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Managing COPD --- Recent Advance
蔡熒煌
長庚醫院胸腔暨重症科
長庚大學呼吸照護學系
Revised 2006
Definition of COPD
• Chronic Obstructive Pulmonary Disease (COPD)
is a preventable and treatable disease with some
significant extrapulmonary effects that may
contribute to the severity in individual patients.
• Its pulmonary component is characterized by
airflow limitation that is not fully reversible.
• The airflow limitation is usually progressive and
associated with an abnormal inflammatory
response of the lung to noxious particles or gases.
COPD: Linking Structure with Function
Driving pressure (parenchyma)
Resistance (small airways)
Airflow
=
limitation
The Nature of Small-Airway Obstruction in
Chronic Obstructive Pulmonary Disease
GOLD
stage 4
GOLD GOLD
stage 3 stage 2
GOLD stages
0 and 1
0.25
V:SA (mm)
0.20
0.15
0.10
0.05
0.00
0
20
40
60
FEV1
Hogg JC et al., NEJM 2004;350:2645-2653
80
100
120
Mechanisms of Uneven Ventilation in COPD
• Unequal lung compliances and airway resistances of
lung units leads to a wide distribution of RC-constants
• Asynchronously emptying results in a changing gas
concentration at the mouth
• Contributes to air trapping
Clinical Course of COPD: Disease Progression
COPD
Expiratory Flow Limitation
Air Trapping
Hyperinflation
Exacerbations
Breathlessness
Deconditioning
Inactivity
Reduced Exercise
Capacity
Poor Health-Related Quality of Life
Disability
Disease progression
Death
age 40-50
50-55
55-60
60-70
Five leading causes of death by the year 2020
Ischaemic heart
disease
Cerebrovascular
disease
COPD
Lower respiratory
infections
Trachea, bronchus
and lung cancers
0
2,000
4,000
6,000
8,000
10,000
12,000
Of the six
leading causes
of death in the
United States,
only COPD has
been increasing
steadily since
1970.
Source: Jemal A. et al. JAMA 2005
Percent Change in Age-Adjusted
Death Rates, U.S., 1965-1998
Proportion of 1965 Rate
3.0
3.0
2.5
2.5
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
–59%
–64%
–35%
+163%
–7%
2.0
2.0
1.5
1.5
1.0
1.0
0.5
0.5
0.0 0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
Number Deaths x 1000
COPD Mortality by Gender,
U.S., 1980-2000
70
60
Men
50
40
Women
30
20
10
0
1980
1985
1990
1995
2000
22
Mortality rate per 100,000
20
22.2
ICD-9 A323:
ICD-9 490 Bronchitis, not specified as acute or chronic
491 Chronic bronchitis
492 Emphysema
493 Asthma
ICD-9
490-493, 496
18 16.4
16
15.8
14
15.1
ICD-9
496
12
10
7.1
8
6
4
2
ICD-9
490-493
( A 323 )
ICD-9
496 Chronic airways
obstruction,
not elsewhere classified
0.6
19811982
1984
1986
1988
1990
1992
1994
1996
1998
Trend of Mortality of Chronic Airway Obstruction
－ Related Diseases in 21 Years in Taiwan
2000
慢阻肺病患門診就醫狀況
4,000,000
3,500,000
3,000,000
2,500,000
2,000,000
1,500,000
1,000,000
500,000
0
1998 1999 2000 2001 2002 2003 2004 2005
門診人數COPD
就醫人次COPD
醫療費用COPD
慢阻肺病患住院治療
250,000
200,000
150,000
100,000
50,000
0
1998
1999
住院人數COPD
2000
2001
2002
住院人次COPD
2003
2004
2005
住院費用COPD（萬）
Medical Cost --- COPD vs. Asthma
2,500,000
2,000,000
1,500,000
1,000,000
500,000
0
1998
1999
2000
COPD OPD
COPD Admission
2001
2002
2003
2004
2005
Asthma OPD
Asthma Admission
Data from BNHI Taiwan : * 1,000 NT
Medical Cost and COPD Severity
• There is a striking direct
relationship between the
severity of COPD and
the cost of care, and the
distribution of costs
changes as the disease
progresses.
