COPD : a stepwise or a hit hard approach?

Ferreira, A. J.; Reis, A.; Marçal, N.; Pinto, P.; Bárbara, C.
COPD : a stepwise or a hit hard approach?

Author: Ferreira, A. J.,Reis, A.,Marçal, N.,Pinto, P.,Bárbara, C.
Publisher: Elsevier España
Year: 2016
Source: https://repositorio.ulisboa.pt/bitstream/10451/27426/1/COPD.pdf
Re
Po
Pneumol.
2016;22(4):214---221
www. e po pneumol.o g
SPECIAL
ARTICLE
COPD:
A
s epwise
o
a
hi
ha d
app oach?
A.J.
Fe ei aa,b,
A.
Reisc,
N.
Ma c¸al d,
P.
Pin oe, ,
C.
Bá ba ae, ,∗,
on
behal
o
he
GI
DPOC-G upo
de
In e esse
na
Doenc¸a
Pulmona
Obs u i a
C ónica
aPulmonology
Depa men ,
Cen o
Hospi ala
Uni e si á io
de
Coimb a,
Po ugal
bFacul y
o
Medicine,
Uni e si y
o
Coimb a,
Po ugal
cPulmonology
Depa men ,
Cen o
Hospi ala
Tondela-Viseu,
EPE,
Po ugal
dPulmonology
Depa men ,
Hospi al
de
Vila
F anca
de
Xi a,
Po ugal
eChes
Depa men ,
Cen o
Hospi ala
Lisboa
No e,
Lisbon,
Po ugal
En i onmen al
Heal h
Ins i u e
(ISAMB),
Facul y
o
Medicine,
Uni e si y
o
Lisbon,
Po ugal
Recei ed
22
Augus
2015;
accep ed
27
Decembe
2015
A ailable
online
27
Feb ua y
2016
KEYWORDS
COPD;
S epwise;
Hi
ha d;
S ep-up;
ICS
wi hd awal;
B onchodila o s;
ICS
Abs ac
Cu en
guidelines
di e
sligh ly
on
he
ecommenda ions
o
ea men
o
Ch onic
Obs uc i e
Pulmona y
Disease
(COPD)
pa ien s,
and
al hough
he e
a e
some
undispu ed
ecom-
menda ions,
he e
is
s ill
deba e
ega ding
he
managemen
o
COPD.
One
o
he
hind ances
o
deciding
which
he apeu ic
app oach
o
choose
is
la e
diagnosis
o
misdiagnosis
o
COPD.
A e
a
p ope
diagnosis
is
achie ed
and
se e i y
assessed,
he
choice
be ween
a
s epwise
o
‘‘hi
ha d’’
app oach
has
o
be
made.
Fo
GOLD
A
pa ien s
he
s epwise
app oach
is
ecommended,
whils
o
B,
C
and
D
pa ien s
his
emains
deba able.
Mo eo e ,
in
pa ien s
o
whom
inhaled
co icos e oids
(ICS)
a e
ecommended,
a
s ep-up
o
‘‘hi
ha d’’
app oach
wi h
iple
he apy
will
depend
on
he
pa ien ’s
cha ac e is ics
and,
o
pa ien s
who
a e
being
o e - ea ed
wi h
ICS,
ICS
wi hd awal
should
be
pe o med,
in
o de
o
op imize
he apy
and
educe
excessi e
medica ions.
This
pape
discusses
and
p oposes
s epwise,
‘‘hi
ha d’’,
s ep-up
and
ICS
wi hd awal
he -
apeu ic
app oaches
o
COPD
pa ien s
based
on
hei
GOLD
g oup.
We
conclude
ha
all
app oaches
ha e
beneﬁ s,
and
only
a
ca e ul
pa ien
selec ion
will
de e mine
which
app oach
is
be e ,
and
which
pa ien s
will
beneﬁ
he
mos
om
each
app oach.
©
2016
Sociedade
Po uguesa
de
Pneumologia.
Published
by
Else ie
Espa˜
na,
S.L.U.
This
is
an
open
access
a icle
unde
he
CC
BY-NC-ND
license
(h p://c ea i ecommons.o g/licenses/by-
nc-nd/4.0/).
∗Co esponding
au ho .
E-mail
add esses:
[email p o ec ed],
[email p o ec ed]
(C.
Bá ba a).
h p://dx.doi.o g/10.1016/j. ppnen.2015.12.012
2173-5115/©
2016
Sociedade
Po uguesa
de
Pneumologia.
Published
by
Else ie
Espa˜
na,
S.L.U.
This
is
an
open
access
a icle
unde
he
CC
BY-NC-ND
license
(h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
COPD:
A
s epwise
o
a
hi
ha d
app oach?
215
In oduc ion
Cu en
guidelines
di e
sligh ly
on
he
ecommenda ions
o
ea men
o
Ch onic
Obs uc i e
Pulmona y
Disease
(COPD)
pa ien s,
mainly
because
pa ien
s a iﬁca ion
is
no
consensual
ac oss
guidelines.1 --- 5 Al hough
he e
a e
some
undispu ed
ecommenda ions,
such
as
smoking
cessa ion,
physical
ac i i y
p og ams,
and
inﬂuenza
and
pneumococcal
accina ion,
he e
is
s ill
deba e
ega ding
he
manage-
men
o
COPD.6---12 The
he apeu ic
app oach
p oposed
by
he
Global
Ini ia i e
o
Ch onic
Obs uc i e
Lung
Disease
(GOLD),
and
based
solely
on
he
GOLD
classiﬁca ion
o
COPD,2is
no
en i ely
sa is ac o y,
gi en
he
a iabili y
wi hin
GOLD
g oups,
namely
ega ding
hospi aliza ions
and
mo ali y.13 Howe e ,
he apy
has
o
be
based
on
some
clas-
siﬁca ion
sys em,
and
he
GOLD
classiﬁca ion
is
he
mos
widely
accep ed,
e en
wi h
i s
ca ea s.
