Baii Medica!JOurna!(3a″ 抽edり 2019,Volume 8,Numberl:341-346P―iSSN.2089‐ 1180,E‐ :SSN:2302-2914

亀RIblЬ hed byOじ coverSys

ABSTRA(T

Background: Subcutaneous immunotherapy (SCIT) is an

established recommended treatment for allergk asthma. 5(ttprovides symptomatic relief, and it is potentially curative. ltsbuild-up phase represents vital information t0 improve patientcompliance and treatrnent 0ut(0mes.

Aim: Ihis (udy aims t0 assess the build-up phase outcomes ofsubcutaneous immunodrerapy (5OT) for pediatric allergic asthma.Methods: The retrospective cohort study comprised 65 rhildrenwith allergk asthma due to house dust mites at the end of inithlbuild-up phase of SOI (l months) fiom 2009 until 2012 at onehospital in Surabaya, lndonesia. pre-S0T cliniral evaluationincluded shn prick tests for Der p 1 and Der f l, eosinophil countstesl, and the reversibility of forced expiratory volume in a second.

The serum level of IFN-y ffHl). lt-4 (IH,), T6f-p [.,), and I[-17

' Allergy-{mmunology Divi$on,

Pediatric Health Department,

Farulty of Medicine, Universitas

Airlangga - Dr.Soetqno General

Hospital, Surabaya, lndonesia

* fonespondence to:

Anang Endaryanto,

Allergplrnrnundogy Division,

Pedia8ir Health Departmen[

taculty of Medicine, lJnirmrsitas

Aidangga - Dr. Soetomo GmenlHospital, Surabaya, lndonesia

aen daryanio.aelzrgmail.rom

Receive■ 2019‐03Ю3

A(cepted:2019‐ 03■3

Pub!ished:20190441

INTRODUCTION

House dust mite (HDM) allergen exposure isincreasingly recognized as an essential causeof allergic asthma in children, particularly inIndonesia. The prevalence of asthma in Indonesiaranges from 3-16%. HDM allergens inducesensitization in 77% of asthmatic patients.r,2Subcutaneous immunotherapy (SCIT) is anestablished recommended treatment for allergicasthma with a broad and potential evidenie-based treatment.3 n Although data are limited., theefficacy of allergen-specific immunotherapy againstpediatric asthma in Surabaya, Indonesia has beenreported in a small number of placebo-controlledsfudies.7 ro

SCIT provides symptomatic relief and ispotentially curative. The immunologic mechanismsof SCIT include all parts of the immune system.Regulatory T cells (!*) have a major pivotal rolein the immunotherapy triumph. In addition toLu", elevated suppressor cytokine levels (TGF-p),

Open access: www.balimedicaljournal.org and ojs.unud.ac.idlindex.php/bm1

The build-up phase outcome of subcutaneousimmunotherapy for pediatric allergic asthma:

A retrospective cohort study fromSurabaya, lndonesia

Anang Endaryantotx

Keywords: Pediatri( asthma, S(f, allergir mediatorGte this Artide: Endaryanto, A. 2019. Ihe build-up phase outrome ofsubcutaneous immunothenpy for pediatric allergic asthma:rettospective cohort studyfrom Surabaya, lndonesia. Eali tledkol loumalg(1):141-346. D0l: 1 0.i5562lbmj v8i1.1481

suppression of TH, cells, increased titers of IgG{well as gradual declines in the number and functi

(TH17)Were measured宙 a enzソ melinked immunosorbent

(EuSA)attheend Oftheintia:bul:dttp phase ofSCll

Resuk,Of the 65 sampた s,48(73.8%)exttbned

improvement after three months, including lZ (56.9%)

controlled asthma ar against '11 (15.9%) controlled

respectively. tosinophil counts, l[4, and lL-17 levels were

among sublerts who did not have an improvement, whereas

showed lowrr IFN-y levels and smaller wheal diameters forDer p 1 or Der f 1. Total lgt and TGt-p levels tmre not signilicantdifferent according to the asthma refinement.(onclusion: At the end of the build+p phase, S0Timprovement in most subjects with allergic asthma, andout(ome was associated with eosinophil counts, wheal

for Der p I and Derf l, as wellas IFN-y, lL4, and l[-17levels.

both of basophils and mast cells also conto the successful treatinent.1l The afOn3inend

immune mechanisms are connected and related

care costs within three months of iniand produces sustained clinical benefits aftercompletion of a treatment course, approximately 3years.''' Clinically successful SCIT is accompaniby dtered dlergen‐ specinc T cell resPOnsi

as a decreased THr/THr ratio, enhanced TGFsecretion, and T induction.ro

SCIT is admfnistered at a physician's officeleast wery six weeks for 3-5 years,,r but itnot usually confer immediate symptom :

