Dr Kaushik Saha SMART

8/16/2019 Dr Kaushik Saha SMART

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Kaushik SahaMD, DTCD, FCCP (USA)Consultant Pulmonologist Assistant Professor, Burdan Medi!al CollegeSuraksha Khardah"enith Su#er s#e!ialist $os#ital

SMART THERAPYSMART THERAPY


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95

70

75

80

85

90

Time (months)-1 0 1 2 3 6 9 12

Pauwels R et al NEJM 1997 FACET Study

run-in

F E V

1 ( %

p r e

d i c t e d )

ADDITION OF FORMOTEROL TO INHALED STEROIDADDITION OF FORMOTEROL TO INHALED STEROID

Bud 2!"

Bud #!"Bud 2!" $ Fr& 12!"

Bud #!" $ Fr& 12!"

Addi'" r&ter *etter t+,' -.Addi'" r&ter *etter t+,' -.↑

d/e I0Sd/e I0S

N ter,'ce er 1 r N ter,'ce er 1 r

#32 ,/t+&,tic p,tie't/

FEV1453% predicted

' 4#!" I0S d,i

FA0ET /tudFA0ET /tud

OPTIMA ST6DY7 /i&i,r re/ut/ i' &id8&der,te ,/t+OPTIMA ST6DY7 /i&i,r re/ut/ i' &id8&der,te ,/t+

%&B'rne P et al ACCM *++


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INFLAMMATIONINFLAMMATION

SYMPTOMSSYMPTOMS

Atp

9e'e/

0ORTI0OSTEROIDS0ORTI0OSTEROIDS

ASTHMA 0ONTROLASTHMA 0ONTROL

-n.ironmentalfa!tors

0OMPONENT 20OMPONENT 2

Add:' eectAdd:' eect

SYMPTOMSSYMPTOMSSYMPTOMSYMPTOM

0ONTROL0ONTROL

LALA 22:A"'i/t/:A"'i/t/


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ADD:ON THERAPIES FOR ASTHMAADD:ON THERAPIES FOR ASTHMA

Hi"+ d/eHi"+ d/e

i'+,ed /terid/i'+,ed /terid/

Add LA i'+,ed ;Add LA i'+,ed ;22:,"'i/t:,"'i/t

(&/t eectie)(&/t eectie)

Add < d/e t+ep+i'Add < d/e t+ep+i'e

(c+e,pe/t)(c+e,pe/t)

Add ,'ti:eu=trie'eAdd ,'ti:eu=trie'e(e// eectie ,'d e.pe'/(e// eectie ,'d e.pe'/

/f not !ontrolled0/f not !ontrolled0

L< d/e i'+,ed /terid/L< d/e i'+,ed /terid/(- !" d,i r e//)(- !" d,i r e//)

LABA80S 0&*i',ti'LABA80S 0&*i',ti'

I'+,er/I'+,er/


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TREATMENT OF ASTHMA7 0ELL6LAR EFFE0TSTREATMENT OF ASTHMA7 0ELL6LAR EFFE0TS

Viru/>

Ade'/i'eE.erci/e

F"

Bron!ho!onstri!tion

A'ti"e'A'ti"e'

Mast !ell Plasma leak Sensor' ner.

a!ti.ation

A06TEA06TE

INFLAMMATIONINFLAMMATION LABALABA

AIR?AYAIR?AY

HYPERRESPONSIVENESHYPERRESPONSIVENES

Ma!ro#hageMa!ro#hage -osino#hil -osino#hil

T1!ell T1!ell 0HRONI00HRONI0INFLAMMATIONINFLAMMATION

Dendriti! !ell Dendriti! !ell

I0SI0S


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EVOL6TION IN ASTHMA THERAPYEVOL6TION IN ASTHMA THERAPY

N ,d@u/t&e't i'N ,d@u/t&e't i'

c'trer c'trer

0ONVENTIONAL0ONVENTIONAL

M e

d i c ,

t i '

6 / e

M e

d i c ,

t i '