One
o
he
hind ances
o
deciding
which
he apeu ic
app oach
o
choose
is
la e
diagnosis
o
misdiagnosis
o
COPD.
Pa ien s
who
a e
no
diagnosed
a
he
ea ly
s ages
o
he
disease
canno
ecei e
he
ea ly
ea men
which
has
been
shown
o
be
beneﬁcial.6,11,14 On
he
o he
hand,
pa ien s
misdiagnosed
wi h
as hma
o
As hma-COPD
o e lap
synd ome
(ACOS),
will
be
o e ea ed
wi h
inhaled
co i-
cos e oids
(ICS),
and
a e
likely
o
see
no
imp o emen
in
hei
symp om
bu den.
In
ac ,
wo
ecen
analyses
showed
ha ,
in
cu en
clinical
p ac ice,
ICS
a e
being
p esc ibed
inapp op ia ely,15,16 and
ha
housands
o
pa ien s
may
be
o e ea ed.
A e
a
p ope
diagnosis
is
achie ed,
and
se e i y
assessed,
he
choice
o
a
s epwise
o
‘‘hi
ha d’’
app oach
has
o
be
made,
and
i
o
GOLD
A
pa ien s
he
s ep-
wise
app oach
is
ecommended,2 o
B,
C
and
D
pa ien s
his
emains
deba able.17 The
a gumen
o
he
s epwise
app oach
is
o
no
o e ea
pa ien s,
bu
some
pa ien s
may
beneﬁ
om
a
‘‘hi
ha d’’
app oach,
wi h
he
aim
o
maximal
b onchodila ion.12,13,18---20 In
pa ien s
who
will
beneﬁ
om
dual
b onchodila ion,
a
long-ac ing
mus-
ca inic
an agonis /long-ac ing
be a-agonis
(LAMA/LABA)
ﬁxed-dose
combina ion
is
ad an ageous.11,12,21---24 Also,
in
pa ien s
o
whom
ICS
is
ecommended,
a
s ep-up
o
‘‘hi
ha d’’
app oach
wi h
iple
he apy
will
depend
on
he
pa ien ’s
cha ac e is ics.2,4,5,17 Fo
pa ien s
who
a e
being
o e ea ed
wi h
ICS,
ICS
wi hd awal
should
be
pe -
o med,
in
o de
o
op imize
he apy
and
educe
excessi e
medica ions.21,22,25---28 Howe e ,
his
aises
ano he
ques ion:
how
o
decide
when
a
pa ien
is
being
o e ea ed?
The e
a e
cu en ly
no
eliable
o
accu a e
bioma ke s
o
esponse
o
he apy
and
disease
p og ession,
so
he
decision
conce n-
ing
ICS
wi hd awal
mus
be
based
on
he
a ailable
objec i e
es s
and
subjec i e
ins umen s.2
Resul s
om
a
ecen
UK
P ima y
Ca e
Se ing
e ospec-
i e
s udy
showed
ha ,
24
mon hs
a e
COPD
diagnosis
and
p esc ip ion
o
ini ial
he apy,
se e al
ea men
s a egies
a e
used:
swi ch
in
medica ion,
s epwise,
s ep-up
and
ICS
wi hd awal,28 sugges ing
ha
he e
is
an
unme
clinical
need
o
eﬁne
he apy
beyond
GOLD
and
o he
in e na ional
and
na ional
guidelines.
This
pape
discusses
and
p oposes
s epwise
and
‘‘hi
ha d’’
he apeu ic
app oaches
o
COPD
pa ien s
based
on
hei
GOLD
g oup.
An
al e na i e
ea men
app oach,
based
on
pheno ypes,
is
add essed
elsewhe e.29 We
sugges
wo
subg oups
o
GOLD
A
and
GOLD
B
pa ien s,
wi h
di e en
he apeu ic
app oaches.
Finally,
we
conclude
ha ,
in
COPD,
he apy
should
be
ailo ed
o
he
pa ien ,
aking
in o
consid-
e a ion
co-mo bidi ies,
p esence
o
hype inﬂa ion,
his o y
o
ch onic
b onchi is,
le els
o
physical
ac i i y,
and
each
indi idual
pa ien
cha ac e is ics.
GOLD
A
pa ien s
I
is
di ﬁcul
o
iden i y
asymp oma ic
GOLD
A
pa ien s
wi h
no
exace ba ions,
gi en
ha
hey
ha e
no
eason
o
seek
medical
help.
Spi ome ic
sc eening
o
asymp oma ic
indi-
iduals
is
no
suppo ed
by
e idence,
al hough
in
indi iduals
o e
40
yea s
old
and
wi h
a
smoking
his o y
o
>10
pack
yea s,
spi ome y
may
be
pe o med
wi h
he
aim
o
ea ly
diagnosis.1Indeed,
some
o
hese
pa ien s
a e
iden iﬁed
du ing
sc eenings,
bu
many
o
hose
who
a e
no
eligible
o
sc eening
(e.g.,
non-smoke s),
may
emain
undiagnosed.11
Also,
hese
pa ien s
end
o
unde es ima e
hei
symp oms
and
adap
hei
daily
ac i i ies
by
exe cise
sel -limi a ion,1
hence
epo ing
o
be
asymp oma ic.
These
uniden iﬁed
pa ien s
canno
ecei e
he
ea ly
ea men ,
which
has
been
shown
o
be
beneﬁcial.6,11,14
Iden iﬁca ion
o
GOLD
A
pa ien s
Besides
sc eening,
hese
pa ien s
a e
mainly
iden iﬁed
in
ou
si ua ions:
(a)
in
clinical
isi s
o
o he
causes
o
complain s;
(b)
when
hey
a e
subjec ed
o
es s
o
non-
espi a o y
easons;
(c)
in
he
eme gency
oom
due
o
an
acu e
episode;
o
(d)
du ing
p e-su ge y
es ing.
