Treatment choices for patients

Treatment choices for patients

with asthma or COPD
with asthma or COPD
Jo Riley
Jo Riley
Lead Nurse For Oxfordshire
Lead Nurse For Oxfordshire
Respiratory Serice
Respiratory Serice

!hat is the difference"
!hat is the difference"
# $s it all a%out "&
$s it all a%out "&
&
$nhaled steroids
$nhaled steroids
& Lon' actin'
Lon' actin'
(
(
) )
a'onists
a'onists
& Short actin' (
Short actin' (
) )
a'onists
a'onists
# !here do these fit in"
!here do these fit in"
&
Short actin' anticholiner'ics
Short actin' anticholiner'ics
&
Lon' actin' anticholiner'ics
Lon' actin' anticholiner'ics

!hat is the difference"
!hat is the difference"
# *sed at different sta'es of the diseases
*sed at different sta'es of the diseases
# Different doses
Different doses
# Different outcomes
Different outcomes
# Different licenced indications
Different licenced indications

+sthma
+sthma
Smooth muscle
Mucous plug
Basement
membrane
Epithelium
Mucous glands
Adapted from Jeffery PK. Am J Respir Crit Care Med. 2001;164:S28-S38.
44
Normal
airway
Asthmatic
airway

Aims of asthma Treatment -
Aims of asthma Treatment -
2008
2008
No daytime symptoms
No daytime symptoms
No Night time waking due to asthma
No Night time waking due to asthma
No exacerbations
No exacerbations
No need for rescue 2 agonist
No need for rescue 2 agonist
No actiity !imitation
No actiity !imitation
Norma! !ung function "#$%& '80()
Norma! !ung function "#$%& '80()
*inima!+no aderse effects for
*inima!+no aderse effects for
medication
medication

2000
1985
1980
ICS treatmet
!trod"#ed
19$2
Sa%&"tamo%
!trod"#ed
1968
'!(ed )o*e Com&!at!o
prod"#t* !trod"#ed
1995
Progression of asthma therapy
1990
+a"#, of
%o--a#t!-
2 -a-o!*t*
.!-, "*e of
*,ort-a#t!-
2 -a-o!*t*
/ro#,o*pa*m If%ammat!o 0emode%%!-
19$5
I#rea*ed "*e of
ICS
A1) Com&!at!o
prod"#t* !trod"#ed

Adults

Steppin' up treatment"
Steppin' up treatment"
# Chec, compliance with existin' therapies
Chec, compliance with existin' therapies
# Chec, understandin'
Chec, understandin'
# Chec, $nhaler techni-ue
Chec, $nhaler techni-ue
# .liminate tri''er factors where possi%le
.liminate tri''er factors where possi%le

Adults

$ntroducin' inhaled steroids
$ntroducin' inhaled steroids
# +dults or children
+dults or children
&
usin' inhaled %eta ) a'onist / times a wee,
usin' inhaled %eta ) a'onist / times a wee,
or more
or more
&
hain' symptoms / times a wee, or more
hain' symptoms / times a wee, or more
&
!a,in' at ni'ht once a wee, or more
!a,in' at ni'ht once a wee, or more
# Consider in adults and children who hae
Consider in adults and children who hae
had an exacer%ation re-uirin' oral steroids
had an exacer%ation re-uirin' oral steroids
in the last ) years
in the last ) years

!hich inhaled steroid"
!hich inhaled steroid"
# 0eclometasone &either
0eclometasone &either
&
1ar 2344mc' & 544mc' daily in adults6 or
1ar 2344mc' & 544mc' daily in adults6 or
&
Clenil modulate 2)44mc'7844 mc' daily in adults6
Clenil modulate 2)44mc'7844 mc' daily in adults6
# 0udesonide 2)44 & 844mc' daily in adults6
0udesonide 2)44 & 844mc' daily in adults6
# Fluticasone 2344 & 544mc' daily in adults6
Fluticasone 2344 & 544mc' daily in adults6
# Ciclesonide 2394mc' daily in adults6
Ciclesonide 2394mc' daily in adults6
# :ometasone 2544 & 844mc' daily in adults6
:ometasone 2544 & 844mc' daily in adults6

Adults

Step /; $nitial add7on therapy
Step /; $nitial add7on therapy
#
The first choice as add7on therapy to inhaled steroids in adults
and children2<73) years6 is an inhaled lon'7actin' %eta
)
a'onist
2L+0+6
#
+ddin' a L+0+ should %e considered %efore 'oin' a%oe a dose
of 544 mc' 0DP or e-uialent and certainly %efore 'oin' a%oe
844mc'
#
Lon'7actin' %eta
)
a'onists are effectie at proidin'
%ronchodilation oer a sustained period= They increase lun'
function> improe symptoms and reduce incidence of
exacer%ation
#
L+0+s are not licensed as monotherapy in the treatment of
asthma
1. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British
Guideline on the Management of Asthma: A National Clinical Guideline. Revised
Edition, !!".

