webcaSt 2 MONOGRaPH

Highlights of Webcast February 3, 2011

Supported by an educational grant from Vertex Pharmaceuticals, Inc.

JULY 2011 | Prepared by JHUSOM and IJHN in collaboration with DKBmed

CONTENTS
CE Information...............................................................................................................i articles CF Management: Treatment Approaches to Mild or Asymptomatic CF Patients .........1 Emerging Disease-Modifying Therapies for CF ...........................................................4 Adherence Improvement in CF Patients: Tips and Strategies .....................................4

References ...................................................................................................................7

IMPORtaNt ce INfORMatION This activity is provided by the Institute for Johns Hopkins Nursing, based on two live webcasts presented by the Johns Hopkins University School of Medicine and IJHN on December 2, 2010 and February 3, 2011. StateMeNt Of Need Incorporating screening protocols, new data on symptomatic treatment modalities and up-to-the-minute research ndings, this program will address the core patient care gaps: n Clinicians do not have adequate knowledge to effectively discuss emerging treatments for the symptoms of CF. n CF clinicians require increased knowledge to more effectively answer their patients' questions about emerging therapies targeted to the prevention/remission of primary disease. n CF clinicians are unprepared to make optimal use of screening data (newborn and other). n CF clinicians are not aware of emerging best practices in improving patient adherence to therapeutic interventions. accRedItatION StateMeNt The Institute for Johns Hopkins Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. cRedIt deSIGNatION Nurses: 1.0 contact hour Educational Activity is provided by the Institute for Johns Hopkins Nursing. Each newsletter carries a maximum of 0.5 contact hour Education Activity provided by the Institute for Johns Hopkins Nursing; or a total of 1.0 contact hours for the two newsletters in this program. To obtain contact hours, you must complete this Education Activity and post-test before July 21, 2013. i StateMeNt Of ReSPONSIbIlIty The Institute for Johns Hopkins Nursing and the American Nurses Credentialing Center do not endorse the use of any commercial products discussed or displayed in conjunction with this educational activity. Meghan Ramsay, MS, cRNP Clinical Coordinator Johns Hopkins Adult Cystic Fibrosis Program Baltimore, MD The following relationships have been reported for this activity: Planner/Faculty Disclosure Michael P. boyle, Md, fccP Lecture titles n Recent Treatment Guidelines for the Adult CF patient n Emerging Disease-Modifying CF Therapies n Treatment Approaches for the Asymptomatic/Mild adult patient n Adherence Improvement Models Company Grants/Research Support: Vertex Pharmaceuticals, Inc. Consultant: Bayer, Pharmaxis, Vertex Pharmaceuticals, Inc. Peter J. Mogayzel, Jr., Md, Phd Discloses that he has no financial relationship with commercial supporters. Meghan Ramsay, MS, cRNP Discloses that he has no financial relationship with commercial supporters. J. Stuart elborn, Md, fRcP Discloses that he has no financial relationship with commercial supporters. eitan kerem, Md Discloses that he has no financial relationship with commercial supporters. Grants to investigators at The Johns Hopkins University are negotiated and administered by the institution which receives the grants, typically through the Ofce of Research Administration.

enduring Materials
Release date: July 22, 2011 Expiration Date: July 21, 2013 POlIcy ON SPeakeR aNd PROvIdeR dISclOSuRe It is the policy of the Institute for Johns Hopkins Nursing that the speaker and provider disclose real or apparent conicts of interest relating to the topics of this educational activity, and also disclose discussions of unlabeled/unapproved uses of drugs or devices during their presentation(s). The Institute for Johns Hopkins Nursing has established policies in place that will identify and resolve all conicts of interest prior to this educational activity. Detailed disclosures are made below. faculty

Michael P. boyle, Md
Associate Professor of Medicine Director, Johns Hopkins Adult Cystic Fibrosis Program Baltimore, MD Stuart elborn, Md, fRcP Professor of Respiratory Medicine Centre for Infection and Immunity Queen's University of Belfast Northern Ireland Peter J. Mogayzel, Jr, Md, Phd Associate Professor of Pediatrics Director, Johns Hopkins Cystic Fibrosis Center Baltimore, MD

