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Pulmonary Rehabilitation For Chronic Obstructive Pulmonary Disease (PDFDrive)

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Canadian Agency for Agence canadienne

Drugs and Technologies des médicaments et des


in Health technologies de la santé

t e c h n o l o g y r e p o r t

HTA
Issue 126
Pulmonary Rehabilitation for Chronic
Obstructive Pulmonary Disease: Clinical,
Economic, and Budget Impact Analysis
March 2010

Supporting Informed Decisions


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Cite as: Hailey D, Jacobs P, Stickland M, Chuck A, Marciniuk DD, Mayers I, Mierzwinsky-Urban M.
Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease: Clinical, Economic, and
Budget Impact Analysis [Technology report number 126]. Ottawa: Canadian Agency for Drugs and
Technologies in Health; 2010.

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Canadian Agency for Drugs and Technologies in Health

Pulmonary Rehabilitation for Chronic Obstructive Pulmonary


Disease: Clinical, Economic, and Budget Impact Analysis

David Hailey, MSc PhD Grad RIC1


Philip Jacobs, DPhil2
Michael Stickland, PhD2
Anderson Chuck, MPH PhD2
Darcy D. Marciniuk, MD, FRCP(C), FCCP3
Irvin Mayers, MD, FRCPC2
Monika Mierzwinski-Urban, MLIS4

March 2010

1
Institute of Health Economics, Edmonton, Alberta
2
University of Alberta, Edmonton, Alberta
3
University of Saskatchewan, Saskatoon, Saskatchewan
4
Canadian Agency for Drugs and Technology in Health, Ottawa, Ontario
Reviewers
External Reviewers
These individuals kindly provided comments on this report.

Paul Hernandez, MDCM FRCPC Michelle McIsaac, MA


Associate Professor of Medicine, Health Economist,
Dalhousie University University of Melbourne
Halifax, Nova Scotia Victoria (Parkville), Australia

W. Darlene Reid, BMR(PT) PhD Ron Goeree, MA


Professor, Department of Physical Therapy, Associate Professor, Clinical
University of British Columbia Epidemiology & Biostatistics,
Vancouver, British Columbia McMaster University
Director, PATH Research Institute,
St. Joseph’s Healthcare Hamilton
Hamilton, Ontario

Nick Barrowman, PhD


Senior Scientist,
Children’s Hospital of Eastern Ontario
Clinical Research Institute
Ottawa, Ontario

CADTH Peer Review Group Reviewers


Robert Dales, MD MSc FRCPC Chris Skedgel, MDE
Professor of Medicine, Research Health Economist, Department
University of Ottawa of Medicine
The Ottawa Hospital Dalhousie University
Ottawa, Ontario Halifax, Nova Scotia

This report is a review of existing public literature, studies, materials, and other information and
documentation (collectively the “source documentation”),which are available to CADTH. The
accuracy of the contents of the source documentation on which this report is based is not
warranted, assured, or represented in any way by CADTH and CADTH does not assume
responsibility for the quality, propriety, inaccuracies, or reasonableness of any statements,
information, or conclusions contained in the source documentation.

CADTH takes sole responsibility for the final form and content of this report. The statements and
conclusions in this report are those of CADTH and not of its Panel members or reviewers.

Authorship
David Hailey coordinated the project, steered the preparation of the protocol, and integrated the
components of the study. He led and drafted the clinical review, contributed to the economic
analysis, and coordinated the response to reviewers’ comments.

i PR for COPD: Clinical, Economic, and Budget Impact Analysis


Philip Jacobs developed the study plan, was responsible for the review of economic literature,
steered development and use of the economic model, and drafted the economic analysis and
budget impact sections.

Michael Stickland participated in the clinical review, including study selection, data extraction,
and quality assessment. He provided advice on the economic review and aspects of the economic
analysis.

Anderson Chuck contributed to the review of economic studies, developed the economic analysis
model and budget impact analytic framework, and contributed to the drafting of the economic
analysis and budget impact sections.

Darcy Marciniuk contributed to the preparation of clinical sections of the report, including
provision of advice on practice guidelines, and contributed to the economic analysis.

Irvin Mayers contributed to the development and preparation of the clinical review and provided
clinical input to the economic model.

Monica Mierzwinski-Urban prepared the literature search strategy, performed literature searches,
wrote the methods section on literature searching, and verified references.

Acknowledgment
The authors acknowledge the contribution of Sarah McGill for providing referencing support and
a quality check of the references in the final version of the report.

Conflicts of Interest
Dr. Paul Hernandez is the Medical Director of the Pulmonary Rehabilitation Program at the
Capital District Health Authority. He is also a member of the COPD and Pulmonary
Rehabilitation Committee with the Canadian Thoracic Society. Dr. Michael Stickland received a
speaker’s honorarium from GlaxoSmithKline Inc.

PR for COPD: Clinical, Economic, and Budget Impact Analysis ii


iii PR for COPD: Clinical, Economic, and Budget Impact Analysis
EXECUTIVE SUMMARY
The Issue
Chronic obstructive pulmonary disease (COPD) causes disability and impaired quality of life. In
2006, more than 10% of all hospitalizations in Canada were due to COPD. Pulmonary
rehabilitation (PR) can be used to assist in the management of COPD. In Canada, there is poor
access to PR because of limited program capacity. Policy-makers and health care providers need
advice to help with decision-making about the future establishment and use of PR programs.
Information on the cost-effectiveness, budget impact, and operational needs of PR programs and
the impact of program elements on clinical outcomes would be helpful for decision-makers.

Objectives
The objectives of this assessment were to evaluate the effect of PR programs for COPD on
clinical and economic outcomes, and to assess their health services impact.

The research questions were:


 What is the clinical effectiveness of PR and pharmacotherapy (together) compared with
pharmacotherapy alone for adults with COPD?
 What is the effectiveness of specific elements of PR programs for adults with COPD?
 What is the cost-effectiveness of PR and pharmacotherapy compared with pharmacological
therapy alone in adults with COPD?
 What is the health services impact of implementing PR for adults with COPD in Canada?
 What are the recommendations for the use of PR in current COPD clinical practice guidelines
that are relevant to the Canadian context?

Methods
Literature searches were conducted to obtain clinical and economic data using bibliographic
databases and grey literature sources. Systematic reviews of clinical and economic literature
were undertaken. Recommendations and judgments on evidence were extracted from relevant
clinical practice guidelines.

A cost-effectiveness analysis was undertaken to compare the costs and health outcomes of usual
care (pharmacotherapy) to the costs and health outcomes of usual care plus PR. PR consisted of
three sessions per week at 2.5 hours per session over six weeks. A health system perspective was
taken.

In the budget impact analysis, COPD prevalence data were used to estimate the number of
patients recommended to receive PR. The desired capacity for PR in each year is estimated as
current capacity plus the number of additional persons served each year. The budget impact of
the additional services was estimated by multiplying the unit cost of PR by the additional persons
served per year. A time horizon of ten years was used.

PR for COPD: Clinical, Economic, and Budget Impact Analysis iv


Clinical Effectiveness of Pulmonary Rehabilitation
The studies that are included in this review showed that, when compared with the usual care
(pharmacotherapy) of patients with stable COPD, PR plus usual care is effective in the short term
(up to three months), as indicated by improvement in exercise capacity, health-related quality of
life (HRQL), and mental health. In some studies, however, the improvements in outcomes were
below the minimal clinically important differences. Some longer-term studies found that the
benefits from the use of PR disappeared in 12 months or less. Others found that the benefits were
sustained for two to three years. Reductions in health care utilization, as indicated by the number
of hospital admissions or the length of stay, were reported in studies of variable quality.

The findings suggested that patients with COPD can benefit from the use of PR regardless of
age, sex, and disease severity. Home-based PR programs provided similar benefits to those
obtained from hospital outpatient PR programs. The appropriate duration and content of PR
programs is unclear. Information on comparisons of PR with other treatments and on the
effectiveness of components of PR programs was limited. Four clinical practice guidelines were
identified as being relevant to Canada. Common themes included support for the use of PR for
patients with COPD who have dyspnea and reduced exercise capacity, and the inclusion of
education as a component of PR.

Economic Analysis
If the duration of efficacy of PR is 18 months, the incremental cost-effectiveness ratio of usual
care plus PR compared with usual care is $27,924 per additional quality-adjusted life-year
(QALY) gained.

Health Services Impact


If it is assumed that only the moderate and severe cases need PR, then 1,505 additional persons
would be served annually in Canada over a ten-year period for an added annual cost of $1.8
million. If 25% of persons with COPD need PR, this cost would rise to $33.9 million annually
for 100% uptake or $19 million if 67% of those who are in need used the services. If all persons
with COPD needed PR, the additional annual cost would be $168 million.

Conclusions
The use of PR improves short-term exercise capacity, HRQL, and mental health outcomes for
patients with COPD. More work is needed to confirm the factors that contribute to the successful
long-term management of COPD after PR. There is limited information on the effectiveness of
specific elements of PR programs. There are issues relating to patient characteristics and the
operation of PR and maintenance programs that require consideration by those who establish or
implement these services.

The cost-effectiveness of PR will depend on the duration of benefits. If the duration of the
efficacy of PR is18 months, the incremental cost-effectiveness ratio or ICER of usual care plus
PR compared with usual care is $27,924 per additional QALY gained. In the most likely scenario
from the budget impact analysis, an additional 15,900 persons per year would need PR, and an
additional budget of $19 million would be required annually.

v PR for COPD: Clinical, Economic, and Budget Impact Analysis


TABLE OF CONTENTS
EXECUTIVE SUMMARY .............................................................................................................iv

ACRONYMS AND ABBREVIATIONS ......................................................................................viii

1 INTRODUCTION...................................................................................................................1
1.1 Background and Setting in Canada...............................................................................1
1.2 Overview of Technology................................................................................................2

2 ISSUE ...................................................................................................................................3

3 OBJECTIVES .......................................................................................................................3

4 CLINICAL REVIEW ..............................................................................................................4


4.1 Methods.........................................................................................................................4
4.1.1 Literature searches..........................................................................................4
4.1.2 Selection criteria ..............................................................................................5
4.1.3 Selection method.............................................................................................5
4.1.4 Data extraction strategy...................................................................................5
4.1.5 Strategy for validity assessment......................................................................6
4.1.6 Data analysis methods ....................................................................................6
4.2 Results ..........................................................................................................................7
4.2.1 Quantity of research available .........................................................................7
4.2.2 Study characteristics .......................................................................................7
4.2.3 Clinical practice guidelines ............................................................................22
4.2.4 Data analyses and synthesis.........................................................................22
4.2.5 Elements of PR programs .............................................................................25

5 ECONOMIC ANALYSIS .....................................................................................................26


5.1 Review of Economic Studies: Methods .......................................................................26
5.1.1 Literature searches........................................................................................26
5.1.2 Selection criteria ............................................................................................26
5.1.3 Selection method...........................................................................................26
5.1.4 Data extraction strategy.................................................................................27
5.1.5 Strategy for quality assessment ....................................................................27
5.1.6 Data analysis methods ..................................................................................27
5.2 Review of Economic Studies: Results.........................................................................28
5.2.1 Results of search strategy .............................................................................28
5.2.2 Review of pulmonary rehabilitation versus no rehabilitation..........................28
5.2.3 Summary of results........................................................................................31
5.3 Primary Economic Evaluation: Methods......................................................................32
5.3.1 Type of economic evaluation.........................................................................32
5.3.2 Target population...........................................................................................32
5.3.3 Comparators..................................................................................................32
5.3.4 Perspective....................................................................................................32
5.3.5 Effectiveness .................................................................................................32
5.3.6 Time horizon..................................................................................................33
5.3.7 Modelling .......................................................................................................33
5.3.8 Valuing outcomes ..........................................................................................35

PR for COPD: Clinical, Economic, and Budget Impact Analysis vi


5.3.9 Resource use and costs ................................................................................35
5.3.10 Discount rate .................................................................................................36
5.3.11 Variability and uncertainty .............................................................................36
5.4 Primary Economic Evaluation: Results .......................................................................39
5.4.1 Analysis and results.......................................................................................39

6 HEALTH SERVICES IMPACT............................................................................................42


6.1 Population Impact........................................................................................................42
6.2 Budget Impact .............................................................................................................42
6.2.1 Method...........................................................................................................42
6.3 Planning, Implementation, Utilization, and Legal or Regulatory Considerations........46
6.4 Ethical Considerations.................................................................................................46
6.4.1 Efficiency versus equity .................................................................................46
6.4.2 Process or procedural issues ........................................................................47

7 DISCUSSION......................................................................................................................47
7.1 Summary of Results ....................................................................................................47
7.2 Strengths and Weaknesses of This Assessment ........................................................49
7.3 Generalizability of Findings .........................................................................................50
7.4 Knowledge Gaps .........................................................................................................50

8 CONCLUSIONS..................................................................................................................51

9 REFERENCES....................................................................................................................52

APPENDIX 1: Literature Search Strategy


APPENDIX 2: Clinical Studies Data Collection Form
APPENDIX 3: Quality Assessment Instrument for Clinical Studies
APPENDIX 4: Quality Assessment Form for RCTs
APPENDIX 5: Tables for Clinical Review
APPENDIX 6: Material from Clinical Practice Guidelines
APPENDIX 7: Economic Studies Data Extraction Form
APPENDIX 8: Economic Studies that Compared PR to No Rehabilitation
APPENDIX 9: Budget Impact Analysis Model Results
APPENDIX 10: Excluded Publications

vii PR for COPD: Clinical, Economic, and Budget Impact Analysis


ACRONYMS AND ABBREVIATIONS
ACCP American College of Chest Physicians
AACPR American Association of Cardiovascular and Pulmonary Rehabilitation
ADL activities of daily living
BODE BODE index for COPD (Body mass index, airflow Obstruction, Dyspnea,
Exercise Capacity)
BPQ Breathing Problems Questionnaire
CAO chronic airflow obstruction
CET cycle endurance test
COPD chronic obstructive pulmonary disease
COPM Canadian Occupational Performance Measure
CRQ Chronic Respiratory Disease Questionnaire
CTS Canadian Thoracic Society
ESWT Endurance Shuttle Walk Test
FEV1 forced expiratory volume in one second
FFM functionally active fat-free mass
GOLD Global Initiative for Chronic Obstructive Lung Disease
HADS Hospital Anxiety and Depression Scale
HRQL health-related quality of life
HTA Health Technology Assessment
ICER incremental cost-effectiveness ratio
IMT INSPIRATory muscle training
ISWT incremental shuttle walking test
ITT maximal incremental treadmill test
LABA long-acting beta agonist
LVRS lung volume reduction surgery
Maugeri RFQ Maugeri Foundation Respiratory Failure Questionnaire (MRF-28)
MCID minimal clinically important difference
MET metabolic equivalent task
MRF-28 Maugeri Foundation Respiratory Failure Questionnaire
NETT National Emphysema Treatment Trial
NIPPV non-invasive positive pressure ventilation

PR for COPD: Clinical, Economic, and Budget Impact Analysis viii


NNT number needed to treat
NRCT non-randomized controlled trial
NSD no significant difference
PEFR peak expiratory flow rate
PFSDQ-M Modified Pulmonary Functional Status and Dyspnea Questionnaire
PR pulmonary rehabilitation
QALY quality-adjusted life-year
QLI quality of life index
QWB Quality of Well-Being Scale
RCT randomized controlled trial
SF-36 Short Form (36) Health Survey
SGRQ St. George’s Respiratory Questionnaire
SOBQ San Diego Shortness of Breath Questionnaire
STAI State-Trait Anxiety Inventory
TDI Transition Dyspnea Index
3MWD three-minute walk distance
6MRT six-minute ring test
6MWD six-minute walk distance
6MWT six-minute walk test

ix PR for COPD: Clinical, Economic, and Budget Impact Analysis


1 INTRODUCTION
1.1 Background and Setting in Canada
Chronic obstructive pulmonary disease (COPD) is a condition that is characterized by airflow
obstruction. The airflow obstruction is usually progressive, not fully reversible, and does not
change over months. COPD is predominantly caused by smoking. The airflow obstruction is due
to a combination of airway and parenchymal damage as the result of chronic inflammation that
differs from that seen in asthma. COPD is associated with symptoms, disability, and impaired
quality of life, all of which may respond to pharmacological and other therapies. In some cases,
these therapies have limited or no impact on the airflow obstruction.1,2

Of adults over the age of 34 years who were surveyed in the Canadian Community Health
Survey of 2005, 4.4% reported that they had been diagnosed with COPD by a health
professional.1 The results from Austria indicate that the prevalence of COPD may be
underestimated by at least 50% in individuals 40 years of age and over when self-reported
physician-diagnosed COPD is used as a measure.1 Consequently, these figures may under-
represent the actual prevalence of COPD.1 For adults over the age of 65 years — the largest
hospitalized group in Canada — over 10% of all hospitalizations in 2006 were due to COPD. In
2004, COPD was the cause of 4% of all deaths in Canada.1

The goals of COPD management are to prevent disease progression, reduce frequency and
severity of exacerbations, alleviate breathlessness and other respiratory symptoms, improve
exercise tolerance and daily activity, treat exacerbations and other complications, improve health
status, and reduce mortality.2 The means to achieve these goals is the optimized use of
pharmacologic and non-pharmacologic interventions. Both are effective and have independent
benefits for the patient.2 An option for optimizing the non-pharmacologic management for many
patients with COPD is pulmonary rehabilitation (PR).2

The American Thoracic Society and the European Respiratory Society have defined PR as “an
evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic
respiratory diseases who are symptomatic and often have decreased daily life activities.
Integrated into the individualized treatment of the patient, pulmonary rehabilitation is designed
to reduce symptoms, optimize functional status, increase participation, and reduce health-care
costs through stabilizing or reversing systemic manifestations of the disease. Comprehensive
pulmonary rehabilitation programs include patient assessment, exercise training, education, and
psychosocial support.”3

The 2007 Canadian Thoracic Society (CTS) guidelines outlined a comprehensive approach to the
chronic management of COPD, starting with inhaled bronchodilators. Other therapies may
include inhaled corticosteroids, inspired oxygen, and surgery.2 The use of PR has been shown to
improve functional exercise capacity and quality of life, while reducing acute exacerbations and
hospitalizations.4 The use of PR with concomitant pharmacotherapy has been shown to be a
more effective therapeutic strategy for improving health outcomes in COPD compared with
traditional pharmacological management with inhaled bronchodilators,4,5 and has emerged as a
recommended standard of care for patients with chronic lung disease.4

PR for COPD: Clinical, Economic, and Budget Impact Analysis 1


In Canada, there is poor access to PR for COPD because of limited program capacity. It was
determined in a 2005 survey that 1.2% of the COPD population in Canada had access to PR. In
2005, eight provinces indicated they had programs.6 The number of patients eligible for PR may
increase as the population ages. There is also an increasing number of younger patients with
COPD (from smoking and from talc lung) and an increasing number of female patients. There is
no specific programming for younger patients, who may have different needs compared with
those in older age groups.

A Canadian study that compared the direct costs for patients with COPD before and after they
enrolled in a rehabilitation program in Alberta indicated that the implementation of PR programs
in Canada would cost between C$220 million and C$307 million annually. The overall savings
in direct health care costs could be up to C$172 million per year. The impact on productivity
costs would be minimal, because most patients with severe COPD are older individuals who are
not in the work force.7

1.2 Overview of Technology


The American College of Chest Physicians (ACCP) and the American Association of
Cardiovascular and Pulmonary Rehabilitation (AACPR)4 note that the American Thoracic
Society and European Respiratory Society’s joint definition of PR focuses on three features of
successful rehabilitation:
 Multidisciplinary: PR programs integrate expertise from health care disciplines into a
comprehensive and cohesive program that is tailored to each patient’s needs.
 Individual: Patients with disabling lung disease require individual needs assessment,
individual attention, and a program that is designed to meet realistic individual goals.
 Attention to physical and social function: PR pays attention to psychological, emotional,
and social problems, and to physical disability; and helps to optimize medical therapy to
improve lung function and exercise tolerance.

The ACCP/AACPR state that, in current practice, PR typically includes exercise training,
education, instruction in respiratory and chest physiotherapy techniques, and psychosocial
support. For the ACCP/AACPR guidelines, comprehensive PR was defined as an intervention
that includes one or more of these components beyond exercise training, which is considered to
be an essential and mandatory component.4 The main goal of PR is the restoration of the patient
to the highest possible level of independent functioning. This goal is accomplished by helping
patients become more physically active and learn more about COPD, treatment options, and how
to cope. Patients are encouraged to become involved in providing their own health care, become
more independent in daily activities, and become less dependent on health professionals and
expensive medical resources. Instead of focusing on reversing the disease, rehabilitation is used
to reduce symptoms and to reduce disability.4

Pulmonary rehabilitation programs require a health professional who has the expertise to conduct
an exercise program and who is trained in cardiopulmonary resuscitation. A multidisciplinary
team of health professionals may be involved in the educational component of the program.8
The components of a program include:8

2 PR for COPD: Clinical, Economic, and Budget Impact Analysis


 Patient assessment (obtain medical history; assess smoking, nutritional status, exercise
capacity, quality of life, breathlessness, and patient’s goals)
 Patient exercise training (design an exercise program; determine appropriate exercise,
including intensity, duration, and frequency)
 Patient education (hold educational sessions on the role and correct use of medications;
breathing techniques; managing breathlessness; physical exercise; nutrition; healthy eating;
lung diseases; coping with chronic lung disease; and management of depression, anxiety, and
panic attacks)
 Program evaluation (evaluate the effectiveness of the program based on patient outcomes —
for example, exercise capacity, quality of life, breathlessness; obtain patient feedback;
communicate with patient’s physician)
 Maintenance (if possible, continue to provide one supervised session a week for
maintenance, encourage patients to undertake a home exercise program).

The approaches taken vary between programs. All programs provide aerobic exercise and
education sessions, but some exclude strength training or psychosocial and behavioural
interventions. There may also be differences in the content and presentation of educational
sessions. The numbers and length of sessions differ, and there is variation in the use of home
exercise between sessions and the support that is offered during maintenance after the
completion of PR.

Patients who participate in PR programs also have concomitant pharmacotherapy that is


generally equivalent to that provided in usual care for the management of COPD.

2 ISSUE
COPD causes disability and impaired quality of life. The use of PR can assist in the management
of COPD. In Canada, there is poor access to PR because of limited program capacity. Policy-
makers and health care providers need advice to help with decision-making about the future
establishment and use of PR programs. Information on the effectiveness, cost-effectiveness,
budget impact, and operational needs of PR programs and the impact of specific program
elements on clinical outcomes would be helpful for decision-makers. Policy-makers have
commented positively on the usefulness of guidelines, such as those from the CTS, as a source of
advice.

