Y Hpc VigT NAM THANG 9 • Sp'flAC BI$T/2012
DAC DIEM LAM SANG VA CAN LAM SANG CON HEN PHE QUAN KHAU PHAT DO RHINOVIRUS 01 THE EM
Nguyen Thi Di^u Thiiy*
T6M
ikr
Hen la mpt benh viem man tinh du'dng thd vdi cac giai doan bCtng phat xen lan cac thdi Icy thuyen giam. Nhiem virus du'dng ho hap, nhat la F^inovinis (RV) duOc coi la yeu to chu yeu khdi phat cdn hen cap d ca ngutfi Idn va tre em.
Nghien cuXi du'dc tien hanh nhSm xac djnh ty le nhian Rhinovirus trong cxSn hen cap 6 tre em va danh gia mot so dSc diem cua cOn hen cap khdi phat do Rhinovirus. Day la nghien ci?u tien ciTu mo ta tren benh nhan du'di 15 tuoi, trong cdn hen phe quan cap. Ket qua nghien cuXi cho thay trong 146 benh nhan hen phe quan du tieu chuan tham gia nghien CUXJ, 72,6% tre nhiem Rhinovirus trong cdn hen cap. So sanh trong cdn hen cap gife nhom tre cai nhiem RV va nhdm tre khong nhiem RV cho thay nhom tre nhiem RV co nguy cd mac cdn hen cap nang hdn (0R=5,1;
95% a : 1,69-15,44), trieu chutig kho khe Giu'dng gap nhieu hdn. Ty le tSng bach cau trong mau d nhom nhiem RV la 68,5% so vdi nhom khong nhiem RV la 45%, su" khac biet cd ^ nghTa thong ke (p<0,05). Ty le tang bach cau ai toan d nhom co nhiem RV la 34,9% so vdi 15% d nhdm khdng nhiem RV. Ket luan: Nhiem Rhinovirus la nguyen nhan thu'dng gap gay khdi phat cdn hen cap d tre em va lam tang nguy cdn hen cap n|ng.
Tu'kh6a:CxiT\ hen cap, Rhinovirus SUMMARY
THE CLINICAL AND INVESTIGAHVE
FEATURES OF ASTHMA ATTACKS INDUCED BY RHINOVIRUS IN CHILDREN Abstracts: Asthma is a chronic airway inflammation in which the aculs periods in combination with the remission periods. Viral respiratory infection, especially Rhinovirus (RV) has been seen as the main trigger induced asthma exacerbation in both adults and children.
This study was conducted to Indentify the prevelance of Rhinovirus infection in children with acute asthma and evaluate some features of acute asthma induced by RV. This was a discriptive and prospective study in children with acute asthma under 15 year of age. The results showed that there were 146 childhood asthma in aculs periods, and 72.6% of them were infected RV. Children with RV infection had higher risk of seveve asthma exacerbation compared with children without RV infection (0R=5.1; 95% CI: 1.69-15.44), wheezing was often seen In RV infected children. The pecentage of white blood cell in RV Infected group were 68.5% compared to 45% in non RV infected group, it was statistically sinificant difference (p<0.05). The pecentage of blood eosinophils were 34.9% in RV Infected children in comparison to 15% in non RV infected children.
Conclusion: Rhinovirus infection was the main trigger induced asthma exacerbation in children and increased risk of seveve acute astiima.
Key words: Kute asthma, Rhinovirus
* Dai hoc YHa npi
99
CHUYEN Bi: Hpl NGH| KHOA HpC N G A N H NHI KHOA T O A N QUP'C I-AN THCT IX
I. OAT VAN o l
Hen I^ b?nh vi8m m ^ tinh du&ng thd vdi cdc thiri k^ biing ph4t xen kS cic thdi k^
thuySn gidm. C6 nhiAu nguyen nhdn khde nhau gdy khdi phdt con hen cip. TCr thjp nifin 1970, nhilm virus dudng h6 hip dui?c xdc dinh id mpt trong cdc y^u t6 gdy khdi phdt con hen cip d cd tri em vd ngudi Idn.
