ĐOÀN CẬPNHẬT GINA &hen kho ́trị

CP NHT GINA

& HEN PH QUN KH TR

PGS. TS. Nguyn Vn on

G

IN

A

lobal

itiative for

sthma

Global Strategy for Asthma

Management and Prevention

1. nh ngha v tng quan

2. Chn on v phn loi

3. Thuc iu tr HEN

4. Chng trnh qun l v phng nga Hen PQ

5. p dng cc hng dn v HEN vo h thng y t

nh ngha Hen PQ

Ri lon vim mn tnh ng dn kh

Nhiu t bo v thnh phn t bo tham gia

Vim mn tnh, co tht ph qun, tng p ng ng dn kh

Hi phc

Lm sng

1. Bn t/c: ho, kh kh, nng ngc, kh th Bn : ti li, xut hin v m, lin quan thi tit, tng or xut hin khi TX kch thch

2. C cc t kh th cp phi nhp vin Trong cn kh th cp phi c ran ngy, ran rt

Ngoi cn sinh hot gn nh bnh thng

Chn on Hen PQ

Chc nng h hp

Thuc iu tr hen

1. ICS

2. ICS + LABA

3. Khng Leukotriene

1. SABA ht

2. Anticholinergic

3. Theophylline

Thuc ct cn

(Reliever Medications)

1. To mi quan h tt gia BN v thy thuc

2. Nhn bit v gim TX vi cc yu t nguy c

3. nh gi, iu tr v theo di Hen PQ

4. X tr t kch pht ca Hen PQ

5. Cc trng hp c bit

Qun l v phng nga Hen PQ (5 components)

* Kh nng chuyn i l c lp vi thi gian Bateman et al. ERS 2006

Hen kim sot

Hen khng kim sot

Hen vo cn cp

Hen kim sot mt phn

KH NNG CHUYN I GIA CC MC KIM SOT HEN

MC O KIEM SOAT HEN

ac iem Kiem soat

Tat ca nhng iem di ay

Kiem soat mot phan

Cac tieu ch co the hien dien

trong bat ky tuan nao

Khong kiem soat

Trieu chng ban ngay Khong co

( 2/tuan) > 2 lan/ tuan

Xuat hien 3 yeu

to cua Hen kiem

soat mot phan

trong bat k tuan

nao

Gii han hoat ong Khong Co

Trieu chng ban

em/thc giac Khong Co

Co nhu cau dung thuoc

cat cn

Khong

( 2 lan/tuan) > 2 lan/tuan

Chc nang ho hap

(PEF hay FEV1)

Bnh thng

Kim sot

Kim sot mt phn

Khng kim sot c

t kch pht

MC KIM SOT

Duy tr v tm c bc kim sot

thp nht

Xt tng bc t kim

sot

Tng bc cho n khi t kim sot

iu tr t kch pht

IU TR/HNH NG

NHNG BC IU TR GIM TNG

BC

1

BC

2

BC

3

BC

4

BC

5

GI

M

T

NG

BC IU TRI

BC

1 BC

2 BC

3 BC

4 BC

5

Gio duc hen

Kim sot mi trng

Chu vn 2 tc dung nhanh khi cn

Chu vn 2 tc dung nhanh khi cn

CHON 1 CHON 1 THM 1 THM 1

ICS liu thp * ICS liu thp cung chu vn 2 tc dung keo dai

ICS liu trung binh hoc cao cung chu vn 2 tc dung keo dai

Glucocorticosteroid

ung

Khng leukotriene ** ICS liu trung binh hoc cao

Khng leukotriene Liu php khng th anti-IgE

ICS liu thp cung thuc khng leukotriene

Theophylline dang phong thich keo dai

ICS liu thp cung Theophylline dang phong thich keo dai

* Glucocorticosteroid dang hit ** Cht i vn thu th hoc cht c ch s tng hp

Vung mau xanh l chinh la iu tr kim sot c la chn u tin

TR

I L

IU

KI

M

SO

T

B

NH

GIM TNG

Khi no dng thuc d phng

iu tr d phng t bc II - IV

Bc 2 l iu tr khi u cho hu ht cc

trng hp ngi bnh hen n khm c triu

chng hen dai dng m cha dng

corticosteroid.

Bc 3 l khm ln u cho thy hen khng

kim sot ngha l c 3 tiu ch trong ct hen

kim sot mt phn hoc ACT < 19 im.

Tng v gim bc iu tr hen?