6 / e

M,i'te','ceM,i'te','ce

$ pr'$ pr' SABASABA

FA0ETFA0ET

OPTIMAOPTIMA

9OAL9OAL

Bude/'ide8r&terBude/'ide8r&ter

Futic,/'e8/,&eterFutic,/'e8/,&eter

SMART SMART

SSi'"e i'+,eri'"e i'+,er MM,i'te','ce,i'te','ce

AA'd'd RReieereieer TT+er,p+er,p

F6T6REF6T6RESi'"e i'+,er7Si'"e i'+,er7

M,i'te','ce reie M,i'te','ce reie

Com2ination inhalerCom2ination inhaler

re#la!es SABAre#la!es SABA

M,i'te','ceM,i'te','ce

$ pr'$ pr' Bud8r& Bud8r&

STAYSTAY

STEAMSTEAM

STEPSTEP

0OSMOS0OSMOS SMILESMILE

0OMPASS0OMPASS

AHEADAHEAD


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Morning P-F (34min)

D,/ Tre,t&e't

C-

CC

C2

C3

C

C5

- 12 2 2# C

STAY /tud ('253)STAY /tud ('253)

Bud8r& (Fi.ed) $ SABA- . Bud $ SABA

***

Bud8r& (SMART)

%&B'rne P et al0 ACCM *++5

Change in as nee

inhalations4da'

-

:

:-

:#

:12

:1

- 12 2 2#

PG


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E e ' t / 8 p

, t i e ' t 8 e , r

E e ' t / 8 p

, t i e ' t 8 e , r

STAY ST6DY7 SEVERE EA0ERBATIONSSTAY ST6DY7 SEVERE EA0ERBATIONS

1

2

C

-

C3

-

Bude/'ide -.Bude/'ide -.

$$ ter*ut,i'eter*ut,i'eBud8r&Bud8r&

$$ ter*ut,i'eter*ut,i'e

%&B'rne P et al0 ACCM *++5

1

Bud8r&Bud8r&

$ Bud8r&$ Bud8r&

SMARTSMART

Mder,te ,/t+&, ('253)


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Bud:Fr& SMABud:Fr& SMABud:Fr& $ SABABud:Fr& $ SABA

B6D $ SABAB6D $ SABA S,&:FP $ SABS,&:FP $ SAB

Bud:Fr& $ r&terBud:Fr& $ r&ter 6 6 I0S d/e c&p,rI0S d/e c&p,r

(BDP eJui,e't/)(BDP eJui,e't/)

E.,cer*,ti'/E.,cer*,ti'/

K81 p,tie't/8rK81 p,tie't/8r

11

22

CC

--

STEAMSTEAM0+e/t 20+e/t 2

STEPSTEP0MRO 2-0MRO 2-

STAYSTAY AR00M 23AR00M 23

SMILESMILEL,'cet 2L,'cet 2

0OMPASS0OMPASSI0P 25I0P 25

AHEADAHEAD Re/p Med 2-Re/p Med 2-

1111

33

2323

33

33

11

1122

SMART RED60ES SEVERE EA0ERBATIONSSMART RED60ES SEVERE EA0ERBATIONS

du*e:*i'd /tudie/ (' du*e:*i'd /tudie/ (' 1-C311-C31))


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SMARTSMART

Bud8r& ,/Bud8r& ,/ re/cuere/cue t+er,pt+er,p,/


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0OMBINATION INHALERS DIFFER0OMBINATION INHALERS DIFFER

Si&i,r tSi&i,r t

utic,/'eutic,/'e

Si&i,r tSi&i,r t

*ude/'ide*ude/'ide

Fr&terFr&ter

12+ *r'c+di,tr 12+ *r'c+di,tr

R,pid '/etR,pid '/etS+rt /ide eect/S+rt /ide eect/

Steep d/e:re/p'/eSteep d/e:re/p'/e

(u ,"'i/t)(u ,"'i/t)

S,&eterS,&eter

12+ *r'c+di,tr 12+ *r'c+di,tr

S


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NSFP8/,& (3823 *d)

Bud8r& i.ed d/e

(-812 *d)

