Tap chl Tai Mui Hgng Vi$t Nam - Volume (58-16). N 4 - June, 2013
DANH GIA Mirc BQ CAI THIf N CHAT LlTpNG CUpC SONG 6 BENH NHAN VIEM MUI DI iTNG VOl DI NGUYEN DERMATOPHAGOIDESPTERONYSSINUS DlTpC DIEU TRI
BANG MIEN DICH DAC HIEU D I / O N G Dl/Ol LlTOl
Vu Trung Kien', Phfm Klin Hiti/, Va Minh Thuc', Phung Chi Thi^n', Tdng Xuan Hi^
T6M TAT
Bgt van te: Diiu Iri VMDU theo ca chi benh sinh hay li(U phdp miin dich (LPMD) cd hieu qud yd kinh le han hdn cdc phuong phdp diiu tri khdc, LPMD dudng duai luoi eg nhieu uu diem han cdc dudng dua thudc khdc. Muc tieu: Ddnh gid muc dg cdi thien chdt luang cugc sdng a benh nhdn viem mui di ung vai di nguyen Dermatophagoides pleronyssinus duac dieu Iri bdng gidm man cdm duang dudi ludi. Boi tirfng va phinmg phdp nghiin cuu: Gom 45 benh nhdn chdn dodn VMDU" vdi Dp, nghien cuu tiin ciru, lu ddi chung tgi Benh vien DHY Hdi phdng, Benh vien Tai MUi Hgng Trung uqng. Kit qui:
Chdl lugng cugc sgng (CLCS) cdi thien a tdt cd cdc linh vuc ciing nhu diim trung binh chung, su khdc biet sg vdi trudc dieu Iri cd y nghia thing ke vdi p < 0,01. Diim CLCS cdi thien trung binh 45% a benh nhdn VMDU'. Kit luan: CLCS a benh nhdn VMDU do di nguyen Dermatophagoides pleronyssinus sau diiu Iri miin dich ddc hieu duang dudi ludi cdi thien trung binh 45% so vdi Irudc dieu Iri.
Tit khda: viem mui di img
ASSESSMENT LEVEL OF QUALITY OF LIFE IN PATIENTS ALLERGIC RHINITIS TO DERMATOPHAGOIDES PTERONYSSINUS BY USING SUBLINGUAL
IMMUNOTHERAPY
Vu Trung Kien, Pham Kien Huu, Vu Minh Thuc, Phung Chi Thien, TangXuan Hai Introduction: the treatment of patients with allergic rhinitis following the pathogenic mechanism or immunotherapy showed more effective and economic than other methods.
Sublingual immunotherapy (SLIT) had more advantages than those of others. Objective: lo evaluate the efficacy of clinics of allergic rhinitis lo Dermatophagoides pleronyssinus (Dp) after SLIT and the change of laboratory parameters Patients and Method: including 45 palieitls with allergic rhinitis lo Dp met criteria of aulacontrolled follow-up study al Haiphong Medical University Hospital. ENT Hospital Results: Quality of life (QoL) improved in all areas as well as general the difference compared lo before treatment was statistically significant with p <0.01. Point of QoL average improvement of 45% in patients allergic rhinilis. Conclusion: QoL decreased in patients' allergic rhinitis by allergens Dermatophagoides pleronyssinus after treatment sublingual immunotherapy improvement of 45% compared with pre-trealment.
Key words: allergic rhinilis
'Bai hpc Y Thai Binh,
^Dai hoc Y Dircrc Ip H6 Chi Minh,
^B?nh vien Tai Mui Hong TW,
•"Dai hoc Y Hai Phong,
'B$nh vi?n Httu Nghi da khoa Nghe An Nhan bai 25/4. Duyet in 5/5.