Successful clinical outcomes require a strongpatiecommitment to treatment adherence.

each otheq acting at different times duringAllergen-specific immunotherapy reduces

data suggest that patient demographics,and insurance characteristics may subst

剣

　　　「̈

12. Komentar unruk karya penelitian : 'Judur Artikel: Distribution of iNoS Exprgssion ofiNoS Expressions and rNF Neutrophil cells as well as pGE2 and Sl00 schwanh cellDermal Nerves in The Erythema Nodosum Leprosum patients, penulis: I Gusti i,lyomanDBrmaputa, Nanny Herwanto, Luh Mas Rusyati, Wibi Riawan, Anang enaaryatto, CitaRosita sigit Prakoeswa' Nama Jumal: Bali Medical Joumar (Mari IueJr), vot-urne .iumat:7, Nomor Jurnal: I, Tahun Terbit Jumal: 201g, Halaman : Z6i_266,lSSN: 20g9- l l g0,2302'2914, Penerbit: Fakuhas Kedokteran universitas udayana ': joumar intemasionalpenulisT simtest 105 peer review ada?enelitian pada kasus'leprosi dengan p"."ni.prostaglandin pe(ahanka sistm syarafpenelitian cukup baik tulisan baii dan berlnanfaatunmk pengobatan kedepan

13. Komentar untuk karya penelitian : 'Judul Artiker: Home Humidity Increased p.isk ofTuberculosis in.Children Living with Adurt Active Tubercurosis case., eenrtis:3ua1i

-

Lestari, Florentina Sustini, Anang Endaryanto, Retno Asih, Nama Jumal: UniversaMedicina- Volume Jumal: J0. Nomor Jumal: 3, Tahun Terbit Jumat: ZOtt, Halarran:138-145, ISSN: 2407-2230, t90?-3062, penerbil: Universa Medicina bv FaculiviMedicine Trisakti University': ISSN onrine penulis 3 peer review adu penetitian

l

membuktikan humiditas rumah lebih 75% anak akan ierkena TBC dioerluk* r"ri,n",dengan huminiditas yang baik penelirian baik tulisan baik bermanfaai *gJ ib, I

'-'14' Komentar untuk karya penelitian ; 'Judur Artikel: proteksi probiotik pada Mrfuo."Il::f Y*:i1y+g Terpanjang Lipopotisakarida Eschericha coli, p.nrLii, afpf,r-i*auf,Attlrryah. Ariani Setiawati. Andy Darma. Anang Endaryanro, I Kerut Sudiana, \bzaRanuh, Subijanto MS, Nama Jumal: Jumal Medlka Indonesiana , Volume lumatj+0,NomorJumal:2, Tahun Terbit Jumal: 2012, Halaman: 80_35, ISSN: yZS_llSi,): -'Penerbit: FK IINDIP Semarang,: ISSN online penulis4 peer review adaPenelitian pa mencit yg erpajan LpS E colo lemaru proLiotik memberikan peliniunsanpada mucosa usus ileumnya Penelitian baik tulisan cuku dan bermanfaat '

.l-.-

1 5. Kome ar untuk karya penelitian : ,Judul Artikel: Studi Observasional pasca-:Pemasaran Formula Isolar prorein Kedelai pada Bayi dengan C";otu Sug..iiiAiergiTerhadap Protein Susu Sapi, penulis: Zakiudin Mu;asir, 6i"" Mrki"rd A;;; i'Fndervanro Lat,rr narni L,,'.--^..,^r:Tcrhadap PrOtch susu Sapt Pentllls:Z]kl:饉 nl、

lun,gr,5hatiukri:F:Alan[EnぬwantO,Ketut Dcwi Kumarawatl,Bud Sc`abudh“ an,s話話1。 :。 ,‐J」蠣:高島HudyOno,Mdva Lo面 sa,A`面 Saね■7an,Nallla JumJ:Sai f`瓢■:Iぶ:Nomor Jurnal:4,Tahun Terbit Jurna1 2013,Halaman:237-243,ISSN:0854r5030,PenerЫt Badan pcneめれkaan Doher Anak lndoneStt ISsN oJ品pCttfl::W,dalcndⅢ an,PJapr∝ CⅢSuSu kcddecukupm」 :ぶ 葛 I灘mnggandkan anよ yg」 ctti dgn sutt sapl,pCndilan balk ttilヽ all:岳IL::

16 Komcntar untuk karya penchdan:り udul Artikcl:Kcscsuaian GcJala KlinisHagl uji Tusuk Kuli dan uji ProvOkaj Makanapada RLakξ