13

1

3

- # 1 12 1- 12

Bud8r& SMART(28 *d $ ,/ 'eeded)

p2C

P , t i e ' t / < i t + / e e

r e e . , c e r * , t i

' / ( % )

D,/ /i'ce r,'d&i/,ti'

Time to first se.ere e7a!er2ationTime to first se.ere e7a!er2ation

Kuna P et al80 /nt Clin Pra!t8 *++9

0OMPASS7 SMART VS FIED DOSE 0OMBINATION0OMPASS7 SMART VS FIED DOSE 0OMBINATION


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D,/ /i'ce r,'d&i/,ti'

P ,

t i e '

t / <

i t + / e e r e e .

, c e r * ,

t i ' /

( % )

12 1# 2- C C

23

2

13

1

3

a2e K et al0 3an!et *++:

SMILE ST6DY7 0OMPARISON OF RELIEVER THERAPSMILE ST6DY7 0OMPARISON OF RELIEVER THERAP

Ter*ut,i'eTer*ut,i'e

PG1

Fr&terFr&ter

PG3

Bud8r&Bud8r&

Time to first e7a!er2ationTime to first e7a!er2ation

Bud8r& &,i'e','ce *dBud8r& &,i'e','ce *d $ reieer7


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FP8/,& 23823FP8/,& 23823

.an der ;oude $ et al0 Pulm Pharm Ther *++<

LABA TIME 0O6RSELABA TIME 0O6RSE

1

#

5

B,/ei'e

F E V

F E V

1 1 ( % o f

b a s e l i n e )

( % o f

b a s e l i n e )

Ti&e (&i')

3 1 13 2 23 C

Bud8r& 28Bud8r& 28

P,ce*P,ce*

Met+,c+i'eMet+,c+i'e


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0ELLS IN ASTHMA EA0ERBATIONS0ELLS IN ASTHMA EA0ERBATIONS

Viru/e/Viru/e/

Aer"e'/Aer"e'/Put,'t/Put,'t/

Epit+ei,Epit+ei,

ce/ce/M,/t ceM,/t ce

Y Y Y Y Y Y

Hi/t,&i'eHi/t,&i'e0/:LT/0/:LT/P9DP9D22 etcetc

Br'c+c'/tricti'P,/&, e,=,"e

EA0ERBATIONEA0ERBATION

Fr&terFr&ter


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3

1

13

2

23

P1

P3

Tre,t&e't

N e u

t r p

+ i / '

( . 1 C 8 & &

C ) S#utum neutro#hilsS#utum neutro#hils

Formoterol *


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2

-

#

p2 p

S p u t u & '

e u t r

p + i / ( % )

0'tr :2


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QQ NE6TROPHILS IN VIRAL EA0ERBATIONSNE6TROPHILS IN VIRAL EA0ERBATIONS

Asthmati! !hildren (n?*>) Asthmati! !hildren (n?*>)

N e

u t r p

+ i /

( . 1

D 8 & L )

@orila M" et al0 ACCM *+++

pG1

1

2

C

-

Acute Recer

Sputu& 'eutrp+i/Sputu& 'eutrp+i/

L

I L : #

( ' "

8 &

L )

3

1

13

2

pG1

Acute Recer

Sputu& IL:#Sputu& IL:#

-#ithelial !ells-#ithelial !ells

IL:#IL:#

@eutro#hils@eutro#hils

hino.irushino.irusFr&terFr&ter

2:receptr/


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0 2 4 6 8

:C

:2

:1

1

Ti&e (


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i2son P et al0 Am es#ir Crit Care Med *++

S p u

t u &

e /

i '

p + i /

( % )

S p u

t u &

e /

i '

p + i /

( % )

3

-

C

2

1

P,ce*P,ce*

Bude/'ide

Si'"e d/e *ude/'ide (2-!")


