![Indice Certificaci n APAP Release 2[1].0 en Detalle](https://static.fdocuments.us/doc/165x107/577d26b51a28ab4e1ea1f38f/indice-certificaci-n-apap-release-210-en-detalle.jpg)
GDao - APAP and Asthma - University Blog...
17
10/15/16 1 + From “A” to “Wheeze” Acetaminophen’s Role in the Asthma Epidemic Gretchen Dao, PharmD Community Pharmacy PGY1 Resident H-E-B/University of Texas at AusGn October 21, 2016 + A 7-year-old child on controller therapy for asthma has a temperature of 100.1°F and a new prescripEon for an anEbioEc. Her mother tells you that the pediatrician recommended that she should also get “something OTC for the fever”. Do you recommend: A. Acetaminophen? B. Ibuprofen? 2 + Learning ObjecEves nDiscuss the role of acetaminophen (APAP) in the asthma epidemic in children nEvaluate safety of other alternaGves nProvide appropriate analgesic/anGpyreGc recommendaGons for children with asthma 3
Transcript of GDao - APAP and Asthma - University Blog...
10/15/16
1
+
From“A”to“Wheeze”Acetaminophen’sRoleintheAsthmaEpidemic
GretchenDao,PharmDCommunityPharmacyPGY1ResidentH-E-B/UniversityofTexasatAusGn October21,2016
+A7-year-oldchildoncontrollertherapyforasthmahasatemperatureof100.1°FandanewprescripEonforananEbioEc.Hermothertellsyouthatthepediatricianrecommendedthatsheshouldalsoget“somethingOTCforthefever”.
Doyourecommend:
A. Acetaminophen?
B. Ibuprofen?
2
+LearningObjecEves
n Discusstheroleofacetaminophen(APAP)intheasthmaepidemicinchildren
n EvaluatesafetyofotheralternaGves
n Provideappropriateanalgesic/anGpyreGcrecommendaGonsforchildrenwithasthma
3
10/15/16
2
+BackgroundAsthma
4
+AsthmaStaEsEcs
Data,StaGsGcs,andSurveillance.CenterforDiseaseControlandPrevenGon.(2016)
5
10.5millionphysicianoffice
visits
$50+billionspentperyear
1.8millionEDvisits
49%ofchildrenwithasthma
missed>1dayofschool
Data,StaGsGcs,andSurveillance.CenterforDiseaseControlandPrevenGon.(2016)
6
10/15/16
3
Data,StaGsGcs,andSurveillance.CenterforDiseaseControlandPrevenGon.(2016)
7
8.4%
Data,StaGsGcs,andSurveillance.CenterforDiseaseControlandPrevenGon.(2016)
8
+Whatcausesasthma?
n Environmentaltriggers
n AirwayinfecGons
n GeneGcs
n “HygieneHypothesis”
WhatIsAsthma?U.S.NaGonalLibraryofMedicine.(2014)
???APAP???
9
10/15/16
4
+Whatisasthma?
Image:Haderer&Muller,illustratedfortheAmericanCollegeofChestPhysicians.(2016)
10
+
Cellmediatedimmunity&DelayedhypersensiEvity AllergicinflammaEonVarnerAE,BusseWW,LemanskeRF.AnnAllergyAsthmaImmunol.(1998)
11
Pathophysiology
COX-2
éê
+APAPandAsthmaThreeMainQuesGons
1. DoesfrequentAPAPuseleadtoasthmainchildren?
2. DoesfrequentAPAPuseworsensymptomsinchildrenwhoalreadyhaveasthma?
3. ArethealternaGves(i.e.ibuprofen)anysafer?
Litonjua.NEnglJMed.(2016)
12
10/15/16
5
+From“A”to“Wheeze”ObservaGonalStudies
13
+TheFirstHypothesis:Varner,etal.(1998)
NoEcedin1980s:Pediatricaspirin(ASA)usedecreased
✚Childhoodasthmaprevalenceincreased
VarnerAE,BusseWW,LemanskeRF.AnnAllergyAsthmaImmunol.1998;81(4):347-51.