• The hospitalization and
ambulatory oxygen
costs soar as COPD
severity increases
Key Indicators for Considering a
COPD Diagnosis
•Consider COPD and perform spirometry if
any of these indicators are present in an
individual over age 40. These indicators are
not diagnostic by themselves, but the presence
of multiple key indicators increases the
probability of a diagnosis of COPD.
Spirometry is needed to establish a diagnosis
of COPD.
Key Indicators for Considering a
COPD Diagnosis
• Dyspnea that is:
–
–
–
–
Progressive (worsens over time).
Usually worse with exercise.
Persistent (present every day).
Described by the patient as an “increased effort to breathe,”
“heaviness,” “air hunger,” or “gasping.”
• Chronic cough: May be intermittent and may be unproductive.
• Chronic sputum production: Any pattern of chronic sputum
production may indicate COPD.
• • History of exposure to risk factors:
– Tobacco smoke (including popular local preparations).
– Occupational dusts and chemicals.
– Smoke from home cooking and heating fuel.
Risk Factors for COPD
Nutrition
Infections
Socio-economic
status
Aging Populations
Diagnosis of COPD
EXPOSURE TO RISK
FACTORS
SYMPTOMS
cough
tobacco
sputum
occupation
indoor/outdoor pollution
dyspnea

SPIROMETRY
Airway Patency is Fundamental
• Spirometry is the gold standard for the
diagnosis and assessment of COPD
• Measuring post-bronchodilator FEV1 is
essential for the classification of severity of
COPD
Spirometry
Diagnosis of COPD in practice (II)
 For the diagnosis and
assessment of COPD,
spirometry is the gold standard
 Healthcare workers involved in
the diagnosis and management
of COPD patients should have
access to spirometry
 Spirometry should be
undertaken whenever
respiratory problems are
suspected
GOLD workshop report 2001
Spirometer
Spirometry: Normal and COPD
FEV1 (l)
5
FVC
Normal
FEV1
FVC
4
3
COPD
FEV1
2
1
FEV1
FVC
FEV1/FVC
Normal
4.15
5.2
80%
COPD
2.35
3.9
60%
0
0
1
2
3
4
Time (S)
Adapted from GOLD workshop report 2001
5
6
Diagnosis of COPD
• Existing COPD prevalence data show remarkable
variation due to differences in survey methods,
diagnostic criteria, and analytic approaches
• Survey methods can include:
– Self-report of a doctor diagnosis of COPD or
equivalent condition
– Spirometry with or without a bronchodilator
– Questionnaires that ask about the presence of
respiratory symptoms
COPD is Under-appreciated and
Under-diagnosed
Example from Japan:
 NICE Survey of COPD prevalence
 NICE study population was comprised of
2343 Japanese subjects aged ≥ 40 years.
 Carried out in several regions of Japan
using standardized methods
COPD Prevalence Rate (adjusted)*
in Population  40 years
10.00%
8.5%**
8.00%
6.00%
4.00%
2.00%
0.3%
0.00%
Study
MHW Survey
5.3 vs 0.2M COPD patients in Japan ≥40 years
*Adjusted for age, sex, cluster
**8.5-10.9% depending on criteria
Fukuchi et al. Respirology 2004;9:458-65
COPD Prevalence Survey (NICE) in Japan
9% Had prior diagnosis
Undiagnosed
Diagnosed
Did not have prior diagnosis: 91%
Fukuchi et al. Respirology 2004;9:458-65
Prevalence of GOLD Stage 1+
COPD1, Guangzhou, China
MEN
15.3%
1 FEV
WOMEN
7.6%
1/FVC<0.70,
post BD
• The Latin American
Project for the
Investigation of
Obstructive Lung
Disease (PLATINO)
examined the prevalence
of post-bronchodilator
airflow limitation (Stage
I: Mild COPD and
higher) among persons
over age 40 in five
major Latin American
cities each in a different
country – Brazil, Chile,
Mexico, Uruguay, and
Venezuela
四十歲以
上成年人
抽煙或吸
入污染接
觸者
Is it Inevitably All Downhill ?
How we can change the
clinical course of COPD?