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3

1

13

2

23

C

C3

-

d, d, C +ur/C +ur/

P 0 P 0

2 2

A M P

K & "

8 &

A M P

K & "

8 &

pG1

d, Cd, C d, 5d, 5

pG1pG1

P,ce*P,ce* 0ice/'ide (-0ice/'ide (-" d,i)" d,i)

Adenosine mono#hos#hate !hallenge Adenosine mono#hos#hate !hallenge

RAPID ONSET OF STEROID EFFE0T ON AHRRAPID ONSET OF STEROID EFFE0T ON AHR

-rin - et al0 Chest *++>

Eect ' ,ir


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S0FS0F

Epit+ei,Epit+ei, ce/ce/

M,/t ce/M,/t ce/

INHALED STEROIDSINHALED STEROIDS

Ade'/i'eAde'/i'e

Aer"e'Aer"e'0d ,ir 0d ,ir

Br'c+c'/tricti'Br'c+c'/tricti'

EFFE0T OF STEROIDS ON AIR?AY MAST 0ELLSEFFE0T OF STEROIDS ON AIR?AY MAST 0ELLS


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3

1

13

I L : D

( p "

8 & )

-" 1"

0ice/'ideP*

IL:IL:

-rin - et al0 Chest *++>

/ndu!ed s#utum0 hours after inhaled steroid /ndu!ed s#utum0 hours after inhaled steroid

#E+8++

1

2

C

M I P : 1 T

( p "

8 & L )

MIP:1MIP:1

-" 1"

0ice/'ideP*

#E+8++

RAPID EFFE0T OF I0S ON SP6T6M 0YTOUINESRAPID EFFE0T OF I0S ON SP6T6M 0YTOUINES

T+2 LYMPHO0YTES IN ASTHMAT+2 LYMPHO0YTES IN ASTHMA


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T+2 LYMPHO0YTES IN ASTHMAT+2 LYMPHO0YTES IN ASTHMA

IL:-IL:- IL:1CIL:1C IL:3IL:3Y Y

Y Y Y Y

Mast !ell Mast !ell

I"EI"E

-osino#hil

Th* l'm#ho!'teTh* l'm#ho!'te

T ce receptr T ce receptr

0DC0DC 0D2#0D2#

0:/ti&u,ti'0:/ti&u,ti'

A'ti"e':pre/e'ti'" ce (de'driticA'ti"e':pre/e'ti'" ce (de'dritic

9ATA:C

9 C 9 O9ATA C RE96LATION


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9ATA:C RE96LATION9ATA:C RE96LATION

0DC0DC 0D2#0D2#

T+2 ct=i'e "e'eT+2 ct=i'e "e'e

T+2 ceT+2 ce

@u!leus@u!leus

C'to#lasmC'to#lasm

IL:- IL:3 IL:1CIL:- IL:3 IL:1C

9ATAC9ATAC

pC#MAPUpC#MAPU

PP

I&prti':I&prti':

Aer"icAer"ic

i',&&,ti'i',&&,ti'Manee!hotesuan K et al0 /mmunol *++:

9ATA C RE96LATION9ATA C RE96LATION


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9ATA:C RE96LATION9ATA:C RE96LATION

0DC0DC 0D2#0D2#

T+2 ct=i'e "e'eT+2 ct=i'e "e'e

T+2 ceT+2 ce

@u!leus@u!leus

C'to#lasmC'to#lasm

IL:- IL:3 IL:1CIL:- IL:3 IL:1C

pC#MAPUpC#MAPU

I&prti':I&prti':

Aer"icAer"ic

i',&&,ti'i',&&,ti'

9ATAC9ATAC

9R9R

0rtic/terid0rtic/terid

MUP:1 "e'eMUP:1 "e'e9R9R 9R9R

MUP:1MUP:10rtic/terid/0rtic/terid/ 9ATA:C9ATA:C

(T+2 ct=i'e e.pre//i'(T+2 ct=i'e e.pre//i'

• R,pid '/etR,pid '/et

• Pte't eectPte't eect• Pr'"ed eectPr'"ed eect

9R9R

EFFE0T OF 0ORTI0OSTEROIDS ON IL 3EFFE0T OF 0ORTI0OSTEROIDS ON IL 3


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2 - # 1 12 1- 1 1# 2 22 2-

Ti&e (+)

