ACC

8oard kev|ew 2011

CCD art II
S|dney S. 8raman MD ICC
rov|dence, kI
D|sc|osures
ConsulLanL Sunovlon, 8l, loresL
non-promouonal Speaker CSk, CenenLech
uesnon 1
A 4S year o|d man |s smok|ng 1 pack of c|gareues a day. ne adm|ts
to chron|c da||y cough and sputum producnon. ne |s GCLD stage II
CCD

Wh|ch of the fo||ow|ng statements about h|m |s true?
a) Pe ls more suscepuble Lo exacerbauons because of hls
chronlc bronchlus sympLoms
b) Pls sympLoms predlcL emphysemaLous changes on hls
chesL radlograph
c) Pls sympLoms (cough and phlegm) do noL predlcL fuLure
dlsease progresslon
d) unreporLed exacerbauons of chronlc bronchlus are
common buL Lhey do noL have a slgnlcanL lmpacL on a
pauenLs quallLy of llfe
Iactors Assoc|ated W|th Increased k|sk
for Lxacerbanons
lncreased age
SeverlLy of alrway obsLrucuon
(lLv
1
lmpalrmenL)
Chronlc bronchlal mucous
hypersecreuon
Longer durauon of CCu
roducuve cough and wheeze
LlevaLed cough and spuLum
Anublouc or sysLemlc corucosLerold use
ln Lhe pasL year
rlor use of medlcauons for CCu
8acLerlal colonlzauon
Comorbld condluons
(e.g., cardlovascular dlsease)
oor healLh-relaLed quallLy of llfe

.

LCLISL: Iactors Assoc|ated W|th Increased
Lxacerbanon Irequency
5.72
1.11
1.07
2.07
1.08
0
1
2
3
4
5
6
7
Exacerbation During
Previous Year
FEV (per 100 mL
decrease)
SGRQ Score (per 4 point
increase)
Positive History for
Reflux/Heartburn
White Cell Count (per
increase of 1000/mL)
1
O
d
d
s

R
a
t
i
o

f
o
r

!
2

v
e
r
s
u
s

0

E
x
a
c
e
r
b
a
t
i
o
n
s

P<0.001
P<0.001
P<0.001
P<0.001
P=0.002
N=2138
Hurst JR, et al. N Engl J Med. 2010;363:1128-1138.
L|evated Lxacerbanon k|sk Assoc|ated W|th
Cough and Sputum roducnon
*
* P<0.0001
P
e
r
c
e
n
t

w
i
t
h

!
2

E
x
a
c
e
r
b
a
t
i
o
n
s

p
e
r

Y
e
a
r

Burgel P-R, et al. Chest. 2009;135:975-982.
Lar|y Chron|c 8ronch|ns Symptoms Are
red|cnve of D|sease rogress|on
Guerra S, et al. Thorax. 2009;64:894-900. Permission requested.
Years of Follow-up
0 5 10 15 20 25 30
C
u
m
u
l
a
t
i
v
e

S
u
r
v
i
v
a
l

C
u
r
v
e
s

f
o
r

A
l
l
-
C
a
u
s
e

M
o
r
t
a
l
i
t
y

0.0
0.2
0.4
0.6
0.8
1.0
Age < 50 years
No C. Bronchitis
(N = 653)
Age < 50 years
C. Bronchitis
(N = 46)
Age ! 50 years
No C. Bronchitis
(N = 661)
Age ! 50 years
C. Bronchitis
(N = 51)
Anthonisen NR, et al. Am Rev Respir Dis. 1986;133:14-20.
ke|anonsh|p 8etween Lung Iuncnon
and Morta||ty
1
2
Years
100
90
80
70
60
0
3
FEV
1
Normals
!50%
40-49%
30-39%
<30%
%

s
u
r
v
i
v
i
n
g

Surv|va| by Lung Iuncnon Impa|rment
GOLD 3/4
GOLD 2
GOLD 1
No Lung Disease
Restrictive Disease
GOLD 0
Mannino et al, Thorax 2003;58:388-393