IMPORtaNt ce INfORMatION Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor, but may receive salary or other support from the institution to support their effort on the project(s). ackNOwledGeMeNt Of cOMMeRcIal SuPPORt Supported by an educational grant from Vertex Pharmaceuticals, Inc. Off-label PROduct dIScuSSION The following speakers have disclosed that their presentation will reference unlabeled/unapproved uses of drugs or products: Michael P. boyle, Md, fccP Program Director Lecture title/Products Emerging Disease-Modifying CF Therapies: Ataluren/PTC-124, VX-770, VX-809 eitan kerem, Md Guest Faculty Lecture titles/Products Treatment Approaches for the Asymptomatic/Mild CF Child and Adult: Ataluren/PTC-124 & VX-770

All other speakers have indicated that they will not reference unlabeled/ unapproved uses of drugs or products. dISclaIMeR The opinions and recommendations expressed by the faculty and other experts whose input is included in this program are their own. This material is produced for educational purposes only. Please review the complete prescribing information of specic drugs or combination of drugs, including indications, contraindications, warnings and adverse effects before administering pharmacologic therapy to patients. cOPyRIGHt All rights reserved the Johns Hopkins University School of Medicine, the Institute for Johns Hopkins Nursing and DKBmed. POSt-teSt aNd evaluatION A post-test and evaluation is included in the activity. Upon completion of both, participants receiving a grade of 70% or above will receive a CNE certicate.

Peter J. Mogayzel, Jr., Md, Phd Program Director Lecture titles/Products n Recent Treatment Guidelines for the Pediatric CF patient: Tobramycin n Emerging Disease Modifying CF Therapies: Denufosol, Mannitol n Pediatric Issues in the Treatment of Mild Lung Disease, Early Intervention Studies For Treatment of Pseudomonas (EPIC AND ELITE): Tobramycin J. Stuart elborn, Md, fRcP Guest Faculty Lecture titles/Products n Recent Treatment Guidelines: an International Perspective: Tobramycin n An International Perspective On Emerging Disease-Modifying CF Therapies: Denufosol, Mannitol

ii

cf Management: treatment approaches to Mild or asymptomatic cf Patients Dr. Mogayzel, Dr. Boyle, Ms. Ramsay and Dr. Kerem
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Evaluate how increased screening can improve pediatric and adult patient outcomes with current therapies and how those who are newly screened may be affected by the approval of CFTR modulators Integrate this information into current clinical practice to more effectively advise and counsel patients, manage patient expectations, and improve patient quality of life for the pediatric and adult patient Discuss best practices for treating infectious processes in CF patients Describe how the pre-symptomatic diagnosis of children alters approach to therapy Detail the differences in prophylactic use of therapies vs. symptomatic care Develop more efficacious individual care plans for pediatric and adult patients

mortalityinindividualswithCF.2 Thispointis underscoredbyarecentstudywhichshowedthat respiratoryinfectionwithmucoidPAissignicantly associatedwithincreasedseverityofbronchiectasis, suggestingthatattemptstopreventbronchiectasis shouldincludereducingexposuretoandearly eradicationofPA.3 Multiplestudieshavelooked atthebestmethodsforearlyeradicationofPAafter initialinfection,butanotherapproachmightbeto preventPAinfectionaltogetherusingantibiotic prophylaxis.4 Arecenttrialexaminedwhether3 monthlycyclesof3-weektreatmentswithoral ciprooxacinandinhaledcolistincouldreducethe incidenceofPAinfectioninchildrenwithCF, comparedtoplacebo.Unfortunately,after3yearsof follow-up,thisregimendidnotsignicantlyreduce theriskofinitialorchronicPAinfection,butinstead causedshiftsinbacterialcolonization,includingan increaseinnon-PAgram-negativebacteria,whose clinicalsignicanceisunknown.5 Despitemultipletrials,aconsensushasyettobe reachedonthebestantibioticregimenforearly PAeradication.Recently,theEPICtrialcompared cycledandculture-basedregimensinCFpatients ages1 12yearsatrstisolationofPAfroma respiratoryculture.Inafactorialdesign,trial participantswereassignedfor18monthsto anti-pseudomonaltreatmenteitheronascheduled quarterlybasis(cycledtherapy)orbasedon recoveryofPAfromquarterlyrespiratorycultures (culture-basedtherapy).Theyweretreatedwith inhaledtobramycin(300mgBID)for28days, combinedwitheitheroralciprooxacin(15 20 mg/kgBID)ororalplacebofor14days.The primaryendpointswerethetimetopulmonary exacerbationrequiringIVantibioticsor hospitalizationforrespiratorysymptoms,and theproportionofpatientswithnewPA-positive respiratoryculturesduringthestudy.Indata presentedatthe2009NorthAmericanCF Conference,investigatorsshowedthatculture-based therapywaseffectiveateradicatingPAinthevast majorityofpatients.Moreover,theadditionof ciprooxacintoinhaledtobramycindidnotenhance eradiation.Thisstudyalsodemonstratedthatcycled useoftobramycin,eitherwithorwithoutoral
1