:?R+ adice on L+0+@s
:?R+ adice on L+0+@s
# At present the benefits of long-acting
At present the benefits of long-acting
2 agonists outweigh the risks and it
2 agonists outweigh the risks and it
is important that patients take their
is important that patients take their
asthma medicine as prescribed to
asthma medicine as prescribed to
them! "atients should discuss any
them! "atients should discuss any
concerns regarding their asthma
concerns regarding their asthma
treatment with their doctor! #eb
treatment with their doctor! #eb
2$$%
2$$%
http&''www!mhra!go(!uk'Safetyinformation')ener
http&''www!mhra!go(!uk'Safetyinformation')ener
alsafetyinformationandad(ice'"roduct-
alsafetyinformationandad(ice'"roduct-
specificinformationandad(ice'Asthma'inde*!htm
specificinformationandad(ice'Asthma'inde*!htm

Com%ination inhalers
Com%ination inhalers
Section 5=/=/= 0TS )448
Section 5=/=/= 0TS )448
# A
A
there is no difference in efficacy in 'iin'
there is no difference in efficacy in 'iin'
inhaled steroid and lon'7actin'
inhaled steroid and lon'7actin'
(
(
) )
a'onist in
a'onist in
com%ination or in separate inhalersB
com%ination or in separate inhalersB
# A
A
Once a patient is on sta%le therapy>
Once a patient is on sta%le therapy>
com%ination inhalers hae the adanta'e of
com%ination inhalers hae the adanta'e of
'uaranteein' that the lon'7actin' (
'uaranteein' that the lon'7actin' (
) )
a'onist is
a'onist is
not ta,en without inhaled steroidB
not ta,en without inhaled steroidB
Supported %y Oxfordshire 'uidance in prescri%in'
Supported %y Oxfordshire 'uidance in prescri%in'
APoints 0ulletin Oxfordshire PCT Col 3D236 4E
APoints 0ulletin Oxfordshire PCT Col 3D236 4E
:ay )448B
:ay )448B

L+0+@s and com%inations
L+0+@s and com%inations
# Salmeterol <4mc' 0D
Salmeterol <4mc' 0D
# Formoterol 97)5mc' 0D
Formoterol 97)5mc' 0D
# Seretide <4 F 3)< F )<4mc' ) 0D
Seretide <4 F 3)< F )<4mc' ) 0D
# Sym%icort 344F9 F )44F9 37) 0D
Sym%icort 344F9 F )44F9 37) 0D

GO+L
GO+L
Gainin' Optimal +sthma controL
Gainin' Optimal +sthma controL
"rimary endpoint&
#
+etermine the proportion of patients who achie(ed guideline-
defined control with S+LFFP 2salmeterolFfluticasone propionate6
compared to FP
Secondary Endpoints&
# ,umulati(e proportion of patients achie(ing control in phase --
#
+ose if -,S and time to re.uired to achie(ed first guideline-defined
asthma week
#
"roportion of patients who achie(ed /otal ,ontrol
#
Asthma 0uality of 1ife 0uestionnaire
# 2ate of e*acerbations
#
Morning predose #E3
4
Bate#an et al. A#. $. Res%ir. &rit. &are 'ed !!( 1$0) "*+,"((.

32416
"#otro%%ed
a*t,ma
pat!et*
SA+3'P
250 &.d.
'P 250 &.d.
SA+3'P
100 &.d.
'P 100 &.d.
Grou%s entered into a (
,week run,in
Stero!d a!4e
5
612098
500 m#-
/)P e7"!4.
61163
850091000 m#-
/)P e7"!4.
612155
St"dy Strata 9 &a*ed o pre4!o"* tota% da!%y do*e of ICS
3
2
1
5
Com&!at!o !,a%er* are ot orma%%y %!#e*ed for t,e treatmet of *tero!d a:4e pat!et*

St"dy treatmet
Bate#an et al. A#. $. Res%ir. &rit. &are 'ed !!( 1$0) "*+,"((.
GO+L study desi'n
GO+L study desi'n

, ( ! ( 1 ( *+ - -+
.ral %rednisolone /
SA0123 -!! 4.d.
SA0123 -! 4.d.
or 23 -! 4.d.
5eek
3hase I
3hase II
",week control assess#ent
(,week control assess#ent
SA0123 1!! 4.d.
or 23 1!! 4.d.
SA0123 -!! 4.d.
or 23 -!! 4.d.
Bate#an et al. A#. $. Res%ir. &rit. &are 'ed !!( 1$0) "*+,"((.
GO+L study plan stratum 3 and )
GO+L study plan stratum 3 and )
6isit 1 * ( - +
" 7 8

("

Total Control;
achieed with sustained treatment
20
80
0
60
40
H

o
f

p
a
t
i
e
n
t
s
44;<
29;<
16;
28;
SA+3'P P,a*e II 'P P,a*e II
SA+3'P P,a*e I 'P P,a*e I
Strat"m 2
65$$ 6583
Strat"m 3
Bate#an et al. Am. J. Respir. &rit. &are 'ed !!( 18!) "*+,"((.
<p=0.001
656$ 6568

0ow dose I&S 9S:
'oderate dose I&S 9S*:

23 Seretide


Ti#e to control 9weeks:
, -!; o< %atients
< p=0.001
8 =
1! -=
Bate#an et al. A#. $. Res%ir. &rit. &are 'ed !!( 1$0) "*+,"((.
Guideline7defined control;
Guideline7defined control;
time to achiee control
time to achiee control

Percenta'e of patients who still had
Percenta'e of patients who still had
Total Control at the end of <) wee,s
Total Control at the end of <) wee,s
Stratu# 9low dose I&S:
n>-88 n>-"*
=%?!.!!1
Boushey @ et al. A4stract %resented at the 5orld Asth#a 'eeting, 2e4ruary !!(, Bangkok, Thailand.
Seret!de P,a*e I 'P P,a*e I
62;
69;<
!
1!
!
*!
(!
-!
+!
8!
"!
7!
1!!
;

o
f

p
a
t
!
e

t
*
Stratu# * 9#oderate dose I&S:
n>-+8 n>-+"
69;<
$3;

GO+L conclusions
GO+L conclusions
#
Guideline7defined control is achiea%le and sustaina%le
in a si'nificant proportion of patients
#
:ore patients achiee Guideline7defined control with
S+LFFP than with FP alone> at a lower $CS dose
#
S+LFFP compared with FP> more patients can achiee
'uideline7defined control;
& .arlier
& !ith fewer exacer%ations
& !ith more symptom free days
& !ith more rescue free days
&
!ith a %etter -uality of life
Bate#an et al. A#. $. Res%ir. &rit. &are 'ed !!( 1$0) "*+,"((.

