• Nenhum resultado encontrado

Association between chronic stress and immune response to influenza vaccine in healthcare workers

N/A
N/A
Protected

Academic year: 2021

Share "Association between chronic stress and immune response to influenza vaccine in healthcare workers"

Copied!
9
0
0

Texto

(1)

w w w . e l s e v i e r . p t / r p s p

Original

Article

Association

between

chronic

stress

and

immune

response

to

influenza

vaccine

in

healthcare

workers

Ema

Sacadura-Leite

a,b,c,∗

,

António

Sousa-Uva

b,c

,

Helena

Rebelo-de-Andrade

d,e

,

Sancha

Ferreira

a

,

Regina

Rocha

a

aOccupationalHealthDepartmentofHospitaldeSantaMaria/CHLN,Lisbon,Portugal bNationalSchoolofPublicHealth/NewUniversityofLisbon,Lisbon,Portugal

cCMDTCentrodeInvestigac¸ãodaMaláriaeDoenc¸asTropicaisPublicHealth,Lisbon,Portugal dNationalInstituteofHealth,INSA,Lisbon,Portugal

eFacultyofPharmacy,UniversityofLisbon,Lisbon,Portugal

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received15April2013 Accepted27September2013 Availableonline19December2013

Keywords: Antibodyresponse Healthcareworkers Influenzavaccine Psychologicalstress

a

b

s

t

r

a

c

t

Introduction:Chronicstresscaninfluenceimmuneresponsetovaccines.Healthcareworkers areexposedtostressorsandbiologicalhazards,thehealtheffectsofwhichmaybeprevented throughvaccination.

Objectives:Thisstudyaimstoevaluate theassociationbetweenstressinnursesand:(1) insufficientresponsetoinfluenzavaccine,assessedonemonthaftervaccination(T1);(2)

thedropinhaemagglutination-inhibition(HAI)antibodies(ab)sixmonthsaftervaccination (T6).

Methods:Anestedcase–controlstudywascarriedoutwith136healthyhospitalnurses. Individualinterviews,theGeneralHealthQuestionnaire(GHQ12)andMaslachBurnoutInventory

(MBI-HSS)wereappliedinordertodeterminethepresenceofstress,usingthetriangulation methodatthebeginningofthestudy(T0).Influenzavaccinewasadministeredandtitres

ofHAIaboveeachstraincomposinginfluenzavaccinebeforevaccination(T0),atT1andT6

wereassessed.

Results:Therewasnostatisticallyrelevant(5%)relationshipbetweenstressandthe insuffi-cientimmuneresponsetothevaccineatT1.Nevertheless,therewasanassociationbetween

stressandthedropinHAIabAH1atT6,whenweassessedstressbythetriangulationmethod

usinganinterview(p=0.006),GHQ12(p=0.045)andcombinationofcriteria(p=0.001),even

aftermultivariateanalysis(respectively,p=0.01,p<0.05andp=0.002).Theoddsratioswere, respectively,3.64,2.73and5.22.

Conclusions:Theassociationwefound,betweenchronicstressandthedropinHAIabat T6, corroboratesthehypothesis thatstresscannegatively influenceimmune response.

Therefore,itseemsreasonableto considerthis issuewhen weimplementvaccination programmesforhealthcareworkers.

©2013EscolaNacionaldeSaúdePública.PublishedbyElsevierEspaña,S.L.Allrights reserved.

Correspondingauthor.

E-mailaddress:ema.leite@chln.min-saude.pt(E.Sacadura-Leite).

0870-9025/$–seefrontmatter©2013EscolaNacionaldeSaúdePública.PublishedbyElsevierEspaña,S.L.Allrightsreserved.

(2)

Stresse

crónico

e

a

imunidade

à

vacina

contra

a

gripe

em

profissionais

de

saúde

Palavras-chave:

Anticorpos

Profissionaisdesaúde Vacinacontraagripe Stresse

r

e

s

u

m

o

Introduc¸ão: Ostressecrónicopodeinfluenciararespostaimunitáriaàvacinac¸ão.Os profis-sionaisdesaúdeestãoexpostosastressoresdenaturezaprofissionaleaindaaagentes biológicoscujosefeitospoderãoserprevenidospelavacinac¸ão.

Objetivos: Estudaraassociac¸ãoentreapresenc¸adestressee(1)a“insuficiente”resposta imunitáriaàvacinacontraagripe,avaliadaummêsapósavacinac¸ão(T1);(2)areduc¸ãodos

títulosdeanticorposdirigidosàshemaglutininas(HAI)seismesesapósavacinac¸ão(T6).

Métodos: Realizou-seumestudocaso-controloincorporadonumestudodecoortescoma participac¸ãode136enfermeiroshospitalaressaudáveis.Realizaram-seentrevistas individu-aiseaplicaram-seosquestionáriosTheGeneralHealthQuestionnaire(GHQ12)eMaslachBurnout

Inventory(MBI-HSS)paradeterminac¸ão da presenc¸a destresse crónicopelo métododa triangulac¸ão,noiníciodoestudo(T0).Foiadministradaavacinacontraagripee

determinou-seostítulosdeHAIdirigidosacadaestirpecomponentesdavacinacontraagripe,antesda vacinac¸ão(T0),emT1eemT6.

Resultados: Nãoseencontrouassociac¸ãosignificativa(5%)entreapresenc¸adestressea “insuficiente”respostaàvacinacontraagripeemT1.Contudo,encontrou-seumaassociac¸ão

entreapresenc¸adestresseadiminuic¸ãodotítulodeHAIdirigidosàestirpeA(H1N1)emT6

quandoseavaliouapresenc¸adestressepelométododatriangulac¸ãousandoaentrevista (p=0,006),oGHQ12(p=0,045)eacombinac¸ãodostrêscritérios(p=0,001),quesemanteveapós

análisemultivariada(respetivamentep=0,01,p<0.05ep=0.002).Osoddsratioajustadosforam de3,64,de2,73ede5,22.

