Nghien cii'u khoa hpc
Ap dung dieu trj dif phong va
cat cdn hen phe quan bang symbicort (budesonide/formoterol)
Nguyin Thj Van*, Pham Thj Thuy Duong*
TOIVITAT
Muc tieu; danh gia hieu qua du phdng va cat can cua Symbicort tren benh nhan hen phi quan.
Bdi tifong va phuong phap.- nghien ciiu tiin cdu, thii nghiem lam sang 86 benh nhan HPQ chua duac kiim soat tai phdng kham tu van, khoa Di iing - MDLS,Benh vien Bach Mai tCr 1/2008-10/2008.
Ke't qua; hieu qua diiu tri du phdng dat duac sau 3 thang diiu tri la 80,2%, sau 6 thang dat 84,9%.
Hieu qua diiu trj cat can dat 77,9% sau 3 thang diiu tri va 82,6% sau 6 thang. Tac dung phu hay gap la nhip tim nhanh 5,8% khdng gap benh nhan nao bi nhiim nam Candida hiu hong. Ke't luan;
diiu tri du phdng va cat can HPQ bang Symbicort dat kit qua cao, an toan.
TLT khoa: Hen phi quan, Symbicort.
LDATVANDE
Symbicort II tbudc diSu trj hen phS quan mdi bao gdm tbudc hit corticosteroid (budes- onide) v l tbudc cudng bSta 2 (formoterol) cd tic dting nhanh v l keo dii. Bang su hien dien ca hai loai tbudc trong mdt dng hit, Symbicort dugc td chuc hen toln cau khuySn c l o diing trong diSu trj du phdng va cat can trSn benh nban hen phS quan hay cdn ggi la lieu pblp SMART. Phuang phap dieu trj hen phS quan mdi nly da v l dang dugc Ip dirng tai nbiSu nai trSn thS gidi, va da cho nbirng kSt qua kha quan.
O Viet Nam, cho dSn nay van chua cd dS tii nio nghiSn ciiu ve hieu qua ctia Symbicort trong diSu tri du phdng v l cat can trSn benb nhan HPQ. Vi vay, chiing tdi tien hinh nghiSn cuu dS tii nay nham muc tieu:
* Khoa Dj Ung miin dich lam sang - Benh vien Bach Mai
Ddnh gid hiiu qud du phdng vd cat con cua Symbicort tren benh nhdn hen phi quan.
w. DOI mm UA PHiruNG
PHAP NGHIEN CUU 1. Doi tugng nghien cuuDoi tugng nghiSn ciiu gdm 86 benh nhan HPQ chua dugc kiem solt, trong do nam 30, nir 56, tudi trung binb la 36,9 ± 11,15, tai phdng kbIm tu vln HPQ khoa Dj irng- MDLS Benh vien Bach Mai tir thing 1 nam 2008 dSn thing 10 nam 2008.
2. Phuxmg phap nghien cuu
Nghiin cihi tiin cuu, thii nghiem lam sdng Tat c l cle benh nhan dugc chan doln xlc djnh la HPQ chua dugc kiSm solt theo GINA 2006, tudi tir 18 dSn 55 tudi, cic benh nhan nay dugc diing tbudc Symbicort 160/4,5mcg 2 hit/ngay chia 2 lan sing, tdi cleh nhau 12 gid v l hit thSm tbudc
kbi eln (khdng qui 8 hit/ngay). CIc benh nhan nly dSu dugc dinh gil vS lam sang, CNHH vl diem sd test ACT trudc diSu trj va sau diSu tri 1 thing, 3 thing, 6 thing. Hieu qui diSu tri du phdng dugc dinh gil sau diSu trj it nhat 3 thing dua va su cai thien miic do kiem solt vl diSm sd ACT so vdi trudc diSu tri. Hieu qui diSu trj cat can dugc dinh gil la CO hieu qui khi benh nhan hit thSm tbudc
khi can cat dugc can HPQ ma kbdng phai tbay ddi phac dd diSu trj nhu: nhap vien cip ciru hay diing thSm tbudc khlc de cat can HPQ. Ngoli ra cdn theo ddi mdt sd tic dung khdng mong mudn cua Symbicort SMART nhu: nhip tim nhanh, ho, khan gigng, nam Candida hau hgng...