1. Tng bc iu tr hen - Tnh trng hen cha c kim sot trong vng 1 thng.

- Xut hin cn hen cp

- Tng liu ICS 2 ln khng c hiu qu

2. Gim bc iu tr hen? Khi hen c kim sot v duy tr t nht 3 thng

1) Nu ang dng ICS liu trung bnh, cao gim 50% mi ba thng

- Nu ang dng ICS liu trung bnh, cao + LABA

- Nu ang dng thuc kim sot khc ngoi ICS liu trung bnh, cao + LABA

gim liu ICS 50% mi 3 thng, duy tr liu thuc kim sot khc. 2) - Nu ang dng ICS liu thp + LABA

- Nu ang dng ICS liu thp + LABA + khc

ngng thuc kim sot khc ngng LABA 3) Nu ang dng ICS liu thp

chuyn dang dng liu thp dn c th ngng iu tr thuc.

1. Khng (2 ln/tun) c triu chng ban ngy

2. Khng gii hn hot ng 3. Khng c triu chng hay

thc gic ban m 4. Khng (2 ln/tun) s dng

thuc ct cn 5. Chc nng h hp (PEF hay

FEV1) bnh thng

Tiu chun hen c kim sot theo GINA

T l p ng vi cc tiu ch khc nhau sau 18 thng iu tr bng ICS

AHR: airway hyperresponsiveness

AHR l 1 marker vim

AHR: tnh tng p ng PQ Nhu cu thuc ct cn

Bt thng PEF Bt thng FEV1

Khi tr (thng)

% c

i t

hi

n

2 4 6 18

T/C m

Woolcock Clin Exp Allergy Rev 2001; GINA 2009

Ngng iu tr

GINA: c th ngng thuc nu hen vn c kim sot vi liu thp nht

v khng c triu chng ti pht trong 1 nm (bng chng D)

Test Kim sot Hen NGI LN - ACT

TRNH CC YU T KCH PHT CN HEN

Vt nui

Nm mc

Con gin

Phn hoa Cc mi hc

Khi (thuc l, nhang, bp ci, du, gaz)

Thuc Aspirin Mt s thc n

Cm cm Thay i thi tit Vn ng gng sc

Con b nh

Nhng iu quan tm c bit

Nhng iu c bit cn quan tm qun ly hen:

1. Thai nghen

2. Phu thut

3. Vim mui, vim xoang, va polyp mui

4. Hen ngh nghip

5. Cc bnh nhim trng ng h hp

6. Tro ngc d dy thc qun

7. Hen kch pht bi aspirin

8. Phn ng phn v va hen

HEN KH TRI

THUT NG HEN KH TRI

Hen kh tr (difficult to control asthma)

Hen nng (severe asthma)

Hen khng tr (therapy refractory asthma)

Hen ph qun ph thuc corticosteroid

(steroid-dependent asthma)

NH NGHA HEN KH TR

HEN KH (Difficult Asthma) l hen khng kim

sot, c t cp thng xuyn, tc nghn ng

th ko di v hay thay i, lun c nhu cu

phi dng kch thch giao cm b2 gim triu

chng, mc d dng liu ICS ti a lin tc

trong 6 12 thng.

nh ngha ca ERS - ERJ; 1999; 13:1198-208

HEN KHNG TR (refractory asthma) gm 1 tiu chun chnh+ 2 tiu chun ph

Tiu chun chnh:

1. Phi dng corticoid ung > 50% thi gian.

2. Phi dng ICS liu cao (>1200 mcg beclomethasone).

Tiu chun ph:

1. Phi iu tr kt hp LABA, LTRA, Xanthines mi ngy.

2. Triu chng hen mi ngy phi dng thuc ct cn.

3. FEV1 < 80% ko di, dao ng PEF/ ngy > 20%

4. Khm cp cu v hen 1 ln / nm

5. Phi dng corticoid ung v t cp 3 ln/ nm.

6. Hen nng ln khi gim > 25% liu ICS hoc OS.

7. Tin s tng b cn Hen cp nng da t vong.

nh ngha ca ATS - AJRCCM 2000; 162: 2341-51

NH NGHA HEN KHNG TR

HEN NNG (Severe Asthma) l thut ng dng

ch bnh nhn b hen khng tr, bnh nhn c

hen vn kh kim sat mc d c nh gi k

lng v chn an, x tr v c theo di

trong thi gian t nht 6 thng ti bc s chuyn

khoa v hen.