Therapy at Each Stage of COPD
I: Mild
II: Moderate
III: Severe
IV: Very Severe
FEV1/FVC < 70%
• FEV1/FVC < 70%
• FEV1/FVC < 70%
• FEV1 > 80%
predicted
• 50% < FEV1 <
80%
predicted
• FEV1 < 30%
predicted
• FEV1/FVC < 70% or FEV < 50%
1
predicted plus
• 30% < FEV1 <
chronic
50% predicted
respiratory failure
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting
bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if
repeated exacerbations
Add long term
oxygen if chronic
respiratory failure.
Consider surgical
treatments
The Fletcher-Curve
Smoking Cessation Slows Lung Function Decline in
Mild COPD: The Lung Health Study at 11 Years
Sustained quitters
Intermittent quitters
Continuous smokers
2.9
2.8
2.7
2.6
2.5
2.4
2.3
2.2
2.1
2.0
0
1
2
3
4
5
6
7
8
9
10
Anthonisen NR et al. Am J Respir Crit Care Med. 2002:166:675-9.
Calverley PMA and Walker P. Lancet 2003;362:1053-1061
11
Smoking Cessation Slows Lung Function Decline in
Mild COPD: The Lung Health Study at 11 Years
Anthonisen NR et al. Am J Respir Crit Care Med. 2002:166:675-9.
Calverley PMA and Walker P. Lancet 2003;362:1053-1061
Rate of Death per 1000 Person-Years
Effect of Smoking Cessation on Cause of Mortality
3.5
Special Intervention
Usual Care
3.0
2.5
2.0
1.5
1.0
0.5
0
CHD
CVD
Lung
Cancer
Other Respiratory Other
Cancer Disease
Cause of Death
Unknown
Anthonisen et al. Ann Intern Med.
2005;142:233-239
Bronchodilators in Stable COPD
• Bronchodilator medications are central to
symptom management in COPD.
• Inhaled therapy is preferred.
• The choice between Beta2-agonist, anticholinergic,
theophylline or combination therapy depends on
availability and individual response in terms of
symptoms relief and side effects.
Inhalation Medication
• Short acting beta-2 agonist (SABA)
– Rescue use
•
•
•
•
Long acting beta-2 agonist (LABA)
Long acting anticholinergic agent
Steroid
Combination of steroid and LABA
吸入劑型藥物之吸入道具
Metered-Dose Inhalers (MDI)
Nebulizer
Dry Powder Inhalers (DPI)
Change from Baseline in Trough FEV1 Over
1 Year (Versus Ipratropium)
200
Δ Trough FEV1 (mL)
Tiotropium (n=329)
150
100
50
ΔT-I=
160 mL
0
-50
Ipratropium (n=161)
-100
8
50
92
182
273
364
Test day
P<0.0001 at all timepoints
Vincken W et al. Eur Respir J (2002)
Mean FEV1 Over 6 Months in Combined
Salmeterol Trials
Day 1
Day 169
Tiotropium (n=386)
1.35
1.30
ΔT-S=
70 mL†
FEV1 (L)
1.25
Salmeterol (n=388)
1.20
1.15
ΔT-P=
210 mL*
1.10
Placebo (n=362)
1.05
1.00
0.95
-60
-10
30
60
120
180
Time after administration (minutes)
*P<0.0001; †P<0.001
Brusasco V et al. Thorax (2003)
2003 Canadian COPD Guidelines
ISOLDE: Lack of effect of ICS on FEV1 decline
373
372
1.50
Start of Double-Blind
Treatment
298
269
246
1.40
235
216
FEV1
(L)
288
241
222
Randomization and
Start of Oral Steroid Trial
1.30
168
194
174
141
FP MDI 500 mcg b.i.d. (n=376)
Placebo b.i.d. (n=375)
1.20
-3
0
3
12
24
Time (months)
36
Burge et al. BMJ. 2000; 320:1297-1303.
Effects of Inhaled Steroids:
Long Term Placebo-Controlled Studies
Efficacy
Variables
Primary:
FEV1
Secondary:
Symptoms
Exacerb.
Q of L
MD visits
Bronchial
responsive-ness
ISOLDE
EUROSCOPE
Copenhagen
Lung Health
Study
No effect
No effect
No effect
No effect
NR
25%
less 
NR
NR
NR
NR
NR
No effect
No effect
NR
NR
~dyspnea
NR
No effect
MD visits
NR
NR
NR
Reduced
NR = not reported
Exacerbations Drive Morbidity and Mortality
A downward spiral
COPD exacerbations lead to:
Decline in
lung function1
Increased
symptoms
(breathlessness)2
Worsening
quality of life3
Increased risk
of hospitalisation4
1.