Follow up in Years
20 10 0
P
r
o
p
o
r
t
i
o
n

S
u
r
v
i
v
i
n
g

1.0
.8
.6
.4
.2
0.0
CCD Sever|ty C|ass|hcanon
u|monary and System|c Lects
8CDL

8ody-Mass Index
Degree of A|row Cbstrucnon
Dyspnea
Lxerc|se Capac|ty Index
Celli et al NEJM 2004350:1005-12
FEV
1
Stage BODE
Months
1.0
0.8
0.6
0.4
0.2
0.0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 4 8 12 16 20 24 28 32 36 40 44 48 52
Stage I (> 50%) predicted
Stage II (36-50%) predicted
Stage III (! 35%) predicted
Quartile 1 (BODE 0-2)
Quartile 2 (BODE 3-4)
Quartile 3 (BODE 5-6)
Quartile 4 (BODE 7-10)
P
r
o
b
a
b
i
l
i
t
y

o
f

s
u
r
v
i
v
a
l

P<0.001 P<0.001
Celli BR, et al. N Engl J Med. 2004;350:1005-1012.
Surv|va| |n CCD

uesnon 2

A 63 year old man, smoker of 1-2 packs of clgareues a day,
has CCLu SLage lll CCu. Pe complalns of chronlc cough
and dyspnea and has 2-3 exacerbauons of hls sympLoms
each year LreaLed aL home wlLh oral anubloucs and
corucosLerolds. Whlch sLaLemenL ls Lrue abouL Lhls man?
uesnon 2
Wh|ch statement |s correct?
a) unllke asLhma, bacLerlal lnfecuons and noL vlral lnfecuons
are Lhe cause of hls exacerbauons
b) 1he frequency of hls exacerbauons ls llkely Lo worsen as hls
lung funcuon deLerloraLes
c) 8ecovery of lung funcuon buL noL sympLoms occurs wlLhln
Lhe rsL week followlng an exacerbauon
d) 8CuL lndex wlll predlcL severlLy and noL frequency of
exacerbauons
Lp|dem|o|ogy of Lxacerbanons:
Irequency Increases w|th Dec||n|ng ILV
1
Donaldson GC, Wedzicha JA. Thorax. 2006;61:164-168.
FEV
1
(1)
2.5
2.0
0.5
0
< 1.25 1.25 1.54 > 1.54 2.40
3.0
1.5
E
x
a
c
e
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b
a
t
i
o
n
s

p
e
r

Y
e
a
r

2.50
1.0
Irequent Lxacerbanons Are Assoc|ated W|th
More kap|d Dec||ne |n u|monary Iuncnon
*
-40.1
-2.94
-32.1
-0.72
-45
-40
-35
-30
-25
-20
-15
-10
-5
0
Frequent Exacerbators
Infrequent
Exacerbators
FEV
1
(mL) PEF (L/minute)
A
n
n
u
a
l