Once
iden iﬁed,
i
is
impe a i e
no
o
lose
hese
pa ien s
o
ollow-up,
as
hey
will
e en ually
e ol e
o
o he
GOLD
g oup
and
he apy
will
ha e
o
be
adjus ed.
A
co ec
diag-
nosis
is
o
he
u mos
impo ance,
since
i
leads
o
bo h
unde ea men
and
o e ea men
(e.g.,
COPD
diagnosed
as
as hma).
We
sugges
an
ac i e
case-ﬁnding
app oach
o
he
iden-
iﬁca ion
o
GOLD
A
pa ien s.
We
u he
p opose
ha
hese
pa ien s
a e
ﬂagged
whene e
hey
a e
diagnosed
and,
he ea e ,
ha
hey
a e
managed
by
hei
gene al
p ac-
i ione ,
in
close
coope a ion
wi h
a
pulmonologis .
Recommended
he apeu ic
app oach
o
GOLD
A
pa ien s
Gi en
ha
hese
pa ien s
a e
o en
excluded
om
Ran-
domized
Clinical
T ials
(RCTs),
he e
a e
no
sys ema ic
da a
a ailable
on
which
he apy
should
be
used
o
how
hey
will
espond.6Should
hey
be
ea ed?
When?
Wi h
which
med-
ica ion
and
how?
How
will
hey
p og ess
wi h
o
wi hou
he apy?
A
s udy
based
on
he
ECLIPSE
coho
showed
ha ,
a
3
yea s
ollow-up,
57%
o
pa ien s
ini ially
assigned
o
GOLD
A
emained
in
he
A
g oup,
whils
he
emaining
43%
p og essed
o
o he
GOLD
g oups.13 Based
on
his
s udy,
all
GOLD
A
pa ien s
should
ecei e
ea men .
Cu en
guidelines
gene ally
ecommend
o
hese
pa ien s
smoking
cessa ion,
physical
ac i i y
p og ams,
and
inﬂuenza
and
pneumococcal
accina ion.
Also,
he
use
o
a
sho -ac ing
be a-agonis
(SABA)
o
a
sho -ac ing
216
A.J.
Fe ei a
e
al.
musca inic
an agonis
(SAMA)
as
needed
is
mos ly
consen-
sual,
al hough
LABA
o
LAMA
may
be
used
as
al e na i e
he apies.1 --- 5 Some
au ho s
specula e
ha
ea ly
in e en ion
wi h
long-ac ing
b onchodila o s
may
imp o e
pa ien -
epo ed
ou comes.11 Howe e ,
one
majo
issue
wi h
hese
pa ien s
is
compliance
o
long- e m
d ugs,6and
pa ien
edu-
ca ion
is
undamen al
in
delaying
COPD
e olu ion.
In
GOLD
A
pa ien s,
bo h
pheno ype3,6,30 and
co-
mo bidi ies1 --- 5 should
be
aken
in o
accoun
when
choosing
be ween
a
LABA
o
a
LAMA,
wi h
he
aim
o
achie ing
he
bes
ou comes
and
delaying
disease
p og ession.
Bo h
LAMAs
and
LABAs
ha e
shown
simila
p oﬁles
ega ding
FEV1and
dyspnea
imp o emen ,
exe cise
ole ance,
exace ba ions
educ ion
and
sa e y.21,23,24,26,31---40 Howe e ,
he e
is
some
e idence
ha
LAMAs
may
delay
lung
unc ion
decline34,35
and
dec ease
all-cause
mo ali y,34 and
may
be
mo e
e ec-
i e
han
LABAs
in
p e en ing
exace ba ions.41 Despi e
his,
and
al hough
LABAs
do
no
seem
o
inﬂuence
mo ali y,42
wo
s udies
showed
supe io i y
in
p o iding
be e
symp-
oma ic
imp o emen
han
a
LAMA.43,44 These
da a
sugges
ha
LAMAs
should
be
p e e ed
o
pa ien s
a
highe
isk
o
exace ba ions,
whils
LABAs
would
be
be e
o
symp-
oma ic
con ol,
al hough
i
depends
on
he
indi idual
clinical
esponse
o
each
pa ien .
I
a
LABA
is
chosen,
inda-
ca e ol
may
be
p e e able
o
o he
comme cially
a ailable
LABAs
since,
besides
ha ing
all
he
abo e
men ioned
ad an-
ages
o
LABAs,
i
is
he
only
once-daily
LABA
wi h
s udies
designed
o
in es iga e
exace ba ions45,46 and
p o ed
able
o
educe
hem,
al hough
in
mode a e
o
se e e
pa ien s.39,40
Howe e ,
e idence
is
s ill
oo
sca ce
o
p opose
a
ecom-
menda ion
be ween
a
LABA
and
a
LAMA.
Also,
he
ﬁnancial
aspec
should
no
be
dis ega ded
when
choosing
be ween
a
LABA
o
a
LAMA,
as
some
pa ien s
may
no
be
able
o
a o d
some
he apies
and
espond
well
o
mo e
a o dable
al e na i es.
Dual
b onchodila ion
is
no
an
op ion
o
hese
pa ien s.
Finally,
gi en
he
he e ogenei y
o
COPD,
e en
pa ien s
classiﬁed
as
belonging
o
he
A
g oup
show
a
la ge
a iabili y.
We
p opose
ha
g oup
A
pa ien s
need
o
be
sub-di ided
in o
wo
g oups,
AX1
and
AX2,
and
he
he apeu ic
app oach
should
be
based
on
his
subdi ision
---
Table
1.
We
u he
ecommend
ha ,
i
a
LABA
is
chosen,
inda-
ca e ol
may
be
p e e able
as
i
also
educes
he
a e
o
exace ba ions.
