C sticfibrosis

February19,2012 Otology

Authors
BalasubramanianThiagarajan

Abstract
Cysticfibrosisisanautosomalrecessivedisorderaffectingtheexocrineglands.Itcausesthesecretions fromtheseglandstobecomethickandviscous.Thereisatendencytoinvolvemultipleorgansystems. Thisarticlediscussestheetiopathogenesis,clinicalfeaturesandmanagementofthisproblem.

C sticfibrosis
Introduction: Cysticfibrosisisanautosomalrecessivedisorderaffectingtheexocrineglands.Itcausesthesecretions fromtheseglandstobecomethickandviscous.Thereisatendencytoinvolvemultipleorgansystems. Commonlyinvolvedorgansystemsinclude:Nose,paranasalsinuses,gastrointestinaltract,skinand reproductivesystem.Theincidenceisratherhighincaucasians.FiguresreportedfromUnitesStatesis about1per2500livebirths1.Thishighincidencehasbeenattributedtoimproveddiagnostictools. Chronicrhinosinusitisandnasalpolyposisarerathercommoninthesepatients.Studiesrevealthatthe extentofsinusdiseasemayhaveabearingonpulmonarysymptoms2. Pathophysiologyofcysticfibrosis: Cysticfibrosisiscausedduetodefectsinvolvingcysticfibrosisgenewhichcodesfortransmembrane conductanceregulatorprotein(CFTR)whichfunctionsaschloridechannel.Thischloridechannelis regulatedbyCyclicAMP.Mutationsinvolvingcysticfibrosistransmembraneconductanceregulator proteinresultsinabnormalitiesinvolvingchloridetransportacrossepithelialcells/mucosalsurfaces. SixtypesofdefectsinvolvingCFTRgeneshavebeenidentifiedincysticfibrosis3. CompleteabsenceofCFTRproteinsynthesis DefectivematurationandearlydegradationofCFTRprotein(themostcommonmutation) DisorderedregulationduetodecreasedATPbindingandhydrolysis Defectivechlorideconductance Diminishedtranscriptionduetopromoterorsplicingabnormality Acceleratedchannelturnoverfromthecellsurface CFTRmutationshaveverypoorpenetrance.Thisindicatesthatgenotypedoesnotpredicttheseverity ofthedisorder. DefectiveCFTRcausesdecreasedsecretionofchlorideandincreasedreabsorptionofsodiumand

wateracrossepithelialcells.Thiscausesareductionintheheightoffluidliningtheepithelium. Thereisalsoassociateddehydrationofmucincausingittothikcn.Italsoprovestobemorestickierthan normalmucoussecretion.Bacteriagetsadherenttothismaterialcausingsmoulderinginfection. Secretionsintherespiratorytract,Gastrointestinaltractandsweatglandsareincreasedinviscosity makingitdifficulttoclear. Clinicalmanifestationsofcysticfibrosis: Thisisdependentontheorgansinvolved.Probabledisordersinclude: Nasalpolyposis Sinusitis Chronicdiarrhoea Rectalprolapse Pancreatitis Cholelithiasis Cirrhosisofliver Pathophysiologyofsinusitisinpatientswithcysticfibrosis: Exactmechanismisstillnotclear.Sincechlorideionscannotbeexcretedsodiumionsgetsreabsorbed excessively.Thisincreasesthethicknessandviscosityofthemucousblanket.Normalciliapresentinthe noseandparanasalsinusesfinditdifficulttopushthisviscidsecretionsoutofthesinus/nasalcavities4. Thiscausesaccumulationofmucinwithinthesinuscavity.Thisaccumulatedmucinisanexcellent culturemediumforcolonizingbacteria.Thisisoneofthemajorreasonschronicsinusinfectionsinthese patients. Otherfeaturespredisposingtosinusinfectionsinthesepatientsinclude: Ciliarydysfunction Increasedsecretionofinflammatorymediators Pseudomonasaeruginosacolonization Pseudomonascolonizationofnasalcavityiscommonlyreportedinpatientswithcysticfibrosisassociated withnasalpolypi,whereasitisnotsocommoninpatientswithcysticfibrosiswithoutnasalpolyposis5. Pseudomonasorganismsproducetoxinswhichhasdeleteriouseffectsonthenormalciliarybeat.These toxinsinclude:HemolyzinandPyocyanin.OutofthesetwotoxinsPyocyaninslowsdowntheciliarybeat appreciablycausingmucinstasiswithinnoseandparanasalsinuses.Pyocyaninhasbeensuspectedto playsomeroleinthedevelopmentofnasalpolyposisinthesepatients6. Roleofallergyinthepathophysiologyofnasalpolyposisinpatientswithcysticfibrosis: Roleofallergyinthepathophysiologyofnasalpolyposisinpatientswithcysticfibrosisisstillnotclear. Statisticalprevalanceofatopyinpatientswithcysticfibrosisdoesnotdiffersignificantlybetweenthose withnasalpolyposisandthosewithoutnasalpolypi7.Howevercurrentstudiesrevealthatpatientswith