C
h
a
n
g
e

**
* P<0.05 versus infrequent exacerbators; ** P<0.001 versus infrequent exacerbators
Donaldson GC, et al. Thorax. 2002;57:847-852.
Lno|ogy of ALCCD
Papi A, et al. Am J Respir Crit Care Med. 2006;173:1114-21.
Causes of exacerbations requiring hospitalization in patients (N=64)
23.4%
21.8%
25.0%
29.7%
Bacteria
Bacteria
and Virus
Virus
Non-infectious
Inc|dence of V|rus Detecnon W|th Ck
|n Adu|t opu|anons
Population
Virus General Adult High Risk COPD Inpatient COPD ICU COPD
RSV 4.5-11.6% 4.3-12.0% 2.6-15.3% 6.5%
Influenza A 18.4% 3.4% 15.6-17.6% 13.1%
Influenza B 1.9% NR 4.7% 5.6%
Rhinovirus 10.5% 25.6% 11.7-24.7% 6.5%
Coronavirus 0.8% 8.5% 7.8% 2.8%
Parainfluenza 1.1% 5.1% 3.9% 10.3%
Metapneumovirus 1.5-3.4% 0% 0% 2.8%
Adenovirus 0.8% 0% 1.3% NR
NR = not reported
Adapted from Ramaswamy M, et al. COPD. 2009;Feb:64-75.
V|ra| Infecnon and the CCD Lxacerbanon
lnvesugaLed Lhe role of vlral lnfecuon ln Lhe exacerbauon of
CCu uslng C8 Lechnology
39 were assoclaLed wlLh vlral lnfecuon
lnammaLory markers hlgh (lL-6, brlnogen)
vlral lnfecuons assoclaLed wlLh more severe sympLoms and
longer durauon of lllness (13 d)
8hlnovlrus was predomlnanL vlrus (38)
Seemungal et al AJRCCM 2001; 164:1618-1623
kecovery Irom Lxacerbanons:
V|ra| Versus Non-v|ra|
Non-Viral Exacerbation
Viral Exacerbation
80
0
0
100
40
20
10 20 30 40
Days from Onset of Exacerbation

50 60
%

E
x
a
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b
a
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i
o
n
s

R
e
c
o
v
e
r
e
d

60
P=0.006 for viral versus non-viral infections
. Seemungal T, et al. 2001. . American Journal of Respiratory and Critical Care Medicine. 164:1618-1623.
kesp|ratory Syncyna| V|rus (kSV) I||ness |n the
L|der|y
rospecuve sLudy of healLhy and hlgh-rlsk elderly (chronlc hearL and
lung dlsease)
8Sv developed annually ln 3-7 percenL of healLhy & 4-10 percenL of
hlgh-rlsk adulLs
8Sv was ldenued ln 142 and lnuenza A ln134 hosplLallzed pauenLs.
(n=1388)
8Sv and lnuenza A resulLed ln slmllar LCS, lCu use and morLallLy (8
vs 7)
8Sv lnfecuon accounLed for 10.6 of hosplLallzauons for pneumonla
& 11.4 CCu
Falsey AR et al NEJM 2005;352:1749-1759
In Stab|e CCD n|gh resence of kSV Is Assoc|ated
W|th More kap|d Dec||ne |n ILV
1
A
n
n
u
a
l

D
e
c
l
i
n
e

i
n

F
E
V
1

(
m
L
/
y
e
a
r
)

*
* P=0.01 versus lower RSV
Wilkinson TM, et al. Am J Respir Crit Care Med. 2006;173:871-876.
D
a
i
l
y

M
e
d
i
a
n

P
E
F
R

a
s

%

B
a
s
e
l
i
n
e

u|monary Iuncnon kecovers S|ow|y
Aher an Lxacerbanon
Seemungal TA, et al. Am J Respir Crit Care Med. 2000;161:16081613.
Days
100
99
96
95
-14
101
98
97
-9 -4 1 6 11 16 21 26 31
Exacerbation
1|me Course and kecovery of anents W|th
CCD Lxacerbanon
Medlan recovery of Ll8 paralleled sympLom recovery 6-7
days
AL day 33, Ll8 reLurned Lo normal ln 73 of pauenLs, 86
aualned sympLomauc recovery
AL 90 days, 7 had noL reLurned Lo Ll8 basellne
CreaLer dyspnea and falls ln l1s as well as colds aL onseL
of exacerbauon are assoclaLed wlLh longer recovery umes.
Seemungal et.al. Am J Resp Crit Care Med 2000;161:1608-1613
1he 8ody Mass Index, Cbstrucnon, Dyspnea,
Lxerc|se Capac|ty (8CDL) Index red|cts
Lxacerbanon Irequency
Hodgev VA, et al. Folia Med . 2006;48:18-22.
M
e
a
n