emerging Issues in the Pediatric cf Population.

Earlyinterventions,includingsupportfornutritional statusanderadicationofPseudomonas aeruginosa (PA),canhaveasignicantimpactonfuture pulmonarystatusinchildrenwithCF.The importanceofearlynutritionwasdemonstrated bya2003studybyKonstanandcolleagues.They investigatedtherelationshipbetweengrowth,as ameasureofnutritionalstatus,andpulmonary functioninyoungchildren.Individualswith weight-for-age(WFA)belowthe5thpercentileat age3hadlowerpulmonaryfunctionatage6, comparedwiththoseabovethe75thpercentilein WFA.Pulmonaryfunctionwashighestinpatients whoseWFAremainedabovethe10thpercentile fromage3to6(FEV1 10019%predicted)and lowestinthosewhoremainedbelowthe10th percentile(8421%predicted).1 ChronicPAinfectionhasalsobeendemonstrated toreducelungfunctionandincreasemorbidityand
AOTC: CF Summit Webcast 2 Monograph

2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

ciprooxacin,didappeartobesuperiorover culture-basedtherapy.
emerging Issues in adult diagnosed cf Patients.

Althoughithaslongbeenassociatedprimarilywith children,improvementsincareaswellasincreasing numbersoflatediagnoseshavesubstantially increasedtheproportionofadultsintheCF population.AccordingtotheCysticFibrosis Foundation(CFF)PatientRegistry,in1990about 30%ofCFpatientswereadultsaged18yearsand older.By2009,morethan47%wereadults.6 While themajorityofCFpatientsarestilldiagnosedas youngchildren(53%by6monthsofageand74% byage2)manyarediagnosedasteenagers,and agrowingpercentagearenotdiagnoseduntil adulthood.TheproportionofCFdiagnosesafterthe ageof18increasedfrom7.7%in1995-2000to9.9% in2001-2005(p=0.01).Thisincreasehasbeen attributedatleastpartiallytomorewidespreaduse ofgenetictesting,whichcandetectCFmutationsin individualswhopresentwithrespiratorysymptoms butnormalorindeterminatesweattestresults.7 Dr.Boyledescribedtheclinicalcharacteristicsof thisdistinctCFpopulation.Individualswhoare diagnosedwithCFasadultstendtohaveadifferent setofmutationsfromthosediagnosedaschildren, leadingtomilderdiseaseanddifferingclinical presentations.7 Adult-diagnosedCFpatientsare oftenpancreaticsufcient,andlesslikelytohave thegastrointestinalsymptomsassociatedwith childhoodCF.7,8 NewlydiagnosedadultCFpatients aremorelikelytopresentwithpulmonarysymptoms thannewlydiagnosedpediatricpatients,andmore likelytocarryPAandnontuberculousmycobacterial infectionsatthetimeofdiagnosis.Asignicant percentageofadult-onsetCFpatientshavenasal polypsorsinusdisease,andmanyalsopresentwith idiopathicpancreatitisormaleinfertility.Akey characteristicofthisgroupaswellisthat approximately25%ofthosediagnosedasadults haveindeterminateornormalsweatchloride.7 Despitethesedifferencesinpresentation,mostCF patientswhoarediagnosedasadultspresentwith signicantlossoflungfunction,suggestingthat
AOTC: CF Summit Webcast 2 Monograph

earlierdetectionwouldimproveoutcomesfor theseindividuals.Dr.Boyleemphasizedthatthe combinationofbilateralbronchiectasis(withor withoutmucoidPAcolonization)with1of3 additionalfactorsshouldraisesuspicionofCF: recurrentnasalpolyposis,recurrentunexplained pancreatitis,ormaleinfertility.