Workshop Hen Nng (Paris 2006) Chanez et al, JACI 2007

NH NGHA HEN NNG

T l HPQ kh tr

TIP CN HEN KH TR

nh gi bnh nhn HPQ kho tr 1. Tin s HPQ

Tui khi pht

Tin s gia nh HPQ

Phng php iu tr v p ng iu tr

2. t cp

Tn sut t cp

S ln nhp vin cp cu HPQ v ICU

3. Yu t mi trng

Tip xc vi d nguyn, ngh nghip

Tin s ht thuc

4. Bnh l phi hp

Vim mui xoang

ang dng thuc NSAIDs, chn beta, ACE, estrogen

GERD

Ngng th khi ng

nh hng ca chu k kinh

Bnh l tm thn

5. Khm

BMI

Bng chng ca bnh phi hp

Bng chng bnh l tim mch

Bng chng ca tc dng ph do thuc

6. nh gi HPQ nng

PFT

Challenge tests

IgE

Eosinophil

Test ly da

XN chn on bnh l phi hp

J Allergy Clin Immunol 2007;119:1337-48.

Chn on nhm

Tun th iu tr kem

Yu t thc y

B st bnh i

km

Th lm sng

c bit 5 BC TIP CN X TR

HEN KH TRI

CHN ON NHM

1. COPD (nhn mnh trong GINA 2014)

2. Gin ph qun

3. Vim qu pht Amidan VA tr em.

4. Ri lan vn ng dy thanh m.

5. Suy tim tri do TMCT m thm ngi gi.

6. Tng p lc ng mch phi

7. Ri lan trm cm

8. Churg Strauss Vasculitis

9.

Tun th iu tr km

Thi gian khm bnh t vn

Hng dn dng thuc xt

Kim tra bnh nhn vic tun th iu tr

Trnh cc yu t kch thch

Nng cao kin thc bnh hen cho bnh nhn

BNH NHN HEN KH THNG C

NHIU BNH I KM

1 co-morbid factor

13%

2 co-morbid factors

35%3 co-morbid factors

39%

4 co-morbid factors

8%

5 co-morbid factors

5%

Ten Brinke A, Eur Respir J 2005

BNH I KM TC NG TRN HEN

C cng c ch sinh l bnh: VMDU.

Yu t gy nhiu gy chn on nhm: bo ph, SAHS

(the sleep apnea hypopnea syndrome).

Yu t thc y: GERD, nhim khun h hp, ht

thuc l, ri lon tm thn kinh.

Yu t lm gim p ng, gim tun th iu tr : bo

ph, ht thuc l, ri lon tm thn kinh.

TH LM SNG C BIT

Am J Respir Crit Care Med Vol 178. pp 218224, 2008

X TR HEN KH TR

Gio dc bnh nhn

iu tr bnh km theo

Thuc trong iu tr hen kh tr

GIO DC BNH NHN

Hiu bit v bnh hen

Xy dng bng k hoch hnh ng

S tun th iu tri

Ngng thuc l

Chng nga

IU TR BNH KM THEO

GERD

Bo ph v OSA (obstructive sleep apnea)

Ri lon lo u, trm cm

Vim mi d ng

CC HNG iU TR HEN KH TR

Steroid ung Khng IgE

? Khng TNF alfa?

Bronchoplasty?

Tiotroprium v HPQ kh tr

LA CHN MI CHO HPQ KH TR

THIT K NGHIN CU TIOTROPRIUM BNH NHN HPQ NNG

Peters S, et al, N Engl J Med 2010; 363: 1715

Tiotropium v HPQ kh tr


Morning PEF Evening PEF

Pre-b.d FEV1 (L) Asthma Control Days (No./14 days)

Tiotropium nh iu tr nng bc trong HPQ nng


Perc

en

tag

e p

ati

en

ts

38

5.4 7.4

50

45

40

35

25

20

15

10

5

0

30

4.8

10.2 11.4

17.5

5.4 7.2

Overall response rates: Tiotropium = 41.5% Salmeterol = 44.5% Double dose ICS = 34.9%

Kerstjens et al. N Engl J Med 2012; 367:1198

*

**

Nghin cu 912 bnh nhn, c chia ngu hin thnh hai nhm mt nhm dng tiotropium 5 mcg (n=256), mt nhm dng placebo (n=256) trong 48 tun

chc nng phi ci thin trong 24

tun

Gim nguy c t cp HPQ ti

31%(p

Thermoplasty v HPQ kh tr


Thermoplasty iu tr HPQ nng

Castro M, et al, Am J Respir Crit Care Med 2010; 81 : 116

Thiu k nghin c

T T T

Baseline

4 weeks >3 weeks >3 weeks

Follow-up

Assess

3mo.