~ζ

im;:FξfMakanan,Pendtt Az宙 n LuЫs,wisnu B_lialltこ Anang En3町語o:馬 鳳NamaJumJ:BcrkJa■ mu Keschatan Ktllldall kchmi vJ轟 1:JumalilJumali l,Tahun Tcrbit Jurnal:2019,Halarllan:106‐ 116,ISSN:2450-4082,1Pcnerblt B賀 /SMF]mu Kesehatall Ku‖ ldan Kdalnin FK UNAIR―RSUDSi6SN omhc rndヽ 3 peer К宙ewada lcndilnlcr」 mょmmによJt LEkcsesuJall antara haJl■ itusuk kJl dengan lla● lJpおigittlgEII』轟詰baik ttllisan baik dan bennafaat utk kcdcpan `~~ ~~~~-0-r‐

・・‐・̂ヽ

17.Komentar untuk hヮa pendman:Iudゴ A面kcl:Enahnced Ef「lcacy ofImmunOtteraphy h ChhOOd Altr」cttStⅢ

りyPЮЫ∝おS,P:I轟 :ご鳳 範

:15,

,2338-

EndttantO,MIalnllawat NamaJumJI Mttdah Fdh Mcdica“屁 ::ζ猛 :v

Jun al:54,NOmorJumali l,Tahun Terbit Jumal:2018,Halarnan:64-74,ISSN:

8393,2599-056X,Pcncrbit:GRAヽ 41K FK UNAIR,DOI:http 77/dx doi ory10 20473/fmi v54i1 80551 1SSN onlinc pcnuhs i pecr re宙 cw

雪りI翌■弯,1ぬn dCtty aЫ hTa pa,a aP,k dCngan ttli語 だ」subi心が

baik tulisan balk khusus utk pcnycbab alcrgi bcl:nanhat

18. Komentar untuk karya penelitian : ,Judul Anikel: Gambaran Klinis Steven

Syndrome dan Toxic Epidermal Necrolysis pada pasien Anak, penulis: AnnisaAnang Endaryanto, Afif Nurul Hidayati, Nama Jumal: Berkala Ilmu KesehatanKeJamin, Volume Jumal: 30, Nomor Jurnal: 2, Tahun Terbit Jumal; 201g, Hala110,6SN:1978‐ 4279,25494082,Pcnc曲 :iaysMFi品 蓬轟:面温 iKelamin FK UNAIR― RSUD Di Soctomo,DOl:

terdapat

influence treatment adherence. " Patient educationregarding the treatment course and the slow effectare important factors for improving complianceand treatment outcomes.r" One-third of treatedpatients fail to complete SCIT. Among those whocomplete SCIT, another one-third (34.6yo) didnot believe that the therapy was eftbctive.': TheSCIT satisfaction scores at the end of treafmentwere higher than those in the first year of therapyamong adherent patients.'s The duraUon of SCITmay be prolonged (5 years or more) depending onthe clinical response ofthe subjects. Currently, nospecific laboratory tests or biomarkers are availableto distinguish patients who will relapse tiomthose who will enjoy prolonged clinical remissionafter discontinuing SCIT." The duration of SCITshould be individualized from the patients clinicalresponse, disease severiry adverse events (AEs),and preferences.zr)The build-up phase (3 months)clinical outcomes of SCIT represent valuableinformation for patient education to improvepatient compliance and treatment outcomes. Thosecould be according to disease severity, clinicalresponse, and immune response to SCIT.

METHODS

SubjectsThe retrospective cohort study comprised 65children vdth allergic asthma due to HDMallergens who finished the initial build-up phaseof SCIT (3 months) from 2009 until 2012 at Dr.Soetomo General Hospital in Surabaya, Indonesia.The subjects were 6-17 years old and they had adiagnosis of asthma as defi.ned by the AmericanThoracic Society (i.e., "a disease characterized byincreased responsiyeness ofthe trachea and bronchito various stimuli and manifested by widespreadnarrowing of the airway that changes in severityeither spontaneou^sly or as a result of therapy") for3 3 months. The inclusion criteria were as follows:pre-bronchodilator forced expiratory voiume in Is (FEVI)'60% and € 907o of the Polgar predictednormal value, reveals the reversibility criteriadefined as an increase in FEVI , l2o/o fromthe pre-bronchodilator value l5-30 min after tw<r actuationof salbutamol pMDI (100 mg/actuation), and fitsthem with the GINA criteria tcrr uncontrolledasthma.

A skin prick test (SPT) was applied toexamine sensitivity to the following HDMallergens (Allergopharma, Reinbek, Germany):Dermatophagoides pteronys.sinus (Der p l) andDermatophagoides Jarinae (Der f l). ReactMtyto HDM allergens in the SPT was identifiedvia allergen-induced wheals with an equal orlarger diameter mean than histamine-induced

IgE levels were measured usingsystem (Thermo-Fishea U

Informed consentwas obtained from eitherpatient or his or her legal guardians beforeinclusion. The ethics committee of Dr.Hospital approved this study. General dataincluding name, address, age, gender, bodybody height, and telephone number - were collecand recorded for all participants. Amedical and allergy history was obtained forsubjects, especially on allergic asthma andduration, as well as details about allergiescontroller medications for family members.