6 4
Tgp chl Tai MQi Hpng Vifet Nam - Volume (58-16). N°4 - June, 2013
1.0;^T VAN Bt
Vidm mioi di ung (VMDU) la b§nh hay gap trong chuyen khoa tai miii hong, b?nh CO xu huong ngay cang gia tang dac biet a nhimg nuoc cong nghiep hoa. Tin suit VMDU* a chau Au nhu Bi 28,5%, Vuong Qu6c lien hidp Anh 26,5%, Phap 24,5%, TSy Ban Nha 21,5%, Diic 20,6%, Italia 16,9% [1], a cac nuoc Dong Nam A nhu Indonesia 10,90 32,59%, Singapore 42,1%, Philippin 32.5% va 6 Vi?t nam 11.2%. Nguydn nhan gay VMDU" phin Ion la do bui nha, trong do Dermatophagoides pteronyssinus (D.pte) chidm ty le chu ydu (90-95%) [2],[4],[5]. Phuong phap didu tri midn dich dac hieu hay lieu phap midn djch (LPMD) ia phuong phap dieu tri theo co che benh sinh ciia benh VMDU co hieu qua va kinh td hem ban cac phuong phap dieu tri trieu chiing. Phuong phap nay da duac ling dung a nhieu nuac trdn thd gioi. 0 Viet Nam LPMD chi sir dung duong tiem trong da. Hien nay, chua c6 mot nghidn ciiu nao danh gia ve hieu qua cua LPMD duong dudi luoi trong dieu tri VMDU do di nguydn D.pte. Xuat phat tir van de trdn, chiing toi tidn hanh: Ddnh gid muc dp cdi thien chit luong cupc sdng d binh nhdn viem mdi df ung v&i rf/ nguyin Dermatophagoides pteronyssinus duoc diiu tri bdng miin dich ddc hi^u dudng dudi ludi.
2. » 6 l TU'ONG VA PHITONG PHAP NGHIEN cifV
2.1. Bia diem, thoi gian va doi tu-ong nghien cmi
2.1.1. Dia diim nghien cuu
Khoa Mien dich - Di nguyen, Benh vien Tai Mfii Hgng Trung uong. Khoa Di
ling Mien dich Lam sang, Benh vien Dai hoc Y Hai Phong.
2.1.2. Thdi gian nghiin ciru: Nghien cuu duoc tiin hdnh tie 8/2010 din 4/20J2 2.1.3. Ddi tup^g nghiin ciru
Nhihig benh nhan co bidu hien viem mui di ling do D.pte du tieu chuin lira chpn (n=45) 2.1.3.L Tieu chuin chpn Si tuprng nghien cuu
* Tieu chudn chon ddi tuong cho nghien cuu
Duac chgn ngau nhidn vao nghien ciiu tai benh vien neu thoa man cac didu kien sau:
- Liia tuoi: 16-55, khong phan biet gioi tinh.
- Dugc chan doan lam sang la viem miii di ling:
Co tien su di ling: ca nhan da co cac con viem miii di ung nhu tren nhieu nam, ngoai ra ca nhan va gia dinh co the mac cac benh di ling khac hoac khong.
Co nang: hat hai thanh trang, chay mui nuoc trong va ngat hoac tac miii. Cac trieu chiing xuat hien thanh can. Co the giam ngiii hoac khong.
Kham thuc the tai cho: cac benh nhan dugc Idiam ngi soi mui xoang ong ciing dd xac dinh tinh trang tai ch5: nidm mac nhcft nhat, dich nhay xuat tiet, cuon mui phii ne dac biet la qua phat cuon duai...
- Test lay da duong tinh vai di nguyen D.pte.
- Dong y tham gia nghien ciiu va dieu tri ngoai tni toi thidu la 2 nam.
* Tieu chudn logi trie
Benh nhan dang hoac dir kien mang
T9P chi Tai Mui Hpng Vi6t Nam - Volume (58-16). N°4 - June, 2013
thai trong dgt dieu tri.
Benh nhan dang mic b§nh dj ling khong phai do D.pteronyssinus.
Benh nhan mic benh tim mach, gan than, ho hap a giai doan mat bii.
Benh nhan dang c6 can tam than.
Benh nhan bi mic benh tu mien.
Benh nhan dang hi benh iy nhiem khuan cap a mui xoang. Neu tinh trang trdn chi la bgi nhiem tren benh nhan viem miii di iing co dii tidu chuan lua chgn tren thi chung toi didu tri hdt dot bgi nhiem roi tiep tuc lay vao nhom nghien cuu..
Benh nhan dang dieu tri trong vong 2 tuan truoc do bang cac thuoc: khang histamin, corticoid, thuoc kich thich adrenergic (vi du nhu Salbutamol...), hoac cac bai thuoc dong y chua di iing noi chung. Ciing nhu tren cac benh nhan nay sau khi diing dieu tri cac thuoc tren 2 tuan se dugc chgn vao nhom nghidn cuu neu co dii tieu chuan lua chgn.