Sym%icort AS:+RTB
Sym%icort AS:+RTB
+ new approach to asthma
+ new approach to asthma
mana'ement for some of your
mana'ement for some of your
patients
patients

!hat is Sym%icort S:+RT
!hat is Sym%icort S:+RT
I
I
"
"
# The mana'ement of persistent asthma with a
The mana'ement of persistent asthma with a
sin'le inhaler
sin'le inhaler
as %oth maintenance and relieer medication
as %oth maintenance and relieer medication
# +dult patients 238 years and oer6 ta,e an
+dult patients 238 years and oer6 ta,e an
ade-uate fixed maintenance dose>
ade-uate fixed maintenance dose>
with additional relieer inhalations of Sym%icort
with additional relieer inhalations of Sym%icort
as needed
as needed
# The use of a separate relieer inhaler is NOT
The use of a separate relieer inhaler is NOT
re-uiredJ
re-uiredJ
# Sym%icort S:+RT simplifies mana'ement
Sym%icort S:+RT simplifies mana'ement
=A short,acting 4ronchodilator #ay 4e reAuired <or %ro%hylaBis o< eBercise induced asth#a

!hy is Sym%icort
!hy is Sym%icort
I I
suita%le
suita%le
for %oth maintenance and relieer
for %oth maintenance and relieer
therapy"
therapy"
# Lon' actin' %eta a'onist
Lon' actin' %eta a'onist
%ronchodilators are not all the same
%ronchodilators are not all the same
# Formoterol has rapid %ronchodilator
Formoterol has rapid %ronchodilator
actiity
actiity
&
Faster than salmeterol
Faster than salmeterol
3 3
&
Similar to sal%utamol
Similar to sal%utamol
) )
# Sym%icort reliees %ronchoconstriction
Sym%icort reliees %ronchoconstriction
faster than Seretide
faster than Seretide
/ /
C 3al#Avist et al. Eur Res%ir $ 1778D
C Se4erovE E, Andersson A Res%ir. 'ed. !!!D
C 3al#Avist ', et al. 3ul# 3har#acol Ther !!1

J
544F3)K' 544F3)K'
Smile
344F<44K' 844F)5K' 544F3)K'
,ompass
JJ
344F)4473444
K'
JJ
5447844F3)7)
5K'
,osmos
)44F3)K' 844K' )44F3)K'
Stay
844K' 544F3)K'
Step
544K' )44F3)K'
Steam
Seretide
5
Symbicor
t
#i*ed
+ose
5
B6+
5
SMA2/ Study
Sym%icort S:+RT
Sym%icort S:+RT
I
I
eidence
eidence
%ase
%ase

BFG) 4udesonideD H ) %lus SABA reliever #edicationD = ) also 0ABA reliever #edicationD
== ) dosage adIusta4leD Goses re<er to total daily #aintenance dose

Oerall conclusions of Sym%icort
Oerall conclusions of Sym%icort
S:+RT studies
S:+RT studies
# Sym%icort S:+RT consistently reduces the rate of seere
Sym%icort S:+RT consistently reduces the rate of seere
exacer%ations compared to other treatments
exacer%ations compared to other treatments
& ?i'h7dose $CS L as needed S+0+ ?i'h7dose $CS L as needed S+0+
3 3

) / ) /
& Fixed dose Sym%icort L as needed S+0+ or L+0+ Fixed dose Sym%icort L as needed S+0+ or L+0+
5 5
& Seretide L as needed S+0+ Seretide L as needed S+0+
< <

9 9
# Sym%icort S:+RT achiees this with
Sym%icort S:+RT achiees this with
& less use of relieer medication less use of relieer medication
3 3

) / 9 ) / 9

&
a lower steroid load a lower steroid load
3 3

) / 5 < ) / 5 <

# Sym%icort S:+RT is potentially more conenient than
Sym%icort S:+RT is potentially more conenient than
multiple inhalers and is a si'nificant therapeutic adance
multiple inhalers and is a si'nificant therapeutic adance
in the mana'ement of asthma
in the mana'ement of asthma
(. Ra4e J2 et al. 0ancet !!+
-. Juna et al. Int $ &lin 3ract !!8.
+. 6ogel#eier et al. Eur Res%ir $ !!-
C Ra4e et al, &@EST !!+
C Scicchitano et al, &urr 'ed Res .%in !!(
C .KByrne et al, A# $ Res%ir &rit &are 'ed !!-

?ow to prescri%e Sym%icort
?ow to prescri%e Sym%icort
S:+RT
S:+RT
This will depend upon the seerity of asthma of the
This will depend upon the seerity of asthma of the
indiidual patient
indiidual patient
# Primary Care & The maMority of patients will %e
Primary Care & The maMority of patients will %e
well controlled on;
well controlled on;
# Symbicort 2$$'7 4 inhalation bd plus as needed Symbicort 2$$'7 4 inhalation bd plus as needed
# Secondary care
Secondary care
# Sym%icort )44F9> 3 or ) inhalations %d plus as needed Sym%icort )44F9> 3 or ) inhalations %d plus as needed

Adults

Adults

&hildren age -,1 yrs

C,!%dre +e** t,a 5 yr*

1. 1. In the %ast ( weeks, how #uch o< the ti#e did your asth#a kee% you <ro# In the %ast ( weeks, how #uch o< the ti#e did your asth#a kee% you <ro#
getting as #uch done at work, school or at ho#eL getting as #uch done at work, school or at ho#eL