B
O
D
E

I
n
d
e
x

S
c
o
r
e

P=0.002
_
_
0
1
2
3
4
5
6
7
8
9
Frequent Exacerbators Infrequent Exacerbators
0.0
0.2
0.4
0.6
0.8
1.0
0 10 20 30 40 50 60
Time (months)
P
r
o
b
a
b
i
l
i
t
y

o
f

s
u
r
v
i
v
i
n
g

p<0.0001
p<0.001
p=0.07
34 exacerbations
12 exacerbations
No exacerbation
CCD Lxacerbanons: Impact Surv|va|
Soler-Catalua JJ et al. Thorax. 2005;64:925-31
uesnon 3
Wh|ch of the fo||ow|ng therapeunc measures has no
|mprovement on year|y exacerbanon rate?
a) lnhaled corucosLerold
b) Cral corucosLerold
c) Long Lerm anublouc prophylaxls
d) neumococcal vacclne
e) 8oumllasL
Inuenza Vacc|nanon: k|sk for Any
Lxacerbanon
Lvaluauon of resulLs from randomlzed cllnlcal Lrlals lndlcaLes LhaL
lnacuvaLed lnuenza vacclne reduces exacerbauons ln CCu
pauenLs
1he magnlLude of Lhls beneL ls slmllar Lo LhaL seen ln large
observauonal sLudles, and was due Lo a reducuon ln
exacerbauons occurrlng Lhree or more weeks aer vacclnauon,
and due Lo lnuenza
1here ls a mlld lncrease ln LranslenL local adverse eecLs wlLh
vacclnauon, no evldence of lncrease ln early exacerbauons
Poole PJ, et al. Cochrane Database Syst Rev. 2006;CD002733.
Relative Risk (95% CI)
COPD hospitalization
All-cause mortality
COPD hospitalization
All-cause mortality
Pneumococcal vaccination
Pneumococcal + influenza
vaccination
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2.0
neumococca| and Inuenza Vacc|nanons
keduce CCD Lxacerbanons


Nichol et al. Arch Intern Med. 1999;159:2437-2442
neumococca| Vacc|nanon |n CCD
neumon|a kates Improved |f <6S yrs and ILV1 <40
Alfageme I, et al. Thorax. 2006;61:189-195.
C
u
m
m
u
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a
t
i
v
e

P
r
o
p
o
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t
i
o
n

o
f

P
a
t
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n
t
s

W
i
t
h
o
u
t

P
n
e
u
m
o
n
i
a

Log rank = 6.68
P=0.0097
Time (days)
1.00
0.90
0 250 750 1250
0.95
0.80
0.85
0.75
0.70
500 1000
Vaccinated = 91
Control = 116
C
u
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m
u
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a
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i
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e

P
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i
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n

o
f

P
a
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n
t
s

W
i
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h
o
u
t

P
n
e
u
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o
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i
a

Log rank = 3.85
P=0.0498
Time (days)
1.00
0.90
0 300 900 1500
0.95
0.80
0.85
0.75
0.70
600 1200
Vaccinated = 132
Control = 114
Age <65
FEV1 <40%
ICS Decreases Lxacerbanon k|sk
Burge PS, et al. BMJ. 2000;320:1297-1303.
A
n
n
u
a
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E
x
a
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b
a
t
i
o
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R
a
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e

* P=0.026 versus placebo
*
0.99
1.32
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
Fluticasone Placebo
1CkCn: Lower Lxacerbanon kate W|th
LA8A |us ICS
Calverley PM, et al. N Engl J Med. 2007;356:775-789.
* P<0.05 versus placebo
*
*
*
*
*
*
*
*
1.13
0.8
0.19
0.97
0.64
0.16
0.93
0.52
0.17
0.85
0.46
0.16
0
0.2
0.4
0.6
0.8
1
1.2
Moderate or Severe Requiring Systemic
Steroids
Requiring
Hospitalization
A
n
n
u
a
l