Sd lieu nghiSn ciiu dugc xir ly theo chuang trinh SPSS 12.0.
III. KET QUA NGHIEN CUU VA BAN LUAN
1. Mot s6 dac diem trudc khi dieu trj
Bdng 1. Dgc diem diiu tri dif phdng
Cd Kbong
Tdng
Dieu tri du phdng SdBN
25 61 86
Ty IS % 29,1 70,9 100 Chiing tdi nhan thay 70,9% khdng dugc diSu trj
du phdng hen tai nhl, kSt qua nay tuong tu nhu kSt qui ciia Trang Thanh Thuy II72,1 % va cao hon mot elch ding kS so vdi kSt qui ciia nghiSn ciiu AIRIAP;
khdng diSu trj du phdng d chau A -Thai Binh Duong la 90%, cdn tai Viet Nam la 89% [1],[6].
Tuy nbiSn, ty IS nay van cdn cao han rat nhiSu so vdi cac t i c gia nudc ngoai, c6 IS do dieu kien kinh tS nudc ta cdn thap, gil thuoc lai cao so vdi thu nhap ctia ngudi dan va nhiSu ngudi benh cung chua cd quan diSm dung ve diSu trj du phdng HPQ.
Bdng 2. Phdn bd binh nhdn theo miic do kiim sodt
Mitc do kiem soat Khong kiem soat Kiem soat mot phln
Tdng
Sd benh nhan 76
10 86
Ty le % 88.4 11,6 100 Benh nhan HPQ khdng dugc kiem solt
chiSm ty IS rat cao 88,4%, chi cd 11,6% benh nhan cd muc do kiem solt hen mgt phan. DiSu nay phan anh tinb hinh kiSm solt hen tai cdng ddng cdn rat kem. Theo sd lieu ctia nghiem ctru AIRIAP - nghiSn cuu vS thuc trang quan ly hen tai chau A Thai Binh Duang - tinh hinh kiem solt hen tai Viet Nam hien rat thap, 99% cac trudng hgp chua dat dugc tiSu chuSn kiem solt hen [6]. YSu td cdt loi ctia van dS nay la bac sy va benh nhan chua dinh g i l dting miic do kiSm
soat hen ciia benb nhan. Trinh do phlt hien hen chua dugc kiSm soat cdn thap do ban chS trong chuyen mdn vS hen tai tuySn ca sd. Ben canh dd, muc do hiSu biSt vS benh tat cdn ban chS trong cdng ddng. Benh nhan hen chii quan' tudng rang tinh trang hen ciia minh da dn djnh do vay tu y bd tbudc, khdng tii khIm. Nglnh Y tS chua dua ra phic dd hudng dan diSu tri ciia Viet Nam. Chinh sacb bao hiem cung chua dugc phd cap rdng rai, chua cung ung du tbudc du phong hen cho ngudi benh.
4 0 IY HOC LAM SANG So 46 (Thang 11/2009)
DIEN DAN Y HOC
Nghien cu'u khoa hpc
Bang 3. Phdn bd binh nhdn theo diem sd ACT Diem ACT
<14 15-19 20-24 25 Tong
Sd benh nhan 50 24 12 0 86
Ty le % 58,1 27,9 14,0 0,0 100 Chiing tdi nhan thay khdng cd benh nhan nio
dat diS'm tdi da 25 diem, diSu dd cd nghia la khdng cd benb nhan nio dat tiSu chuan kiSm solt hen tot.
Chi ed mdt ty IS nhd 14% benh nhan dat tir 20-24 diem (kiSm soat hen mgt phan) cdn lai 86% benh nhan cd diS'm sd ACT < 19 (khdng kiem soat). Nhu vay, khi so sinh vdi kSt qua d bang 2, cbiing toi
2. Hieu qua dieu tri du phdng
Bdng 4. Hieu qud diiu tri
nhan thly test kiem soat hen ACT cd the giiip bic sy ciing nhu benh nhan dinh gil mirc do kiem solt hen nhanh chdng, chinb xlc va phd hgp vdi nai dong benh nhan (dac biet nai khdng cd hd hap ky).
