1. Management of COPD: Lost Opportunities?
Kamyar Afshar, DO
Assistant Professor of Clinical Medicine
Director, USC Center for Advanced Lung Disease

2. Objectives Background Information on COPD
Surrogates of mortality in COPD
Current management strategies
How effective are we?
Barriers to effective COPD care
Proposed Model

3. Definition of COPD Chronic obstructive pulmonary disease
(COPD) is a disease state characterized by
persistent blockage of airflow from the
lungs
The airflow limitation is usually
progressive
Underwhelming definition?

4. Risk Factors for COPD
Main risk factor

5. Defense cells are normally present in the lungs
Defense cells are normally present in the lungs. When stimulated they increase in number and release protease (enzyme that breaks down lung tissue) unless counteracted by antiproteases (eg. Alpha 1-antitrypsin)

6. Domino Effect of Smoking
Airway inflammation recruits higher levels of the defense cells (neutrophils and macrophages) in the lungs; they in turn increase in the number and release of proteases
Tobacco use enhances the release of the protease enzyme as well as enhancing its activity
Tobacco also inhibits the a1AT function (decreased protective enzymes)
All this can lead to………..

7. Severe COPD/Emphysema

8. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
Proportion of 1965 Rate
3.0
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
2.5
2.0
1.5
1.0
0.5
–59%
–64%
–35%
+163%
–7%

9. COPD Mortality by Gender, U.S., 1980-2000
Number Deaths x 1000

10. Surrogates of COPD Mortality

11. Lung function over time
Rate of 35 mL/year
Modified version of Fletcher and Peto’s graph Br Med J 1977;1:1645
* Tobacco destroys a1AT function

12. Trajectory of a Patients with COPD Which part is more important
Trajectory of a Patients with COPD Which part is more important? Or other?
Symptoms
Exacerbations
Deterioration
End of Life
: FEV1, 6 min walk test; BODE index
Time

13. Classification of COPD Severity by Spirometry
FEV1 % pred
Mild Stage I
80
Moderate Stage II
50–80
Severe Stage III
30–50
Very severe Stage IV
<30
FEV1, Surrogate of Mortality?
Mannino DM. GOLD Classification of lung disease and mortality: findings from the
Atherosclerosis Risk in Communities (ARIC) study. Respir Med 2006;100:

14. Surrogates of Mortality 6-min walk
Are there strategies to improve the distance thereby decreasing mortality?
Pinto-Plata VM. The 6-min walk distatne: change over time and value as a predictor
Of survival in severe COPD. Eur Respir J 2004;23:28-33

15. Management of COPD Grading Shortness of Breath to Detect Exacerbations
Grade
Degree of breathlessness related to activity 1
Not troubled by breathlessness except on strenuous exercise 2
SOB when hurrying or walking up a slight hill 3
Walks slower than contemporaries on level ground because of breathlessness, or has to stop for breath when walking at own pace 4
Stops for breath after walking about 100 m or after a few minutes on level ground 5
Too breathless to leave the house, or breathless when dressing or undressing
Modified MRC

16. Surrogates of Mortality Dyspnea
Nishimura K. Dyspnea is a better predictor of 5-year survival than airway obstruction
In patients with COPD. Chest 2002;121:

17. Celli B. The body-mass index, airflow obstruction, dyspnea and exercise capacity
in chronic obstructive pulmonary disease. N Engl J Med 2004;350:

18. Trajectory of a Patients with COPD Which part is more important
Trajectory of a Patients with COPD Which part is more important? Or other?
Symptoms
Exacerbations
Deterioration
End of Life
: FEV1, 6 min walk test; BODE index
Time

19. Classification of COPD Severity by Spirometry
FEV1 % pred
Mild Stage I
80
Moderate Stage II
50–80
Severe Stage III
30–50
Very severe Stage IV
<30
Hurst JR, et al. Susceptibility to exacerbation in COPD.
N Engl J Med 2010;363:

20. Seemungal TAR. Time course and recovery of exacerbations in patients with
Chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:

21. COPD Exacerbation Definition
An acute change in a patient’s baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in therapy
Causes of exacerbation can be both infectious and non-infectious
Suissa S ,et al. Long-term natural history of COPD:
Severe exacerbations and mortality. Thorax 2012;67:

22. Worse Prognosis in Frequent Exacerbators
≥3 acute exacerbations requiring hospitalisation is associated with a risk of death 4.30 times greater than for those patients not requiring hospitalization
Time (months) 10 20 30 40 50 60
0.2
0.4
0.6
0.8
1.0
Probability of surviving
p<0.0001 A B C
p=0.069
p<0.0002
Group A
Patients with no acute exacerbations
Group B
Patients with 1–2 acute exacerbations of COPD requiring hospital management
Group C
Patients with ≥3 acute exacerbations of COPD requiring hospital management
Key message:
Patients with more exacerbations have a higher risk of mortality
Soler-Cataluña et al. Thorax 2005; 60:

23. Current COPD Management Strategies

24. While incurable, proper management of COPD can:
COPD Management Goals
While incurable, proper management of COPD can:
Improve quality of life
Improve exercise (functional) capacity
Reduce exacerbation rates and prevent progression of disease
Prevent and treat complications
Reduce mortality
It will not improve lung functions

25. Therapy based of stage of COPD
IV: Very Severe
FEV1/FVC < 70%
FEV1 < 30% predicted
or FEV1 < 50% predicted plus chronic respiratory failure
III: Severe
FEV1/FVC < 70%
30% < FEV1 < 50% predicted
II: Moderate
FEV1/FVC < 70%
50% < FEV1 < 80%
predicted
I. Mild
FEV1/FVC < 70%
FEV1 > 80% predicted
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Add long term oxygen if chronic respiratory failure. Consider surgical treatments

26. Combined Assessment of COPD Prediction for Exacerbations
Patient is now in one of
four categories:
A: Less symptoms, low risk
B: More symptoms, low risk
C: Less symptoms, high risk
D: More symptoms, high risk 4
(C)
(D)
> 2 3
(Exacerbation history)
Risk
(GOLD Classification of Airflow Limitation)
Risk 2
(A)
(B)
<2 1
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
Symptoms
GOLD 2011

27. Manage Stable COPD: Pharmacologic Therapy
Groups A, B, C or D severity assessment based on:
FEV1: GOLD 1, 2, 3 and 4
Symptoms (mMRC or CAT questionnaires) score
Exacerbations/year
(C)
(D)
 LABA/ICS or LAMA
  LABA/ICS or LAMA
LABA + LAMA
LABA/ICS + LAMA; LABA/ICS + PDE4; LAMA + PDE4
 SABA or SAMA p.r.n.
 LAMA or LABA
SABA + SAMA; LABA or LAMA
LABA + LAMA 
(A)
(B)
GOLD 1
GOLD 2
GOLD 3
GOLD 4
Exacerbations per year ≥2
<2
Reference:
Revised GOLD
mMRC 2+
CAT 10+
mMRC 01 CAT <10
GOLD 2011

28. Phenotypic Variance All patients COPD
should be treated distinctly because there is a phenotypic variance (behave differently):
COPD/Emphysema
COPD/Chronic Bronchitis
COPD/Asthma
Exacerbator phenotype
Alpha 1-antitrypsin deficiency

29. Co-Morbidities for COPD
DivoM. Comorbidity and risk of mortality in patients with COPD. Am J Respir Crit Care 2012;186:

30. Co-Morbidities for COPD
Diagnosis
Men (%)
Women (%)
Myocardial Infarction 27 14
Congestive Heart Failure 3 7
HTN 57 53
Dyslipidemia 49 54
GERD 60 68
Sinus issues 51 65
Anxiety/Depression 44
Osteoporosis 12 39
Cancer 4 6
Diabetes 26 25
Stroke 11 16
Known barrier to successful smoking cessation
& adherence
DivoM. Comorbidity and risk of mortality in patients with COPD. Am J Respir Crit Care 2012;186:

31. Is this related to tobacco + alcohol? Or something else?
Cirrhosis
Emphysema CXR
Is this related to tobacco + alcohol? Or something else?

