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Epidemiology of Complex Chronic
Comorbidities of COPD
David M. Mannino, M.D.
Professor
Department of Preventive Medicine and
Environmental Health
University of Kentucky, College of Public Health
COPD Phenotypes (NEW)
Clinical
Physiologic
Dyspnea
Frequent Exacerbator
Low BMI
Pulmonary Cachexia
ICS-responsive
Depression and Anxiety
Non-smokers
Airflow limitation
Rapid decliner
BD-responsiveness
Hyperrresponsiveness
Hypercapneic
Poor exercise tolerance
Hyperinflation
Low DLCO
Pulmonary hypertension
Radiologic
Emphysema
Airways disease
Friedlander et al, COPD 2007; 4: 355-384
COPD Progression
Fletcher et al, The Natural History of Chronic Bronchitis and Emphysema, 1976
Natural History of Chronic Airflow Obstruction
Adapted from Fletcher and Peto, Burrows
Survival by Lung Function Impairment
1.0
Normal
GOLD 1
.9
GOLD 0
Survival
Restricted
.8
GOLD 2
.7
GOLD 3 or 4
.6
0
2
4
6
Years
Mannino et al, Resp Med, 2006
8
10
12
What do COPD Patients Die From?
(rate per 1,000 person-years)
Normal
Restricted
GOLD 0
GOLD 1
GOLD 2
GOLD 3/4
0
10
COPD
20
ASCVD
Mannino et al, Resp Med, Jan 2006
30
Lung Cancer
40
Other
Slide 3b
50
What is Progression of COPD?
Health
Incident Disease
0
At Risk
I
Mild
II
Moderate
III
Severe
IV
Very Severe
Progressive Disease
Prevalent Disease
???
“Restriction”
*GOLD
Death
Guidelines. Am J Respir Crit Care Med. 2004;163:1256-1276.
COPD – Consequences and Comorbidities
COPD 2008 ; 5: 235-256
COPD – Consequences and Comorbidities
COPD 2008 ; 5: 235-256
Sevenoaks and Stockley, Resp Res 2006
Clinical Overlap Between COPD
and Asthma
COPD
Smoking history
Asthma
Early and/or family
history
Progressive dyspnea;
productive cough
Intermittent wheezing;
hay fever; atopy
Bronchodilator
response: AC>BA
Bronchodilator
response: BA>AC
Neutrophilic
inflammation
AC= Anticholinergic
BA= 2-agonist.
Eosinophilic
inflammation
Airflow Limitation
Adapted by Christopher B. Cooper, MD.
Barnes. Chest. 2000;117:10S-14S; Balmes et al, for the American Thoracic Society. Am J
Respir Crit Care Med. 2003;167:787-796.
Diagnosed Lung Disease and Lung Function
Impairment in the US Adult Population
Asthma
5.5%
Chronic bronchitis
3.2%
Emphysema
1.5%
Airflow obstruction int.
1.6%
Airflow obstruction ext.
3.1%
NHANES III
NHANES III Current Diseases as a Proportional Venn Diagram.
Soriano et al. Chest. 2003;124:474-481.
Percent with COPD
Life time Asthma and GOLD 2+ COPD
Findings from NHANES 3
Predictors of Airway Obstruction by Diagnosis and Smoking Status
100
10
1
Current Smokers
Former Smokers
From NHANES III, 1988-1994 (In Review, Resp. Med.)
Never Smokers
Mortality by Disease Status
None
Asthma only
COPD only
Asthma and COPD
From NHANES III, 1988-1994 and Follow-up through 2006 (In Review, Resp. Med.)
COPD and Comorbid Disease
From Holguin and Mannino (Chest, 2005), NHDS data
Does COPD Cause Lung Cancer?