I L : 3 ( p "

8 & )

3

1

13 @asal la.age0 ha' fe.er su2e!t@asal la.age0 ha' fe.er su2e!t

9r Pe'9r Pe'

EFFE0T OF 0ORTI0OSTEROIDS ON IL:3EFFE0T OF 0ORTI0OSTEROIDS ON IL:3

Si&i,r re/ut/


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-osino#hils-osino#hils

Et,.i'/

Mast !ellsMast !ells@eutro#hils@eutro#hils

Fr&terFr&ter Bude/'ideBude/'ide

Bude/'ide8r&terBude/'ide8r&ter

0ELL6LAR EFFE0TS OF WRES06EX Fr&ter8Bude/'id0ELL6LAR EFFE0TS OF WRES06EX Fr&ter8Bude/'id

Th* !ellsTh* !ells

IL:3

EPLAINS ?HY B6D8FORMEPLAINS ?HY B6D8FORM

IS THE MOST EFFE0TIVE RELIEVERIS THE MOST EFFE0TIVE RELIEVER


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Bude/'ideBude/'ide

13 C -3 53

13

C

-3

53

Nr&,

A/t+&,

Ti&e (&i'ute/)

Y Z ,

<

( ! 8 &

i ' 8 & )

1 2 C

13

C

-3

53

S,*ut,&S,*ut,&

Y Z ,

<

( ! 8 &

i ' 8 & )

Nr&,

A/t+&,

Ti&e (&i'ute/)

BRON0HIAL BLOOD FLO? IN ASTHMABRON0HIAL BLOOD FLO? IN ASTHMA

Paredi P et al0 es es *++5

Bude/'ide7 r,pidBude/'ide7 r,pid *r'c+i, *d


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INTERA0TIONS BET?EENINTERA0TIONS BET?EEN

0ORTI0OSTEROIDS AND ;0ORTI0OSTEROIDS AND ;22:A9ONISTS:A9ONISTS

lu!o!orti!oidre!e#tor

G* 1Adreno!e#tor

• Eect crtic/terid/ ' ;Eect crtic/terid/ ' ;22:,"'i/t eect/:,"'i/t eect/

0rtic/terid

A'ti:i',&&,tr eect

• Eect ;Eect ;22:,"'i/t/ ' crtic/terid eect/:,"'i/t/ ' crtic/terid eect/

;2:A"'i/t

Br'c+di,t,ti'

LABA8I0S ON EPITHELIAL RANTES (00L3)LABA8I0S ON EPITHELIAL RANTES (00L3)


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LABA8I0S ON EPITHELIAL RANTES (00L3)LABA8I0S ON EPITHELIAL RANTES (00L3)

-dards M et al0 ACMB *++:

BEAS2B epit+ei, ce/ i'ected


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Metha!holine PC Metha!holine PC *+ *+ *


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0ON0L6SIONS0ON0L6SIONS

0rtic/terid/ ,'d ;0rtic/terid/ ,'d ;22

:,"'i/t/ ,ect diere't ,'d:,"'i/t/ ,ect diere't ,'d

c&pe&e't,r ,/pect/ ,/t+&, p,t+p+/i"c&pe&e't,r ,/pect/ ,/t+&, p,t+p+/i" QQ Fr Fr &ter duri'" e.,cer*,ti'/7&ter duri'" e.,cer*,ti'/7

• Reer/e/ *r'c+c'/tricti'Reer/e/ *r'c+c'/tricti'• I'+i*it/ &,/t ce &edi,tr ree,/eI'+i*it/ &,/t ce &edi,tr ree,/e• I'+i*it/ 'eutrp+i/I'+i*it/ 'eutrp+i/

QQ BBude/'ide +,/ude/'ide +,/ r,pidr,pid ,cti' ' i',&&,ti',cti' ' i',&&,ti'

::↓

eNO e/ &,/t ce 'u&*er/ (,de'/i'e) T+2 &p+eNO e/ &,/t ce 'u&*er/ (,de'/i'e) T+2 &p+c