3 OBJECTIVES
The objectives of this health technology assessment were to evaluate the effect of PR programs
for COPD on clinical and economic outcomes, and to assess the health services impact.

The research questions were:


1. What is the clinical effectiveness of PR and pharmacotherapy (together) compared with
pharmacotherapy alone for adults with COPD?
2. What is the effectiveness of elements of PR programs for adults with COPD?

PR for COPD: Clinical, Economic, and Budget Impact Analysis 3


3. What is the cost-effectiveness of PR and pharmacotherapy compared with pharmacological
therapy alone in adults with COPD?
4. What is the health services impact of implementing PR for adults with COPD in Canada?
5. What are the recommendations for PR in current COPD clinical practice guidelines that are
relevant to the Canadian context?

4 CLINICAL REVIEW
A protocol for the clinical review was written before the research was started and followed
throughout the review process.

4.1 Methods
4.1.1 Literature searches
The search strategies that were developed by the information specialist [MM], with input from
other members of the project team, underwent an internal peer review by another CADTH
information specialist. There were no language restrictions.

The following bibliographic databases were searched through the Ovid interface: MEDLINE,
Medline In-Process & Other Non-Indexed Citations, Embase, BIOSIS Previews, and CINAHL.
Parallel searches were conducted in PubMed, The Cochrane Library, and the Health Economic
Evaluations Database (HEED). The search strategy comprised controlled vocabulary, such as the
National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main
search concepts were chronic obstructive pulmonary disease and pulmonary rehabilitation or
exercise therapy. Methodological filters were applied to limit retrieval to randomized controlled
trials (RCTs), observational studies, health technology assessments (HTAs), systematic reviews,
practice guidelines, and economic studies. The detailed search strategies appear in Appendix 1.

The search was restricted to articles that were published from 1998 onwards. Ovid AutoAlerts
were set up to send monthly updates with new literature. Updates were performed on HEED,
PubMed, and Cochrane Library databases.

Grey literature (literature that is not commercially published) was identified by searching the
websites of HTA and related agencies, professional associations, relevant conference
proceedings, and other specialized databases. Google and other Internet search engines were
used to search for web-based information. These searches were supplemented by hand searching
the bibliographies and abstracts of key papers and conference proceedings, and through contacts
with appropriate experts and agencies. A final grey literature update occurred during the writing
of the report.

4 PR for COPD: Clinical, Economic, and Budget Impact Analysis


4.1.2 Selection criteria

a) Inclusion criteria
 Comparative studies that included the use of PR programs for adults with COPD and that
reported outcomes in terms of morbidity or mortality, health-related quality of life (HRQL),
exercise capacity, other patient-centered end points such as shortness of breath or activity
limitation, and health-care utilization. The studies could include the use of PR in any
setting. The comparators included pharmacological therapy and other approaches to the
management of COPD.
 Non–comparative studies that included the long-term follow-up of patients after PR, and
reported outcomes in terms of morbidity, mortality, HRQL, exercise capacity, or use of
health services.
 Comparative studies that considered the efficacy or effectiveness of components of PR
programs.
 Studies that addressed differences in the efficacy or effectiveness of PR based on
subgroups, patient characteristics, or provision of rehabilitation.
 HTAs and systematic reviews that considered the use of PR programs for adults with
COPD.
 Clinical practice guidelines for the management of COPD that were judged to be relevant to
the Canadian context.

b) Exclusion criteria
 Studies on the use of PR programs only for conditions other than COPD.
 Case reports, implementation studies, chart reviews, focus groups, and interviews.
 Narrative reviews, correspondence, and commentaries.
 Duplicate publications of the same study.

4.1.3 Selection method

Two reviewers (DH and MS) independently applied the selection criteria to the titles and
abstracts that were found during the literature search. Full-text articles were obtained for
abstracts that met the selection criteria and those for which decisions could not be reached. Full-
text articles were included if they met the selection criteria. Any discrepancies were resolved by
consensus. The clinical practice guidelines that are relevant to the Canadian context were
selected by three of the authors (DM, IM, MS), based on their clinical experience with PR in
Canada.

4.1.4 Data extraction strategy

Two reviewers (DH, MS) independently extracted data from the selected publications using a
data abstraction form that was created before the research was started (Appendix 2). Any
disagreements were resolved by consensus.

The extracted information included the study design, setting, and duration; patient numbers and
characteristics; components of the PR program and reported measures of efficacy; clinical
outcomes related to HRQL; exercise capacity; hospital stay; exacerbations; and treatment-related
adverse effects.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 5


Non-English language papers that were judged to be of appropriate quality based on the abstracts
and contents were translated. Information was extracted from the abstracts of other relevant non-
English language papers.

4.1.5 Strategy for validity assessment

The quality of the selected studies was evaluated independently by two reviewers (DH and MS),
taking into account study design and study performance and linking both to judgments on study
reliability9 (Appendix 3). Any disagreements were resolved by consensus. Based on the quality
scores, each study was assigned to one of five categories:
 High quality (high degree of confidence in study findings)
 Good quality (some uncertainty in the study findings)
 Fair quality (some limitations that should be considered in the implementation of the study
findings)
 Poor to fair quality (substantial limitations in the study findings, which should be used
cautiously)
 Poor quality (study findings have unacceptable uncertainty).

The quality of selected RCTs was also assessed using the Jadad Scale10 (Appendix 4).

Quality assessment was not attempted for not-translated, non–English language papers or
abstracts.

4.1.6 Data analysis methods

Exercise capacity and HRQL were the primary indicators of efficacy and effectiveness. Mental
health, use of health services, numbers of acute exacerbations, and mortality were also
considered when relevant data were reported. The selected studies that evaluated PR programs
varied in components, duration, and patient populations. Also, various methods were used to
assess changes in exercise capacity, HRQL, and other outcomes of PR. Because of this lack of
homogeneity across studies, the pooling of results was considered to be unrealistic. A series of
qualitative reviews were prepared by two reviewers (DH and MS) to summarize the relevant
information that could be used to answer the research questions of this HTA. For each selected
study, the outcomes of interest were discussed, and any discrepancies were resolved by
consensus.

Between-group differences in outcomes were interpreted as the means and corresponding 95%
confidence intervals, if such information was included in a publication. If a publication excluded
such details, other measures of between-group comparisons were used; for example, P values
and associated conclusions of statistical significance.

The clinical significance of reported point estimates of differences in outcome was judged with
reference to minimal clinically important differences (MCIDs) that were determined for tests and
measurement scales. MCIDs were defined as follows:

6 PR for COPD: Clinical, Economic, and Budget Impact Analysis


a) Exercise tolerance measures
 Six-minute walk test (6MWT), 54 metres11
 Incremental shuttle walking test (ISWT), 47.5 metres12
 Endurance shuttle walk test (ESWT), 85 seconds13
 Maximal incremental treadmill test, 10 Watts14
 cycle endurance test (CET), 100 seconds.15

b) Quality of life measures


 Chronic Respiratory Disease Questionnaire (CRQ), 0.5 points for each domain16
 St. George’s Respiratory Questionnaire (SGRQ), 4 points17
 Short Form (36) Health Survey (SF-36), 5 points for composite scores18
 Quality of Well-Being Scale (QWB), 0.03 units.19

c) Mental health measures


 Beck Depression Inventory, 5 points20
 Hospital Anxiety and Depression Scale (HADS), 1.5 points.21

The effect sizes were estimated as Cohen’s d, using difference of the means for intervention and
control groups divided by the pooled standard deviations, and classified according to Cohen’s
definition of “small, d = 0.2; medium, d = 0.5; and large, d = 0.8.”22

4.2 Results
4.2.1 Quantity of research available

The report selection process is shown in Figure 1. The literature search identified 3,082 citations,
and 318 articles were retrieved after preliminary screening. From these, 102 papers on 100
unique studies and five practice guideline documents were selected for inclusion in the review.
The most common reasons for excluding citations were use only of narrative reviews or
commentaries, failure to deal with full PR programs (those that included education and, in some
cases, other components in addition to exercise training), inappropriate study design (for
example, small case series), insufficient information, and non-relevance to PR for COPD.

4.2.2 Study characteristics

a) Overview of pulmonary rehabilitation programs and studies


Pulmonary rehabilitation and its evaluation is complex. The studies that are included in this HTA
reflected the variation in the components of PR programs and the method of implementation.

Patients: There was variation between studies in the severity of COPD among the patients who
were recruited. The selection criteria in many studies excluded patients with comorbidities (for
example, heart disease, malignancy, bone and joint disease).

Setting: PR programs were offered in inpatient, outpatient, and home-based settings, and in
combinations of these settings.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 7


Figure 1: Selection of Reports on Clinical Studies

3,082 citations identified from


electronic search and screened

4 citations identified from


other sources and screened

2,768 citations excluded

318 potentially relevant reports


retrieved for scrutiny

211 reports excluded:


 narrative reviews, commentaries (56)
 insufficient information (45)
 did not relate to full PR programs (25)
 inappropriate study design (59)
 not relevant to PR for COPD (22)
 duplicate publications (4)

102 reports on 100 unique studies,


5 guideline documents

COPD = Chronic obstructive pulmonary disease; PR = pulmonary rehabilitation

8 PR for COPD: Clinical, Economic, and Budget Impact Analysis


Program components: All PR programs included aerobic exercise and education, and some
excluded strength training, or nutritional and psychosocial interventions.

Duration of PR: The numbers and duration of sessions varied between programs. The number
of sessions ranged from 11 to 96, and the number of weeks from three to 52.

Follow-up time: In those studies where data were collected after the end of the PR program, the
follow-up lasted from one to 60 months.

Study design and performance: Though many studies in the review were of good quality, not
all were RCTs. In some studies, not all aspects (patient selection, description of the interventions,
specification and analysis of study data, patient disposition [enrollment, adherence, attrition, and
loss to follow-up], and outcomes reported) were adequately covered. Many studies had small
numbers of patients and limited power.

Measures of PR outcome: A variety of methods were used in the studies to measure changes in
exercise tolerance and HRQL, thereby complicating the comparison of results across studies. The
methods that were used for exercise tolerance included the 6MWT, ISWT, ESWT, and CET.
Those that were used to measure HRQL included the SGRQ, CRQ, QWB, and SF-36.

Reporting of study results: Most of the papers reviewed reported study outcomes in terms of
the statistical significance of changes from baseline (the baseline in some studies was the
beginning of the PR program and in other studies it was the end of the PR program). A minority
of papers included confidence intervals in the presentation of results.

Clinical significance of study results: Many of the reviewed studies did not discuss the clinical
significance of findings. A comparison of between-group differences in outcomes to relevant
MCIDs has been made in this report. Mean changes in outcomes that are below the MCIDs
indicate that the PR program was not clinically effective for a large proportion of the study
participants.

There are other, less easily described influences on the effectiveness of PR programs. Coultas
and McKinley commented that because of the complexity of starting and sustaining behaviour
change, the variation in outcomes between PR programs may be influenced by patient factors,
and by the attitudes and skills of team members. Little is known about the influence of patient or
team characteristics on outcomes.23

Additional details about the studies appear in Appendix 5, Tables A1 to A15.

b) Efficacy and effectiveness of pulmonary rehabilitation


Most of the evidence on the efficacy and effectiveness of PR and pharmacotherapy was obtained
from studies in which the outcomes of patients in PR programs were compared with those of
patients who received usual care (typically pharmacological treatment alone). For longer-term
outcomes, the comparisons of PR approaches and observational studies were also considered.

In the two following sections, which present the studies that reported outcomes in terms of
exercise capacity and HRQL, the change in outcome in comparative studies refers to the

PR for COPD: Clinical, Economic, and Budget Impact Analysis 9


between-groups difference in the mean change in outcome from baseline unless otherwise
specified.

Exercise capacity and health-related quality of life


Short term outcomes: This section on short-term outcomes includes studies with outcomes of
three months or less, which in many cases cover those measures that are obtained at the end of a
PR program. The studies that reported short-term outcomes of PR programs (up to three months
from the start of PR) ― including setting, program components, study design, quality ranking,
and outcomes of interest ― appear in Appendix 5, Table A1.

PR after admission for exacerbation: In a high-quality study, Man et al.24 assessed the effects of
early PR (rehabilitation shortly after discharge) for patients who had been admitted to hospital
because of acute exacerbations. The use of PR led to statistically and clinically significant
improvements in exercise capacity and health status at three months (ISWT median difference 60
metres, SGRQ −12.7 [−5.0, −20.4]). This study was considered in an earlier review that included
studies using exercise only in rehabilitation and suggested that the use of PR is effective for
patients with COPD after acute exacerbation.25

In a good-quality study, Eaton et al.26 found no difference between groups in change in exercise
capacity or in HRQL as measured using the CRQ scale. Those who completed the PR program,
however, had statistically significantly higher scores in the physical component of the SF-36
quality of life questionnaire than the usual care group.
In a retrospective cohort study, Clini et al.27 considered the effectiveness of early inpatient PR
after admission with acute exacerbation. After a four-week PR program, there was clinically
significant improvement in exercise capacity and HRQL across all grades in the Medical
Research Council (MRC) dyspnea scale . For all patients, the mean change in the six-minute
walk distance (6MWD) was 65.3 metres [63.2, 67.5], with 56% reaching the MCID. The
proportion of patients reaching 350 metres was higher in the most severe MRC grades. The mean
change in SGRQ score was −5.9 [−6.45, −5.34] and higher than MCID for all MRC grades.

Studies on patients with stable COPD: Twelve studies included patients with serious but stable
COPD in different settings, and in PR programs of varying length and structure. Seven were of
high or good quality,28-34 four of fair quality,35-38 and one of poor to fair quality.39 All twelve
studies found short-term improvement in exercise capacity. The mean change in exercise capacity
was greater than the MCID in four studies. Karapolat et al.28 found that benefits tended to
deteriorate during the first month after outpatient PR. The mean values of the change in 6MWD
were 107 metres at eight weeks and 58 metres at 12 weeks. In a study on outpatient PR, Griffiths et
al.34 found a mean change in ISWT results of 76 metres at eight weeks. In a study on home PR,
Oh36 found a change in 6MWD of 68 metres after 8 weeks. Riario-Sforza et al.39 reported that, at
the end of a six-week outpatient PR program, 64% of participating patients (Global Initiative for
Chronic Obstructive Lung Disease [GOLD] stages I to IV) had an increase in 6MWD of at least
54 m (the MCID) compared with 13% in a usual care control group. The number needed to treat
(NNT) in the overall intervention group was 2. The same NNT was obtained for patients at GOLD
stages II, III, and IV, and it was 8 for those at stage I.

Six studies had mean changes in 6MWD that were less than the MCID: Boxall et al.,31 35 metres
(home PR with housebound patients, 12 weeks); Barakat et al.,29 38 metres (outpatient, 14

10 PR for COPD: Clinical, Economic, and Budget Impact Analysis


weeks); Singh et al.,32 47 metres (home PR, four weeks); Theander et al.,30 24 metres (outpatient,
12 weeks); Na et al.,35 14 metres (home, 12 weeks); and Skumlien et al.,37 19 metres (inpatient,
four weeks). The change in exercise capacity was also below MCID in Regiane Resqueti et
al.’s38 study, which used the three-minute walk distance or 3MWT (16 metres, home PR, nine
weeks). Elçi et al.33 (outpatient and home, 12 weeks) found an increase in 6MWD values
between 1 and 3 months (24 metres), but the relationship to MCID is unclear because the
baseline value was not reported.

Ten of eleven studies found improvements in HRQL. In eight of the 10 studies, the changes in
mean HRQL scores were greater than the MCID. Boxall et al.,31 Barakat et al.,29 Karapolat et
al.,28 Na et al.,35 and Skumlien et al.,37 used the SGRQ; Singh et al.,32 and Oh,36 the CRQ; and
Griffiths et al.,34 both instruments. Barakat et al.29 also reported a decrease in the risk of death as
measured using the BODE index: body mass, airflow obstruction, dyspnea, exercise capacity.
The changes in CRQ scores in Regiane Resqueti et al.’s study38 were below the MCID. Theander
et al.30 could not detect a statistically significant difference in fatigue (using the Canadian
Occupational Performance Measure and the Fatigue Impact Scale) or health status between the
PR and usual care groups (SGRQ and SF-36). Elçi et al.33 found an improvement in SGRQ and
SF-36 scores between 1 and 3 months but did not report baseline values.

Overall, these results are generally consistent with those included for earlier studies that were
considered by Lacasse et al.5

Studies reported in non-English language papers: In an RCT, Jang and Jung (Korea)40
considered outpatient PR for eight weeks, with one session per week that included exercise
training, education, and counselling. The program was reported by the authors to be effective in
improving self-efficacy, dyspnea, exercise endurance, and HRQL (Quality of Life Index
Pulmonary Version III) in patients with COPD, with statistically significant improvements in
each of these measures. Ciric et al. (Serbia)41 found that a 21-day PR program improved exercise
tolerance and dyspnea when compared with medical therapy alone for patients with mild, severe,
and very severe COPD. The mean changes in 6MWD were greater than the MCID for the groups
with mild and very severe disease. In a randomized trial, Ringbaek et al. (Denmark)42 reported
on an eight-week PR program for patients with moderate COPD and found “insignificant
improvement in well-being” and an increase of 29 metres in a walk test.

Longer-term outcomes after PR:


This section includes studies that obtained longer-term outcomes, some related to the use of
maintenance programs after the end of PR. Studies that reported longer-term outcomes after PR
appear in Appendix 5, Table A2. All involved home-based programs, most of which occurred
after or in association with outpatient or inpatient PR. For longer-term outcomes, a key factor
may be the type and intensity of maintenance strategy that is adopted after the completion of PR.
The following studies include comparisons of PR and usual care, and of maintenance programs
and usual care after the completion of PR.

In a high-quality study, van Wetering et al.43 found that PR plus long-term (20 months)
maintenance was effective in patients with COPD, exercise impairment, and less advanced
airflow obstruction. After 24 months, the intervention group had improved changes in SGRQ
score and cycle endurance test (CET) time compared with baseline. No improvement in 6MWD

PR for COPD: Clinical, Economic, and Budget Impact Analysis 11


was noted. The mean change in CET remained above the MCID at 20 months follow-up. The
mean change in SGRQ score was greater than the MCID at four months and lower than the
MCID at later follow-up.

Regiane Resqueti et al.38 found that patients with severe or very severe COPD (GOLD III or IV)
maintained an increase in exercise capacity at six months, although the mean between-group
differences were below the MCID. Between-group differences were below the MCIDs for all
domains of the CRQ.

In high-quality studies, Engström et al.44 and Güell et al.45 reported longer-term outcomes after
extended PR interventions. Engström et al.44 found that lasting effects on physical fitness were
achieved with an outpatient program over 12 months, although changes in the mean values for
6MWD remained below the MCID. No effects were shown on HRQL, as measured using the
SGRQ. Güell et al.45 considered the outcomes of a six-month PR program plus a further six
months of weekly supervised breathing exercises. The benefits in exercise capacity that were
achieved persisted for 18 months, with changes in the mean values for 6MWD above the MCID.
There were clinically significant increases at six months for the PR group in all domains of the
CRQ, with differences from controls continuing at 18 months follow-up. The values of all
domains of the CRQ were greater than the relevant MCIDs.

In the follow-up to post-PR findings, Na et al.35 found that the short-term change in exercise
tolerance was not maintained at one year after the end of PR.

In a good-quality study on a six-week outpatient PR program, Finnerty et al. found that benefits
were maintained at 24 weeks.46 The difference in 6MWD scores was above the MCID at follow-
up (67 metres [−1.6, 135.6]). The difference in SGRQ scores was above the MCID at follow-up
(−7.1 [−14.7, 0.54]). In a good-quality study, Griffiths et al.34 found that, after a six-week PR
program, the differences in mean scores of the SGRQ and CRQ remained higher than the MCIDs
at 12 months. The values of exercise capacity, measured using the ISWT, were lower than the
MCID at 12 months.

In a good-quality study on the use of a home PR program for patients with very severe COPD
who were on long-term oxygen treatment, Fernandez et al.47 found that the difference in 6MWD
total scores was above the MCID after 12 months (66 metres). They47 also found that the
difference in SGRQ total score was above the MCID after 12 months (−12.2).

In a prospective cohort study with long-term follow-up, Cote and Celli48 reported mortality and
BODE index scores for two years after PR, and hospitalization details for one year before and
after PR (116 participants in the PR group and 130 participants in the usual care group). The
study quality was rated as poor to fair. There were 13 deaths (eight respiratory-related) in the PR
group and 66 deaths (57 respiratory-related) in the usual care group (Kaplan-Meier log rank
analysis P < 0.0001). Cote and Celli defined a one-unit change in the BODE index as being
clinically significant. After rehabilitation (three months from baseline), 83 (71%) participants in
the PR group had an improvement of more than one unit, 29 (25%) participants had an
improvement of two units, 25 participants (21.6%) had no change, and 8 participants (6.9%) had
a worse index score. The PR group had an initial improvement in the BODE index of 19% (three

12 PR for COPD: Clinical, Economic, and Budget Impact Analysis


months), which returned to baseline after one year and remained stable at two years. The usual
care group had a decline in the BODE index of 4% after one year and 18% at two years
(P < 0.001 between groups for all time points). These findings were described by the authors
as indicating the beneficial effects of PR and subsequent maintenance exercise.

In a German-language paper, Göhl et al.49 reported findings from a small RCT of a PR


intervention over 12 months. There were statistically significant improvements from baseline for
SGRQ total and SF-36 composite scores for the PR group, but not for the controls. The
difference in 6MWD from baseline for the PR group was 79 metres (P = 0.003), with no
statistically significant difference for the controls, indicating that the change in exercise capacity
was above the MCID.

Studies on maintenance after PR: du Moulin et al.50 concluded that home-based exercise
training was as effective as maintenance in patients with moderate COPD, with benefits in
exercise tolerance and HRQL at six months. The differences in changes to mean 6MWD
between intervention and control groups after the end of PR were 20 metres at three months and
46 metres at six months (statistically significant). Changes during PR were not reported so that
the relationship of the overall change in exercise tolerance to the MCID is uncertain. A similar
pattern was found for mean CRQ total scores (differences of 0.4 at three months and 0.7 at six
months).