cysticfibrosiswhomanifestwithpositiveskinpricktesthavebeenfoundtobecommonlycolonizedby pseudomonas.Asstatedpreviouslypseudomonascolonizationhasaroletoplayinthepathophysiology ofdevelopmentofnasalpolypiinthesepatients.Henceithasbeenwidelypostulatedwhetheritisthe allergicreactionperseorallergicreactiontofungicouldbethecausefornasalpolyposisinthese patients.Allergicreactiontoaspergillusfumigatushasbeendocumentedinpatientswith bronchopulmonaryaspergillosisinpatientswithcysticfibrosis8. Pathologicaldifferencesbetweennasalpolypiinpatientswithcysticfibrosisandinthosewithoutcystic fibrosis: Histopathologicalcharacteristicsdifferbetweennasalpolypifoundincysticfibrosisfromthoseofnon cysticfibrosispatients. Thetablegivenbelowprovidesjustaglimpseintothehistopathologicaldifferencesbetweenthesetwo entities. Nasalpolypiincysticfibrosis Neutrophilicinfiltration Basementmembraneofpolypthinand delicate Submucosalhyalinizationabsent Mucousglandscontainacidmucin Nasalpolypicommoninchildrenwithcystic fibrosis Nasalpolypiinnoncysticfibrosispatients Eosinophilicinfiltration Thickbasementmembrane Submucosalhyalinizationpresent Mucousglandscontainneutralmucin Nasalpolypiareratherrareinchildrenwithoutcystic fibrosis

Ithasbeensuggestedthatallchildrenwithnasalpolyposisshouldundergosweattesttoruleoutcystic fibrosis.Sweatchloridelevelofmorethan60mEq/Lisconsideredtobediagnosticofcysticfibrosis.This shouldeventuallybefollowedupbygenetictestingandpropercouncelling. Roleofimagingindiagnosis/evaluationofpatientswithcysticfibrosis: Routinexraysareofnovalueinthesepatients.CTscanofnoseandparanasalsinusesisthepreferred radiologicalinvestigationofchoiceinthesepatients. CTscanfindingsinclude: Frontalsinushypoplasia Maxillarysinusexpansionwithmedialization Lossofmedialmaxillarywall Mucoceleformationinmaxillarysinuses Frontalsinushypoplasiahasbeenattributedduetodiminishedpostnatalgrowthofthesesinusesdueto thepresenceofchronicinflammation. Management: Medical: Thisshouldbeconsideredtobethefirststepinaseriesofsteps.

