www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Inflammatory
markers
in
palatine
tonsils
of
children
with
obstructive
sleep
apnea
syndrome
夽
Vitor
Guo
Chen
a,∗,
Viviane
Maria
Guerreiro
da
Fonseca
a,
Jônatas
Bussador
Amaral
b,
Cíntia
Meirelles
Camargo-Kosugi
b,
Gustavo
Moreira
c,
Eduardo
Macoto
Kosugi
a,
Reginaldo
Raimundo
Fujita
aaUniversidadeFederaldeSãoPaulo(UNIFESP),EscolaPaulistadeMedicina(EPM),DepartamentodeOtorrinolaringologiae CirurgiadeCabec¸aePescoc¸o,SãoPaulo,SP,Brazil
bUniversidadeFederaldeSãoPaulo(UNIFESP),EscolaPaulistadeMedicina(EPM),DepartamentodeOtorrinolaringologiae CirurgiadeCabec¸aePescoc¸o---CentrodePesquisaTranslacionaldeOtorrinolaringologiaeCirurgiadeCabec¸aePescoc¸o,São Paulo,SP,Brazil
cUniversidadeFederaldeSãoPaulo(UNIFESP),EscolaPaulistadeMedicina(EPM),InstitutodoSono,SãoPaulo,SP,Brazil
Received26March2018;accepted2August2018 Availableonline31August2018
KEYWORDS Inflammation mediators; Obstructivesleep apnea; Palatinetonsil; Child Abstract
Introduction:Obstrutivesleepapneasyndromeischaracterizedbyrepeatedepisodesofupper airwayobstruction,associatedwithintermittenthypoxiaandhypercapnia,andthemainrisk factor inchildhood isadenotonsillar hypertrophy. The lymphocytes in these structures are responsibleforlocalandsystemicimmuneresponses.
Objective: Verifythelevelsoftheinflammatorymarkers,IL-1,IL-4,IL-6,IL-8,IL-10,IL-15, TNF-␣, CRP and␣1-GP,in thetonsils ofchildren with andwithoutobstructive sleepapnea syndrome.
Methods:Thiscross-sectionalprospectivestudyincluded34childrenwithcomplainsof snor-ing,difficultybreathingduringsleeporrecurrenttonsillitis.Patientsunderwenttoacomplete otorhinolaryngologicalexamination,nasalendoscopyandpolysomnographyandweredivided into twogroupswith17 childreneach:obstructivesleepapneasyndromegroupandcontrol group.Allunderwentanadenotonsillectomy.Cytokinesweremeasuredinthecollectedtonsils (ELISAandMultiplexmethods).
夽 Pleasecitethisarticleas:ChenVG,FonsecaVM,AmaralJB,Camargo-KosugiCM,MoreiraG,KosugiEM,etal.Inflammatorymarkersin
palatinetonsilsofchildrenwithobstructivesleepapneasyndrome.BrazJOtorhinolaryngol.2020;86:23---9.
∗Correspondingauthor.
E-mail:vitor.chen@unifesp.br(V.G.Chen).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.
https://doi.org/10.1016/j.bjorl.2018.08.001
1808-8694/©2018Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
Results:StatisticallysignificantincreasingwereobservedbetweenIL-8andIL-10cytokinesof patientswithobstructivesleepapneawhencomparedtothecontrolgroup;alsobetween c-reactiveproteinand␣1-GPofthetonsilscorticalregioninchildrenwithobstructivesleepapnea syndromewhencompared withthemedullaryregion.There werenostatisticallysignificant differencesfortheremaininginflammatorymediators.
Conclusion:Aftertheanalysisofthelevelsofproandanti-inflammatorymarkers(IL-1,IL-4, IL-6,IL-8,IL-10,Il-15,TNF-␣,CRP,␣1-GP)inthetonsils,weobservedhigherlevelsofmarkers IL-8andIL-10inpediatricpatientswithobstructivesleepapneasyndrome.
© 2018 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). PALAVRAS-CHAVE Mediadoresde inflamac¸ão; Apneiaobstrutivado sono; Tonsilapalatina; Crianc¸a
Marcadoresinflamatóriosemtonsilaspalatinasdecrianc¸ascomsíndromedaapneia obstrutivadosono
Resumo
Introduc¸ão:Asíndromedaapneiaobstrutivadosonoécaracterizadaporepisódiosrepetidos deobstruc¸ãodasviasaéreassuperiores,associadosahipóxiaintermitenteehipercapnia,eo principalfatorderisconainfânciaéahipertrofiaadenotonsilar.Oslinfócitosnessasestruturas sãoresponsáveisporrespostasimuneslocaisesistêmicas.
