dyspnea in copd · wedzicha, j., et al., nejm, 2016. om y) ∆=–0.25, p
TRANSCRIPT
SGK/SGP 2016
Dyspnea in COPD
Prof. Michael TammHead of Pneumology and Comprehesive
Lung Center University Hospital Basel
GOLD GuidelinesFE
V1
% p
red
> 8
0%
50
-80
%
30
-50
%<3
0%
MMRC0 – 1 2 – 4
Nu
mb
er o
f A
ECO
PD
0 –
1=
>2
Assessments:
- Symptoms
- Airflow obstruction
- Risk of AECOPD
- Comorbidities
A) Low risk, less symptoms
B) Low risk, more symptoms
C) High risk, less symptoms
D) High risk, more symptoms
Dyspnea in COPD
• Bodyplethysmography
– FEV1 ? reversibility ? NO ?
– hyperinflation ?
• Diffusion capacity
– proportional/disproportional ?
• Blood gases
– pO2 pCO2
• CT thorax
– bronchiectasis/mucuspluging/emphysema
Dyspnea in COPD
• Echo
– LEF
– Diastolic dysfunction
– Pulmonary hypertension
• Ev MPS
• SPECT
– thromboembolic disease
– potential for LVR
PH-COPD in end-stage COPD
PH-COPD in end-stage COPD
210 199
16
25 35
PAH vs. PH-COPD
PAH vs. PH-COPD
PAH vs. PH-COPD: CPET
PAH vs. PH-COPD: CPET
PAH vs. PH-COPD: CPET
PAH vs. PH-COPD: CPET
PH-COPD: Endothelin ReceptorAntagonists
• Distance walked in 6 min– Bosentan group: 339 ± 81 to 329 ± 94 m at week 12; p = 0.040)
– Placebo group: 331 ± 116 to 331 ± 123 m at week 12; p = 0.100)
• Arterial PO2– Bosentan group: 65.2 ± 10.5, 58.8 ± 8.6 and 60.7 ± 7.5 mmHg at
baseline, 4 weeks and 12 weeks, respectively
– Placebo group: 66.1 ± 15.1, 64.4 ± 6.9 and 65.7 ± 10.9 mmHg, respectively.
• FEV1: 51.3 ± 31,4 %pred
• mPAP at rest: 31.3 ± 7.3 mmHg
• PCWP: 12.8 ± 5.6 mmHg
PH-COPD: aerosolized Iloprost
Hyperinflation in COPD= Dyspnea
TORCH Study
• 6000 Patients 3 years
• Primary endpoint:
Mortality
• Sekundary endpoints:
– Exacerbations
– Lung function
– Quality of life /Dyspnea
Fluticason
Fluticason + Salmeterol
Calverley et al, NEJM 2007
Calverley et al. NEJM 2007
Calverley et al. NEJM 2007
Calverley et al. NEJM 2007
ICS/LABA TORCH
• Quality of Life Scores yes
• FEV1 yes
• FEV1 decline no
• Hyperinflation ?
• VO2/endurance/6 min distance?
• Exacerbations yes
• Comorbidities ?
• Mortality no/yes
UPLIFT Study
Primary endpoint:
– FEV1 (Slope of decline)
Sekundary endpoints:
– Quality of life
– Exacerbations
– Mortality
6000 Patients 4 years Tiotropium versus Placebo
70% ICS and/or LABA
Tiotropium
Control
0 6 12 24 30 36 42 4818
Hazard ratio = 0.87
95% CI: (0.76, 0.99)
P = 0.034 (log-rank test)
20
15
10
5
0
Pro
ba
bil
ity o
f d
ea
th f
rom
an
y c
au
se
[%
]
Months
Mortality
Exacerbations
0
20
40
60
80
0 6 12 18 24 30 36 42 48
Pro
ba
bilit
y o
f e
xa
ce
rba
tio
n (
%)
Tiotropium Control
Hazard ratio = 0.86,
(95% CI, 0.81, 0.91)
p < 0.0001 (log-rank test)
Month
FEV1
1.00
1.10
1.20
1.30
1.40
1.50
FE
V1 (
L)
Tiotropium Control
* **
**
**
**
0
6 12 18 24 30 36 42 480 1
Month
* * **
** * *
*
Post-Bronch FEV1
= 47 – 65 mL
Pre-Bronch FEV1
= 87 – 103 mL
*P<0.0001 vs. control
Quality of Life
35
40
45
50
SG
RQ
To
tal
Sc
ore
(U
nit
s) Tiotropium (n = 2478) Control (n = 2337)
0
6 12 18 24 30 36 42 480
Month
* **
** *
**
Imp
rovem
en
t
SGRQ Total Score = 2.3 units
*P<0.0001 vs. control
Tiotropium UPLIFT
• Quality of Life Scores yes
• FEV1 yes
• FEV1 decline no
• Hyperinflation ?
• VO2/endurance/6 min distance ?
• Exacerbations yes
• Comorbidities ?