Managing mild or asymptomatic cf. Whenasked abouttheirdisease,CFpatientsoftenunderestimate theirdiseaseseveritycomparedtotheassessment oftheirphysiciansandoverestimatetheiradherence totreatmentregimens.9 Ms.RamsaynotedthatCF patientswithmildorasymptomaticdiseaseare particularlylikelytounderestimatetheneedfor preventivemeasuresandtherapeuticinterventions. Itisimportanttoensurethatthesepatients understandtheCFFrecommendationsdesignedto protecttheirhealthandslowpulmonarydecline. Patientawarenessofhealthstatuscanbepromoted bymakingsuretheyseeandunderstandtheresults ofcultures,pulmonaryfunctiontests,andchest imaging.Patientswithpoortreatmentadherence shouldbeinvestigatedforthereasonswhy,and counseledonself-carestrategies.

Dr.Keremprovidedaninternationalperspectiveon careforasymptomaticCFpatientswithmildlung disease.Hesaidthatroutinecareinhispractice includesfrequentclinicvisits(asmuchasevery month)thatincludemeasurementsofweightand height,pulmonaryfunctiontesting,sputum cultures/inducedsputumtesting,anddiscussionof adherenceissues.Patientsalsoreceivebiannualhigh resolutionchestCTscans,aswellasoralglucose tolerancetestingonceayearaftertheageof10if theyhavepancreaticinsufciency.Otherstandard therapiesformildlysymptomaticorasymptomatic patientsincludenutritionalinterventionssuch aspancreaticenzymeandfatsolublevitamin supplementation,andairwayclearancetherapies suchashypertonicsalineandphysiotherapy. BecauseofthedemonstratedimpactofPAinfection onmorbidityandmortality,PAnegativepatientsare segregatedfromPApositivepatients,andreceive aggressiveantibiotictherapyfornewlydiagnosed infections.2,10
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2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

therapy Q&a Q: In patients who are infected with both Pa and Staphylococcus aureus (Sa), we often nd that if we treat only the Pa infection, the results are inconsistent until anti-Sa therapy is added. what is your approach to co-infection? A: Our experience is that the effects of co-infection vary between patients, but we do believe that SA infection can play an important role in exacerbations and chronic symptoms. We usually focus initially on the PA infection, but add SA treatment if clinical response is inadequate. Moreover, we often target SA as well as PA when treating exacerbations, particularly when the SA is Methicillin Resistant Staph Aureus (MRSA) Q: any suggestions on choice of inhaled antibiotics when a cf patient is chronically infected with bacteria such as achromobacter xylosoxidans or Stenotrophomonas maltophilia? Q: Have there been any studies looking at in vitro antibiotic sensitivities and in vivo application of those antibiotics for the various cf pathogens? A: Achromobacter xylosoxidans and Stenotrophomonas maltophilia are challenges because of resistance. One can start by looking at culture sensitivities to provide some guidance on treatment selection, but it is important to consider that resistance in vitro does not always correlate with a lack of response in vivo. Colistin is one option that could be considered for patients with these infections, and there are some reports of inhaled aztreonam being helpful against Achromobacter . It is important to be aware that in vitro sensitivities are designed to assess sensitivity to drug levels achievable with intravenous (IV) antibiotics. The inhaled antibiotics that are used in CF are able to achieve much higher tissue levels that those assessed in sensitivity testing. Thus there is some evidence of efcacy of inhaled antibiotics even in the setting of resistant organisms. This lack of correlation also holds true for IV administration in some cases. A 2003 study by Smith and colleagues
AOTC: CF Summit Webcast 2 Monograph