Moullec et al.51 found that an approach that linked home exercise with self-help association
programs (patient-run support groups) produced benefits in exercise capacity and HRQL at six
months that were maintained at 12 months after the start of the program. At the end of a four-
week PR program, the mean changes of 6MWD were below the MCID, and those for the SGRQ
were greater than the MCID. After six months of the maintenance program, the intervention
group had higher values for 6MWD than controls (difference 74.2 m, 95% CI [37.7 to 110.5]).
The intervention group also had higher scores in the SGRQ domains of symptoms difference of
−6.7 [−16.2 , 2.7]), activities (difference −20.2 [−33.4, −7.1]), and impacts (difference −17.0
[−28.1, −5.8]). These differences were maintained at 12-month follow-up (6MWD difference
75.8 [32.0 ,11.6], SGRQ symptoms difference −18.5 [−30.9, −6.2], SGRQ activities difference
−27.0 [−40.0, −14.0], SGRQ impacts difference −32.4 [−42.0, −22.8]). All differences were
above the MCIDs.

Steele et al.52 evaluated the effectiveness of a post-PR exercise adherence intervention for a
home exercise program. The experimental group received weekly telephone calls, a home visit,
and a pedometer for self-monitoring. At the end of PR, the mean increase in 6MWD for all
participants was 45 metres (below the MCID). After 20 weeks post-PR, 6MWD had decreased
by 10.7 metres in the intervention group and by 35.4 metres among controls (P = 0.023). At 52
weeks, the differences from post-PR values were −21 metres and −39.6 metres, respectively.
There were no differences between the groups in HRQL. The authors concluded that there was
no long-term benefit from using the intervention in a sedentary group of patients with chronic
lung disease (85% had COPD).

Ries et al.53 evaluated a 12-month maintenance program after PR. The intervention included
weekly telephone contacts and monthly supervised reinforcement sessions. During the
intervention, exercise tolerance (maximum treadmill workload and 6MWD) and overall health

PR for COPD: Clinical, Economic, and Budget Impact Analysis 13


status ratings were better maintained in the experimental group than among patients who had
standard care. There were no between-group differences for self-efficacy or generic and disease-
specific HRQL. By 24 months, there were no statistically significant group differences, and
patients returned to levels that were close to pre-rehabilitation measures. Ries et al. concluded
that the program produced modest improvements in the maintenance of benefits after PR.

Other studies reporting longer-term outcomes after PR: Other studies that reported longer-term
outcomes after PR appear in Appendix 5, Table A3.

Romagnoli et al.54 compared the outcomes of patients who participated in three PR programs
over 12 months with those who participated in two programs. They found that there were
improvements in 6MWD and SGRQ scores after the end of each PR program. The changes in
mean values for each program were below the MCIDs, and the benefits were partially lost
between programs. When compared with baseline, the mean values of 6MWD were above the
MCID at the end of the second and third PR programs, and those of SGRQ scores were above
the MCID at the start of the third program.

Verrill et al.55 compared outcomes after 12 weeks and 24 weeks of PR in seven outpatient
programs. They found that physical performance continued to improve with up to 24 weeks of
PR (6MWD above the MCID). HRQL and dyspnea improved after 12 weeks, and the
improvement was maintained at 24 weeks.
Two observational studies from Norway indicated that there were benefits after lengthy PR and
maintenance.56,57 After a home PR program that lasted 12 months, improvements in HRQL were
maintained to two years, with a mean total SGRQ score above the MCID at one year and below
it at two years. The exercise capacity did not change from baseline, and it did not deteriorate
over two years.56 In the second study,56,57 a one-year PR program was followed by a further year
of regular exercise sessions. Participants improved HRQL and exercise tolerance in the first year,
with no further clinically relevant improvement in the second year. This status was maintained
three years after the end of the program. The mean values of the 6MWD and SGRQ total score
remained above the MCIDs. At two years, the mean difference in 6MWD from baseline was 86
metres (63, 109), and the mean difference of total SGRQ score from baseline was −11.1 (−13.9,
−8.4). Self-reported data indicated that participants continued to exercise regularly during the
three years after the program.
c) Mental health outcomes
Ten studies reported mental health outcomes, usually in the short-term, and measured using
several instruments (Appendix 5, Table A4). Six studies compared PR with usual care and
showed a benefit from using rehabilitation.26,33,58-61 In good-quality studies, Paz Diaz et al.58 and
Elçi et al.33 found improvement in anxiety and depression in the PR groups, although Elçi did not
report separate scores for the two conditions. In Paz Diaz et al.’s study, the between-group
difference in the Beck Depression Inventory was above the MCID. Eaton et al.26 and Kayahan et
al.59 found improvements in anxiety and no improvements in scores for depression, compared
with usual care. The mean change in score using the HADS in Eaton’s study was below the
MCID. In a study of poor to fair quality, Kozora et al.60 found a decline in depressive symptoms
(below the MCID for the Beck Depression Inventory) and did not measure anxiety. Güell et al.61
found improvements in all components of the Millon Behavioral Health Inventory and suggested

14 PR for COPD: Clinical, Economic, and Budget Impact Analysis


that the use of PR may decrease psychosocial morbidity even without a psychological
intervention.

Three studies62-64 compared PR groups using different approaches (different numbers of


supervised and home sessions,63 with or without progressive muscle relaxation,64 or in a cold
climate versus a warm climate).62 A reduction in scores of anxiety and depression were noted.
Two studies reported longer-term outcomes. Both groups in Haugen and Stavem’s62 study had
HADS scores of depression below baseline and less than the MCID, at eight-month follow-up.
One group was also below the baseline score in anxiety and above the MCID. O’Neill et al.63
found that the differences from baseline in anxiety and depression declined from six weeks to six
months after PR, consistent with trends in exercise capacity and HRQL (Table A13). All changes
in scores were below the MCID. Both groups in Lolak et al.’s64 study had mean changes in
HADS scores for anxiety and depression that were greater than the MCID, but the between-
group differences did not exceed the MCIDs.

De Godoy et al.65 found improvements in anxiety and depression in patients whose PR programs
included psychotherapy.

d) Effect of pulmonary rehabilitation on chronic obstructive pulmonary disease


exacerbations
Few reports of studies evaluating PR included details about exacerbations in the reported
outcomes. Güell et al.45 and Cote and Celli48 found there were statistically significantly fewer
exacerbations in the PR groups than among patients who received usual care (Appendix 5, Table
A5). In the other studies (Appendix 5, Table A5), there were fewer exacerbations in a group
receiving PR plus tiotropium compared with PR alone,66 exacerbations were less frequent in a
warm climate than a cool climate62 and there was no difference between groups receiving
outpatient or home PR.67 In an RCT, van Wetering et al.43 found there was no difference between
intervention and usual care groups during four months of PR and 20 months’ maintenance.

e) Effects on health care utilization


Studies that included health-care utilization — mostly in terms of hospitalization of patients with
COPD — appear in Appendix 5, Table A6. In good-quality studies, Eaton et al.26 and Man et
al.24 considered patients who had been hospitalized with exacerbations. There were trends to
lower rates of COPD-related re-admission among patients who received PR. Man et al. reported
a statistically significant decrease in the number of emergency visits per patient (0.10 versus
0.43, P = 0.01).

In a high-quality study, Güell et al.45 found lower admission rates over the two years after PR
among patients who had participated in the program compared with those who received usual
care (0.6 versus 1.3). The difference did not reach statistical significance. Griffiths et al.34 found
lower mean admission rates and length of stay for patients who had participated in a PR program
(respiratory-related admissions 1.4 versus 1.9, P = 0.044, hospital days 9.4 versus 18.1, P =
0.048).

The six other studies48,51,56,57,68,69 that reported hospitalization after PR and usual care used
before-after approaches, with data for 12 months before PR being compared with those after the
end of rehabilitation. All but one of these found statistically significant reductions in the number

PR for COPD: Clinical, Economic, and Budget Impact Analysis 15


of hospital admissions or number of hospital days after PR. One study was of good quality51,
four were of poor to fair quality,48,56,57,68 one was of poor69 quality, and some used self-reported
data.51,69 Golmohammadi et al.7 did another before-after analysis of an outpatient program that
provided education, counselling, and rehabilitation. Utilization for a comparison group of non-
attendees with COPD was also used. The program saved $33 in utilization.

Ambrosino et al.66 reported fewer hospitalizations in a PR plus tiotropium group than in a PR


only group, but the group sizes were small. Wittmann et al. found a greater decrease in hospital
admissions among patients who had a training intervention plus PR than among those who had
PR alone (0.13 versus 0.21 over 12 months, P < 0.001).70

In a comparison of outpatient and home PR, Maltais et al.67 found there was no difference in the
number of admissions (0.45 and 0.42 per patient). Romagnoli et al.54 found no statistically
significant difference in the number of admissions among patients who had participated in two or
three PR programs.

f) PR and other treatments


Pharmacological therapy: Three studies reported comparisons of PR and tiotropium with PR
alone (Appendix 5, Table A7). In a high-quality study, Ambrosino et al.66 found that the addition
of tiotropium to PR did not improve 6MWT performance compared with PR alone. There were
no differences between groups in HRQL as measured using the SGRQ. The mean changes in
6MWD and SGRQ scores for both groups were below the MCIDs, except the SGRQ score for
the tiotropium group at the end of PR. There was a statistically significant improvement in
perceived dyspnea in the tiotropium group at the end of PR, but not at follow-up. Casaburi
et al.71 found that tiotropium plus exercise training increased exercise endurance of a constant
work rate treadmill task when compared with exercise training alone (difference at end of PR:
5.35 minutes [0.69, 10.00]; difference at end of 12-week follow-up: 6.60 minutes [1.15, 12.02]).
The differences in SGRQ scores for the two groups were 3.86 at end of PR and 4.43 at follow-
up, the latter being above the MCID. It appears that the rehabilitation that was used in this study
consisted only of exercise training, instead of PR. A sub-study found that the use of tiotropium
enhanced the efficacy of exercise training as measured by self-reported participation on physical
activity, although the response rate was low.72

A lower quality study73 found that six weeks of PR gave no additional benefits to patients who
were already taking tiotropium.

Airway therapies: Duiverman et al. (Appendix 5, Table A8) compared the use of non-invasive
positive pressure ventilation (NIPPV) with PR to PR alone.74 They suggest that NIPPV augments
the benefits of PR in patients with chronic hypercapnic failure by reducing dyspnea and the work
of breathing. While the NIPPV group improved in the fatigue domain of the CRQ compared with
the group receiving PR alone, there were no statistically significant differences between groups
in the CRQ total. There was no difference between groups in changes in 6MWD, which were
below the MCID.

In a poor to fair quality prospective study on inpatients with severe COPD (GOLD IV), Köhnlein
et al.75 found that those using NIPPV plus PR had better exercise tolerance and HRQL than those
using PR alone. The difference in 6MWD changes between the groups was statistically

16 PR for COPD: Clinical, Economic, and Budget Impact Analysis


significant, with the mean value of the intervention group exceeding the MCID (82 metres versus
50 metres, effect sizes 0.89 and 0.52). There were also statistically significant differences
between groups in changes to the mental health component of the SF-36 (NIPPV group
difference 13.9, effect size 0.73 versus PR group difference 8.0, effect size 0.44).

In a high-quality study, Eves et al.76 compared the use of PR, while patients were breathing a
mixture of helium and oxygen (60%, 40%), with the use of PR alone. Patients without
hypoxemia and with COPD who breathed this mixture during a PR program had increased
intensity and duration of exercise, which resulted in greater improvements in constant load
exercise time and HRQL (change in exercise time 9.6 versus 4.4 minutes, P = 0.047, change in
SGRQ score −7.6 versus −3.6, P = 0.049).

Oxygen therapy is an effective intervention to reduce dyspnea in COPD. The addition of


supplemental oxygen to maintain arterial oxygenation during exercise, which is standard care in
rehabilitation, differs from the addition of oxygen to reduce dyspnea for patients who are not
hypoxemic. A previous review concluded that the use of supplemental oxygen during physical
exercise in non-hypoxemic patients does not provide a clinically relevant benefit.77

Surgical procedures: Two studies considered PR and lung volume reduction surgery (LVRS)
(Appendix 5, Table A9). Pompeo et al.78 found that there were short-term improvements in
subjective dyspnea, inspiratory muscle strength, and exercise capacity after either treatment. The
improvements after PR were smaller and less stable than those after LVRS (change in 6MWD at
six months 31 metres versus 93 metres). The LVRS group had more late complications in
hospital than those who had PR (19 versus 4), but fewer long-term complications (3 versus 9).

Mercer et al.79 had similar findings. PR plus bilateral LVRS gave greater improvement than PR
alone in dyspnea with exercise, exercise tolerance, and subjective functional state at six months
after surgery in patients with severe COPD (change in 6MWD at six months 29 metres versus
193 metres). There was one surgery-related death.

Neuromuscular electrical stimulation in PR: In a small, fair quality RCT, Vivodtzev et al.80
compared PR plus electrical stimulation with PR alone in severely disabled patients with low
BMI (Appendix 5, Table A10). PR plus electrical stimulation produced greater improvement in
overall HRQL and in dyspnea during the performance of daily tasks than PR alone (change in
Maugeri Foundation Respiratory Failure Questionnaire [MRF–28] scores –15% versus zero,
P = 0.035 and −1.7 versus −0.2, P = 0.05). There was also improvement in 6MWD (greater than
MCID in the intervention group), although the difference between groups was not statistically
significant. The authors suggest that clinical interest in electrostimulaton is directed towards
disabled patients who are unable to perform usual exercise regularly.

g) PR context and operation


There were studies that addressed other aspects of PR relevant to the operation of programs,
including patient characteristics and program settings.

Patient characteristics: Several studies considered issues related to patients who are candidates
for PR. These studies appear in Appendix 5, Table A11.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 17


Age profile: Baltzan et al.81 found that an inpatient PR program benefited patients with COPD
who were 80 years of age or older. There was no statistically significant difference in hospital
stay (28.7 days [21.9, 24.3] versus 32.2 days [27.1, 37.3], P = 0.35) or in days spent in
rehabilitation, compared with a younger age group. The values of 6MWD, two-minute stair test,
and Global functional score improved for both groups. The mean difference in 6MWD was
above the MCID for the younger group and below it for the 80-and-over group. In a study of
poor to fair quality, Fabre et al.82 found that older (more than 65 years) and younger (65 years or
less) patients with COPD benefited from training at maximal workload, although peak power
was statistically significantly higher in the younger age group. The mean differences were above
the MCID in both groups. In a Japanese language paper on a before-after study, Ando et al.83
found similar improvements in exercise capacity for older (77 years) and younger (70 years)
groups after PR, although a Kaplan-Meier analysis indicated poorer outcomes in the older group
over the next three years.

Disease severity: Riario-Sforza et al.84 found that patients with COPD and a history of acute
exacerbations had less favourable PR outcomes than those without a history of acute
exacerbations (mean 6MWD difference 31 metres versus 58 metres, P = 0.028).

Two fair-quality studies reported that patients of all MRC dyspnea grades had similar benefits
from PR, including statistically and clinically significant improvement in exercise capacity
(mean differences in ISWT were above MCID for all grades).85,86 In a study of poor to fair
quality, Garrod et al.87 reported benefits for patients with different MRC grades, including those
with mild COPD. They found that only mild- and moderate-grade patients had clinically
significant improvements on the 6MWD and SGRQ, as judged by the mean scores being greater
than the MCIDs. The proportions of patients with a 6MWD greater than 54 metres (the MCID)
were 81% for grades 1 and 2, 59% for grades 3 and 4, and 46% for grade 5. The corresponding
proportions for those with an SGRQ of more than 4 units were 50%, 50%, and 39% respectively.

Carone et al.88 observed similar outcomes after PR for patients with or without chronic
respiratory failure, suggesting that PR is suitable for more severe patients with COPD (change in
6MWD 48 metres for both groups, change in SGRQ scores −8.3 versus −11.1, P > 0.05). Two
poor-quality studies found that patients with severe ventilatory limitations can improve exercise
tolerance with PR,89 and that the most physically impaired patients obtained the greatest
benefit.90

Adherence to rehabilitation: In a comparison of patients with COPD having medical treatment


and those receiving LVRS,91 surgical patients and those with more than 20% forced expiratory
volume in one second (FEV1) and higher education were more likely to complete PR (attendance
at 10 or more sessions 73.3% versus 85.4%, P < 0.0001). Patients with depression or anxiety
symptoms, and those at greater distance from a PR program, were less likely to complete the
program. Heppner et al.92 found that regular walking post-PR was associated with a slower
decline in HRQL and walking self-efficacy. There was no effect on the decline in exercise
tolerance.

18 PR for COPD: Clinical, Economic, and Budget Impact Analysis


Previous treatment with PR: In a good-quality study, Ries et al.93 found that patients with no
previous PR benefited more than those who had received previous PR (change in 6MWD
101.7 metres versus 60.7 metres, P < 0.01, change in SGRQ scores −5.1 versus −2.6, P = 0.01).

Gender: In fair-quality studies, Haave et al.94 and Lizak et al.85 found that PR had similar effects
for women and men. Skumlien37 found that men improved 6MWD statistically significantly
compared with women (women difference −8 metres [−36, 21], P =0.58; men difference 33
metres [13, 53], P = 0.003). Six men and one woman improved 6MWD by more than the
associated MCID. The reasons for the poor performance in the 6MWT are unclear. Twelve of 18
men and five of 15 women had a change in SGRQ that was greater than the associated MCID (P
= 0.08).

Comparisons of settings for PR: Appendix 5, Table A12 shows studies that compared the
performance of PR programs in different settings. Two high-quality studies indicated that
outpatient and home-based PR programs can give similar benefits to patients with COPD.67,95
Another high-quality study found that there was no difference in outcomes between patients who
were treated in a cold climate (Norway) and those treated in a warm climate (Spain).62

Duration of PR: Four studies compared outcomes from different numbers or types of PR
sessions (Appendix 5, Table A13). O’Neill et al.63 found no difference in the effectiveness of two
PR approaches with differing numbers of supervised outpatient and home sessions. Some
changes resulting from the use of PR were maintained at two months (difference between groups
in ISWT 3.9 metres, ESWT 131 seconds, CRQ total 9.2) and then were mostly dissipated by six
months (ISWT 0.6 metres, ESWT 87 seconds, CRQ total 6.7). Both groups achieved at least
80% adherence to home exercises over a six-week period, as indicated by diary records.
In a study of fair quality, Sewell et al.96 found that a shortened four-week supervised PR program
plus three weeks unsupervised rehabilitation at home gave similar results in a seven-week
program at the comparable time point of seven weeks and at six months follow-up. This followed
an earlier study97 that found greater benefits from the seven-week program compared with a
four-week program without subsequent home PR.

An observational study98 of poor to fair quality found that 10 weeks of PR produced limited
clinical benefits compared with those after 20 weeks PR among outpatients with mild to
moderate chronic airways obstruction. Eighteen of the 25 participants had COPD.

Verrill et al.55 compared outcomes after 12 weeks and 24 weeks of PR, and found that physical
performance continued to improve up to 24 weeks. HRQL and dyspnea improved after 12 weeks,
and improvement was maintained at 24 weeks.

Approaches to exercise training: The following studies addressed approaches to exercise


training that might be relevant to PR programs (Appendix 5, Table A14).

Carrieri-Kohlman et al.99 compared outcomes from different numbers of supervised exercise


sessions and from unsupervised home exercise. The use of a greater number of supervised
training sessions (24) improved exercise performance more than the use of four supervised
sessions and the use of no supervision. At 12 months, the changes from baseline in the endurance

PR for COPD: Clinical, Economic, and Budget Impact Analysis 19


treadmill test were 8.1 minutes (3.2, 13.0) compared with 1.9 minutes (−2.8, 6.5), and 1.1
minutes (−3.9, 6.1) for the no-supervision and four supervised session groups, respectively.
There was no statistically significant difference in the 6MWT between groups, and the changes
were below the MCID. At four, eight, and 12 months, all groups improved their mean CRQ
dyspnea subscale scores above the MCID. There was no statistically significant difference
between groups for any CRQ subscale at 12 months.

Sewell et al.100 found that general exercise training was as effective as individually targeted
training in PR. There was no additional benefit with a more complex goal-directed, individually
targeted rehabilitation approach that included exercises based on the individual’s daily activities.

Puhan et al.101 compared the outcomes of high-intensity continuous exercise with interval
exercise (high-intensity alternating with low-intensity exercise). They found no statistically
significant difference between groups in HRQL, exercise capacity, or muscular strength. They
concluded that interval exercise is no less effective than high-intensity continuous exercise and is
better tolerated (fewer breaks and better adherence to protocol).

In a good-quality study, Mador et al.102 found that interval training was well-tolerated but
showed no advantages over continuous training in exercise tolerance or HRQL.

Varga et al.103 found that continuous and interval training had similar effects in patients with
COPD, and claimed that both were superior to a self-managed program according to the results
of an incremental exercise test. The study seemed to be in the context of an “exercise only”
program instead of full PR. In an observational study, Hsieh et al.104 compared the outcomes of
patients who completed or did not complete a program that included high-intensity training. Both
groups had similar improvements in 6MWD. Only those who completed the high-intensity
exercise in PR improved maximal exercise capacity.

Magadle et al.105 considered the effects of adding INSPIRATory muscle training (IMT) to
exercise training. They found that, after six months of IMT, there was a small, statistically
significant improvement in SGRQ in the intervention group. They concluded that IMT provides
additional benefits to those undergoing an exercise program and is worthwhile, even if patients
have undertaken a previous exercise program. There was no difference in exercise capacity or
FEV1, and some data are not presented. IMT was undertaken after patients had started exercise
training, and the program involved exercise training alone without other components of PR (such
as education).

h) Specific elements of PR programs


Studies on PR and education or counselling: Education is an integral component of PR.4 The
studies that considered the effectiveness of education or counselling during PR appear in
Appendix 5, Table A15. In a high-quality study, Wittmann et al.70 looked at the effect of
structured group behaviour training followed by the development of individualized action plans
for patients. Patients who received these additional components of patient education in an
inpatient PR program had clinically significant changes in HRQL (group changes in total SGRQ
score −2.7 versus +0.4, P < 0.01).They also had improvements in hospital stay. The absence of
change in SGRQ scores for the control group (PR program only) seems surprising in view of the
drop in questionnaire scores after PR.

20 PR for COPD: Clinical, Economic, and Budget Impact Analysis


De Blok et al.106 used a pedometer with exercise counselling as an addition to a PR program.
When compared with PR alone, there was an increase in the number of steps per day after nine
weeks of rehabilitation (1,787 versus 1,220 over seven days, including rehabilitation) and in
exercise capacity (20.8 metres versus 5.8 metres for the 2MWT) but the differences between
groups did not reach statistical significance.

In a study of an outpatient PR centre, Norweg et al.107 found that patients who had activity-
specific training combined with exercise had statistically significantly greater changes in HRQL
scores than those who received exercise training plus a lecture series (CRQ total score mean
difference 3.56, P = 0.03). There was no statistically significant difference between these groups
and an exercise training group in either exercise tolerance or self efficacy.

