Chronic Obstructive Pulmonary Disease and Pulmonary Rehabilitation

1
Chronic Obstructive Pulmonary Disease and
Pulmonary Rehabilitation

• Peter Frith
• Respiratory Services
• Southern Adelaide Health Service

2
Plan

• What is COPD
• How to diagnose COPD correctly
• Matching treatment to patient and disease
  severity
• Thinking about co-morbidities / consequences
• Roles for drug therapy
• Roles for other interventions
• In particular, Pulmonary Rehabilitation

3
COPD Definition

• Inflammatory disease of the airways and lungs
• Triggered by inhaling noxious particles
• Some genetic factors
• Causing consistent symptoms
• Causing progressive dyspnoea and cough /- sputum
  
• Characterised by airflow limitation
• Poorly responsive to bronchodilators and steroids
• Preventable, treatable, but incurable

4
COPD is a syndrome

Chronic Bronchitis

Emphysema
COPD

AirflowLimitation
Asthma
1. NHLBI/WHO. 2004. Available at
www.goldcopd.com 2. McKenzie DK et al. Med J
Aust 2003 178 (Suppl) S1S40.
5
COPD-X Management Plan
McKenzie DK et al. Med J Aust 2003 178 (Suppl)
S1S40
6
Diagnosis of COPD

• Consider a clinical diagnosis of COPD in any
  patient over age 35 who has..
• Dyspnoea
• Chronic cough
• Sputum production
• Exposure to risk factors for the disease
• Confirm diagnosis by spirometry
• FEV1/FVC ratio lt0.70
• Comorbidities are common in COPD and should be
  actively identified

7
Symptoms dont predict Clinical Diagnosis
Frith P, Crockett A, et al. TSANZ, ERS, 2004
8
COPD is under-diagnosed in Australia

• Random sample from Melbourne electoral roll1
• 1224 adults (45-70 years old)
• 79 (6.5) had COPD
• 34 of these had no respiratory diagnosis from
  their doctor

Matheson M, et al. Int Med J 2006 36 92-99
9
Underdiagnosis of COPD in the United States

• Over 12.7 million people in the United States
  diagnosed with COPD1
• NHANES III indicates approximately 24 million US
  adults have impaired lung function indicating
  COPD2,3
• Most (70) patients with undiagnosed COPD are lt65
  years of age

30 Age 65
70 ltAge 65
Percent with Undiagnosed COPD
1. Pleis JR, et al. Vital Health Stat. 2006132
1-153 2. Mannino DM, et al. MMWR Surveill Summ.
2002511-16 3. Mannino DM, et al. Proc Am
Thorac Soc. 20074502-306.
10
Underdiagnosis of COPD in China

• A survey of 25,627 adults in China indicated that
  8.2 had COPD (FEV1/FVC lt0.70)

Zhong N, et al. Am J Respir Crit Care Med.
2007176753-760.
11
COPD Misdiagnosis Is Common in Women
Hypothetical Male Patient With COPD Symptoms
Diagnosed as COPD by 65 of physicians
65
49
Hypothetical Female Patient With COPD Symptoms
Diagnosed as COPD by 49 of physicians
COPD symptoms in women were most commonly
misdiagnosed as asthma
Chapman KR, et al. Chest. 20011191691-1695.
12
Diagnosis through point-of-care tests

• The FEV1 / FEV6
• Simple lung function tool
• Uses FEV6 as a surrogate marker of FVC
• Measures FEV1, FEV6 and the ratio of FEV1/FEV6
• Enables easy screening of respiratory conditions
• Is a reliable indicator of whether full
  spirometry testing is required

13
Differential Diagnosis COPD and Asthma
COPD
ASTHMA

• Chronic cough
• Onset in mid-life
• Symptoms slowly progressive
• Long smoking history
• Dyspnoea during exercise
• Largely irreversible airflow limitation

• Onset early in life (often childhood)
• Symptoms vary from day to day
• Symptoms at night/early morning
• Allergy, rhinitis, and/or eczema also present
• Family history of asthma
• Largely reversible airflow limitation