We
also
ecommend
ha
he apy
should
be
ailo ed
o
he
pa ien ,
aking
in o
conside a ion
co-mo bidi ies,
Table
1
P oposed
di ision
o
GOLD
A
pa ien s
in
wo
sub-
g oups
and
espec i e
he apeu ic
app oaches.
Sub-g oup
cha ac e is ics
The apeu ic
app oach
AX1:
FEV1>
80%;
no
wo sening
o
FEV1in
annual
assessmen
SABA
o
SAMA
only
SOS
AX2:
50%
<
FEV1<
80%;
and/o
wo sening
o
FEV1in
annual
assessmen
LABA
o
LAMA
FEV1---
o ced
expi a o y
olume
in
1
second;
SABA
---
sho
ac -
ing
␤2-agonis ;
SAMA
---
sho
ac ing
musca inic
an agonis ;
LABA
---
long
ac ing
␤2-agonis ;
LAMA
---
long
ac ing
musca inic
an ag-
onis .
p esence
o
hype inﬂa ion,
his o y
o
ch onic
b onchi is,
le els
o
physical
ac i i y
and
ad e se
e ec s
o
each
d ug.
Finally,
all
COPD
pa ien s
should
be
o e ed
a
comple ely
ee
smoking
cessa ion
p og am,
including
consul a ions
and
he apy.
GOLD
B
pa ien s
Cu en
guidelines
gene ally
ecommend
o
hese
pa ien s
smoking
cessa ion,
physical
ac i i y
p og ams,
inﬂuenza
and
pneumococcal
accina ion,
and
pulmona y
ehabili a ion.1 --- 5
All
guidelines
ag ee
ha
b onchodila o s
a e
he
baseline
he apy
o
all
s ages
o
COPD,
bu
he
choice
o
which
b onchodila o
o
use
is
le
o
he
physician.12 Also,
mos
guidelines
gene ally
ecommend
a
s epwise
app oach,
and
dual
b onchodila ion
only
when
one
b onchodila o
is
no
su ﬁcien
o
p o ide
sa is ac o y
symp om
elie .12 GOLD
ecommends
LAMA
o
LABA
as
he
ﬁ s
choice
medica ion
and
LAMA
+
LABA
as
he
al e na i e
choice.2I
indeed
he
choice
is
a
s epwise
app oach,
hen
which
long-ac ing
b on-
chodila o
should
be
used,
a
LABA
o
a
LAMA?
As
al eady
discussed
abo e,
e idence
is
s ill
oo
sca ce
o
p opose
a
ecommenda ion.
On
he
o he
hand,
Agus i
and
Fabb i
de end
he
‘‘hi
ha d’’
app oach
wi h
dual
b onchodila ion
o
GOLD
B
pa ien s,17 and
he e
a e
se e al
a gumen s
in
a o
o
his
app oach.
G oup
B
and
C
pa ien s
show
a
simi-
la
isk
o
all-cause
mo ali y,13 sugges ing
ha
a
mo e
agg essi e
ea men
app oach
should
be
used
in
hese
pa ien s.
Also,
many
pa ien s
ecei ing
long-ac ing
b on-
chodila o
mono he apy
con inue
o
expe ience
signiﬁcan
symp oms,18 and
dual
b onchodila ion
p o ides
be e
symp oma ic
elie ,12,23,24 imp o es
FEV1in
pa ien s
wi h
mode a e- o-se e e
COPD,23,24,47 and
imp o es
heal h
s a us.23 Mo eo e ,
educ ion
o
hype inﬂa ion,
as
achie ed
wi h
maximal
(dual)
b onchodila ion,
inc eases
exe cise
ole ance,12,31 and
highe
le els
o
physical
ac i i y
a e
associa ed
wi h
a
be e
unc ional
s a us48 and
educed
isk
o
hospi aliza ions
and
mo ali y,49 e en
a
le els
as
low
as
he
equi alen
o
walking
o
cycling
2
h/week.50 Also,
i
has
been
epo ed
ha
objec i ely
measu ed
physical
ac i i y
is
he
s onges
p edic o
o
all-cause
mo ali y
in
pa ien s
wi h
COPD.51 The e o e,
i
can
be
specula ed
ha
dual
b onchodila ion
will
ha e
bo h
sho -
and
long- e m
beneﬁcial
e ec s
in
COPD
pa ien s.
In
pa ien s
who
will
beneﬁ
om
dual
b onchodila ion,
LAMA/LABA
ﬁxed-dose
combina ions
a e
expec ed
o
become
he
new
s anda d
in
COPD
ea men .9In
GOLD
2
o
3
pa ien s,
wi h
o
wi hou
a
his o y
o
exace ba ions,
dual
b onchodila ion
wi h
once-
daily
indaca e ol/glycopy onium
(IND/GLY)
has
clinically
meaning ul
imp o emen s
in
symp oma ic
pa ame e s
e sus
a
salme e ol/ﬂu icasone
combina ion
(SFC)21,22 and
io opium,23 and
is
supe io
o
ea men
wi h
i s
mono-
componen s,
indaca e ol
and
glycopy onium,23 sugges ing
he
exis ence
o
syne gis ic
ac i i y
be ween
he
LABA
and
he
LAMA.11 IND/GLY
also
p o ided
supe io
imp o emen s
in
pa ien - epo ed
dyspnea
and
lung
unc ion
e sus
placebo
and
io opium.24 Mo eo e ,
indaca e ol
and
gly-
copy onium
show
a
e y
as
and
long-las ing
(abou
24
h)
elaxa ion
o
ai way
smoo h
muscle.12 The e
a e
se e al
po en ial
ad an ages
and
beneﬁcial
e ec s
o
ha ing
a
combina ion
o
LABA
+
LAMA
on
he
same
de ice.52
COPD:
A
s epwise
o
a
hi
ha d
app oach?
217
Table
2
P oposed
di ision
o
GOLD
B
pa ien s
in
wo
sub-
g oups
and
espec i e
he apeu ic
app oaches.