Clinical evaluationsBased on Dr. Soetomo General Hospital guidelfor SCIT, the authors reviewed subjects' dime&cal records on &ug prescriptions, theof exacerbation, AEs during immunotherapy,the results of lung function tests and serumIgE levels over the treatment period. The subjecdiary cards recorded symptoms and medicatiscores, including daytime symptoms, limitationactivities, nocturnal symptoms or awakening,for reliever or rescue keatment, lung function,exacerbation history.

The level of asthma control was recordedeach patient's standardized hospital medicalbased on GINA guidelines. Controlledwas defined as daytime symptoms no moretwo types per week, no limitation of activities,nocturnal symptoms or awakening, use ofor rescue treatmealt no more than two typesweek, normal lung function, and nohistory. Second, partially controlled, theof at least one criterion among daytime rymmore than fwice per week, any limitationactivities, any n<lcturnal symptoms or awakenineed for reliever or rescue treatment moretwice per week, less than 80% predicted orlung function result and one or more exacerbatiperyear. Atleast, uncontrolled asthma, theof at least three of the criteria for partial control.

As for each patient, the total numbermedications taken daily (systemicnasal cromoglycate, ocular cromoglycate,2 agonist) was recorded on the daily diary caSymptoms and medication scores were determias the monthly cumulative values obtainedsumming the daily scores. The clinicalalso included SPTs forDerp I and Derf 1, eosicounts, and assessment of the reversibilityFEVI. The immunological assessment includedexamination of the plasma levels of IFN-y (TH

wheals. 'lotal

ImmunoCAPSweden).

i|;o ro,l, rcF-B (T,"s"), r-r7 (rH,?), and tot

Published by DiscoverSys I Bali Med 12019; 8(r):3.t1-3,t6 I doi: t 0.1 5562,/bmj.v8il .14

I oRtctrual ARTICLE

Agc(ycars)

Body Weight(kgs)

Body Hdght(Cm)

Mde/Female(n)

Daytimc wmptOms′ wcck(■ )

LintatiOn oFacthttties/week(n)

Nocturnalsymptoms Or awη kenhg/month(■ )

Need for reliever or rescue trcatment/weck(n)

姉 g ttnctiOn,FEVl(%prcdlcted)

Exacerbatlons/month(n)

Blood eOsinophil count(x106ノ L)

Totd lgE(kU几 )

Skin prick test fOr Der p l,wheal(mm)

Table 1. Demographic and clinical parameters of pre-SCITpatients

____pemOgraphicand clinic1l parameters MeanISD〕

everyweek ftrr 14 weeks, followed by once-maintenance doses. Outcomes were evaluatedthe initial build-up phase.

Statistical analysis

lhe san■ple size of 65 patients provided

power (90%) to detect a difference of l0% amonggroups(a=0.05).Sは isticd analysiswas

via multivariate testing, as well as usedsoftware. Data are presented as the mean + Sf),p-values of 0.05 or less were considered statistisignificant.

RESULTS

Table I showed the demographic and diparameters of the patients (n - 65) prior to

Symptoms and lung functionThe clinical parameters of the subj ects afterthe initibuild-up phase are shown in 'lhble ?..

and lung function significantly differed amsubjects with controlled partially controlled,uncontrolled asthma. Improvements ofandlung function were observed in 48 of65(73.8%)after threc mOnths Of scI■ includi

partiat and complete control in 37 (56.9%) and(26.2yo) subjects, respectively (Table 2).

Laboratory parametersTabie -3 preseated data for variousparameters nfter the initial build-up phase ofThe results illustrated that subjects withasthma had significantly higher eosinophilthan those with controlled or partiallyasthma (p = 0.029). Additionally, IL-4 (p =and IL-IT levels (p= 0.000) were also signelevated among subjects with uncontrolledwhereas these subjects exhibited signi-ficantlyIFN-y levels (p= 0.002) and significantlywheal diameters for Der p I (p = 0.000) andf t 1p = 0.000). Total IgE and TGF-p levels didsignificantly differ according to the improvementasthma.