2.2. PHU'OfNG PHAP NGHIEN C f u 2.2.1. Thiit ki nghiin ciru
Nghien cuu thir nghiem lam sang tu doi chiing truac va sau can thiep nham danh gia hieu qua didu tri mien dich dac hieu ducmg duai luoi a benh nhan viem mQi di ling do di nguyen D.pteronyssinus.
2.2.2. Phuong phdp chpn mdu vd cd mau nghiin cuu.
2.2.2.1 Co mdu nghien ciru - Cdmau cho nghiin ciru can thifp:
[z, _ : , : p (i-p:-Zv pi (i-pi;-p: '-i-p:.' ]•
^ = ^ ; •
'.pl-p2.''
pi: ty le benh nhan VMDU do D.pte truac didu tri (test lay da (+) vai D.pte) -100%.
p2: ty I? b?nh nhan VMDU* do D.pte sau didu tri (test lay da duong tinh voi D.pte) = 80%. (Ky vpng sau 2 nam didu tri MDDH giam 20%).
P = (Pi-P2)/2 = 0,l.
Chgn xic suit th6ng ke sai lim loai 1, a = 0,05(Z(,^,=l,96);
Chgn luc mau (power)=0,8; v6i p=0»2;
Zp = 0,842.
n : s6 b?nh nhan VMDU do D.pte can nghien cuu can thi?p.
Theo cong thiic tren tinh n = 35 b?nh nhan.
Trong nghien ciru cua chiing toi co 45 benh nhdn th\rc hifn dii lieu trinh didu trj mien dich dac hi?u trong thai gian 2 nam theo diing phac do ciia nhom nghidn ciiu.
2.2.2.2. Phuongphdp chpn mdu.
- Chgn cac benh nhan ddn kham tinh trang vidm mui dj ung t^ khoa Di iing Mien dich lam sang, benh vi?n Dai hpc Y Hai phong
- Cac benh nhan dugc didu trj mien dich dac hieu bang di nguyen D.pteronyssinus ciia phong Midn dich Di nguyen, Benh vi?n Tai Mui Hpng Trung uong.
2.2.3. Cdc phmmg phdp vd ky thu&t dp difng trong nghien ciru
2.2.3.1. Ddnh gid chdt lupng cupc song theo bdng chdt luong cudc sdng:
Danh gia nhimg anh huong ciia VMDU len CLCS cua BN trong su6t 1 tuan truoc khi tai kham 6 thoi didm bit dau didu tri va sau 24 thang. Sii dung bp cau hoi RQLQ cua Juniper dd d^nh gia chat lugng cugc song o cac muc [8].
2.2.3.2. Diiu tri miin dich ddc hi$u duong duoi ludi.
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Tap chl Tai MQl Hgng Vi$t Nam -Volume (58-16). N''4-June, 2013
Phac do dieu tri
Bang 2.8. Ph^c 66 di^u trj m\hn djch d$c hi^u du&ng dudi lu&i v&i D.pte
TIti tan cdng (25 ngdy) Ngdy 1-4
1 - 3 - 4 - 6giot
IllUmI Ngdy 5-8
1 - 3 - 6 - 10 gipt
10 IRJml Ngdy 9-16
1 - 2 - 4 - 6 - 8 - 1 2 -
1 6 - 2 0 gipt 100 IR/ml
Ngay 17-26
5 - 6 - 8 - 1 0 -12-14-16 - 1 8 - 2 0
gipt 300IR/ml
Tilt duy tri (300 llVml) BiSu In duy tri, liiu 6n dinh. MOt khi da dgt duHp-c, lieu t6l da dirge su* dgng hang ngdy nhd 16 - 20 gipt n6ng dO 300 IR/ml
Nong dp 300 IR/ ml da chiing to trong cac thu nghiem lam sang co doi chiing la nong dp thich hop nhdt de nhanh chong dgt dugc liiu tich luy hieu qud. [9]
Thdi gian Miu tri: lien tuc trong 2 nam.
2.3. XU" LY SO LIEU: Theo cac phuong phap th6ng kd y sinh hgc, phan mdm SPSS 15.0
3. KET QUA NGHIEN ClTU
3.1. Sir thay d6i diem CLCS lien quae hoat dpng
L LI Li
(narq) ( i w g binti) (nhe) Ihiroiig)
Hinh 3.1. Sy- thay d6i CLCS Ii6n quan hoat ddng.