32. Approximately 3% of COPD patients have alpha 1-antitrypsin deficiency
Cirrhosis
Emphysema CXR
Approximately 3% of COPD patients have
alpha 1-antitrypsin deficiency

33. Prevalence
3.4 million individuals with mutant AAT allele combinations worldwide1
PiZZ = 173,430
PiSZ = 1,011,069
PiSS = 2,260,801
Based on direct population screening studies, prevalence of PiZZ in the US may be 70,000
Only approximately 5,000 individuals in the US are currently diagnosed with PiZZ
95% undiagnosed
Stoller JK. A review of alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2012;185:

34. Alpha1 - Antitrypsin Deficiency
Phenotype
Serum levels
microMolar
Mg/dL
Risk of Lung Damage
Risk of Liver Damage
PiMM
20-53
PiMS
18-52
PiSS
20-48
PiMZ
15-42
80-100
Possibly Increased
PiSZ
10-23
40-80
Increased
PiZZ
3-7
15-50
Very High
High
PiNull
Very high
None
PiMZ: rarely have serum levels below protective threshold
PiSZ: 10% will have levels below protective threshold
PiZZ: below the protective threshold

35. Range of serum levels
Adapted from The Alpha-1 Foundation slide set.
Courtesy of H. Ari Jaffe, MD
Bottom normal level
Protective threshold
When you check the levels in the blood, they may not always be reliable values
Acute phase reactants
Value can be increased 4-fold in an inflammatory state

36. PiMZ and PiMM
When comparing PiMZ and PiMM, the degree of obstruction was more in the PiMZ group
Even in low smoking history, PiMZ individuals had more severe emphysema on the CT scan
Sorheim IC. A1-antitrypsin protease inhibitor MZ heterozygosity is associated with
airflow obstruction in two large cohorts. Chest 2010; 138:

37. Smoking, Lung Function and a1AT 33 PiZZ patients with emphysema
Age of onset of SOB
Avg FEV1 value
Rate of FEV1 decline
Age of Death
Smokers
32 years
38%
316 mL/yr
48 years
Non-smokers
51 years
77%
80 mL/yr
67 years
normal FEV1 declines mL/ yr after age 35
Janus ED. Smoking, lung function and alpha1 antitrypsin deficiency. Lancet 1985;

38. Actively address the Co-morbidity issues
Augmentation therapy for qualified patients w/ Alpha 1-antitrypsin deficiency
Actively address the Co-morbidity issues
Smoking cessation, immunizations
Pulmonary Rehabilitation
Miravitles M, et al. A new approach to grading and treating COPD based on clinical phenotypes: summary of the Spanish COPD guidelines. Prim Care Respir Med J 2013;22:

39. Recommendations vs. Current Practice
De Oliviera JCM. Clinical significance in COPD patients followed
In real practice. Multidisiplinary Respiratory Medicine 2013;8:43

40. Utilization of post exacerbation pulmonary rehab over 3 months
Pulmonary Rehab improves functional capacity as well as exacerbation rates
Usual Care
Pulm Rehab
OR (95% CI) Pulm Rehab vs usual care
P value
Total participants
30 patients
Hospital admission for 2nd exacerbation
10 (33%)
2 (7%)
0.15 (0.03 – 0.72)
0.02
Hospital or ED attendance for 2nd exacerbation
17 (57%)
8 (27%)
0.28 (0.10 – 0.82)
1. Seymour JM. Outpatient pulmonary rehabilitation following acute
exacerbations of COPD. Thorax 2010;65:
2. Puhan MA. Pulmonary rehabilitation following exacerbations for chronic
obstructive pulmonary disease.Cochrane Database Syst Rev 2011;10:CD005305

41. Participate rates in pulmonary rehab
Once enrolled, there is a low drop out from 9.7%
34-49% of participants attend after being referred to pulmonary rehab
Why the discrepancy?
1. Spruit MA. What to do before pulmonary rehabilitation to improve adherence? Chron Respir Dis 2010;7:
2. Harris D. Improving he uptake of pulmonary rehabilitation in patients with COPD. Br J Gen Pract 2008;58:
3. Sohanpal R. Reporting participation rates in studies of non-pharmacological interventions for patients with chronic
obstructive pulmonary disease: a systematic review. Systematic Reviews 2012;1:66