Guring the %ast ( weeks, how o<ten have you had shortness Guring the %ast ( weeks, how o<ten have you had shortness
o< 4reathL o< 4reathL
1. 1. Guring the %ast ( weeks, how o<ten did your asth#a sy#%to#s Guring the %ast ( weeks, how o<ten did your asth#a sy#%to#s
9wheeMing, coughing, shortness o< 4reath, chest tightness or %ain: 9wheeMing, coughing, shortness o< 4reath, chest tightness or %ain:
wake you u% at night, or earlier than usual in the #orningL wake you u% at night, or earlier than usual in the #orningL

Guring the %ast ( weeks, how o<ten have you used your rescue Guring the %ast ( weeks, how o<ten have you used your rescue
inhaler or ne4uliMer #edication 9such as sal4uta#ol:L inhaler or ne4uliMer #edication 9such as sal4uta#ol:L

@ow would you rate your asth#a control during the %ast @ow would you rate your asth#a control during the %ast
( weeksL ( weeksL
S#ore S#ore
Pat!et >ota% S#ore Pat!et >ota% S#ore
&o%yright !!, Nuality'etric Incor%orated. &o%yright !!, Nuality'etric Incor%orated.
Asth#a &ontrol Test Is a Trade#ark o< Nuality'etric Incor%orated. Asth#a &ontrol Test Is a Trade#ark o< Nuality'etric Incor%orated.
Asthma ,ontrol /est8 9A,/:
Asthma ,ontrol /est8 9A,/:

O I#%erial &ollege 0ondon 3age *-
A**e**met: 0oya% Co%%e-e of
A**e**met: 0oya% Co%%e-e of
P,y*!#!a* of +odo t,ree 7"e*t!o*
P,y*!#!a* of +odo t,ree 7"e*t!o*
Outcomes and audit. Thorax 2003; 58 (Suppl I): i!i"2
C
A%%lies to all %atients with asth#a aged 1+ and over.
C
.nly use a<ter diagnosis has 4een esta4lished.
-N /;E 1AS/ <EE= ' M>N/;
?ES N>
A?ae you had difficulty sleepin' %ecause of your asthma
symptoms 2includin' cou'h6"B
A?ae you had your usual asthma symptoms durin' the day
2cou'h> wheeNe> chest ti'htness or %reathlessness6"B
A?as your asthma interfered with your usual actiities
2e='= housewor,> wor,> school> etc6"B
Date F F F

Goals of COPD mana'ement
Goals of COPD mana'ement
N$C.
N$C.
# +ccurate dia'nosis
+ccurate dia'nosis
# Stoppin' smo,in'
Stoppin' smo,in'
# .ffectie inhaled therapy
.ffectie inhaled therapy
# +ccess to pulmonary reha%
+ccess to pulmonary reha%
# Preent and treat
Preent and treat
exacer%ations
exacer%ations
# :ultidisciplinary wor,in'
:ultidisciplinary wor,in'
)>1+
)>1+
2 2
# Preent disease pro'ression
Preent disease pro'ression
# Reliee symptoms
Reliee symptoms
# $mproe exercise tolerance
$mproe exercise tolerance
# $mproe health status
$mproe health status
# Preent and treat
Preent and treat
complications
complications
# Preent and treat
Preent and treat
exacer%ations
exacer%ations
# Reduce mortality
Reduce mortality
1. NI&E !!(
. 3auwels RA et al. !!1.



# Can;
Can;
#
$mproe and preent symptoms
$mproe and preent symptoms
#
Reduce fre-uency and seerity of
Reduce fre-uency and seerity of
exacer%ations
exacer%ations
#
$mproe health status
$mproe health status
#
$mproe exercise tolerance
$mproe exercise tolerance
Pharmacolo'ical treatment

# Short7actin'
Short7actin'
& Short7actin' (
Short7actin' (
) )
a'onists 2S+0+6
a'onists 2S+0+6
&
Short7actin' anticholiner'ics
Short7actin' anticholiner'ics
# Lon'7actin'
Lon'7actin'
& Lon'7actin' (
Lon'7actin' (
) )
a'onists 2L+0+6
a'onists 2L+0+6
&
Lon'7actin' anticholiner'ics
Lon'7actin' anticholiner'ics
# $nhaled corticosteriods 2$CS6
$nhaled corticosteriods 2$CS6
& Com%ination lon' actin' (
Com%ination lon' actin' (
) )
a'onist F
a'onist F
corticosteroids 2L+0+ F $CS6
corticosteroids 2L+0+ F $CS6
Commonly used formulations
of inhaled therapy

# Less %reathlessness
Less %reathlessness
# +%ility to %e more actie
+%ility to %e more actie
# 0etter -uality of life
0etter -uality of life
# $mproed health status
$mproed health status
# Reduced mortality
Reduced mortality
# Reduction in exacer%ations
Reduction in exacer%ations
#
F.C
F.C
3 3
"
"
&
!ould not expect to see improements in
!ould not expect to see improements in
F.C
F.C
3 3
oer time
oer time
!hat are you loo,in' for"

#Assess response by asking&
Assess response by asking&
3 3
#
#
Also ask about an activity that they would like to be able to Also ask about an activity that they would like to be able to
do more easily, and assess any difference after treatment do more easily, and assess any difference after treatment
+ssessin' %enefits of prescri%ed
therapy
1. Jones, P.W. (2001) Health status measurement in chronic obstructive pulmonary disease. Thorax 5, !!0"!!#
Has your
treatment
made a
difference to
you?
Is your
breathing
easier in any
way?
Can you do some
things now that
you couldnt do
before, or the
same things but
faster?
Can you do the same
things as before but are
now less breathless when
you do them?
P@as your
slee%
improvedL
Q