Nh^n xet: Truoc didu tri 100% ddu bi gioi han ho^t d6ng, sau 24 thang didu tri co 33,3% khong con thiy bi gioi han boat
dgng boi anh huong ciia cac trieu chiing VMDU, su giai h ^ hoat dpng dugc cai thi?n c6 y nghTa th6ng ke vai p < 0,01..
3.2. Su- thay doi CLCS lien quan tri^u chirng mui
IJIJ!
Hinh 3 2 Su thay doi CLCS Ii6n quan trigu chung mOi
Nhan xet: 100% BN deu cam thay cac trieu chiing mui anh huong len cugc song, sau 24 thang dieu tri miic do anh huong cua trieu chiing viem miii giam ro ret theo cam nhan cua BN vai 42,2 % khong con thay bi anh huong, va chi con 8,9% cam thay bi anh huong rat nhieu.
3.3. Su- thay d6i CLCS lien quan trieu chirng mat
Hinh 3 3. Su- thay d6i CLCS Ii6n quan tri&u chung mSt
Nhan xet: Truac didu tri 100% benh nhan thiy kho chiu o mit, sau dieu tri 15,5% benh nhan khong bi anh huong boi cac trieu chiing mit. Miic do anh huong truofc va sau didu tri giam co y nghia thong ke voi p< 0,01.
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3.4. Sir anh hirffng len CLCS do cac vin de thirc hanh
w IJ
Hinh 3 4 Sy 5nh huong Ifen CLCS do cdc v^n d^ thyc hSnh
Nhan xet: Hau het c^c van de n^y sinh do trieu chiing nhu hi mui lau mui lau nu6c mit ddu anh huong toi CLCS BN 6 miic nhieu va rit nhieu.. Sau didu tri cam nhan bat tien nay cai thien co y nghia voi p < 0,001.
3.5. Stf anh hu-ong ciia trieu chirng ngo^i mui/mat len CLCS
j u i
I*
Hinh 3.5- Su anh hudng cua trieu chung ngo^i mat/mui I6n CLCS
Nhan xet: 100% BN co bidu hien cac trieu chiing nay va hau het ddu 6 miic rat tram trgng. Sau dieu tri su bieu hien cac trieu chiing nay giam dang ke voi p < 0,001.
3.6. Sir anh hvong ciia roi loan cam xuc len CLCS
In
Nh|n xet: Sau di4u tri trieu chiing lo ling, cdu gian dir(?c cii thien nhieu; 11,1%
b$nh nhan khong con biSu hien lo ling anh hufifng benh nfl-a.
3.7. Khai qu4t chung cic chi s6 CLCS BSng 3.1. S\f thay dii cSc chl so chat lu'p'ng
cuOc s6ng sau di^u trj ^
Chl s6 CLCS
Di^m CLCS TB Chung Hogt dOng Cdc tri$u chi>ng mui Cdc tri$u chijng mat Cdc van de thi^c hanh Cac tn§u chLPng ngoai mui/mdt Cam xuc
Tru^c di^utn X±SD 4,4 ±1.4
2.8 ±1,8 4.6 ±1,4
4,0 ±1,6
4,6 ±1,0
5,0 ± 0,8
4,4 ±1,4 Sau diSu tn
24 thang X±SD 2,4 ± 2,0
1,4 ±1,2 2,6 ± 2.0
2,4 ± 2.0
2,0 ±2.0
2,8 ±2,0
2.6 12.0
%
thay d6i 4 5 %
5 0 % 43%
4 0 %
57%
4 4 %
4 1 % P
p<0,01
Hinh 3-6. Su anh huong cua roi logn cam xuc len CLCS
Nhdn xet: Sau didu tri CLCS cai thien voi su khac biet co y nghia thong ke so vol truoc dieu tri o tat ca cac khia canh cung nhu diem trung binh chung.
4. BAN LUAN
Hi^u qud cdi thi^n chdt luong cudc song cua lieu phdp mien dich dudng dudi ludi
VMDU lam giam CLCS a ca 6 khia canh dugc danh gid trong nghien ciiu cua chiing toi. Trong do CLCS bi anh huong nhidu nhat 6 ITnh virc cac trieu chiing ngoai mui/mat voi cac diu hieu ve sue khoe tinh than (5 didm); va ITnh vuc hoat dgng la it bi anh huong nhit (2,8 didm). Nghien cuu ciia chiing toi cho thiy VMDlT gay la cho benh nhan cam giac met moi, kho chiu, giam t^p trung, dau diu, de cau gat, dd tiic gian hem va 6 nhung ngucri bi benh lau nam hg con
Tgp chl Tai IVIOi Hpng Vr$t Nam - Volume (58-16). N''4 - June, 2013
CO cam giac lo ling vd benh. Nghien cuu cua Trdn Doan Trun^ Cang va cgng su [4]
vd chit luang cugc song trdn 48 benh nhan CO bieu hien vidm mui xoang man tinh co hen phd quan di kem thiy 41,67% c6 vin dd vd giic ngu, co 22,92 % giam hoat dgng thd thao, thu gian c6 22,92 %, cdm giac kho chiu CO 6 62,5% va 43,75% giam kha nang lam viec.