Laboratory yariables at the end of the build-up phase of SCIT

9.3(1.99)

29.4(10.80)

131.7(1277)

33/32

38.1(25.54)

178(724)

4.0(2.48)

3.3(1_45)

60.2(14.45)

1.8(1.18)

739.9(40831)

238.4(219.86)

8.5(3.44)

Skin prick test for Der f 1, wheal (mm initial treatment. The standardized hospitalAbbreviations: SCITi subcutaneous immunotherapy; FEV,, forced expiratory volume records revealed that all subjects were sensitivein i s. HDMs, as evaluated via skjn test (wheal > 3 m

and all met the GINA criteria for uncontrolledTable 2. Clinical parameters after the build-up phase (after 3

months) of SCIT

‖dC麟 h鰐d

Clinical parameters p-value

Daytime symptoms (we&)

Limitation of activities (week)

Nocturnal symptoms/awakening (month)

Need for reliever/rescuetreatment (rveek)

FEV, % predictive

Exacerbations history

04(067)

0.0(0_00)

00(000)

00(000)

87、2(799)

05(052)

6.0(4.37)

0.0(0.00)

1.6(1.79)

1.0(0.70)

75.0(14.23)

1.3(0.80)

169(8.22)

0.5(0.51)

38(2.61)

3.1(1.65)

61.4(15.30

1.8(1.19)

0.000

0.000

0.000

0000

0.001

0.001

Notes: Data are presented as the mean (SD).Abbrevietions; scIT, subcutaneous immunotherapy; FEV,, forced expiratory volumeinls.

ln yitro cytokinc measurcmentsPlasma cytokines levels were measured via ELISAusing a hlman TH,/TH2/T.* cytometric bead arraykit according to the mandfacturer's instructions(BD Biosciences). All samples were examined induplicate.

lmmunotherapyAll subjects conducted SCIT with HDM allergenextract produced by the Dr. Soetomo GeneralHospital Pharmaceutical Unit. The treatment periodwas divided into two phases: an initial build-upphase and a maintenance phase. In the initial build-up phase, subjects received subcutaneous injectionsof gradually increasing doses of allergen extract

Published by DiscoverSys lBoli Med J2019;8(1):341-346 | doi: I 0.1 5562rbml.v8i 1.i 481

Iigtrre I and 2 illustrated that the non-improvqdgroup had significantly higher eosinophil counfs(p = O.OOS) than the improved one (borh partiallycontrolled and controlled asthma), as well as hatdsignificantly higher IL-4 (p = 0.0a5) and IL- l7 levefs

い=0.000.Mcanwhk,In_γ levels o=o.001)

OR10NAL ARTICLE」

Ｌｆ‥ＩＩ

Table 3. Laboratory parameters after the build-up phase {after 3 months) of SCIT

SPT for Der p l(― )

SPT for Derfl(mm)

IgE(kLT几 )

Eosinophil count(X106ノ L)

IFN―Y(Pg/mL)

IL 4(Pg/mL)

TGF‐β(xlm pgノ mL)

L‐ 17(Pg/mL)

76(298)

70(212)

4692(537.21)

548.9(27350)

10.0(8.77)

6.6(9.04)

66.3(38.69)

4.6(02)

Pattallycontrolled

asthma

(n=37)

12.2(7.43)

10.7(5.92)

321.3(31099)

3213(206.17)

11.7(7.42)

1406(880)

56.9(31.73)

5_9(14.78)

Uncontro‖edasthma

(■ =17)

25.4(12.61)

188(8.20)

225.7(34422)

569.2(295.75)

45(2.80)

17.7(91.47)

47.1(2874)

16.6(10.81)

Contro‖ edLaboratory parameters asthma

(n=11)

pvalue

0.000

0.000

0.190

0.029

0.002

0.008

0.302

0.000

（くつこ］●一‐一“ちト

Abbrevietions: SCII subcutaneous immunotherapy; SPT, skin prick test.

| |

圭 日

DIS〔USS:ON

The goals of asthma therapy are to alleviatesymptoms, minimize risks nf adverse outcomes(e.g., hospitalization, loss of lung function), andminimize AEs associated with treatment.2r-:i Inour retrospective cohort study, SCIT using HDMallergen extract improved symptoms andfunction in nearly three-fourths of subjects wit3 rnonths. In line with this finding, thestudies reported that the majority ofreceiving immunotherapy exhibit increased FEf,within 3 months.''" However, these findiconflicted with those obtained by Maggie et al.lo

Larger wheal diameters for Der p 1 and Der fl tin patients with uncontrolled asthma indicates twe can create these variables to predict the clinioutcomes of SCIT.'?; The findings werefrom those of other studies in children andwhich observed significantly higher baselineof specific IgE to HDM allergens in responders.

A previous study demonstrated theof immunotherapy was in line with the

曽８一̈“諮“■〓３・

一∞

Ｔ‐「「コ・　一̈品嵩

「‐‐［一　・　　一］●●tim●●ved CrOup lmprnd G● up l

|

一

，

ル

，

い

L-1

隆

に

帽

膚

Ｆ

Ｌ

1

P=0.184 P-0・ 009

il4 lmproEd G?qp l6!rc[d GrNp

p{.{Xn p=0.000

Laboratory data for the non-improved (uncontrolled asthma)and improved groups (both partially controlled and controlledasthma) at the end of the build-up phase of subcutaneousimmunotherapy.

and wheal diameters for both Der p I (p = O.OOO)

and Der f t 1p = 0.000) were significantly lowerin the non-improved group. Total IgE and TGF-plevels were not significantly different between thegrouPs.