In a study of poor to fair quality, Scherer et al.108 found that patients receiving 12 weeks of PR
with exercise and education had a statistically significant change in mean score for self-efficacy
at six months from baseline. The mean score at six months for patients who had education and
non–supervised exercise at home was not statistically significantly different from the baseline
value.

More information on the efficacy of educational interventions, outside the context of PR, is
provided by Coultas et al.109 In groups of patients with COPD, neither of two nurse-assisted
home care training approaches was effective in improving HRQL or health care utilization.
PR and nutritional intervention: Weight loss is associated with decreased exercise capacity,
decreased health status, decreased mortality, and increased morbidity among patients with
moderate to severe COPD.110 Advice on appropriate diet formed part of the educational
component of many PR programs. A few studies considered specific dietary interventions.

Three studies assessed the influence of creatine supplements on PR (Appendix 5, Table A16).111-
113
None of the studies found that creatine supplements improved exercise performance relative
to the control group.

Fuld et al. found that there was a clinically significant improvement in HRQL in the intervention
group compared with the control group(change in SGRQ total scores −7.7 [−14.9, −0.5]).111 This
difference was associated with a worsening of the activity domain for the PR group only, which
the authors described as “surprising.”

Slinde et al.114 found that an intervention involving detailed advice and follow-up by a dietician
over a 12-month period was successful in maintaining or positively modifying body weight.

In an earlier systematic review, Puhan et al.77 identified two RCTs that assessed the value of
nutritional supplements in rehabilitation for COPD. Neither study showed benefits from the
interventions. Puhan et al. concluded that the evidence for nutritional and other supplemental
interventions was too weak to recommend or discourage their use in clinical practice. The
findings from this clinical review are consistent with that position.

Psychotherapy in PR: De Godoy et al.65 compared the outcomes of patients who had PR that
included a psychotherapy component with those whose rehabilitation excluded such an

PR for COPD: Clinical, Economic, and Budget Impact Analysis 21


intervention. The results showed that patients participating in PR with psychotherapy had
clinically significantly better outcomes after 12 weeks, as measured using the Beck Anxiety and
Depression Inventories, distance walked-weight product, and the SGRQ (Appendix 5, Table A4).
In the groups who received psychotherapy, the mean changes in scores for the Beck Anxiety and
Depression Inventories and for SGRQ total scores were above the MCIDs. The group who did
not have psychotherapy had a worse outcome on the Beck Depression Inventory (mean change in
score was plus two points). The authors concluded that psychotherapy with PR reduces anxiety
and depression, and assists patients in coping with disease-related limitations by reducing
behavioural symptoms, and through influencing exercise capacity and HRQL.

Strength training in PR: The studies that considered the effects of including strength training in
PR appear in Appendix 5, Table A17. Phillips et al.115 found that the inclusion of resistance
training led to statistically significant increases in strength when compared with PR alone, but
there was no difference in exercise capacity. These authors commented that their single-set
resistance training protocol produced improvements comparable to those in studies that used
multi-set resistance training. Alexander et al.116 found no statistically significant difference
between groups in exercise capacity or muscle strength when strength training was added to PR.
Costi et al.117 found that adding unsupported upper extremity exercise training to PR improved
functional exercise capacity in patients with COPD. The authors note that it is difficult to explain
the large difference in 6MWD between the groups (74.4 metres versus 24.2 metres) with only the
intervention group reaching the MCID.

4.2.3 Clinical practice guidelines

Of the 24 practice guidelines that were identified in the literature search, four were considered to
be relevant to the Canadian context. These documents were prepared by the CTS,2,118 ACCP, and
the AACPR,4 the US Department of Veterans Affairs and Department of Defense (VA/DoD),119
and GOLD.120

The development of the selected guidelines followed processes that included comprehensive
reviews of relevant literature, evaluation of evidence by content experts, and formulation of
recommendations by expert committees, taking account of the feedback that was received. The
guidelines provide information on the strength of evidence in support of aspects of PR. The CTS,
ACCP/AACPR, and VA/DoD guidelines give recommendations and indicate the strength of the
recommendations. The GOLD document lists the benefits associated with PR and links these to
the strength of available evidence. The VA/DoD guideline includes judgments on the net effect
of the interventions. Common themes include support for the use of PR by patients with COPD
who have dyspnea and reduced capacity, and inclusion of education as a component of PR.
The recommendations and statements in these guidelines appear in Appendix 6.

4.2.4 Data analyses and synthesis

a) Effectiveness of PR
Studies that are included in this review show that, when compared with usual care
(pharmacotherapy) of patients with stable COPD, PR and pharmacotherapy provides benefits in
the short term (up to three months). In all 12 of the selected studies 28-39, there was improvement
in exercise capacity. Ten of 11 studies found improvements in HRQL, with mean changes being

22 PR for COPD: Clinical, Economic, and Budget Impact Analysis


greater than the MCID in eight studies. The mean values for changes in exercise capacity were
less than the MCID in seven of 11 studies. These findings are consistent with those in earlier
reviews showing improvements in HRQL.4,5 Seven studies were rated as being of good
quality,28-34 four of fair quality,35-38 and one of poor to fair quality.39

Two studies (of high and good quality, respectively)24,26 examining the effects of PR in patients
who had been admitted to hospital because of acute exacerbations reported contrary findings.
One found clinically significant improvements in exercise capacity and health status at three
months; the other found no difference between groups in these measures. A retrospective cohort
study27 found clinically significant improvement in exercise capacity and HRQL across all MRC
grades.

The longer-term comparisons of PR and usual care gave mixed results. A fair-quality, non-
randomized study35 found the disappearance of benefits over time. One high-quality44 and one
fair-quality study38 found that the improvements in exercise capacity were maintained over 12
and six months but with mean values below the MCIDs. Three high- or good-quality studies
found benefits in exercise capacity and HRQL at six months or more, with mean values above
the associated MCIDs. In one of these studies, the benefits in exercise capacity and HRQL were
sustained for 18 months after the end of the PR program.45 A high-quality study found that the
improvement in cycle endurance time (above MCID) was maintained, and HRQL scores
remained greater than those of controls at 20 months post-PR, although PR had no effect on
6MWD.43 A good-quality study found improvements in HRQL measures, but not in exercise
capacity, and remained above the MCID at 12 months.34

Four high- or good-quality studies compared maintenance programs and usual care following the
end of PR.50-53 Two of these studies found that home-based exercise training was effective as
maintenance, with benefits being maintained at six months50 and at 12 months51 after the end of
PR. The other two studies found more limited benefits from maintenance. A 12-month program
produced modest improvements in the maintenance of benefits, with no differences from usual
care at 24 months.53 In the other study, the limited improvement at six months had disappeared
by 12 months.52

A good-quality study, which compared the outcomes of patients who participated in two or three
PR programs over 12 months, found statistically significant improvements after the end of each
PR program, with benefits being totally or partially lost between programs.54 Two observational
studies found benefits after lengthy PR and maintenance programs.56,57 Benefits were maintained
to two years in the first study and to three years after the end of the program in the second study.
Such findings suggest that the benefits of PR can be maintained in the long term, depending on
patient adherence and availability of lengthy rehabilitation and maintenance programs.

COPD is characterized by increased incidences of depression and anxiety. Through the typical
group setting and interaction with health-care professionals, basic PR programs provide social
support to patients. Therefore, PR is likely to improve psychosocial outcomes in patients. Six
comparisons of PR and usual care (four rated as high or good quality) reported improved mental
health outcomes up to three months following PR.26,33,58-61

PR for COPD: Clinical, Economic, and Budget Impact Analysis 23


A reduction in scores for anxiety and depression were noted in four studies that compared PR
using different approaches or in different settings.62-65 In one of these studies, the scores
remained above baseline at eight months.62 In another, the differences from baseline in anxiety
and depression declined from six weeks to six months following PR.63

COPD is a burden to health care, because patients who are poorly managed often experience
exacerbations of their lung condition, present at emergency rooms, and are hospitalized for
several days receiving treatment. A goal of PR is to help patients learn how to self-manage their
disease. Therefore, PR as a component of chronic COPD management2 would help reduce
COPD-related health care utilization. The indications of reduction in health care utilization,
including hospital admissions and length of stay, were included in ten
studies24,26,34,45,48,51,56,57,68,69 that compared PR with usual care. In four high- or good-quality
studies, there was lower utilization by groups who had PR.24,26,34,45 The differences from
comparison groups were statistically significant in one of these.34 Another good-quality study
found a reduction in the number of admissions in two types of PR programs but did not provide a
statistical comparison between them.67

Four studies found reductions in hospital utilization over periods of 12 months. Three of these
studies were of poor to fair or poor quality, and all used before-after designs.

The combined findings indicate that improvements in health outcomes are observed immediately
after PR. The benefits of PR may not be maintained in the months or years after PR. This
indicates that PR can be effective at improving patient health, and that better maintenance
programs help transition patients from the typically clinic-based PR program back into the
community.

PR and other treatments


Several studies examined the effectiveness of adjunct airway therapies in combination with PR.
These included an evaluation of the use of tiotropium in addition to PR. When bronchodilation is
maximized, patients would have reduced dyspnea and could exercise at higher intensities during
PR.66,71,73 It was unclear from these studies whether or not the inclusion of tiotropium in PR
programs offered statistically significant additional benefit.

Studies on the use of NIPPV with PR had contrasting results. A good-quality study found that
this approach offered no advantages over the use of PR.74 In a poor- to fair-quality study,75 those
using NIPPV plus PR had better exercise tolerance and HRQL than patients who only used PR.

Replacing nitrogen with helium in the air that patients breathe reduces the work of breathing,
allowing patients to exercise at higher intensities during PR. A high-quality study found
statistically significant benefits for patients who used a mixture of helium and oxygen during
PR.76 This approach merits further investigation. Two studies (high and good quality) found that
lung volume reduction surgery gave greater improvement than PR alone.78,79 A small study with
severely disabled patients found PR plus electrical stimulation produced greater improvement in
HRQL and 6MWD than PR alone.80

24 PR for COPD: Clinical, Economic, and Budget Impact Analysis


PR context and operation
Patients: Fourteen studies addressed PR in terms of patient characteristics. Three studies (fair
quality, poor to fair quality, and not assessed) found that PR programs benefited patients who
were 80 years or older, 65 years or older, and 77 years old.81-83 A fair-quality study found that
patients with COPD and a history of acute exacerbations had less favourable PR outcomes than
those without.39 Six other studies that considered disease severity (two fair quality,85,86 four poor
to fair or poor quality87-90) reported the benefits of PR among patients with all grades of dyspnea.

Fair- and good-quality studies from the National Emphysema Treastment Trial (NETT) found
that surgical patients and those with more than 20% predicted FEV1 and higher education were
more likely to complete PR, and that those with no previous PR benefited more than those who
had used previous PR.91,93

Two fair-quality studies reported that PR had similar effects in women and men.85,94 Another fair
quality investigation found that men improved their walking distance statistically significantly
compared with women.37

Combined, these studies suggest that patients with COPD can benefit from the use of PR,
regardless of age, disease severity, and sex.

Settings: Two high-quality studies found home-based PR programs provided similar benefits to
patients compared with hospital outpatient PR programs.67,95 Patients with COPD often list
transportation issues as a limitation to PR participation. Therefore, home-based PR programs
would eliminate this barrier to PR participation, while increasing the system’s capacity to deliver
PR. Environmental conditions could affect patient participation and the outcomes derived from
PR. A high-quality study found there was no difference in outcomes between patients treated in a
cold climate and those treated in a warm climate.62

Duration of PR: The appropriate duration and content of PR programs are unclear based on the
studies that were included in this review. One study found that a shortened (four-week) PR
program plus three weeks of home rehabilitation gave similar results to those of a seven-week
program.96 Two studies reported increased benefits at 20 and 24 weeks compared with those at
10 and 12 weeks.63,98

Approaches to exercise training: The use of 24 supervised training sessions improved dyspnea
and exercise performance more than two other exercise approaches with less supervision.99
General exercise training is as effective as individually targeted training.100 Three studies found
that high-intensity continuous exercise and interval exercise gave similar results for exercise
capacity and HRQL.25,102,103 The addition of IMT to exercise training did not produce
statistically significant additional benefit (fair-quality study).105 Combined, these studies indicate
that more supervision is beneficial, while individually prescribed exercise training or high-
intensity training does not seem to be of added benefit.

4.2.5 Elements of PR programs

Little information was obtained from the reviewed studies on the effectiveness of different
components of PR programs. A high-quality study showed benefits to HRQL and hospital stay

PR for COPD: Clinical, Economic, and Budget Impact Analysis 25


from behaviour training and development of individualized action plans for patients.70 Good-
quality studies indicated the feasibility but not the efficacy of using a pedometer with exercise
counselling,106 and showed that supervised physical activity with controlled breathing in activity
training was more effective in improving functional status and HRQL than didactic
instruction.107

Three studies (two good-quality111,112 and one fair-quality113) on the influence of creatine
supplements found no benefits in exercise performance. One found an improvement in HRQL. A
good-quality study found that patients who used PR that included a psychotherapy component
had clinically significantly better outcomes at 12 weeks compared with those whose
rehabilitation excluded such an intervention. Two small studies that considered the effects of
including strength training in PR found that there was no influence on exercise capacity.115,116

5 ECONOMIC ANALYSIS
5.1 Review of Economic Studies: Methods
5.1.1 Literature searches

The literature search strategy was applied for the clinical review and the economic evaluation
(Appendix 1). For the review of economic studies, the main search concepts involved specific
COPD rehabilitation programs and their impact on mortality, morbidity, and HRQL. We added
the descriptors of “cost,” “cost-effectiveness,” “cost benefit,” “cost utility,” “cost consequence,”
“cost impact,” “budget impact,” and “economic.” Methodological search filters were applied to
limit retrieval to economic studies.

5.1.2 Selection criteria

We used the same selection criteria as were chosen for the clinical review, except that the
outcomes of interest were costs and clinical outcomes.

a) Inclusion criteria
We included all studies that were analyses of comparative interventions and that had an
economic component (measured the cost of implementing the technology).

b) Exclusion criteria
We excluded any study that did not report primary data and that did not contain program costs
(but may have included service delivery costs). The approaches that were taken to information
and data retrieval strategies were the same as in the clinical review.

5.1.3 Selection method

Two reviewers (PJ, AC) examined the results of the literature search and independently selected
potentially relevant articles. First, the reviewers applied the inclusion criteria to the search results
to select titles or abstracts that met all criteria. If all criteria were met or if there was uncertainty

26 PR for COPD: Clinical, Economic, and Budget Impact Analysis


or disagreement about an article’s eligibility, the paper was obtained in full text. Second, the
reviewers selected the full texts that met all the inclusion criteria. They compared their findings
and discussed any differences. Disagreements were resolved through consensus, or a neutral
third party (DH) was consulted when needed.

5.1.4 Data extraction strategy

A data extraction form was developed before the research was started (Appendix 7). The data
included study ID, country, description of setting, year, perspective, intervention (type of
services included: education, counselling, and exercise therapy), hours per session, number of
sessions per week, duration of the program, and time horizon. Cost elements included program
costs with component breakdown, utilization costs for COPD, cost for each element, method of
estimating each cost element, clinical outcome (from clinical review), cost-effectiveness ratio,
and quality of study.

The study data were extracted by one reviewer (PJ) and verified by a second (AC). Disagreement
was resolved through consensus, and a neutral third party (DH) was consulted when needed.

5.1.5 Strategy for quality assessment

Our quality score was based on Drummond and Jefferson’s checklist,121 which we adapted to the
current issue of pulmonary rehabilitation. Nine quality-related questions were addressed, and
each was assigned a score of 1 (criteria met positively) or 0 (issue inappropriately addressed):
 Is the perspective clear?
 Does the study include post-program outcomes?
 Does the study include post-program services (utilization)?
 Are all relevant services included?
 Do the authors present physical measures for services?
 Do the authors measure the full cost (for example, including all relevant resources and
overhead costs) of the services?
 Do the authors present unit costs for each service?
 Is an incremental analysis conducted?
 Is uncertainty accounted for?

Other quality indicators, such as the use of discounting, were excluded because they were
irrelevant in this setting.

5.1.6 Data analysis methods

The design of PR varied between studies, and there was no standard. The outcomes that were
used varied and, because program design varied, there was no standard cost measure. As a result,
the authors of this report could not develop an integrative analysis. Therefore, we conducted a
descriptive analysis.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 27


5.2 Review of Economic Studies: Results
5.2.1 Results of search strategy

From the electronic search we obtained 1,494 citations (Figure 2). We obtained eight citations
from other sources, for a total of 1,502 citations. After the screening, we excluded 1,476
citations. Disagreement on 10 citations was resolved by discussion. Of the 26 potential articles
that we retrieved, 17 were excluded. The reasons for exclusion were absence of program costs
(2), foreign language (2), and irrelevant articles (13).

Eight of the nine articles that met our criteria for inclusion were comparisons of PR with no
intervention. One was a comparison of inpatient PR with outpatient PR. Of the eight articles that
compared PR with no PR, seven focused on outpatient rehabilitation and one on a combination
of inpatient and outpatient rehabilitation.

5.2.2 Review of pulmonary rehabilitation versus no rehabilitation


Eight papers compared PR to no rehabilitation (Appendix 8). Five studies were published after
2000 and three were published in the late 1990s. In seven papers, the rehabilitation was
conducted in an outpatient setting. In one paper, the intervention started in the inpatient setting
and then continued in the outpatient setting.

a) White et al.122
White et al. conducted a pre-post study of a six-week, 30-hour total PR program. The program
included exercise, education, and counselling. The outcomes included distance walked in six
minutes and components of the CRQ.123 Costs included program costs, with no utilization of
health services. Of 42 persons who began the program, 36 completed it. At six weeks, three of
the four CRQ components (dyspnea, emotion, and mastery) increased at a clinically important
and statistically significant level. Changes in the fourth component, fatigue, were not clinically
significant. The cost of the program was estimated at £400 per person. There was no incremental
ratio, and we assigned the study a quality score of 2 out of a maximum of 9 points.

b) Scherer and Schieder124


Scherer and Schieder compared a one-year pre-program with up to five years post-program
analyses of hospital utilization. The intervention took 54 hours (36 1½ hour interventions) over a
12-week period. The program had three components — education, counselling, and exercise
training. There were no health outcomes assessed. The only outcome was a questionnaire, six
years after the end of the program, asking how many days the person was hospitalized during
one year before the program and each of five years afterwards. The study found that
hospitalization was lower in each of the four years after the program; there were difficulties with
data in the fifth year. The cost of the program was estimated to be between $1,500 and $2,000.
There was no incremental ratio. We rated the study a score of 3 out of 9 because of the lack of
measurements.

28 PR for COPD: Clinical, Economic, and Budget Impact Analysis


Figure 2: Selection of Reports on Economic Studies

1,494 citations identified from


electronic search, screened

8 citations from other


sources, screened

1,476 citations excluded

26 potentially relevant reports


retrieved for scrutiny

17 reports excluded:
 no program cost (2)
 foreign language (2)
 not relevant (13)

9 reports on unique studies included

c) Troosters et al.125
Troosters et al. conducted a randomized trial of outpatient PRcompared with usual care. The
intervention lasted six months. In the first three months, the patients visited the clinic three times
a week for 1.5 hours. In the subsequent three months, the patients visited twice weekly. The
intervention lasted for a total program contact time of 90 hours. The intervention consisted only
of exercise. The main outcomes were the CRDQ and the 6MWT. Of the 50 patients who
participated in each arm of the trial, 37 completed the program in the intervention arm, and 33 in
the control arm. A final observation was made at 18 months after entry to the program. The
increase in the four components of CRDQ at the end of the six-month program was clinically and
statistically significant. There was a statistically significant increase in the 6MWD at 18 months.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 29


The cost of the program was US$2,615 per person. Utilization was not measured. We gave the
study a quality score of 4 out of 9, because of missing information.

d) Jenkins et al.126
Jenkins et al. conducted a baseline post-analysis of an exercise program. The program was held
in a clinic, and patients attended twice a week for one hour. The program lasted eight weeks (16
hours in total). Of the 72 patients who were enrolled, 57 completed the program. The outcomes
were the CRQ and SF-36, which were measured at the end of the eight-week period. The authors
measured program costs but did not measure utilization of health services related to COPD. The
program costs excluded overhead costs. In total, the program cost was A$249 per person. The
outcomes increased at eight weeks, compared with baseline, and were clinically significant. We
rated the study a score of 5 out of 9, because of the lack of follow-up data, incomplete measures
of costs, and no comparison group.

e) Griffiths et al.127
Griffiths et al. conducted a randomized trial in an outpatient setting that compared PR to usual
care. The patients attended three two-hour sessions for six weeks (36 hours). The program
included education, counselling, and exercise sessions. Of the 99 patients who were enrolled in
the study group, 92 completed the program; and of the 101 in the control group, 88 completed
the program. The final observation period was at 12 months. The outcomes were the SF-36, from
which quality-adjusted life-years (QALYs) were derived. The study included care related to the
patient’s condition, for up to one year. The cost of the intervention included operating costs,
overhead costs, and transportation costs. The results indicated that the net difference in QALYs
was + 0.03. The cost of the intervention program was £725 (Cdn$1,450), and the cost of health
care was £1,671 for the study group and £1,826 for the control group over the observation
period. Using probabilistic analysis, 95% of all observations fell below £17,000 per QALY. We
assigned a quality score of 9/9 to the study.

f) Golmohammadi et al.7
Golmohammadi et al. conducted a before-after analysis of an outpatient program. Participants
completed the program in six weeks (three days per week) or eight weeks (two days per week).
The sessions lasted 2.5 hours. The program provided education, counselling, and rehabilitation.
The program costs included operating and overhead costs. The observation period for outcomes
was the duration of the program and for costs it was twelve months. Hospitalization and
outpatient services were measured for one year before and one year after the program. Utilization
for a comparison group of non-attendees with COPD was also used. The outcomes for the 210
program participants were based on the SGRQ. The program cost per person was $1,092, and the
program saved $344 in utilization. We assigned a quality score of 5/9 because of a lack of a
comparison group.

g) Cecins et al.128
Cecins et al. conducted a before-after analysis of an outpatient program. The program offered
education and exercise therapy. The program had two sessions a week for eight weeks. Each
session lasted 1.25 hours. The outcomes were measured at baseline and after eight weeks using
the CRDQ, and utilization was measured after one year. Program costs included operating and
overhead expenses. Of the 256 persons who enrolled in the program, 187 completed the
program. The program cost A$292 per person, and overall there were savings of A$397,000. The

30 PR for COPD: Clinical, Economic, and Budget Impact Analysis


outcomes were statistically significant. We assigned a rating score of 7 and noted that an
appropriate control sample was missing.

h) Goldstein et al.129
Goldstein et al. conducted a combined inpatient-outpatient program for patients with severe
COPD. The inpatient program lasted eight weeks (five days per week), and the outpatient portion
lasted eight weeks. The program was an RCT with the comparison group being usual care. The
program included counselling, education, and exercise therapy. The observation period lasted 24
weeks. The outcomes included walking distance in a given time and CRDQ. The program costs
included overhead and operating expenses. The authors excluded utilization for COPD. The
results showed that CRQ improved in the study group, with the difference in CRQ mastery being
0.7. The program cost $12,251 per person; the same services that were used by the control group
cost $663. The authors provided a cost per unit, with the cost for achieving a clinically
significant outcome being $28,893. We assigned this study a quality score of 7, and note that
utilization for COPD is missing.

i) Clini et al.130
Clini et al. compared inpatient to outpatient pulmonary rehabilitation in patients with chronic
airway obstruction (a combination of patients with COPD and with asthma). The inpatient group
was offered 11 daily sessions over 19 days, each session lasting three hours. The outpatient
group was offered 21 sessions over eight weeks. These sessions also lasted three hours. The
intervention in each arm included education, counselling, rehabilitation, and exercise. The
observation period was the period of the intervention. The patients were assigned to each arm
using randomization. The outcomes included respiratory muscle strength, maximal inspiratory
pressure, and expiratory pressure. The program costs included operating costs, overhead costs,
and transportation costs of providing the rehabilitation services. The costs of hospital stay were
excluded. Health services use was excluded. The outpatient services cost more (€3,677) than
inpatient services (€2,720), because there were more outpatient sessions. The outcomes were
similar. We assigned a quality score of 6/9. The study did not have any information on post-
program utilization and outcomes.