Kdt qua nay tuong d6ng voi cac nghien ciiu trdn thd gioi truoc day chi ra ring:
VMDU anh huong len CLCS chii ydu 6 cac khia c ^ siic khoe tinh thin khac v6i HPQ chu ydu anh huong Idn khia canh siic khoe thd chit [3],[5].
Ban vd moi tuong quan giiia miic dg trieu chiing va miic do suy giam CLCS.
Mgt s6 tac gia chi ra ring giua didm CLCS va didm trieu chiing miii co m6i tuong quan 6 miic trung bmh (r < 0,05) nhung co y nghia th6ng kd. Trong do CLCS tuong quan nhieu hon vcri trieu chiing hit hoi va n ^ a miii. Chiing toi nhan thiy, a thai didm bat diu dieu tri hau hdt BN bidu hien cac trieu chiing nang (chii yeu la hit hoi va chay miii) va tuong ung ia tinh trang CLCS hi suy giam rat nhidu voi diem CLCS trung binh la 4,4. Sau hai nam miic do bieu hien trieu chiing giam di ro ret, d6ng thoi didm CLCS ciing cai thien co y nghia con 2,4.
Mac du khong tinh dugrc he so tuong quan do khong danh gia BN 6 nhidu thoi didm nhung vdi nhimg kdt qua nhu tren ggi y m6t SIT tuong quan tuyen tinh giira diem CLCS va mijc do bieu hien trieu chung.
Kdt qua nghidn ciiu ciia chiing toi cho thiy, sau 2 ndm didu trj LPMD duong duoi lu5i, CLCS cai thien 6 tit ca cac Imh vuc ciong nhu diem trung binh chung, su khac biet so voi truac didu tri co y nghia thong kd vdi p < 0,01. Ndu CLCS cai thien 30%
so vdi truoc didu tri dugfc coi la bien phap
didu tri CO hi?u qua, thi trong nghien ciiu cua chiing toi didm CLCS cai thien trung binh 45%. D6i chieu vdi cac nghien ciiu cua ciia nhidu tac gia khac trdn thd gioi:
Alain Didier cho bidt CLCS cai thien 20 % so voi "gia dugc" 6 BN VMDU vai phin hoa; Ciprandi [38] didu tri giai man cam o BN da man cam thi didm CLCS cai thien a tat ca cac muc voi p < 0,01; Kimihiro Okobu dieu trj mien dich cho benh nhan VMDU voi phan hoa tuydt tiing co su cai thien cac muc CLCS vai p < 0,05; Sabina Rak didu tri LPMD a benh nhan VMDU voi phan hoa voi cac lidu di nguydn khac nhau cho kdt qua cai thien CLCS phu thugc lidu tir 17% tdi 26% so voi nhom chiing; va mgt so nghidn ciiu khac cho kdt qua cai thien didm CLCS trong khoang tir 20% ddn 30% so voi gia dugc, hoac vai p < 0,01 va 0,05 [l],[3],[5],[6],i7], [8],[9]. D6i chidu cac didu kien tien hanh didu tri ciing nhu phuong phap danh gia ket qua chiing toi thay rang su khac biet ve ket qua cua chiing toi CO thd do cac li do sau.- Thu nhdt,trong cac nghien cihi trdn, doi tugng benh nhan ddu la VMDU theo miia vdi phan hoa, ma LPMD lai bat dau didu tri truoc miia hoa it nhat la 8 tuan, vi vay thai diem danh gia ban dau hau nhu BN khong co trieu chiing hoac bieu hien nhe nen CLCS a liic bit diu nghidn ciiu khong bi anh huong nhidu. Thii hai, do kdt qua danh gia deu la so voi nhom chiing khoe manh, khac vdi so sanh tinh trang CLCS 6 thai didm khoi diu ciia chinh benh nhan. Vi vay sir cai thien diem CLCS thap hon la hgp ly. Thii ba do cong cu dd danh gia CLCS khac nhau, hau hdt su dung Bang CLCS ciia Juniper, kdt hgp sii dung bang SF - 36, hoac cac bang CLCS dac thCi quoc gia, vi vay day ciing la nguyen nhan tao ndn khac biet.