Conclusões: Aassociac¸ãoencontradaentreapresenc¸adestressecrónicoeareduc¸ãodo títulodeHAIemT6vemapoiarahipótesedequeostressepoderáinfluenciar

negativa-menteamanutenc¸ãodostítulosdeanticorpos,mesmoemindivíduosadultosnãoidosos. Assim,parecerazoávelconsideraresteaspetoquandosepretendeimplementarprogramas devacinac¸ãodirigidosaprofissionaisdesaúde.

©2013EscolaNacionaldeSaúdePública.PublicadoporElsevierEspaña,S.L.Todosos direitosreservados.

Introduction

Healthcareworkersareexposedtomanystressors,someof

themrelatedwithorganisationalworkconditionsandothers, morespecifictothisprofession,relatedwiththeiractivityof caringfortheill.1–3

Chronicstressandburnout seemtobeverycommon in

nurses.4–6 Forexample,López-Castilloandcolleaguesfound

highlevelsofemotionaldisturbancedeterminedbythe Gen-eralHealthQuestionnaire(GHQ28)in39%ofhospitalnurses.7

Amongstthe consequencesofchronicdistress,whether

theyare related or not withwork, are the possibleeffects

on the immune system, including effects on the immune

responsetovaccination.

Healthcareworkersarestronglyadvisedtobevaccinated againstinfluenzainordertoprotectthemselvesagainstthe disease,reducestaff absenteeismandminimisethe riskof nosocomialtransmissionto the patientsthey takecare of. Vaccinationisapossiblemodelforimmuneresponse,

test-ingmostlythehumoralimmuneresponse.Vaccinatedpeople

developantibodies (ab) that bind and neutralise the virus, inmostcasesabagainstthesurfaceglycoprotein hemagglu-tinin.Thoseabcanbeusedasmarkersofprotectionagainst thedisease,8causedbystrainsthataresimilartothevaccine

composition.

According to meta-analysis by Segerstrom and Miller,

chronicexposuretostressorssuchastakingcareofspouses

with dementia, unemployment and suffering from

physi-cal disability is associated with a smaller ab response to influenza vaccine.9 Somereviewsalsosuggest thatchronic

stressisassociatedwithasmallerabresponsetoinfluenza vaccine.10–12

Generally speaking, studies evaluating the association

between chronicstress and immuneresponse toinfluenza

vaccine showed relatively consistent results inold people. In those people, chronic exposure tostressors was associ-atedwithchronicanxietyandsymptomsofdepressionanda lowerresponsetoinfluenzavaccine,incomparisontoa con-trolgroup.13–17

Theuseofastandardizeddoseofantigenwhichpromotes

agoodimmuneresponseinmostadults,couldmakeit

dif-ficultthedetectionoftheinfluenceofchronicstressinthe

immune responsetovaccinationinyounger adults,witha

robustimmunesystem.

Olderpeoplehaveaweakerimmunesystem,relatedwith

age, so this could be an explanation for the greater

con-sistencyofresultsshowinga negativeassociation between

chronic stress and immune response to vaccines inthem.

Vedharaandcolleaguesdidnotfindanyassociationbetween

taking care of spouses with multiple sclerosis and ab

(3)

However,thoseadultsshowedsimilarstresslevelsasthe con-trolgroup.

In younger adults, such as university students, some

studies19–22 found an association between stress,

charac-terised in different ways, and the immune response to

influenzavaccine(assessedbyabtitresorbyresponserate) onemonthaftervaccination.However,otherstudiesdidnot findthatassociation.23–25

Some of the studies found an association between

stress and a drop in ab titres assessed 4–6 months after

vaccination,19–23,25evenintheyoungestadults.Thedropin

theabtitresassociatedwithstresswasonlyobservedagainst onestrainofvaccinecomponents,suggestingthatdifferent exposuresor differentpastvaccinationscanberesponsible forthoseresults.

Inanoccupationalcontextofhealthcaresettings,where healthcareworkersareinthelabourmarket(andare there-forenotveryold),butaresimultaneouslyexposedtochronic stressorsandbiologicalriskhazards,itseemsimportantto studytheinfluenceofstressonimmuneresponsetoinfluenza vaccine.

Therefore, this study analyses the association between

stressinnursesand:(1)insufficientresponsetoinfluenza vac-cine,assessedonemonthaftervaccination(T1);(2)thedrop

ininfluenza aemagglutination-inhibition (HAI) abtitres six monthsaftervaccination(T6),ascomparedtoonemonthpost

vaccinationHAIabtitres.

Materials

and

methods

Studydesignandparticipants

Thestudywasanestedcase–controlstudy,conductedoversix monthsinauniversityhospitalduringthe2007/2008influenza season.Subjectswerehospitalnurseswhowerenottakingany regularmedication,includingdrugsthatcouldaffect immu-nity(suchascancertherapydrugsorcorticosteroids).Theydid nothaveanymedicalconditionthatcouldaffecttheimmune responseandtheyalsohadnomajorsurgeryinthepreceding threemonths.Theydidnothaveahistoryofdrug consump-tionoralcoholconsumptiongreaterthan10unitsperweek, nordid theyhandlecitotoxic drugs orwork regularly with ionisingradiation(n=136).Thehospital’sEthics Committee approvedthestudyandalltheparticipantssignedtheir agree-menttoparticipatinginit.

One-monthandsix-monthdrop-outcriteria:

• clinical diagnosis of medical condition that may affect

immuneresponseafterthebeginningofthestudyortaking anyregularmedicationthatcanaffectimmunity(assessed byinterview,atT1andT6);

• workplacechangeswithregularexposuretoionising radia-tionsorcitotoxicdrugshandling;

• clinical influenza symptoms with virus identification in

nasalororopharyngealswab,duringthesixmonthsofthe study;

• ariseinHAIAbtitretoA(H1N1),A(H3N2)orBstrainssix

monthsaftervaccination,ascomparedwiththetitres mea-suredonemonthaftervaccination.SuchariseinHAIAb

titresuggestsanexposuretoinfluenzastrainsduringT1and

T6insteadofadelayedresponsetothevaccine.

Stressassessment

Structuredindividualinterviewswereconductedatthe begin-ningofthestudy(T0)inorderto:

• identify socio-demographic characteristics and possible

confoundable variables related with immunity (physical

exercise,nutritionalparameters,nutritionalsupplements,

hours of sleep per day, smoking habits, shiftwork) and

influenzavaccinationhistory;

• identifywork-relatedandnon-work-relatedstressors,using aLikertscalefrom1to5;

• assessperceivedstress,usingaLikertscalefrom1to5; • identify stress-related behavioural changes or

psychoso-maticsymptoms.