R
a
t
e

Placebo (N=1524)
Salmeterol (N=1521)
Fluticasone (N=1534)
Combination Therapy
(N=1533)
1|otrop|um Decreases k|sk for
Lxacerbanons
Casaburi R, et al. Eur Respir J. 2002;19:217-224.
* P=0.045 versus placebo
*
0.76
0.95
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
E
x
a
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b
a
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i
o
n
s

p
e
r

P
a
t
i
e
n
t
-
Y
e
a
r

Tiotropium Placebo
Hazard ratio = 0.86,
(95% CI = 0.81, 0.91)
P<0.0001 (log-rank test)
Months
Tiotropium
Control
0
20
40
60
80
0 6 12 18 24 30 36 42 48
P
r
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b
a
b
i
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i
t
y

o
f

e
x
a
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r
b
a
t
i
o
n

(
%
)

0.85/yr
0.73/yr; P<0.001
(14% reduction)
ULII1 Study - Lects on Lxacerbanons
Tashkin DP, et al. N Engl J Med. 2008;359:1543-1554.
37
Annb|onc rophy|ax|s keduces
Lxacerbanons
Suzuki T, et al. Chest. 2001;120:730-733.
60
P
e
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n
t

o
f

P
a
t
i
e
n
t
s

w
i
t
h

E
x
a
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b
a
t
i
o
n

*
* P<0.007 versus control
11
56
40
30
20
10
0
Erythromycin Control
50
Macro||des revents CCD Lxacerbanons
Seemungal TAR, et al. AJRCCM 2008
Median time to 1
st
exacerbation
271 days Macrolide; 89 days Placebo

Proportion of Participants Free from
Acute Exacerbations of
COPD for 1 Year
Albert RK et al NEJM 2011
Median time to exacerbation
266 Azithro 174 Placebo

-21%
(CI -31;-9)
P=0.0011

Mean rate
exacerbations
(moderate or
severe)
per patient
per year

*Hanania et al. Am J Respir Crit Care Med 2010;181:A4435
Fabbri et al Lancet 2009;374:695-703.
koum||ast S|gn|hcant|y keduces
Lxacerbanons When Added to LA8A*
CCD 1herapy 8y Stage
0 1-Mild 2-Mod 3-Severe 4-Very Sev
At risk FEV
1
! 80% FEV
1
! 50% FEV
1
! 30% FEV
1
< 30%
Avoid risk factors; yearly flu shot
PRN /
SABD
PRN / Reg
SABD
PRN / Reg
SABD
PRN / Reg
SABD
Albuterol
Ipratropium
Combination
+ LABD
(TIO / LABA) +
REHAB
+ LABD
(TIO / LABA) +
REHAB
+ LABD
(TIO / LABA)
+ REHAB
+ ICS + ICS +PDE-4
+ O
2
/LVRS?
GOLD 20013
uesnon 4
A 6S year o|d panent w|th GCLD Stag III CCD has [ust been entered
|nto a pu|monary rehab|||tanon program. Wh|ch of the fo||ow|ng |s
an un||ke|y outcome of th|s program?
a. 8educed rlsk of unplanned admlsslon
b. 8educed hosplLallzauon readmlsslon raLes
c. lmprovemenL ln lvC and lLv1
d. lmprovemenL ln walklng ume
Lects of u|monary kehab|||tanon aher
nosp|ta| Adm|ss|on for an Lxacerbanon
7
20
33
23
0
5
10
15
20
25
30
35
Hospital Admission for Exacerbation ED Visit for Exacerbation
PEPR (n=30)
Usual Care (n=30)
P
e
r
c
e
n
t