found that the in vitro susceptibilities of PA isolates were not directly correlated with clinical results after IV tobramycin/ceftazidime therapy for CF exacerbations.11 Sometimes patients get better on an antibiotic to which they are resistant, while others do not get better even when their cultures are sensitive and the antibiotic that is chosen would be expected to work. Q: If inammation actually does present before infection would it be sensible to use a safe anti-inammatory treatment in newly diagnosed cf patients? are such treatments currently available? Q: If a child had been treated for 10 years with ibuprofen treatment (age 10 to 20) 1000 mg twice daily and it was benecial with no side effects, does it make sense to continue treating with ibuprofen throughout adulthood? A: Current CFF guidelines recommend the chronic use of oral ibuprofen to slow the loss of lung function in children with CF, 6 years of age and older and with FEV1 greater than 60% predicted (level of evidence, fair; net benet, moderate; grade of recommendation, B). Because subtherapeutic doses of ibuprofen might actually exacerbate pulmonary inammation, it is also recommended that pharmacokinetic studies be done on each patient receiving high dose ibuprofen to ensure that appropriate serum levels are reached.10 This necessity makes the use of ibuprofen somewhat labor-intensive in CF patients. The data to support the use of ibuprofen is for a focused age group of school age and adolescent children, so it shouldnt be used outside of that age range. It is unknown if this therapy is valuable in younger patients or in older patients, although it is possible that there may be some value. There appears to be a higher risk of side effects, particularly gastrointestinal bleeding, in adults in the studies that have been performed, so we do not tend to continue it in after childhood. Renal toxicity is also a potential issue, especially when patients being treated with other renal toxic therapies. While we believe that inammation is important, there arent any other therapies directed towards
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2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

inammation at the moment. Ongoing trials are looking at N-acetylcysteine and inhaled glutathione but there are no clinical results available yet for these therapies. Q: Is it possible to deliver a beta agonist with hypertonic saline, instead of delivering a beta agonist before hypertonic saline? A: This question relates back to a question that asked after the rst webcast (see rst newsletter), and our discussion of the potential for combination therapies that might ease some of the burden of treatment of CF. There are denitely patients out there who are combining these therapies, but it is probably not a good idea for patients who actually have bronchospasm. Such patients will need at least 15 minutes for the beta agonist to take effect in order to get the full benet of the inhaled saline. Theres no evidence for the efcacy of combining the two, while at the same time there is a risk that the beta agonist will be needed early to help open the airway.

disorderscausedbynonsensemutations.14-16 Approximately5-10%ofCFpatientscarry nonsensemutationsintheCFTRgene.17 Phase2studiesofatalurenhaveshownthatit improvesfull-lengthCFTRexpressionandion channelfunctioninadultandpediatricCFpatients carryingatleastoneCFTRnonsenseallele.18,19 Thisimprovementisassociatedwithtrendstowards improvementsinpulmonaryfunctionandCF-related coughing.19 Aninternationalphase3,randomized, double-blind,placebo-controlledtrialofataluren recentlycompletedenrollmentat238patients.The trialwillinvestigatetheeffectsof48weeksof atalurenonForcedExpiratoryVolumeover1second (FEV1)astheprimaryoutcome.Otheroutcome measureswillincludeassessmentofpulmonary symptoms,exacerbations,andhealthrelatedquality oflife.20 Atalurenisalsobeingtestedinboyswith Becker/Duchennemusculardystrophywithnonsense mutations,whereitwasrecentlyshowntoreducethe declinein6-minutewalkdistanceover48weeks.21

emerging disease-Modifying therapies for cf Dr. Kerem

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adherence Improvement in cf Patients: tips and Strategies Dr. Boyle, Dr. Kerem, and Ms. Ramsay
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Evaluate international disease modifying therapies that affect CFTR Review the novel therapies on the horizon

CFiscausedbymutationsinthegeneencoding thecysticbrosistransmembraneconductance regulator(CFTR),anionchannelthathelpsmaintain thebalanceofsodiumandchlorideacrosscell membranes.OneclassofCFmutations,designated ClassI,resultsinprematureterminationof CFTR-encodingmessengerRNA(mRNA),leading tolittleornoproductionoffull-lengthCFTR.One ofseveralnewdisease-modifyingtherapiesforCF thatareunderdevelopmentisataluren,orPTC124, anoraltherapythatpromotesread-throughof prematurestopcodons,alsoknownasnonsense mutations.12 AtalurenisindevelopmentforCF, musculardystrophy,13 hemophilia,andother
AOTC: CF Summit Webcast 2 Monograph

Describe and discuss currently successful CF adherence improvement model Analyze how the pending approval of CFTR modulating therapies may impact adherence

Asformanychronicdiseases,patientswithCF oftenhavetroublewithlongtermadherenceto therapeuticregimens.Studieshaveidentied differenttypesofadherence,whichshouldbe approacheddifferentlyintheclinic.Patientswith erraticadherenceunderstandandagreewiththe necessityforinterventionsbuthavetrouble consistentlymaintainingtheirtreatmentregimens duetolifecircumstances,disorganization,orother reasons.Forthesepatients,itisimportantto simplifyregimensasmuchaspossible,address

