copd guidelines update and newer therapies

COPD: Guidelines Update and
Newer Therapies
•
The Problem
•
Pathogenesis
•
Key Clinical Concepts
–
Life Prolonging vs. Symptomatic Therapy
–
Spirometry - The Sixth Vital Sign
–
Use of clinical practice guidelines
•
COPD Exacerbations
•
New Horizons
Outline
Percent Change in Age-Adjusted Death
Rates, U.S., 1965-1998
0
0.5
1.0
1.5
2.0
2.5
3.0
Proportion of 1965 Rate
1965 - 98
–59% –64% –35% +163% –7%

Coronary
Heart
Disease
Stroke Other CVD COPD
All Other
Causes
COPD in the United States
Age-Adjusted Death Rates* for COPD by State: 1995-1997
Deaths/100,000 Pop
Highest 46-61 (11)
High 41-45 (13)
Low 36-40 (13)
Lowest 19-35 (13)
*Morbidity and Mortality: 2000 Chart Book on Cardiovascular, Lung, and
Blood Diseases. May 2000.
x
x
x
COPD - Pathogenesis
Tobacco Smoke
Chronic Inflammation*
Emphysema
Chronic Bronchitis
*CD8+ T-lymphocytes
Macrophages
Neutrophils
IL-8 and TNFα
ProteinasesOxidative Stress
Host factors
Anti-oxidants Anti-proteinases

Repair Mechanisms
COPD Therapy Concepts
•
Life prolonging vs. symptomatic
therapies
•
Spirometry - the 6th vital sign
•
Use of clinical practice
guidelines
COPD Therapy
•
Smoking Cessation
•
Oxygen
•
Reduce exacerbations
•
Pulmonary Rehabilitation
•
LVRS (selected patients)
•
Lung Transplantation
•
MDI Therapy
–
SA beta-2 agonists
–
LA beta-2 agonists
–

SA and LA Anticholinergics
•
Theophylline
•
Corticosteroids (inhaled or
oral)
•
Combination Preparations
–
SABA and anticholinergic
–
LABA and corticosteroids
Prolong Life Symptomatic
Spirometry - The Sixth Vital Sign
0
5
1
4
2
3
Liter
1
654
32
FVC
FVC
FEV
1
FEV
1

Normal
COPD
3.900
5.200
2.350
4.150
80 %
60 %
Normal
COPD
FVC
FEV
1
FVC
FEV
1
/
Seconds
Indications: Symptoms or >10 pack year smoker
COPD Practice Guidelines
•
European Thoracic Society - 1995
•
American Thoracic Society - 1995
•
British Thoracic Society - 1997
•
Veterans Administration - 1998, 2001
•
GOLD - 2003* (http:/www.goldcopd.com)

•
ACCP/ACP - 2001* (Ann Int Med 134:595,
2001)
* Evidence-based
Consensus and Evidence-based Guidelines
For comparisons:
Stoller JK. New Eng J Med 346:988, 2002
GOLD Workshop Report
Four Components of COPD
Management - www.goldcopd.com
1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic
4. Manage exacerbations
Management of COPD
Stage 0: At Risk
Characteristics Recommended Treatment
•
Risk factors
•
Chronic symptoms
- cough
- sputum
•

No spirometric
abnormalities
•
Adjust risk factors
•
Immunizations
Management of COPD
Stage I: Mild COPD
Characteristics Recommended Treatment
•
FEV
1
/FVC < 70 %
•
FEV
1
> 80 % predicted
•
With or without
symptoms
•
Short-acting
bronchodilator as
needed
Management of COPD
Stage II: Moderate COPD
Characteristics Recommended Treatment
•
FEV
1

/FVC < 70%
•
50% < FEV
1
< 80% predicted
•
With or without symptoms
•
Treatment with one or
more long-acting
bronchodilators
•
Rehabilitation
Management of COPD
Stage III: Severe COPD
Characteristics Recommended Treatment
•
FEV
1
/FVC < 70%
•
30% < FEV
1
< 50% predicted
•
With or without symptoms
•
Treatment with one or
more long-acting
bronchodilators

•
Rehabilitation
•
Inhaled glucocortico-
steroids if repeated
exacerbations (>3/year)
Management of COPD
Stage IV: Very Severe COPD
Characteristics Recommended Treatment
•
FEV
1
/FVC < 70%
•
FEV
1
< 30% predicted or
presence of respiratory
failure or right heart failure

•
Treatment with one or more long-
acting bronchodilators
•
Inhaled glucocorticosteroids if
repeated exacerbations (>3/year)
•
Treatment of complications
•
Rehabilitation