Virus dugrc tim thiy khodng 80% trong cdc giai dojn khd khi ti txi hgc dudng vd t i 50%
din 75% trong cdc giai do?m khd khi cip tinh d ngudi Idn [12]. Cd nhilu virus dudng hd hip dugc tim thiy trong giai do^n ndy nhu Rhinovirus, virus hgp bdo hd hip, virus ciim, d ciim, adenovirus, coronavirus, trong dd Rhinovirus (RV) chiem tdi 65% [12]. Theo Holgate, phan Idn cdc con hen cip dugc khdi phdt bdi virus dudng ho hip, md Rhinovirus dudng nhu thudng gdp nhit [9]. Com hen cap gay ra bdi virus thudng xdy ra vdo miia thu, dong hodc diu xuan, khi md thdi tiet thuan Igi cho Rhinovirus phdt triSn [11]. Cdc nghien cHu tren thS gidi hi$n nay chi ra ring Rhinovirus ddng vai trd rit quan trgng trong khdi phdt con hen cip, ngay ci ti txi nhd dudi 2 tudi. Tai Vi?t Nam, cdc cdng trinh nghien ciiu ve vai trd cua Rhinovirus trong vigc 1dm bung phdt con hen cip cdn chua nhieu. Bi ddnh gid vai trd cila Rhinovirus trong khdi phdt con hen cip d txi em, chiing tdi tiSn hanh nghidn ciiu de tdi ndy nhdm 2 myc tieu sau;
1. Xdc dinh ty If nhiim Rhinovirus trong can hen cdp a tre em diiu ir; nfi h-u Igi khoa Miin dich • Di iing - Bfnh vifn Nhi Trung uong.
2. Nhfn xet mgt so ddc diim Idm sang vd cgn Idm sang eda can hen phi qudn liin quan din vai h-d eda Rhinovirus a tre em.
II. 06l TU9NG VA PHUONG PHAP NGHIEN COl 2.1- D6i tatfng: Tit cd cdc bgnh nhi hong con hen cip dugc dieu hi ngi tni t^ khe MiSn Djch-Di iing b^nh v i ^ Nhi Trung Ubii hong thdi gian tir 12/2010 den 08/2011.
Ti&u chudn l\ea chgn bfnh nhdn - B^nh nhdn dudi 15 tu6i.
- Chin dodn xdc djnh hen phi qudn thei ti^u chuin cila GINA [6,7]
- B|nh nhdn trong con hen cip vd dugi phdn d9 nitag nhg theo GINA 2006 [6]
- Nhdp vign ttong 3 ngdy diu kl tii kh cd tri^u chimg khdi phdt con hen
Tieu chudn logi trit
Bgnh nhdn cd con khd thd do cdi nguyen nhdn khde nhu: Com hen tim, tidn khi mdng phoi, dj vdt dudng thd...
- Bgnh nhdn cd cdc benh phii hgp nhit Cudng gidp, logn nhjp tim, suy tim ndng, tim bim sinh, cao huyet dp, thip tim, bgnh gan mdt...
- Tr6 khdng trong con hen cip - Nhdp vign sau 3 ngdy tii khi khdi ptit com hen
- Bgnh nhdn vd gia dinh khong ding ^ tham gia nghien ciiu
2.2-Phinrag phdp: nghiSn ciiu tiin cilu moid
amSu: ^^f^i—I
Trong dd: - DO tin cdy chip nhjn li 95%Z„n=I,96
- P Id t^ lg tr6 hx)ng con hen cip rf nhilm virus, liy p=0,9 [14].
- d Id h | so cho p h ^ trong nghiSn ciiu la 5%
1,96x1,96x0,9x0.1 = 138
- Cdy djch ty hau tim Rhinovirus 4W th\rc hign t?i khoa Vi sinh Bgnh vi§n ^ . Trung iTcmg, theo phuong phdp phin lilg
Y HOC VigT NAM THANG 9 • stf OAC BI$T/2012 chudi men (PCR) tren mdy Bio Rad
CFX96™ Real - Time System CC3071.