Objetivo:Dosarosmarcadoresinflamatórios,IL-1,IL-4,IL-6,IL-8,IL-10,IL-15,TNF-␣,PCRe ␣1-GP,nastonsilasdecrianc¸ascomesemsíndromedaapneiaobstrutivadosono.
Método: Estudamosprospectivamente34crianc¸asquesequeixavamderonco,dificuldadepara respirar duranteo sono outonsilites recorrentes. Os pacientesforam submetidos a exame otorrinolaringológicocompleto,endoscopianasalepolissonografiaeforamdivididosemdois gruposcom17crianc¸ascada:síndromedeapneiaobstrutivadosonoecontrole.Todosforam submetidosàadenotonsilectomia.Ascitocinasforammedidasnastonsilascoletadas(métodos ELISAeMultiplex).
Resultados: Comdiferenc¸asestatisticamentesignificantes,observou-seaumentodascitocinas IL-8eIL-10empacientescomapneiaobstrutiva dosonoemcomparac¸ãoaogrupocontrole, assimcomoaumentodosníveisdeproteínaCreativaede␣1-GPnaregiãocorticaldastonsilas decrianc¸asportadorasdesíndromedaapneiaobstrutivadosonoemcomparac¸ãocomaregião medular.Nãohouvediferenc¸asestatisticamentesignificantesparaorestantedosmediadores inflamatórios.
Conclusão:Apósaanálisedosníveisdemarcadorespróeanti-inflamatórios(IL-1,IL-4,IL-6, IL-8,IL-10,Il-15,TNF-␣,PCR,␣1-GP)nastonsilas,observamosníveismaisaltosdemarcadores IL-8eIL-10empacientespediátricoscomsíndromedaapneiaobstrutivadosono.
© 2018 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Obstructivesleepapneasyndrome(OSAS)isoneofthe sleep-disordered breathing (SDB) defined as repeated episodes of upperairway obstruction, associated withhypoxia and intermittent hypercapnia.1 SDB includes primary snoring,
upperairwayresistancesyndromeand,asthemost impor-tantcondition,OSAS.2SDBisverycommoninchildhoodand
itisestimatedthat3%---26%ofyoungchildrenhavehabitual snoringand1.2%---5.7%haveOSAS.3---5
It is suggested that OSAS can induce a systemic pro-inflammatoryresponse andits magnitudecanbe involved in the final morbidity.6 Alberti et al.7 measured the
lev-elsofthepro-inflammatorycytokinesIL-1,IL-6andTNF-␣ andanti-inflammatorycytokinesIL-10andTGF-inpatients
with OSAS. An increase in TNF-␣ and IL-6 was observed, whencomparedwiththecontrolgroup.Recently,ithasbeen shown that the spontaneous TNF-␣ production by mono-cytesisincreasedinadultpatientswithmoderateorsevere OSAS and that it regresses after treatment with Continu-ousPositiveAirPressure(CPAP).8Gozaletal.9demonstrated
thatsurgical treatmentofOSAS(astandard treatmentfor the disease in children) resulted in significant reductions in TNF-␣ levels, with reciprocal sleep latency prolonga-tion.Furthermore,ithasbeenshownthatC-ReativeProtein (CRP)isrelatedtoOSAS-mediatedcognitivemorbidity.10The
increaseinserumlevelsofCRP,IL-6andTNF-␣areimportant risk factors for atherosclerosis, cerebrovascular accident (stroke)andcardiovasculardiseases,11andtheirlevelsare
only the pro-inflammatory cytokines, but also blocks the expression of anti-inflammatory cytokines, such as IL-10, that inhibits awide rangeof pro-inflammatoryresponses, includingthoseaffectingthevesselwall.15---17
The main risk factors for OSAS in childhood is adeno-tonsillar hypertrophy,obesity,neuromusculardiseases and craniofacial alterations.18 Beyond these factors, palatine
and pharyngeal tonsil hypertrophy stand out as the main etiologies.19---21 The exact mechanism underlying
follicu-lar lymphoid proliferation and hyperplasia remains poorly understood. In adults,thereareseverallines of evidence suggestingthatlocalandsystemicupperairway inflamma-tionentailsthepathophysiologyofupperairwaymechanical dysfunction.Ithasbeenshownthatthenumberofimmune cells is significantly higher in the mucosa and muscle of adults with OSAS.22 Similar increases in systemic and
regionalinflammatorymarkers havealsobeen reportedin childrenwithOSAS.10Therefore,itisassumedthatcell
pro-liferationinthepalatinetonsiltissueofchildrenwithOSAS isdifferentfromthatinchildrenwithrecurrenttonsillitis, possiblyreflectingthepathologicalmechanismsandtypesof cellinvolvedinupperairwaylymphoidtissueproliferation inthesetwosituations.23 Consideringthat,theaimof the
presentstudywastoassessOSAS’impactoninflammatory patternofpalatinetonsilsofchildren.