Assess

6mo.

Assess

9mo.

Assess

12mo.

N = 288 (ITT)

Thermoplasty iu tr HPQ nng Primary Endpoint : Thay i AQLQ trong 12 thng


AQ

LQ

Sc

ore

*

5.5

3 months

* Posterior probability of superiority = 95%

*

6 months 3 months 12 months

6.0

5.0

5.71 5.71 5.68

5.80 Bronchial Thermoplasty

N = 173

Sham

N = 95 5.56

5.40

5.48 5.49

Average score

Thermoplasty iu tr HPQ nng


Ra

te (

Ev

en

ts/ s

ub

jec

t/ y

ee

ar

t cp HPQ nng

*

16.2

7.4

Bronchial Thermoplasty Sham

100

90

80

70

50

40

30

20

10

0

60

Khm li bt thng

Vo EU Nm vin

* Posterior probability of superiority = 95%

*

Kt qu:

Ci thin cht lng cuc sng v gim t l t cp HPQ

Tuy nhin khng lm thay i t l kim sot HPQ

Roflumilast-c ch PGE 4 v HPQ kh tr


Roflumilast iu tr bnh nhn HPQ

Run-in period

Roflumilast 500 mg/day

Double-blind

Open-label extension period

1 - 3 weeks

12 weeks 40 weeks

Randomization

Roflumilast 500 mg/day 250 g/day

100 g/day

b2-agonist

p.r.n.



Inclusion criteria:

Patients with chronic, stable asthma Age 15 to 70 years FEV1 50% and 85% of predicted value Reversibility FEV1 15% or PEF variability 15%

Bateman ED, et al. Efficacy and safety of roflumilast in the treatment of asthma. Ann Allergy Asthma Immunol 2006;96:679-86.

12 tun nghin cu Roflumilast

100, 250, 500 g

40 tun nghin cu Roflumilast

500 g

Patients (N) 693 456

Median age in years

(range) 40 (16 70) 42 (17 71)

Male / Female (%) 48 / 52 49 / 51

Mean FEV1 SD (L)

100 g: 2.43 0.61

250 g: 2.38 0.63

500 g: 2.47 0.68

2.79 0.83

FEV1 SD (% predicted) 73 9 85 17

Previous ICS (%) 39.4 43.6

Smokers/Ex-smokers (%) 26 25

Roflumilast iu tr HPQ thit k nghin cu

Bateman ED, et al. Ann Allergy Asthma Immunol 2006;96:679-86.

Thay i FEV1

Roflumilast (g/day)

100 250 500 0

100

Ch

an

ge

vs

ba

se

lin

e (

mL

) (L

SM

ea

n)

200

300

400

*

p = 0.0017

*

*

Bateman ED, et al. Ann Allergy Asthma Immunol 2006;96:679-86.

0

Ch

an

ge

vs

ba

se

lin

e (

L / m

in)

(LS

Me

an

an

d S

EM

)

20

40

60

80

100

12 52 Time (weeks)

26 16 39 Endpoint 1

Khng IgE v HPQ kh tr


25 nghin cu

Omalizumab lm gim t cp

HPQ v thi gian nm vin

Gim liu ICS cn s dng

kim sot HPQ

Published Online: 12 January 2014

iu tr t bo ch Th2 v HPQ kh tr


C ch p ng min dch HPQ d ng v

cc phng php iu tr mi

Anti-IL4R

Anti-IgE

Gim mn cm c hiu vi d nguyn

Mepolizumab khng IL-5 iu tr HPQ nng tng bch cu i toan

Pavord et al. Lancet 2012;380:651-59

Nghin cu a trung tm, m i, ngu nhin c i chng ti 81 trung tm HPQ trn 13 quc gia vi n= 621 bnh nhn HPQ nng tng bch cu i toan cho kt qu

Gim t cp ca HPQ sau 12 thng iu tr

Lebrikizumab khng IL13 iu tr HPQ

Ci thin FEV1 sau 12 tun iu tr

Dupilumab khng IL4 iu tr HPQ nng

KT LUN

GINA CP NHT khng c nhiu thay i

HEN KH TR ch c

Ngun Gc Ti Liu

Ti liu ny c trnh by trong Hi Ngh Hen Ton Cu t chc ti bnh vin Bch Mai H Ni ngy 08/05/2014.

Ti liu c chia s min ph ti website: http://chiaseykhoa.com nhm phc v bn c trong hc tp, nghin cu, lm vic

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ĐOÀN CẬPNHẬT GINA &hen kho ́trị