*se short7actin' %ronchodilator 2anticholiner'ic or (
*se short7actin' %ronchodilator 2anticholiner'ic or (
) )

a'onist6 as needed
a'onist6 as needed
$f $f still symptomatic still symptomatic> try com%inin' > try com%inin'
therapy with a short7actin' ( therapy with a short7actin' (
) )
a'onist a'onist
and a short7actin' anticholiner'ic and a short7actin' anticholiner'ic
-f still symptomatic use a long-acting bronchodilator -f still symptomatic use a long-acting bronchodilator

2anticholiner'ic and F or ( 2anticholiner'ic and F or (
) )
a'onist6 a'onist6
$n moderate or seere COPD; $n moderate or seere COPD;
$f $f still symptomatic still symptomatic> ) or more exacer%ations consider a > ) or more exacer%ations consider a
com%ination of lon'7actin' %ronchodilators and inhaled com%ination of lon'7actin' %ronchodilators and inhaled
corticosteroid corticosteroid
$f $f still symptomatic still symptomatic> consider addin' theophylline > consider addin' theophylline
.R
N$C. mana'ement of sta%le
COPD
$%&' &linical (uideline. &hronic obstructive pulmonary disease " mana)ement o* chronic obstructive pulmonary disease in adults in primary and secondary care. 200+

(
(
)
)
a'onists
a'onists
Short-acting Short-acting
Salbutamol, terbutaline Salbutamol, terbutaline
Quick onset of action Quick onset of action
In COPD can be used regularly in In COPD can be used regularly in
addition to as needed addition to as needed
First line treatment in nely First line treatment in nely
diagnosed COPD !ere diagnosed COPD !ere
breat!lessness is t!e "resenting breat!lessness is t!e "resenting
sym"tom sym"tom
First aid treatment for breat!lessness First aid treatment for breat!lessness
at all stages of t!e disease at all stages of t!e disease

Lon'7actin' (
Lon'7actin' (
)
)
a'onists
a'onists
# Salmeterol #ormoterol
Salmeterol #ormoterol
# Reduce need for short actin' rescue
Reduce need for short actin' rescue
%ronchodilators
%ronchodilators
# $mproe -uality of life
$mproe -uality of life
# :ay improe symptoms
:ay improe symptoms

Action&
Action&
#
Same as short7actin' %ut last
Same as short7actin' %ut last
for 3) hours
for 3) hours
#
Salmeterol has slower onset
Salmeterol has slower onset
of action than formoterol
of action than formoterol
#
Side effects> cautions and
Side effects> cautions and
interactions; same as short7
interactions; same as short7
actin' %ut may also cause
actin' %ut may also cause
hypertensionO eleated
hypertensionO eleated
cardiac ris,
cardiac ris,
Lon'7actin' (
Lon'7actin' (
)
)
a'onists
a'onists

In!ibit muscarinic rece"tors In!ibit muscarinic rece"tors
#ork by blocking #ork by blocking
"arasym"at!etic ner$ous system "arasym"at!etic ner$ous system
%educes contraction of airay %educes contraction of airay
smoot! muscle &rat!er t!an smoot! muscle &rat!er t!an
causing bronc!odilation' causing bronc!odilation'
%educe $iscous mucus %educe $iscous mucus
secretions secretions
(ntic!olinergic drugs act on (ntic!olinergic drugs act on
c!olinergic tone, t!e only c!olinergic tone, t!e only
re$ersible mec!anism of COPD re$ersible mec!anism of COPD
+nticholiner'ics
+nticholiner'ics

Short7actin' anticholiner'ics
Short7actin' anticholiner'ics

$pratropium %romide
$pratropium %romide

Should %e used four7

Should %e used four7
times a day
times a day

*sually 'ien in
*sually 'ien in
com%ination with
com%ination with
sal%utamol
sal%utamol

Non7selectie %indin' to
Non7selectie %indin' to
:
:
3 3
:
:
) )
:
:
/ /
receptors in the
receptors in the
smooth muscle
smooth muscle

2Com%ient inhaler
2Com%ient inhaler
discontinued June )4486
discontinued June )4486

#
Tiotropium 38 mc' dry
Tiotropium 38 mc' dry
power capsule
power capsule
#
Tiotropium )=< mc' soft
Tiotropium )=< mc' soft
mist inhaler 2Respimat6
mist inhaler 2Respimat6
#
!or,s on the
!or,s on the
parasympathetic
parasympathetic
nerous system
nerous system
3 3
1. ,inc-en,W. et al. (2002) %mproved health outcomes in patients .ith &/P0 durin) 1 yr1s treatment .ith tiotropium. Eur Respir. J 12, 202"21
Lon'7actin' anticholiner'ics
Lon'7actin' anticholiner'ics

$nhaled corticosteroids
$nhaled corticosteroids
# $n moderate to seere COPD
$n moderate to seere COPD
#
2F.C
2F.C
3 3
P<4H predicted6
P<4H predicted6
# Reduce exacer%ation rates
Reduce exacer%ation rates
# Reduce rate of decline in health
Reduce rate of decline in health
related -uality of life
related -uality of life
# +ll studies carried out on hi'h dose
+ll studies carried out on hi'h dose
# Lon'7term side effects
Lon'7term side effects

Corticosteroids in COPD
Corticosteroids in COPD
# -nhaled
-nhaled
corticosteroids in
corticosteroids in
combination with
combination with
bronchodilators
bronchodilators
# .idence shows fewer
.idence shows fewer
exacer%ations and slower
exacer%ations and slower
reduction in health status
reduction in health status
# Recommended if;
Recommended if;
#
F.C F.C
3 3
P<4H P<4H
# ) or more exacer%ations in a ) or more exacer%ations in a
year year
# Side effects; oral
Side effects; oral
candidiasis> hoarse oice>
candidiasis> hoarse oice>
s,in %ruisin'
s,in %ruisin'

