Transcript Slide 1

GOLD Website Address
http://www.goldcopd.org
Which of the following have been shown to
reduce mortality in COPD?
a) Long term inhaled corticosteroids in
patients with FEV1 < 50 %
b) Long term oxygen therapy for patients with
baseline PaO2 < 55 mmHg, O2 sat < 88%
c) Pulmonary rehabilitation for patients with
moderate and severe disease
d) Lung transplantation
e) B and D
Burden of COPD
-
-
Affects more than 5% of US population
Third leading cause of death in US
Twelfth leading cause of morbidity in US
Costs:
Direct medical costs about $29.5 billion/yr
Total costs about $49.9 billion in 2010
Global Strategy for Diagnosis, Management and Prevention of COPD
Definition of COPD
n
n
COPD, a common preventable and treatable
disease, is characterized by persistent airflow
limitation that is usually progressive and
associated with an enhanced chronic
inflammatory response in the airways and the
lung to noxious particles or gases.
Exacerbations and comorbidities contribute to
the overall severity in individual patients.
Global Strategy for Diagnosis, Management and Prevention of COPD
Mechanisms Underlying
Airflow Limitation in COPD
Small Airways Disease
Parenchymal Destruction
• Airway inflammation
• Airway fibrosis, luminal plugs
• Increased airway resistance
• Loss of alveolar attachments
• Decrease of elastic recoil
AIRFLOW LIMITATION
Bronchiole
Air passage
narrowed by
plugged and
swollen mucous
membrane
Mucus and pus
impede action of
respiratory cilia
Chronic
Bronchitis
Presence of chronic
productive cough for
3 months in each of
two successive years in
a patient in whom other
causes of chronic cough
have been excluded
Emphysema
Destruction of the
alveolar wall
damages
pulmonary
capillaries by
tearing, fibrosis,
or thrombosis
Walls of individual
sacs torn (repair
not possible)
Inelastic
collapsible
bronchioles
Enlarged air sacs
due to destruction
of alveolar walls
(bullae)
Abnormal permanent
enlargement of the air
spaces distal to the
terminal bronchioles
accompanied by
destruction of their
walls and without
obvious fibrosis
Global Strategy for Diagnosis, Management and Prevention of COPD
Risk Factors for COPD
Genes
Infections
Socio-economic
status
Aging Populations
Alpha-1-Antitrypsin Deficiency
n
Genetic deficiency of the protective anti-protease alpha-1-antitrypsin,
predisposing to emphysema (destruction of alveolar walls) due to the
unopposed action of neutrophil (and other) elastases.
n
Suspect in patients with:
1.
2.
3.
4.
5.
COPD in a never smoker
COPD at a very young age
Strong family history of COPD
Emphysema more prominent in lung bases
COPD with unexplained liver disease
n
Diagnosis via serum level, genetic testing
n
Treat with alpha-1-antitrypsin replacement therapy. Intermittent IV
infusion slows the rate of decline in lung function in those with airflow
obstruction
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
SYMPTOMS
shortness of breath
chronic cough
sputum
EXPOSURE TO RISK
FACTORS
tobacco
occupation
indoor/outdoor pollution
è
SPIROMETRY: Required to establish
diagnosis
Spirometry: Obstructive Disease
Normal
5
Volume, liters
4
3
FEV1 = 1.8L
2
FVC = 3.2L
FEV1/FVC = 0.56
1
1
2
3
4
Time, seconds
5
6
Obstructive
Pulmonary Function Tests in
COPD
Spirometry
–  FEV1
–  FEV1/FVC
–  FEF25-75%
Lung Volumes
– May show
• Normal – mild
disease
• Air trapping - 
RV,  FRC,
•  RV/TLC
Diffusing Capacity
– Low in emphysema
– Normal in chronic
bronchitis
8
Peak expiratory flow rate
6
Forced exhalation
4
2
FEV1 (notch added
by auto timer)
0
-2
Forced inhalation
-4
-6
Normal
1 2
3
4
Vital Capacity
COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
 Assess symptoms
 Assess degree of airflow
limitation using spirometry
 Assess risk of exacerbations
 Assess comorbidities
Symptom Assessment
Chronic Obstructive
Pulmonary Disease
William P Sexauer, MD
Division of Pulmonary and Critical
Care Medicine
Thomas Jefferson University
Global Strategy for Diagnosis, Management and Prevention of COPD
Classification of Severity of Airflow
Limitation in COPD*
In patients with FEV1/FVC < 0.70:
GOLD 1: Mild
FEV1 > 80% predicted
GOLD 2: Moderate
50% < FEV1 < 80% predicted
GOLD 3: Severe
30% < FEV1 < 50% predicted
GOLD 4: Very Severe FEV1 < 30% predicted
*Based on Post-Bronchodilator FEV1
Global Strategy for Diagnosis, Management and Prevention of COPD
Assess Risk of Exacerbations
To assess risk of exacerbations use
history of exacerbations and
spirometry:
 Two or more exacerbations within
the last year or an FEV1 < 50 % of
predicted value are indicators of
high risk.