14
DecreaseduseofASAmaybeafactorinfacilitaGngallergicsensiGzaGonand
asthma.Hypothesis
+
Cellmediatedimmunity&DelayedhypersensiEvity AllergicinflammaEonVarnerAE,BusseWW,LemanskeRF.AnnAllergyAsthmaImmunol.1998;81(4):347-51.
15
TheFirstHypothesis:Varner,etal.(1998)
COX-2
ASA
êé
APAP?
10/15/16
6
+
VarnerAE,BusseWW,LemanskeRF.AnnAllergyAsthmaImmunol.1998;81(4):347-51.
TheFirstHypothesis:Varner,etal.(1998)
CorrelaEon?Coincidence?
16
+TheFirstHypothesis:Varner,etal.(1998)n Conclusion:n EliminaGonofpediatricASAmaybeanimportantcontributor
n RelaGonshipbetweenAPAPandasthmaisunproven,furtherinvesGgaGonisneeded
VarnerAE,BusseWW,LemanskeRF.AnnAllergyAsthmaImmunol.1998;81(4):347-51.
17
+EpidemiologicalEvidence:Shaheen,etal.(2000)
n Background:n AnimalstudiesshowedthatAPAPdepletesglutathione(GSH)inlungs
n GSHisananGoxidantthatmaydefendagainstoxidaGvestressofasthmainflammaGon
n IncreasedGSHlevelsinairwaysofadultswithasthma
Shaheen,etal.Thorax.2000;55(4):266-70.
18
FrequentAPAPuseisassociatedwithasthma.Hypothesis
10/15/16
7
+EpidemiologicalEvidence:Shaheen,etal.(2000)
Shaheen,etal.Thorax.2000;55(4):266-70.
19
• PopulaGonbasedcase-control• SurveyonfrequencyofASA/APAPuseinpeoplewithasthmavs.without
• Controlledforconfoundingriskfactors
Design
• Aged16-49y• Defined“asthmaGc”or“non-asthmaGc”basedonscreeningquesGons
• N=1574(664casesvs.910controls)ParEcipants
+EpidemiologicalEvidence:Shaheen,etal.(2000)
Shaheen,etal.Thorax.2000;55(4):266-70.
20
+EpidemiologicalEvidence:Shaheen,etal.(2000)
Shaheen,etal.Thorax.2000;55(4):266-70.
21
10/15/16
8
+EpidemiologicalEvidence:Shaheen,etal.(2000)n Conclusion:n Frequent(daily/weekly)APAPuse,possiblyoveruse,posiGvelyassociatedwithasthman Dose-relatedresponse-causal?
n UnlikelythatrelaGonshipisauributabletohigherprevalenceofco-morbidity
n ASAavoidancecanonlyexplainpartoftheassociaGon,notall
Shaheen,etal.Thorax.2000;55(4):266-70.
22
+AnEcologicalLook:Newson,etal.(2000)
Sofar:
n Varner:êASAàéAPAPàéasthma?
n Shaheen:frequentAPAPçèasthma?
Newson,etal.EurRespirJ.2000;16(5):817-23.
23
CountrieswithhighernaGonalAPAPsalesareassociatedwithhigherasthma
symptomprevalence.Hypothesis
+AnEcologicalLook:Newson,etal.(2000)
Newson,etal.EurRespirJ.2000;16(5):817-23.
24
• Linearregressionanalysis:• InternaGonalsymptom-prevalencedata• NaGonalper-capitaAPAPsales
Design
• Aged6-7y,13-14y• N=?(22countries)ParEcipants
10/15/16
9
+AnEcologicalLook:Newson,etal.(2000)
Newson,etal.EurRespirJ.2000;16(5):817-23.
25
+AnEcologicalLook:Newson,etal.(2000)
Newson,etal.EurRespirJ.2000;16(5):817-23.
26
English-speakingcountries
+AnEcologicalLook:Newson,etal.(2000)
n “Anglophoneeffect”n English-speakingWesterncountriestendtohave:n Highestprevalenceofasthmasymptomsn HighestAPAPsales
n Posthocanalysis:n AllassociaGonsbetweenAPAPandasthmasymptomsàabolishedornon-significant
Newson,etal.EurRespirJ.2000;16(5):817-23.