#>ral steroids
>ral steroids
#Recommended for use
Recommended for use
in exacer%ation when
in exacer%ation when
there is insufficient
there is insufficient
response to increased
response to increased
%ronchodilators
%ronchodilators
#Re'ular use not
Re'ular use not
recommended in COPD
recommended in COPD
#Numerous side effects
Numerous side effects
with lon' term use of
with lon' term use of
oral preparations
oral preparations

# Symbicort @$$ /urbohaler and
Symbicort @$$ /urbohaler and
Seretide A$$ Accuhaler
Seretide A$$ Accuhaler
# Reduce exacer%ation rates
Reduce exacer%ation rates
# Reduce %reathlessness
Reduce %reathlessness
# $mproe health status
$mproe health status
# $mproe lun' function
$mproe lun' function
Inhaled steroids not licensed for use
Inhaled steroids not licensed for use
in COPD ece!t as combination
in COPD ece!t as combination
Com%ination inhalers
Com%ination inhalers

Oral therapy in COPD
Oral therapy in COPD
# Theophyline
Theophyline
&
*seful for some & 0e aware of side effects and dru'
*seful for some & 0e aware of side effects and dru'
interactions
interactions
# :ucolytics
:ucolytics
&
Thin mucus thus aidin' expectoration= Reduce
Thin mucus thus aidin' expectoration= Reduce
exacer%ations when they wor,
exacer%ations when they wor,
# +ntidepressants
+ntidepressants
&
Screen all seere patients for depression and anxiety
Screen all seere patients for depression and anxiety

!hat do we ,now a%out
!hat do we ,now a%out
improin' surial in COPD"
improin' surial in COPD"
# Smo,in' cessation
Smo,in' cessation
3>) 3>)
# Lon' term oxy'en therapy
Lon' term oxy'en therapy
/>5 />5

# Lun' olume reduction sur'ery
Lun' olume reduction sur'ery
< <
# Can pharmacotherapy improe surial"
Can pharmacotherapy improe surial"
9 9
1. Anthonisen et al. Annals o< Internal 'edicine, !!- 1() **,*7, . NI&E Guideline &.3G. National &olla4oration &entre <or
&hronic &onditions ThoraB !!(, *. Nocturnal .Bygen Thera%y Trial Grou%. Ann Intern Med 17"!, (. 'R& 5orking 3arty. ancet
17"1., -. 2ish#an et al. N !ngl J Med !!*., +. &elli BR. 3redicting #ortality in chronic o4structive %ul#onary disease) chasing the
P@oly GrailQ. Am J Respir Crit Care Med !!+D 1$3) 17",177

TORC?; main o%Mecties
TORC?; main o%Mecties
# "rimary obBecti(e
"rimary obBecti(e
&
The effect of Seretide
The effect of Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
T: T:
s control on
s control on
all7cause mortality oer / years in patients with
all7cause mortality oer / years in patients with
moderate7to7seere COPD
moderate7to7seere COPD
# Secondary obBecti(es
Secondary obBecti(es
&
The effect of Seretide
The effect of Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
T: T:
on the rate of
on the rate of
moderate and seere exacer%ations oer / years
moderate and seere exacer%ations oer / years
&
The effect of Seretide
The effect of Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
T: T:
on health
on health
status 2SGR16 oer / years
status 2SGR16 oer / years
& Post7%ronchodilator F.C
Post7%ronchodilator F.C
3 3
?e*t&o et a%. @"r 0e*p!r J 2004
SGRN > St. GeorgeKs Res%iratory
Nuestionnaire

.fficacy endpoints
.fficacy endpoints
# :ortality %enefits are important> %ut may
:ortality %enefits are important> %ut may
%e of less releance if other endpoints are
%e of less releance if other endpoints are
not met
not met
# Three pillars of COPD mana'ement
Three pillars of COPD mana'ement
&
.xacer%ations
.xacer%ations
&
?ealth status
?ealth status
&
Lun' function
Lun' function

TORC? results; Summary
TORC? results; Summary
# Seretide
Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
Q shows a trend towards
Q shows a trend towards
improed surial s control oer / years which is
improed surial s control oer / years which is
non7statistically si'nificant
non7statistically si'nificant
# Seretide
Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
Q shows sustained
Q shows sustained
exacer%ation reduction oer / years s control
exacer%ation reduction oer / years s control
# Seretide
Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
Q improes and sustains -uality
Q improes and sustains -uality
of life oer / years s control
of life oer / years s control
# Patients feel %etter for lon'er on
Patients feel %etter for lon'er on
Seretide
Seretide
T: T:
<44
<44
+ccuhaler
+ccuhaler
Q 2s control6
Q 2s control6
GSJ Gata on 2ile SERT&.G.2!1 ?-!; 2E6
1

New Licence
New Licence




Seretide
Seretide
T: T:
<44 +ccuhaler
<44 +ccuhaler
T: T:
is now
is now
indicated for the symptomatic treatment
indicated for the symptomatic treatment
of patients with COPD with a F.C
of patients with COPD with a F.C
3 3
P94H
P94H
predicted normal 2pre7%ronchodilator6
predicted normal 2pre7%ronchodilator6
and a history of repeated exacer%ations>
and a history of repeated exacer%ations>
who hae si'nificant symptoms despite
who hae si'nificant symptoms despite
re'ular %ronchodilator therapy
re'ular %ronchodilator therapy
3 3
)* Seretide SPC &+uly ,
t!
-../'
SFC0S120./03-/,40) Se"tember -../

$NSP$R. study
$NSP$R. study

Inestigating New Standards
for Prophy!axis In Reduction
of Exacerbations
,

,
N

N
-

-
.

