Pharmacological treatment of COPD : new evidence

Pires, N.; Pinto, Paula; Marçal, N.; Ferreira, A. J.; Rodrigues, C.; Bárbara, Cristina
Pharmacological treatment of COPD : new evidence

Author: Pires, N.,Pinto, Paula,Marçal, N.,Ferreira, A. J.,Rodrigues, C.,Bárbara, Cristina
Publisher: Elsevier
Year: 2019
Source: https://repositorio.ulisboa.pt/bitstream/10451/39643/1/COPD_new_evidence.pdf
Pulmonol.
2019;25(2):90---96
www.jou nalpulmonology.o g
REVIEW
Pha macological
ea men
o
COPD
---
New
e idence
N.
Pi esa,
P.
Pin ob,c,
N.
Ma c¸al d,
A.J.
Fe ei ae, ,
C.
Rod iguesg,
C.
Bá ba ab,c,∗,
on
behal
o
GI
DPOC
---
In e es
G oup
on
Ch onic
Obs uc i e
Pulmona y
Disease
aPulmonology
Depa men ,
Hospi al
San a
Ma ia
Maio ,
Ba celos,
Po ugal
bChes
Depa men ,
Cen o
Hospi ala
Lisboa
No e,
Lisbon,
Po ugal
cEn i onmen al
Heal h
Ins i u e
(ISAMB),
Facul y
o
Medicine,
Uni e si y
o
Lisbon,
Po ugal
dPulmonology
Depa men ,
Hospi al
de
Vila
F anca
de
Xi a,
Po ugal
ePulmonology
Depa men ,
Cen o
Hospi ala
Uni e si á io
de
Coimb a,
Po ugal
Facul y
o
Medicine,
Uni e si y
o
Coimb a,
Po ugal
gCen o
Hospi ala
de
Coimb a,
Po ugal
Recei ed
13
Sep embe
2018;
accep ed
14
Oc obe
2018
KEYWORDS
FLAME;
P e-GOLD
pa ien s;
Diagnosis;
Algo i hm
Abs ac
Ch onic
Obs uc i e
Pulmona y
Disease
(COPD)
is
cu en ly
he
4 h
leading
cause
o
dea h
wo ldwide
bu
is
p ojec ed
o
be
he
3 d
leading
cause
o
dea h
by
2020.
In
Po ugal,
he
es ima ed
p e alence
o
COPD
in
he
Lisbon
egion
is
14.2%,
and
a
la ge
p opo ion
o
unde diagnosed
disease
has
been
de ec ed.
In
2016,
a
Po uguese
panel
o
expe s
p oposed
pha macological
ea men
app oaches
o
COPD
based
on
he
e idence
a ailable
a
he
ime.
Howe e ,
gi en
ha
he
GOLD
2017
epo
in oduced
conside able
changes
o
he
2016
e sion,
and
ha
new
e idence
has
eme ged
ega ding
ea men
op ions,
hese
p oposals
need
o
be
upda ed.
Also,
and
based
on
se e al
s udies,
he
concep
o
P e-GOLD
pa ien s,
which
has
diagnos ic,
p ognos ic
and
he apeu ic
implica ions,
is
in oduced,
along
wi h
a
p oposed
algo i hm
o
he
iden iﬁca ion
and
ea men
o
hese
pa ien s.
©
2019
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 ess:
[email p o ec ed]
(C.
Bá ba a).
In oduc ion
Ch onic
Obs uc i e
Pulmona y
Disease
(COPD)
is
cu en ly
he
4 h
leading
cause
o
dea h
wo ldwide
bu
is
p ojec ed
o
be
he
3 d
leading
cause
o
dea h
by
2020.1In
Po ugal,
he
es ima ed
p e alence
o
COPD
in
he
Lisbon
egion
is
14.2%,
h ps://doi.o g/10.1016/j.pulmoe.2018.10.005
2531-0437/©
2019
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/).
Pha macological
ea men
o
COPD
-
New
e idence
91
and
a
la ge
p opo ion
o
unde diagnosed
disease
has
been
de ec ed.2
In
2016,
a
Po uguese
panel
o
expe s
p oposed
pha -
macological
ea men
app oaches
o
COPD
based
on
he
e idence
a ailable
a
he
ime.3Howe e ,
he
GOLD
2017
epo 4in oduced
conside able
changes
o
he
2016
e sion.5Acco ding
o
he
2017
s a egy,
COPD
pa ien s
con inue
o
be
sepa a ed
in o
A,
B,
C
o
D
acco ding
o
symp oms
and
exace ba ions.