Methods
Studypopulation
Thirty-fourpatientsassistedataPediatric Otorhinolaryngol-ogyClinicaged3---12yearsofbothgenders,whounderwent tonsillectomy from October 2013 to June 2014 for OSAS, primary snoring or recurrent tonsillitis treatment, were prospectivelyevaluated.
OSAS was considered present when polysomnography parametersdemonstratedobstructiveApnea Index(AI)≥1 eventperhourorApnea-HypopneaIndex(AHI)≥1.5events perhourandminimaloxygensaturation(SpO2nadir)≤92%. So,absenceofOSASwasconsideredwhenpolysomnography parametersdemonstratedAI<1eventperhourorAHI<1.5 eventsperhour andSpO2nadir>92%.Primarysnoringwas considered in the presence of habitual snoring with the absenceofOSASconfirmedbypolysomnography.And recur-renttonsillitiswasconsideredbytheParadise’scriteria24in
theabsenceofOSASconfirmedbypolysomnography. Inclusioncriteria:
- Agebelow12years;
- SurgicalindicationfortonsillectomyduetoOSAS,primary snoringorrecurrenttonsillitis;
- TonsillectomyperformedbetweenOctober2013andJune 2014;
- Childrenor parents/guardians whoaccepted to partici-pateinthestudy.
Exclusioncriteria:
- Establishedorunderinvestigationsyndromewithorofacial alterations;
- Pulmonaryorcardiacdiseasesandobesity;
- Establishedor underinvestigation diseases ofmetabolic ormyopathicorigin;
- Upperairwayinfectionatthetimeofsurgery; - Immunodeficiency;
- Previoustonsillectomy;
- Didnotunderstandtheinitialinstructions;
- Didnotundergotheassessmentsinpredeterminedperiods accordingtostudyprotocol.
Studydesign
ThisstudywasapprovedbytheInstitutionalReview Board underprotocolnumber97,863andwritteninformedconsent wasobtainedfromallchildren’sparentsand/orguardians.
It was a cross-sectional study based on two groups: OSASgroup,formed by17childrenwithOSASandwithout recurrent tonsillitissubmitted to tonsillectomy; and Con-trolgroup,formed by17childrenwithoutOSASsubmitted totonsillectomy due toprimary snoring and/or recurrent tonsillitis.
Afterinclusion and exclusioncriteriawere considered, children were submitted to bilateral tonsillectomy (with orwithoutadenoidectomy)undergeneralanesthesiainan operatingroomofuniversity’shospital.Palatinetonsilswere removedtogetherwiththeircapsulesbycold-knifesurgery, briefly stored in a container with dry ice at −80◦C and carriedtothelabtobeprocessed.Palatinetonsilswere sec-tionedintotwoparts,corticalandmedullaryzonesandthe following inflammatory proteins concentration were mea-sured:Alpha-1acidglycoprotein(␣1-GP),C-ReativeProtein (CRP),Interleukin(IL)-1,IL-4, IL-6,IL-8, IL-10,IL-15and tumornecrosisfactor(TNF)-␣.
Inflammatorymediators’concentrationswerecompared betweencorticalandmedullaryzonesforeach group,and thentotalconcentrationsofeachgroupwerecompared.