We also applied the Portuguese versions of the General

Health Questionnaire (GHQ12) and Maslach Burnout Inventory

(MBI-HSS orMBI) exhaustion scale atthe beginning ofthe

study(T0).AlfaCronbachforthosescaleswas0.855and0.874

respectively.

Inordertoassessthepresenceofchronicstress,weapplied

the triangulation method at T0, as suggested by Cox and

colleagues,26infourdifferentways:

• throughinterviews:weaccepted thepresenceofchronic

stress using interviews if therewere identified stressors classifiedas4or5,plusperceivedstressclassifiedas4or5, plusatleastonebehaviouralchangeoronepsychosomatic symptomstress-related;

• throughGHQ12:weacceptedthepresenceofchronicstress

usingGHQ12iftherewereidentifiedstressorsclassifiedas4

or5,plusGHQ12higherthan2,plusatleastonebehavioural

changeoronepsychosomaticsymptomstress-related;

• throughMBI:weaccepted thepresenceofchronicstress

usingMBIiftherewereidentifiedstressorsclassifiedas4or 5,plusMBIexhaustionscalehigherthan24,plusatleastone

behaviouralchangeoronepsychosomaticsymptom

stress-related;

• combinationofcriteria:weacceptedthepresenceofstress usingcombinationofcriteriaiftherewasstressusing inter-viewand stressusingGHQ12 orif therewasstressusing

interviewandstressusingMBIexhaustionscale.

Vaccinationandlaboratoryprocedures

Venous blood was drawn at three stagesbetween October

2007andApril2008:(i)immediatelybeforeinfluenza vacci-nation(T0);(ii)onemonthfollowingimmunisation(T1);and

(iii)sixmonthsafterT0(T6).

The samples rested 1hat ambient temperature

follow-ingcentrifugationat3500rpmfor10min.Serawerestoredat −20◦Cuntilused.AllthesamplesdrawnatT0,T1andT6were

processedatthesametimeandunderthesameconditions. Acommerciallyavailable2007/2008trivalentinfluenza

vac-cine,withtherecommendedcompositionforthatseasonin

(4)

deltoidmuscle,duringOctober.Allthevaccinesbelongedto

thesamegroup(AFLUA290AD).

Haemagglutinationinhibitionreactionwasusedtoassess specificHAIabtitreagainstinfluenzaA(H1N1),A(H3N2)and

Bstrains included inthe influenza vaccine, in accordance

withtheWorldHealthOrganisation’smanual.27Immediately

beforethelaboratorialprocedures,theseraweretreatedbya

Receptor-DestroyingEnzyme(RDE)inordertoremoveunspecific agglutininsandinhibitors.

The reference antigens were diluted to obtain 4 units

against haemmaglutinin per 25␮l and incubated with the

treated sera samples. Erythrocytes were then added to

thefluid.

HAIAbtitrecorrespondedtotheinverseofthelastdilution

ofserum that completelyinhibited haemagglutination. We

usedprogressivedilutions,startingwith1:10upto1:20.480. Theserologicalparametersobtainedwere:

• HAI Ab titre against influenza A(H1N1), A(H3N2) and B

strainsincludedininfluenzavaccine,before(T0)andafter

vaccination(T1andT6);

• riseinHAIAbtitreagainstinfluenzaA(H1N1),A(H3N2)andB

strainsincludedininfluenzavaccine,assessedonemonth

after vaccination(comparedtoHAI Abtitreimmediately

beforevaccination);

• dropinHAIAbtitreagainstinfluenzaA(H1N1),A(H3N2)and

Bstrainsincludedininfluenzavaccine,betweenT1andT6.

Definitions

ForanalysisatT1andatT6,wedefinedthefollowinggroups:

respondersatT1(onemonthaftervaccination):participants

thatshowed, atT1,atleastafourfold riseinHAI abtitre

comparedtothetitrebeforevaccination;

non-respondersatT1(onemonthaftervaccination):

partic-ipantsthatdidnotshow,atT1,afourfoldriseinHAIabtitre

comparedtothetitrebeforevaccination;

HAIabtitredropgroupatT6(sixmonthsaftervaccination):

participantswithatleastafourfoldriseinHAIabtitreatT1,

butwhoshowedadropinHAIabtitreatT6,ascomparedto

HAIabtitreatT1;

nochangeinHAIabtitregroupatT6(sixmonthsafter

vac-cination):participants withatleastafourfold rise inHAI abtitreatT1, butwithnochangeinHAIabtitreatT6, as

comparedtoHAIabtitreatT1.

Statisticalanalyses

Fordichotomousvariables,weusedtheQui-squareandFisher exacttestsanddeterminedtheoddsratio.

Fornumericalvariables,weusedtheKolmogorov–Smirnov

andShapiro–Wilkteststoassessnormaldistributionin non-respondersandresponders(T1)andintheHAIAbtitredrop

groupandnochangeinHAIAbtitregroup(T6).

For normal distributions, the T Student test was used

to compare means, and the Levene test to assess variance

homogeneity. For no normal distributions, we applied the

Mann–Whitneytesttocomparemedians.

Wealsousedthemultivariateanalysisanddeterminedthe adjustedoddsratiofortheconfoundingvariables.

Weconsideredastatisticalsignificanceof5%.Alltestswere runintheStatisticalPackageforSocialSciences–SPSS®software,

version14.0forWindows.

Results

Westudied136nurses,mostofwhomwerefemale(83.8%),

Caucasian(96.3%)anddidnotsmoke(77.9%).Theiraverage agewas33andthemedianagewas29(22–63yearsold).Only oneparticipantwasmorethansixtyyearsofage.

Morethanonehalfoftheparticipantshadbeengivenan influenzavaccineshotatleastoneofthefourseasonspriorto thebeginningofthestudy(52.9%),mostlyintheyear imme-diatelybefore(44.1%).Nursesincludedinthestudyworked mostlyonashiftworkbasis(70.6%),hadacorporalindexmass (kg/m2)between18.5and24.9(72.1%)andsleptatleast7hper

day(66.2%).Themajoritydidnottakevitaminsupplements (86.8%)orfishoil(98.5%).Only54.4%didregularphysical exer-ciseand46.3%ateyogurtdaily.