o
f

P
a
t
i
e
n
t
s

P=0.02
PEPR = post-exacerbation pulmonary rehabilitation Seymour JM, et al. Thorax. 2010;65:423-428.
u|monary kehab|||tanon
Overall (47/46)
Risk ratio (95% CI)
0.17 (0.04 to 0.69)
0.40 (0.09 to 1.70)
1.5
Risk of unplanned
hospital admission
.5 1 .25
Favours usual care Favours rehabilitation
.75
Study
(rehabilitation/
usual care group)
Man (20/21)
Murphy (13/13)
Length of
follow-up
3 months
6 months
Weight in %
44%
19%
0.29 (0.10 to 0.82) Behnke (14/12) 18 months 37%
0.26 (0.12 to 0.54)
Chi-Squared 0.70, p=0.71
Puhan MA, et al. Respir Res. 2005;6:54.
u|monary kehab|||tanon:
Lects on anent Acnv|ty
Pitta F, et al. Chest. 2008 ;134:273-280.
7%
20%
0%
10%
20%
30%
40%
50%
3 Months 6 Months
I
m
p
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t

f
r
o
m

B
a
s
e
l
i
n
e

i
n

D
a
i
l
y

W
a
l
k
i
n
g

T
i
m
e
*
* P=0.008 versus baseline
u|monary kehab|||tanon
8eneLs all levels of dlsease severlLy
8educes resplraLory sympLoms
8educes anxleLy and depresslon
8educes medlcal and hosplLal usage
lmproves exerclse performance
lmproves quallLy of llfe
ls Lyplcally provlded as ouLpauenL
Can be lnluaLed as an lnpauenL unul funcuonal ablllLy has lmproved
uesnon S
Wh|ch of the fo||ow|ng statements about system|c |nammanon and
CCD |s correct?
a) SysLemlc markers of lnammauon are elevaLed only ln
CCLu lll and lv CCu (severe and very severe)
b) MeLabollc syndrome ls rare ln CCu pauenLs because mosL
pauenLs have conslderable welghL loss
c) Smokers wlLh and wlLhouL CCu have slmllarly elevaLed
levels of C8
d) CsLeoporosls ln pauenLs wlLh CCu correlaLes wlLh Lhe
degree of sysLemlc lnammauon
System|c Inammanon and |ts Consequences |n
CCD
SysLemlc lnammauon rlses wlLh CCu severlLy
LlevaLed levels of C8, lL-6 llbrlnogen, 1nl" W8Cs
Comorbldlues ln CCu
MeLabollc Abnormallues ln CCu
Cardlovascular ulsease
CsLeoporosls
CasLrolnLesunal ulsease
SkeleLal Muscle uysfuncuon
Anemla of Chronlc ulsease
Angina
Cataracts
Respiratory Infection
Myocardial Infarction
Fractures
Osteoporosis
Glaucoma
Skin Bruises
Soriano et al. Chest. 2005;128:2099-2107.


!
!
!
!
!
!
!
!
RR in COPD versus non-COPD
R
a
t
e

p
e
r

1
0
,
0
0
0

4 3 2 0 1
0
100
200
300
400
Pneumonia !
CCD Increases k|sk for Med|ca| Lvents
37
25
22.5
19
13
12
11
5
22
14
10
12
8.5
6.5
10
3
0
5
10
15
20
25
30
35
40
RF Pneumonia Heart Failure IHD Hypertension TM Diabetes PVD
I
n