Immunologicalanalysis
The palatine tonsil samples were sectioned into two parts, cortical and medullary. Subsequently, the tissue wasmechanicallydissociated(TissueRuptor,Qiagen,Hilden, Germany)inan Eppendorftube containing400Lof RPMI 1640culturemedium(Sigma---Aldrich,St.Louis,MO,USA). Subsequently,thefragmentswerecentrifugedfor5minat 20.817×gspeed.Afterprotein extractseparation (super-natantphase),proteinsamplequantificationwasperformed usingPierce’sBCAProteinAssayReagentKit(ThermoFisher Scientific,Waltham,MA,USA)asdescribedbelow.
AstandardcurvewasperformedusingBSA(BovineSerum Albumin) standard for each point of the curve, in serial dilutions.Forquantification,2mLofWorkingReagent(WR) wereusedin each Eppendorf tube. The WR mixwas pre-paredasfollows:50partsof BCAReagent Aand1partof BCAReagent B(50:1 ReagentA: B). Thetubes were incu-batedfor30minat37◦Cinthedarkandweresubsequently readinaspectrophotometer(NanoDrop2000ThermoFisher Scientific,Waltham,MA,USA)atawavelengthof562nm.
Aimingtoequatetheassessedproteinconcentrationin allsamples,itwasstandardizedthatallwereata concen-trationof3000g/mL.
Afterbeing subsequently placedin 2mL conicaltubes, these samples were stored at −80◦C. ␣1-GP was ana-lyzed by ELISA reading kit (USCN Life Science), CRP by Milliplex-HumanCVDPanel3readingkit(MERK®),andIL-1, IL-4,IL-6, IL-8, IL-10,IL-15and TNF-␣ byMilliplex-Human Cytokine/Chemokinereadingkit(MERK®),followingthe pro-ceduresandrecommendationsofeachkitmanufacturer.
Statisticalanalysis
Normal distribution of data was verified by Kolmogorov---Smirnov test. The comparison between inflammatorymediatorsfoundinthecorticalandmedullary zones of each group was performed by Student’s t-test
for dependent samples or the Wilcoxon test, depending onthepresence or absenceof normalityin data distribu-tion,respectively. Comparison of inflammatory mediators between groups was performed by Student’s t-test for independent samples or the Mann---Whitney U-test, also dependingonthenormalityofdatadistribution.
Forallstatisticalanalysis,p-valuesbelow5%were con-sideredsignificant.
Results
Thirty-fourpatientswereincludedinthisstudy:17children intheOSASgroupand17childreninthecontrolgroup. Fif-teenpatientsweremales.Meanagewas7.55yearsoldand medianof8.5years.
Only CRP and ␣1-GP were significantly differently expressedbetweencorticalandmedullaryzonesintheOSAS Group.Thecorticalzoneshowedhigherlevelsofthese pro-teins(Table1).
In the Control Group, only IL-1 was differently expressed,presenting higherlevelsin themedullary zone (Table2).
When comparing the total inflammatory mediators’ concentration between the OSAS and Control Group, the OSASGrouppresentedsignificantlyhigherlevelsofIL-8and IL-10thantheControlGroup(Table3).
Statistically significant differences were found for the levelsofIL-8andIL-10mediators.
Discussion
Adenotonsillarhypertrophy is the main pathophysiological mechanism underlying obstructive sleep apnea syndrome (OSAS) in children. The literature shows that there is increased expression of several inflammatory response mediators in the tonsils of patients with OSAS.7,11,23 This
idea emphasizesthe hypothesis that theincrease in local inflammationinchildrenwithsleepapneacanpromote ton-silproliferation.23
Inthepresentdissertation,itwasobservedthatthe lev-elsofinflammatorymediatorsIL-1,IL-4,IL-6,IL-15,TNF-␣, CRPand␣1-GPinthetonsilsofchildrenwithOSASshowedno significantdifferencewhencomparedtothegroupwithout OSAS.Nevertheless,asignificant increasewasobserved in IL-8andIL-10levelsinpatientswithOSAS,whencompared withthecontrolgroup.Similartowhatwasdescribed,other authorsreportedthatelevatedlevelsofIL-8,achemokine thatplaysakeyroleinneutrophilandmonocyteadhesion to the vascular endothelium,have been demonstrated in patientswithOSAS.13Agrenetal.25foundanincreased
pro-ductionofIL-8andIL-10inhypertrophictonsilsofchildren withOSAS.However,thisfindingalsooccurredinthetonsils ofchildren withrecurrenttonsillitis, evenwithoutclinical signsofinfection.Furthermore,theyobservedanincrease inothercytokines,namelyIL-2,IL-4,IL-6,TNF-␣,TNF-and IFN-␥.