Associationbetweenchronicstressandnon-responders atT1

Onemonthaftervaccination(T1),wedidnotfindany

associ-ation ofstatisticalsignificancebetweennon-respondersfor A(H1N1)virus strain included inthe influenza vaccine and

thepresenceofchronicstressatT0,assessedinfour

differ-ent ways.Similarly,there wasalsono associationbetween non-respondersforA(H3N2)ornon-respondersforBstrains

includedintheinfluenzavaccineandchronicstressatT0.To

simplifythetable,wenamedrespondersornon-responders

forA(H1N1)andforA(H3N2)asrespondersornon-responders

AH1andAH3respectively(Table1).

Aemagglutination-inhibitionantibodiestitresatT0in respondersandnon-respondersatT1

UsingtheKolmogorov–SmirnovandShapiro–Wilktests,wefound thatthereisnonormaldistributioninnon-responders and

responders at T1 for the considered continuous variables

(p<0.001). Therefore, we applied the Mann–Whitney test to comparemediansbetweenHAIabtitresatT0inresponders

and non-responders at T1. We found that non-responders

AH1 atT1 had significantly higherHAI abAH1 titresatT0

than respondersAH1atT1.Thesamehappenedwith

non-respondersAH3atT1 andnon-respondersBatT1,whohad

significantlyhigherHAIAH3titresatT0andHAIBtitresatT0

thanthecorrespondingresponders(Table2).

Associationbetweenchronicstressanddropin aemagglutination-inhibitionabtitresatT6

AtT6(sixmonthsaftervaccination),thepresenceofstressin

theHAI abAH1 titredropgroupwashigherthanintheno

changeinHAIabAH1 titregroup,whenweassessedstress

byalltheconsidereddifferentways,beingstatistically signi-ficativewhenweassessedthepresenceofchronicstressby

(5)

Table1–Stressinnon-respondersandinrespondersAH1,AH3andBatT1. HAIabgroupsatT1 Chronicstress

assessment Stressin non-respondersatT1 Stressin respondersatT1 Statisticalanalysis (Qui-squaretest) n(%) n(%) OR(95%CI) p AH1(n=135) Non-responders:45 Responders:90 Stress(interview) 28(62.2) 46(51.1) 1.575(0.759–3.272) 0.221 Stress(GHQ12)a 19(42.2) 44(48.9) 0.764(0.371–1.572) 0.464 Stress(MBI)b 16(35.6) 36(40.0) 0.828(0.394–1.738) 0.617

Stress(combinationofcriteria)c 20(44.4) 41(45.6) 0.956(0.466–1.963) 0.903

AH3(n=136) Non-responders:50 Responders:86 Stress(interview) 27(54.0) 47(54.7) 0.974(0.484–1.961) 0.941 Stress(GHQ12)a 20(40.0) 43(50.0) 0.667(0.329–1.351) 0.259 Stress(MBI)b 15(30.0) 37(43.0) 0.568(0.271–1.190) 0.132

Stress(combinationcriteria)c 20(40.0) 41(47.7) 0.732(0.361–1.483) 0.386

B(n=135) Non-responders:59 Responders:76 Stress(interview) 31(52.5) 43(56.6) 0.850(0.429–1.683) 0.640 Stress(GHQ12)a 24(40.7) 39(51.3) 0.651(0.327–1.293) 0.219 Stress(MBI)b 22(37.3) 30(39.5) 0.912(0.453–1.836) 0.796

Stress(combinationofcriteria)c 24(40.7) 37(48.7) 0.723(0.364–1.437) 0.354

OR–oddsratio;95%CI–95%confidenceinterval.

a GeneralHealthQuestionnaire(GHQ 12). b MaslachBurnoutInventory(MBI). c Stress(interviewandGHQ

12)orstress(interviewandMBI).

triangulationmethodatT0usinginterviews,GHQ12andthe

combinationofthethreemethods.Onthecontrary,wedidnot findanystatisticallysignificantassociationbetweenthe oth-ersHAIabtitredropgroupsatT6andthepresenceofchronic

stress(Table3).

Associationbetweenotherpossibleconfoundingvariables andaemagglutination-inhibitionabAH1titredropgroup atT6

Someconditionsthatcanaffectimmunitycouldhavebeen

possibleconfoundingfactors,whenweconsideredthe asso-ciationbetweenstressandtheHAIabAH1titredropgroupat

T6.UsingtheKolmogorov–SmirnovandShapiro–Wilktests,we

foundthatthereisnonormaldistributioninHAIabAH1titre

dropgroupatT6andinnochangeinHAIabAH1titreatT6for

theconsideredcontinuousvariables(p<0.001).Therefore,we appliedtheMann–Whitneytesttocomparetheirmedians.

Thestatisticalanalysesdidnotfindanysignificant differ-encebetweengroupsatT6forthevariables(continuousand

dichotomous)takenintoconsideration(Table4).

Multivariateanalysisandadjustedoddsratiosforstress, ageandaemagglutination-inhibitionabAH1titresatT0 andT1consideringaemagglutination-inhibitionabAH1 titredropgroupatT6

Stress–assessedbyinterview,GHQ12orusingthecombination

ofthethreemethods–wastheexclusivevariableassociated withHAIabAH1titredropgroupatT6,butwealsotooktheage

variableintoconsiderationinthemultivariateanalysis.That

optionwasmadebecauseageisastrongfactorinfluencing

immunityand,inthesimpleanalysis,themediandifference betweengroupswouldbedifferentifweconsidereda confi-dencelevelof90%(insteadof95%).