H
o
s
p
i
t
a
l

M
o
r
t
a
l
i
t
y

(
a
s

%

o
f

d
i
s
c
h
a
r
g
e
s
)
COPD
No COPD
Holguin et al. Chest. 2005;128:2005-2011.
IHD = ischaemic heart disease, CHF =
congestive heart failure, RF = respiratory
failure, PVD = pulmonary vascular disease,
TM = thoracic malignancy
Death Due to Co-Morb|d|nes |s More
Common |n CCD
System|c Inammanon k|ses
w|th CCD Sever|ty
Franciosi et al. Pulm Pharmacol Ther. 2006;19:189-199.
CRP TNF-!
Severe
COPD
Moderate
COPD
Mild
COPD
Healthy
0
Serum C-Reactive Protein (mg/L)
20 30 40 50 60 70 10
Severe
COPD
Moderate
COPD
Mild
COPD
Healthy
0 40 100 60 80 20
Serum TNF-Alpha (pg/mL)
*
* P<.05 versus other groups
Pinto-Plata et al. Thorax. 2006;61:23-8.
Ck |s L|evated |n anents w|th CCD
versus Smokers and Nonsmokers
Sin et al. Am J Med. 2003;114:10-14.
A|row Cbstrucnon and Csteoporos|s |n
CCD
Kim B-J, et al. Clin Endocrinol. 2007;67:152-158.
NTx=N-terminal telopeptide of type I collagen, BCE=bone collagen equivalent
0-50 0-00 0-50 1-00
150-50
100-50
50-50
0-50
Log
10
hsCRP (mg1)
U
r
i
n
a
r
y

N
T
x

(
n
M

B
C
E
/
u
)

*"=0-288, P<0-001
Premenopausal
Women

0-10
0-00
0-10
0-20
Normal
(N = 30)
Osteoporia
(N = 109)
Osteoporosis
(N = 50)
P for trend = 0-282
L
o
g
1
0

h
s
C
R
P

(
m
g
1
)

8one 1urnover and Csteoporos|s
are Corre|ated w|th Inammanon
Severe COPD Use of ICS
Adjusted Odds Ratio
for Osteoporotic
Fracture
No No 1.06
No Yes 1.08
Yes No 1.47*
Yes Yes 1.48*
* P<.05
De Vries et al. Eur Respir J. 2005;25:879-884.
CCD, ICS, and Csteoporonc Iracture
Systemic
*
*
McEvoy et al. Am J Resp Crit Care Med. 1998;157:704-709.
* P<.05 versus no corticosteroid
Inha|ed versus Cra| Corncostero|d Use
and Iracture k|sk |n CCD
49
50
51
52
53
54
55
COPD (N=40) No COPD (N=46)
F
a
t
-
f
r
e
e

M
a
s
s

(
k
g
)
Iat-free Mass |s keduced |n CCD
Sergi et al. Respir Med. 2006;100:1918-1924.
*
* P<0.05
50.7
53.9
CHI = creatine height index, a measure of skeletal muscle mass, Normal CHI #80% predicted, Low CHI <80% predicted
* P<.05 for between-group difference
"
*
*
Eid et al. Am J Respir Crit Care Med. 2001;164:1414-1418.
ke|anonsh|p between Ske|eta| Musc|e Mass
and Inammatory Markers |n CCD
*
* P<.05 vs no COPD
Rana et al. Diabetes Care. 2004;27:2478-2484.
reva|ence of D|abetes n|gher |n anents
w|th CCD
*
* P=0.032 vs no COPD
Bolton CE, et al. COPD. 2007;4:121-126.
1.68
1.13
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
COPD (n=56) No COPD (n=29)
H
O
M
A

I
n
s
u
l
i
n

R
e
s
i
s
t
a
n
c
e
Insulin resistance was significantly correlated with
circulating TNF-" and IL-6
Insu||n kes|stance |s L|evated |n CCD anents and
Corre|ated w|th Inammatory Markers
* MeLabollc syndrome #3 of Lhe followlng: abdomlnal obeslLy, elevaLed
Lrlglycerldes, reduced PuL-C, hyperLenslon, hyperglycaemla
Marquis et al. J Cardiopulm Rehabil. 2005;25:226-232.
reva|ence of Metabo||c Syndrome n|gher
|n CCD
System|c Inammanon and Increased k|sk of
Card|ovascu|ar D|sease
0
1
2
3
4
5
6
7
Sin DD & Man SF. Circulation 2003; 107: 15141519.
C
a
r
d
i
a
c