Sub-g oup
cha ac e is ics
The apeu ic
app oach
BX1:
mMRC
=
2;
AND
FEV1>
70%;
AND
no
ca dio ascula
co-mo bidi ies
a)
i
no
medica ed,
ini ia e
LABA
o
LAMA
BX2:
mMRC
>
2;
OR
FEV1<
70%;
OR
wi h
ca dio ascula
co-mo bidi ies
LABA
+
LAMA
(‘‘hi
ha d’’
app oach)
+
ehabili a ion
wi h
exe cise
aining
mMRC
---
modiﬁed
Medical
Resea ch
Council
dyspnea
scale;
FEV1
---
o ced
expi a o y
olume
in
1
second;
LABA
---
long
ac ing
␤2-
agonis ;
LAMA
---
long-ac ing
musca inic
an agonis .
Finally,
gi en
he
he e ogenei y
o
COPD,
e en
pa ien s
classiﬁed
as
belonging
o
he
B
g oup
show
la ge
a iabili y.
We
p opose
ha
g oup
B
pa ien s
need
o
be
sub-di ided
in o
wo
g oups,
BX1
and
BX2,
and
he
he apeu ic
app oach
should
be
based
on
his
subdi ision
---
Table
2.
We
u he
ecommend
ha ,
when
he
ea men
o
choice
is
dual
b onchodila ion,
a
combina ion
o
LABA
+
LAMA
on
he
same
de ice
is
p e e able.
GOLD
C
and
D
pa ien s
In
addi ion
o
all
gene al
ecommenda ions
o
GOLD
B
pa ien s,1 --- 5 guidelines
sugges :
LAMA
and/o
LABA,
wi h
o
wi hou
ICS,1,2,4 wi h
ICS
ecommended
o
pa ien s
wi h
equen
exace ba ions
ha
a e
no
adequa ely
con olled
by
long-ac ing
b onchodila o s;2,4 a
s epwise
o
s ep-up
app oach,
o
immedia e
iple
he apy,
depending
on
e-
quency
o
exace ba ions;5no
ecommenda ion
o
ICS
on
he
non-exace ba o
pa ien
pheno ype.3Agus i
&
Fabb i
p opose
a
s epwise
o
s ep-up
app oach
depending
on
dys-
pnea
and
isk
o
exace ba ions,
espec i ely.17 A
ecen
analysis
showed
ha ,
in
cu en
clinical
p ac ice,
how-
e e ,
g oup
D
pa ien s
a e
mo e
equen ly
p esc ibed
iple
he apy,
ega dless
o
pulmona y
unc ion
and
isk
o
exace ba ions,16 which
is
con a y
o
wha
he
guidelines
ecommend.
Rega ding
dual
b onchodila ion,
se e al
andomized
clin-
ical
ials
in
GOLD
2
o
4
pa ien s,
wi h
o
wi hou
a
his o y
o
exace ba ions,
showed
ha
dual
b onchodila ion
wi h
IND/GLY
imp o es
symp oms,21---24,37 and
p e en s
mode a e
o
se e e
COPD
exace ba ions.37 In
he
SHINE,23 BLAZE24 and
SPARK37 s udies,
pa ien s
al eady
on
ICS
he apy
a
base-
line
main ained
he
ICS
du ing
he
s udy,
whe eas
in
he
ILLUMINATE21 and
LANTERN22 s udies
pa ien s
on
ICS
he -
apy
be o e
s udy
s a
unde wen
a
washou
pe iod.
Taken
oge he ,
hese
da a
sugges
ha
dual
b onchodila ion
is
an
app op ia e
ea men
op ion
o
pa ien s
wi h
se e e
and
e y
se e e
COPD.
C
and
D
subg oups
The apeu ic
op ions
ha e
o
conside
he
h ee
C
and
D
sub-
g oups:
Table
3
P oposed
he apeu ic
app oach
o
C
and
D
pa ien s.
C/D
Sub-g oup
The apeu ic
app oach
C1
LAMA
D1
LAMA
+
LABA
C2
LABA
+
ICS
D2
LABA
+
ICS
+
LAMA
C3,
D3
LABA
+
ICS
+
LAMA
C1,
D1
---
pa ien s
a
high
isk
due
o
poo
unc ion;
C2,
D2
---
pa ien s
a
high
isk
due
o
exace ba ions;
C3,
D3
---
pa ien s
a
high
isk
due
o
bo h
poo
unc ion
and
exace ba ions;
LABA
---
long
ac ing
␤2-agonis ;
LAMA
---
long-ac ing
musca inic
an ago-
nis ;
ICS
-
inhaled
co icos e oid.
-
C1,
D1
(high
isk
due
o
poo
unc ion)
-
C2,
D2
(high
isk
due
o
exace ba ions)
-
C3,
D3
(high
isk
due
o
bo h
poo
unc ion
and
exace ba-
ions)
We
p opose
ha
he
he apeu ic
app oach
is
based
on
hese
subg oups
---
Table
3.
When
he
ea men
o
choice
is
dual
b onchodila ion,
a
combina ion
o
LABA
+
LAMA
on
he
same
de ice
is
p e e able.
Fo
C1
and
D1
pa ien s,
a
s ep-
wise
o
‘‘hi
ha d’’
app oach
should
be
decided
depending
on
symp oms,
wi h
he
‘‘hi
ha d’’
app oach
ecommended
in
s ongly
symp oma ic
pa ien s.
Fo
C2,
D2,
C3
and
D3
pa ien s,
a
s ep-up
app oach
o
immedia e
iple
he apy
should
be
decided
depending
on
he
equency
o
exace -
ba ions.
We
sugges
he
pa ien
o
be
e-assessed
e e y
3
mon hs
du ing
a
one
yea
pe iod
a e
ini ia ion
o
ICS
(spi ome y,
he
Modiﬁed
Medical
Resea ch
Council
Dyspnea
Scale
(mMRC),
he
COPD
Assessmen
Tes
(CAT),
inﬂamma-
ion,
symp oms).