零t∫WI鵡Ⅷs徹樵i歯

ｌ圭

上

Figure 1.increased against post-immunotherapy." ri Onother hand, post-immunotherapic TGF-pwere also turned up progressively as gained from theprevious stud'-'. r:' r6'i- The wheal diameters for Der pI and Der f I represent the reactivity of patients tothe HDM allergens, which is caused by high levelsof allergen-specified IgE. IgG, levels were remainedlow after HDM SCIT in some patients.'s High IgG.levels are associated with high levels of IFN-y as wellas a previous research confirmed high IgG. levdswere in line with high levels of IL-10 and TGF-p.:'Higher IFN-1 levels in uncontrolled asthma

（ＥＥ〉【●鷺Ｏ

Ｌｇ●ＥＥＯ」読

|

1 ‐

|

344

krp@d Gep

P=0・001 p=0.045

Nor hprmd C@D tnFmd CranpM

P{.192 P-'=lt.ffiO

Figure 2. Serum cytokine levels in the non-improved (uncontrolled asthma)and improved groups (both partial controlled and controlledasthma) at the end of the build-up phase of subcutaneousimmunotherapy.

patients indicated an opportunity to provide otherimmunomodulators as adjunct immunotlerapies.oo

Most clinical trials that evaluated the efficacy ofSCIT had a treatment period of approximately l-2years. I' The current studyevaluated an earlyefficarybecause the effects of SCIT after the build-up phaseare considered as important data for a patienteducation program to improve compliance andtreatrnent outcomes. Nevertheless, the endotypephenotlpe, and severity of allergic diseases differamong patients. In this regard" lower eosinophilcounts and stronger THr and T immune responseswere significantly associated with uncontrolledasthma at the end of the build-up phase of SCITin pediatric allergic asthma provoked by HDMallergens.

CONCLUSION

This retrospective cohort study found that SCITimproved symptoms rn 73.8Yo of pediatric allergicasthrna at the end of the build-up phase. Theimproved outcome was associated with lowereosinophil counts, lower IL-10 and IFN-y levels,higher IL-4 levels, and smaller wheal diameters forDerplandDerfl.

Published by Discoversys lBaliMed)2019;8(1):341-346 ldoi: 10.15562,,bmj v8r1.'t48l

LEMITAT:ONS

■ e present study had scveral lhitauons

addition to its retrospective nature, the lackcontrol group that did not receive SCIT madedifficult to estimate the true effectiveness of SCIT.addition, the study covered maintenance duratiof 3 months in patients at a single institution.

FUNDING

None

CONFLiCT OFINTEREST

None

REFERENCESl. Moustaki M, Loukou I, Tsabouri S, Douros K. The

of Sensitization to Allergen in Asthma PredictionPreven● On.Fro″′ル

`″

′″ 2017;5:166.Published 2017

31 do■・lo 3389′фoこ201700166

4

IOhan]Httm Sircgar・ Llly lsa,Sup五 atnO,助 abarOedaln

■oeb、 Rita Ev・alina A翡 ociatlon beth・ecn bronchid asthma

in attDPic children and their numbcr OFslblings_P4`満 ′′百“L′ο″ぃj●

“●2014;54(5):289-93

EIliott l Kelly SE,IohnStOn A,Skldmorc B,Gomes■ WeusGA Allergen immunotherapy tOr the treatment oF allcrglc

rh■k and/or asttma m ulnbrclla面 飩 cMA′ OP“_

201■5(2)373385EAACI Guiddincs_Muraro A,Robcrts G,edltors Allcrg“

Immunothcraw Guiddines Part 2: Recommcndato畔;

2017:1‐ 168 1SBlヾ Numbcr:978-3-9524815-1-6. ‐

卜td M,AFacI,Boi滅 s,Butt Щ C」dcron卒 ,

Canonlca w CoXI.,DcmOly R Frcw Al et al lnternatiOn‖

Conscn・sus On(ICON)Allergy lmmunothcrapy(AIT)_ア

轍 解 軸

renew oF the recent literature 宙tll recomalendationS

IAbsmct].IPIセ“

arゎ″′′ル"`"げル́響 ι rlli″ ο●gノ・2013;