Bdi vay, trie nghiSm kiem solt hen dugc GINA khuySn clo sir dung nhu II mdt cdng cu da dugc thEm djnh diing de danh gia kiSm solt hen [4].
du phdng cua Symbicort Hieu qua dieu tri du pbdng
Sau diSu tri 3 thang Sau dieu tri 6 thang
Cd bieu qua SdBN
69 73
% 80,2 84.9
Khong hieu qua SdBN
17 13
% 19,8 15,1
Tdng SdBN
86 86
%_
100 100 Trong tdng sd 86 benb nhan tham gia nghiSn
ciiu, 80,2% benh nhan dat dugc hieu qua diSu trj du phong sau 3 thing diSu tri va sau 6 thing ty IS nly tang tdi 84,9%. Nhu vay, ty IS tblnb cdng dat dugc tuong ddi cao, tbeo chiing tdi sd dT cd dugc hieu qui nhu trSn la do trong tblnb pban ciia symbicort c6 chira ca tbudc corticosteroid dang hit (budesonide) vl thuoc cudng beta tic dimg keo dii (formoterol) bdi vay hieu qui cai thien chirc nang phoi va trieu
chiing hen phS quan tdt ban nhiSu so vdi viec diing corticosteroid don thuan. DiSu nay ciing da dugc chirng minh qua mgt sd nghiSn ciiu ciia cac tic gil nudc ngoai nhu Lallo 2000, Bateman 2003 va Buhl nam 2003 [2],[3],[7].
Hieu qua diSu trj du phdng dugc danh gil thdng qua su cai thien vS muc do kiSm solt cQng nhu su tang sd diSm ACT sau diSu tri bang Symbicort.
Bdng 5. Thay ddi vi miic do kiim sodt trudc vd sau diiu tri
Thdi diem Trudc dieu tri Sau dieu tri 1 thang Sau dieu tri 3 thang Sau dieu tri 6 thang
Mure do kiem soat ( N=86) Kbong KS
n 76 22 13 9
% 88,4 25,6 15,1 10,5
KS mgt pban n
10 58 43 16
% 11,6 67,5 50,0 18,6
Kiem soat n
0 6 30 61
%
M
6,9 34,9 70.9
P p<0,001 p<0,001 p<0,001 Mirc do kiem solt hen cd su thay ddi rd ret trudc
vl sau khi diSu trj. Cu the la trudc khi diSu trj khong cd benh nhan nao dat tiSu chuan kiSm soat hen nhung sau diSu trj sd BN dat kiS'm solt ben ngay cang tang dan vl dac biet sau 6 thing diSu trj da cd tdi 70.9% BN dat miic kiSm solt hen tdt. Su khlc
biet nay cd y ngbTa thdng kS vdi p<0,001. Day cung la mdt ket qua tuong ddi cao pban Inh hieu qua diSu trj du phdng eiia tbudc symbicort. Nhu vay cd the ndi nSu nhu BN tuan tbii dieu trj du phdng tdt thi cd thS dat dugc kiSm solt hen toi uu va tir dd giam dugc ty IS tir vong do hen.
•> •> ^ . ^ Bdng 6. Thay ddi diim sd test ACT trudc vd sau diiu tri
Thdi diem Trudc DT SDT 1 thang SDT 3 thang SDT 6 thang
Diem sd test ACT (N=86)
<14 n 50
8 5 4
% 58,1
9,3 5,8 4,6
15-19 n 24
12 9 6
% 27,9 14,0 10,5 7,0
20-24 n 12 59 47 14
% 14,0 68,6 54,7 16,3
25 n 0 7 34 62
% 0,0 8,15 39,5 72,1
P
p>0,05 p<0,05 p<0,05 Hieu qui diSu trj du phdng ciing dugc thS hien
thong qua su thay ddi diem so ACT trudc va sau khi diSu trj. Theo ket qua nghien ctru ciia chiing tdi, trudc khi diSu trj khong cd BN nao dat diSm ACT tdi da la 25 diSm, nhung sau khi diSu trj sd BN dat diS'm tdi da ngay clng tang dan vl dac biet sau 6 thing diSu trj cd tdi 72,1% BN dat diem ACT tdi
da la 25 diSm, diSu dd cd nghTa II dat mirc kiSm solt hen tdt. KSt qui nly ciing tuong tu nhu kSt qua vS su thay ddi mirc do kiSm solt dinh gil theo 6 tiSu chi ciia GINA nhu da trinb bIy d trSn. Nhu vay kSt qui nghiSn ciiu nly ciia chting toi lai mdt lan nGa khang djnh vai trd ctia trac nghiSm kiem soat hen trong viec theo ddi va dinh gil MDKS hen.