5.2.3 Summary of results

In eight of nine studies, the intervention was on an outpatient basis. These eight studies did not
have a common intervention. Rehabilitation or exercise was provided in all of them, patient
education was provided in six, and counselling was provided in three. The cost per participant
ranged from US$292 to US$2,615. In the full-service group, the cost ranged from US$800 to
US$1,450. Therefore, the mean cost was approximately $1,100. There were insufficient data on
utilization to make generalizations. The best documented study of health system costs was
Griffiths’s127 study, which showed a reduction of approximately 150 GB Pounds Sterling in the
intervention group. As a result, it was not possible to provide a numerical cost-effectiveness
result.

The outcomes were better in the study groups, but the outcome measures were not uniform.
Whether the study used CRQ, QALYs, or SGRQ, the outcomes were better during the study
period. In the two studies with physical measures, the outcomes improved.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 31


5.3 Primary Economic Evaluation: Methods
5.3.1 Type of economic evaluation

We conducted a cost-utility analysis because the outcomes focussed on changes in HRQL that
are affected by COPD exacerbations. Survival is not a key outcome indicator because of the
short-term impact of PR.

5.3.2 Target population

The patients with COPD in the economic model were representative of those who had COPD in
a national (United States) population consisting of 79% males, 21% females, 87% white, those of
an average age of 61 years (standard deviation 7.7), and 97% current or former smokers.131 All
persons with COPD, whatever the severity, are included in the analysis, because all are potential
candidates for PR use.

5.3.3 Comparators

The cost-utility analysis was used to compare the costs and health outcomes between usual care
(pharmacotherapy) and usual care plus pulmonary rehabilitation. Usual care as pharmacotherapy
is assumed to be optimal (it is assumed that all persons with COPD get long-acting anti-
cholinergics). It is assumed that persons with stage 2 and 3 (GOLD criteria) COPD also get
combination therapy (long-acting beta agonists and corticosteroids). PR includes exercise
therapy, education, and counselling. The PR program consisted of three sessions per week at 2.5
hours per session over six weeks (total of 45 hours), which is the approximate average based on
all programs that reported such data. Pulmonary rehabilitation is given to patients once.
Pharmacotherapy is continual COPD care.

5.3.4 Perspective

A health system perspective was taken in the analysis. This includes government and private
payers. We included all the resources that are used to produce pulmonary rehabilitation, all
affected health services, and all pharmaceuticals. For pharmaceuticals, government plans vary by
province. We have included all drug costs. Pulmonary rehabilitation is not provided widely in
any province. It is not an “insured” service that is federally mandated. Because it is a “health
service,” its full cost is included.

5.3.5 Effectiveness

Based on the clinical review, there is evidence that the use of PR reduces the risk of
exacerbations compared with usual care. There is no evidence of a differential impact on
mortality, and there was little information describing usual care. Nevertheless, a baseline
treatment is needed for the comparative analysis. In this analysis, usual care is based on the
CTS guidelines of providing for stage 1 COPD and long-acting anti-cholinergics, and CT for
stages 2 and 3.

32 PR for COPD: Clinical, Economic, and Budget Impact Analysis


5.3.6 Time horizon

Based on the clinical review, no studies evaluated the efficacy of PR longer than three years.
Hence, it is uncertain whether or not the benefits of PR will last that long without a booster.
Accordingly, the base case simulation model evaluates PR in one scenario ― an 18-month
horizon.34 There is evidence of a one-year program with a home exercise booster having a
positive impact at three years.56 This alternative is covered in a sensitivity analysis.

5.3.7 Modelling

All analyses were conducted using Microsoft EXCEL and TreeAge Pro Suite (TreeAge Software
Inc; Williamstown, MA). The simulation model is based on an epidemiologic model of the
natural progression of COPD (Figure 3). The assumptions and sources appear in Table 1. In the
model, patients are divided into three mutually exclusive disease severity categories:132
 Stage 1 disease was defined as forced expiratory volume in one second (FEV1) 50.0% or
more of predicted.
 Stage 2 disease was defined as FEV1 of 35.0% to 49.9% of predicted.
 Stage 3 disease was defined as FEV1 less than 35.0% of predicted.

It is assumed that at baseline, 93% of the patient population had stage 1 disease, 4% had stage 2
disease, and 3% had stage 3 disease.131 Over time, less severe stages of COPD progress to more
severe stages because of declining FEV1. Using estimates of the mean rate of FEV1 reduction for
each severity group from the literature, the model simulates the three-month transition
probability for a person in stage1 progressing into stage 2 and a person in stage 2 progressing
into stage 3.

For each three-month cycle, there is a probability of death. All-cause mortality rates for COPD
were estimated to be 3.92% in stage 1, 6.16% in stage 2, and 9.24 % in stage 3 disease.133 All-
cause mortality was chosen because patients with COPD may die from the complications of
COPD and other causes, and the distinction may be unclear. Furthermore, there is an increasing
frequency of exacerbations and a possible increased risk of mortality associated with the more
severe stages of COPD. COPD exacerbations can be divided into three mutually exclusive
categories:134
 Mild: Defined as worsening of symptoms requiring routine physician services and the use of
medications or antimicrobials (exacerbation therapy).
 Moderate: Defined as clinical episodes requiring emergency department services.
 Severe: Defined as requiring inpatient care (including exacerbation therapy).

a) Economic model
The economic model is shown in Figure 3. Exacerbations, which are the primary driver of health
services utilization costs, negatively affect HRQL. For each comparator, all patients are followed
over six intervals. During each interval, they face a probability of mild, moderate, or severe
exacerbations, depending on the severity of the person’s COPD. They stay in a given cycle,
progress to a higher level of severity, or die. Over the 18-month period of the model, each person
accrues exacerbations (by severity), health outcomes (QALYs), and health services utilization
and costs. The resulting 18-month costs and health outcomes of each comparator are compared
with the alternative to estimate the cost-effectiveness analysis.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 33


Figure 3: Simulation Model for Economic Analysis

34 PR for COPD: Clinical, Economic, and Budget Impact Analysis


5.3.8 Valuing outcomes

a) Health outcomes
HRQL is measured in QALYs. A QALY based on the EQ-5D was obtained for the duration of
each of the three stages (Table 1). The EQ-5D provides descriptive health status scores ranging
from −0.59 to 1.00.135 A score of 0.0 represents death, and a score of 1.0 represents perfect
health. Negative scores represent health states that are considered to be worse than death. The
minimally important clinical difference for the EQ-5D is 0.074.135 A QALY weight is applied to
each stage of COPD (baseline index of HRQL associated with the stage of COPD). For each
exacerbation event, QALYs are reduced by a specific amount, depending on the severity of the
exacerbation (Table 1).

5.3.9 Resource use and costs

a) Model inputs
Model inputs (for example, probabilities, costs, and outcomes) are derived from the clinical and
economic review in this report, published literature, and databases. Canadian data will be used
whenever possible.

Costs: The cost of care consists of the costs of routine maintenance, exacerbations,
pharmacotherapy, and pulmonary rehabilitation (Table 1). Routine maintenance services for
persons with COPD were based on those found in Oostenbrink et al.’s136 study. The amount of
services for routine maintenance care varied according to severity.

The number of exacerbations by level of severity (Table 1) is based on data from recent studies.
The services and costs increase with severity. A mild exacerbation leads to a physician visit and
use of medications, a moderate one may lead to the use of additional emergency services, and a
severe one may lead to the use of additional hospitalization, including ICU care. We used service
estimates for Ontario from Mittmann et al.137 for the two higher levels of severity. All others
were derived for Alberta (Table 1).

The pharmacotherapy costs of alternative treatment regimens were based on recommended doses
and 2008 drug prices as listed in the 2008 Alberta Health and Wellness drug plan formulary. The
cost of the pulmonary rehabilitation program consisted of the costs of administration (13%), rent
(3%), staff, and supplies, based on Golmohammadi’s7 study.

All costs were updated to 2008 levels using the General Consumer Price Index, which was
obtained from Statistics Canada.

b) Criteria for cost-effectiveness


The analysis will identify the differences in costs and QALYs between usual care, and usual care
and PR. The criteria for concluding that PR is cost effective are (all comparisons are to usual
care):
 If usual care plus PR is more costly and less effective, then usual care plus PR is not cost-
effective.
 If usual care plus PR is less costly and more effective, then usual care plus PR is cost-
effective.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 35


 If usual care plus PR is more costly and more effective, then it is uncertain whether usual
care plus PR is cost-effective, because it depends on whether or not decision-makers deem
the additional effectiveness to be worth the additional costs.
 The ICER is the ratio between the differences in costs and in QALYs between usual care
and usual care plus PR. The ICER is compared with a minimally acceptable value
(represents a decision-maker’s willingness to pay for an additional unit of improvement)
to conclude whether usual care plus PR is cost-effective. A cost per QALY threshold of $
Cdn 50,000 is commonly used as a threshold for determining cost-effectiveness.138
Therefore, usual care plus PR is considered to be cost-effective if its ICER is below a
threshold of $50,000 per QALY gained.

5.3.10 Discount rate

All costs were discounted at 5% for the base case, and at 3% and 0% for sensitivity. Given the
18-month time span of the study, the discount rates are of minor importance to the results and are
not reported in the sensitivity analysis.

5.3.11 Variability and uncertainty

a) Sensitivity analysis
A probabilistic sensitivity analysis was conducted using 100,000 Monte Carlo simulations to
generate the distribution of potential costs and effectiveness associated with each treatment.

We conducted one-way sensitivity analysis for the following variables:

Relative risk from pulmonary rehabilitation: The only estimate for this variable was obtained
from Güell et al.45 (0.48). We used probability estimates ranging from a low value of 0.28 to a
high value of 0.68.

Program cost: We assumed a low value of $250 per person128 and a high value of $5,400130 per
person. We also estimated the cost at which the ICER was equal to $50,000.

Duration of benefits: There was variation in the estimates of the duration of benefits. The most
common measure was twelve months.34,44,49,51 Güell et al.45 reported an impact at 18 months, and
Lomundal and Steinsbekk56 reported an effect at three years, although the latter was with a
booster. We estimated cost-effectiveness at two years, three years, and the base case, which was
for 18 months.

Program uptake: In our base case, we assumed a program uptake of 80%. We also estimated
the cost-effectiveness with a 60% uptake.

Exacerbations: There are differences in the literature on exacerbation rates. We used an


alternative set of rates, based on Sin et al.132 This set of numbers had fewer exacerbations
overall, with almost all the difference being in the mild and moderate groups. Severe cases had
the same number of exacerbations.

36 PR for COPD: Clinical, Economic, and Budget Impact Analysis


Table 1: Model Inputs
Base Case
Inputs Stage 1 Stage 2 Stage 3 Distribution Sources
132
Baseline distribution of patients 93% 4% 3% None
132
Progression to next stage of disease 2.97% 9.94% Not Uniform
(2.87 to 3.07) (9.84 to applicable
10.04)
139
All-cause mortality rates (events/100 person years) 3.92 6.16 9.24 Uniform
(3.72 to 4.12) (5.85 to (8.78 to
6.47) 9.71)
Exacerbations per person, per year a. Gamma All stage 1 and mild stage 2:140
Mild b. Beta Moderate stages 2 and 3: 141
Moderate 0.13 (0.02) b 0.87(0.02) b 2.43 (2.1) a Severe stages 2 and 3: 142
Severe 0.09 (0.01) b 1.9 (1.8) a 2.3 (1.9) a
0.007(0.003)b 0.08 (0.01)a 0.2 (0.01)a
45 *
Relative risk from pulmonary rehabilitation 0.48 (0.02) 0.48 (0.02) 0.48 (0.02) Beta
136,143
Quality-adjusted life-years (annual) 0.8971 (0.11) 0.750 (0.27) 0.549 Beta
(0.31)
136
Reduction in cyclic QALY when the person None
experiences a:
Mild exacerbation 5% 5% 5%
Moderate exacerbation 15% 15% 15%
Severe exacerbation 70% 70% 70%
63
Adherence 80% 80% 80%
136
Annual cost of maintenance for person with $194 $186 $495 Gamma for volumes with Alberta
COPD ($174 to $214) ($205 to ($445 to 2008 prices
$212) $545)
137
Cost of a mild exacerbation $68 $68 $68 Gamma
($61 to $75) ($61 to $75) ($61 to
$75)
137
Cost of a moderate exacerbation $305 $305 $305 Gamma
($275 to $336) ($275 to ($275 to
$336 $336
137
Cost of a severe exacerbation $5,555 $5,555 $5,555 Gamma
($4909 to ($4909 to ($4909 to
$5,999) $5,999) $5,999)

PR for COPD: Clinical, Economic, and Budget Impact Analysis 37


Table 1: Model Inputs
Base Case
Inputs Stage 1 Stage 2 Stage 3 Distribution Sources
144
Average daily cost of LAAC $2.10 $2.10 $2.10 Gamma
144
Average daily cost of combination therapy Not applicable $3.13 $3.13 None
Cost of a PR program $1,211 $1,211 $1,211 Triangular Base cost based on estimate of
($250 to ($250 to ($250 to $1,092,7 adjusted to 2008 by
$2,500) $2,500) $2,500) Canadian Consumer Price Index
* The standard error was estimated from conducting 500 Monte Carlo simulations on the separate exacerbation estimates reported for the control and intervention groups.

LAAC = long-acting anticholinergics; PR = pulomonary rehabilitation


NOTE: Values for distribution are in parentheses.
a
Gamma distribution
b
Beta distribution .

38 PR for COPD: Clinical, Economic, and Budget Impact Analysis


5.4 Primary Economic Evaluation: Results
5.4.1 Analysis and results

a) Base case
In the base model, costs and outcomes are driven by exacerbations. For the entire group of
persons with all severity levels and without rehabilitation, the average number of mild
exacerbations per year was 0.968. With rehabilitation, the average number of mild exacerbations
was 0.624 per year (a difference of 0.344). The average person had 1.456 moderate
exacerbations without rehabilitation and 0.904 exacerbations with rehabilitation (a difference of
0.552). The average person had 0.336 severe exacerbations without rehabilitation and 0.236 with
rehabilitation (a difference of 0.1). Mild exacerbations only included those for which a physician
visit was required. Some mild exacerbations may not have required care, but these are not
reported in most studies.

In the base-case model, a person with usual care and no rehabilitation had an average of 1.107
QALYs for an 18-month period. A person with rehabilitation had 1.149 QALYs over the 18-
month period of the model. A person in “perfect” health would have a QALY of 1.500 during an
18-month period.

In the base-case model, the cost per person without rehabilitation (including drugs and other
maintenance costs) and costs for treating exacerbations over an 18-month period was $2,025.
When rehabilitation is added, the costs increase to $3,209. The increased costs of rehabilitation
($1,211) are offset by a reduction in maintenance costs, so that the net difference is $27.

b) Probabilistic results
The cost-effectiveness of rehabilitation is calculated as the difference between costs and
outcomes ($27,924 per QALY). The probabilistic results appear in Figure 4. The curve is steep,
and almost 90% of all observations in the probabilistic analysis fall below $50,000 per QALY,
which is an often-used threshold.

c) One-way sensitivity analysis


The results of the one-way sensitivity analyses appear in Table 2. We varied the key
effectiveness variable, the relative risk of exacerbations with PR (base value 0.48) from 0.28 to
0.68. At 0.28, the ICER was almost $50,000. At 0.68, the ICER was $17,550 per QALY. Within
a broad range of effectiveness, PR is cost-effective (under a threshold value of $50,000 per
QALY).

We varied the program costs from $250 to $5,400 per person, which is the range of programs in
our literature review. At a program cost of $5,400, the ICER is $120,516 per QALY. PR would
not be cost-effective if the program cost was this high. If the program cost were $2,300 per
person, the cost per QALY threshold of $50,000 would be reached.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 39


We varied the duration of program benefits. The cost per QALY is $39,000 if the duration is 12
months and $69,000 if the duration is six months. The longest period observed in the literature
was 36 months, with a booster, which we estimated to cost $250. PR is more cost-effective with
a booster, because the cost per QALY was $15,787.
The 60% adherence rates increased the ICER to $37,000. The revised (lower) numbers of
exacerbations increased the cost per QALY to $49,000.

Table 2: Results of One-Way Sensitivity Analyses


Variable Value-Tested ICER
Base case All base values $26,962 per QALY
Relative risk of an exacerbation with or
without PR
High value .68 $17,550 per QALY
Low value .28 $49,864 per QALY
Program cost per person
Low value $250 $2,570 per QALY
High value $5,400 $120,516 per QALY
Duration of benefits 6 months $69,000 per QALY
12 months $39,000 per QALY
24 months $20,163 per QALY
36 months with $250 $15,787 per QALY
booster per year
Exacerbations per year:
Mild (stages 1/2/3) .159/.153/0 $49,911 per QALY
Moderate (stages 1/2/3) .006/.365/.679
Severe (stages 1/2/3/) .004/.071/.251
Adherence 60% $37,000 per QALY
ICER = incremental cost-effectiveness ratio; PR = pulmonary rehabilitation; QALY = quality-adjusted life-year

40 PR for COPD: Clinical, Economic, and Budget Impact Analysis


Figure 4: Probabilistic Results for Cost-Effectiveness

Acceptability Curve

0.9

0.8

0.7
Probability Cost-Effective

0.6

0.5

0.4

0.3

0.2

0.1

0
0 50000 100000 150000 200000 250000
Willingness to Pay

PR for COPD: Clinical, Economic, and Budget Impact Analysis 41


6 HEALTH SERVICES IMPACT
6.1 Population Impact
Few people with COPD receive PR. In 2006, it was reported that approximately 775,000 persons
in Canada over the age of 35 years were diagnosed with COPD.145 The estimate for the capacity
of all PR programs in 2005 was 8,927 persons,6 which is approximately 1.1% of the COPD
population. It is unrealistic to assume that the capacity will meet all the recommended
rehabilitation in one year. Therefore, the element of time must be considered in our analysis.

Time enters into our budgetary analysis in two ways. First, it takes time to bring additional
resources to PR. Health care providers plan for programs and then procure space and equipment.
Appropriate personnel, including therapists, are hired from other positions, or they are trained.
When a decision is made to increase rehabilitation services, it takes years for the health regions
to put the resources into place.

Second, because of the large number of persons with COPD who are not served, health regions
will probably be unable to serve the entire target population using standard program designs. We
can estimate the number of people who will or will not be served over a specified time frame.
The budget analysis is then conducted over this period.

6.2 Budget Impact


6.2.1 Method

a) Budget impact model


In the budget impact model, the goal is to meet the total need for PR over a selected time frame.
We have chosen a time horizon of ten years to bring a more modest amount of resources into
use. We begin the model using the Canadian COPD prevalence in 2006 for our baseline estimate.
In each of the following ten years, the COPD population is increased by the COPD incidence and
reduced according to the COPD mortality rate.

Using COPD prevalence data, we estimate the number who are recommended to receive PR
(who are in need) using different assumptions. The desired capacity for PR in each year is
estimated as current capacity plus the number of additional persons served. We define the latter
variable (additional persons receiving PR) so that the cumulative number served equals the total
needs of the population by ten years.

To estimate the budget impact of the additional services, we multiply the unit cost of PR by the
number of additional persons served per year.

b) Data
COPD prevalence: We obtained an estimate of the population in each province by age group
(35 to 44 years, 45 to 54 years, 55 to 64 years, 65 to 74 years, and 75 years or older) for 2008
from Statistics Canada. We obtained the country-wide percentage of persons in each age group
who had been diagnosed with COPD from the Public Health Agency of Canada’s chronic disease

42 PR for COPD: Clinical, Economic, and Budget Impact Analysis


website. These data were based on the 2006 Statistics Canada Canadian Community Health
Survey. We used the prevalence rate and the Canadian age-specific populations to obtain the
number of persons with COPD nationally.

COPD incidence: The incidence of COPD was based on a study from Rotterdam, the
Netherlands,146 which included persons over the age of 55 years. We used this estimate because
Canadian data were unavailable. The incidence was 9.2 per 1,000 person-years. Using the
baseline number of persons with COPD in that study (11.6% of the baseline population), we
estimated the incidence rate as a percentage of the baseline prevalence, which was 7.9%.

COPD mortality: The mortality rate is the overall average Canadian rate of COPD mortality in
2006.145

Need for PR: We used different estimates to obtain the number of persons in each province who
are recommended for PR.
 The guidelines of the National Institute for Health and Clinical Excellence (NICE) in
England suggest that 25% of persons with COPD are moderate or severe, and these persons
should be targeted.147 We used these numbers (assuming 100% uptake) in our first estimate
of program expansion because Canadian estimates were unavailable. Canadian guidelines are
similar to those of NICE.
 According to the NICE guidelines, there is an uptake of 67% in the UK. We adjusted the rate
obtained in the first estimate by 67% to obtain a second estimate.
2
 According to the CTS guidelines, all persons with COPD should receive PR, because early
therapy has been shown to be beneficial. Therefore, in our third estimate, we assume that all
persons should be offered services.
 Using estimates from the United States National Health and Nutrition Examination
Survey,132 7 % of persons with COPD have been classified as moderate or severe (FEV1 less
than 50%). In a separate estimate, we will assume that only these persons will be provided
with rehabilitation.