Furthermore,BeyerandcolleaguesshowedthatbasalHAI ab AH1 titres influenceHAI abAH1 titres onemonthafter

Table2–HAIantibodiesAH1,AH3andBtitresatT0innon-respondersandinrespondersAH1,AH3andBatT1. HAIantibodiesatT0 Non-respondersatT1 RespondersatT1 Statisticalanalysis(Mann–Whitneytest)

Md(min–max) Md(min–max) Mddifferences p

HAIabAH1titresatT0in non-respondersAH1(n=45) andrespondersAH1(n=90)at T1 640.0(80–10,240) 20.0(10–1280) 620.0 <0001 HAIabAH3titresatT0in non-respondersAH3(n=50) andrespondersAH3(n=86)at T1 160.0(10–5120) 20.0(10–1280) 140.0 <0001 HAIabBtitresatT0in non-respondersB(n=59) andrespondersB(n=76)atT1 160.0(20–10,240) 60.0(10–640) 100.0 <0001 Md-median.

(6)

Table3–StressinHAIantibodiestitredropgroupandinnochangeinHAIAbtitregroupAH1,AH3andBatT6. HAIabgroupsatT6 Chronicstress

assessment

StressinHAIabtitre dropgroupatT6

Stressinnochangein HAIAbtitregroupatT6

Statisticalanalysis (Qui-squaretest)

n(%) n(%) OR(95%CI) p

AH1(n=88) HAIabtitredrop group:57 NochangeinHAIab titregroup:31 Stress(interview) 36(63.2) 10(32.3) 3.600(1.427–9.084) 0.006 Stress(GHQ12)a 33(57.9) 11(35.5) 2.500(1.012–6.176) 0.045 Stress(MBI)b 25(43.9) 10(32.3) 1.641(0.656–4.104) 0.288 Stress(combination ofcriteria)c 34(59.6) 7(22.6) 5.068(1.875–13.70) 0.001 AH3(n=81) HAIabtitredrop group:48 NochangeinHAIab titregroup:33 Stress(interview) 25(52.1) 21(63.6) 0.621(0.251–1.539) 0.302 Stress(GHQ12)a 26(54.2) (51.5) 1.112(0.458–2.703) 0.814 Stress(MBI)b 20(41.7) 16(48.5) 0.759(0.311–1.851) 0.544 Stress(combination ofcriteria)c 23(47.9) 18(54.5) 0.767(0.315–1.865) 0.558 B(n=76) HAIabtitredrop group:51 NochangeinHAIab titregroup:25 Stress(interview) 26(51.0) 17(68.0) 0.489(0.179–1.335) 0.160 Stress(GHQ12)a 27(52.9) 12(48.0) 1.219(0.468–3.177) 0.686 Stress(MBI)b 17(33.3) 13(52.0) 0.462(0.174–1.226) 0.118 Stress(combination ofcriteria)c 22(43.1) 15(60.0) 0.506(0.191–1.339) 0.167

OR–oddsratio;95%CI–95%confidenceinterval.

a GeneralHealthQuestionnaire(GHQ 12). b MaslachBurnoutInventory(MBI). c Stress(interviewandGHQ

12)orstress(interviewandMBI).

Table4–Variablesdistribution(stressnotincluded)inHAIabAH1titredropgroupatT6andinnochangeinHAIabAH1

titregroupAH1atT6.

Variables HAIabAH1titredrop

groupatT6(n=57)

NochangeinHAIab AH1titregroupatT6

(n=31)

Statisticalanalysis(Fishertestor Qui-squaretestorMann–Whitney

test)

n(%) n(%) OR(95%CI) p

Malegender 5(8.8) 7(22.6) 0.330(0.095–1.145) 0.103a

Caucasian 53(93.0) 31(100) 0.631(0.536–0.743) 0.293a

Shiftwork 35(61.4) 23(74.2) 0.553(0.211–1.453) 0.250a

Dailysleephours<7 20(35.1) 8(25.8) 0.643(0.244–1.699) 0.372b

Smokers 10(17.5) 9(29.0) 0.520(0.185–1.461) 0.211b

Vitaminsupplements 10(17.5) 4(12.9) 1.436(0.410–5.025) 0.762a

Fishoilconsumption 0(0.0) 0(0.0)

Dailyconsumptionofyogurts 27(47.4) 15(48.4) 0.960(0.400–2.304) 0.927b

Noregularphysicalactivity 29(50.9) 11(35.5) 1.883(0.765–4.634) 0.166b

Pastinfluenzavaccine 17(29.8) 12(38.7) 0.673(0.268–1.687) 0.397b

Influenzavaccineat2006 14(24.6) 11(35.5) 0.592(0.229–1.533) 0.278b

HAIabAH1atT0≥40 25(43.9) 17(54.8) 0.643(0.267–1.551) 0.325b

Variables HAIabAH1titredrop

groupatT6(n=57)

NochangeinHAIab AH1titregroupatT6

(n=31)

Statisticalanalysis(Fishertestor Qui-squaretestorMann–Whitney

test)

Md(min–max) Md(min–max) Mddifferences p

Age 31.0(23.0–63.0) 26.0(22.0–56.0) 5.0 0.072c

Bodyindexmass 22.7(17.7–37.8) 22.0(18.0–37.5) 0.7 0.793c

HAIabAH1titresatT0 20.0(10–640) 40.0(10–1280) −20.0 0.276c

HAIabAH1titresatT1 1280.0(40–20,480) 1280.0(160–20,480) 0.0 0.265c

Md–median.

a Fishertest. b QuiSquaretest. c Mann–Whitneytest.

(7)

Table5–Multivariedanalysis(multiplelogisticregression)forstress(assessedbytriangulationmethodusingGHQ12,

usinginterviewandusingthecombinationofthethreemethods)inHAIabAH1titredropgroupatT6consideringage,

HAIabAH1titresatT0andatT1.

Chronicstressassessment Consideredvariablesin multivariedanalysis Statisticalanalysis (multiplelogistic regression) AdjustedOR(95%CI) p GHQ12a Age 1.038(0.989–1.089) 0.134 Stress 2.733(1.039–7.186) 0.042 HAIabAH1atT0 0.998(0.995–1.000) 0.100 HAIabAH1atT1 1.000(1.000–1.000) 0.793 Interview Age 1.043(0.994–1.094) 0.083 Stress 3.643(1.371–9.684) 0.010 HAIabAH1atT0 0.999(0.996–1.001) 0.236 HAIabAH1atT1 1.000(1.000–1.000) 0.987 Combination of criteriab Age 1.044(0.994–1.096) 0.087 Stress 5.223(1.828–14.924) 0.002 HAIabAH1atT0 0.999(0.996–1.001) 0.255 HAIabAH1atT1 1.000(1.000–1.000) 0.892

AdjustedOR–adjustedoddsratio;95%CI–95%confidenceinterval.

a GeneralHealthQuestionnaire(GHQ 12). b Stress(interviewandGHQ

12)orstress(interviewandMBI).

vaccination.28Therefore,wealsoconsideredHAIabAH

1titres

atT0andT1inthemultivariateanalysis.