3. Hieu qua dieu trj cat con
Bdng 7. Hiiu qud diiu tri cdt con cua Symbicort Hieu quii dieu trj cat
con Sau dieu tri 3 thing Sau dieu tri 6 thing
Cd hieu qua SdBN
67 71
% 77,9 82,6
Khdng hieu qua SdBN
19 15
% 22,1 17,4
Tdng SdBN
86 86
% 100 100 Symbicort khdng cht cd hieu qua cao trong
diSu trj du phong hen ma cdn cd hieu qua trong diSu trj cat can hen phS quan. DiSu nay cung da dugc GINA 2006 de cap den vdi noi dung nhu sau:
"Formoterol/budesonide trong ciing mgt dng hit dS ngiia con vl cat con cd hieu qua cao trong duy tri kiem soat hen vl gilm cic dgt kjch phlt" [4].
Theo kSt qua nghien ciiu cua chting toi, trong long sd 86 benb nhan tham gia nghiSn ctiu, 77,9%
CO hieu qui diSu trj cat con sau 3 thing diSu trj vl 82,6% benh nhan cd hieu qua diSu trj cat con sau 6 thing diSu tri. Nhu vay, ty IS thanh cdng dat dugc la tuang doi cao. Sd dT cd dugc kSt qua nhu trSn la do trong thinh phan ciia Symbicort ngoai coricoid dang hit con chira formoterol II tbudc cudng beta 2 tic dting keo dii va cd hieu qua khdi phat tic dirng nhanh chi sau 1-3 phiit tuong tu salbutamol nSn ngoai tic dung du phdng kiem soat hen symbicort con CO tie dung cat con HPQ hay con dugc ggi II lieu pblp SMART. TrSn thS gidi da cd nhiSu cdng trinh nghien ctru cbung minh vS kha nlng cit can vl kiSm solt HPQ cua Symbicort SMART, trong do phai ke dSn mgt sd nghiSn ciru tieu bieu nhu:
nghiSn ciiu STAY, SMILE, COMPASS. NghiSn ciru COMPASS dugc thuc hien gan day ciia tic gia Kuna v l cdng su nam 2006 vdi muc dich so sanh hieu qui sir dung Symbicort SMART vdi liSu cao cd djnh kem terbutaline ciia Symbicort hoac Seretide. Day II mdt nghiSn ciru ngau nhiSn mu doi dugc theo ddi trong 6 thing [5]. KSt qua ctia nghiSn ciru nly cho thay sir di.ing Symbicort SMART tang thdi gian pbdng ngua can kjch pblt dau tiSn (giam nguy ca tiic thi 33% so vdi Seretide; 26% so vdi Symbicort liSu cao cd djnh), ciing nhu gilm ty IS dot kjch phat nang (gilm 39% so vdi Seretide; 28%
so vdi Symbicort liSu cao cd dinh) va benh nhan diSu trj theo phuang phap SMART can dung it tbudc corticosteroid bit hon nhdm benh nhan diSu trj bang Seretide va liSu cd djnh (liSu ICS trung binh 11 755; 1000 va lOOOmcg/ngly). Tic gia kSt luan ring sir dirng Symbicort SMART dan dSn giam rSt nhiSu ty IS dgt kjch phlt can hen nang, giam sd lugng nhap vien vl diSu trj cap ciru hen, va giam ca tdng lugng cortieoid su dung dudng hit va udng so vdi nhom diing liSu cd djnh cao cua Symbicort hoac salmeterol/fluticasone va la lieu
4 2 IY HOC LAM SANG So 46 (Ttiang 11/2009)
Nghien cii'u khoa hpc
pblp dS sir dung, hieu qua ban de kiem solt hen phS quan [5].