Howe e ,
p e ious
GOLD
epo s
s a iﬁed
pa ien s
conside ing
h ee
isk
a iables
---
o ced
expi a o y
olume
in
1
second
(FEV1),
symp oms
and
exace ba ions.5The
implica ions
o
hese
changes
a e
ha
pa ien s
who
we e
p e iously
conside ed
a
isk
due
o
poo
lung
unc ion
only
(C
o
D),
will
now
be
classiﬁed
as
A
o
B,
espec i ely,
wi h
epe cussions
in
he
he apeu ic
s a egy
ecommended.
The
mos
ecen
GOLD
20181did
no
in oduce
changes
o
he
GOLD
2017
classiﬁca ion.4
Also,
he
FLAME
s udy6 --- 8 p o ided
new
e idence
ega d-
ing
ea men
op ions
o
B
and
D
pa ien s,
showing
ha
indaca e ol/glycopy onium
was
mo e
e ec i e
han
salme e ol/ﬂu icasone
in
educing
and
p e en ing
COPD
exace ba ions
in
pa ien s
wi h
a
his o y
o
exace ba ions
du ing
he
p e ious
yea ,
and
ha
his
e ﬁcacy
was
inde-
penden
o
di e en
cu o s
o
baseline
blood
eosinophilia.
Finally,
and
based
on
se e al
s udies,9---13 he
concep
o
P e-GOLD
pa ien s,
which
has
diagnos ic,
p ognos ic
and
he apeu ic
implica ions,
is
in oduced,
along
wi h
a
p o-
posed
algo i hm
o
he
iden iﬁca ion
and
ea men
o
hese
pa ien s.
P e-GOLD
pa ien s
The
diagnosis
o
COPD
equi es
a
a io
o
FEV1 o
o ced
i al
capaci y
(FVC)
o
less
han
0.70
as
assessed
by
spi ome y
a e
b onchodila o
use.4Howe e ,
a
ecen
s udy
epo ed
ha
50%
o
smoke s
wi h
p ese ed
pulmona y
unc ion
ha e
espi a o y
symp oms,
including
exace ba ions,
limi a ion
o
ac i i y,
and
g ea e
ai way-wall
hickening
wi hou
emphysema.
Among
symp oma ic
cu en
o
o me
smoke s,
42%
used
b onchodila o s
and
23%
used
inhaled
glucoco icoids,
wi hou
any
e idence
base.9This
s udy
con-
ﬁ med
p e ious
ﬁndings
epo ing
ha
he
e ec
o
ch onic
smoking
on
he
lungs
is
subs an ially
unde es ima ed
i
jus
spi ome y
is
used.10 In
ac ,
pos -salbu amol
FEV1change
is
simila
in
pa ien s
wi h
COPD
and
smoking
con ols11;
a
signiﬁcan
p opo ion
o
smoke s
wi h
emphysema
bu
wi hou
ai way
limi a ion
had
al e a ions
in
hei
quali y
o
li e,
numbe
o
exace ba ions
and
di using
capaci y
o
he
lungs
o
ca bon
monoxide
(DLCO)
alues.12 Taken
oge he ,
all
hese
s udies
conﬁ m
ha
FEV1is
an
un eliable
measu e
o
symp om
bu den
and
exace ba ions
in
smoke s,
bu
lea e
a
gap
on
how
o
ea
hese
pa ien s
in
o de
o
educe
symp oms
and
p e en
exace ba ions.13 We
p opose
a
diag-
nos ic
and
ea men
algo i hm
o
e alua e
and
medica e
hese
pa ien s
---
Fig.
1.
E e y
smoke
o
o me
smoke
wi h
symp oms
and
exace ba ions
should
unde go
spi ome y.
I
spi ome y,
pos -b onchodila o
FEV1/FVC
<
0.70,
alues
a e
consis en
wi h
he
GOLD
2018
c i e ia
o
COPD,
he
pa ien
should
be
ea ed
acco dingly.
I
he
alue
o
FEV1/FVC
is
be ween
0.6
and
0.8,
spi ome y
should
be
epea ed
on
a
sepa a e
occasion,1since
his
a io
may
change
as
a
esul
o
biological
a ia ion.14,15 I
he
ini ial
FEV1/FVC
a io
is
less
han
0.6
i
is
e y
unlikely
ha
i
will
ise
abo e
0.7
spon aneously.15 I
spi ome y
alues
a e
no
in
acco dance
wi h
he
GOLD
2018
c i e ia
o
COPD,
and
symp oms
and
exace ba ions
con inue
o
pe sis ,
he
pa ien
should
be
checked
o
occul
ai ﬂow
obs uc ion
using
he
Lowe
Limi
o
No mal
(LLN)
ange.16 I
he
LLN
is
achie ed,
he
pa ien
should
be
diagnosed
wi h
COPD
and
ea ed
acco ding
o
GOLD
2018.1I
no ,
and
symp oms
and
exace ba ions
con inue
o
pe sis ,
a
comple e
assessmen
should
be
done,
including
a
ho acic
Compu e ized
Tomog aphy
(CT)
scan
o
he
di e en ial
diagnosis
o
emphysema,
cance
and
o he
lung
pa hologies.