- Xet nghi$m mdu xdc djnh sd lugng b?ch ciu vd t J lg bach cdu di toan
- Khdm 1dm sdng ddnh gid tri^u chiing, miic d$ ndng ciia con hen cip
2.3 Cdc chi si nghiin cuu
- Ty lg nhiem Rhinovmis trong con hen cip - Trigu chiing cua con hen cip - Moi lien quan giOa nhiem RV vdi miic dg ndng cua com hen
- So sdnh s6 lugmg b^ich ciu trong con
hen cip giOa nhdm cd nhilm RV vd nhdm khdng nhilm RV. Sd lugmg bgch ciu tdng khi h-en 10000/mm''
- So sdnh t^' lg bach ciu di toan trong con hen cip gitta nhdm cd nhilm RV vd nhdm khdng nhilm RV. Bach cau di toan dugc ggi id tdng khi ty 1$ phin trdm cao tren 5%
- Thdi gian diiu trj tsd b^nh vi$n vi con hen cip.
Kit qud nghien ciru dugc phdn tich va xil ly bdng phin mIm SPSS 16.0
III. KlT QuA
NghiSn ciiu cho thiy cd 106 bgnh nhi HPQ cd kit qud xit nghigm duong tinh vdi Rhinovinis trong sd 146 bgnh nhi dugc chi djnh idm xdt nghidm, chiim 72,6%.
Bdng 3.1- Mdi lien quan giiia nhilm RV vdi trieu chiingldm sdng cila HPQ
Tri|u chihig Sot
Kho khe Co keo cd ho hap
Sp02
Co Khonq
Cd Khdnq
Co Khdnq
>95%
91%-95%
<91%
Nhlem RV C6(n)
16 90 103 3 102
4 44 59 3
Khonq (n) 10 30 34 6 40 0 15 23 2
P
>0,05
<0,05
>0,05
>0,05 Cac tri$u chiing lam sang trong con hen cap giiia nhom co nhiem RV va nhdm khong nhiem RV la tirong tu nhau. Tuy nhien dau hieu kho khe hay g§p hon 6 nhdm tr^ cd con hen cip khdi phdt do nhilm RV (103/106= 97%) so vdi nhdm khdng nhilm RV (34/40=85%), sir phdc biet nay c6 y nghia thdng k6 vdi p<0,05.
Bing 3.2- M d i l i e n q u a n g i i i a
MiJc d g n ^ n g
Nhe Tmnq binh Ndnq CBnq
n h i e m R V v d i m i i c d $ ndng c o n h e n N h l e m RV
Co n ( ° / o ] 1(0,9) 57 ( 6 3 , 2 ) 3 8 ( 3 5 , 9 ) 106
K h o n g n
(%)
0 36 (90)
4(10) 40
C$ng n(<>/o) ' 1 (0,7) 103 (70,4)
42 (28,9) 146
OR
5,1
95%CI
1,69-15,44
CHUYEN Bi: Hpl NOH| KHOA HpC NGANH NHI KHOA TOAN QUOC I-AN THO IX
Con hen cip mure dg ndng gdp d 35,9% b§nh nhi nhdm cd nhilm RV so vdi 10% i nhdm khdng nhilm RV. Nhdm b$nh nhdn HPQ cd nhilm RV cd nguy co mdc ccm hen n|n hon nhdm khdng nhilm RV (0R= 5,1; p<0,05).
Bdng 3.3. Moi liSn quan giOa nhilm RV vdi s6 luiyng bjich ciu mdu ngojii yi Thaydfil so lu'dng b^ch
cdu Tdnq Binh thudnq
Nhiim RV C6- n (°/o)
73 (68,9) 33 (31,2)
Kh&ng- n (%) 18 (45) 22 (55)
OR 2,70
9 5 % a 1,25-5,83 Nhdm bgnh nhi HPQ cd nhilm RV cd tdng b^ich ciu mdu Id 68,9% so vdi 45% d nhon khdng nhilm RV. Trong con hen cip, nhdm bSnh nhi nhilm RV cd nguy co tdng b?ch ciu mit cao gip 2,7 lin so vdi nhdm b^nh nhi HPQ khdng nhilm RV, sv khic bi^t niy cd ^ nghia thing kf (P<0,05).