From the Global Strategy for the Diagnosis,
Management, and Prevention of Chronic Obstructive
Pulmonary Disease, Global Initiative for Chronic
Obstructive Lung Disease (GOLD) 2008
http//www.goldcopd.org.
14
Risk Factors for COPD
GOLD Update. 2006.
14
15
Age, Smoking Severity of COPD
GOLD stage 1 (mild) GOLD stage 2 (moderate) GOLD
stage 3-4 (severe)
From Plan and operation of the Third NHANES,
198894. Series 1 programs and collection
procedures. Vital Health Stat, 1 1994 Jul 1407
16
COPD Impact

• COPD is in the top four conditions in Australia
  for
• Prevalence
• Mortality
• Hospitalisations
• Individual burden
• Costs

17
Burden of COPD in Australia1

• GOLD stages I to IV over 2 million
• 47 are of working age (15-64)
• 57 females
• Stages II to IV (symptomatic) 1.2 million
• 10.2 prevalence in over-40 year-olds2
• projected to double by 2050
• Costs are enormous and largely hidden
• Direct health-related costs 0.9 billion
• Lost productivity costs 6.8 billion
• Indirect costs 1.2 billion

1 Access Economics. Economic impact of COPD and
cost effective solutions. ALF. 2008 2 Buist AS et
al. The BOLD Study. Lancet 2007 370741-750
18
Volume of Airway Wall Tissue Correlates
Significantly with Disease Progression
GOLD Stage 4
GOLD Stage 3
GOLD Stage 2
GOLD Stages 0 and 1
0.25 0.20 0.15 0.10 0.05 0
VSA (mm)
0 20 40
60 80 100 120
FEV1
Hogg JC et al. New Engl J Med 2004 350
26452653.
19
Sputum Neutrophils vs Decline in Lung Function
P lt 0.01
100
90
80
70
Neutrophils in Induced Sputum ()
60
50
40
0
gt 30
lt 20
20 30
FEV1 Decline (mL/Year)
Stanescu et al. Thorax. 199651267-271.
20
Systemic Inflammation is greater with more severe
COPD
CRP (mg/L) TNF-a
(?g/mL)
Severe COPD
Severe COPD
Moderate COPD
Moderate COPD
Mild COPD
Mild COPD
Healthy
Healthy
0
20
30
40
50
60
70
10
0
40
100
60
80
20
Franciosi et al. Pulm Pharmacol Ther.
200619189-199.
21
Progression of COPD
2.9
2.8
2.7
Sustained Quitters
2.6
2.5
Intermittent Quitters
2.4
FEV1 (Liters)
2.3
2.2
Continuous Smokers
2.1
2.0
0
1
2
3
4
5
6
7
8
9
10
11
Year
Anthonisen et al. Am J Respir Crit Care Med.
2002166675-679.
22
Systemic Comorbiditites in COPD

• Cardiovascular
• Angina
• CHF
• Arrhythmias
• Systemic Hypertension
• Pulmonary Hypertension
• Metabolic
• Diabetes
• Obesity
• Orthopaedic
• Osteoporosis
• Locomotive

• Gastrointestinal
• Ulcer Disease
• Hematologic
• Malignancies
• Anaemia
• Psychiatric
• Depression
• Insomnia
• Ophthalmologic
• Cataracts

Agusti et al. Eur Respir J. 200321347-360
Sevenoaks, Stockley. Respir Res. 2006770-78
Gartlehner et al. Ann Fam Med. 20064253-262.
23
Effect of BMI on mortality
Chailleux, E. et al. Chest 20031231460-1466
24
Hospitalisation due to comorbidities
Holguin et al. Chest. 20051282005-2011.
25
Progression of COPD
Noxious stimulus
Lunginflammation
COPD
Mucushypersecretion
Airwayobstruction
Continued smoking
Impairedmucus clearance
Exacerbation
Exacerbation
Submucosal glandhypertrophy
Alveolardestruction
Exacerbation
Hypoxemia
Ventilatory Failure
DEATH
GOLD Update. 2006.
26
Interim Summary