Trong nghiSn ctru ciia chiing tdi, hieu qua diSu trj cat can ciia Symbicort dugc danb gia qua
Bdng 8. Nhu cdu nhap vien cdp ciiu
2 chi tiSu chinb dd II su thay ddi vS nhu cau nhap vien cip ciru va nhu cau diing thSm tbudc khlc dS' elt can trong q u i trinh diSu trj so vdi trudc khi diSu tri.
Thdi diem Trudc dieu tri Sau dieu tri 1 thing Sau dieu tri 3 thing Sau dieu tri 6 tbang
Nhap vien cap citu ( N So benh nhdn
36 10 9 5
Ty le % 41,9 11,6 10,5 5,8
f=86) P p>0,05 p<0,05 p<0,05 Nhu chiing ta da biSt nhap vien cap ciiu do hen
cbiing td benb nhan hen van cdn cd nhung dgt kjch phlt nang va benh hen chua dutx ks tdt. Theo kSt qui nghien ciiu ciia chiing tdi trudc khi diSu trj cd tdi
41,9% cd nhu cau can phai nhap viSn cap ciiu nhung sau diSu tri ty IS nay giam dan va dac biet sau 6 thing cht cd 5,8% BN cd nhu cau nhap vien cap ciiu vi hen.
Sy khlc biet nay cd y nghTa thdng kS vdi p<0,05.
Bdng 9. Nhu cdu dung thim thude khde de cdt corn HPQ
Thdi diem Sau diSu trj 1 thang Sau diSu tri 3 thang Sau diSu tri 6 thang
Nhu cau dung them thuoc khac Cd
n 23 12 10
% 26,7
14,0 11,6
Khdng n 63 67 71
% 73,3 86,0 88,4
P p>0,05 p>0,05 p>0,05 Hieu qua diSu trj elt con cdn dyoc the hien qua su
thay ddi vS nhu cau sir dung thuoc khac dS cat con trong qui trinh diSu trj. Theo kSt qua nghiSn cuu ciia chiing toi, sau diSu trj 1 thing nhu cau sir dung thSm
thuoc khac dS cit con van cdn chiSm ty IS tuong ddi cao II 26,7%, nhung sau 3 thing, 6 thing ty le nly gilm dan. Tuy nhiSn su khlc biet nay khdng cd y nghTa thdng kS vdi p>0,05.
4. Mot so tac dung khong mong muon cua Symbicort SMART
Bdng 10. Mot sd tdc dung khdng mong mudn cua Symbicort SMART Tac dung phu
Nbiic dau Kbin tieng Ho
NbiSm Candida bau bong Nbip tim nhanh
Kbac
Sd benh nhan (n=86) 2
3 1 0 5 3
Ty le % 2,3 3,4 1,2 0,0 5,8 3,4 Trong tdng sd 86 benh nhan tham gia nghien
ciru chi cd 16,3% benh nhan bj mgt trong cle tic dung phti ciia tbudc. Trong dd, tic dirng phu hay gap nhat II nhjp tim nhanh chiSm 5,8% (5 benh nhan) dac biet II kbdng gap benh nhan nao bi nhiSm nam Candida hau hgng, cdn lai gap mgt sd tic diing khlc nhu khan tieng 3,4% nhtre dau 2,3%, ho 1,2%.
Sd dT tic dting phu gay nhip tim nhanh hay gap ban cic t i c dting phti khlc la bdi vi trong tblnb phan ciia tbudc cd chua chat cudng beta 2 tac dting keo dii (formoterol) cd thdi gian khdi phlt tac dung ngan (1-3 phiit) gidng nhu salbutamol nSn nd cd thS' gay nhjp tim nhanh khi phai diing nhieu Ian trong ngly de cat can hen phS quan.
Tuy nhien, nhiing tic dung phu tren khdng gay nguy hiS'm cho ngudi benh, dung nap tdt vl khdng c2n phai xtr tri gi thSm.
IV. KET LUAN
Qua nghien ciiu diSu trj 86 benh nhin hen phS quan chua kiem soat bang lieu pblp Symbicort SMART chiing tdi riit ra nhirng kSt luan sau:
- Hieu qua diSu trj du phdng sau 3 thing dat 80,2%, sau 6 thing dat 84,9%.