Rega dless
o
whe he
he
CT
scan
is
posi i e
o
nega i e
o
emphysema/ai way-wall
hickening,
he
pa ien
should
unde go
a
ial
wi h
a
b onchodila o
and
be
e-assessed
3 --- 6
mon hs
la e .
This
concep
o
p e-GOLD
pa ien s
we
he e
in oduce
is
e y
simila
o
ha
ecen ly
p oposed
by
Celli
and
Agus i.17
In
hei
wo k,
he
au ho s
a gue
ha
indi iduals
who
ha e
symp oms
simila
o
hose
o
pa ien s
wi h
COPD
(namely,
dyspnea,
cough
and/o
spu um
p oduc ion)
and
s uc u al
lung
abno mali ies
bu
wi hou
pe sis en
ai ﬂow
limi a-
ion
may
be
classiﬁed
as
‘‘P e-COPDs’’.
The
‘‘P e-COPDs’’
idea
has
wide
implica ions
han
ou
p e-GOLD
concep ,
as,
acco ding
o
hose
au ho s,
no
pas
o
cu en
exposu e
o
ciga e e
smoke
is
equi ed.
GOLD
A
pa ien s
GOLD
2017/2018
clea ly
s a e
ha
he
goals
o
ea men
o
s able
COPD
a e
o
educe
symp oms
and
isk,
by
imp o -
ing
exe cise
ole ance
and
heal h
s a us
and
p e en ing
disease
p og ession,
exace ba ions
and
mo ali y.1,4 Resul s
om
a
la ge
ecen
s udy
show
ha
exace ba ions
accele -
a e
lung
unc ion
loss
in
subjec s
wi h
es ablished
COPD,
pa icula ly
when
hey
a e
se e e
and
occu
in
pa ien s
wi h
mild
disease.18 This
is
no
su p ising
since
pa ien s
wi h
mild
disease
ha e
be e
lung
unc ion
and
he e o e
mo e
o
lose.
Also,
wo
ecen
expe
e iews
sugges
ha
mo e
agg essi e
ea men s
should
be
implemen ed
in
he
ea lie
s ages
o
COPD,19 in
o de
o
slow
disease
p og es-
sion
and
imp o e
Quali y
o
Li e
(QoL),20 hus
ob aining
he
bes
possible
ou come.19 Cu en
da a
suppo
main enance
ea men
wi h
a
long-ac ing
b onchodila o
in
his
pa ien
g oup.20 Gi en
he
abo e,
he
a ionale
o
ch onic
he -
apy
o
GOLD
A
pa ien s
is
o
p e en
exace ba ions
and
slow
disease
p og ession.
The
GOLD
2016
epo
p oposed
sho
ac ing
be a
agonis s
(SABA)
o
sho
ac ing
musca inic
an agonis s
(SAMA)
as
ﬁ s
choice
he apy
in
hese
pa ien s,
wi h
long
ac ing
be a
agonis s
(LABA)
o
long
ac ing
mus-
ca inic
an agonis s
(LAMA)
o
SABA/SAMA
as
he
al e na i e
choice.5Be o e
he
GOLD
2017
epo
was
published,
one
expe
opinion
pape
p oposed
a
SABA
o
SAMA
when
pos -
b onchodila o
FEV1/FVC
<
0.70
wi h
occasional
dyspnea
and
a
LABA
o
LAMA
when
dyspnea
is
pe sis en ,21 and
ano he
expe
p oposed
he
di ision
o
GOLD
A
pa ien s
in o
wo
sub-g oups:
pa ien s
wi h
FEV1>
80%
and
wi h
no
wo sening
o
FEV1in
he
annual
assessmen
should
be
ea ed
wi h
a
SABA
o
SAMA
only
in
SOS,
and
pa ien s
wi h
50%
<
FEV1<
80%
and/o
wo sening
o
FEV1in
he
annual
assessmen
should
be
ea ed
wi h
a
LABA
o
LAMA.3Howe e ,
acco ding
o
92
N.
Pi es
e
al.