Global Strategy for Diagnosis, Management and Prevention of COPD
Assess COPD Comorbidities
COPD patients are at increased risk for:
•
•
•
•
•
•
Cardiovascular diseases
Osteoporosis
Respiratory infections
Anxiety and Depression
Diabetes
Lung cancer
These comorbid conditions may influence mortality
and hospitalizations and should be looked for
routinely, and treated appropriately.
Global Strategy for Diagnosis, Management and Prevention of COPD
(C)
(D)
>2
(B)
1
3
2
(A)
1
0
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
Symptoms
(mMRC or CAT score))
(Exacerbation history)
4
Risk
(GOLD Classification of Airflow Limitation)
Risk
Combined Assessment of COPD
Global Strategy for Diagnosis, Management and
Prevention of COPD
Combined Assessment
of COPD
When assessing risk, choose the highest risk
according to GOLD grade or exacerbation history
Patien
t
Characteristic
Spirometric
Classification
Exacerbations mMRC
per year
CAT
A
Low Risk
Less Symptoms
GOLD 1-2
≤1
0-1
< 10
B
Low Risk
More Symptoms
GOLD 1-2
≤1
>2
≥ 10
C
High Risk
Less Symptoms
GOLD 3-4
>2
0-1
< 10
D
High Risk
More Symptoms
GOLD 3-4
>2
>2
≥ 10
The term “BODE” refers to which of the
following:
a) a term used in discussing prognosis
with patients and families
b) a composite scoring system that describes
prognosis in patients with COPD
c) a world class skier with an ego and atitude
to match his considerable talent
d) all of the above
BODE Index
Points
Body mass index (Kg/m2)
Obstructive airways disease
(FEV, % pred)
Dyspnea (MMRC scale)
Exercise (6-min walk dist, m.)
0
1
2
3
>21
≤21
≥ 65
50-64
36-49
≤35
0-1
2
3
4
≥350
250-349
150-249
≤149
Celli BR et al., NEJM 2004; 350:1005-12
BODE Index
 Score of 0 to 2
 Score of 3 to 4
 Score of 5 to 6
 Score of 7 to 10
Celli BR et al., NEJM 2004; 350:1005-12
Preventive/General Measures
-
Smoking cessation: counseling
pharmacologic aids
- Avoid environmental/occupational exposures
-
Vaccinations: influenza, pneumococcal
-
Encourage physical activity
COPD Risk & Smoking Cessation
FEV1 (% of value at age 25)
100
Never smoked or not
susceptible to smoke
75
Smoked regularly
and susceptible to
effects of smoke
Stopped smoking
at 45 (mild COPD)
50
Disability
Stopped smoking
at 65 (severe COPD)
25
Death
0
25
50
Age (years)
Adapted from Fletcher C et al. Br Med J. 1977;1:1645–1648.
75
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: COPD Medications
Beta2-agonists
Short-acting beta2-agonists
Long-acting beta2-agonists
Anticholinergics
Short-acting anticholinergics
Long-acting anticholinergics
Combination short-acting beta2-agonists + anticholinergic in one inhaler
Methylxanthines
Inhaled corticosteroids
Combination long-acting beta2-agonists + corticosteroids in one inhaler
Systemic corticosteroids
Phosphodiesterase-4 inhibitors
Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: Pharmacologic Therapy
(Medications in each box are mentioned in alphabetical order, and
therefore not necessarily in order of preference.)
Patient
First choice
Second choice
Alternative Choices
A
SAMA prn
or
SABA prn
LAMA
or
LABA
or
SABA and SAMA
Theophylline
B
LAMA
or
LABA
LAMA and LABA
SABA and/or SAMA
Theophylline
LAMA and LABA
PDE4-inh.