2.
3.
4.
5.
Donaldson et al. Thorax 2002;57(10):847–52
Donaldson et al. ERJ 2003;22:931–936
Seemungal et al. Am J Respir Crit Care Med 1998;157:1418–1422
Groenewegen et al. Chest 2003;124(2):459–67
Soler-Cataluna, et al. Thorax 2005;60:925-931
Increased risk
of mortality4,5
The clinical course of COPD: consequences
of exacerbations
COPD
Expiratory flow limitation
Air trapping
Hyperinflation
Reduced
health-related
Exacerbations
quality of life
Increased mortality
with exacerbation
hospitalizations
Breathlessness
Deconditioning
Exacerbations
Inactivity
Reduced exercise
capacity
Accelerated
decline
in FEV1
Poor health-related quality of
Disability
Disease progression
Increased health
life resource
utilization and
direct costs
Death
Natural History of COPD
Lung Function
Never smoked
Exacerbation
Smoker
Exacerbation
Exacerbation
Time (Years)
Fletcher C. Br Med J. 1977;1:1645-1648
Severe exacerbations and mortality in COPD
COPD (N=304,
FEV1=46% pred.)
5 yrs
Exacerbations vs. Mortality (N=116)
No exacerb.
(N=163)
1-2 exacerb.
requiring
hospital
admission
(N=60)
 3 exacerb.
(N=36)
JJ Soler-Cataluna et al., Thorax 60:925, 2005
Prognosis after Exacerbations
No exacerbations
p < 0.0002
p < 0.0001
 2 exacerbations
p = 0.069
 3 exacerbations
304 men with COPD classified according to number of exacerbations in first year
Soler-Cataluña et al. Thorax 2005;60:925
Moderate (n= 54)
Maintenance
medications
Severe (n= 54)
11,012
10,385
13,276
Very Severe (n= 54)
16,277
Non-ICU
hospitalization
42,117
73,876
3,193
ICU management
51,578
102,876
1,178
Emergency visits 5,366
6,748
Comparison of annual direct medical cost in different
Severity of COPD patients (Chiang CH. VGH-Taipei, 2003)
Acute Exacerbation Prevention
•
•
•
•
ICS
LABA
Anti cholinergic
Combination
2003 Canadian COPD Guidelines
Inhaled Corticosteroids
Regular use of high dose inhaled corticosteroids alone
should only be considered when patients with
moderate to severe COPD have recurrence of acute
exacerbations.
The only evidence of a significant effect with inhaled
corticosteroids is in reducing the rate of exacerbation
(Alsaeedi 2002).
(Level of Evidence: 1 A)
Can Respir J 2003; 10(Suppl A): 11A-33A.
Relative Risk of Exacerbations in COPD
Patients Treated With ICS: A Meta-analysis
Reference
Favors ICS
Favors Placebo
Vestbo et al. 1999
Bourbeau et al. 1998
Burge et al. 2000
Lung Health Study, 2000
Weir et al. 1999
Paggiaro et al. 1998
Overall relative risk = 0.70
95% CI = 0.58 to 0.84
Overall
0
0.5
1.0
1.5
2.0
Relative Risk
Alsaeedi et al. Am J Med. 2002;113:59-65
2.5
3.0
Relative Risk of Exacerbations in COPD
Patients Treated With LABA: A Meta-analysis
Reference
Favors LABA
Favors Placebo
Wadbo et al. 2002
Van Noord et al. 2000
Chapman et al. 2002
Rossi et al. 2002
Dahl et al. 2001
Aalbers al. 2002
Overall relative risk = 0.79
95% CI = 0.69 to 0.90
Overall
0
0.5
1.0
1.5
2.0
Relative Risk
Sin et al JAMA 2003;290: 2301–2312
2.5
3.0
Salmeterol/fluticasone in COPD
Moderate/severe exacerbations
Placebo
1.0
SALM 50µg bd
Exacerbation rate
FP 500µg bd
SALM/FP 50/500µg bd
*
*
#*
0.5
0
* p<0.002 vs placebo
# p=0.059 vs SALM
Moderate/severe exacerbations
requiring OCS
Baseline: FEV1 <50% predicted
Calverley et al. Lancet 2003;361:449-456
Budesonide/formoterol (Bud/Form) in COPD
Rate of severe exacerbations
Calverley
Szafranski
Rate of severe
Bud/Form BudesonideFormoterol
exacerbations
vs placebo (%)
Bud/Form BudesonideFormoterol
5
0