SMOKER o FORMER SMOKER
+
SYMPTOMS and/o EX
ACER
BATIONS
SPIROMET
RY
GOLD 2018
COPD C i e ia
GOLD 2018
COPD C i e ia
Pha macological
ea men
Pe sis en
symp oms and/o
exace ba ions
COPDChes CT and PFT comple ed
wi h DLCO
Pe sis en
symp oms and/o
exace ba ions
Emphysema o
wall hickness
TRIAL THERAPY
wi h b onchodila o and e-assessmen
a e 3-6 mon hs
Repea 1x
*< lowe limi o no mal = < 5 h pe cen ile
Figu e
1
P oposed
diagnos ic
and
ea men
algo i hm
o
e alua e
and
medica e
p e-GOLD
pa ien s.
he
GOLD
2017
epo ,4FEV1should
no
longe
guide
ea -
men ,
bu
symp oms
and
exace ba ion
isk
ins ead,
and
as
such,
ecommenda ions
o
hese
pa ien s
a e
ei he
a
sho -
o
a
long-ac ing
b onchodila o ,
which
can
be
swi ched
o
ano he
class
o
b onchodila o
i
he e
is
no
symp om
elie ,
and
con inued
o
discon inued
depending
on
symp-
oma ic
beneﬁ .
The e o e,
gi en
ha
he
cu en
goals
o
main enance
he apy
a e
o
educe
symp oms
and
p e en
exace ba ions,
hen
a
LABA
should
be
chosen
o
he
o me
(symp oms
educ ion),22 and
a
LAMA
o
he
la e
(exace -
ba ions
p e en ion)
since
i
has
been
epo ed
o
be
supe io
o
LABA
ega ding
exace ba ion
p e en ion.23,24 Dual
b on-
chodila ion
wi h
LABA/LAMA
should
no
be
o e ed
o
hese
pa ien s
because
hey
a e
nei he
equen
exace ba o s
no
e y
symp oma ic.
I
is
wo h
no ing
ha ,
depending
on
he
ins umen
used
o
he
classiﬁca ion
o
symp oms,
he
modiﬁed
Medical
Resea ch
Council
scale
(mMRC)
o
he
COPD
assessmen
es
(CAT),
a
pa ien
may
be
classiﬁed
as
A
o
B25,26 and
he e o e
bo h
ins umen s
a e
ecommended.
We
p opose
ha
ch onic
main enance
he apy
wi h
a
LABA
o
a
LAMA
should
be
o e ed
o
GOLD
A
pa ien s.
We
ag ee
wi h
GOLD
2018
in
ha
a
swi ch
o
ano he
class
o
b onchodila o
can
be
made
i
he e
is
no
symp om
elie ,
and
he apy
should
be
con inued
o
discon inued
depending
on
symp oma ic
beneﬁ .
GOLD
B
pa ien s
Al hough
inhaled
co icos e oids
(ICS)
a e
no
ecommended
as
main enance
he apy
o
GOLD
B
pa ien s,3,5,21,27 eal-
wo ld
s udies
o
baseline
cha ac e is ics
o
pa ien s
en olled
in
RCTs
show
ha
up
o
51.8%
o
hese
pa ien s
a e
s ill
medica ed
wi h
ICS.28---33 In
a
pape
om
2016,
we
specu-
la ed
ha
his
was
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
exace ba e
o
de e io-
a e,
which
is
no
ue.3Ou
specula ion
is
now
suppo ed
by
e idence
om
he
FLAME
s udy,
ha
andomized
a
o al
o
1680
pa ien s
o
he
indaca e ol/glycopy onium
110/50
␮g
once-daily
g oup
and
1682
o
he
salme e ol/ﬂu icasone
50/500
␮g
wice-daily
g oup,
and
showed
ha
o
GOLD
B
pa ien s
wi h
a
his o y
o
a
leas
one
exace ba ion
du ing
he
p e ious
yea ,
indaca e ol/glycopy onium
was
mo e
e ec i e
han
salme e ol/ﬂu icasone
in
p e en ing
COPD
exace ba ions,
i espec i e
o
p io
ICS/LABA/LAMA
he apy,7and
was
associa ed
wi h
no
de ec able
inc ease
Pha macological
ea men
o
COPD
-
New
e idence
93
Table
1
p oposed
di ision
o
GOLD
B
pa ien s
in
wo
subg 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
0
exace ba ions;
AND
no
ca dio ascula
co-mo bidi ies
(a)
i
no
medica ed,
ini ia e
LABA
o
LAMA
BX2:
mMRC
>
2
OR
1
exace ba ion
wi hou
hospi aliza ion
OR
wi h
ca dio ascula
co-mo bidi ies
LABA
+
LAMA
(‘‘hi
ha d’’
app oach)
mMRC
---
modiﬁed
Medical
Resea ch
Council
dyspnea
scale;
LABA
---
long
ac ing
␤2-agonis ;
LAMA
---
long-ac ing
musca inic
an agonis .