Salineirrigation: Regularsalineirrigationofnasalcavitiesclearsthenasalsecretions,andalsogetsridofinflammatory mediatorsfromthenasalmucousmembrane.Crustsbecomesoftonexposuretosalineandcanhence beeasilyremovedafterthewash.Childrenwhounderwentregularsalinewashoftheirnasalcavitieson aregularbasisrarelyneededsurgeryfornasalpolyposis. Topicalbabyshampoolavagehasfoundfavourrecently.Ithelpsinremoving/dislodgingbiofilmsfrom insidethenasalcavity9. Roleofsteroids: Useoftopicalsteroids10havebeenfoundtoplayanimportantroleinreducingthesizeofnasalpolypiin thesepatients.Ithasbeendemonstratedinchildrenwhoareonsystemicsteroidsfortheirlungcondition showedasignificantreductioninthesizeofnasalpolypi. Roleofantibiotics: Sincepsudeomonasinfectionsplayanimportantroleinthedevelopmentofnasalpolypiinpatientswith cysticfibrosis,antibiotictherapydirectedagainstpseudomonasorganismplaysanimportantrole. TopicalTobramycincanbeusedasnasalwashinthesepatients.Thisnotonlyreducedthe pseudomonasnasalloadbutalsocausedasignificantreductioninthesizeofnasalpolypi.Thiswas reportedwidelybyMossetal11. RoleofDornasealpha12: Inpatientswithcysticfibrosis,alargeamountofDNAreleasedfromdegeneratingneutrophilshavebeen implicatedasthecauseofincreasedviscosityofnasalsecretions.Dornasealphaarecombinanthuman deoxyribonucleasewhenadministeredinthesepatientshasreducedtheviscosityofbronchialandnasal secretions.Intranasaladministrationofthisdrughashadbeneficialeffectsinthesepatients. RoleofIbuprofen: Upregulationofcyclooxygenase(COX)enzymeshasbeenidentifiedinnasalpolypiofpatientswithcystic fibrosis.Highdoseibuprofenwhichblockstheseenzymeshasshownpromiseinthesepatients.High doseibuprofenhasreducedthesizeofnasalpolypiinthesepatients13. Surgery: Roleofsurgeryinthesepatientsisonlywhenconservativemedicalmanagementfails.Majorrisk involvedinsurgeryisduetobleeding.SincethesepatientshavevitaminKmalabsorption,coagulation disordersarecommon.Aftersurgerynasalblockisdramaticallyreduced.Endoscopicsinussurgical procedureshavereplacedtheconventionalpolypectomy.Recurrenceiscommoninthesepatientseven aftersuccessfulremoval.Recurrenceiscommoninabout60%oftreatedpatients.Inpatientswith maxillarysinusmucocelesawidemiddlemeatalantrostomywillfacilitateitsdrainage.

CoronalCTscanofnoseandparanasalsinusesinapatientwithcysticfibrosis

Pictureshowingnasalpolyposiswithinfected secretionsinapatientwithcysticfibrosis

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References
1. 1.DodgeJA,LewisPA,StantonM,WilsherJ(2007)CysticfibrosismortalityandsurvivalintheUK: 1947 2003.EurRespirJ29:522 526 2. 2.FriedmanEM,StewartM(2006)Anassessmentofsinusqualityoflifeandpulmonaryfunctionin childrenwithcysticfibrosis.AmJRhinol20:568 572 3. 3.RoweSM,ClancyJP.Advancesincysticfibrosistherapies.CurrOpinPediatr.Dec200618(6):604 13. 4. RutlandJ,ColePJ.Nasalmucociliaryclearanceandciliarybeatfrequencyincysticfibrosiscompared withsinusitisandbronchiectasis.Thorax.198136:654658.

5. HenrikssonG,WestrinKM,KarpatiF,WikstromAC,StiernaP,HjelteL(2002)Nasalpolypsincystic fibrosis.Clinicalendoscopicstudywithnasallavagefluidanalysis.Chest121:40 47 6. 6.WilsonR,PittT,TaylorG,WatsonD,MacDermotJ,SykesD,RobertsD(1987)Coleinhibitthe beatingofhumanrespiratoryciliainvitro.JClinInvest79:221 229 7. 7.HadfieldPJ,RoweJonesJM,MackayIS(2000)Theprevalenceofnasalpolypsinadultswithcystic fibrosis.ClinOtolaryngolAlliedSci25:19 22 8. 8.ShoseyovD,BrownleeKG,ConwaySP,KeremE(2006)Aspergillusbronchitisincysticfibrosis. Chest130:222 226 9. 11.ChiuSG,PalmerJN,WoodworthBA,DoghramjiL,CohenMB,PrinceA,CohenMA(2008)Baby shampoonasalirrigationsforthesymptomaticpostfunctionalendoscopicisinussurgerypatient.AmJ Rhinol22:34 37 10. 9.HadfieldPJ,RoweJonesJM,MackayIS(2000)Aprospectivetreatmenttrialofnasalpolypsin adultswithcysticfibrosis.Rhinology38:63 65 11. 10.MossR,KingV(1995)Managementofsinusitisincysticfibrosisbyendoscopicsurgeryand serialantimicrobiallavage.ArchOtolaryngolHeadNeckSurg121:566 572 12. 12.CimminoM,NardoneM,CavaliereM,PlantulliA,SepeA,EspositoV,MazzarellaG,RaiaV (2005)Dornasealfaaspostoperativetherapyincysticfibrosissinonasaldisease.ArchOtolaryngolHead NeckSurg131:1097 1101 13. 13.LindstromDR,ConleySF,SplaingardML,GershanWM(2007)Ibuprofentherapyandnasal polyposisincysticfibrosispatients.JOtolaryngol36:309 314