I
n
f
a
r
c
t
i
o
n

I
n
j
u
r
y

S
c
o
r
e

High CRP
No Obstruction
Low CRP
Moderate
Obstruction
High CRP
Moderate
Obstruction
Low CRP
Severe
Obstruction
High CRP
Severe
Obstruction
P for Trend = 0.001
CRP = C-Reactive Protein
uesnon 6
A SS year o|d obese man presents w|th |ncreas|ng dyspnea and ank|e
swe|||ng (k greater than L). u|monary funcnon tests show that he
|s GCLD Stage II w|th an ILV1 of 2.2 ||ters. Arter|a| b|ood gases show
a pn of 7.37 aCC2 of SS and a aC2 of 68. What |s the most ||ke|y
cause of h|s worsen|ng dyspnea?
a) CCu
b) CbsLrucuve Sleep Apnea
c) ulmonary embollc dlsease
d) Comblned ulmonary llbrosls and Lmphysema Syndrome
our patient
ke|anonsh|p between ILV
1
and aCC
2
|eve|
|n CCD
S|eep-d|sordered breath|ng and CCD: 1he over|ap
syndrome
More severe nocLurnal hypoxemla Lhan elLher dlsease
alone.
auenLs wlLh CCu and CSA have a subsLanually greaLer
rlsk of morbldlLy and morLallLy, compared Lo Lhose wlLh
elLher CCu or CSA alone.
lmproved survlval and reduced exacerbauons ln pauenLs
wlLh Lhe over|ap syndrome who are LreaLed wlLh
conunuous posluve alrway pressure
Marin JM et alAm J Respir Crit Care Med. 2010;182:325-31.
Todd N et al Fibrogenesis Tissue Repair. 2011; 4: 6
Comb|ned u|monary I|bros|s and Lmphysema
Syndrome-beuer prognos|s than II?
CenLrllobular and/or parasepLal
emphysemas ln upper lung zones
coexlsL wlLh pulmonary brosls
lnlower lobes ln lndlvlduals
Men >40 pack years, exposure Lo
agrochemlcal compounds
Assoclauons: C1 dlsease (8A, sysLemlc
sclerosls, mlxed C1 dlsease) pulmonary
hyperLenslon, lung cancer,
Lung volumes may be nl., uLCC very
low, exerclse hypoxemla
u|monary nypertens|on |n CCD
rlmarlly due Lo hypoxlc vasoconsLrlcuon of small pulmonary arLerles
LhaL evenLually resulLs ln sLrucLural changes lncludlng lnumal
hyperplasla and smooLh muscle hyperLrophy and hyperplasla
non-hypoxemlc facLors may also conLrlbuLe
elevaLed pulmonary caplllary wedge pressure (from dlasLollc le venLrlcular
dysfuncuon
gas Lrapplng wlLh lncreased lnLra-Lhoraclc pressure
sysLemlc lnammauon wlLh vascular remodellng
emphysema-assoclaLed caplllary loss.
small vessel vascular abnormallues occur very early ln Lhe course of Lhe dlsease
and may lead Lo large vessel remodellng
u|monary nypertens|on |n CCD
A dlameLer >28mm and a rauo of A dlameLer Lo
ascendlng aorLa (A) dlameLer >1 (A/A >1) as measured by
C1 are markers of pulmonary vascular remodellng and
exhlblL moderaLe Lo sLrong correlauons wlLh lnvaslve
measures of pulmonary arLery pressure
Ng CS, et al A CT sign of chronic pulmonary arterial hypertension: the
383 ratio of main pulmonary artery to aortic diameter. J Thorac Imaging. Oct
384 1999;14(4):270-278.
C1 w|thout contrast at the |eve| of the |eh
and r|ght ma|n pu|monary arter|es.
1he Downward Sp|ra| |n CCD
COPD
Airway
obstruction
Exacerbation
Mucus
hypersecretion
Continued
smoking
Lung
inflammation
Alveolar
destruction
Impaired
mucus clearance
Submucosal gland
hypertrophy
Exacerbation
Exacerbation
Hypoxemia
DEATH
GOLD 2007
1nANk CU ICk CUk A11LN1ICN!