• Mortality no/yes
WISDOM Studie
Primary endpoint
Time to 1st moderate or severe on-treatment exacerbation during 12-month randomised period
Magnussen H et al. Withdrawal of Inhaled Glucocorticoids and Exazerbations of COPD. Respir Med 2014;108:593-9
Secondary endpoints
Included lung function, health status (SGRQ) and dyspnea (mMRC)
Estimated probability of moderate or severe COPD exacerbation
1243
1242
1059
1090
927
965
827
825
763
740
646
646
694
688
615
607
581
570
14
19
No. at risk
ICS
ICS withdrawal
0.6
0.4
0.2
0.0
0 6 12 18 24 30 36 42 48 54
ICS
ICS withdrawalEstim
ate
d p
rob
ab
ility
Time to events (weeks)
0.1
0.3
0.5
Hazard ratio, 1.06 (95% CI, 0.94–1.19)
P=0.35 by Wald’s chi-squared test
Magnussen H et al. Withdrawal of Inhaled Glucocorticoids and Exazerbations of COPD. Respir Med 2014;108:593-9
Adju
ste
d m
ean (
SE
) change
from
baselin
e in
FE
V1
(mL)
**p<0.01; ***p<0.0001 vs ICS; restricted maximum likelihood repeated measures model; baseline values 970 mL for ICS, 981 mL for ICS withdrawal
Week
ICS
ICS withdrawal
***
**
1223
1218
1135
1135
1114
1092
1077
1058
970
935
n
ICS withdrawal
ICS
38 mL
43 mL
100 µg BID 0 µg (placebo)250 µg BID
Mean change from baseline in lung function: FEV1
ICS withdrawal
Magnussen H et al. Withdrawal of Inhaled Glucocorticoids and Exazerbations of COPD. Respir Med 2014;108:593-9
FLAME STUDY
0 6 12 19 26 32 38 5245
0
10
20
30
40
50
60
70
80
90
100
Wa
hrs
ch
ein
lic
hk
eit
fü
r e
ine
Ex
aze
rba
tio
n (
%)
Hazard ratio, 0.84
(95% CI, 0.78-0.91) P<0.001
Alle
16%
Risiko-
Reduktion
Hazard ratio, 0.78
(95% CI, 0.70-0.86) P<0.001
Moderate oder schwere
22%
Risiko-
Reduktion
Hazard ratio, 0.81
(95% CI, 0.66-1.00) P=0.046
schwere
(Hospitalisationen)
19%
Risiko-
Reduktion
Indacaterol/Glycopyrr. 110/50 μg, 1x tgl.
Salmeterol/Fluticason 50/500 μg, 2x tgl.
Wedzicha, J., et al., NEJM, 2016
Zeit (Tage)
An
ge
pa
sste
r m
ittle
rer
SG
RQ
-C-
Ge
sa
mts
co
re
48
47
46
45
44
43
42
Tag 0
(Baseline)
0Tag 29 Tag 85 Tag 183 Tag 267 Tag 365
Mittlerer LS-
Unterschied = -
1,3
P < 0,001
Mittlerer LS-
Unterschied = -
1,2
P = 0,001
Mittlerer LS-
Unterschied = -
1,3
P = 0,003
Mittlerer LS-
Unterschied = -
1,8
P < 0,001
Mittlerer LS-
Unterschied =
0
P = NS
Salmeterol/Fluticason 50/500 μg 2x tgl. (n = 1593)
Indacaterol/Glycopyrronium 110/50 μg 1x tgl. (n = 1602)
Verb
esseru
ng
SGRQ-C-Responder*: Indacaterol/Glycopyrronium 49,2 %; Salmeterol/Fluticason 43,7 %
(OR 1,30; P < 0,001)Analyse der mITT. *Ansprechen definiert als eine Verbesserung von ≥ 4 Einheiten im SGRQ-C
LABA/LAMA significantly improved Quality of Life as compared to LABA/ICS
Wedzicha, J., et al., NEJM, 2016
∆=–0.25, P<0.001
Ad
just
ed m
ean
ch
ange
in r
escu
e m
edic
atio
n u
se f
rom
b
asel
ine
(pu
ffs/
day
)
0
–0.25
–0.50
–0.75
–1.0
–1.25
–1.5
32
Baseline rescue medication use was 4 puffs per day, on average, in both treatment groups
LABA/LAMA significantly decreased rescue medication use compared with LABA/ICS at Week 52
Wedzicha et al. N Engl J Med, 2016
Exercise ToleranceTiotropium vs. Placebo
Maltais F et al. Chest 2005; 128: 1168-1178
450
550
650
750
850
-10 0 10 20 30 40 50
Sekunden
Belastungsdauer
+ 236 s
+ 41,5%
* *
#
# p < 0,05
* p < 0,01
Tiotropium (n = 131)
Placebo (n = 130)
Studientag
Exercise ToleranceTiotropium plus Rehabilitation vs. Placebo plus Reha
Casaburi R et al. Chest 2005; 127:809-817
Belastungsdauer
* * * p < 0,05 Tiotropium ( 55)
Placebo (n = 53)
Studienwoche
+ 42%+ 32%
+ 16%
Rehabilitation8
12
16
20
24
0 4 8 12 16 20 24
Min
ute
n
LVR Indication
• FEV1 < 35 % • TLC > 125 %• RV > 200 %• RV/TLC > 0.6• 6’ Gehtest < 300 m• VO2max < 12 ml/kg/min
SPECT
National Emphysema Treatment Trial
LVRS – FEV1
15
20
25
30
35
40
45
50
Prä OP 3M 6M 9 M 12M 15M 18M
Verlauf
FE
V1%
FEV1 % VC MAX
LVRS – Air Trapping
40
50
60
70
Prä OP 3M 6M 9 M 12M 15M 18M
Verlauf
RV
% T
LC
Mean RV % TLC
Bronchoscopic LVR
Valves: efficacy predictors
Coils: Long term Follow-up
Summary
• Dyspnea in COPD can be caused by
– Hyperinflation
– Emphysema/ diffusion problem
– Pulmonary hypertension
– Comorbidities
• Treatment is mainly based on bronchodilatation and REHAB
• In specific cases, oxygen, lung volume reduction, transplantation