We
u he
ecommend
ha ,
i
he e
we e
no
exace ba ions
du ing
12
mon hs,
COPD
was
s able,
and
assessed
pa ame e s
a e
wi hin
he
expec ed
ange,
wi h-
d awal
o
ICS
could
be
conside ed.
ICS
Al hough
ICS
a e
no
indica ed
o
pa ien s
wi hou
exace ba ions,2---5,17 ICS/LABA
o
e en
iple
he apy
is
widely
p esc ibed
in
eal-li e
managemen
o
COPD,
e en
in
pa ien s
wi h
mild
o
mode a e
COPD
se e i y.
Bo h
Gene al
P ac i ione s
and
specialis s
in
espi a o y
medicine
o en
use
iple
he apy
e en
o
pa ien s
who
a e
no
su e -
ing
om
se e e
COPD.8Al hough
he
easons
o
his
a e
unclea ,
we
specula e
ha
his
is
mainly
due
o
he
gene -
alized
idea
ha
a
pa ien
aking
ICS
will
be
mo e
con olled
han
a
pa ien
who
is
no
on
ICS
he apy,
and
will
no
exac-
e ba e
o
decompensa e.
This
is
no
ue.
In
ac ,
pa ien s
who
do
no
need
ICS
he apy
will
be
o e medica ed,
will
no
beneﬁ
om
iple
he apy,
and
will
su e
all
he
possible
ad e se
e en s
o
ICS,
namely
pneumonia.
A
ecen
e iew
om
UK
gene al
p ac ice
showed
ha ,
in
2009,
pa ien s
in
all
GOLD
s ages
we e
ecei -
ing
iple
he apy.15 The
ques ion
o
whe he
he
less
se e e
pa ien s
we e
equen
exace ba o s,
and
hus
being
ea ed
acco ding
o
he
cu en
guidelines,
emained
unan-
swe ed.
Ano he
ecen
analysis
conﬁ med
ha ,
in
cu en
clinical
p ac ice,
ICS
a e
indeed
used
inapp op ia ely.16
218
A.J.
Fe ei a
e
al.
These
epo s
indica e
ha
ICS
p esc ip ion
does
no
ol-
low
he
cu en
guidelines
and
housands
o
pa ien s
may
be
o e ea ed.
Wi hd awal
om
ICS
I
pa ien s
a e
indeed
being
o e ea ed,
hen
hey
will
no
only
be
subjec ed
o
he
ICS’
nume ous
side
e ec s
bu
hey
will
also
no
beneﬁ
om
he
ICS,
ende ing
he
isk/beneﬁ
a io
o
he
ICS
oo
high
o
jus i y
i s
use.
A
sys ema ic
e iew
om
2011
on
ials
wi h
wi hd awal
o
ICS
ound
no
e idence
ha
wi hd awing
pa ien s
om
ICS
in
ou ine
p ac ice
led
o
impo an
de e io a ion
o
ou comes,
namely
equency
o
exace ba ions
and
exe cise
ole ance.
Only
one
o
he
included
ials
epo ed
a
signiﬁcan
decline
in
lung
unc ion.53 The
ILLUMINATE21 and
he
LANTERN22 s udies
showed
ha ,
in
GOLD
2
and
3
pa ien s
wi h
o
wi hou
one
mode a e
o
se e e
exace ba ion
in
he
p e ious
yea ,
ICS
can
be
sa ely
wi hd awn,
and
once-daily
IND/GLY
p o ided
signiﬁcan ,
sus ained,
and
clinically
meaning ul
imp o e-
men s
in
lung
unc ion
e sus
wice-daily
SFC.
In
addi ion,
IND/GLY
p o ided
signiﬁcan
symp oma ic
beneﬁ
and
was
supe io
o
SFC
in
achie ing
b onchodila ion
and
educing
he
a e
o
exace ba ions.
Ano he
s udy
in
which
ICS
he -
apy
was
ei he
swi ched
o
wi hd awn,
in
pa ien s
wi h
mode a e
o
se e e
COPD,
showed
ha
ICS
can
be
sa ely
discon inued,
and
he
addi ion
o
ﬂu icasone---salme e ol
o
io opium
may
imp o e
lung
unc ion
and
dec ease
hospi-
aliza ions,
bu
does
no
a ec
a es
o
exace ba ions.26 The
OPTIMO
s udy,27 a
eal-li e
s udy,
showed
ha
ICS
may
be
wi hd awn,
p o ided
app op ia e
he apy
wi h
b onchodila-
o s
is
main ained,
bu
he
WISDOM
s udy54 showed
ha
ICS
wi hd awal
had
no
e ec
on
exace ba ions
bu
led
o
a
dec ease
in
pulmona y
unc ion.
The
di e en
esul s
om
he
OPTIMO
and
WISDOM
s udies
may
lie
in
one
simple
ac :
in
he
OPTIMO27 s udy
pa ien s
had
an
a e age
FEV1≈71%
p edic ed,
being
p obably
non-exace ba o
GOLD
B
pa ien s,
and
he e o e
did
no
need
ICS,
whils
he
WISDOM54 s udy
pa ien s
had
much
mo e
se e e
ai way
limi a ion
(FEV1≈34%
p edic ed,
GOLD
3
and
4),
p obably
ﬁ ing
he
c i e ia
o
ICS
use,
and
we e
hus
a ec ed
by
wi hd awal.
Ano he
explana ion
o
hese
esul s
lies
in
he
design
o
he
WIS-
DOM
s udy,
whe e
e en
pa ien s
who
had
ne e
been
on
ICS,
ecei ed
an
ICS-con aining
iple
he apy
o
6
weeks
be o e
andomiza ion.
