1. GOLD Website Address

2. 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

3. 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

4. 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.

5. Mechanisms Underlying Airflow Limitation in COPD
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

7. Chronic Bronchitis
Bronchiole
Air passage narrowed by plugged and swollen mucous membrane
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
Mucus and pus impede action of respiratory cilia

8. Emphysema
Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis
Enlarged air sacs due to destruction of alveolar walls (bullae)
Destruction of the alveolar wall damages pulmonary capillaries by tearing, fibrosis, or thrombosis
Inelastic collapsible bronchioles
Walls of individual sacs torn (repair not possible)

9. Aging Populations Risk Factors for COPD Genes Infections
Global Strategy for Diagnosis, Management and Prevention of COPD
Risk Factors for COPD
Genes
Infections
Socio-economic status
Aging Populations

11. Alpha-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:
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
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

12. indoor/outdoor pollution
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
EXPOSURE TO RISK
FACTORS
SYMPTOMS
shortness of breath
tobacco
chronic cough
occupation
sputum
indoor/outdoor pollution è
SPIROMETRY: Required to establish diagnosis

13. Spirometry: Obstructive Disease
Normal 5 4 3
Volume, liters
FEV1 = 1.8L
FVC = 3.2L
FEV1/FVC = 0.56 2
Obstructive 1 1 2 3 4 5 6
Time, seconds

14. Pulmonary Function Tests in COPD8 6 4 2 -2 -4 -6
Peak expiratory flow rate
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
Forced exhalation
FEV1 (notch added by auto timer)
Forced inhalation
Normal COPD
Vital Capacity

15. Assess degree of airflow limitation using spirometry
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

16. Symptom Assessment

17. Chronic Obstructive Pulmonary Disease
William P Sexauer, MD
Division of Pulmonary and Critical Care Medicine
Thomas Jefferson University

18. In patients with FEV1/FVC < 0.70:
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 % < FEV1 < 80% predicted
GOLD 3: Severe % < FEV1 < 50% predicted
GOLD 4: Very Severe FEV1 < 30% predicted
*Based on Post-Bronchodilator FEV1

19. 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.

20. COPD patients are at increased risk for: Cardiovascular diseases
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.

21. (C) (D) (B) (A) Risk Risk Symptoms
Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD 4
(C)
(D)
> 2 3
(Exacerbation history)
Risk
(GOLD Classification of Airflow Limitation)
Risk 2
(A)
(B) 1 1
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
Symptoms
(mMRC or CAT score))

22. Spirometric Classification Exacerbations per year
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
Patient
Characteristic
Spirometric Classification
Exacerbations per year
mMRC
CAT A
Low Risk
Less Symptoms
GOLD 1-2
≤ 1
0-1
< 10 B
More Symptoms
> 2
≥ 10 C
High Risk
GOLD 3-4 D

23. 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

24. BODE Index Points 1 2 3 Body mass index (Kg/m2) >21 ≤211 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 4
Exercise (6-min walk dist, m.)
≥350
≤149
Celli BR et al., NEJM 2004; 350:

25. BODE Index  Score of 5 to 6  Score of 7 to 10  Score of 0 to 2
Celli BR et al., NEJM 2004; 350:

26. Preventive/General Measures
Smoking cessation: counseling
pharmacologic aids
- Avoid environmental/occupational exposures
Vaccinations: influenza, pneumococcal
Encourage physical activity

27. COPD Risk & Smoking Cessation
100
Never smoked or not
susceptible to smoke 75
Smoked regularly
and susceptible to
effects of smoke
Stopped smoking
at 45 (mild COPD)
FEV1 (% of value at age 25) 50
Disability
Stopped smoking
at 65 (severe COPD) 25
Death 25 50 75
Age (years)
Adapted from Fletcher C et al. Br Med J. 1977;1:1645–1648.

28. 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

29. ICS+LABA and PDE4-inh. or
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
LABA
SABA and SAMA
Theophylline B
LAMA and LABA
SABA and/or SAMA C
ICS + LABA
PDE4-inh. D
ICS and LAMA or
ICS + LABA and LAMA or
ICS+LABA and PDE4-inh. or
LAMA and LABA or
LAMA and PDE4-inh.
Carbocysteine

30. 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 ;8:

31. 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)

32. “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:
No signif difference in rate of FEV1 decline between groups
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 ;15:

33. Tiotropium vs Salmeterol
NEJM ;12:

34. Azithromycin in COPD
NEJM 365;8: /25/11

35. 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

36. Other Therapies Oxygen: Non-invasive ventilation (NIV):
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

37. Benefits of Pulmonary Rehabilitation
Strength of Evidence*
Reduction in dyspnea 1A
Increased exercise ability
Psychosocial benefits (reversal of anxiety and depression) 2B
Improved quality of life
Reduction in health care utilization
Prolongation of life (?) --
*From Joint ACCP/AACVPR Evidence-Based Guidelines on Pulmonary Rehabilitation, 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

38. 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. 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

39. 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: /15/11