SABA and/or SAMA
Theophylline
ICS and LAMA or
ICS + LABA and LAMA or
ICS+LABA and PDE4-inh. or
LAMA and LABA or
LAMA and PDE4-inh.
Carbocysteine
SABA and/or SAMA
Theophylline
C
D
ICS + LABA
or
LAMA
ICS + LABA
or
LAMA
TORCH Study
6112 COPD patients (FEV1 < 60%) randomized to
salmeterol/fluticasone (50/500), salmeterol, fluticasone, or placebo
followed for 3 years. Primary outcome was all cause mortality.
Results:
1. No signif difference in mortality between groups (S/F vs
placebo, p=0.052)
2. All components reduced exacerbations compared to placebo
3. S/F and fluticasone improved HRQL vs placebo
4. All components improved lung function vs placebo
5. Both fluticasone groups had higher pneumonia rates than placebo
NEJM 2007 356;8:775-789
COPD Interventions Shown to
Reduce Mortality
-
Smoking cessation for patients with early disease
-
Home oxygen therapy for persistent baseline
hypoxemia
-
Lung Volume Reduction Surgery for very
selected patients (upper lobe predominant
emphysema, low exercise capacity after rehab)
“UPLIFT” Study
5993 COPD patients (FEV1 < 70%) randomized to tiotropium once daily
vs placebo and followed for 4 years. LABA and ICS not excluded.
Primary outcome measure was rate of decline in FEV1.
Results:
1.
No signif difference in rate of FEV1 decline between groups
2.
Tiotropium improved:
Pulmonary function – p < 0.001
HRQL (St George’s) – p < 0.001
Exacerbations – p < 0.001
Incidence of respiratory failure – p < 0.05
NEJM 2008 359;15:1543-54
Tiotropium vs Salmeterol
NEJM 2011 364;12:1093-103
Azithromycin in COPD
NEJM 365;8:689-698 8/25/11
Pharmacologic Interventions shown to reduce
COPD Exacerbations
Inhaled LA beta-agonists
Inhaled LA anticholinergics
Inhaled corticosteroids for patients with FEV1 <
50%
Azithromycin
Phosphodiesterase-4 inhibitor - roflumilast
In select subgroup: chronic bronchitis phenotype
FEV1 < 50%
Frequent exacerbations
Other Therapies
Oxygen:
Long term (home) oxygen if baseline PO2  55 mmHg, O2 Sat  88%
As needed during acute exacerbations
Non-invasive ventilation (NIV):
1. During acute or acute-on-chronic hypercapneic respiratory failure –
avoid intubation
2. Part-time use (nocturnal) for chronic hypercapneic respiratory failure
Benefits of Pulmonary
Rehabilitation
Benefit
Strength of Evidence*
Reduction in dyspnea
1A
Increased exercise ability
1A
Psychosocial benefits (reversal of
anxiety and depression)
2B
Improved quality of life
1A
Reduction in health care utilization
2B
Prolongation of life (?)
--
*From Joint ACCP/AACVPR Evidence-Based Guidelines on Pulmonary Rehabilitation, 2007 Definition of
Rating Scale: 1- Strong; 2 – Weak. A – High; Finding consistently supported by well-designed RCT’s; B –
Moderate; Based on findings from RCT’s with inconsistent results or methodologic limitations; C – Low;
Supported by observational studies
Surgical Options for COPD
Lung Volume Reduction Surgery for Emphysema
1. Age < 75
2. Ex-smoker > 6 months
3. FEV1 < 45% pred; RV > 150% pred
4. Dyspnea despite max medical therapy, incl Pulmonary Rehab
5. *Emphysema with upper lobe predominance
6. *Low exercise capacity post-rehab (F < 25W, M < 40W)
Bullectomy
1.
2.
3.
4.
Giant Bulla > 30% of hemithorax
Severe and/or progressive dyspnea despite maximal medical therapy
PFT evidence of air-trapping (RV > 150 % pred.)
CT evidence of compression of surrounding normal lung parenchyma
Lung Transplantation
- COPD now the
#2 indication for lung transplant in US
- REFERRAL CRITERIA:
BODE index of 7-10
or
at least one of the following:
a. FEV1 < 20% and either DLCO < 20% or
homogenous distribution of emphysema
b. Pulmonary hypertension/cor pulmonale despite
O2 therapy
c. History of hospitalization for exacerbation with acute
hypercapnia (PCO2 > 50 mm Hg)
Kotloff, Thabut AJRCCM 184:159-171
7/15/11