells lining the lungs and other organsurrently, modulation therapy focuses on:corrector therapy (lumacaftortezacaftorto unfold proteinotentiatortherapy (ivacaftorto move CFTR to the surfaceworks on gating

defect /mutation to fix faulty channel or dysfunction of protein in cell surfaceOr combo of corrector / potentiatortherapy CFTR Modulator TypesHelp chloride flow through CFTR protein channel at the cell surfaceThe CFTR protein is shaped like a tunnel that can be closed by a gatePotentiatorshold the gate open so chloride can g

o throughExample: ivacaftorKalydecoCorrectorsHelp the CFTR protein to form the right 3D shape so that it is able to moveor trafficto the cell surfaceThese drugs help the CFTR protein form the right shape, traffic to the cell surface, and stay there longerExample: lumacaftortezacaftorCombination of Potentiator/CorrectorsHold th

e gate of the CFTR protein open so enough chloride can pass through to reduce the symptoms of CFExample: tezacaftorivacaftorSymdeko®) or lumacaftorivacaftorOrkambiAmplifiersIncrease the amount of CFTR protein that the cell makesCurrently under development and are being tested; not yet available to patients��cff.

org 60 62 ��Cff.org CFTR Modulators currently cover multiple mutations in Class II V categories How CFTR modulators work in a person with an F508del mutation (click on image to play video) 63 Rescue of G551D with a potentiator: ivacaftor (Kalydeco) (click on image to play v

ideo) 64 Infection Prevention & Controlindividuals with CF are a risk to each other by transmission of CF pathogensDroplets can travel ~ 6 ft (previously thought ~3 ft)Droplets remain suspended 45 minutes 2 hours after a patient leaves the roomhealthcare settings Infection Prevention and Control: Inpatient Units at UR stethosc

ope (with alcohol wipe or Caviwipe) prior to and after patient contactmucusplayroom) so patients with CF can be coordinatedoutside of exam rooms get wiped with CaviWipes Infection Prevention and Control: Outpatient Clinic at UR into waiting areastethoscope with either alcohol wipe or Caviwipe prior to and following patient co

ntactagain wears a mask until exit from buildingperform hand hygiene and wear a mask; mask changed every 30 minutes or if damp Infection Prevention and Control Vog and Cambridge masks are NOT approved by the CFF as effective methods of infection control b/c of inability to disinfectDisposable masks are recommended by the CFF a

nd approved at URMC as part of Modified Pulmonary Precautions; should be discarded/replaced after 30 minutes and when soiled Psychosocial Factors: The Short Listup therapies with illness)One thing the patient can control; a known “trigger” to make caregivers upset Depression, Anxiety and CFtimes more likely to experi

ence depression, anxiety or both compared to people in the general populationIf left untreated, people with CF may have lower lung function & BMI, more inpt stays, lower quality of life, higher health care costs, and inability to manage treatment plans effectively9) and Anxiety (GAD7) performed in outpatient clinic by social w

orker��cff.org and Quittner et al, 2014 Patient Independence/Transition of Care Ages 6 - 9 years: B egin to answer questions about symptoms and health with help from parent Begin to learn the n ames of medications and purpose for each (age appropriate slang terms) Begin to understand reason

for a irway clearance , and technique /frequency used Begin to discuss recognition of respiratory/GI baseline and symptoms that indicate a change Begin to discuss school issues (telling teachers and friends about CF , enzyme use during school , field trips, bathroom use, importance of access water and salty

snacks) Begin to discuss why some people have CF and others do not ; explaining CF to friends Ages 10 - 12 years: Patient an swer s questions independently about symptom s and health Use proper names for medications and purpose for each Begin to independently set up/use airway clearance; continue discussion

of why this is important Continue discussion of respiratory/GI baseline and symptoms that indicate a chang e Continue discussion of school issues (telling teachers and friends about CF, enzyme use during school, field trips, bathroom use, importance of access water and salty snacks) Continue discussion of wh