3 101002/al●21141

EndaryantQ A &Irmawati, M Enhanced Ettcacy ofSubllngllal lmmunoふ craPy in Childhood Ancrgic Asth“ぃ

by Problodcs ttlla tta`′ J4ぁ"“

:“´201&54(641.1020473ノfmi v5411.8055 1

器 挽“枷 :驚〕瘍 露暇 霧 蠍 」FP織 蹄

2014 Mar12 D()I:10_1007ノ s40521-014-0013-1 1

1ncOrvala C, 斑anO‐ Sfor2a GG, IncOrvala S, FratiR Sublinttal immunotheraFy m alerglc asthmaCurrent c宙 dence and needs tO meet.■

""771ο″`λ

fF′

2010,5(3)128-32〔 Accesscd on_March 2019]htps:ノ /ぃぃはncbi nim nih.gov/Pmcノ artlcles/PMC2930649ノ _

HttsmQ A Spcclic immunotlleralDy fOr alerglc alseascs.

■`″

″″rra n′。"“

,′′′2005:45(7-8)137-44Martln H,Taube C.Re」 atory T cells and regulatlcln

of」lerpc面 rル唸y dlsease ス"I Cli"Eη

レ"″ "d‐

2012;1(2):166-78 Publishcd 2012 Nov 15.

Hankln CS, Cox L BronstOne へ W・an3 z A■ er〔ぽimmunotheraPy:rcduced health carc cOsts ul adults and

chidrcn、●th allcrgic rhhius iAbsttact]Jス ル19C″“fr:":“

"οr 2013 AP● 131(4)1084-91 DO■ 1010164・

jaci 2012 12.662.

１４

１

１

１

司ヨ「引司

扁―

【９ミ

霞

Ｉ

●■

ニ

ヨ〓

ニロ

taot lfrprdd Croup lnprGd cmp

Ｅ

Ｅ‘い‐〓」

一　

　

　

　

　

一

・　

　

一　

・

３〓ヽこ）●‐〓

ORIGINAL ARTICL[

16.

Penagos M,Elfan AQ Durhaln SR,Scaddmgい _Duration

ofフ ■ヽergen IInmunotherapy for Long― Tcrm EElcacy in

Allcrglc RhinocOnJunCtlut■ s CII″ Trear opliο ぉ Afla92018,5(3):275-290

A鳳お CA,ALiis M 卜Icchanisms oF ancrgen_spec面 c

immunothcrapy and inmunc tolcrttcc tO alcrgcns 将orra

nルなッ orga″ ェ 201■8(1):17_PubLshed 2015 Ma,14dol:10.1186/s40413‐ 015-0063-2

Rolnick SI PaW10SkI PA,IIedblom BD,Aschc SE,Bruzek

RI Patientぬaracter■ stics associated、 柄th medlcation

adhcrence C″"ノ

Иθ′R● 2013,11(2)54-65

Musa R Al―Ahmad M, Arinlodzic N, Al― Hcrz ヽ～1

Comphancc uth ancrgCn mmuncthcr理 ッ“

d ttttOrs

anccting compliance alnong Padents wlth rcsplratory

a■crglcs.I14“ 17arrl″ rFl″ ″″。r77`た 2016;13(3):514-517.

Tsabttrl S, Mavroudl A, Fckctca G, Gtubas 磁 _

SubcutancOus and Sublingud lnlmullothempy h Allerglc

Asthma in Chlldrcn Fro●riセ′arF 2017;5:82_Pllbllshcd

2017 Apr21 DO■ 103389/tped.201700082

Gchncik A,Demir S,Olga,M,ヽ seVer H,Khlshigmren 3,

0谷eker■ (blak礎

"B,Bttμ

oZtlrk S_HItt adhC“nce

to subcutatlcous unmunotherapy in a red― hi study ttom

a largc tcrdaγ medICal ccntet A'ル rg/Aslλ II′ PF●02017Nov l:38(6):78-84 DOli10 2500/tap 2017 38 4091.

P""GB,3crnarani R,Pcroni n et al clmical practlce

rcconlntendations tOr 』ergen― Nspeciic intlunotherapy

in ch」 drell: the ltalan consellsus report_ I「 ar′ Fしrfrarr

2017;43(1)13 Publお hed 2017 1an 23_ DOI:101186ノs13052-016-0315-y

Tsabourl,IIIawoudi S,Fckctea A,価 bas C Subcutancous

arld Sublingual lnllnunothcralッ in Alcrglc Asthmain Chlldren ルリ42tご ぉ :″ Pc′麟ム甫

“ 20171 5 10_3389/

摯 と2017.00082.