•
Long-term oxygen therapy if
respiratory failure
•
Consider surgical options
Bronchodilator Therapy
•
Inhaled therapy (with spacer) preferred
•
Long-acting preparations more convenient
•
Combined preparations improve effectiveness and
decrease risk of side effects
–
Ipratroprium-albuterol
–
Fluticasone-salmeterol
–
Budesonide-formoterol
•
MDI almost always as effective as nebulizers (in equal
doses)
Some General Principles
Effectiveness of
BronchodilatorTherapy?
•
FEV1 does not always correlate with symptoms
–
Concept of “dynamic hyperinflation” in COPD
•

Quality of life issues are important
–
Chronic fatigue
–
Depression
–
Physical immobility
–
Dyspnea
COPD - Surgical Options
•
Giant Bullous Disease
–
Consider bullectomy if see normal lung compression
•
Lung Volume Reduction Surgery*
–
FEV1 (<20% pred) plus diffuse emphysema or Dlco<20%
pred = high risk of surgical death
–
Upper lobe emphysema and low exercise capacity =
decreased mortality, increased exercise and QOL
•
Lung Transplantation
–
FEV1<25% predicted, younger patient
–
3-5 year mortality 55%
*NETT Research Group. N Eng J Med 348:2059, 2003
COPD Exacerbation

•
Worsening dyspnea
•
Increased sputum purulence
•
Increase in sputum volume
•
Severe - all 3 elements
•
Moderate - 2 elements
•
Mild - 1 element plus:
•
URI in past 5 days
•
Fever without
apparent cause
•
Increased wheezing or
cough
•
Increase (+20%) of
respiratory rate or
heart rate
Definition Elements Severity
Modified from Anthonisen et al. Ann Int Med 106:196, 1987
COPD Exacerbations
Frequency
(per year)
Number

(patients)
SGRQ Symptoms Activities Impacts
0-2
Infrequent
32 48.9 53.2 67.7 36.3
3-8
Frequent
38 64.1 77.0 80.9 50.4
Mean = 3 Total =70
0.0005 0.0005 0.001 0.002
Effect on Quality of Life
Seemungal et al. A JRCCM 157:1418, 1998
COPD Exacerbation
•
109 pts (mean FEV1 = 1.0 L
over 4 years
•
Frequent exacerbators:
–
faster decline in PEFR and
FEV1
–
more chronic symptoms
(dyspnea, wheeze)
–
no differences in PaO2 or
PaCO2
Donaldson et al. Thorax 57:847, 2002
Effects on Lung Function Decline
Infrequent

Frequent
Conclusion:
Frequent exacerbations
accelerate decline in lung
function
COPD Exacerbation
Bacterial
Infection
50%
Viral
Infection
25%
Air
Pollution
5%
Unknown
20%
Exacerbation
Acute
Inflammation
Pathophysiology - Current Hypothesis
Chronic Inflammation
Therapy of COPD Exacerbation
Variable
ACCP-ACP
ACCP-ACP
GOLD
GOLD
Diagnostic CXR for admissions CXR, EKG, ABG,
sputum culture, lytes, cbc

Bronchodilators Ipratroprium, add B2
agonist. No
methylxanthine
B2 agonist, add
ipratroprium. Yes
methylxanthine
Delivery system None preferred Not discussed
Antibiotics Yes, in selected (severe).
Duration unclear
Yes, with purulence, Rx
local sensitivities
Guidelines
http:/www.goldcopd.comAnn Int Med 134:595, 2001
Therapy of COPD Exacerbation
Variable
ACCP-ACP
ACCP-ACP
GOLD
GOLD
Steroids Yes, for up to two
weeks
Yes, oral or IV for 10-14 days
Oxygen Yes Yes - target PaO2 60 torr or Sat of
90% with ABG check
Chest PT No Maybe - for atelectasis or sputum
control
Mucokinetics No Not discussed
Guidelines
http:/www.goldcopd.comAnn Int Med 134:595, 2001
Therapy of COPD Exacerbation

Variable
ACCP-ACP
ACCP-ACP
GOLD
GOLD
Mechanical
Ventilation
Yes - use NIPPV in
severe exacerbation
Yes if ≥2 of:
Severe dyspnea,
access. muscle or
paradox, pH <7.35 and
PCO2 >45, RR>25
Other
LMWH, fluids, diet
Guidelines
http:/www.goldcopd.comAnn Int Med 134:595, 2001
COPD Therapy - New Horizons
•
Newer anti-inflammatory agents
–
Matrix metalloproteinase inhibitors
–
Specific phosphodiesterase (PDE4) inhibitors
•
Cilomilast
•
Rofumilast
•

Piklanilast
•
Anabolic steroids
•
Repair agents
–
Retinoic acid
•
Long-acting anti-muscarinic agents
–
tiotropium