Cost of PR: We assume that the per person cost of pulmonary rehabilitation is $1,211. This is
based on Golmohammadi’s Alberta estimate for an outpatient program in 20047 of $1,092,
adjusted to 2008 by 110.9% using the Canadian Consumer Price Index.148 In the Edmonton
program, the services included exercise therapy, education, and counselling. The program
required persons to attend three times per week at 2.5 hours per session for six weeks (a total of
45 hours). There were 10 persons per class. The costs of this program consisted of administration
costs (13%), rent (3%), and the remainder for staff and supplies. All are operating costs that are
incurred by the health services or regions.

Based on our economic literature review, there is a range of costs in programs. The differences
are due to program content, the number of hours, and the size of the group. In our sample of five
programs for which data were available (Jenkins et al,126 Troosters et al.,125 Golmohammadi et
al.,7 Griffiths et al.,127 and White et al.122), two programs offered only exercise therapy; and three
offered exercise therapy, counselling, and education. Total hours ranged from 16126 to 90,125 with
the mode between 30 and 40 hours. Class size was between eight and 12 except in the Troosters
et al.125 study, which had a staff to patient ratio of 1:1. As a result, there was a range in costs

PR for COPD: Clinical, Economic, and Budget Impact Analysis 43


from $250126 to $2,500.125 The mode was $1,200. Therefore, we used two additional values in
sensitivity analyses: $250 per person and $2,500 per person.

We estimated the cost of treating the entire target population and the additional cost of meeting
their needs. The latter estimate was obtained by deducting the current costs of serving the 8,927
persons, based on the 2005 national capacity estimates.6

c) Results
Details of the Canada-wide impact of expanding PR for the COPD population appear in
Appendix 9. In Model 1, we use the baseline assumptions with no provision for program
expansion; the volume of services remains at the current level (8,927 persons served) for ten
years. At the end of that period, 89,000 persons will have been served, and the need for the
surviving COPD population will have grown to 371,000 persons. Therefore, there will be
approximately 281,000 persons who meet the NICE criteria, but who are unserved. There will be
no additional budgetary needs.

In Model 2, we assume a need for PR of 25% of persons with COPD (as in the NICE
assumptions), with a 100% uptake. At the end of the ten-year period, the need will be for
371,000 persons served. To meet the need, approximately 28,000 additional persons will be
served per year. This means an additional budget of $33.9 million annually. If only 67% of those
who are in need use the services (Model 3), 15,900 additional places are needed annually. This
requires an additional budget of $19 million annually.

In Model 4, we make our estimates based on the assumption that all persons with COPD need
PR. With this assumption, 139,000 additional persons will be served annually for an additional
annual cost of $168 million. In Model 5, we assume that only the moderate and severe cases
need PR. This will require that 1,505 additional persons are served annually, for an added cost of
$1.8 million.

In Table 3, we present a provincial breakdown of the estimated budgetary impact of the different
models. The percentage breakdown is based on the distribution of the population who is over 65
years.

44 PR for COPD: Clinical, Economic, and Budget Impact Analysis


Table 3: Provincial Estimates of Cost of Providing Services to COPD Population
Jurisdiction Per Cent Model 2 Model 3 ($) Model 4 ($) Model 5 ($)
of Total ($)
Newfoundland and 1.7 561,077 318,597 2,791,352 30,058
Labrador
Prince Edward 0.4 151,413 85,977 753,278 8,111
Island
Nova Scotia 3.1 1,042,202 591,794 5,184,945 55,832
New Brunswick 2.4 826,403 469,257 4,111,348 44,272
Quebec 24.4 8,270,399 4,696,186 41,145,163 443,057
Ontario 38.2 12,967,029 7,363,076 64,510,856 694,662
Manitoba 3.5 1,198,568 680,583 5,962,863 64,209
Saskatchewan 3.0 1,032,296 586,169 5,135,665 55,302
Alberta 9.2 3,132,974 1,778,998 15,586,516 167,838
British Columbia 13.7 4,650,640 2,640,776 23,136,894 249,141
Yukon 0.1 29,009 16,472 144,320 1,554
Northwest Territory 0.1 28,301 16,070 140,800 1,516
Nunavut 0.0 13,443 7,633 66,880 720
Canada 33,903,755 19,251,589 168,670,880 1,816,273

d) Discussion
In Canada, an estimated 8,900 persons with COPD receive PR services annually. The estimated
total cost of serving these persons is $10.7 million. We estimated the impact on the provincial
budgets of providing additional services. If the Canadian guidelines are followed and services are
provided to all persons, then the provinces spend an additional $168 million annually over the
following ten years. This will allow them to gradually cover the entire population in need. If
more restrictive estimates of need are used, then the budgetary needs will be less. For example, if
we use NICE’s assumptions, then the provinces will spend an additional $19 million annually.

In our model, we assume that there is a backlog of need, and that it will take ten years to
eliminate it. In the interim, there will be persons with unmet needs. Given the large additional
resource requirements and competing needs in the public systems, any larger expansion to reduce
the time needed to eliminate this backlog would be unrealistic.

The proportion of persons who receive PR is low (approximately 1.1% in Canada). The same is
true in other developed countries. For example, Yohannes and Connolly149 estimated that in
England between 1.0% and 1.5% of the COPD population received such services in 2001. In
France, the Fédération Française des Associations et Amicales de malades, insuffisants ou
handicapés respiratoires estimates that of a COPD population of 3.5 million, of whom 900,000
have severe symptoms, 30,000 persons receive PR annually. This is approximately 0.8% of the
people who have COPD.150 In Australia, the proportion of persons with COPD who receive PR is
approximately 1%.151 These numbers remained low, despite the availability of evidence on PR
for over a decade.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 45


Given the chronically low level of attention given to PR and the looming high budgetary needs,
current budgetary requirements may not be realistic. One alternative would be to focus on less
costly models of care. For example, Jenkins et al.126 studied a model of 16 hours in total, with a
quarter of the cost of the inexpensive model that we used in the analysis. There is little evidence
about the relative efficacy of models with varying levels of resource intensity.

The limitations in information used in our analysis may have biased our results. First,
commentators stated that COPD is incompletely reported, and that the true incidence is higher
than the figures used in our analysis.145 If regions increased surveillance and the number of
persons diagnosed, this would increase the need for PR. Second, we did not account for mortality
in our estimate of patients served. Although the number would be small (approximately 1%
annually), some of those who received PR would die during the period analysed, and the need
would be greater than we stated, although this would not affect the order of magnitude of the
results. Third, we assumed that the addition appeared in the first year of the program. In fact, it
would take years to increase the capacity, and costs would be lower in the earlier years.

The time horizon of ten years is an example. Any longer horizon would mean more persons
would not be served in the interim. If health regions had a shorter adjustment period, then a
greater strain would be placed on the health care system.

6.3 Planning, Implementation, Utilization, and Legal or


Regulatory Considerations
Planners would need to consider the elements to be offered in a PR program, the duration of the
program, and the nature and availability of subsequent maintenance. The availability of
appropriately qualified health professionals would be essential. The economic model used in this
assessment indicates that an incremental ICER for PR compared with usual care was $27,924.
Information from the clinical review suggests that the duration of PR effectiveness will be
relatively short in most programs.

Those who plan and operate PR services should consider levels of participation in rehabilitation
and maintenance programs. The ACCP/AACPR guideline notes the difficulties in achieving
long-term patient participation. A relatively small proportion of patients who are offered a
community-based exercise maintenance program will accept it and adhere to it. For example,
Cockram et al. reported participation in PR and a subsequent community-based maintenance
exercise program.152 Of 467 patients (80% with COPD) who were referred to a PR service, 230
entered PR. Eighty-four of the 172 patients who completed PR chose the maintenance program,
and 46 were attending at follow-up.

6.4 Ethical Considerations


6.4.1 Efficiency versus equity

Access to PR services in Canada is limited. Information from studies in the clinical review is
consistent with the conclusions of earlier reviews4,5 that PR provides comparable benefit to all

46 PR for COPD: Clinical, Economic, and Budget Impact Analysis


age groups and for all degrees of disease severity. There seems to be no single basis for selecting
particular groups of patients for PR.

6.4.2 Process or procedural issues

An issue in the provision of effective PR is the ability to achieve high levels of patient
participation and compliance with rehabilitation processes. There is evidence to suggest that
higher levels of patient supervision in PR programs are associated with better outcomes. The
duration and extent of benefits from the use of PR will be associated with how well patients
accept and comply with maintenance programs. The ACCP/AACPR guideline notes that shorter
program duration can reduce the cost per patient served and spread limited resources. On the
other hand, longer program duration may produce greater gains and improved maintenance of
benefits.4 Increasing levels of contact with rehabilitation professionals will have resource
implications, but failure to meet these implications will tend to lower the effectiveness of the
intervention.

7 DISCUSSION
7.1 Summary of Results
When compared with the usual care of patients with stable COPD, PR provides benefits in the
short term (up to three months) as indicated by improvement in exercise capacity, HRQL, and
mental health.28-39 The mean values of changes in exercise capacity, however, were less than the
MCID in most studies. These findings are consistent with those of earlier reviews showing
improvements in HRQL.4,5 Studies on the effects of PR in patients who had been admitted to
hospital because of acute exacerbations had contrary findings,24,26,27 so that the effects on
exercise capacity and health status are uncertain for such groups. The differences in the
definition of what is “ usual care” has been suggested as a reason for the discrepancy between
the two studies.26

Studies that considered longer-term outcomes of PR made a less certain picture. The
disappearance of benefits over time occurred in a fair-quality non-randomized study.35 One high-
quality study44 and one fair-quality study38 found that improvements in exercise capacity were
maintained over 12 and six months with mean values below the MCIDs. Five high- or good-
quality studies found improvements at six months or more,34,43,45-47 with some benefits being
sustained for 18 and 20 months, respectively, in two studies.43,45 Two observational studies found
that improvements to 6MWD and HRQL were maintained to two and three years.56,57

Two studies that compared maintenance programs and usual care after the end of PR found that
home-based exercise training was effective in maintenance, with benefits being maintained at six
months50 and 12 months.51 Two other studies52,53 found limited benefits from maintenance.

Ten studies26,33,58-65 that reported mental health outcomes found improvements in anxiety and
depression, with scores above the MCIDs in eight studies.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 47


There were indications of reduction in hospital admissions and length of stay after PR. In three
of the four better-quality studies, the differences in comparison groups were not statistically
significant.24,26,45

It was unclear from reviewed studies whether the inclusion of tiotropium in PR programs offered
statistically significant additional benefit.66,71,73 A high-quality study found statistically
significant benefits in patients using a mixture of helium and oxygen during PR.76 Two studies
comparing PR and LVRS plus PR found that surgery gave greater improvement than PR
alone.78,79

The results from several studies suggest that patients with COPD can benefit from the use of PR
regardless of patient age,81-83 disease severity,84-86,88 and sex.85,94 More higher-quality studies
would be desirable. Home-based PR programs provided similar benefits to patients compared
with hospital outpatient PR programs.67,95 The appropriate duration and content of PR programs
are unclear based on the studies. Studies on approaches to exercise training indicated that more
supervision is beneficial.99 Individually prescribed exercise training or high-intensity training
does not seem to be of added benefit.77,100,102 Little information was available on the
effectiveness of components of PR programs.

A comparative summary of eight of nine studies in the economic review where PR was offered
on an outpatient basis7,122,124-129 showed that the mean cost per participant was approximately
$1,100. It was not possible to provide a numerical cost-effectiveness. The outcomes were better
in the intervention groups, but the outcome measures were not uniform.

The primary economic assessment was a cost-effectiveness analysis that compared the costs and
health outcomes between usual care (pharmacotherapy) and usual care plus PR in three sessions
per week for six weeks. When the duration of efficacy of PR was 18 months, the cost per person
of PR was $27 more than usual care (incorporating maintenance costs and utilization from
exacerbations) and generated 0.042 additional QALYs. The incremental cost-effectiveness ratio
of PR compared with usual care was 27,924 per additional QALY gained. This result is within
the acceptability threshold of $50,000, and the results hold up for a variety of changes, except if
the cost of PR is high (more than $2,300 per person).

The budget impact analysis reflected current levels of demand and PR services in Canada. It was
assumed that there is a backlog of need and that it would take ten years to eliminate it. Further
expansion of services was unrealistic because of the large additional resource requirements and
competing needs in the public health care systems. If it is assumed that only the moderate and
severe cases need PR, 1,505 additional persons would be served annually in Canada, for an
added cost of $1.8 million. If 25% of persons with COPD needed PR, this would rise to $33.9
million annually for 100% uptake or $19 million if 67% of those in need had used the services. If
all persons with COPD needed PR, the additional annual cost would be $168 million.

48 PR for COPD: Clinical, Economic, and Budget Impact Analysis


7.2 Strengths and Weaknesses of This Assessment
The assessment included a clinical review that considered short-term and longer-term outcomes
of PR, efficacy of other treatments and components of PR, and the context and operation of PR
programs. The quality of publications was assessed. A cost-effectiveness analysis, which was
used to compare the costs and health outcomes of usual care and usual care plus PR, drew mainly
from Canadian and US data. The budget impact analysis included several models based on
different scenarios for demand, and took account of the availability of PR programs in Canada.
Weaknesses in the assessment were mainly linked to limitations in the primary data. The studies
that were included in the clinical review related to PR programs that varied in components,
duration, and patient populations. The selected studies used several methods to assess the
outcomes of PR, which contributed to heterogeneity. Consequently, the derivation of summary
statistics was considered to be unrealistic, and a series of qualitative reviews were prepared.
Many of the papers presented findings on outcomes with reference to P values and did not give
confidence intervals. In the economic review, the variation in PR design and measured outcomes
between studies meant that an integrative analysis could not be developed, because there was no
standard cost measure.

Because there was interest in the more recent literature on PR, the literature search was restricted
to publications from 1998 onward, and there was no analysis of earlier material. Points from the
earlier literature were considered through the use of systematic reviews. In the clinical review,
with one exception, data from non-English language papers were limited to what was available
in the abstracts and some of the tables. The appraisal of quality was not possible for these
publications. It is considered likely, however, that more information from these studies would
have made little difference to the overall findings of this review.

Of the 34 papers in the clinical review that were used to assess exercise capacity, HRQL and
mental health outcomes, 26 were RCTs, with a mean Jadad score of 2.4. This reflects the absence
of double blinding in most of the RCTs. Of the 34 papers, 65% were of high or good quality and
21% of fair quality. Of the 47 papers included in other parts of the clinical review, 37% were of
high or good quality and 36% of fair quality. None of the 14 studies that addressed patient
characteristics were RCTs.

One of the nine studies in the economic review met all nine of the quality criteria, and two others
met seven. The studies in the economic review varied in interventions, patients treated, and
methods of analysis. There was no “modal” value of costs, and outcome data had to be taken
from the clinical review. One study from the clinical review presented adequate results for the
number of exacerbations, which was a driving variable. Nevertheless, the results were sensitive
to a variety of values of the relative risk of PR on exacerbations.

If the true incidence of COPD is higher than that used in the economic analysis, and regions
increased surveillance and persons diagnosed, this would increase the demand and need for PR.
Some of those who received PR would die during the period analyzed, although this would not
affect the order of magnitude of the results. It was assumed that the additional resources
appeared in the first year of the program, but it would take several years to increase the capacity,
so costs would be lower in the earlier years.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 49


7.3 Generalizability of Findings
The findings of the studies comparing PR with usual care that reported short-term outcomes are
consistent with those from earlier work4,5 and can be considered to be generalizable. The
findings that outpatient and home-based PR programs can give similar benefits to patients with
COPD are probably also generalizable. The generalizability of studies reporting longer-term
outcomes is less clear. Sustained benefits from PR have been achieved in some settings but not
in others, and more work seems to be needed to confirm factors that contribute to longer-term
success. The findings from studies on age profile and disease severity are consistent with
previous experience, but generalizability is unclear because of limited study quality.

The primary economic evaluation made several assumptions, but the overall findings can be
considered to be generalizable. The cost-effectiveness was within the acceptable range and did
not vary with key operational variables. Several assumptions are made in the budget impact
analysis, but overall findings are generalizable to Canadian jurisdictions.

7.4 Knowledge Gaps


The AACP/AACPR guideline4 notes that more research is needed to clarify the relative impact
of the factors that can affect the duration of benefits from short-term PR. These include the
maintenance program structure, content, and location; exacerbations of respiratory disease; and
complications of other medical comorbidities. More work is needed to evaluate the optimal
methods to incorporate short-term rehabilitation strategies into long-term disease management
programs for patients with chronic lung disease.

Some studies in the clinical review suggest that successful outcomes after PR may be associated
with the use of longer programs and maintenance. Longer duration PR programs would provide
more stimulus. Therefore, patients would see greater health benefits. Extended programs,
however, would be more costly ― with implications for budget impact ― and represent a greater
time commitment by patients.

There seems to be a need for better information on patient characteristics and the optimum
structure and operation of PR programs. The approaches vary between programs. Limited
information was obtained in the clinical review on the efficacy of individual components of PR.
The same can be said for the economic review. Given the lack of longer-term data on outcomes,
we need information on the decay of benefits and the possible need for boosters. While the short-
term benefits of PR are established, the extent of these benefits may be unclear because many
studies excluded patients with comorbidities and those who had recent exacerbations.

There was little information from the clinical review on the efficacy and effectiveness of adjunct
therapies for PR. The evidence of benefit from adjunct therapies would need to be compelling for
them to be adopted in routine use. While such therapies might maximize health outcomes for
patients who received PR, they would present additional costs to those of standard PR programs.
As basic PR programs typically provide clinically significant improvements in HRQL and
exercise capacity, it is likely a better use of resources to increase PR capacity across Canada,
instead of working to maximize gains in the small patient group who are already receiving PR.

50 PR for COPD: Clinical, Economic, and Budget Impact Analysis


8 CONCLUSIONS
This assessment confirms findings from earlier work that PR is effective in improving short-term
exercise capacity, HRQL, and mental health outcomes for patients with stable COPD. The use of
PR may also be associated with reductions in hospitalization, but better-quality studies are
needed. There is evidence that, in some settings, the benefits of PR can be sustained in the longer
term, but at other centres the benefits decline over six to 18 months after the completion of
rehabilitation. More work is needed to confirm the factors that contribute to the successful long-
term management of COPD after PR. There is limited information on the effectiveness of
elements of PR programs. Issues that relate to patient characteristics and the operation of PR and
maintenance programs need to be considered by those who establish and provide these services.

If the duration of effectiveness of PR is 18 months, as in some of the studies from the clinical
literature, the ICER of usual care plus PR compared with usual care is $27,924 per additional
QALY gained. This is within the range of acceptability according to current thresholds, and the
results are not highly sensitive to variations in the values of the model variables.

The estimates of additional costs of PR services in Canada ranged from $1.8 million to $168
million annually. In the most likely scenario, corresponding to 25% of persons with COPD
needing PR and a 67% uptake, another $19 million would be needed annually.

PR for COPD: Clinical, Economic, and Budget Impact Analysis 51


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survey. Clin Rehabil 2004;18(4):444-9.
150. Fédération Française des Associations et Amicales de Malades, Insuffisants ou Handicapes Respiratoires
(FFAAIR). Paris: FFAAIR; 2007. Available: http://www.ffaair.org/index.php (accessed 2009 Sep 29).
151. The Australian Lung Foundation. Pulmonary Rehabilitation. Bowen Hills (AU): The Foundation; 2009.
Available: http://www.lungfoundation.com.au/content/view/197/197 (accessed 2009 Jul 23).
152. Cockram J, Cecins N, Jenkins S. Maintaining exercise capacity and quality of life following pulmonary
rehabilitation. Respirology 2006;11(1):98-104.
153. Hailey D, Ohinmaa A, Roine R. Published evidence on the success of telecardiology: a mixed record. J
Telemed Telecare 2004;10(Suppl 1):36-8.

60 PR for COPD: Clinical, Economic, and Budget Impact Analysis


APPENDIX 1: LITERATURE SEARCH STRATEGY
OVERVIEW
Interface: Ovid
Databases: Ovid BIOSIS Previews <1989 to present>
Ovid CINAHL - Cumulative Index to Nursing & Allied Health Literature
<1982 to present>
Ovid EMBASE <1980 to present>
Ovid Medline <1950 to present>
Ovid Medline In-Process & Other Non-Indexed Citations <December 21
2008>

Note: Subject headings have been customized for each database.