Natond Asthma EducatiOn and Preventon Progratn,

■感rd Lpett Palld m dle DiagnoJs atnd Muagementof A価m&Expcrt Pancl RcpOlt 3:G面 dcl五

“lor thc

Diagnosls and Managcmcnt of Asulma.Bcthcsda(MD)

Na」¨ al Hcart,Lung,and B100d lnsuttt(us);2007Att SecuOn t Managing Asthma Long Tcrlni Ove面 飩

Availablc

“

m: ht,s:/1…、nCbi・ l■ll■l.nll■ gov/booLsノ

NBK7234/Scichlone N,COntinO A,Fig1101i GB,Pagllno G,Bellia

4ヽ Paucnt pCrspectlvcs h thc managcFnCnt Of ttthma:

improvlng patient outcomes tllrol1311 Cdlcal sdecEcln of

tleatmcnt op● KIns R′

"″r)、キ ″AJ与

`″Fに 2010,4■ 7‐ 23_

Published 2010 Fё b 4

Braldo E Failurc in ¨ぜhnta contra reasms andconscqllences_Sderltr/ca`C´ f"'201■ 201■ 549252

GNA.Dittcult tO_Treat&Sevcre Asthma in Adolescent

and Adult Patlcntt Diagnosis and Managemcnt A GINA

Potket Cruidcおr Hcalth Professionals Global hitiat市 c IOr

Ashma.2018、神内Iglnasthma.org.

Yttelen A Allcrgen specinc immunotheraⅣ in pc■ atHc

allcr」 casima.As滋 勲`Atts.201●

6(3)139-48

Magje Pよ―Kec Llt Occupation」 Asthma INcwslcttcrl

昴 撃 οllg撚″r“

"げAルOMり 201■ 29-30

Chen3 L ChCn L Fu Q tt S,Li H,Lin tt Tan c,ctal_Chinese Soclety of■ 出crgy Guidehnes for Diagnosls

and Trcatmcnt of Allcrgic Rhinitis.■ Jlag/五 sЙ″′I"22●″ο:R“ 2018 Jul,10(4):300-353 DO■ org/104168ノ

aal■ 2018.10.4.300

Lcc IH,Kim S― C,Choi H,IIng C― G,Ban C―Ⅵ Shin YS,et al.SubcutancOus lmmunOtheraPγ fOr Allergic Asthmain a SInglc Ccntcr of Korc■ Ettcacy・ Safctt and Clinlcal

RespOnsc Predictors′κ"`′

″」Иε′Str 2017,32:1124-1130_

DO■ Org/10_33464kms 2017 32 7 1124

|

||||‐ || ||

|

Taketmi E A"譴L DAQ,S"dettt M.C,Gc轟 ,

org/10 1lH/J1365-2222 2008 03005 x l

17_

IMelet ■ et al_ In vivo sutch to IL‐ 10-secretulg T

rcgulato,cellS in high dose dlcrgen αposure/●“

r21′′げEXP′ri“

“14'並afr,″。20512(2008):2887-2898

Francis M urd Sharon M. \{ahl. I)ysregulation ofSignaling Pathr*'ays in the Absence of TGF-pL /2002; 169(10〉 59417.DOI:hjimmund_169_105941

36 卜`art〔

n-1ばuioz, M_■ , Pinedaj ■, 卜

`通

ios, ■,FontM., Nevot S", Bosque, M., Palomo, J.1., Tr

A., et al. Changes in IL-IO and specificassociated to successful f)ermatophagoidesimmunotherapy in children during the 6rst yeiltreatment [Abstract]. Allergologia et2013, 41 (Issllc l) 4-10_ DO■ ORG/10_ALLER 2011 12.005

Sh田可 i,MH,KΨ pcn,lH・,Akdis,M,IcnScn Jarollnl,

Knd,EF,Kleine Tebbe,1,BOllle,B,Ch恐コらAM_、

al. Biomukers for monitoring dinical efficacy ofimmunotherapy for allergic rhinoconjunctivitisallcrglc a"hula an EAAα Posltlon Paper.Aた こy,201Z(8):1156-1173.

FllJ燎 H,SOyM MB,Akdis M,Akals CA Mccharuslns OfallCFgcn SPcdic unmunothcrapy Crllll「

・●"s′

A,ルrgy_2012:

2(1):2 DOI:101186/2045-7022-2-2

Vltaltti G,PavOnc R Gughdmo■ SPata10 G,Talsaperl● た

Theimmunomodulttory ettct ofProllbu“ bevOnd atOォ :

an update lAbstractl.′ ■S″`“

● 2014 Ap■ 51(3)320-31、

DOI:10_3109/027709032013862259 1

Tosca MA,IicaH A,01cesc R,Marscglia G,Sacco O,

CIPrmdi G Imnlunotherapy md Asthma in Chidren_

F“″′ルル′れ 201&6231.DO■ 10.3389ノ oed 2018.00郎 1

Thiswork is lkensed undera(reative (ommons Attribution

PuЫむhed by Dお coverSys 1 3● ″〃edノ 20128(1)341‐3461dd:1015562/bmjv31

||

BY