2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

circumstancesthatmaybepreventingadherence, andprovidefrequentfollow-upandencouragement. Intelligentnon-adherencereferstothepatient whodeliberatelyaltersordiscontinuestherapydue tounderlyingbeliefsthattheirmedicationisnot reallyneeded,thatdiscontinuingwillnotimpact theirhealth,orthatuseofcertainmedicationswill causesideeffects.Thesepatientsshouldreceive personalizedfeedbackontherelationshipbetween adherenceandhealthoutcomes,asdepictedinFEV1 plotsandchestCTscans.Itmayalsohelptoinvolve thepatientinthedecision-makingprocessandlink therapytotheirpersonalgoals. Unwittingnon-adherencereferstothepatientwho justdoesntunderstandtheirtherapiesandisthusnot followingthecorrectregimen.Thesepatientswill benetfromongoingeducationandcounselingthat emphasizesthebasic,mostimportantconceptsof CFself-careinasimpliedfashion. Considerableresearchonchronicdiseasesshows thatthemorecomplexandtime-consumingthe treatmentregimen,thelowertheadherence.22 ResearchonadultandpediatricCFpatientshad identiedanumberoffactorsthatcanimprove adherence,includingeducationonthedisease,the treatmentregimen,andthepotentialconsequences ofnon-adherence,aswellasgoodcommunication withhealthcareprovidersthatimprovesknowledge andpromotestrust.23,24 Thefacultyidentiedanumberofstrategiesthat canbeusedtopromotepatientadherenceinCF. Thesestrategiesincludemakingeffectiveuseof thetelephonebyencouragingpatientstocallas wellascallingthemonaregularbasis,havingthem comeinforfrequentfollow-upvisits,reviewing pharmacyinformationtomakesuretheyarelling theirprescriptions,andinvolvingasocialworker ifneededtohelpidentifyandremoveobstaclesto adherence.Itcanbehelpfultoelicitinformation frompatientsabouttheirtypicaldayandthenshow themhowtottheirtreatmentsintoit.Foradults thatarenewlydiagnosed,ithelpstondouthow theycametobediagnosedandhowtheyfeelabout
AOTC: CF Summit Webcast 2 Monograph

theirdiagnosis.25 Awrittentreatmentplanisalso usefultomakesurepatientsunderstandandcan rememberthedetailsoftheirregimens.24 Dr.Kerememphasizedtheneedtorespectpatients asindividualsandprovidechoicessopatientsfeel theyhavesomeautonomyintheirself-care,theneed toeducateandworkwithpatientssotheyunderstand theneedforadherenceonarationallevel,andthe importanceofencouragingthemandprovidinghope forthefuture.
adherence Improvement Q&a Q: do you have any advice on counseling Muslim and Jewish patients who require the use of porcine enzymes for pancreatic insufciency? A: It is our understanding that the dietary restrictions of the Muslim and Jewish traditions do not apply to items that are needed to maintain health. Patients should be informed of the source of the enzymes so they can consult with religious leaders if they have questions about this issue. It is important to consider a number of other cultural practices that may affect the health of CF patients. Many religious traditions include fasting over holidays, which can become a nutritional challenge for CF patients. Cultural or religious beliefs may also cause patients or their families to try home remedies, including remedies that may be contraindicated for individuals with CF. Studies have shown that many CF patients are interested in or have tried complementary or alternative therapies but there are no studies that show whether these practices have any benet.25, 26 Another frequent cultural health belief held by some people is an objection to taking medications of any kind; a belief that all medicines are bad. This belief leads some patients to refuse therapies, particularly antibiotics, or to refuse immunizations such as u shots. It is important for practitioners to keep open the lines of communication so they can spend time educating their patients on the potential health consequences of some of these beliefs and practices.