• Spirometry is the Gold Standard diagnostic tool
  for COPD
• Spirometry helps differentiate asthma from COPD
• Respiratory symptoms are unreliable nonspecific
• symptoms are often not reported or sought
• Symptom-based questionnaires are complex
  unreliable
• Spirometry is seen to be unrewarding
• Simple airflow measurement is feasible and
  reliable
• Doctors can be trained to appreciate
  point-of-care case detection tools for COPD
• Non-respiratory (and respiratory) co-morbidities
  must be considered in patient management

27
Stages of COPD Treatment
From the Global Strategy for the Diagnosis,
Management, and Prevention of Chronic Obstructive
Pulmonary Disease, Global Initiative for Chronic
Obstructive Lung Disease (GOLD) 2008
http//www.goldcopd.org.
28
Interventions that help in COPD

• Remove stimulus (NB smoking)
• Improve lifestyle (eg nutrition, activity)
• Vaccinations
• Medications
• Pulmonary rehabilitation
• Disease Management
• Self-treatment protocols
• Oxygen for hypoxaemia
• Palliative strategies

29
Effects of ICS alone on Mortality
30
All-cause mortality at 3 years in TORCH
Probability of death ()
18 16 14 12 10 8 6 4 2 0
HR 0.825, p0.052 17.5 risk reduction
2.6 absolute reduction
Placebo
Ser
SFC
0
12
24
36
48
60
72
84
96
108
120
132
144
156
Time to death (weeks)
Number alive
1524 1533 1521 1534
1464 1487 1481 1487
1399 1426 1417 1409
1293 1339 1316 1288
Vertical bars are standard errors
Calverley et al. NEJM 2007
31
Long-acting bronchodilators prevent COPD
Exacerbations
P.025
1.8
DBPCRCT 6 months n 1,2007
1.6
1.49
1.4
1.23
1.2
1.07
1.0
Number of Exacerbations per Patient Year
0.8
0.6
0.4
0.2
0.0
Tiotropium
Salmeterol
Placebo
Brusasco V, et al. Thorax. 200358399-404.
32
Tiotropium prevents COPD exacerbations
Placebo included salbutamol, inhaled and oral
steroids (up to 10 mg/day of prednisone or
equivalent) and theophyllines
Adapted from Barr RG et al. Thorax 20066185462
33
ICS prevent Exacerbations
34
Cost-Effective Solutions

• Early diagnosis offers earlier interventions
• Detecting airflow limitation increases quit
  smoking rates
• Bednarek M et al. Thorax 2006 61869-873
• Telling people their lung age increases quit
  smoking rates
• Parkes G et al. BMJ May 2008
• Smoking cessation reduces lung function decline
  and prolongs life
• Fletcher C, Peto R. BMJ 1977 i1645-1648
• Burchfeld CM et al. Am J Respir Crit Care Med
  1995 1511778-1785
• Anthonisen NR et al. Am J Respir Crit Care Med
  2002 166675-679

35
Cost-Effective Solutions

• Disease Management reduces hospitalisation with
  COPD
• Supported discharge programs
• Sala E et al. Eur Respir J 2001 171138-1142
• Chronic disease integrated management programs
• Rea H et al. Intern Med J 2004 34608-614
• Self management education by case manager
• Bourbeau J et al. Am J Chest Phys 2006
  1301704-1711
• Self management programs
• Effing T et al. Cochrane Database Syst Rev 2007
  Issue 4

36
Cost-Effective Solutions

• Pulmonary Rehabilitation
• Improves maximum exercise capacity and activity
• Improves quality of life and emotional burden
• Reduces dyspnoea and fatigue
• Reduces hospitalisation and primary care resource
  use
• Improved confidence and reduced dependency
• Cambach W et al. Arch Phys Med Rehabil 1999
  80103-111
• Lacasse Y et al. Cochrane Database Syst Rev 2002
  Issue 3
• Lacasse Y et al. Cochrane Database Syst Rev 2006
  Issue 2

37
Limitations in Activities for COPD Patients
100
lt 65 Years gt 65 Years P lt 0.05
80

60
Subjects limited ()
40
20
0
Sportsand Recreation
Normal Physical Exertion
Social
Sleep
Household Chores
SexLife
Family
Activity
Rennard et al. Eur Respir J. 200220799-805.
38
Goals Pulmonary of Rehab

• Control alleviate symptoms
• Improve activity tolerance
• Promote self-reliance independence
• Decrease need for acute resources
• Improve quality of life