Otherresults, differentfromthosefoundin thisstudy, have been described in the literature. Lindberg et al.26
assessedthemarkersIL-1␣,IL-1,IL-2,IL-4,IL-6,IL-8,IL-10, TNF-␣ and TNF- in the suspension of hypertrophic ton-sil cells withsevere OSAS withno historyof infection vs.
tonsilswithrecurrentinfections. Levels ofIL-1,IL-2and IL-6showedasignificantincreaseintherecurrent tonsilli-tisgroupwhencomparedtothehypertrophygroup.Yokoe27
reportedthatIL-6andCRPlevelswereelevatedinpatients with OSAS when compared to an obese control group,
Table1 Comparisonbetweenvaluesofinflammatorymediatorsinthecorticalandmedullaryzoneofpalatinetonsilsfrom OSASGroupexpressedinpg/mL.
Mediator PalatinetonsilsOSASgroup p
Cortical Medullary Mean SD Mean SD IL-1ß 99.58 113.78 104.49 115.85 0.62 IL-4 6.16 1.58 7.17 2.92 0.20 IL-6 6.68 4.49 6.63 3.38 0.97 IL-8 1,009.27 881.07 1,168.13 1,151.96 0.42 IL-10 13.74 12.64 12.42 11.21 0.55 IL-15 3.80 0.84 3.92 1.39 0.54 TNF-␣ 47.66 22.53 53.13 29.30 0.24 CRP 15.68 18.41 8.84 11.06 0.04 ␣1-GP 10.48 9.92 7.00 6.22 0.05
IL,interleukin;TNF,tumornecrosisfactor;CRP,C-reactiveprotein;␣1-GP,alpha1-glycoprotein;SD,standarddeviation;OSAS,obstructive sleepapneasyndrome;pg/mL,picogrampermilliliter.
Table2 Comparisonbetweenvaluesofinflammatorymediatorsinthecorticalandmedullaryzoneofpalatinetonsilsofthe ControlGroup,expressedinpg/mL.
Mediator Palatinetonsilscontrolgroup p
Cortical Medullary Mean SD Mean SD IL-1ß 60.21 44.82 134.30 187.74 0.02 IL-4 6.36 3.39 6.62 3.29 0.88 IL-6 7.22 5.62 7.23 4.38 0.60 IL-8 665.22 630.84 663.67 509.48 0.30 IL-10 9.05 8.63 12.34 16.29 0.41 IL-15 3.90 1.02 4.03 1.45 0.49 TNF-␣ 43.03 14.73 45.79 13.02 0.58 CRP 12.04 11.00 13.87 15.56 0.46 ␣1-GP 10.98 9.33 11.31 12.07 0.81
IL,interleukin;TNF,tumornecrosisfactor;CRP,C-reactiveprotein;␣1-GP,alpha1-glycoprotein;SD,standarddeviation;OSAS,obstructive sleepapneasyndrome;pg/mL,picogrampermilliliter.
Table3 ComparisonbetweenvaluesoftotalinflammatorymediatorsofthepalatinetonsilsofpatientswithandwithoutOSAS, expressedinpg/mL.
Mediator Palatinetonsils p
OSASgroup Controlgroup
Mean SD Mean SD IL-1ß 102.03 112.98 97.26 139.67 0.34 IL-4 6.67 2.37 6.49 3.29 0.20 IL-6 6.66 3.91 7.22 4.96 0.32 IL-8 1,088.77 1,012.05 664.44 565.13 0.04 IL-10 13.08 11.77 10.69 12.95 0.04 IL-15 3.86 1.13 3.96 1.24 0.46 TNF-␣ 50.39 25.86 44.41 13.77 0.41 PCR 12.26 15.34 12.96 13.32 0.30 ␣1-GP 8.74 8.33 11.15 10.63 0.21
IL,interleukin;TNF,tumornecrosisfactor;CRP,C-reactiveprotein;␣1-GP,alpha1-glycoprotein;SD,standarddeviation;OSAS,obstructive sleepapneasyndrome;pg/mL,picogrampermilliliter.