Re/cue Bud8r& &, +,e e'+,'ced eect/Re/cue Bud8r& &, +,e e'+,'ced eect/ : Mecu,r i'ter,cti' *et


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SIN9LE INHALER THERAPYSIN9LE INHALER THERAPY

M,i'te','ce t+er,p7M,i'te','ce t+er,p7

Hi"+ eectieHi"+ eectieRe/cue t+er,p7Re/cue t+er,p7

Hi"+ eectieHi"+ eectie

THERE IS A STRON9 S0IENTIFI0 RATIONALETHERE IS A STRON9 S0IENTIFI0 RATIONALE

FOR B6D8FORM SMART THERAPY IN ASTHMFOR B6D8FORM SMART THERAPY IN ASTHM

Barnes P8 S!ientifi! rationale for using a single inhaler forBarnes P8 S!ientifi! rationale for using a single inhaler for

asthma !ontrol8 -ur es# *++9H*505>915I: asthma !ontrol8 -ur es# *++9H*505>915I:

0+,pter - A/t+&, M,',"e&e't0+,pter - A/t+&, M,',"e&e't


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0+,pter - A/t+&, M,',"e&e't0+,pter - A/t+&, M,',"e&e't

,'d Pree'ti' Pr"r,&,'d Pree'ti' Pr"r,&

0&p'e't C7 A//e// Tre,t ,'d0&p'e't C7 A//e// Tre,t ,'d

M'itr A/t+&, Tre,t&e't/M'itr A/t+&, Tre,t&e't/

Treating to a!hie.e !ontrol0 Ste# 0 elie.er Treating to a!hie.e !ontrol0 Ste# 0 elie.er

medi!ation #lus one or to !ontrollersmedi!ation #lus one or to !ontrollers

I , c&*i',ti' i'+,er c't,i'i'" r&ter ,'dI , c&*i',ti' i'+,er c't,i'i'" r&ter ,'d

*ude/'ide i/ /eected it &, *e u/ed r *t+ re/cue*ude/'ide i/ /eected it &, *e u/ed r *t+ re/cue

,'d &,i'te','ce T+i/ ,ppr,c+ +,/ *ee' /+


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I0SI0S

L< d/eL< d/e

Or,Or,/terid/terid

I0S Hi"+ d/eI0S Hi"+ d/e

LABALABA

Step 1 Step 2 Step C Step - Step 3Step 1 Step 2 Step C Step - Step 3

S+rt:,cti'" ;S+rt:,cti'" ;22:,"'i/t ,/ 'eeded:,"'i/t ,/ 'eeded

LABA8I0SLABA8I0S

Or,Or,

/terid/terid

Mid Mid Mder,te SeereMid Mid Mder,te Seere

Epi/dic Per/i/te't Per/i/te't Per/i/te'tEpi/dic Per/i/te't Per/i/te't Per/i/te't

EVOL6TION OF ASTHMA TREATMENTEVOL6TION OF ASTHMA TREATMENT

Futic,/'e $ /,&eterFutic,/'e $ /,&eter

Bude/'ide $ r&terBude/'ide $ r&ter

SMARTSMART

Ne< tre,t&e't/Ne< tre,t&e't/

r /eere ,/t+&r /eere ,/t+&

(1:3% p,tie't/(1:3% p,tie't/'eeded'eeded

A'ti:I"EA'ti:I"E

A'ti:TNFA'ti:TNF

Ot+er>Ot+er>

• BDP8r&terBDP8r&ter

• Futic,/'e8r&terFutic,/'e8r&ter• M&et,/'e8r&terM&et,/'e8r&ter• 0ice/'ide8r&ter0ice/'ide8r&ter

• M&et,/'e8i'd,c,ter >>M&et,/'e8i'd,c,ter >>

SMART LIUELY TO BE THE MOSTSMART LIUELY TO BE THE MOST

EFFE0TIVE THERAPY FOR ASTHMAEFFE0TIVE THERAPY FOR ASTHMA

FOR 13 YEARSFOR 13 YEARS


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THANK YOU

Dr Kaushik Saha SMART

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