Wefoundthatstress,assessedbytriangulation method

usingGHQ12, usinginterview andusingthecombinationof

thethreemethods,maintainedtheassociationwithHAIab

AH1 titre drop group at T6. The association between HAI

abAH1titredropgroupatT6andtheothersvariablesdidnot

revealanystatisticalsignificance(Table5).

Whenweassessedstressbytriangulationmethodusing

GHQ12,themodelwasstatisticallysignificant(p<0.029)and

suitable,giventhatnullhypothesiswas notrejectedinthe Hosmer–Lemeshowtest(p<0.106).Themodelshoweda valid-ityrateof65.9.

Whenweassessedstressbytriangulationmethodusing

interview,themodelwasstatisticallysignificant(p<0.009)and suitable,giventhatnullhypothesiswas notrejectedinthe Hosmer–Lemeshowtest(p<0.761).Themodelshoweda valid-ityrateof71.6.

Whenweassessedstressbytriangulationmethodusing

thecombination ofthe threemethods,the modelwas

sta-tistically significant (p<0.002)and suitable, giventhat null

hypothesis was not rejected in the Hosmer–Lemeshow test

(p<0.679).Themodelshowedavalidityrateof73.9.

Discussion

and

conclusions

Whenhumanbeingsare exposedtochronicstressors,they

may respond to them with neuroendocrine changes that

includethereleaseofneuropeptides,monoaminesand

hor-mones. Most of those substances are able to change the

immunecellsbehaviour.29

Psychologicalchronicstresscanchangeantibody(ab) pro-ductionandkineticsaftervaccination,inparticularafterthe influenzavaccineisgiventoelderlypeoplewhotakecareof spouseswithdementia.9–12

Various studies of elderly people have found an

asso-ciation betweenexposure toa long-term stressor (such as

dementiaspousecaregiving)andasmallproportionofthem who reachedatleastabHAItitresthatwere fourfoldwhat

they had before flu vaccination, assessedone monthafter

vaccination.13–15Bereavementandmarriageseemtobe

asso-ciatedwithantibodyresponsetoinfluenzavaccinationinthe elderlyaswell.17

In our study, as insome other studies involving young

adults,18,23–25 wedid notfind any association between the

presenceofchronic stress innurses andthe proportionof themthatreachatleastfourtimestheabHAItitrelevelsthey hadbeforefluvaccination.Onthecontrary,otherstudieshave foundanassociationamongperceiveddistress,19lifeevents,20

neuroticism21andloneliness22andtheimmuneresponseto

fluvaccination,assessedonemonthorfiveweeksafter. Itispossiblethatmethodologicalissuescanexplain dis-crepanciesinresultsverifiedinstudieswithyoungergroups, suchas:(1)differentwaysofcharacterisingindependent vari-ables;(2)sampleswithdifferingdemographiccharacteristics anddimensions;(3)differinghistoriesoffluvirusexposure.

Withrespecttothelatterissue,ourstudyfoundthat non-respondershadsignificantlyhigherabHAIAH1N1,AH3N2and

BtitresatT0thanrespondergroups.Therefore,aspostulated

byBeyerandcolleagues,28abHAItitresatT

0,showedtobean

importantconfoundingvariablewhenstudyingthe

relation-shipbetweenstressandimmuneresponsetofluvaccineone

monthaftervaccinationandmustbeconsidered.

Nevertheless,wefoundanassociationbetweenthe pres-enceofchronicstress(measuredinthreedifferentways)anda dropinabHAI(AH1N1)atT6.Otherstudiesalsofoundan

asso-ciationbetweendistress,19,25lifeevents,20lifeeventsweighed

withperceivedstress,23neuroticism,21orloneliness22anda

drop inabHAIfour tosixmonthsaftervaccination.Those associationswerefoundforatleastonestraincomposingthe fluvaccine.

(8)

Ourstudyfoundalargeproportionofnurseswithchronic stressintheHAIabAH1titredropgroupatT6,ascompared

tothenochangeinHAIAbAH1titregroupatT6,whenwe

measuredstressbytriangulationmethod,usinginterviewor GHQ12toassessperceivedstress,andusingthecombination

ofthethreemethods(asdescribedinthemethodssection).We didnotfindanystatisticallysignificantassociationwhenwe assessedthepresenceofstressbythetriangulationmethod

but using the MBI exhaustion scale to measure perceived

stress.ApossibleexplanationisthefactthattheMBI exhaus-tionscalemeasuresspecificallywork-relatedstressandthe possibleimmunologicrepercussionsofchronicstressseemto beindependentofthestresssource.

As described in other studies,19–23,25 the association

betweenstressandadropinabHAIatT6 didnotoccurfor

allthevaccinestrainscomponents.

Strainnoveltycan beanimportantfactorinthat analy-sis,asarguedbyotherauthors.15,20Pressmanandcolleagues,

forexample,onlyfoundanassociation betweenstressand

adropinHAIab,fourmonthsaftervaccination,forastrain thatwas notincludedinprevious vaccinationsthe partici-pantsreceived.25Inourstudy,theexclusivestrainthatwas

not included in flu vaccines in the three preceding years

wastheA(H1N1)strain.

InPortugalthepredominantcirculatingstrainswithhigh fluactivitysince1990havebeenA(H3N2)andB.From1990to

thebeginningofthestudy,theA(H1N1)strainwasonly

pre-dominantin2005,simultaneouslywithstrainB,and2005was ayearwithverylowfluactivity.30WealsoknowthatAstrains

undergomoredriftmutationsthanBstains,31sothiscan

con-tributetotheirbeingarelativenoveltyfortheparticipants’

immunesystem.

