2024年3月17日发(作者：光环助手下载)

OriginalResearch

COPD

OralorIVPrednisoloneinthe

TreatmentofCOPDExacerbations*

ARandomized,Controlled,Double-blindStudy

,MD;,MSc;han,MD,PhD;

,MD,PhD;ens,MD,PhD;and

Berg,MD,PhD,FCCP

Background:TreatmentwithsystemiccorticosteroidsforexacerbationsofCOPDresultsin

italization,corticosteroidsaregenerallyadministered

ucteda

studytodemonstratethattherapywithoralprednisolonewasnotinferiortotherapywithIV

prednisoloneusingadouble-blind,double-dummydesign.

Methods:PatientshospitalizedforanexacerbationofCOPDwererandomizedtoreceive5days

oftherapywithprednisolone,entfailure,theprimaryoutcome,was

definedasdeath,admissiontotheICU,readmissiontotheICUbecauseofCOPD,orthe

intensificationofpharmacologictherapyduringa90-dayfollow-upperiod.

Results:Atotalof435patientswerereferredforaCOPDexacerbationwarrantinghospitaliza-

tion;107patientswererandomizedtoreceiveIVtherapy,and103toreceiveoraltherapy.

Overalltreatmentfailurewithin90dayswassimilar,asfollows:IVprednisolone,61.7%;oral

prednisolone,56.3%(one-sidedlowerboundofthe95%confidenceinterval[CI],؊5.8%).There

werealsonodifferencesinearly(ie,within2weeks)treatmentfailure(17.8%and18.4%,

respectively;one-sidedlowerboundofthe95%CI,؊9.4%),late(ie,after2weeks)treatment

failure(54.0%and47.0%,respectively;one-sidedlowerboundofthe95%CI,؊5.6%),andmean

(؎SD)lengthofhospitalstay(11.9؎8.6and11.2؎6.7days,respectively).Over1week,

clinicallyrelevantimprovementswerefoundinspirometryandhealth-relatedqualityoflife,

withoutsignificantdifferencesbetweenthetwotreatmentgroups.

Conclusion:TherapywithoralprednisoloneisnotinferiortoIVtreatmentinthefirst90days

estthattheoralrouteispreferableinthetreatmentofCOPD

exacerbations.

Trialregistration:ntifier:NCT00311961.

(CHEST2007;132:1741–1747)

Keywords:COPD;exacerbation;IVprednisolone;oralprednisolone

Abbreviations:CCQϭClinicalCOPDQuestionnaire;CIϭconfidenceinterval;GOLDϭGlobalInitiativefor

ChronicObstructiveLungDisease;MCIDϭminimalclinicallyimportantdifference;SGRQϭRespiratory

Questionnaire

OPDisamajorhealthproblemworldwide,and

bothmorbidityandmortalityarerising.

1

Char-

acteristicoftheclinicalcourseofCOPDareacute

episodesofdeteriorationinsymptomsandrespira-

xacerba-

tionsfrequentlyrequirehospitalization,whichalso

constitutesthelargestcomponentoftotalhealth-

carecostsforCOPD.

2

Systemiccorticosteroidshave

C

beendemonstratedtobebeneficialinthetreatment

ofCOPDexacerbations.

3,4

Systemiccorticosteroid

Foreditorialcommentseepage1728

treatmentleadstoshorterhospitalstaysandquicker

recoveryofFEV

1

.

5

Italsoleadstoadecreasein

treatmentfailureandreducestherelapseratein

CHEST/132/6/DECEMBER,2007

1741

thefirst1to3monthsafterinitialtreatment.

6,7

These

andothersmallerstudies

8–14

varyconsiderablyin

thoughcurrentguidelinessuggestthattheoralroute

ofadministrationispreferable,theoptimalrouteof

administrationofsystemiccorticosteroidsinthe

treatmentofexacerbationsofCOPDhasnotbeen

er,thepreferredrouteof

administrationvariesmarkedlybetweencountries.

Manyhospitalsroutinelyadministerthecorticoste-

roidsIV,ationaleforthis

routelacks,sincethereiscloseto100%bioavailabil-

ityofprednisolonefollowingoraladministration

under

Oral

normal

corticosteroids

conditions.

15

aremoreconvenienttoadmin-

isterbecausethereisnoneedforIVaccess,fewer

personnelarerequiredforstartingandmonitoring

therapy,the-

sizedthatoraladministrationisnotinferiortoIV

administrationofprednisoloneinthetreatmentof

patientshospitalizedforanexacerbationofCOPD.

Wethereforeconductedaprospective,randomized,

double-blind,double-dummy,placebo-controlled,

parallel-groupclinicalstudywithtreatmentfailureas

theprimaryoutcome.

MaterialsandMethods

Patients

PatientsreferredtotheIsalakliniekenhospitalforanexacerbation

ofCOPDwereenrolledinthestudyfromJune2001toJune2003.

InclusioncriteriawereanageofϾ40years,ahistoryofatleast10

pack-yearsofcigarettesmoking,andevidenceofairflowlimitation.

AirflowlimitationwasdefinedasanFEV

1

/FVCratioofϽ70%and

anFEV

1

ofϽ80%predicted(atleastGlobalInitiativeforChronic

ObstructiveLungDisease[GOLD]severitystageII).

