GOLD Website Address
http://www.goldcopd.org
Which of the following have been shown to reduce mortality in COPD?
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
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 COPDBurden 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
- 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 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•Airway inflammation•Airway fibrosis, luminal plugs•Increased airway resistance
Parenchymal Destruction•Loss of alveolar attachments•Decrease of elastic recoil
AIRFLOW LIMITATION
Chronic Bronchitis
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
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
Bronchiole
Air passage narrowed by plugged and swollen mucous membrane
Mucus and pus impede action of respiratory cilia
EmphysemaEmphysemaAbnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis
Inelastic collapsible bronchioles
Enlarged air sacs due to destruction of alveolar walls (bullae)
Walls of individual sacs torn (repair not possible)
Destruction of the alveolar wall damages pulmonary capillaries by tearing, fibrosis, or thrombosis
Global Strategy for Diagnosis, Management and Prevention of COPD
Risk Factors for COPD
GenesGenes
InfectionsInfections
Socio-economic Socio-economic statusstatus
Aging PopulationsAging Populations
Alpha-1-Antitrypsin DeficiencyAlpha-1-Antitrypsin Deficiency
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.
Suspect in patients with:1. COPD in a never smoker2. COPD at a very young age3. Strong family history of COPD4. Emphysema more prominent in lung bases5. COPD with unexplained liver disease
Diagnosis via serum level, genetic testing
Treat with alpha-1-antitrypsin replacement therapy. Intermittent IV infusion slows the rate of decline in lung function in those with airflow obstruction
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.
Suspect in patients with:1. COPD in a never smoker2. COPD at a very young age3. Strong family history of COPD4. Emphysema more prominent in lung bases5. COPD with unexplained liver disease
Diagnosis via serum level, genetic testing
Treat with alpha-1-antitrypsin replacement therapy. Intermittent IV infusion slows the rate of decline in lung function in those with airflow obstruction
SYMPTOMS
chronic cough chronic coughshortness of breathshortness of breath
EXPOSURE TO RISKFACTORS
tobaccotobaccooccupationoccupation
indoor/outdoor pollutionindoor/outdoor pollution
SPIROMETRY: Required to establish diagnosis
SPIROMETRY: Required to establish diagnosis
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
sputum sputum
Spirometry: Obstructive Disease
Volu
me,
liters
Time, seconds
5
4
3
2
1
1 2 3 4 5 6
FEV1 = 1.8L
FVC = 3.2L
FEV1/FVC = 0.56
Normal
Obstructive
8
6
4
2
0
-2
-4
-6
Vital Capacity1 2 3 4
Peak expiratory flow rate
Forced exhalation
FEV1 (notch added
by auto timer)
Forced inhalation
Normal 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
Pulmonary Function Tests in COPD
Pulmonary Function Tests in COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Assess symptomsAssess degree of airflow limitation using spirometry
Assess risk of exacerbations
Assess comorbidities
Assess symptomsAssess degree of airflow limitation using spirometry
Assess risk of exacerbations
Assess comorbidities
Chronic Obstructive Pulmonary DiseaseChronic Obstructive Pulmonary Disease
William P Sexauer, MD
Division of Pulmonary and Critical Care Medicine
Thomas Jefferson University
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
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.
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
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.
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
Combined Assessment of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPD
Ris
k (G
OLD
Cla
ssifi
catio
n of
Air
flo
w L
imit
atio
n)
Ris
k (E
xace
rbat
ion
hist
ory)
> 2
1
0
(C) (D)
(A) (B)
mMRC 0-1CAT < 10
4
3
2
1
mMRC > 2CAT > 10
Symptoms(mMRC or CAT score))
Patient Characteristic Spirometric Classification
Exacerbations per year
mMRC CAT
ALow Risk
Less SymptomsGOLD 1-2 ≤ 1 0-1 < 10
BLow Risk
More SymptomsGOLD 1-2 ≤ 1 > 2 ≥ 10
CHigh Risk
Less SymptomsGOLD 3-4 > 2 0-1 < 10
DHigh Risk
More SymptomsGOLD 3-4 > 2 > 2
≥ 10
Global Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPDWhen assessing risk, choose the highest risk according to GOLD grade or exacerbation history
The term “BODE” refers to which of the following:
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
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 IndexBODE Index
Points
0 1 2 3
Body mass index (Kg/m2) >21 ≤21
Obstructive airways disease (FEV, % pred) ≥ 65 50-64 36-49 ≤35
Dyspnea (MMRC scale) 0-1 2 3 4
Exercise (6-min walk dist, m.) ≥350 250-349 150-249 ≤149
Celli BR et al., NEJM 2004; 350:1005-12
Score of 0 to 2
Score of 3 to 4
Score of 5 to 6
Score of 7 to 10
BODE IndexBODE Index
Celli BR et al., NEJM 2004; 350:1005-12
Preventive/General MeasuresPreventive/General Measures
- Smoking cessation: counseling
pharmacologic aids
- Avoid environmental/occupational exposures
- Vaccinations: influenza, pneumococcal
- Encourage physical activity
- Smoking cessation: counseling
pharmacologic aids
- Avoid environmental/occupational exposures
- Vaccinations: influenza, pneumococcal
- Encourage physical activity
FE
V1 (
% o
f va
lue
at
age
25
)
Age (years)Adapted from Fletcher C et al. Br Med J. 1977;1:1645–1648.
COPD Risk & Smoking CessationCOPD Risk & Smoking Cessation
0
25
50
75
100
25 50 75
Death
Disability
Never smoked or not susceptible to smoke
Smoked regularlyand susceptible toeffects of smoke
Stopped smoking at 45 (mild COPD)
Stopped smoking at 65 (severe COPD)
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.)
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
ASAMA prn
or SABA prn
LAMA or
LABA or
SABA and SAMA
Theophylline
BLAMA
or LABA
LAMA and LABASABA and/or SAMA
Theophylline
C
ICS + LABAor
LAMALAMA and LABA
PDE4-inh.SABA and/or SAMA
Theophylline
D
ICS + LABAor
LAMA
ICS and LAMA orICS + LABA and LAMA or
ICS+LABA and PDE4-inh. orLAMA and LABA or
LAMA and PDE4-inh.
CarbocysteineSABA and/or SAMA
Theophylline
TORCH StudyTORCH 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
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
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)
- 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“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
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 SalmeterolTiotropium vs Salmeterol
NEJM 2011 364;12:1093-103 NEJM 2011 364;12:1093-103
Azithromycin in COPDAzithromycin in COPD
NEJM 365;8:689-698 8/25/11 NEJM 365;8:689-698 8/25/11
Pharmacologic Interventions shown to reduce COPD Exacerbations
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
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 TherapiesOther 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
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
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 COPDSurgical 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. Giant Bulla > 30% of hemithorax
2. Severe and/or progressive dyspnea despite maximal medical therapy
3. PFT evidence of air-trapping (RV > 150 % pred.)
4. CT evidence of compression of surrounding normal lung parenchyma
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. Giant Bulla > 30% of hemithorax
2. Severe and/or progressive dyspnea despite maximal medical therapy
3. PFT evidence of air-trapping (RV > 150 % pred.)
4. CT evidence of compression of surrounding normal lung parenchyma
Lung TransplantationLung 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
- 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