-I- Ty IS benh nhan dat dugc kiSm solt hen tang len dang ke theo thu ty thdi gian 6,9%, 34,9%, 70,9% so vdi trudc khi diSu tri 0,0% (p<0,001).
-I- Ty IS benh nhan dat diem sd ACT tdi da 25 diSm ciing tang ISn rd ret theo thirty thdi gian 8,1%, 39,5%, 72,1% so vdi trudc khi diSu trj la 0,0%
(p<0,05).
- Hieu qua diSu trj cat con ciia Symbicort SMART dat 77,9% sau 3 thing diSu tri vl 82,6% sau 6 thing diSu trj.
-I- Sau diSu trj 1 thing, 3 thing, 6 thing nbu cau nhap vien cap ciiu ngly cang giam dan theo thirty la 11,6%, 10,5%, 5,8% so vdi trudc khi diSu trj la 41,9% (p<0,05).
+ Sau dieu trj 3 thing, 6 thing nhu cau diing them tbudc khac de cat con trong qui trinh dieu tri cd xu hudng giam dan theo thir ty 14,0%, 11,6% so vdi sau diSu trj 1 thing II 26,7% (p>0,05).
- Tie dung phu thudng gap la nhjp tim nhanh chiSm 5,8% sau dd la khan tiSng chiSm 3,4%, nhiic dau 2,3% vl khdng cd benh nhan nao bj nhiSm nam Candida d hau hgng. CIc tic dung nly khdng gay nguy hiSm cho ngudi benh, cd thS dung nap tot va khdng can xu tri gi thSm.
TAI LIEUTHAM KHAO
1. Trang Thanh Thuy (2006), "Ddnh gid hiiu qud Combivent khi dung cat con khd tha trin binh nhdn hen phi quan tgi khoa Di iing - MDLS, Binh vien Bgch Mai", Ludn vdn Thgc syy hgc, Hd Ndi, tr 57-60.
2. Bateman ED, Bantje TA, Joao Gomes M, Toumbis M, Huber R, Eliraz A (2003), "Symbicortd is more effec- tive than a higher dose of fluticasone in moderate persistent asthma". Am J Resp Med; 2(3)275-281.
3. Buhl R , Creemers JPHM, Vondra V, Martelll NA, Naya IP, Ekstrim T (2003), "Once-daily budes- onide/formoterol in a single Inhaler in adults with moderate persistent asthma". Resp Med; 97:323- 330.
4 GINA (2006), "component 3: assess, treat and mon- itor asthma" p 57- 63.
5. Kuna, et all (2006), "Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacer- bations". Eur Respir J ; 28(Suppl 50): 205s, Abs P1228.
6. Lai CK, De Guia TS, Kim YY, Kuo SH, Mukhopadhyay A, Soriano JB, et al (2003). "Asthma Insights and Reality in Asia-Pacific Steering Committee. Asthma control in the Asia-Pacific region: the Asthma Insights and Reality in Asia- Pacific Study". J Allergy Clin Immunol;
lll(2):263-8.
7. Lalloo UJ, Malolepszy J et al 1(2000), "Low dose Symbicort (budesonide/formoterol) is more infective than double-dose Inhaled corticosteroid in mild asth- ma. Allegy Clin Immunol int; 12 ( suppl 2): 435 + poster + AstraZeneca, data on file SI.
SUMMARY
ASSESSMENT OF MAINTENANCE A N D REUEVER THERAPY EFFICACY BY SYMBICORT IN ASTH- MA PATIENTS
Object: to evaluate Maintenance And Reliever Therapy efficacy by Symbicort in asthma patients. Subjects and methods: the prospective study on 86 patients with uncontrol asthma in Bach Mai Hospital from 1/2008 to 10/2008. Results: maintenance efficacy is 80.2% after treatment 3 months and 84.9% after treat- ment 6 months. Reliever efficacy is 77.9% after treatment 3 months and 82.6% after treatment 6 months.
Side effects: rapid heart rate 5.8%, headache 2.3%. Conclusion: symbicort SMART therapy eficacy is very high and safety.
Keywords: asthma, symbicort.
4 4 IY HOC LAM SANG So 46 (Ttiang 11/2009)