Mo eo e ,
he
OPTIMO
s udy
explic-
i ly
excludes
pa ien s
wi h
a
‘‘his o y
o
as hma’’,
whils
he
WISDOM
s udy
excludes
pa ien s
wi h
a
‘‘cu en
diagnosis
o
as hma’’,
which
makes
i
possible
o
pa ien s
wi h
ACOS
o
be
included
in
he
WISDOM
s udy.
A
e y
ecen
UK
P ima y
Ca e
Se ing
e ospec i e
s udy
shows
ha ,
in
newly
diagnosed
COPD
pa ien s,
wi h-
d awal
om
ICS
is
common
a e
12
o
24
mon hs
o
he apy
ini ia ion.28 Un o una ely,
and
al hough
included
pa ien s
we e
classiﬁed
as
GOLD
1
o
4,
ea men
app oaches
used
we e
no
s a iﬁed
by
GOLD
s age.
Rega dless
all
a ailable
e idence,
he e
is
a
gene alized
conce n
among
physicians
ha ,
i
a
pa ien
is
wi hd awn
om
ICS,
ha
pa ien
will
decompensa e
o
exace ba e.
E en
i
he
pa ien
is
e-assessed
and
does
no
ha e
indi-
ca ions
o
ICS,
he
eluc ance
o
wi hd aw
emains.
This
conce n
s ems
mainly
om
he
esul s
o
he
TORCH19,20,42
ial,
which
con inced
he
communi y
o
physicians
ha
ICS
imp o es
se e al
ou comes,
slows
disease
p og ession
and
educes
mode a e- o-se e e
exace ba ions,
e en
i
ailing
o
show
a
beneﬁcial
e ec
o
ICS
on
all-cause
mo ali y
a es.
Howe e ,
in
ligh
o
mo e
ecen
da a,
as
p esen ed
abo e,
he e
is
no
e idence-based
eason
o
such
a
conce n.
Ano he
hind ance
o
deciding
whe he
o
wi hd aw
om
ICS
o
no
is
misdiagnosis,
e.g.
COPD
misdiagnosed
as
as hma,
o
suspicion
o
he
ACOS
pheno ype.
The
only
way
o
o e come
his
hind ance
is
o
a ain
a
p ope
diagnosis.
Finally,
pa ien s
p e e
o
be
wi hd awn
om
ICS
due
o
he
gene al
pe cep ion
ha
co icos e oids
a e
‘‘dange ous’’
---
and
indeed
hey
can
be,
i
no
p ope ly
p esc ibed.
We
ecommend
ha
A
and
B
pa ien s
wi hou
exace ba-
ions,
who
a e
o e ea ed
wi h
ICS,
should
be
wi hd awn
om
ICS
in
o de
o
op imize
he apy
and
educe
exces-
si e
medica ions,
p o ided
hey
a e
no
ACOS,
and
kep
on
close
su eillance.
C
and
D
pa ien s
wi hou
exace ba ions
should
also
be
wi hd awn
om
ICS,
wi h
e-assessmen s
ec-
ommended
e e y
3
mon hs
du ing
a
one
yea
pe iod.
How
o
wi hd aw
om
ICS?
The
wo
op ions
a e
wi hd awal
o
ICS
wi h
o
wi hou
ape ing
o .
The
UK
P ima y
Ca e
Se ing
e ospec i e
s udy
does
no
speci y
how
wi hd awal
om
ICS
was
achie ed.28 Bo h
he
ILLUMINATE
s udy21 and
he
LANTERN
s udy22 men ion
a
washou
pe iod
o
up
o
7
days,
bu
also
do
no
speci y
i
his
pe iod
was
wi h
o
wi hou
ape ing
o .
Aa on
e
al.
also
do
no
speci y
how
ICS
was
discon inued.26 The
OPTIMO
s udy27 does
no
men ion
how
ICS
was
wi hd awn,
bu
he
WISDOM
s udy54 does
speci y
ha
ICS
was
ape ed
o
o e
a
12
week
pe iod.
Gi en
he
lack
o
conc e e
da a,
we
can
only
specula e
ha
i
a
pa ien
does
no
need
ICS,
hen
he e
is
no
need
o
ape
o .
In
addi ion,
as
i
is
a
non-sys emic
medica ion,
he e
is
no
scien iﬁc
a ionale
o
ape ing
o .
We
ecommend
ha
pa ien s
wi h
no
exace ba ions
du -
ing
12
mon hs
and
who
a e
s able
should
be
wi hd awn
om
ICS.
Tape ing
o
is
no
necessa y
and
ICS
should
be
wi h-
d awn
in
a
single
s ep.
We
sugges
GOLD
A
and
B
pa ien s
be
e-assessed
e e y
6
mon hs,
and
Gold
C
and
D
pa ien s
e e y
3
mon hs,
du ing
a
one
yea
pe iod
a e
ICS
wi h-
d awal
(spi ome y,
mMRC,
inﬂamma ion,
symp oms).
We
u he
ecommend
ha ,
in
C
and
D
pa ien s,
i
he e
we e
exace ba ions
du ing
6
mon hs,
o
i
pulmona y
unc ion
consis en ly
dec eases,
he e
should
be
a
s ep-up
wi h
ICS.
Which
pa ien s
will
beneﬁ
om
ICS?
The e
is
a
need
o
bioma ke s
o
esponse
o
he apy
and
disease
p og ession,
so
ha
he
momen
o
he apeu-
ic
adjus men s
can
be
de e mined
in
a
imely
way.
Some
bioma ke s
o
disease
ac i i y
and
p og ession
ha e
been
p oposed,55,56 bu
much
mo e
esea ch
needs
o
be
done
be o e
hese
a e
clinically
applicable,
and
can
guide
pe -
sonalized
managemen
o
COPD
pa ien s.
