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

Symptom AssessmentSymptom Assessment

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