Bdng 3.4. Mii liSn quan gitta nhilm RV vdi bgich ciu di toan mdu B^chdlu
dl toan Tdnq Binh thudnq
Nhilm RV C6- n (%)
37(34,9) 69(65,1)
Khdnq- n (%) 6(15) 34(85)
OR 3,04
9 5 % a 1,11-9,61 Trong con hen cap, bgnh nlu nhiem RV cd tdng b?ch ciu ii toan chiem 34,9% so vdi 15% d nhdm khdng nhilm RV, su khde bigt ndy cd y nghta thong ke vdi p<0,05.
Bang 3.5- Mdi lien quan gitta nhiem RV vd thdi gian ndm vign SS ngdy nilm vl|n
trung btnh RV{-i-) RV{-)
5,11 ± 2,26 6,35 ± 3,08 p=0,009 Nhdm nhilm Rhinovirus cd thdi gian diiu trj trung binh ngin hom nhdm khdng nhilu RV, s\r khac bigt cd y nghTa thong ke (p=0,009).
IV. BAN LU$N
NghiSn ciiu chi ra rdng ty lg nhilm RV tiong con hen cip Id 72,6%. RV dugc cho Id nguySn nhdn hing diu gdy khdi phdt con hen cip d tre em. Mgt nghiSn cilu mdi ddy t?ii Australia chi ra rdng 78% cdc con hen cap khdi phdt do nhilm virus, vd ti-ong so niy 83% Id nhiem Rhinovirus [8] Nghien ciru tren 50 txi HPQ tir 4- 12 tuoi cho thiy RV dugc phdt hiSn trong 82% vd virus hgp bdo hd hip (RSV) dugc phdt hiSn ti-ong 12% cdc tiudng hgp dang cd con hen cip. Sau 6 tiiin.
nhdm bgnh nhdn ndy dugc xSt nghi|m Iji vuus dudng hd hip vd chi thiy cd 44% bsnh nhdn cd RV t»i dudng hd hip [10]. Dieu niy cho thiy RV cd vai ttd ddng kl tiong khdi phdt ccm hen cip d ti-S em, nhit Id nhdm tre Idn. RV cd vai ti-d khdi phdt con hen cip it mgi Ilia tuli. Nghien ciiu ciia Zhao vi cgng s\i cho thiy ty lg nhiem RV d trd dudi 2 tuSi ti-ong con hen cip Id khi cao, ti-Sn 70% [lU Dieu ndy cho thiy RV cd thi don thuan hojt phoi hgip vdi cdc virus khic nhu RSV pS con hen cip, ndng d ti-6 dudi 2 tuli. Ngbifn
Y Hpc V I | T NAM T H A W G 9 • Sp" BAC BlgT/2012
:ira ciia Jackson tren trd dudi 3 tudi cho kit jui tuong tu, nlu nhiem cd RV vd RSV ludng hd hip, khd ndng gdy ccm khd khe khd thd tang ISn hom 10 lin so vdi cdc tid khdng nhilm cdc virus trSn [13].
4.1- Moi liSn quan giii-a RV vdi trigu chiing con HPQ
Khd khS Id trigu chiing chu yiu trong con hen cip. Nhdm bSnh nhi HPQ cd nhilm RV cd tiiSu chiing khd khe Id 97% so vdi nhdm khdng nhiem RV Id 85%. Nhilm virus id nguyen nhdn hdng diu gdy khd khd d trS em cd CO dja qud min [2,5]. 6 nghiSn cdu ndy, tren 70% bgnh nhdn cd kit qud RV duong tinh, vdi tten 60% cd phdn img qud man vdi it nhdt vdi mOt lo?ii dj nguySn, diiu do Iy gidi trigu chung khd khe tdng cao d nhdm RV duong tinh.
