dr kaushik saha smart
TRANSCRIPT
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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
-
8/16/2019 Dr Kaushik Saha SMART
37/37
THANK YOU