27
10/15/16
10
+AnEcologicalLook:Newson,etal.(2000)
n Conclusion:n NaGonalAPAPsalesposiGvelyassociatedwithprevalenceofasthmasymptoms
n “Anglophoneeffect”n LikelyduetoconfounderstronglyassociatedwithEnglish-speakingcountries
n WarrantsfurtherinvesGgaGon
Newson,etal.EurRespirJ.2000;16(5):817-23.
28
+LimitaEonstoObservaEonalStudiesn Weakstrengthofevidence
n ConfoundingbyindicaGonn CausalassociaGonisdifficulttodetermine
n Exposuredatanotlinkedtoindividuals
30
+Pu_ngItAllTogetherMeta-Analysis
31
10/15/16
11
+Meta-Analysis:Garcia-Marcos,etal.(2011)
n 41sub-studiesn Infants,children,adults,pregnantwomenn Longitudinal,cross-secGonal
n PooledOR=1.48n “…nomacerwhattypeofstudy,age,orEmeofexposure,thereisalwaysaposiEveassociaEonbetweenexposureandrespiratorysymptoms”
Garcia-MarcosL,Sanchez-SolisM,Perez-FernandezV.CurrOpinAllergyClinImmunol.2011;11(3):162-73.
32
+Meta-Analysis:Garcia-Marcos,etal.(2011)
33
Garcia-MarcosL,Sanchez-SolisM,Perez-FernandezV.CurrOpinAllergyClinImmunol.2011;11(3):162-73.
+WhatAboutAlternaEves?APAPvs.Ibuprofen
34
10/15/16
12
+FirstRandomizedControlledTrial:Lesko,etal.(2002)
Lesko,etal.Pediatrics.2002;109(2):E20.
35
• Short-termuseofibuprofenincreasesasthmamorbidityinchildrenHypothesis
• Randomized,double-blind,APAP-controlled• MeasuredhospitalizaGonandoutpaGentvisitsforasthma
Design
+FirstRandomizedControlledTrial:Lesko,etal.(2002)
Lesko,etal.Pediatrics.2002;109(2):E20.
36
• Aged6m-12ywithasthmaandfever
• N=1879ParEcipants
• APAP12mg/kg,ibuprofen5mg/kg,ibuprofen10mg/kg
• Followedx4weeksIntervenEon
+FirstRandomizedControlledTrial:Lesko,etal.(2002)
Lesko,etal.Pediatrics.2002;109(2):E20.
37
• NodifferenceinhospitalizaGonrates• OutpaGentvisitssignificantlylowerinibuprofengroup
Results
10/15/16
13
+
Cellmediatedimmunity&DelayedhypersensiEvity AllergicinflammaEon
FirstRandomizedControlledTrial:Lesko,etal.(2002)
38
COX-2
ASA
êé
APAP?
Ibu
ê
+FirstRandomizedControlledTrial:Lesko,etal.(2002)n Conclusion:n ComparedtoAPAP,ibuprofenhaslowerriskofasthmamorbidity
n Duetonoplacebo-control,cannotdeterminewhetherdifferenceisduetoAPAPincreasingriskoribuprofendecreasingrisk
Lesko,etal.Pediatrics.2002;109(2):E20.
39
+AVICATrialSheehan,etal.(2016)
Sheehan,etal.NEnglJMed.2016;375(7):619-30.
40
• AsthmamorbidityishigherinAPAPvs.ibuprofeninchildrenwithmildpersistentasthma
Hypothesis
• MulGcenter,prospecGve,double-blind,parallel-group
• 48weeks,measuredexacerbaGonfrequencies
Design
10/15/16
14
+AVICATrialSheehan,etal.(2016)
Sheehan,etal.NEnglJMed.2016;375(7):619-30.
41
• Aged1-5ywithmildpersistentasthma
• N=300ParEcipants
• APAP15mg/kgq6hprn• Ibuprofen9.4mg/kgq6hprnIntervenEon
+AVICATrialSheehan,etal.(2016)
Sheehan,etal.NEnglJMed.2016;375(7):619-30.