in
ad e se
e en s.6The
FLAME
s udy
also
suppo s
ou
p e ious
ecommenda ion
ha
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,3and
u he
sugges s
ha
e en
B
pa ien s
wi h
a
leas
one
exace ba ion
du ing
he
p e ious
yea
can
and
should
be
wi hd awn
om
ICS.6,7 Symp oma ic
pa ien s
a e
mo e
likely
o
expe ience
exace ba ions34 ( he
ECLIPSE
s udy
showed
ha
52%
o
hese
pa ien s
a e
exace ba o s),35
and
he e o e
i
is
o
he
u mos
impo ance
o
con ol
symp oms,
namely
wi h
dual
b onchodila ion,3,21,27 which
is
now
clea ly
suppo ed
by
he
FLAME
s udy
and
o he
s udies
om
he
IGNITE
clinical
de elopmen
p og am
o
indaca e ol/glycopy onium.6,7,36,37 In
he
Sal o d
Lung
S udy,
a
la ge
andomized
open-label
ial
designed
o
mimic
eal-wo ld
condi ions,
a
once-daily
ea men
egi-
men
o
combined
ﬂu icasone
u oa e/ ilan e ol
100/25
␮g
was
compa ed
o
usual
ca e,
and
he
au ho s
concluded
ha
he
ﬂu icasone
u oa e/ ilan e ol
combina ion
was
associ-
a ed
wi h
a
lowe
a e
o
exace ba ions
han
usual
ca e,
wi hou
a
g ea e
isk
o
se ious
ad e se
e en s.38 I
is
ou
opinion
ha
his
s udy
does
no
con adic
he
FLAME
s udy
o
se e al
easons:
in
he
Sal o d
Lung
S udy38 22%
o
he
pa ien s
included
had
a
diagnosis
o
as hma,
he
com-
pa a o
a m
was
usual
ca e
as
de e mined
by
he
gene al
p ac i ione ,
which
esul ed
in
a
a ie y
o
mono he apies
and/o
combina ion
he apies
(88%
o
pa ien s
in
he
usual
ca e
g oup
we e
ecei ing
an
ICS-con aining
egimen),
and
unila e al
c osso e
was
pe mi ed.
The e o e,
he
conclu-
sions
d awn
by
he
au ho s
ha e
se e al
possible
sou ces
o
bias
and
i
is
no
possible
o
conclude
om
hese
da a
whe he
ﬂu icasone
and
ilan e ol
is
mo e
e ec i e
han
a
LABA/LAMA
a
educing
exace ba ions.
The
ECLIPSE35 and
FLAME6,7 s udies
g ouped
pa ien s
acco ding
o
he
GOLD
2016
epo 5 hus
including
FEV1as
a
isk
c i e ion.
F om
GOLD
2017
onwa ds1,4 FEV1is
no
longe
a
c i e ion
o
isk,
only
symp oms
and
exace ba ions.
The
FLAME
s udy
s a es
ha
19.3%
o
pa ien s
had
≥2
exace ba-
ions,
and
hese
will
now
be
he
GOLD
D
pa ien s;
as
o
he
emaining
pa ien s
in ol ed
in
he
s udy,
hose
wi h
≤1
exac-
e ba ion
wi hou
hospi aliza ion,
will
be
now
classiﬁed
as
GOLD
B.
In
ac ,
since
he
GOLD
2017
classiﬁca ion,1,4 i
is
o
be
expec ed
ha
many
pa ien s
o me ly
classiﬁed
as
GOLD
D
would
now
be
classiﬁed
as
GOLD
B,
because
hey
we e
classiﬁed
as
GOLD
D
due
o
FEV1.
These
GOLD
B
pa ien s
a e
he
mos
he e ogeneous
and
uns able,
and
may
e en ually
exace ba e.35 Thus,
he
conclusions
o
he
FLAME
s udy
hold
ue
ega dless
o
he
GOLD
s a iﬁca ion.
Howe e ,
wi h
his
new
classiﬁca ion,
and
as
many
o -
me
GOLD
D
pa ien s
will
now
be
conside ed
GOLD
B,
hey
a e
p obably
on
ICS
he apy,
as
ecommended
o
GOLD
D
pa ien s.
These
pa ien s,
p e iously
classiﬁed
as
GOLD
D
due
o
FEV1and
no
due
o
exace ba ions,
should
be
wi hd awn
om
ICS.