Nhdm benh nhi HPQ cd nhiem RV cd triSu chiing sdt Id 15,4%, so vdi nhdm khdng nhilm RV Id 33,4%. RV la virus gdy cdm Ijinh, vdi cdc ttiSu chimg nhu ho, dau hgng, chiy miii vi sdt Vi thi nhdm nhilm RV thudng cd tiieu chung sdt tren lam sing. Tuy nhien chiing tdi liy nhigt do t?i thdi dilm lignh nhdn nhdp vign, t^ thdi diem nay tre cd the dd hSt sdt, vi till khdng cd stf khic biSt vl trigu chiing sit gitta nhdm cd nhilm RV vd nhdm khdng nhilm RV. TriSu chiing khde eda con hen cap nhu CO kSo CO hd hip khdng cd su khde biSt gitta nhdm nhilm RV vd nhdm khdng nhilm RV vi ddy Id cdc triSu chiing dac trung eda con hen gay ra do bit cii nguyen nhdn gi.
SpOi Id mdt chi sd nhdm danh gid miic d§ suy hd hip tiong con hen cip. Fuji nghiSn ciiu vl SpOz trong com hen cap nhdn thiy ring Sp02 thip gdp d hiu hit cdc ttS nhilm RV typ C, tuy nhiSn svr khac biSt khdng cd ^ nghia tiling kS. d nham txi nhd dudi 1 tuli, nhdm nhiem RV giim SpOa mgt cich cd i nghla tiling kS so vdi nhdm khdng nhilm RV
[5]. Nghien cdu cua chiing tdi cho thiy hon 50% b$nh nhdn nhdp viSn cd SpOa gidm dudi 95%, tiong dd nhdm nhiem RV Id 58,4% vi nhdm khdng nhilm RV Id 62,5%. Nhdm txi dudi 1 tuoi cd Sp02 gidm mdt cdch rd igt cd thi do cic txi ndy cd biin chiing viSm phoi kSm theo vi ddy Id biin chiing rit hay gdp d trS nhd sau can hen cip.
4.2-Mli liSn quan giCi-a nhiem RV vdi miic d$ n$ng com hen cap
Kit qud nghiSn ciiu eda chiing tdi cho thiy nhdm bgnh nhdn nhilm RV cd nguy co mdc con hen cip miic dd ndng cao gip 5 lin nhdm khdng nhilm RV. NghiSn ciiu eda Come vd c0ng sy: chi ra bSnh nhdn nhilm RV thudng cd cdc triSu chiing trong con hen cip vdi miic dg ndng hon vd thdi gian bj bgnh keo ddi hon [3]. Message va cdng s\r cung nhdn thdy ring nhilm RV liSn quan clidt che vdi cdc trigu chiing cua dudng hd hip dudi, idm gidm chiic ndng hd hdp, tdng tinh kich dng dudng thd. Khi tdi lugng virus cang cao, trieu chiing lam sdng cang ndng nl [15].
4.3-Moi lien quan giiia RV vdi thay doi sl lirgng b^ch cau trong mdu
Kit qud nghiSn ciiu cho thdy bgnh nhi nhilm RV cd tdng sd bach cdu (68,9%) vd tdng bjich ciu di toan (34,9%) ttong mdu so vdi nhdm bSnh nhi khdng nhiem RV. RV la virus chu yiu gdy cdm ignh, la mdt ttong cdc tdc nhan chii yiu gay khdi phdt con hen cip.