Pe haps
he
mos
p omising
a ailable
ma ke
is
spu um
eosinophilia,
and
mos
ecen ly
also
blood
eosinophilia.57 COPD
pa ien s
wi h
spu-
um
eosinophilia
>
3%
seem
o
espond
be e
o
bo h
ICS

COPD:
A
s epwise
o
a
hi
ha d
app oach?
219
and
sys emic
co icos e oids.10,58---61 As
o
ci cula ing
le els
o
C- eac i e
p o ein
(CRP),
esul s
om
di e en
s udies
a e
con o e sial,
and
CRP
may
no
be
a
sui able
bioma ke
in
COPD,
due
o
i s
low
speciﬁci y
and
high
a iabili y.58
We
ecognize
ha
he e
a e
cu en ly
no
accu a e
bioma ke s
o
guide
he apy
in
COPD.
We
p opose
ha
CAT
should
be
used
in
all
consul a ions,
in
o de
o
moni o
he -
apeu ic
esponse,
gi en
i
is
a
p edic o
o
exace ba ions.
ICS
class,
dose
and
pneumonia
The
consensus
is
ha
ICS
use
inc eases
he
isk
o
pneumonia
in
pa ien s
wi h
COPD,1,2,4,20---22,36,62 and
e en
a
ecen
ICS,
ﬂu icasone
u oa e,
has
been
associa ed
wi h
an
inc eased
pneumonia
isk
and
dea hs
om
pneumonia
in
COPD
pa ien s.62---64 Howe e ,
some
s udies
ﬁnd
a
e y
small
di e -
ence
in
he
isk
o
pneumonia
wi h
ICS.21,22,26 These
dissimi-
la
esul s
may
s em
om
he
ac
ha
some
s udies
a e
oo
sho
o
pa ien s
o
de elop
pneumonia,
and/o
ha
se -
e al
ICS
classes
and
doses
a e
used
in
di e en
s udies.
Bo h
ﬂu icasone
and
budesonide
ha e
been
epo ed
o
inc ease
he
isk
o
pneumonia,64---67 bu
esul s
conce ning
a
dose
e ec
ange
om
no
di e ence
be ween
ﬂu icasone
and
budesonide,65 o
ﬂu icasone
being
associa ed
wi h
a
highe ,
dose
dependen
isk,
when
compa ed
o
budesonide,66 o
ﬂu icasone
no
being
dose
dependen ,
while
budesonide
shows
a
signiﬁcan
di e ence
be ween
he
wo
commonly
used
doses.67 The
gene al
dose-e ec
o
ICS
on
pneumo-
nia
isk
has
been
conﬁ med
in
a
la ge
USA
e ospec i e
coho
s udy,
bu
he
use
o
se e al
ICS
classes
p ecludes
any
conclusion
ega ding
speciﬁc
ICS
class- ela ed
dose-e ec .68
Resul s
conce ning
he
ue
e ec
o
di e en
ICS
classes
and
doses
on
he
isk
o
pneumonia
emain
inconclusi e.
Mo e
s udies
a e
needed
o
allow
an
e alua ion
o
whe he
di e en
classes
o
ICS
a e
associa ed
wi h
di e en
pneu-
monia
isk
in
COPD
pa ien s.
Gi en
he
con o e sy
su ounding
ICS
he apy
in
COPD
pa ien s,
we
sugges
ha
a
wi hd awal
o
s ep-up
app oach
should
ake
in o
accoun
he
abo e
ecommenda ions
bu
be
ailo ed
o
he
pa ien ,
aking
in o
conside a ion
each
indi idual
pa ien
cha ac e is ics.
Conclusions
Bo h
s epwise
and
‘‘hi
ha d’’
app oaches
ha e
bene-
ﬁ s.
Only
a
ca e ul
pa ien
selec ion
will
de e mine
which
app oach
is
be e ,
and
which
pa ien s
will
beneﬁ
he
mos
om
each
app oach.
In
COPD,
he apy
should
be
ailo ed
o
he
pa ien ,
aking
in o
conside a ion
co-mo bidi ies,
p es-
ence
o
hype inﬂa ion,
his o y
o
ch onic
b onchi is,
le els
o
physical
ac i i y,
and
each
indi idual
pa ien
cha ac e is-
ics.
E hical
esponsibili ies
P o ec ion
o
human
and
animal
subjec s.
The
au ho s
decla e
ha
no
expe imen s
we e
pe o med
on
humans
o
animals
o
his
s udy.
Conﬁden iali y
o
da a.
The
au ho s
decla e
ha
no
pa ien
da a
appea
in
his
a icle.
Righ
o
p i acy
and
in o med
consen .
The
au ho s
decla e
ha
no
pa ien
da a
appea
in
his
a icle.
Conﬂic
o
in e es
The
au ho s
decla e
collabo a ing
and
ecei ing
ees
om
pha maceu ical
companies
o he
han
No a is
ei he
h ough
pa icipa ion
in
ad iso y
boa d
o
consul ancy
mee ings,
cong ess
symposia,
clinical
ial
conduc
o
in es iga o -ini ia ed
ials.
Role
o
unding
sou ce
Funding
o
his
pape
was
p o ided
by
No a is
Po ugal.
Funding
was
used
o
access
all
necessa y
scien iﬁc
bibliog-
aphy
and
co e
mee ing
expenses.
No a is
Po ugal
had
no
ole
in
he
collec ion,
analysis
and
in e p e a ion
o
da a,
in
he
w i ing
o
he
pape
and
in
he
decision
o
submi
he
pape
o
publica ion.
Acknowledgemen s
The
au ho s
wish
o
hank
No a is
Po ugal
o
he
und-
ing
o
his
pape ,
which
was
used
o
access
all
necessa y
scien iﬁc
bibliog aphy
and
co e
mee ing
expenses.
Re e ences
1.
Di ecc¸ão
Ge al
de
Saúde.
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n
028/2011
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Diagnós ico
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COPD : a stepwise or a hit hard approach?

Abstract

COPD : a stepwise or a hit hard approach?