0
–10
–10
–20
–20
*p<0.05 vs placebo
*
*p<0.05 vs placebo
p=0.043 Symbicort vs formoterol
–30
*
–30
W Szafranksi et al., ERJ 2003;21:74-
p=0.015 Symbicort vs formoterol
PM Calverley et al., ERJ
ICS and LABAs improve symptoms and
lung function via different mechanisms
Inhaled corticosteroids
reduce
LABAs inhibit
Inflammation
Structural changes
Airway constriction
Increased
neutrophils and
CD8+ lymphocytes
Alveolar destruction
Smooth muscle
contraction
Elevated IL–8, TNF
Glandular
hypertrophy
Protease/antiprotease
imbalance
Collagen deposition
Airway fibrosis
Symptoms
 FEV1
Exacerbations
Increased
cholinergic tone
Loss of elastic recoil
Sensory nerve
activation
Veterans Administration –
Exacerbation Trial
Exacerbations/patient-year
19% reduction
1.2
Exacerbation days/patient-year
20
21% reduction
15
0.8
10
P<0.001
P=0.003
0.4
5
1.05
0.85
0
16.0
12.6
Placebo
Tiotropium
0
Placebo
Tiotropium
Niewoehner et al. Ann Intern Med. 2005;143:317
Risk of a New Exacerbation
0.4
20 %
Probability of
Exacerbation
0.3
0.2
Placebo group
Tiotropium group
P=0.028
0.1
0.0
0
30
60
90
120
Study
788 Days
743
Patients at risk, n
Tiotropium group
838
Placebo
832
772
Niewoehner et al. Ann Intern Med. 2005;143:317
709
150
690
663
180
658
619
514
454
Effect of Current Drugs on
Exacerbation Frequency of COPD
Szafranski
Brusasco
TRISTAN
Szafranski
TRISTAN
Brusasco
Percentage change
(versus placebo)
10
0
-10
-2
-20
-17
-20
-30
-40
-50
Formoterol
Salmeterol
Salmeterol
-24
-25
-28
Formoterol/ Salmeterol/ Tiotropium
budesonide Fluticasone
COPD: Defining the Clinical Course and
Implications of Therapeutic Interventions
• Changing the Clinical Course
– Prevent the PFT decline
• Smoking cessation
• pharmacotherapy
• Pulmonary rehabilitation
– Prevent of exacerbations
– Impact on survive
• Systemic co morbidity
COPD and Systemic Disorders
• COPD involves several systemic features, particularly in severe
disease,
• Increased concentrations of inflammatory mediators, including
TNF-, IL-6, and oxygen-derived free radicals, may mediate some
of these systemic effects.
• There is an increase in the risk of cardiovascular diseases, which is
correlated with an increase in C-reactive protein (CRP)21.
COPD and Systemic Disorders
• Data from the Netherlands show that up to 25% of
the population 65 years and older suffer from two
comorbid conditions and up to 17% have three.
• COPD and lung cancer. Whether this association
is due to common risk factors (e.g., smoking),
involvement of susceptibility genes, or impaired
clearance of carcinogens is not clear.
COPD and Co-Morbidities
•
COPD patients are at increased risk:
• Myocardial infarction, angina
• Osteoporosis
• Respiratory infection
• Depression
• Diabetes
• COPD and lung cancer
GOLD: COPD Pharmacotherapy
New
0: At Risk
I. Mild
II. Moderate
III. Severe
IV. Very severe
Characteristics
•Chronic symptoms
•Exposures to risk
factors
•Normal spirometry
•FEV1/FVC<70%
•FEV1>80%
•With or without
symptoms
•FEV1/FVC<70%
•50%>FEV1<80%
•With or without
symptoms
•FEV1/FVC<70%
•30%>FEV1<50%
•With or without
symptoms
•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 bronchodilator when needed
Add regular treatment with one or more long-acting bronchodilators
Add rehabilitation
Add inhaled glucocorticosteroids if repeated
exacerbations
Add long-term
oxygen if chronic
respiratory failure
Consider surgical
treatments
NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease.