16,17

Anexac-

erbationofCOPDwasdefinedasahistoryofincreasedbreathless-

nessandthepresenceofatleasttwoofthefollowingsymptomsfor

atleast24h:increasedcoughfrequencyorseverity;increased

sputumvolumeorpurulence;edwere

patientswhohadsignsofaverysevereexacerbation

with

on

significant

hospital

admission(arterialpHϽ7.26orPaco

orunstablecomorbidity,whohadahistory

2

Ͼ9.3kPa),

ofasthma,hadpartici-

patedinanotherstudywithinthe4weeksbeforehospitaladmission,

werepreviouslyrandomizedintothisstudy,hadclinicallysignificant

*FromtheDepartmentofPulmonology(,Grotjo-

han,

Netherlands;

andvanden

and

and

Berg,

theDepartment

),

of

Isala

Pulmonology

Klinieken,Zwolle,the

ningen,

Kerstjens),UniversityMedicalCenter

(

The

conflicts

authors

theNetherlands.

Groningen,Gro-

products

ofinterest

have

exist

reported

withany

tothe

companies/organizations

ACCPthatnosignificant

whose

Manuscript

or

2007.

received

servicesmay

January

bediscussed

23,2007;revision

inthisarticle.

acceptedMay30,

Reproduction

from

org/misc/).

theAmerican

ofthis

College

articleis

of

prohibited

ChestPhysicians

without

(ournal.

writtenpermission

Correspondence

monology,

to:,MD,Isala

e-mail:

POBox10500,Zwolle8000GM,the

klinieken,

Netherlands;

Pul-

DOI:10.1378/chest.07-0208

@

1742

findingsonchestradiographyotherthanfittingwithsignsofCOPD,

aknownhypersensitivitytoprednisolone,orwhowereknowntobe

dywasapprovedbythehospital

medicalethicscommittee,andallpatientsgavewritteninformed

consent.

StudyDesign

Patientswererandomizedusingacomputerminimizationpro-

gram

18

forthefollowing10parameters:useoforalprednisolone;use

ofinhaledcorticosteroids;theophyllineuse30daysbeforehospital

admission;admissiontothehospitalbecauseofanexacerbationof

COPDinthelastyear;age(Ͻ65orՆ65years);gender;smoking

history(Ͻ50orՆ50pack-years);useofsupplementaloxygenat

home;Pco

2

(Ͻ5.4orՆ5.4kPa);andtimesincethediagnosisof

COPD(ie,Ͻ5,5to10,10to15,orϾ15years,orunknown).

Patientsreceivedeithera5-daycourseofIVororalprednisolone,

60mg,andplacebo

5days,allpatients

receivedoralprednisoloneinadosageof30mgoncedaily,which

subsequentlywastaperedwith5mgdailyto0mgoraprior

ientsreceivednebulizedipratropium

bromideandalbuterolfourtimesdailytogetherwithoralamoxi-

cillin/ofallergytothisregimen,doxycycline

etrywasmeasuredondays1and7.

19

Onthe

samedays,

RespiratoryQuestionnaire(SGRQ),

20

achangeinscoreofՆ4

points,constitutingtheminimalclinicallyimportantdifference

(MCID).

21

Health-relatedqualityoflifewasmeasureddailyinthe

firstweekusingthe24-hversionoftheClinicalCOPDQuestion-

naire(CCQ),

22

withachangeofՆ0.4pointsconstitutingthe

MCID.

23

Therespiratoryphysiciandecidedthedateofhospital

dischargeandwasfreetointensifypharmacologictherapyifclinical

tswerefreetowithdrawat

low-upperiodwas90dayswithoutpatientvisitsat

days42and90.

StudyEndPoints

Theprimaryoutcomewastreatmentfailure,definedasdeath

fromanycause,admissiontotheICU,readmissiontothehospital

becauseofCOPD,orthenecessitytointensifypharmacologic

ensificationofpharmacologictreatmentwas

definedastheprescriptionofopen-labelcorticosteroids,theoph-

ylline,entfailurewassubdividedintoearly

failure,thefirst2weeksafterrandomization,andlatefailure,

tientsreceivedadditional

medication,asmentionedabove,fromtheirgeneralpractitioner,

aryoutcomes

werechangesfromdays1to7inFEV

1

,SGRQscores,CCQ

scores,andlengthofhospitalstay.

StatisticalAnalysis

nning

committee

Ͼ15%better

decided

(thatis,

that

produced

ifresults

atreatment

withIV

failure

prednisolone

ratethat

were

was

15%lower)thantheratewithoralprednisolone,thenclinicians

wouldjudgethatthebenefitsofIVtherapyclearlyoutweighthe

renceintherateof

treatmentfailureofՅ15%wasdeemedtobesufficienttoaccept

thatoralcorticosteroidswerenotinferiortoIVtherapyinpatients

l,256patientswere

requiredtohave80%powerwithaone-sided␣-statisticof5%and

anexpectedtreatmentfailurerateof37%.

6

Todeterminenoninfe-

riorityinaccordancewiththestudydesign,thelowerboundofa

one-sided95%confidenceinterval(CI)fordifferenceswasused.

OriginalResearch