In
a
p e ious
pape
we
p oposed
ha
GOLD
B
pa ien s
should
be
di ided
in
wo
subg oups,
BX1
and
BX2,
and
he
he apeu ic
app oach
should
be
based
on
his
subdi ision.3
Since
GOLD
2017
led
o
changes
in
COPD
pa ien
classiﬁca-
ion,
in
his
pape
we
ha e
adap ed,
ou
p oposal
as
shown
in
Table
1.
We
p opose
ha
ICS
should
no
be
gi en
o
GOLD
B
pa ien s
as
main enance
he apy.
We
u he
p opose
ha
p e iously
GOLD
D
pa ien s
now
conside ed
GOLD
B
pos
GOLD
2017
and
who
a e
on
ICS
he apy
should
be
wi hd awn
om
i ,
and
be
moni o ed
3 --- 6
mon hs
la e .3
GOLD
C
pa ien s
Acco ding
o
he
2017/2018
GOLD
C
new
classiﬁca ion,1,4 he
g oups
C1
(high
isk
due
o
poo
lung
unc ion)
and
C3
(high
isk
due
o
bo h
poo
unc ion
and
exace ba ions)3no
longe
exis
and
all
GOLD
C
pa ien s
will
be
classiﬁed
as
high
isk
based
only
on
exace ba ions.
The e o e,
he
main
he apeu-
ic
goal
will
be
o
educe
he
isk
o
exace ba ions.
As
ini ial
he apy
should
consis
o
a
single
long
ac ing
b onchodila-
o ,
a
LAMA
should
be
p e e ed
o
a
LABA
since
i
has
been
epo ed
o
be
be e
a
p e en ing
exace ba ions.23,24
We
ag ee
wi h
GOLD
2018
ha
hese
pa ien s
should
s a
he apy
wi h
jus
LAMA
and
hen,
i
exace ba ions
con inue,
should
p e e ably
be
swi ched
o
LABA/LAMA,
ins ead
o
LABA/ICS,
al hough
he
la e
emains
an
op ion.
GOLD
D
pa ien s
How
o
s a
he apy
Many
guidelines
ha e
ecommended
LABA/ICS
and/o
LAMA
as
ﬁ s -line
he apy
o
highe
isk
pa ien s.3,5 Howe e ,
some
disc epancies
exis ,
and
he
he apy
app oach
o
hese
pa ien s
is
no
s aigh o wa d.3,21,27,33 A
me a-analysis
om
2015
concluded
ha
LAMA/LABA
seemed
o
be
a
be e
op ion
o
ea ing
GOLD
D
pa ien s
(as
deﬁned
p e-GOLD
2017/2018)
han
LABA/ICS.39 The
FLAME
s udy
suppo s
his
conclusion,
a o ing
indaca e ol/glycopy onium
e -
sus
salme e ol/ﬂu icasone
in
p e en ing
exace ba ions
in
GOLD
D
pa ien s
(as
deﬁned
p e-GOLD
2017/2018),6includ-
ing
pa ien s
wi h
p io
iple
he apy.7When
compa ed
wi h
salme e ol/ﬂu icasone,
indaca e ol/glycopy onium
was
be e
a
p e en ing
all
exace ba ions
and
delaying
he
ime
o
ﬁ s
exace ba ion,
any
exace ba ion
(p
<
0.001),
mode a e- o-se e e
exace ba ions
(p
<
0.001)
and
se e e
94
N.
Pi es
e
al.
exace ba ions
(p
=
0.046).
The
imp o emen
o e
ime
in
he
o al
sco e
on
he
S .
Geo ge’s
Respi a o y
Ques ion-
nai e
o
COPD
pa ien s
(SGRQ-C)
was
signiﬁcan ly
g ea e
han
salme e ol/ﬂu icasone
a e
day
85.
Also,
a
week
52,
he
pe cen age
o
pa ien s
who
had
a
clinically
impo -
an
dec ease
o
a
leas
4
poin s
in
he
o al
sco e
on
he
SGRQ-C
was
signiﬁcan ly
highe
and
he
use
o
escue
medica ion
was
signiﬁcan ly
imp o ed
o
he
pa ien s
in
he
indaca e ol/glycopy onium
ea men
a m
e sus
hose
in
he
salme e ol/ﬂu icasone
a m.
On
subg oup
analysis,
he
ad an age
o
indaca e ol/glycopy onium
was
pa ic-
ula ly
ele an
o
cu en
smoke s,
pa ien s
wi h
se e e
ai ﬂow
limi a ion,
GOLD
D
pa ien s,
pa ien s
wi h
1
exac-
e ba ion
in
he
p e ious
yea ,
and
p e ious
use
o
LABA
o
LAMA.