Finally,inourstudy,theA(H1N1)influenzastrainprovedto

bethemostimmunogenicone,showingariseintheHAIAb

titregeometricmeanof11.1.A(H3N2)andBstrainsshowed

risesof6.2and 4.6times,respectively, betweenT0 andT1.

Itispossiblethatthebestimmunogenicityobservedforthe A(H1N1)strainwasrelatedwiththefactthatsome

partici-pantshadhadaprimaryinfectionwithanA(H1N1)strain,so

theresponsetoA(H1N1)antigenshavebeenmorerobustin

them.32Thatcouldbeafactorthatmayinfluencethe

detec-tionoftheassociationbetweenstressanddropsinHAIabafter aperiodoftime.

Given that our sample was not a randomised sample

becauseitdependedonnursesvoluntarilybeingvaccinated andparticipatinginthestudy,weanalyseddistribution dif-ferencesforsomevariablesintheHAIabAH1titredropgroup

atT6andthenochangeinHAIAbAH1titregroupatT6thatare

notincludedindropoutcriteria.Astherearealotofvariables

forwhichwedonotyetknow iftheycaninfluence

immu-nity,westudiedthosethataremostreferredtointherelevant literature.33

We did not find any differences in the distribution of

thestudiedvariablesinthetwogroupsatT6.Nevertheless,

wedecidedtoincludeabAH1 titresatT0, abAH1 titresat

T1 and age in multiple logistic regression. The reason for

includingthefirsttwovariableswasthestrongsuggestionin literaturethattheycaninfluenceabtitresaftervaccination (immuneresponse),28eventhoughwefoundnoreferencesto

theinfluencetheyhaveonadropintitressixmonthsafter

fluvaccination.Ageisstronglyrelatedwithimmunity33but

wedidnotfindanydifferenceintermsofagebetweenthe

twogroupsconsideredatT6atthesignificancelevelwe

con-sidered(5%).Ifweconsideredasignificancelevelof10%the

result would be different. Hence, we also included age in

themultivariateanalysis.

Afterthemultivariateanalysis,westillfoundan associ-ation withstatistical significance between the presenceof chronicstressandtheHAIabAH1titredropgroupatT6,when

weassessedstressinthreedifferentways,allofthemusing thetriangulationmethod,assuggestedbyCoxandcolleagues, asagoodwayofmeasuringstress.26Therefore,the

relation-shipthatwefoundbetweenchronicstressandadropinHAIab atT6supportsthethesisthatstresscannegativelyinfluence

HAIabtitressomemonthsafterfluvaccinationeveninpeople inadultsundertheageof60.Aswecouldnotice,thisisthefirst study assessingthe associationbetweenchronicstress and immuneresponsetoinfluenzavaccineinhealthcareworkers, whoisanimportanttargetgroupforinfluenzavaccine. There-fore,inanoccupationalhealthenvironment,itisreasonable toconsiderthepossibleinterferenceofchronicstresswithab titreswhenweimplementvaccinationprogrammestoprevent biologicaloccupationalrisks.

Funding

AutoridadeparaasCondic¸õesdeTrabalho(ACT)fundedthe laboratorialevaluationofthestudy.

Conflicts

of

interest

Theauthorshavenoconflictsofinteresttodeclare.

r

e

f

e

r

e

n

c

e

s

1.ChangEM,DalyJW,HancockKM,BidewellJ,JohnsonA, LambertVA,etal.Therelationshipsamongworkplace stressors,copingmethods,demographiccharacteristicsand healthinAustraliannurses.JProfNurs.2006;22:30–8.

2.GrahamIW,AndrewsT,ClarckL.Mutualsuffering:Anurse’s storyofcaringforthelivingastheyaredying.IntJNursPract. 2005;11:277–85.

3.XianyuY,LambertVA.Investigationoftherelationships amongworkplacestressors,waysofcopingandthemental healthofChineseheadnurses.NursHealthSci.2006;8:147–55.

4.LindstromK.Workorganizationandwell-beingofFinnish healthcarepersonnel.ScandJWorkEnvironHealth. 1992;18:90–3.

5.SchaufeliWB.Burnout.In:Firth-CozensJ,PayneRL,editors. Stressinhealthprofessionals.Chichester:JohnWiley&Sons; 1999.p.17–32.

6.WolfgangAP.Jobstressinthehealthprofessions:Astudyof physicians,nursesandpharmacists.BehavMed.1988;14:43–7.

7.López-CastilloJ,GurpeguiM,Ayuso-MateosJL,LunaJD,Catala J.Emotionaldistressandoccupationalburnoutinhealthcare professionalsservingHIV-infectedpatients:Acomparison withoncologyandinternalmedicineservices.Psychother Psychosom.1999;68:348–56.

8.HuntM.Virology:Influenzavirus:Orthomyxovirus.In:Hunt RC,editor.Microbiologyandimmunologyonline.Chapter

(9)

thirteen[Internet].Columbia,SC:SchoolofMedicine, UniversityofSouthCarolina;2011.Availablefrom:

http://www.microbiologybook.org/mhunt/flu.htm[cited 12.07.11].

9. SegerstromSC,MillerGE.Psychologicalstressandthehuman immunesystem:Ameta-analyticstudyof30yearsofinquiry. PsycholBull.2004;130:601–30.

10.BurnsVE.Stressandantibodyresponsetovaccination: Implicationsofanimalstudiesforhumanclinicalresearch. ExpertRevVaccines.2004;3:141–9.

11.BurnsVE,CarrolD,RingC,DraysonM.Antibodyresponseto vaccinationandpsychosocialstressinhumans:

Relationshipsandmechanisms.Vaccine.2003;21: 2523–34.

12.CohenS,MillerGE,RabinBS.Psychologicalstressand antibodyresponsetoimmunization:Acriticalreviewofthe humanliterature.PsychosomMed.2001;63:7–18.

13.Kiecolt-GlaserJK,GlaserR,GravensteinS,MalarkeyWB, SheridanJ.Chronicstressalterstheimmuneresponseto influenzavirusvaccineinolderadults.ProcNatlAcadSciUS A.1996;93:3043–7.

14.GlaserR,Kiecolt-GlaserJK,MalarkeyW,SheridanJF.The influenceofpsychologicalstressontheimmuneresponse tovaccines.AnnNYAcadSci.1998;840:649–55.