Adjusted* Kaplan-Meier Curves for Incident Lung Cancer
Moderate COPD
Restrictive Disease
Mild COPD
No Lung Disease
Mannino et al, Archives Int Med, 2003 ; 163: 1475-1480
*adjusted for age, race sex, education, smoking status, pack years, and years since regular smoking
Interaction of Pack Years and Lung
Function and Lung Cancer Incidence
Incident cases per 1000 person years
25
20
15
60
10
+
9
-5
40
Lung Function
al
m
No
r
0
LD
GO
Re
s
tri
cte
d
1
GO
LD
2
LD
GO
GO
LD
3/
4
0
0
9
-1
>0
9
-3
20
5
Pack-years
Barr et al, AJM 2009: 348- 355
Barr et al, AJM 2009: 348- 355
Barr et al, AJM 2009: 348- 355
Hypertension at Baseline
Percent
60
50
40
30
20
10
0
GOLD 3/4
GOLD 2
Mannino et al, ERJ 2008
GOLD 1
Restricted
GOLD 0
Normal
Diabetes Mellitus at Baseline
Percent
25
20
15
10
5
0
GOLD 3/4
GOLD 2
Mannino et al, ERJ 2008
GOLD 1
Restricted
GOLD 0
Normal
Cardiovascular Disease at Baseline
Percent
30
25
20
15
10
5
0
GOLD 3/4
GOLD 2
Mannino et al, ERJ 2008
GOLD 1
Restricted
GOLD 0
Normal
Risk of Death within 5 Years from Baseline
With 3 Comorbid Diseases
With 2 Comorbid Diseases
With 1 Comorbid Disease
With No Comorbid Disease
100
10
1
GOLD 3/4
GOLD 2
GOLD 1
Restricted
GOLD 0
Normal
Models adjusted for age, sex, race, smoking status, education level, and body mass index
Mannino et al, ERJ 2008
Risk of Hospitalization
With 3 Comorbid Diseases
With 2 Comorbid Diseases
With 1 Comorbid Disease
With No Comorbid Disease
100
10
1
GOLD 3/4
GOLD 2
GOLD 1
Restricted
GOLD 0
Normal
Models adjusted for age, sex, race, smoking status, education level, and body mass index
Mannino et al, ERJ 2008
Multivariate Risk of Recurrent CVD by GOLD Stage
GOLD 3 or 4
.8
Restricted
GOLD 2
.6
GOLD 1/ GOLD 0
Normal
.4
.2
0.0
0
2
4
6
8
10
Years of Follow-up
Johnston et al, Thorax 2008
12
14
16
Multivariate Risk of Incident CVD by GOLD Stage
.8
.7
.6
.5
.4
GOLD 3 or 4
.3
Restricted
.2
GOLD 2
GOLD 1/ GOLD 0
Normal
.1
0.0
0
2
4
6
8
10
Years of Follow-up
Johnston et al, Thorax 2008
12
14
16
Figure 1
GOLD 3 or 4
Restricted
GOLD 2
GOLD 0
GOLD 1
Normal
Johnston et al, Thorax 2008
Figure 2
GOLD 3 or 4
GOLD 2
Restricted
GOLD 0
GOLD 1
Normal
Johnston et al, Thorax 2008
GOLD Classification and Comorbidity
0
At Risk
I
Mild
Normal
Spirometry
Respiratory
Symptoms
(Cough, Sputum)
II
Moderate
FEV1/FVC
<70%
FEV1 ≥ 80%
III
Severe
FEV1 /FVC
<70%
50% ≥ FEV1
< 80%
FEV1 /FVC <
70%
30% ≥ FEV1
< 50%
IV
Very Severe
FEV1 /FVC <70%
FEV1 < 30%
or presence
of chronic
respiratory
failure or right
heart failure
Avoidance of risk factor(s); influenza vaccination
Add short-acting bronchodilators* when needed
Add regular Rx with 1 long-acting bronchodilator.*
Add rehabilitation
Add ICS if repeated exacerbations†
Consider O2 and
surgery
*GOLD
Guidelines. Am J Respir Crit Care Med. 2004;163:1256-1276.
0
Mancini et al. J Am Coll Card 2006;47:2554
Beta-Blockers in COPD Exacerbations
Dransfield et al, Thorax 2008
Lung Function Decline and Comorbid Disease
Fletcher et al, The Natural History of Chronic Bronchitis and Emphysema, 1976
What do COPD Patients Die From?
(rate per 1,000 person-years)
Normal
Restricted
GOLD 0
GOLD 1
GOLD 2
GOLD 3/4
0
10
COPD
20
ASCVD
Mannino et al, Resp Med, Jan 2006
30
Lung Cancer
40
Other
50
Interventions for Chronic Disease
Tobacco Control
Diet
Activity
Obesity Prevention
HealthCanada
End-of-Life – Disease C
Lorenz et al, Ann Intern Med 2008:148:147-159
End-of-Life – Disease A
Lorenz et al, Ann Intern Med 2008:148:147-159
Mannino 2/21/2008 Slide # 41
Conclusions
COPD is part of a complex mix of polymorbid
diseases related to ageing, lifestyle choices,
genetics, and environmental exposures
The future of COPD management will include
better phenotypic characterization and integration
of the polymorbidity associated with COPD as
part of the treatment plan
Chronic Obstructive Pulmonary Disease
COPD is a PREVENTABLE and
TREATABLE disease
ATS/ERS Guidelines for the Treatment of COPD, 2004