As
o
ad e se
e en s,
indaca e ol/glycopy onium
was
no
associa ed
wi h
a
de ec able
inc ease
in
ad e se
e en s
and
he
incidence
o
pneumonia
was
signiﬁcan ly
lowe
in
he
indaca e ol/glycopy onium
g oup
han
in
he
salme e ol/ﬂu icasone
g oup
(3.2%
s
4.8%,
p
=
0.02).
This
was
also
he
ﬁ s
s udy
o
p ospec i ely
analyze
he
ele-
ance
o
blood
eosinophilia
in
COPD,
and
he
esul s
we e
simila
o
blood
eosinophilia
<
2%
compa ed
o
≥2%.
O he
analyses
in
subg oups
deﬁned
acco ding
o
di e en
cu -
o s
o
baseline
blood
eosinophil
coun s
p o ided
simila
esul s.6,8
Da a
om
he
ﬁ s
head- o-head
s udy
(TRIBUTE)
compa ing
a
iple
combina ion
o
LABA/LAMA/ICS
(beclome asone/ o mo e ol/glycopy onium,
100/6/12.5
␮g,
wo
inhala ions
wice-daily)
wi h
a
dual
combina ion
o
LABA/LAMA
(IND/GLY)
ha e
jus
ecen ly
been
published.40 The
TRIBUTE
s udy
en olled
symp oma ic
pa ien s
(CAT
≥
10)
wi h
a
FEV1<
50%
and
a
his o y
o
a
leas
one
documen ed
mode a e
o
se e e
exace ba ion
in
he
pas
yea .
The
p ima y
endpoin
analysis
showed
a
15%
educ ion
in
he
a e
o
mode a e
o
se e e
exace ba ions
a o ing
he
iple
combina ion
when
compa ed
wi h
he
dual
combina ion
(p
=
0.043).
I
should
be
no ed
ha
no
signiﬁcan
di e ence
be ween
ea men
egimens
was
obse ed
when
mode a e
and
se e e
exace ba ions
we e
analyzed
sepa a ely
(p
=
0.118
and
p
=
0.189,
espec i ely)
o
o
he
ime
o
ﬁ s
mode a e
o
se e e
exace ba ion
(p
=
0.219)
and
ime
o
ﬁ s
se e e
exace ba ion
(p
=
0.405).
In
addi ion,
he
p e-speciﬁed
subg oup
analyses
sugges
ha
pa ien s
wi h:
FEV1<
30%,
o
emphysema
o
a
mixed
pheno ype,
o
>1
exace ba ion
in
he
p e ious
12
mon hs,
o
lowe
blood
eosinophils
(<2%
o
<200
cells/␮L)
may
no
de i e
any
beneﬁ
om
LABA/LAMA/ICS
compa ed
wi h
LABA/LAMA.
In e es ingly,
he
incidence
o
pneumonia
was
simila
be ween
he
wo
egimens.
The
esul s
om
TRIBUTE
a e
en i ely
in
line
wi h
he
cu en
GOLD
ec-
ommenda ions
and
indica e
ha
pa ien s
wi h
ch onic
b onchi is
and
ele a ed
blood
eosinophil
coun s
will
be
mo e
likely
o
beneﬁ
om
a
iple
combina ion
egimen.
Recen
da a
om
he
IMPACT
s udy
also
appea
o
be
in
line
wi h
he
GOLD
ecommenda ions
wi h
iple
he apy
wi h
ﬂu icasone
u oa e/umeclidinium/ ilan e ol
showing
beneﬁ s
in
pa ien s
wi h
equen
exace ba ions
and
in
hose
wi h
a
se e e
exace ba ion
in
he
12
mon hs
p e ious
o
s udy
en ollmen
when
compa ed
wi h
ﬂu icasone
u oa e/ ilan e ol
and
umeclidinium/ ilan e ol.41 Despi e
his,
and
as
men ioned
by
Suissa
&
D azen,
in
an
Edi o ial
on
he
IMPACT
s udy42:
‘‘Howe e ,
he
selec ed
ial
pa ien s,
mos
o
whom
we e
al eady
ea ed
wi h
inhaled
glucoco -
icoids
and
some
o
whom
had
a
his o y
o
as hma,
we e
no
he
na u al
popula ion
in
which
o
s udy
his
ques ion,
po en ially
a iﬁcially
inﬂa ing
he
obse ed
e ec i eness
o
he
iple- he apy
inhale
o e
dual
b onchodila o
ea men ’’.