.
,

,
/

/
$
$



O%Mecties
O%Mecties
# O%Mectie
O%Mectie
&
To study the relatie effects of Seretide
To study the relatie effects of Seretide
I I
<44
<44
+ccuhaler
+ccuhaler
I I

%=d= 2salmeterol <4mc'Ffluticasone
%=d= 2salmeterol <4mc'Ffluticasone
propionate <44mc'6 and Spiria
propionate <44mc'6 and Spiria
I I
?andihaler
?andihaler
I I

2tiotropium %romide6 38mc' o=d= on the rate
2tiotropium %romide6 38mc' o=d= on the rate
of healthcare utilisation COPD exacer%ations
of healthcare utilisation COPD exacer%ations
and related outcomes oer 345 wee,s in
and related outcomes oer 345 wee,s in
su%Mects with seere COPD=
su%Mects with seere COPD=
See#ungal et al. $ &.3G !!8
A##",a%er ad Seret!de are re-!*tered trademarA* of t,e B%a(oSm!t,K%!e -ro"p of
#ompa!e*
Sp!r!4a ad .ad!,a%er are re-!*tered trademarA* of /oe,r!-er I-e%,e!m

.ndpoints
.ndpoints
# Primary .ndpoint
Primary .ndpoint
&
Rate of healthcare utilisation exacer%ations
Rate of healthcare utilisation exacer%ations
# Other .ndpoints
Other .ndpoints
&
Rate of symptom7defined exacer%ations
Rate of symptom7defined exacer%ations
&
Time to withdrawal
Time to withdrawal
& Post7dose F.C
Post7dose F.C
3 3

&
?ealth status as measured %y SGR1
?ealth status as measured %y SGR1
&
+ll7cause mortality
+ll7cause mortality
&
+derse eents R +.s of special interest
+derse eents R +.s of special interest
2E6
1
> 2orced EB%iratory 6olu#e in 1 second
SGRN > St GeorgeKs Res%iratory Nuestionnaire
See#ungal et al. $ &.3G !!8

Oerall Study Conclusions 3
Oerall Study Conclusions 3
# First head to head study of two of the main
First head to head study of two of the main
pharmacolo'ical a'ents used in the mana'ement of
pharmacolo'ical a'ents used in the mana'ement of
COPD=
COPD=
# No differences %etween the treatments for
No differences %etween the treatments for
exacer%ation rate and lun' function at ) years=
exacer%ation rate and lun' function at ) years=
&
0i''est diary card data set on exacer%ations and
0i''est diary card data set on exacer%ations and
different types of exacer%ations produced to
different types of exacer%ations produced to
date
date
&
Nature of the exacer%ations appears to %e
Nature of the exacer%ations appears to %e
different
different

Oerall Study Conclusions )
Oerall Study Conclusions )
# Patients on SFC compared with those on T$O hadO
Patients on SFC compared with those on T$O hadO
&
improed R sustained ?eath Status=
improed R sustained ?eath Status=
&
statistically si'nificant reduction in all cause mortality
statistically si'nificant reduction in all cause mortality
# :ore pneumonias were reported on SFC than on
:ore pneumonias were reported on SFC than on
T$O
T$O
&
These do not appear to hae led to increased mortality
These do not appear to hae led to increased mortality
or detriment in health status
or detriment in health status
# This study proides important new findin's for the
This study proides important new findin's for the
understandin' of COPD exacer%ations=
understandin' of COPD exacer%ations=

*PL$FT
*PL$FT
I I
&
*PL$FT
*PL$FT
is a uni-ue> 57year> landmar, trial inolin'
is a uni-ue> 57year> landmar, trial inolin'
nearly 9444 patients
nearly 9444 patients
3 3
&
+ll patients were allowed to use all other
+ll patients were allowed to use all other
respiratory medications> except inhaled
respiratory medications> except inhaled
anticholiner'ics= Patients were then randomised to
anticholiner'ics= Patients were then randomised to
receie tiotropium or place%o 2control6
receie tiotropium or place%o 2control6
3 3
&
59H of patients in the trial were classified as
59H of patients in the trial were classified as
hain' mild COPD as per N$C. 'uidelines
hain' mild COPD as per N$C. 'uidelines
3>) 3>)

SP$R$C+
SP$R$C+
I I
2tiotropium6 demonstrated
2tiotropium6 demonstrated
lon'7term sustained improements in
lon'7term sustained improements in
lun' function s= control
lun' function s= control
& !hile SP$R$C+ did not !hile SP$R$C+ did not
alter the rate of decline alter the rate of decline
in lun' function> the in lun' function> the
primary study endpoint> primary study endpoint>
it achieed and it achieed and
sustained lun' function sustained lun' function
improements s= improements s=
control control
3 3
& SP$R$C+ sustained SP$R$C+ sustained
improements s= improements s=
control for up to 5 years> control for up to 5 years>
delayin' the clinical delayin' the clinical
course of the disease course of the disease
3 3

SP$R$C+ achieed sustained lon'7
SP$R$C+ achieed sustained lon'7
term improements in -uality of life
term improements in -uality of life
s= control
s= control
&
SP$R$C+ sustained statistically si'nificant
SP$R$C+ sustained statistically si'nificant
improements in -uality of life
improements in -uality of life
2total SGR1 score6 for up to 5 years s= control
2total SGR1 score6 for up to 5 years s= control
3 3
# +n improement of +n improement of 5 units is clinically si'nificant 5 units is clinically si'nificant
&
Patients did not return to %aseline SGR1 score oer
Patients did not return to %aseline SGR1 score oer
the 5 years of the study
the 5 years of the study
3 3