y some people have CF and others do not ; explaining CF to friends ��71&#x/BBo;&#xx [1;c.5;Ŷ ;y.7;֘ ;؇.;䙧&#x 94.;܈ ;&#x]/Su;typ; /F;&#xoote;&#xr /T;&#xype ;&#x/Pag;&#xinat;&#xion ;&#x/BBo;&#xx [1;c.5;Ŷ ;y.7;֘ ;؇.;䙧&#x 94.;܈ ;&#x]/Su;typ;&#

xe /F;&#xoote;&#xr /T;&#xype ;&#x/Pag;&#xinat;&#xion ;Taken from Note Templates used for Patients with CF in the Outpatient Clinic Patient Independence/Transition of Care Ages 13 - 15 years: Patient to independently answer questions about symptoms and health Portions of visit independently with parent in waiting room

Names of medications and purpose for each Monitor medications and supplies and inform parent of needs Airway clearance : independently set - up/perform, able to verbalize purpose, technique and frequency Patient to begin to understand yearly tests (blood, sputum, CXR) Patient to begin to understand p

urpose of quarterly visits to CF Center Lifestyle Choices: Smoking, drinking, drugs related to CF Ages 16 - 19 years: Independent clinic visits w ith parent/caregiver involved at the time of visit sum mary Names of medications and purpose for each Monitor medications and supplies and work with parent to o

btain refills, etc Airway clearance: able to verbalize purpose, technique and frequency Patient to begin to understand yearly tests (blood , sputum, CXR) Encourage direct communication via phone or MyChart with CF Care Team ; be aware of date of clinic appointments Lifestyle Choices: job/occupation; college Smoki

ng, drinking, drugs related to CF ��72&#x/BBo;&#xx [1;U.2;ٶ ;w.7;֘ ;֙.;Ⅷ&#x 92.;܈ ;&#x]/Su;typ; /F;&#xoote;&#xr /T;&#xype ;&#x/Pag;&#xinat;&#xion ;&#x/BBo;&#xx [1;U.2;ٶ ;w.7;֘ ;֙.;Ⅷ&#x 92.;܈ ;&#x]/Su;typ; /F;&#xoote;&#xr /T;&#xype ;&#x/

Pag;&#xinat;&#xion ;Taken from Note Templates used for Patients with CF in the Outpatient Clinic Transition to Adult Care(next to Culver Medical Group)checklist and annual transition meetings with the adult groupinterested Special Considerations Five Feet Apart: from CBS Films released in March 2019 yearold Stella spends most

of her time in the hospital as a cystic fibrosis patient. Her life is full of routines, boundaries and selfcontrol all of which get put to the test when she meets Will, an impossibly charming teen who has the same illness. There's an instant flirtation, though restrictions dictate that they must maintain a safe distance betwe

en them. As their connection intensifies, so does the temptation to throw the rules out the window and embrace that attraction https://www.cff.org/fivefeetapart/ Includes discussion guide and areview of infection control precautions 75 Referencesarshall, B., & Accurso, F. (2009). Cystic Fibrosis Foundation EvidenceBased Guide

lines for Management of Infants with Cystic Fibrosis. Journal of Pediatrics; 155: S73Rock, M., & Campbell, P. (2008). Guidelines for Diagnosis of Cystic Fibrosis in Newborns Through Older Adults: Cystic Fibrosis Foundatioonsensus Report. Journal of Pediatrics; 153;S4 S14.uidelines. American Journal of Respiratory Critical

Care Medicine; 180; 802Courand, DB., White, T., & Marshall, B. (2009). CysticFibrosis Pulmonary Guidelines: Airway Clearance Therapies. Respiratory Care; 54; 522Annual North American Cystic Fibrosis Conference.shall, B. (2013). Cystic Fibrosis Pulmonary Guidelines: Chronic Medications for Maintenance of Lung Health. Ameri

can Journal of Respiratory Critical Care Medicine; 187; 680Cystic Fibrosis: A Guide for Patient and FamilyEd. Philadelphia: Lippincott: Barker D. Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries. Thor