42. Barriers to “referral” to PR
Perceived costs
Perceived to only be for end-stage category
Reserved for those with impaired functional status; physical challenges
Patient motivation
Transportation issues
Time

43. Barriers to Effective COPD Management
- Access - Physician Knowledge - Patient Adherence

44. Principles of Value-Based Care
“Patients will have access to healthcare providers and quality of care will be improved, thereby cutting the costs”
Implementing known best practices
Better diagnosis means that the right condition is treated, improving outcomes and avoiding ineffective treatments

45. “Increased Access to Care”
Access (Merriam-Webster dictionary)
A way of getting near, at, or to something or someone
Freedom or ability to obtain or make use of something
An increase by addition < a sudden access of wealth>

46. “Increased Access to Care”
A way of getting near, at, or to office clinic or healthcare provider or tools for proper assessment
Freedom or ability to obtain or make use of educational opportunities
An increase by addition < a sudden access of health; time spent with the provider>

47. Health Care Professional Responsibilities
Ensuring an accurate diagnosis
Determining appropriate phenotype, testing for alpha 1-antitrypsin deficiency
Appropriate monitoring
Spirometry, Dyspnea scoring system, 6 min walk
Recognizing exacerbation events
Prescribing appropriate treatment
Assessing the effectiveness/adherence
Access to the medications (eg. 30 day vs. 90 day supply, financial restrictions, social stigma, etc)

48. Primary Care Setting Surveyed 3,265 patients worldwide1
68% of COPD patients are seen in primary care setting1
32% of COPD patients with pulmonary specialists1
In Family Medicine clinics, 58% (4.6 hours/day) of all visits are for acute problems and their follow up care2
“acute care takes precedence over both prevention and chronic disease management”
Halpern MT. The burden of COPD in the USA. Results from Confronting COPD survey. Resp Med 2003;97:S81-S89
Ostbye T. Is there time for management of patients with Chronic disease in primary care? Ann Fam Med 2005;3:

49. Percentage of patients reporting > 1 class of prescribed medication
Patients reporting at least 1 lab test for COPD during the 12 months prior to the survey
Halpern MT. The burden of COPD in the USA. Results from
Confronting COPD survey. Resp Med 2003;97:S81-S89

50. Barriers to COPD care delivery
Lack of office logistics
Spirometry
Knowledge of guideline recommendations
Proper recognition of COPD and co-morbidities
Time constraints. The recommended minimum time to provide high quality medical management for COPD is………..

51. Duke University
Ostbye T. Is there time for management of patients with
Chronic disease in primary care? Ann Fam Med 2005;3:

52. Influences of COPD Adherence
Bourbeau J. Patient adherence in COPD. Thorax 2008;63:

53. Trialed Protocol
Primary Care: specific clinics with access to spirometry, pulse oximetry, nebulizers and oxygen
Include a trained specialist nurse
Smoking cessation program
Patient education

54. Measures at exacerbation visit 1
Multicenter analysis:
22 month follow up
= 458
Sundh J. Management of COPD exacerbations in primary care: a clinical cohort study.
Prim Care Respir J 2013;22: online ahead print

55. Planned follow-up and time to a second exacerbation
238 pts had a 2nd exacerbation
Extra planned visit to nurse
Extra planned visit or telephone call by doctor
No extra scheduled visit
Sundh J. Management of COPD exacerbations in primary care: a
clinical cohort study. Prim Care Respir J 2013;22: online ahead print

56. In Closing….
A proactive and integrated approach with each discipline utilizing their strengths can improve the quality of life for individuals with COPD
Preventative Care
Immunizations
Social Support Network
Caregivers
Support Group Meetings
Individualized Treatment Plans
Based on phenotypes and exacerbation history
Home spirometry
Address Co-morbidities
Depression, axiety
Pulmonary hypertension
Cardiac disorders
Physician
Primary care
Specialist
Nurse Coordinator
Physical , Respiratory &
Occupational Therapist
Pharmacist
Medical Social Worker
Registered Dietician
Psychologist
Psychiatry

57. THANK YOU