So sanh su cai thien CLCS o benh nhan dieu tri bing khang Histamin, hoac
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Tap chl Tai IVIOi Hpng Vi$t Nam - Volume (68-16). N°4 - June, 2013
Coiticoid, ho3c phoi ht^p. Ciprandi danh gia cai thien CLCS 6 b$nh nhan VMDLT khi dieu tii bing Corticoid xit inui thu dirge kk qua cai thien diem CLCS c6 y nghia 6 5/7 muc CLCS theo RQLQ, tuy nhien c6 biSu hien tdc d\mg phu 6 15% BN. C6n Ciebiada phoi hgp Loratadin v6i Montelukast thu dugc sy cai thi?n d cd 7 myc CLCS theo RQLQ. Sabina Rak chi ra LPMD cai thien CLCS tot hon so voi diSu tn thuoc don thuan. Cac nghien cuu thu dugc ket qua t6t ve hieu qua cai thi?n CLCS. Tuj' nhien hieu qua khong bing voi LPMD, dong thai benh nhan phai chip nhan nguy co tac dung phu. Hon niia diSu tri thuoc khong giai quyet dugc tan g6c nguyen nhan gay benh. Chinh vi vay LPMD van la lira chgn uu tien hon dk di^u tri VMDU [3],[5],[71,[8],[9].
5. KET LUAN
VMDLT lam giam CLCS 6 ca 6 khia canh dugc danh gia trong nghien cuu cua chiing toi.
Diem CLCS trung binh chung giam 45% so vcri truoc dieu tri
Cac van de ve thuc hanh giam 57%
Hoat dpng giam 50%
Cac trieu chung ngoai mui/m4t giam 44%
Cac trieu chimg mui giam 43%
Cam xuc giam 41%
Cac trieu chiing ve mit 40%
TAI LIEU THAM KHAO 1. Ado A.D. (1986), Di ung hgc dai cuang,
Nguoi dich: TSKH. Nguyin Ndng An, IS. Trucmg Dinh Kiet, NXB Mir, Matxcova, tr. 74-85.
2. Pham Quang Chinli (2004), Nghien dm nudi cdy. tdchchiil vd mgt sd ddc linh hod sinh miin dich ciia di nguyen
Dermatophagoides pteronyssinus vd buac ddu ung dung Idm sdng, Luan an Tiin si Sinh hpc, Vien Cong ngh? sinh hpc.
3. Dodn Thi Thanh Ha (2002), Nghien ciiu chdn dodn vd dieu tri mien dich viem mm di ung do dj nguyen bui nhd, Luan dn Tien sT Y hpc, Vien V? sinh dich tl Trung uong, Ha Ngi.
4. Vu Minh Thuc (2009), „Nghien cmi dieu che, tieu chuan hod di nguyen long vu 6 nhiing ngu6i tiep xiic vcri gia cSm trong ngdnh chdn nuoi thii y". Di tdi nghien cuu khoa hgc cap Thdnh phd Hd Ngi, md so: OlC-08/06-2007-2.
5. Vu Minh Thuc, Luang Xuan Hiln, Vo Thanh Quang, Pham Van Thiic va CS (2010), Mgt bui nhd Dermatophagoides pleronyssinus, ly ludn vd thuc hdnh. Nha xudt ban y hgc.
6. Alvarez-Cuesta E., Berges-Gimeno P., Mancebo E.G. (2007), '-Sublmgual immunotherapy with a standardized cat dander extract: evaluation of efficacy in a double blind placebo controlled study". Allergy, 62(7), pp. 810-7.
7. Alam Didier M., et al. (2007), "Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis.", J Allergy Clin Immunol, Tpp. 1-8.
8. Albrecht Bufe et al. (2009), "Safety and efficacy in children of an SQ- standardized grass allergen tablet for sublingual immunotherapy", J. Allergy Clin Immunol, pp. 167-73.
9. Bousquet J., Lockey R.F., Mailing H.. et al ed (1997), "Allergen immunotherapy:
therapeutic vaccines for allergic diseases", Allergy: World Health Organization position paper.
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