Duplicates between databases were removed in Ovid.
Date of Search: December 22, 2008
Alerts: Monthly search updates began January 16, 2009 and ran until September
2009.
Study Types: Systematic reviews; meta-analyses; technology assessments; randomized
controlled trials; controlled clinical trials; observational studies, clinical
practice guidelines, ethics
Limits: Publication years 1998-2008, Human (non-animal), no language limits

SYNTAX GUIDE
/ At the end of a phrase, searches the phrase as a subject heading
.sh At the end of a phrase, searches the phrase as a subject heading
MeSH Medical Subject Heading
fs Floating subheading
exp Explode a subject heading
$ Truncation symbol, or wildcard: retrieves plural or variations of a word
* Indicates that the marked subject heading is a primary topic
? Truncation symbol for one or no characters only
ADJ Requires words are adjacent to each other (in any order)
ADJ# Adjacency within # number of words (in any order)
.ti Title
.ab Abstract
.hw Heading Word; usually includes subject headings and controlled
vocabulary
.pt Publication type
.rn CAS registry number
use b8o89 Limit search line to the Biosis Previews database
use emez " Embase
use nursing " Cinahl
use mesz " Medline
use prem " Medline In-Process & Other Non-Indexed Citations

A-1
Multi-database Strategy

# Searches Results
Concept: COPD
exp Pulmonary Disease,
1 Chronic Obstructive/ use 23507
mesz
Chronic Obstructive
2 30091
Lung Disease/ use emez
*lung disease,
3 13431
obstructive/ use mesz
4 Bronchitis/ use nursing 625
5 Emphysema/ use nursing 670
Lung Emphysema/ use
6 4747
emez
Chronic bronchitis/ use
7 6379
mesz,emez
((obstructive pulmonary
or obstructive airway* or
obstructive airflow or
obstructive lung or
chronic airflow or
8 57670
chronic airway* or
obstructive respiratory)
adj2 (disease* or
disorder* or
obstruction*)).ti,ab.
(obstructive pulmonary
or obstructive airway* or
obstructive airflow or
obstructive lung or
chronic airflow or
chronic airway* or
9 13715
obstructive
respiratory).hw. use
b8o89 adj2 (disease* or
disorder* or
obstruction*).hw. use
b8o89
(COPD or COAD or
chronic bronchi* or
10 86109
CODB or emphysema*
or hyperlucent lung* or

A-2
lung disease obstructive*
or pulmonary diseases
obstructive* or
pneumatosis pulmonum
or pneumonectasia or
volumen pulmonum
auctum or chronic airflow
limitation* or chronic
airway limitation*).ti,ab.
(COPD or COAD or
chronic bronchi* or
CODB or emphysema*
or hyperlucent lung* or
lung disease obstructive*
or pulmonary diseases
obstructive* or
11 8822
pneumatosis pulmonum
or pneumonectasia or
volumen pulmonum
auctum or chronic airflow
limitation* or chronic
airway limitation*).hw.
use b8o89
(chronic adj3
12 53007
obstructive).ti,ab.
chronic.hw. use b8o89
13 adj3 obstructive.hw. use 13003
b8o89
14 or/1-13 147428
Concept: Pulmonary
rehabilitation (PR)
Athletic rehabilitation/
15 35
use emez
Rehabilitation, athletic/
16 215
use nursing
Pulmonary rehabilitation/
17 530
use emez
Rehabilitation,
18 1146
Pulmonary/ use nursing
exp Exercise Movement
19 81445
Techniques/ use mesz
20 exp Exercise therapy/ use 18936

A-3
mesz
exp Exercise/ use
21 178395
mesz,emez,nursing
exp Therapeutic exercise/
22 17248
use nursing
exp physical activity/ use
23 105890
emez,nursing
Muscle training/ use
24 2818
emez
Physical fitness/ use
25 21493
mesz,nursing
26 Fitness/ use emez 9954
Dance therapy/ use
27 234
mesz,nursing
exp Sports/ use
28 99000
mesz,nursing
29 exp Sport/ use emez 39063
exp exertion/ use
30 121539
mesz,nursing
exercise tolerance/ use
31 11455
mesz,emez,nursing
exp Physical endurance/
32 20457
use mesz,nursing
Kinesiotherapy/ use
33 6598
emez,nursing
exp Physical therapy/ use
34 42800
nursing
Physical Therapy
35 21119
Modalities/ use mesz
Musculoskeletal
36 310
manipulations/ use mesz
Home Physical Therapy/
37 201
use nursing
exp Physiotherapy/ use
38 21902
emez
(Rehabilitation/ use
mesz,emez,nursing or
39 Home rehabilitation/ use 7556
emez or exp Home
rehabilitation/ use

A-4
nursing or Rehabilitation
Center/ use
mesz,emez,nursing or
(rehabilitat* or
habilitat*).ti,ab.) and
(pulmonary or lung).ti,ab.
(rehabilitat* or
habilitat*).hw. use b8o89
40 1027
and (pulmonary or
lung).hw. use b8o89
(exercis* or
physiotherap* or physio-
therap* or kinesiotherap*
41 616272
or kinesio-therap* or
aerobic* or sport* or
fitness*).ti,ab.
(exercis* or
physiotherap* or physio-
therap* or kinesiotherap*
42 342938
or kinesio-therap* or
aerobic* or sport* or
fitness*).hw. use b8o89
((weight or weightlift* or
resistance or endurance
43 or strength* or athletic) 49265
adj3 (train* or
exercise*)).ti,ab.
(weight or weightlift* or
resistance or endurance
or strength* or
44 6096
athletic*).hw. use b8o89
adj3 (train* or
exercis*).hw. use b8o89
(Physical* adj3 (fitness*
or train* or ativ* or
45 endur* or therap* or 63772
treat* or retrain* or re-
train* or exert*)).ti,ab.
Physical*.hw. use b8o89
adj3 (fitness* or train* or
ativ* or endur* or
46 92624
therap* or treat* or
retrain* or re-train* or
exert*).hw. use b8o89

A-5
(athletic* or strength* or
physical* or exercis* or
47 11395
fitness*).ti,ab. and
training/ use emez
48 or/15-47 1194718
Results: COPD & PR
49 14 and 48 16039
Concept: Methodology
filter: SRs/MAs/HTAs
(MEDLINE or systematic
review).tw. or Meta-
50 115950
analysis.pt. or Meta-
analysis/ use mesz
exp Technology
51 Assessment, Biomedical/ 7878
use mesz
(Meta analysis or
52 systematic review).ti,ab. 5694
use prem
53 review.ti. use prem 15102
(Meta Analysis or
Systematic Review or
54 Biomedical Technology 20156
Assessment).mp. use
b8o89
(Meta Analysis or
55 Systematic Review).sh. 45829
use emez
56 medline.tw. use emez 23041
exp Meta Analysis/ use
57 7250
nursing
systematic review.pt. use
58 13184
nursing
(meta analy* or
metaanaly* or met analy*
or metanaly* or health
technology assessment*
59 74349
or HTA or HTAs or
biomedical technology
assessment* or bio-
medical technology

A-6
assessment*).ti,ab.
(meta regression* or
metaregression* or mega
60 445
regression*).ti,ab. use
b8o89
((systematic* adj
(literature review* or
review* or overview*))
61 or (methodologic* adj 55871
(literature review* or
review* or
overview*))).ti,ab.
((quantitative adj
(review* or overview* or
62 synthes*)) or (research 1750
adj (integration* or
overview*))).ti,ab.
((integrative adj2
(review* or overview*))
or (collaborative adj
63 7181
(review* or overview*))
or (pool* adj
analy*)).ti,ab.
(data synthes* or data
64 extraction* or data 21342
abstraction*).ti,ab.
(handsearch* or hand
65 6715
search*).ti,ab.
(mantel haenszel or peto
or der simonian or
66 dersimonian or fixed 21482
effect* or latin
square*).ti,ab.
67 or/50-66 249522
Concept: Methodology
filter: economic (with
cost-related QOL)
*Economics/ use
68 12490
mesz,emez,nursing,b8o89
exp Economic
69 101056
Evaluation/ use emez
70 *Economics, Medical/ 4589

A-7
use mesz
*Economics,
71 Pharmaceutical/ use 1525
mesz,nursing
*Economics, Hospital/
72 5729
use mesz
exp "Costs and Cost
73 Analysis"/ use 172342
mesz,nursing
exp decision support
74 57965
techniques/ use mesz
exp Budgets/ use
75 12685
mesz,nursing
exp Models, economic/
76 6231
use mesz
markov chains.sh. use
77 5268
mesz
monte carlo method.sh.
78 19009
use mesz,emez
uncertainty.sh. use
79 4811
mesz,emez,nursing
Quality-Adjusted Life
80 3719
Years/ use mesz
81 Value of life/ use mesz 5091
exp Health status
82 indicators/ use 128044
mesz,nursing
quality of life/ use
83 187536
mesz,emez,nursing
exp Health economics/
84 227305
use emez
exp "health care cost"/
85 103597
use emez
86 Budget/ use emez 7772
Socioeconomics/ use
87 31553
emez
Decision support system/
88 1503
use emez
quality adjusted life year/
89 3971
use emez

A-8
"Economic Value of
90 122
Life"/ use nursing
Health Resource
91 3500
Allocation/ use nursing
Economic Aspects of
92 1937
Illness/ use nursing
(econom* or cost or costs
or costly or costing or
costed or price or prices
or pricing or priced or
discount or discounts or
discounted or discounting
93 1011386
or expenditure or
expenditures or budget*
or afford* or
pharmacoeconomic* or
pharmaco-economic* or
financ*).ti,ab.
(cost* adj2 (util* or
effective* or efficac* or
benefit* or consequence*
or analy* or minimi* or
saving* or breakdown or
lowering or estimate* or
94 variable* or allocation* 209466
or control* or illness or
sharing or life or lives or
affordabl* or instrument*
or technolog* or day* or
fee or fees or charge or
charges)).ti,ab.
(decision adj2 (tree* or
95 20568
analy* or model*)).ti,ab.
((value or values or
valuation) adj2 (money or
96 8269
monetary or life or lives
or costs or cost)).ti,ab.
(markov* or monte
97 54484
carlo).ti,ab.
(sensitivity analys#s or
"willingness to pay" or
98 31077
quality adjusted life or
disability adjusted

A-9
life).ti,ab.
(unit cost? or drug cost?
or hospital cost? or health
99 35191
care cost? or medical
cost?).ti,ab.
(health adj2 (indicator? or
100 71497
status or utilit*)).ti,ab.
101 or/68-100 1702919
Concept: Methodology
filter: QOL
quality of life/ use
102 187536
mesz,emez,nursing
(qol or qoly or qolys or
hrqol or qaly or qalys or
qale or qales or qald or
qtime or daly or euroqol
103 43295
or eq5d or eq-5d or hql or
hqol or h-qol or hrqol or
hr-qol or hye or
hyes).ti,ab.
104 or/102-103 204353
Concept: Methodology
filter: Practice
Guidelines
Guidelines as topic/ use
105 22233
mesz
Health Planning
106 2760
Guidelines/ use mesz
Practice Guidelines as
107 48893
Topic/ use mesz
Clinical Protocols/ use
108 15022
mesz
(Guideline or Practice
Guideline or Consensus
109 23863
Development
Conference).pt. use mesz
110 Standards.fs. use mesz 417839
Practice Guideline/ use
111 100506
emez
Clinical Practice/ use
112 77772
emez

A-10
Clinical Protocols/ use
113 40482
emez
Health Care Planning/
114 21289
use emez
Practice guidelines/ use
115 16133
nursing
exp Protocols/ use
116 10660
nursing
exp consensus
117 development conference/ 6521
use mesz
(practice guidelines or
protocol or critical path
118 15613
or care plan).pt. or
standards.pt. use nursing
(guideline* or standards
119 116643
or best practice).ti.
(guideline* or standards
120 or best practice).hw. use 17814
b8o89
(expert consensus or
consensus statement or
consensus conference* or
121 practice parameter* or 55054
position statement* or
policy statement* or CPG
or CPGs).ti,ab.
(expert consensus or
consensus statement or
consensus conference* or
122 practice parameter* or 7090
position statement* or
policy statement* or CPG
or CPGs).hw. use b8o89
123 or/105-122 860524
Concept: Methodology
filter: RCTs & CCTs
(Randomized Controlled
Trial or Controlled
124 556959
Clinical Trial or Clinical
Trial).pt.
125 Randomized Controlled 6

A-11
Trials as Topic/ use prem
Randomized Controlled
126 58509
Trials as Topic/ use mesz
Controlled Clinical Trials
127 0
as Topic/ use prem
Controlled Clinical Trials
128 3961
as Topic/ use mesz
Clinical Trials as Topic/
129 5
use prem
Clinical Trials as Topic/
130 144891
use mesz
Randomized Controlled
131 163768
Trial/ use emez
132 Randomization/ use emez 26367
Controlled Clinical Trial/
133 54634
use emez
Double-Blind Method.sh.
134 1
use prem
Double-Blind Method.sh.
135 101566
use mesz
Double Blind
136 70768
Procedure.sh. use emez
Double-blind Studies.sh.
137 12341
use nursing
Single-blind Method.sh.
138 1
use prem
Single-blind Method.sh.
139 12762
use mesz
Single Blind
140 7858
Procedure.sh. use emez
Single-blind Studies.sh.
141 3241
use nursing
142 Placebos/ use mesz 28390
143 placebos/ use prem 0
144 Placebo$/ use emez 121040
145 Placebo$/ use nursing 4855
Random Allocation.sh.
146 5
use prem
147 Random Allocation.sh. 63710

A-12
use mesz
Random Assignment.sh.
148 19971
use nursing
Clinical Trials.sh. use
149 52817
nursing
(random$ or sham$ or
placebo$ or (singl$ adj
(blind$ or dumm$ or
150 1768917
mask$)) or (doubl$ adj
(blind$ or dumm$ or
mask$))).ti,ab,hw.
((tripl$ adj (blind$ or
dumm$ or mask$)) or
151 (trebl$ adj (blind$ or 576
dumm$ or
mask$))).ti,ab,hw.
152 trial.ti. 227141
153 or/124-152 2131988
Concept: Methodology
filter: Observational
studies
154 Comparative Study/ 1616393
Evaluation Studies as
155 121342
Topic/
156 evaluation studies.pt. 113940
157 Comparative Study.pt. 1455392
158 Multicenter Study.pt. 104730
159 multicenter study/ 151319
epidemiologic studies/ or
case-control studies/ or
retrospective studies/ or
cohort studies/ or
160 1783643
longitudinal studies/ or
follow-up studies/ or
prospective studies/ or
cross-sectional studies/
(Observational adj2
161 (study or studies or 68111
design)).ti,ab.
(Population adj3 (study
162 164906
or studies)).ti,ab.

A-13
163 control groups/ 6022
((multicent$ or multi-
164 cent$) adj2 (study or 65036
studies)).ti,ab.
((case control* or case-
control* or case
comparison*) adj2 (study
165 120407
or studies or design* or
analysis or analyses or
trial*)).ti,ab.
(cohort adj2 (study or
studies or design$ or
166 137701
analysis or
analyses)).ti,ab.
167 evaluation studies/ 180163
((retrospective* or
prospective* or cross-
section* or longitudinal*
168 or follow-up) adj2 (study 912425
or studies or design$ or
analysis or
analyses)).ti,ab.
((long term or long-term
or longterm) adj2 (study
169 or studies or design or 53237
analysis or analyses or
trial*)).ti,ab.
170 or/154-169 4171013
Concept: Methodology
filter: ethics
exp Ethics/ use
171 225600
mesz,emez,nursing
exp Privacy/ use
172 10927
mesz,emez
exp Privacy/ and
173 Confidentiality/ use 8404
nursing
Computer Security/ use
174 4404
mesz,emez
Data Security/ use
175 2422
nursing

A-14
exp Jurisprudence/ use
176 173418
mesz,nursing
exp Legal aspect/ use
177 232733
emez
exp Informatics/es, lj use
178 134
mesz
exp Informatics/ei use
179 198
nursing
exp Data Collection/es, lj
180 5445
use mesz
exp Data Collection/lj, ei
181 169
use nursing
Medical Records
Systems,
182 860
Computerized/es, lj use
mesz
Computerized Patient
183 100
Record/lj, ei use nursing
(ethic* or moral* or
184 bioethic* or e- 251861
ethic*).ti,ab,hw.
(privacy or confidential*
185 or security or 1080074
safe*).ti,ab,hw.
(legal* or liability or
186 332577
law).ti,ab,hw.
(informed adj2 (consent
187 or decision 72340
making)).ti,ab,hw.
((data or information or
informatics or records or
record or database*) adj3
(disclosure or
188 compromis* or 20088
ownership or property or
modification* or policy
or policies or
protect*)).ti,ab.
"secondary use of
189 408
data".ti,ab.
190 or/171-189 1837113

A-15
Concept: Methodology
filter: humans
191 exp animals/ 22863457
exp animal
192 1273853
experimentation/
193 exp models animal/ 791579
194 nonhuman/ 3153714
195 exp vertebrate/ 29990958
196 animal.po. 0
197 or/191-196 32155762
198 exp humans/ 22289186
199 human.po. 0
200 or/198-199 22289186
201 197 not 200 9866576
Results: COPD & PR &
(SRs OR RCTs OR
observational studies
OR ethics) & human
filter
49 and (67 or 153 or 170
202 5866
or 190)
203 202 not 201 5808
Results: COPD & PR &
(QOL OR Practice
Guidelines)
204 49 and (104 or 123) 2562
205 203 or 204 7068
limit 205 to yr="1998 -
206 5155
2009"
remove duplicates from
207 3240
206
Results: COPD &
economic filter
208 49 and 101 3336
limit 208 to yr="1998 -
209 2785
2009"
remove duplicates from
210 1914
209

A-16
OTHER DATABASES SEARCHED
Cochrane Library Same MeSH, keywords, limits, and study types used as per Medline
Databases search, with appropriate syntax used.
Issue 4 2008

Centre for Reviews and Same keywords and date limits used as per Medline search,
Dissemination Databases excluding study types and Human restrictions.
(CRD)
University of York 2008
Health Economic Syntax adjusted for HEED database
Evaluations Database
(HEED)
http://heed.wiley.com

Grey Literature and Hand Searches

Date of Search: December 2008


Keywords: Included terms COPD, chronic obstructive pulmonary disease, pulmonary
rehabilitation, exercise
Limits: Publication years 1998-present

NOTE: This section lists the main agencies, organizations, and websites searched; it is not a
complete list. For a complete list of sources searched, contact CADTH (http://www.cadth.ca).

Health Technology Assessment Agencies

Alberta Heritage Foundation for Medical Research (AHFMR)


http://www.ahfmr.ab.ca

Agence d’Evaluation des Technologies et des Modes d’Intervention en Santé (AETMIS).


Québec
http://www.aetmis.gouv.qc.ca

Canadian Agency for Drugs and Technologies in Health (CADTH)


http://www.cadth.ca

Centre for Evaluation of Medicines. Father Sean O'Sullivan Research Centre,


St.Joseph's Healthcare,Hamilton, and McMaster University, Faculty of Health Sciences.
Hamilton, Ontario
http://www.thecem.net/

Centre for Health Services and Policy Research, University of British Columbia
http://www.chspr.ubc.ca/cgi-bin/pub

A-17
Health Quality Council of Alberta (HQCA)
http://www.hqca.ca

Health Quality Council. Saskatchewan.


http://www.hqc.sk.ca/

Institute for Clinical Evaluative Sciences (ICES). Ontario


http://www.ices.on.ca/

Institute of Health Economics (IHE). Alberta


http://www.ihe.ca/

Manitoba Centre for Health Policy (MCHP)


http://www.umanitoba.ca/centres/mchp/

Ontario Ministry of Health and Long Term Care. Health Technology Analyses and
Recommendations
http://www.health.gov.on.ca/english/providers/program/ohtac/tech/techlist_mn.html

The Technology Assessment Unit of the McGill University Health Centre


http://www.mcgill.ca/tau/

Therapeutics Initiative. Evidence-Based Drug Therapy. University of British Columbia


http://www.ti.ubc.ca

Health Technology Assessment International (HTAi)


http://www.htai.org

International Network for Agencies for Health Technology Assessment (INAHTA)


http://www.inahta.org

WHO Health Evidence Network


http://www.euro.who.int/HEN

Australian Safety and Efficacy Register of New Interventional Procedures – Surgical


(ASERNIP-S)
http://www.surgeons.org/Content/NavigationMenu/Research/ASERNIPS/default.htm

Centre for Clinical Effectiveness, Monash University


http://www.med.monash.edu.au/healthservices/cce/

Medicare Services Advisory Committee, Department of Health and Aging


http://www.msac.gov.au/

A-18
NPS RADAR (National Prescribing Service Ltd.)
http://www.npsradar.org.au/site.php?page=1&content=/npsradar%2Fcontent%2Farchive_alpha.h
tml

Institute of Technology Assessment (ITA)


http://www.oeaw.ac.at/ita/index.htm

Federal Kenniscentrum voor de Gezendheidszorg


http://www.kenniscentrum.fgov.be

Danish Centre for Evaluation and Health Technology Assessment (DCEHTA). National Board
of Health
http://www.dihta.dk/

DSI Danish Institute for Health Services Research and Development


http://www.dsi.dk/frz_about.htm

Finnish Office for Health Care Technology and Assessment (FinOHTA). National Research and
Development Centre for Welfare and Health
http://finohta.stakes.fi/EN/index.htm

L’Agence Nationale d’Accréditation et d’Evaluation en Santé (ANAES). Ministere de la Santé,


de la Famille, et des Personnes handicappés
http://www.anaes.fr/anaes/anaesparametrage.nsf/HomePage?ReadForm

Committee for Evaluation and Diffusion of Innovative Technologies (CEDIT)


http://cedit.aphp.fr/english/index_present.html

German Institute for Medical Documentation and Information (DIMDI). Federal Ministry of
Health
http://www.dimdi.de/static/de/hta/db/index.htm

Health Service Executive


http://www.hse.ie/eng/

College voor Zorgverzekeringen/Health Care Insurance Board (CVZ)


http://www.cvz.nl

Health Council of the Netherlands


http://www.gr.nl

New Zealand Health Technology Assessment Clearing House for Health Outcomes and Health
Technology Assessment (NZHTA)
http://nzhta.chmeds.ac.nz/

A-19
Norwegian Centre for Health Technology Assessment (SMM)
http://www.kunnskapssenteret.no/

Agencia de Evaluación de Tecnologias Sanitarias (AETS), Instituto de Salud “Carlos III”/ Health
Technology Assessment Agency
http://www.isciii.es/htdocs/investigacion/Agencia_quees.jsp

Basque Office for Health Technology Assessment (OSTEBA). Departemento de Sanidad


http://www.osasun.ejgv.euskadi.net/r52-2536/es/

Catalan Agency for Health Technology Assessment and Research (CAHTA)


http://www.gencat.net/salut/depsan/units/aatrm/html/en/Du8/index.html

CMT - Centre for Medical Technology Assessment


http://www.cmt.liu.se/

Swedish Council on Technology Assessment in Health Care (SBU)


http://www.sbu.se/

Swiss Network for Health Technology Assessment


http://www.snhta.ch/

European Information Network on New and Changing Health Technologies (EUROSCAN).