15.VedharaK,CoxNK,WilcockGK,PerksP,HuntM,AndersonS, etal.Chronicstressinelderlycareersofdementiapatients andantibodyresponsetoinfluenzavaccination.Lancet. 1999;353:627–31.

16.VedharaK,BennettPD,ClarkS,LightmanSL,ShawS,PerksP, etal.Enhancementofantibodyresponsestovaccination intheelderlyfollowingacognitive-behaviouralstress managementintervention.PsychotherPsychosom. 2003;72:245–52.

17.PhilipsAC,CarrolD,BurnsVE,RingC,MacleodJ,DraysonM. Bereavementandmarriageareassociatedwithantibody responsetoinfluenzavaccinationintheelderly.BrainBehav Immun.2006;20:279–89.

18.VedharaK,McDermottMP,EvansTG,TreanorJJ,PlummerS, TallonD,etal.Chronicstressinnonelderlycaregivers: Psychological,endocrineandimmuneimplications.J PsychosomRes.2002;53:1153–61.

19.MillerGE,CohenS,PressmanS,BarkinA,RabinBS,TreanorJJ. Psychologicalstressandantibodyresponsetoinfluenza vaccination:Whenisthecriticalperiodforstressandhow doesitgetinsidethebody?PsychosomMed.2004;66: 215–23.

20.PhilipsAC,BurnsVE,CarrolD,RingC,DraysonM.The associationbetweenlifeevents,socialsupportandantibody statusfollowingthymus-dependentand

thymus-independentvaccinationsinhealthyyoungadults. BrainBehavImmun.2005;19:325–33.

21.PhilipsAC,CarrolD,BurnsVE,DraysonM.Neuroticism, cortisolreactivityandantibodyresponsetovaccination. Psychophysiology.2005;42:232–8.

22.PressmanSD,CohenS,MillerGE,BarkinA,RabinBS,Treanor JJ.Loneliness,socialnetworksizeandimmuneresponseto influenzavaccinationincollegefreshmen.HealthPsychol. 2005;24:297–306.

23.BurnsVE,CarrolD,DraysonM,WhithamM,RingC.Life events,perceivedstressandantibodyresponsetoinfluenza vaccinationinyounghealthyadults.JPsychosomRes. 2003;55:569–72.

24.LarsonMR,TreanorJJ,AderR.Psychosocialinfluenceson responsestoreducedandfull-dosetrivalentinactivated vaccine.PsychosomMed.2002;64:113.

25.PressmanS,CohenS,MillerG,RabinB.Stressandantibody responsetoinfluenzaimmunizationincollegefreshman. BrainBehavImmun.2002;16:208[abstract].

26.CoxT,GriffithsA,Rial-GonzálezE.Researchonwork-related stress.Luxembourg:OfficeforOfficialPublicationsofthe EuropeanCommunities;2000.

27.WorldHealthOrganization.Identificationofisolatesby hemagglutinationinhibition.In:WHO,editor.WHOanimal manual:Diagnosisandsurveillance.Geneva:Department ofCommunicableDiseaseSurveillanceandResponse;2002. p.28–36.

28.BeyerWE,PalacheAM,SprengerMJ,HendriksenE,TukkerJJ, DarioliR,etal.Effectsofrepeatedannualinfluenza vaccinationsero-responseinyoungandelderlyadults. Vaccine.1996;14:1331–9.

29.CohenN,KinneyKS.Exploringthephylogenetichistoryof neural-immunesysteminteractions:Anupdate.In:AderR, editor.Psychoneuroimmunology.London:ElsevierAcademic Press;2007.p.1–38.

30.Rebelo-de-AndradeH,FalcãoJM,CrespoN.Gripesazonal epandémica.ProgramadeIntervenc¸ãodoINSA.Lisboa: InstitutoNacionaldeSaúde;2006.

31.USA.CDC(CentersforDiseasesControlandPrevention). Preventionandcontrolofinfluenza:Recommendationsofthe AdvisoryCommitteeonImmunizationPractices(ACIP). MMWR.2007;56RR-6:1–54.

32.PereiraMS.Globalsurveillanceofinfluenza.BrMedBull. 1979;35:9–14.

33.LoverenHV,AmsterdamJG,VandebrielRJ,KimmanTG, RumkeHC,SteerenbergPS,etal.Vaccine-inducedantibody responsesasparametersoftheinfluenceofendogenous andenvironmentalfactors.EnvironHealthPerspect. 2001;109:757–64.

Imagem

Table 1 – Stress in non-responders and in responders AH 1 , AH 3 and B at T 1 . HAI ab groups at T 1 Chronic stress
Table 4 – Variables distribution (stress not included) in HAI ab AH 1 titre drop group at T 6 and in no change in HAI ab AH 1
Table 5 – Multivaried analysis (multiple logistic regression) for stress (assessed by triangulation method using GHQ 12 , using interview and using the combination of the three methods) in HAI ab AH 1 titre drop group at T 6 considering age, HAI ab AH 1 ti

Referências

Documentos relacionados

leitores e, desse modo, as diferentes formas de ler, distintas aprendizagens e o ensino da leitura. Nesta direção, as mudanças da relação entre leitor e livro, ao longo da história, a

This paper aims at studying the frequence of rhinosinusitis after bone marrow transplant and to study the association between rhinosinusitis and chronic graft versus

study was to assess the association between emotional stress and systemic and oral alterations in nurses working at a public referral hospital in a Brazilian mid-sized city..

The aim of the present study was to estimate vaccine coverage and to identify factors related to vaccination against influenza in the elderly

The action of gracilis (adductor, internal rotator and flexor) is balanced by the sartorius (abductor, external rotator and flexor), increasing hip flexion by 20º

Pretendemos também, neste nosso evento, proporcionar um momento de reflexão sobre estas duas formas de expressão popular, juntando num mesmo espaço alguns

Objectives - The aim of this study was to evaluate the association between Inlammatory Bowel Disease and oral mucosa lesions and symptoms, and complementary to evaluate

This study aimed to examine whether or not renal transplantation result in improvement in oxidative stress and to assess the association between oxidized LDL (ox-LDL) and