NghiSn cim stf thuy ddi tl bdo ttong ddm d bgnh nhan ttong con hen cdp cho thiy bgnh nhdn cd tdng rd rgt cd sd lugng b?ich ciu da nhdn trung tinh vi bjch ciu ai toan khi nhiem RV [3,15]. Mdc dil vai ttd cua RV ttong khdi phdt con hen cap dd dugc nhdn thiy ttt rit lau, tuy nhiSn co chl RV gdy khdi phdt com hen cdn chua rO rdng. Cic nghiSn ciru deu chi ra rdng RV 1dm tdng tinh man cdm dudng thd, tdng gidi phdng cdc chit tiling gian hda
C H U Y S N Bi: Hpl NGHI KHOA HpC N G A N H NHI KHOA T O A N QUgc LAN T H O IX hgc vd kich ling tinh ttjing viSm t?i dudng
thd. RV 1dm tdng svi hda dng dOng vd tich tvi tl bio viSm tju niSm m?c vd Idp dudi niSm m^c dudng hd hip, bao gIm b^ch ciu da nhdn trung tinh vd bfich ciu di toan [16]. RV kich iing viSm m^nh, tdng tich ty tl bdo viSm ttSn bSnh nhdn cd co dja qud min hodc bj hen phi qudn so vdi ngudi binh thudng [3,15]. Hom ntta, RV cu tni tsii mfli, trong dieu kiSn thudn Igi RV ho^t d$ng gdy cdc tiiSu chiing viSm mfli hgng cip, trudc khi khdi phdt con hen cip. ViSm mfli hgng cip do RV thudng khdng idm hiln dii tl bio mdu ngo^i biSn, tuy nhiSn RV ho^t dgng t^o diiu kign cho vi khuin thdm nhdp vd hogt d$ng, gdy viSra mfli hgng cip nhilm khuin.
Diiu ndy I^ gidi m0t phin tdng bfich ciu d bgnh nhdn nhilm RV.
4.4-Moi liSn quan giil-a nhilm RV vd thdi gian ndm vifn
Thdi gian ndm vign trung binh cfla nhdm bSnh nhi cd nhilm RV Id 5,11±2.26 ngdy, cdn d nhdm cd RV dm tinh Id 6,35±3,08 ngdy. Kit qud nghiSn cdu cua chiing tdi cd khde bi$t nghiSn ciiu ciia Nguyen Tiin Dung, khi nhdm bgnh nhan HPQ cd nhilm virus cd thdi gian dieu tii ddi hom nhdm khdng nhiem vuiis [1]. Svi khde bigt ndy cd thi giai ttiich do nhdm nghiSn ciiu ciiatdc gid Nguyen Tiin Dflng Ii trS hen dudi 5 hioi, nguySn nhdn khdi phdt con hen cip do RSV kit hgp vdi cdc nhdm virus khde, thdi gian ndm vign cua tie nhd thudng dii hon. Cdn d nghiSn cihi cua chiing tdi bfnh nhdn khdi phit con hen cip chu yiu do Rhinovirus, I^ gdp nhilu d nhdm ti-e Idn. d nhdm txi niy gia dinh tiiudng cd xu hudng xin ra vign sdm khi tii|u chiing 1dm sdng fliuySn gidm, vi till cd till lim tiidi gian ndm viSn ngdn lai. Hon ntta mdc dfl thdi gian ndm vi$n trung binh ciia nhdm nhilm RV thip hon nhdm khdng
nhilm RV, thdi gian ndy vin cao hon til gian ndm viSn trung binh ttong nhdm virus ) cfla tdc gid Nguyin Tiin Dflng (4,7 ngiy 0,86). Nhdm nghiSn ciru ciia chiing tdi v RV dm tinh vin cd till nhilm vims khd hodc do cdc yiu tl khde khdi phdt con he Trong nghiSn ciiu cua chdng tdi, nhd nhilm RV cd 58,9% cd Sp02 fliip so vi 62,5% d nhdm RV(-), diiu ndy cd till li thdi gian diiu trj nhdm nhilm RV ngdn ho nhdm khdng nhilm. Tuy nhiSn, dl dua la ki ludn chinh xdc vl vin dl ndy cin cd nghi€
ciiu r§ng hon, ding bO hon vl svi phii hg nhilu tdc nhdn khde nhau gdy khdi phit co hen cip d trS em.
V. KiT LUi[lN
Rhinovinis Id mgt trong cdc virus thudnj gdp gdy khdi phdt con hen cip d tiS em Nhilm Rhinovirus 1dm ti-S cd nguy co mi ccm hen cip ndng. Tdng sl lugng b?ch du y, bgch cau di toan ttong mdu ngo^i vj thiidoj gdp ttong con hen cip khdi phdt bdi RV.
T A I L I | U THAM K H A O
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Yamaya M (2003), "Rhinovirus and Asthma". Viral Immunology. 16(2): 99-109 17. Zhao J, Takamura M, Yamaoka A et al
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