SP$R$C+ achieed a lon'7term
SP$R$C+ achieed a lon'7term
reduction in COPD exacer%ations s=
reduction in COPD exacer%ations s=
control
control
&
SP$R$C+ si'nificantly delayed time to first
SP$R$C+ si'nificantly delayed time to first
exacer%ation s= control
exacer%ation s= control
3 3
& SP$R$C+ si'nificantly reduced the ris, of
exacer%ations for up to 5 years s= control
3
# 35H reduced ris, of exacer%ations 2pP4=4436
#
35H reduced ris, of exacer%ations leadin' to hospitalisations 2pS4=44)6

!hilst on treatment> SP$R$C+ reduced
!hilst on treatment> SP$R$C+ reduced
the ris, of mortality s= control
the ris, of mortality s= control
& 39H lower mortality ris, with 39H lower mortality ris, with
SP$R$C+ s= control while patients SP$R$C+ s= control while patients
receied study medication receied study medication
3 3
& .ffect extended to end7of7 .ffect extended to end7of7
treatment period 2day 35546> as treatment period 2day 35546> as
defined %y protocol defined %y protocol
3 3
& .ffect %ecame non7si'nificant .ffect %ecame non7si'nificant
within the /47day follow7up period within the /47day follow7up period
2day 35D46 when> accordin' to 2day 35D46 when> accordin' to
protocol> patients were protocol> patients were
discontinued from their study discontinued from their study
medication medication
3 3

$nhaler deices
$nhaler deices
Consider;
Consider;
&
Patient preference
Patient preference
&
+%ility> physical and co'nitie
+%ility> physical and co'nitie
&
Lifestyle
Lifestyle
&
Cost effectie 2e='=Seretide :D$ ersus
Cost effectie 2e='=Seretide :D$ ersus
accuhaler6
accuhaler6
:ost patients can use inhalers 'ien sufficient
:ost patients can use inhalers 'ien sufficient
trainin'
trainin'
Chec, inhaler techni-ue re'ularly
Chec, inhaler techni-ue re'ularly
Ne%ulisers should not %e 'ien without specialist
Ne%ulisers should not %e 'ien without specialist
assessment
assessment
<hich inhaler de(ice would you consider for
<hich inhaler de(ice would you consider for
an elderly patient with 2A and poor (isionC
an elderly patient with 2A and poor (isionC

+im of $nhaled therapy
+im of $nhaled therapy
Delier hi'h concentration
Delier hi'h concentration
of dru's directly to lun's R
of dru's directly to lun's R
%ronchioles while reducin'
%ronchioles while reducin'
systemic side effects
systemic side effects

Pressurised metered dose inhalers
Pressurised metered dose inhalers
Thin, .ddy Sto%art lorry doin' D4 miles per
Thin, .ddy Sto%art lorry doin' D4 miles per
hour on a country lane tryin' to round the
hour on a country lane tryin' to round the
%endsT
%endsT
Needs to %e slowed down to ne'otiate the
Needs to %e slowed down to ne'otiate the
%ends
%ends

Spacers
Spacers
# Seeral types aaila%le
Seeral types aaila%le
# ?oldin' cham%er R one
?oldin' cham%er R one
way ale
way ale
# Reduces need for hand
Reduces need for hand
%reath co7ordination
%reath co7ordination
# Spacer should %e
Spacer should %e
compati%le with :D$
compati%le with :D$
# 0TS> )44/ 0TS> )44/

Recommendations a%out spacers
Recommendations a%out spacers
Cleanin';
Cleanin';
Clean no more than monthly as more fre-uent
Clean no more than monthly as more fre-uent
cleanin' affects performance 2due to a %uild up
cleanin' affects performance 2due to a %uild up
of static6
of static6
Clean with water and washin' up li-uid and leae
Clean with water and washin' up li-uid and leae
to air dry
to air dry
!ipe mouthpiece clean of deter'ent %efore use
!ipe mouthpiece clean of deter'ent %efore use
NOT. & Columatic 2lar'e olume6 spacer
NOT. & Columatic 2lar'e olume6 spacer
discontinued in Octo%er )44< and reintroduced
discontinued in Octo%er )44< and reintroduced
in Fe% )449
in Fe% )449

Dry powder deices
Dry powder deices
Thin, .ddy Sto%art lorry tryin' to round a
Thin, .ddy Sto%art lorry tryin' to round a
country %end from stationaryTT
country %end from stationaryTT
Needs acceleration
Needs acceleration
to 'et around the %ends
to 'et around the %ends

!hat the 'uidelines say
!hat the 'uidelines say
# $n most cases %ronchodilator therapy should %e
$n most cases %ronchodilator therapy should %e
administered usin' a hand held inhaler deice 2includin'
administered usin' a hand held inhaler deice 2includin'
a spacer deice if appropriate6
a spacer deice if appropriate6
# Find the most suita%le deice 2remem%er that not all
Find the most suita%le deice 2remem%er that not all
dru's come in all deices6
dru's come in all deices6
# Patients must %e trained in the use of the deice and %e
Patients must %e trained in the use of the deice and %e
a%le to demonstrate it@s use satisfactorily
a%le to demonstrate it@s use satisfactorily
# Patients should %e reassessed and re7tau'ht correct
Patients should %e reassessed and re7tau'ht correct
techni-ue re'ularly
techni-ue re'ularly
# The dose of medication should %e titrated to clinical
The dose of medication should %e titrated to clinical
response
response
N$C. Guidelines 2Thorax )4456 N$C. Guidelines 2Thorax )4456

$n addition;
$n addition;
# Does the patient ,now what to ta,e and
Does the patient ,now what to ta,e and
when"
when"
# Does the patient ,now how to store the
Does the patient ,now how to store the
medication safely"
medication safely"
# !hat is the patient actually doin' with the
!hat is the patient actually doin' with the
dru's once home"
dru's once home"

3 %a'
3 %a'
Of dru's
Of dru's
From
From
Patients
Patients
?omeT
?omeT

Ne%uliser collected this wee,T
Ne%uliser collected this wee,T