2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

Q: for Meghan Ramsay: do you actually work with patients schedules to try to t prescribed therapies into their routine? A: Yes we do. Its done on an individual basis. Most people are able to nd a schedule that works for them, but if patients are having trouble getting all of their treatments done, well have them come in for a nursing visit, sit down with them, and help them plan out their day at school or work. We help them plan where they can t their treatments in, in a very detailed way. It does take a lot of time, so we cant do it for every patient, but well try to map out a day for the ones that are really struggling, and then follow up with them and make sure that they are tting everything in. This doesnt have to be done by a nurse. It can be a great role for a social worker to take on. The physical therapists also work on this sometimes when they are trying to get a certain plan across to patients. Theyll see what exercise or airway clearance activities might work with the patients schedule and see what they can do to t them in. Anyone on the care team can be involved in this process. Q: we all have patients who fail to recover their baseline despite an aggressive approach to treatment, including strong attention to adherence and social/nancial barriers. 1. How do you dene "baseline" lung function? 2. How do you approach the discussion of a new, lower baseline after the failure of an aggressive course of treatment? A: Baseline lung function for CF patients is generally considered to include what has been happening over the past 6 months to 1 year of follow-up. Nearly all CF patients lose some lung function over time, so despite the use of aggressive therapies there may be a decline. The change in lung function can occur gradually or in stair-step drops as a result of exacerbations, which can sometimes make dening the baseline difcult. When there is a decline, we try to recover as much function as possible, then agree that there will be a new baseline going forward and continue with the therapies to try to maintain function at the new level.

It is important to make sure that patients and their families understand what the baseline is and how it is important. Accepting that there has been a loss of lung function that does not appear recoverable is a decision not only for the physician but for the patient and their family as well. Conversations around these issues can be difcult, but can be tempered by the fact that lung function decline and recovery is not an exact science and often hard to predict. Unfortunately its a given that most CF patients are going to lose some lung function over time. In the future, we hope this wont be as much of a problem because the new, disease-modifying therapies should more effectively maintain lung function and hopefully will prevent the exacerbations that lead to more rapid decline. Q: what was the life expectancy in 2010 for people who have cf, with good therapy adherence, in the united States? A: We dont have the answer to this question right at the moment. We need more studies of adherence. What we can say, from the few studies that have been done, is that patients with better adherence have fewer exacerbations and better lung function.27 But we dont have good studies of the impact of adherence on survival, although we think it probably plays a key role.