showingtherewasareductionintheselevelsafter treat-ment with CPAP. It was suggested that OSAS systemic inflammation couldexist regardless of obesity. Andersson etal.28demonstratedanincreasedproductionof19
inflam-matory markers (including IL-4, IL-6 and IL-8) in human tonsilswithchronicinfectionandfounddifferentcytokine patternsinrecurrenttonsillitisgroupwhencomparedwith the infectious mononucleosisgroup. Theyrarely observed IL1 and TNF-␣ in the recurrent tonsillitis group. On the other hand, other authors identified high concentrations of IL-1, IL-6 andTNF-␣ in adenotonsillartissues, believ-ing it tobe an expression of local overproductiondue to monocyte-macrophage activation resulting from repeated stimulifrompathogenagents.29 Kimetal.23 observedthat
both the expression and the release of pro-inflammatory cytokines,such asIL-1, IL-6e TNF-␣, were increasedin cellculturesofchildrenwithOSAS.
Eventhoughthesestudiesshowchangesinthelevelsof manycytokinesstudiedinthisdissertation,itisnotpossible toidentify a consensusregarding the differencebetween
patientswithOSASand patientswithrecurrent tonsillitis. Acondition thatmight have contributedfor the factthat themajorityoftheassessedcytokinesdidnotshowany sig-nificantdifferencebetween thegroups (case andcontrol) wasthepossibilitythatbothapneaandrecurrentinfection alterinflammatorymarkerlevels.Perhapsastudycomparing thesegroupsinchildrenwithoutOSAS,recurrenttonsillitis orevenobstructivetonsilscananswerthisquestion.
Taking the present results in consideration --- IL-8 and IL-10 predominance in palatine tonsils of OSAS patients --- one may deduce that palatine tonsils do not seem to bethedeterminantfactor intheinflammatory pathophys-iology of OSAS, especially considering that IL-10 is an anti-inflammatorycytokine.
Another important factor to be discussed is the com-parison of inflammatory marker measurements between thecorticalandmedullaryregions ofthetonsils.CRPand ␣1-GP levels were higher in the cortical region of the tonsilsofpatientswithsleepapneawhencomparedtothe medullaryregion,aresultnotobservedintonsilsofchildren
withoutOSAS.IncreasedCRPserumlevelsinchildrenwith OSAS would be evidence of the presence of a systemic inflammatory process, which could also contribute to increasedproliferationof upperairway lymphoidtissue.30
This difference demonstrated between the cortical and medullaryregionsmayberelatedtothisproliferation.
Some studies on OSAS and cytokines differentiate the groupsaccordingtotheApneaandHypopneaIndex(AHI)or eventhedegreeofsleepapnea.Astudycarriedoutin2012 associatedthe elevated CRP levelsin patients with sleep apneawithitsseverity,regardless ofobesity.30 Many
stud-ieshaveassociatedincreasedTNF-␣serumlevelswithOSAS severity.31 Others have demonstratedthat theincrease in
TNF-␣andIL-6levelswereaccompaniedbyanincreasein theAHIinpatientswithsleepapnea.9However,ChuandLi32
concludedthattheincreasesinTNF-␣andIL-6aremainly influencedbytheobesityfactor.Thepresentstudyexcluded allobese children or thosewith anymetabolic/endocrine diseases,butOSASseveritywasnotconsider.
Anotherbiasis thatallergicsensitizationwasnot spec-ified.Previous studieshave reporteda highprevalence of allergy in children with OSAS.33,34 Moreover, the use of
topicalcorticosteroids in somepatients may have altered cytokineslevels,althoughthebioavailabilityofmostnasal corticosteroidsisverylow.
Lastly,onlypalatinetonsilswereincludedinthepresent study,butpharyngealtonsilsalsoplayanimportantrolein thepathophysiologyofOSASinpediatricpatientsandmay be associated with the inflammatory markers involved in sleepdisorders.Therefore,futureandmorespecific stud-ieswillneedtoevaluatetheseissuesandclarifytheroleof cytokinesinOSASversusrecurrenttonsillitis.
Conclusion
PalatinetonsilsofpatientswithOSASshowedhigher expres-sionofCRP and␣1-GPincorticalthanin medullaryzone, whereaspalatine tonsilsofpatients without OSASshowed higherexpressionofIL-1inmedullarythanincorticalzone. OSASpromoteddifferentpatternofinflammationinpalatine tonsils,withpredominanceofIL-8andIL-10whencompared tocontrols. It is not possible yet to identify a consensus regardingthe differencebetween patients withOSASand patientswithrecurrenttonsillitis.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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