39
Pulmonary Rehabilitation includes

• Education of patient and carers
• training to enable self-management
• Exercise training
• general aerobic training
• upper extremity training
• inspiratory muscle training
• breathing re-training
• Nutritional advice
• Psychosocial support and home care

40
Benefits of Rehabilitation

• Statistically significant changes in
• 6-min walk distance in 89 (by mean 59m)
• MRC dyspnoea in 62 (by mean 0.41)
• CRQ dyspnoea in 67 (by mean 0.65)
• BDI/TDI in 64 (halved from 1.4 to 0.7)
• CRQ mastery in 60 (by mean 0.77)
• VAS peak exercise (by mean 1.1)
• indicates clinically significant changes

de Torres et al. Chest 2002 1211092
41
Pulmonary Rehabilitation Quality of Life
Griffiths et al. Lancet. 2000355362-368.
42
Effects of Pulmonary Rehab (RCT)
Cafarella et al. TSANZ, ATS, ERS 2001-2003
43
Pulmonary Rehab Self-Management (RCT)
Cafarella et al. TSANZ, ATS, ERS 2001-2003
44
Carer health in COPD

• COPD Carers completed more tasks than age-matched
  population norms
• Caregivers social activities were restricted

Cafarella P et al. APSR 2006
45
Cost-effectiveness of Rehab

• RCT (n89) 2 months Inpatient Rehab 4 mo
  maintenance
• CRDQ benefits (Rehab vs usual care)
• dyspnoea NNT for benefit 4.1
• fatigue NNT 4.4
• emotional NNT 3.3
• mastery NNT 2.5
• Total cumulative incremental cost of Pulmonary
  Rehab CAN11,597 pp
• Goldstein et al. Chest 1997112370-379
• 37 reduction in hospital bed-days
• Cecins N et al. Aust Hlth Rev 2008 32415-422

46
Interim Summary

• Pulmonary Rehabilitation is effective and safe
• For the patient
• For the carer
• For health care systems

47
Management in Later Stages

• Disease Management
• Team-care arrangements
• Self-treatment training
• Action plans
• Seamless transitions between home / community
  secondary / tertiary hospitals
• Oxygen therapy
• Palliation for dyspnoea
• Proactive planning for extreme exacerbations

48
Therapy recommendations
Adapted from Pauwels RA, et al. GOLD 2004 Buist
S, et al. GOLD 2006 www.goldcopd.org
49
Therapy recommendations
Discuss advance directives Consider palliative
support
Adapted from Pauwels RA, et al. GOLD 2004 Buist
S, et al. GOLD 2006 www.goldcopd.org
50
Therapy recommendations
Promote and guide non-smoking status
REHABILITATION
Chronic Disease Management
Discuss advance directives Consider palliative
support
Adapted from Pauwels RA, et al. GOLD 2004 Buist
S, et al. GOLD 2006 www.goldcopd.org
51
X - Early Diagnosis and Action in Exacerbations

• Early diagnosis and treatment may prevent
  hospital admission
• Educate patients/carers to recognise early signs
  of deterioration
• Self-management plan
• Prompt assessment and treatment may prevent
  crises
• Assess severity
• Crisis medication pack

McKenzie D, et al. COPDX. MJA 17 March 2003 178
(Suppl)S27-S28
52
X - COPD Exacerbations

• Exacerbations can occur with any severity of COPD
• Most often in the most severe disease
• Exacerbations determine survival
• Cochrane exacerbation treatment reviews
• Antibiotics (speed clearance)
• Systemic steroids (improve survival)
• Early intervention (delay in treating increases
  duration)
• Self-management education (reduces
  re-hospitalisation)
• Action plans (reduce hospitalisations)
• Non-invasive ventilation (speeds recovery from
  ventilatory failure)

53
Summary

• COPD is common, and under-recognised
• Think of the diagnosis of COPD
• Clinical tools are unreliable
• Spirometry is the diagnostic standard
• There are treatments that work
• Improve quality of life, mental health
• Prevent exacerbations
• Prolong life?????
• Pulmonary rehabilitation is the most
  cost-effective (and effective) treatment for COPD