Consequen ly,
he
pa ien
popula ion
in ol ed
in
he
IMPACT
s udy
makes
i
e y
di ﬁcul
o
in e p e
hese
da a
and
come
o
a
clea
conclusion
abou
i s
ele ance
o
he
managemen
o
COPD
pa ien s.
In
ace
o
he
esul s
desc ibed
abo e,
we
ecommend
ha
GOLD
D
pa ien s
should
s a
he apy
wi h
dual
b on-
chodila ion,
and
ICS
should
only
be
used
as
an
add-on
i
pa ien s
ha e
u he
exace ba ions.
We
also
p opose
ha
ICS
should
no
be
gi en
o
hese
pa ien s
as
ﬁ s
line
main-
enance
he apy.
I
and
when
o
add
ICS
A
ecen
pos
hoc
analysis
o
he
WISDOM
s udy
concluded
ha
a
his o y
o
≥2
exace ba ions
pe
yea
plus
an
eosinophil
coun
≥300
cells/␮L
iden iﬁes
indi iduals
a
inc eased
isk
o
exace ba ion
when
ICS
is
discon inued.
These
au ho s
epo
ha
he
mos
consis en
and
g ea es
e ec
was
seen
in
pa ien s
wi h
≥2
exace ba ions
and
≥400
cells/␮L.
Ne e heless,
he
au ho s
ecognize
ha ,
gi en
he
ela-
i ely
small
sample
sizes,
mo e
s udies
a e
needed,
along
wi h
p ospec i e
conﬁ ma ion
o
he
alidi y
o
he
p o-
posed
subg oups
o
ICS- esponsi e
indi iduals.43 New
da a
on
his
subjec
ha e
now
been
p o ided
by
he
SUNSET
s udy
whe e
non- equen ly
exace ba ing
pa ien s
on
long- e m
iple
he apy
wi h
io opium
plus
salme e ol/ﬂu icasone
we e
andomized
o
ei he
con inue
hei
iple
he apy
eg-
imen
o
swi ch
o
indaca e ol/glicopi onium.44 The
swi ch
o
indaca e ol/glycopi onium
led
o
a
small
educ ion
in
lung
unc ion
(-26
mL
in
ough
FEV1)
bu
no
di e ence
in
COPD
exace ba ions
be ween
ea men
g oups.
In
addi ion,
he
s udy
also
demons a es
ha
pa ien s
wi h
highe
blood
eosinophil
coun s
o
≥300
cells/␮L
a e
mo e
likely
o
ben-
eﬁ
om
iple
he apy
as
a
as
loss
o
lung
unc ion
is
conce ned.44
Due
o
he
lack
o
mo e
conclusi e
da a,
he
ec-
ommended
ea men
app oach
is
he
one
p oposed
p e iously.3,21,27
Conclusions
Based
on
he
GOLD
2017/2018
and
on
new
e idence
ha
has
eme ged
ega ding
ea men
op ions
wi h
he
FLAME
s udy,
his
pape
p o ides
an
upda e
on
a
p e ious
p oposal
o
pha macological
ea men
app oaches
o
COPD
pa ien s.
Also,
he
concep
o
P e-GOLD
pa ien s,
which
has
diagnos-
ic,
p ognos ic
and
he apeu ic
implica ions,
is
in oduced,
along
wi h
a
p oposed
algo i hm
o
he
iden iﬁca ion
and
ea men
o
hese
pa ien s.
Financial
suppo
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 ings
expenses.
No a is
Po ugal
had

Pha macological
ea men
o
COPD
-
New
e idence
95
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.
Conﬂic s
o
in e es
Nuno
Pi es
epo s
pe sonal
ees
om
No a is.
Paula
Pin o
epo s
pe sonal
ees
om
No a is.
Nelson
Ma c¸al
epo s
pe sonal
ees
om
No a is,
Te a
and
Boeh inge -Ingelheim.
An ónio
Jo ge
Fe ei a
epo s
pe sonal
ees
om
No a is,
Bial,
Boeh inge -Ingelheim,
GSK,
Tecnin a
and
Te a.
Cidália
Rod igues
epo s
pe sonal
ees
om
No a is.
C is ina
Bá -
ba a
has
no hing
o
disclose.
Re e ences
1.
Global
Ini ia i e
o
Ch onic
Obs uc i e
Lung
Disease.
Global
s a egy
o
he
diagnosis,
managemen
and
p e en ion
o
ch onic
obs uc i e
pulmona y
disease;
2018.
2.
Ba ba a
C,
Rod igues
F,
Dias
H,
Ca doso
J,
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Pharmacological treatment of COPD : new evidence

Abstract

Pharmacological treatment of COPD : new evidence