42
• NosignificantdifferenceinexacerbaGonratesbetweengroups
Results
+AVICATrialSheehan,etal.(2016)
n Conclusion:n Nosignificantdifferencedoesnotnecessarilymeanthattheyareequal(RRCI=0.69-1.28)
n Resultsmaynotbegeneralizableto:n Higherseverityofasthman Non-adherentchildren
n Duetonoplacebo-control,cannotexcludepossibilitythatbothibuprofenandAPAPmaybeassociated
Sheehan,etal.NEnglJMed.2016;375(7):619-30.
43
10/15/16
15
+WhatDoYouThink?RevisiGngthePaGentCase
44
+A7-year-oldchildoncontrollertherapyforasthmahasatemperatureof100.1°FandanewprescripEonforananEbioEc.Hermothertellsyouthatthepediatricianrecommendedthatsheshouldalsoget“somethingOTCforthefever”.
Doyourecommend:
A. Acetaminophen?
B. Ibuprofen?
45
+Reviewer’sThoughts
46
10/15/16
16
+EvidenceChecklist
q Exposureprecedesonsetofdisease
q Plausiblebiologicalmechanism
q Consistencyacrossdifferentstudysewngs
q TemporalrelaGonshiptoexposure
q IdenGficaGonofdose-responseeffect
q SpecificitytocausaGveagentwithnoconvincingalternaGveexplanaGon
q ReversibilityofthecausaleffectWeatherall,etal.ClinExpAllergy.2015;45(1):108-13.
47
✔✔✔✔✔✔
+Conclusion
n MulGpleobservaGonalstudiessuggest:n Dose-relatedrelaGonshipbetweenAPAPuse(possiblyAPAPoveruse)andasthma
n Plausiblemechanism(s)
n ExisGngRCTssuggest:n IbuprofenisnotnecessarilyabeueralternaGve
n MoreRCTsneededtostrengthenevidencen Lackingdataonreversibilityofeffect
48
+Acknowledgements
n Dr.NathanPope
n H-E-B/UTResidents&Preceptors
Evaluator:Prof.MarciaKiger
49
10/15/16
17
+Bibliography
n Data,StaGsGcs,andSurveillance.CenterforDiseaseControlandPrevenGon.hups://www.cdc.gov/asthma/asthmadata.htm.PublishedSeptember8,2016.AccessedOctober3,2016.
n Garcia-MarcosL,Sanchez-SolisM,Perez-FernandezV.Earlyexposuretoacetaminophenandallergicdisorders.CurrOpinAllergyClinImmunol.2011;11(3):162-73.
n LeskoSM,LouikC,VezinaRM,MitchellAA.Asthmamorbidityayertheshort-termuseofibuprofeninchildren.Pediatrics.2002;109(2):E20.
n LitonjuaAA.AcetaminophenandAsthma--ASmallSighofRelief?.NEnglJMed.2016;375(7):684-5.
n NewsonRB,ShaheenSO,ChinnS,BurneyPG.Paracetamolsalesandatopicdiseaseinchildrenandadults:anecologicalanalysis.EurRespirJ.2000;16(5):817-23.
50
+Bibliography
n ShaheenSO,SterneJA,SonghurstCE,BurneyPG.Frequentparacetamoluseandasthmainadults.Thorax.2000;55(4):266-70.
n SheehanWJ,MaugerDT,PaulIM,etal.AcetaminophenversusIbuprofeninYoungChildrenwithMildPersistentAsthma.NEnglJMed.2016;375(7):619-30.
n VarnerAE,BusseWW,LemanskeRF.Hypothesis:decreaseduseofpediatricaspirinhascontributedtotheincreasingprevalenceofchildhoodasthma.AnnAllergyAsthmaImmunol.1998;81(4):347-51.
n WeatherallM,IoannidesS,BraithwaiteI,BeasleyR.TheassociaGonbetweenparacetamoluseandasthma:causaGonorcoincidence?.ClinExpAllergy.2015;45(1):108-13.
n WhatIsAsthma?U.S.NaGonalLibraryofMedicine.hups://www.nhlbi.nih.gov/health/health-topics/topics/asthma.PublishedAugust4,2014.AccessedOctober3,2016.
51
+
From“A”to“Wheeze”Acetaminophen’sRoleintheAsthmaEpidemic
GretchenDao,PharmDCommunityPharmacyPGY1ResidentH-E-B/UniversityofTexasatAusGn October21,2016