April 2001 (Updated 2003).
"Mild" COPD – causes of death
[%]
50
25 % – 39 %
40
30
20
10
0
COPD
cardiovascular
Lung
carcinoma
other
EUROSCOP (n = 18/1277) LUNG HEALTH (n = 149/5887) Postma et al. (n = 22/81)
(n = number of deaths/total number)
R. A. Pauwels et al., NEJM 1999; 340:1948–1953.; N. R. Anthonisen et al., JAMA 1994;
272:1497–1505;
D. S. Postma et al., ARRD 1986; 134:276–280.
COPD and systemic inflammation
Meta-analysis
COPD studies
(n=14)
Markers of
systemic
inflammation
CRP
WQ Gan et al., Thorax 59:574, 2004
COPD and myocardial infarction
Potential role of systemic inflammation
8
NHANES III
survey
(n=6,629)
spirometr
y
CRP
Cardiac
infarction
injury score
DD Sin & SFP Man, Circulation 107:1514,
2003
6
*FEV1/FVC <
0.70, FEV1 < 50
% pred.
4
2
0
High
CRP
severe
High
obstruct. CRP+sever
*
e obstruct.*
COPD and systemic inflammation
Influence of fluticasone on CRP
COPD (n=41,
FEV1=55% pred.)
DD Sin et al.,
AJRCCM 170:760,
2004
ICS >>
placebo
FP 500µg
b.i.d
FP 500µg b.i.d.
FP 1000µg b.i.d.
CRP
Pred. 30
mg/d
COPD and systemic inflammation
ICS>>
RCT
Influence of fluticasone on CRP
FP 500µg b.i.d.
-4 -2 0 2
18
4
6
8 10 12 14 16
weeks
Placeb
o
-20
Change in CRP from
randomization [%]
FP 1000µg
b.i.d.
FP
-40
-60
-80
Pred.
DD Sin et al., AJRCCM 170:760,
2004
Budesonide protects against cardio-ischaemic
events in mild - moderate COPD [EUROSCOP]
COPD patients
35
[n]
Placebo
30
 Budesonide
400 µg
bid
(n=634)
 Placebo (n=643)
3 years
25
20
15
10
5
 Cardio-ischaemic
events
Löfdahl et al., ERS 2005
Budesonide
ICS and mortality in COPD
Pooled analysis of 7 trials (N=5085)
DD Sin et al.,
Thorax 60:992,
2005
6,000 patients randomized: placebo, F,
F/S and S for 3 years
Outcome = mortality
Primary Analysis --all-cause mortality at 3 years
Probability of death (%)
18
16
14
-17.5%
12
10
8
NNT = 39
6
4
2
0
Placebo
0
12
24
Vertical bars are standard errors
36
SFC
48 60 72 84 96 108 120 132 144 156
Time to death (weeks)
Cause of Death on Treatment
(adjudicated by CEC)
7.0
Placebo
SFC
Deaths (%)
6.0
5.0
4.0
3.0
2.0
1.0
0.0
Cardiovascular
Pulmonary
Cancer
Other
Unknown
age 40-50
50-55
55-60
60-70
age 40-50
50-55
55-60
60-70
COPD Comorbidities

Comorbid heterogeneity

Common cause
 Heart failure
 Lung cancer
Complicating



Pneumonia
Coincidential



Diabetes mellitus
Arthritis hip/knee
Depression
84
PATIENT – DISEASE ANOMALY
•
•
•
•
•
•
•
•
COPD – The Disease
Airflow obstruction
Function decline
Continuous treatment
Lifestyle
Regular follow-up
‘Management plan’
Compliance
Effects, safety treatment
•
•
•
•
•
•
•
•
Patient with COPD
Social isolation
Unhealthy environment
Poverty
Poor self-efficacy
Multiple health problems
Disruptive life conditions
Trust & support
Safety line
85
What do we mean by ‘changing the
course of the disease’?
Photos courtesy David Halpin MD