AOTC: CF Summit Webcast 2 Monograph

2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

References

1. KonstanMW,ButlerSM,WohlME,etal.Growthandnutritionalindexesinearlylifepredictpulmonary functionincysticfibrosis.The Journal of Pediatrics. Jun2003;142(6):624-630. 2. UKCysticFibrosisTrustInfectionControlGroup.Pseudomonasaeruginosainfectioninpeoplewith cysticfibrosis:Suggestionsforpreventionandinfectioncontrol.2004;AccessedMarch27,2011. 3. FarrellPM,CollinsJ,BroderickLS,etal.AssociationbetweenmucoidPseudomonasinfectionand bronchiectasisinchildrenwithcysticfibrosis.Radiology.Aug2009;252(2):534-543. 4. StuartB,LinJH,MogayzelPJ,Jr.EarlyeradicationofPseudomonasaeruginosainpatientswithcystic fibrosis.Paediatr Respir Rev.Sep2010;11(3):177-184. 5. Tramper-StrandersGA,WolfsTF,vanHarenNomanS,etal. Controlledtrialofcycledantibiotic prophylaxistopreventinitialPseudomonasaeruginosainfectioninchildrenwithcysticfibrosis.Thorax. Oct2010;65(10):915-920. 6. CysticFibrosisFoundationPatientRegistry:AnnualDataReport2009.2009;AccessedMarch25,2011. 7. KeatingCL,LiuX,DimangoEA.Classicrespiratorydiseasebutatypicaldiagnostictestingdistinguishes adultpresentationofcysticfibrosis.Chest.May2010;137(5):1157-1163. 8. NickJA,ChaconCS,BrayshawSJ,etal.Effectsofgenderandageatdiagnosisondiseaseprogressionin long-termsurvivorsofcysticfibrosis.American Journal of Respiratory and Critical Care Medicine.Sep1 2010;182(5):614-626. 9. AbbottJ,DoddM,WebbAK.Differentperceptionsofdiseaseseverityandselfcarebetweenpatientswith cysticfibrosis,theirclosecompanions,andphysician.Thorax.Jul1995;50(7):794-796. 10. FlumePA,O'SullivanBP,RobinsonKA,etal.Cysticfibrosispulmonaryguidelines:chronicmedications formaintenanceoflunghealth.American Journal of Respiratory and Critical Care Medicine.Nov15 2007;176(10):957-969. 11. SmithAL,FielSB,Mayer-HamblettN,RamseyB,BurnsJL.SusceptibilitytestingofPseudomonas aeruginosaisolatesandclinicalresponsetoparenteralantibioticadministration:lackofassociationin cysticfibrosis.Chest.May2003;123(5):1495-1502. 12. SloanePA,RoweSM.Cysticfibrosistransmembraneconductanceregulatorproteinrepairasatherapeutic strategyincysticfibrosis.Curr Opin Pulm Med.Nov2010;16(6):591-597. 13. FinkelRS.Read-throughstrategiesforsuppressionofnonsensemutationsinDuchenne/Beckermuscular dystrophy:aminoglycosidesandataluren(PTC124).J Child Neurol.Sep2010;25(9):1158-1164. 14. GoldmannT,OverlackN,WolfrumU,Nagel-WolfrumK.PTC124-MediatedTranslationalReadthrough ofaNonsenseMutationCausingUsherSyndromeType1C.Hum Gene Ther.Mar252011. 15. DranchakPK,DiPietroE,SnowdenA,etal.Nonsensesuppressortherapiesrescueperoxisomelipid metabolismandassemblyincellsfrompatientswithspecificPEXgenemutations.J Cell Biochem.Dec 282010. 16. TanL,NarayanSB,ChenJ,MeyersGD,BennettMJ.PTC124improvesreadthroughandincreases enzymaticactivityoftheCPT1AR160Xnonsensemutation.J Inherit Metab Dis.Apr2011;34(2):443-447. 17. KreindlerJL.Cysticfibrosis:exploitingitsgeneticbasisinthehuntfornewtherapies.Pharmacol Ther. Feb2010;125(2):219-229. 18. Sermet-GaudelusI,BoeckKD,CasimirGJ,etal.Ataluren(PTC124)inducescysticfibrosis transmembraneconductanceregulatorproteinexpressionandactivityinchildrenwithnonsensemutation cysticfibrosis.American Journal of Respiratory and Critical Care Medicine.Nov15 2010;182(10):1262-1272. 19. WilschanskiM,MillerLL,ShoseyovD,etal.Chronicataluren(PTC124)treatmentofnonsensemutation cysticfibrosis.Eur Respir J.Jan132011.
AOTC: CF Summit Webcast 2 Monograph
2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed

20. KeremE,WilschanskiM,MelottiP,etal.Phase3studyofataluren(PTC124)innonsensemutationcystic fibrosis(NMCF):demographicandotherbaselinedata.Abstract266.The24thAnnualNorthAmerican CysticFibrosisConference,October21-23,2010.Baltimore,MD. 21. McDonaldCM,HenricsonEK,HanJJ,etal.The6-minutewalktestinDuchenne/Beckermuscular dystrophy:longitudinalobservations.Muscle Nerve.Dec2010;42(6):966-974. 22. IngersollKS,CohenJ.Theimpactofmedicationregimenfactorsonadherencetochronictreatment:a reviewofliterature.J Behav Med.Jun2008;31(3):213-224. 23. KettlerLJ,SawyerSM,WineeldHR,GrevilleHW.Determinantsofadherenceinadultswithcystic fibrosis.Thorax.May2002;57(5):459-464. 24. ModiAC,QuittnerAL.Barrierstotreatmentadherenceforchildrenwithcysticfibrosisandasthma:what getsintheway?J Pediatr Psychol.Sep2006;31(8):846-858. 25. WidermanE.Knowledge,interestsandeducationalneedsofadultsdiagnosedwithcysticfibrosisafter age18.J Cyst Fibros.Jun2003;2(2):97104. 26. TanaseA,ZanniR.Theuseofcomplementaryandalternativemedicineamongpediatriccysticfibrosis patients.J Altern Complement Med.Dec2008;14(10):1271-1273. 27. EakinMN,BilderbackA,BoyleMP,MogayzelPJ,RiekertKA.Longitudinalassociationbetween medicationadherenceandlunghealthinpeoplewithcysticfibrosis.J Cyst Fibros.2011Mar30.[Epub aheadofprint]

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AOTC: CF Summit Webcast 2 Monograph

2011 JHUSOM, IJHN and AOTC: CF Summit Presented by JHUSOM and IJHN in collaboration with DKBmed