University of Birmingham. National Horizon Scanning Centre
http://www.euroscan.bham.ac.uk

National Horizon Scanning Centre (NHSC)


http://www.pcpoh.bham.ac.uk/publichealth/horizon

NIHR Health Technology Assessment Programme / National Coordinating Centre for Health
Technology Assessment (NCCHTA). Department of Health R&D Division
http://www.hta.ac.uk/

NHS National Institute for Clinical Excellence (NICE)


http://www.nice.org.uk

NHS Quality Improvement Scotland


http://www.nhshealthquality.org

University of York NHS Centre for Reviews and Dissemination (NHS CRD)
http://www.york.ac.uk/inst/crd

The Wessex Institute for Health Research and Development. Succinct and Timely Evaluated
Evidence Review (STEER)
http://www.wihrd.soton.ac.uk/

A-20
West Midlands Health Technology Assessment Collaboration (WMHTAC)
http://www.publichealth.bham.ac.uk/wmhtac/

Agency for Healthcare Research and Quality (AHRQ)


http://www.ahrq.gov/

Dept. of Veterans Affairs Research & Development, general publications


http://www.research.va.gov/

VA Technology Assessment Program (VATAP)


http://www.va.gov/vatap/

ECRI
http://www.ecri.org/

Institute for Clinical Systems Improvement


http://www.icsi.org/index.asp

Technology Evaluation Center (Tec). BlueCross BlueShield Association


http://www.bluecares.com/tec/index.html

University HealthSystem Consortium (UHC)


http://www.uhc.edu/

Health Economic

Bases Codecs. CODECS (COnnaissances et Décision en EConomie de la Santé) Collège des


Economistes de la Santé/INSERM
http://infodoc.inserm.fr/codecs/codecs.nsf

Centre for Health Economics and Policy Analysis (CHEPA). Dept. of Clinical Epidemiology and
Biostatistics. Faculty of Health Sciences. McMaster University, Canada
http://www.chepa.org

Health Economics Research Group (HERG). Brunel University, U.K.


http://www.brunel.ac.uk/about/acad/herg

Health Economics Research Unit (HERU). University of Aberdeen


http://www.abdn.ac.uk/heru/

The Hospital for Sick Children (Toronto). PEDE Database


http://pede.bioinfo.sickkids.on.ca/pede/index.jsp

University of Connecticut. Department of Economics. RePEc database


http://ideas.repec.org

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Organizations

The American Thoracic Society


http://www.thoracic.org/

The European Respiratory Society


http://dev.ersnet.org/

The British Thoracic Society


http://www.brit-thoracic.org.uk/

American Association of Cardiovascular and Pulmonary Rehabilitation


http://www.aacvpr.org/

Canadian Thoracic Society


http://www.lung.ca/cts-sct/home-accueil_e.php

Canadian Lung Association


http://www.lung.ca/home-accueil_e.php

Search Engines

Google
http://www.google.ca/

Yahoo!
http://www.yahoo.com

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APPENDIX 2: CLINICAL STUDIES DATA COLLECTION
FORM
Studies on Pulmonary Rehabilitation programs for COPD

Ref ID # 1st author


Reference, date Country

Source of funding
Statement of conflict of interest

Study specification
Study design:
Setting: (e.g. clinic, home care, combination)
Patient selection criteria
Patient recruitment methods
Components of PR program
Comparator treatment
Length of follow up

PR Non - PR
Patient characteristics
Age
Gender
Other

Patient numbers and outcomes


# Eligible/ recruited
# Enrolled
# Discontinued
treatment (reasons)
# Analyzed

A-23
Mortality
Morbidity
FEV1
HRQL
Hospital stay, d
Exacerbations
Treatment – related
adverse effects
Efficacy of individual
components of program
Other
NR = Not reported

A-24
APPENDIX 3: QUALITY ASSESSMENT INSTRUMENT
FOR CLINICAL STUDIES9,153
In this approach, scores are given for study design and for study performance.

For study design, scores are as follows:

Design Score
Large RCT 5
Small RCT 3
Prospective, non-randomized comparative 2
Retrospective comparative 1
Case series 0

Large RCTs are defined as those with at least 50 subjects in each arm.

For study performance, five areas of interest are considered:

Area of interest Points to consider


1 Patient selection Methods of randomization/ selection. Equivalence of
intervention and control groups. Drop outs prior to
commencement of intervention
2 Description/ specification of the interventions Adequate description of the intervention; control
groups adequately specified

3 Specification and analysis of study Sample size; statistical methods used; clear
specification of outcome measures

4 Patient disposal Length of follow-up; drop outs; compliance failures


5 Outcomes reported Fullness and clarity of reporting. Missing results;
statistical summary.
Whether conclusions were consistent with data.
Each of the five areas is given a score of 0, 1 or 2, based on the following judgements:

0 = Relevant information was missing or given in only minimal detail


1 = Reasonable detail was provided but there were some important limitations
2 = Information was satisfactory, there were no significant limitations
Judgements take account of what was done (or omitted) in a study and also of how the study was
reported.

A-25
Reviewers independently assign scores to each study. If there is disagreement on the study
design classification or if individual scores for any performance item differ by more than one,
discrepancies will be discussed and resolved by consensus.

On the basis of the combined performance and design scores (possible maximum score is 15, 10
for performance plus 5 for design) studies will be assigned to one of five categories to give an
indication of the reliability of the findings that they report:

Overall quality Reliability Implications for decision makers


score
11.5 -15 A High quality; high degree of confidence in study findings
9.5 – 11.0 B Good quality; some uncertainty regarding the study findings
7.5 – 9.0 C Fair quality; some limitations that should be considered in any
implementation of study findings
5.5 – 7.0 D Poor to fair quality; substantial limitations in the study, findings should
be used cautiously
5.0 E Poor quality; study findings have unacceptable uncertainty

A-26
APPENDIX 4: QUALITY ASSESSMENT FORM FOR
RCTS
Jadad Scale10
Reviewer _________ Reference ID ________

No. Category Score


1 Randomization:
Was the study described as randomized (i.e. including words such as randomly,
random, randomization)? A trial reporting that it is “randomized” is to receive
one point. Yes =1, No =0
Trials describing an appropriate method of randomization (table of random
numbers, computer generated) receive an additional point. Appropriate =1, not
appropriate =0
If the report describes the trial as randomized and uses an inappropriate method
of randomization (e.g. Date of birth, hospital numbers), a point is deducted.
Inappropriate = -1
2 Double-blinding:
Was the study described as double-blind? A trial reporting that it is “double-
blind” is to receive one point. Yes =1, No =0.
Trials describing an appropriate method of double-blinding (identical placebo:
colour, shape, taste) are to receive an additional point. Yes =1, No =0
If the report describes a trial as double-blind and uses an inappropriate method
(e.g. comparison of tablets vs. injection with no dummy), a point is deducted.
Inappropriate = -1
3 Withdrawals and dropouts:
Was there a description of withdrawals and dropouts? A trial reporting the
number and reasons for withdrawals or dropouts is to receive one point. If there is
no description, no point is given. Yes =1, No =0

Total score (for above 3 categories)

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APPENDIX 5: TABLES FOR CLINICAL REVIEW

Approaches used in the tables


In the “Setting and Patients” column, mean values for FEV1 and age in years are reported by
patient group. Number of patients refers to those recruited to the study. Numbers who
participated are shown in the “Study design and Quality ratings” column.
Components of each PR program are indicated numerically at the top of each entry in the “PR
Program” column. Details of components are at the start of each table (1. aerobic training 2.
strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other)
In the Outcomes columns, changes from baseline and between groups are indicated by ∆.
Percentage values refer to % change compared to baseline. 95% confidence intervals are
presented as [x, y]

Abbreviations Used

ADL: Activities of Daily Living Field Test


BODE: BODE index for COPD (Body Mass Index,
Obstruction, Dyspnoea, Exercise Capacity)
BPQ: Breathing Problems Questionnaire
CAO: Chronic airflow obstruction
COPD: Chronic Obstructive Pulmonary Disease
COPM: Canadian Occupational Performance Measure
CRQ: Chronic Respiratory Disease Questionnaire
d: day
ESWT: Endurance Shuttle Walk Test
FEV1: Forced expiratory volume in one second
FFM: Functionally active fat-free mass
GOLD: Global Initiative for Chronic Obstructive Lung Disease
HADS: Hospital Anxiety and Depression Scale
HRQL: Health – related quality of life
IMT: Inspirational muscle training
ISWT: Incremental Shuttle Walking Test
LVRS: Lung volume reduction surgery
Maugeri RFQ: Maugeri Foundation Respiratory Failure Questionnaire (MRF-28)
MCID: Minimal Clinically Important Difference
MRC: Medical Research Council
MVC: Maximal Voluntary Contraction
NETT: National Emphysema Treatment Trial
NNT: Number needed to treat
NRCT: Non – randomized controlled trial
NSD: No significant difference

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PFSDQ-M: Modified Pulmonary Functional Status and Dyspnea Questionnaire
PR: Pulmonary rehabilitation
QLI: Quality of Life Index
QWB: Quality of Well Being Scale
RAND 36: RAND 36 – item health survey
RCT: Randomized controlled trial
RM: Repetition maximum
SF-36: Short Form (36) Health Survey
SGRQ: St George’s Respiratory Questionnaire
SS: Statistically significant
TDI: Transition Dyspnea Index
VO2 max: Maximal oxygen uptake
6MRT: Six – minute ring test
6MWD: Six – minute walk distance
6MWT: Six – minute walk test

A-29
Table A1: Short term studies of PR
Study Setting & Patients PR program * Study design & Outcomes – exercise capacity Outcomes - HRQL
Quality ratings
Man 2004, Outpatient, 1,2,3 RCT (Baseline and 3 mo): (Baseline and 3 mo):
UK24 n = 42 within 10d of 8 wks, 2h a) PR n = 18 ISWT, median, m SGRQ total
discharge after sessions 2/wk. vs. a) 120 – 210 a) 65.4 – 49.3
admission with Home exercise b) Usual care n = (90m, 75%) (-16, -25%)
exacerbation 20 min/d 16 b) 115 – 90 b) 69.6– 66.2
encouraged (-25m, -22%) (-3, 5%)
FEV1 36.7%/41.7% Follow up 3 mo A: High quality Between groups p = 0.0002 Difference between groups ∆ = -12.7 [-5.0 , -20.40]
post discharge Jadad: 3 p = 0.002, effect size = 0.88
71/70 y
Eaton 2009, Inpatient and outpatient 1,2,3 RCT (Baseline and 3 mo) (Baseline and 3 mo)
New Zealand26 n = 97
inpatient 30 (a) PR n = 47 6MWD CRQ
FEV1 0.8/, 36%/ 0.8, min exercise/ d vs. p > 0.05 between groups
35% outpatient 8 (b) usual care n = a) attendees 245 – 335 (90m, 33%) SF 36, Physical
70/70 y wks, 2d/ wk 50 b) 218 – 313 (95m, 44%) a) attendees 27 – 35.7
follow up to 3 (8.7, 32%)
mo B: Good quality between groups p > 0.05 b) 29 – 31.8
Jadad: 3 (2.8, 10%)
Clini 2009, Inpatient 1,2,3 (4,5 if Observational, 6MWD SGRQ
Italy27 needed) retrospective ∆ Baseline – 4 wks ∆ Baseline – 4 wks
N = 1,826 cohort MRC 2: 51.9 [44.9, 58.9] MRC 2: - 6.53 [- 9.49, - 3.21]
Minimum of 15 MRC 3: 65.2 [ 60.0, 70.4]
FEV1: 50.5% sessions over 4 MRC 4: 62.3 [58.7, 65.9] MRC 3: - 6.76 [ -8.54, - 4.97]
wks (mean 18 MRC 5: 70.3 [66.9, 73.7]
sessions) All patients: 65.3 [63.2, 67.5] MRC 4: - 6.14 [- 7.10, - 5.19]
71y D: Poor – fair % reaching MCID
quality MRC 2: 40 MRC 5: -5.55 [-6.31, -4,78]
MRC 3: 55
MRC 4: 57 All patients: - 5.9 [- 6.45, - 5.34]
MRC 5: 61
All patients: 56
% reaching 350 metres
MRC 2: 4.6
MRC 3: 14.1
MRC 4: 16.8
MRC 5: 21.4
All patients: 17.3
Boxall 2005, Home, housebound 1,2,3 RCT (Baseline and 12 wks): (Baseline and 12 wks):
Australia31 patients, n = 60 a) PR n = 23 6MWD SGRQ total

A-30
Table A1: Short term studies of PR
Study Setting & Patients PR program * Study design & Outcomes – exercise capacity Outcomes - HRQL
Quality ratings
12 weeks, vs. a) 163 – 202 (39m, 24%) a) 56.5 - 50.7
FEV1 average of 11 b) usual care, n = b) 147.5 – 151.7 (4m, 3%) (-5.8, 10%)
0.79/40.5%// home visits 23 between groups ∆ = 35m, p = 0.023, effect size b) 61.0 – 59.6
0.89/37.7% 0.48 (- 1.4, 7%)
78/76 y B: Good quality between groups -4.4, p = 0.020, effect size = 0.35
Jadad:3
Barakat 2008, Outpatient rehab clinic 1,3 RCT (Baseline and 14 wks): (Baseline and 14 wks):
France29 n = 80 14 wk, 3 a) PR, n = 35 6MWD
visits/wk vs. a) 284±18 to 330±19m, SGRQ Total
FEV1 41.9%/ 43.3% b) usual care, n = (46m, 16%) a) 59.6±3.2 to 47.3±2.3, p<0.05 (-12.3, 21%)
36 b) 273±19 to 281 ±22 (8m, 3%) b) 58.5±3.7 to 57±3. (-1.5, 3%)
64/66 y between groups ∆ = 38m, p<0.05 between between groups ∆ = - 10.8, p<0.05
B: Good quality groups. effect size 4.04
Jadad: 3 Effect size 1.85
68% of PR group had improvement > MCID @
14 wk

Elci 2008, Community hospital + 1,2,3, 4 – RCT (1 mo and 3 mo): Values at 1,2, and 3 monthly visits:
Turkey33 home, n = 78 advice, 5 – if a) n = 39 6MWD SGRQ total
FEV1 47.8%, 46.3% needed vs. a) 312.4 – 328.9 (17m, 5%) a) 60.3, 49.2, 45.9
60/58y 3 mo; 24 b) Usual care, n = b) 305.1 – 298.2 (- 11, -14; - 18%, -24%)
sessions + 39 (- 7m, -2%) b) 61.7, 64.4, 65.5
exercises 2/d, effect size 0.46 (+3, +4; 5%, 6%)
5d/wk at home B: Good quality (p = 0.75, 0.001,0.001)
Jadad: 2 SF 36, Global life quality
a) 37.62, 48.33, 49.31
(∆ = 11,13; 28%, 35%)
b) 34.08, 34.33, 31.96(∆ <1)
Karapolat Outpatient, n = 54 1,2,3 RCT (Baseline, 8 wks, 12 wks): (Baseline, 8 wks,12 wks):
2007, Turkey28 a) PR, n = 26 6MWD SGRQ total
FEV1 55%,55% 8 wks, 16 vs. a) 262 – 383 – 309 a) 45.1,28.3, 35.6
sessions. b) usual care, n = (122m, 46%; 47m, 18%) (∆ = -17, 37%; -10, 21%)
65/67y Follow up: 4 19 b) 227 – 242 – 216 b) 50.7, 47.0, 46.5
wks post PR B: Good quality (15 m, 7%; - 11m, 5%) (∆ = -4, -7%; -4, - 8%)
Jadad: 3 between groups ∆ = 107m, 58m, p< 0.05, Effect between groups -13, -6, p <0.05 wks 8 and 12
sizes 1.97, 0.95 effect sizes 0.78, 0.31
Singh 2003, Home care following 1,3 RCT (Baseline and 4wks): (Baseline and 4 wks):
India32 training 4 wks, 2 a) PR n = 20 6MWD CRQ
n = 40 sessions/d, vs. a) 261- 315 Dyspnea

A-31
Table A1: Short term studies of PR
Study Setting & Patients PR program * Study design & Outcomes – exercise capacity Outcomes - HRQL
Quality ratings
supervised b) usual care n = (54m, 21%) a) 3.16 - 4.12, b) 3.50 -3.58, effect size 1.02
FEV1: 28/26 weekly 20 b) 258 - 264 Emotion
(7m, 3%) a) 3.0 – 3.9, b) 3.0 -3.2
59 y B: Good quality between groups ∆ = 47m, Effect size 0.34 Fatigue a) 2.8 – 3.7, b) 2.98 -3.04
Jadad = 1 Mastery a) 2.9 – 3.8, b) 3.1 -3.2
Between group differences 0.88, 0.7, 0.84, 0.8 all
p<0.001

Theander Outpatient 1,2,3 (4 as RCT (Baseline and ∆ after 12 wks): (Baseline & ∆ after 12 wks):
2009, n = 30 required) a) PR n = 12 6MWD SGRQ total
Sweden30 FEV1: 35.1/32.3 12 wks, 2d/wk vs. a) baseline 313, a) 52.5, 7.6 b) 44.5, 2.6
After one mo b) Usual care n = ∆ = 40.6 (13%) , (NSD between groups) between groups ∆ = -3, effect
66/64 y patients 14 p <0.05 size 0.39
received an b) 360, ∆ = 16.5 (5%) SF 36
individualized B: Good quality between groups ∆ = 24.1, effect size 0.29 Physical
home training Jadad: 3 Grip Strength a) 31.4, 10.5 b) 49.2 , 1.1
program a) baseline 261 ∆ = 16 Mental
b) baseline- 332, ∆ = - 5.6 Effect size 0.15 a) 70.1, -4.9 , b) 65.3, -4.0
Fatigue Impact Scale
NSD between groups for frequency, duration or
severity of fatigue
Na 2005, Home 1,2,3,5 NRCT 6MWD SGRQ
Korea35 n = 43 12 wks, at least a) PR, n = 20 (Baseline- 12 wks): Total
5 d/ wk at b) usual care + a) 471 – 508 (37m, 8%) (Baseline- 12 wks):
FEV1: 1.1/41.3%, home, hospital psychosocial, b) 494 – 517 (23m, 5%) a) 45.7 – 35.4,
1.0/39.7% visit every 2 nutritional support – 10.3, -21%)p = 0.001
wks sessions n = 13 Between groups ∆ = 14m,, Effect size 0.27 b) 48.2 – 42.2 ,
64/64 y (-6, -12%) p = 0.017
C: Fair quality between groups ∆ = 4.3. effect size 0.49
Oh 2003, Home 1,2,3,5 RCT (Baseline- 8wks): (Baseline- 8wks):
Korea36 n = 34 a) Home PR n = 6MWD CRQ
FEV1 42.1%/ 44.9% 8 wk telephone 15 a) 351 – 391 (41m, 12%) total
65/67 y support 2d/wk vs. b) 360 – 333 (-27m, -8%) a) 82.0 – 99.5
b) educational between groups ∆ = 68 m, p < 0.001 (17, 21%)
advice only n = 8 Effect size 1.09 b) 89.8 – 87.2
(-3, -3%)
C: Fair quality between groups ∆ = 20.5, p = 0.03, effect size 1.10
Jadad: 2 (Change SS in all subscales except dyspnea)
Skumlien Inpatient, n = 61 1,2,3,4,5 as NRCT 6MWD SGRQ total

A-32
Table A1: Short term studies of PR
Study Setting & Patients PR program * Study design & Outcomes – exercise capacity Outcomes - HRQL
Quality ratings
2007, FEV1 needed a) PR, n = 40 (n (Baseline, ∆ after 4 wks) (Baseline - 4wks)
Norway37 1.3, 45%/ 1.2, 46% =33 for some a) ∆ = 14 (3%), p = 0.132 a) 56 – 49.4 (-6.6, -12%)
GOLD stage II - IV 4 wks; data for outcomes) (7/33 improved by 54m) p = 0.005
63/65 y controls 4 vs. b) ∆ = -5 (-1%), b) 56 – 55.5 (- 0.5, -1%)
months before b) Usual care between groups ∆ = 19, p =0.62, Effect size 0.18 between groups ∆ = - 6.1, p = 0.817, effect size 0.45
and at entry to n = 20 Maximal exercise VO2max:
PR for 3d visits a) 84 mL/min
C: Fair quality ∆ = 6.5, p < 0.0001) 38 mL/min
∆ = 1.0, P =0.116
Muscular strength MVC, leg press, kg
a) ∆ = 23, p <0.0005
b) ∆ = -1, p =0.86
Riario – Storza Outpatient 1,2,3 NRCT 6MWD
2009, Italy39 6 wks, 12 a) PR, n = 222 Change from baseline, 6wks Not reported
n = 284 sessions vs. GOLD 1: 63m
b) usual care, n = GOLD 2: 68.5m
FEV1 = 1.22/ 1.27 62 GOLD 3: 89.1m
69/ 70y GOLD 4: 132m
D: Poor – fair
quality Proportion of patients with ∆ > 54m
a) 142/222, 64%
NNT = 2

b) 8/62, 13%

Regiane Home PR 1,2,3 RCT 3MWD CRQ


Resqueti 2007, n = 38 a) 5 sessions /wk, (baseline, 9wks)
Italy38 GOLD III or IV, 9 wks wks 3-9, physical (baseline, 9 wks) Dyspnea: a) 3.1,3.6
<80yFEV1 therapist contact, b) 3.2 - 3.3
29.6%/27,5% Follow up: 15 n = 14 a) 148m – 167m ( p = 0.001) Fatigue: a) 3.7, 4.2
69/67 y wks from end vs. b) usual care b) 4.1, 4.5
of program + physical b) 179m – 181m Emotional: a) 4.3,4.3
exercise, b) 4.5, 4.5
unsupervised between group ∆ from baseline Mastery: a) 4.3,4 .9
n = 15 16.1m b) 5.1,5.2
C: Fair quality Between groups,
Jadad; 3 Dyspnea: - 0.3
Fatigue: 0.3
Emotional: 0.2

A-33
Table A1: Short term studies of PR
Study Setting & Patients PR program * Study design & Outcomes – exercise capacity Outcomes - HRQL
Quality ratings
Mastery: 0.3
Griffiths 2000, Home maintenance 1,2,3, 4 RCT, single Change from baseline Change from baseline
UK 34 following outpatient PR (advice), 5 blind SGRQ total
n = 200 ISWT
PR 6 wks, 3 x (a) PR + 6 wks 6 wks
FEV1 2h sessions per maintenance, n
0.91/ 0.89 wk. = 99 Between groups :
68/68 y Follow up at 12 vs. between group ∆ = 76 ∆ = - 9.4
mo
(b) Usual care, n CRQ – between group ∆
= 101,
Dyspnea: 6.1
B: Good quality Fatigue: 4.9
Jadad: 2 Emotional: 7.8
Mastery: 4.3

* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-34
Table A2: Studies of longer term outcomes following PR
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings
van Wetering Home maintenance 1,2,3,+ 4 if needed RCT Change from baseline Change from baseline
2009, following outpatient PR PR 30 min sessions, 2/ wk for (a) PR + maintenance, n = 6MWD SGRQ total
Netherlands 43 COPD with impaired 4 mo + 20 mo maintenance 95, 87 @ 4 mo, 77 @ 2y 4 mo
exercise capacity, less with 1/mo visit to vs. a) – 1.4 b) – 15.3, 4 mo
advanced lung function physiotherapist. Allowed 6 p = 0.02 a) – 3.9 b) + 0.3, p = 0.04
obstruction n = 199 extra training sessions/ 3 wks (b) Usual care, n = 91, 88 @ 24 mo 12 mo *
after exacerbation 4 mo, 81@ 2y a) – 15.1 b) – 33.4, p = 0.02 a) – 1.0 b) + 0.4
FEV1 58%/ 60% Cycle endurance time (CET) 24 mo *
66/ 67 y A: High quality 4 mo a) – 0.2 b) + 2.4, p = 0.045
Jadad: 3 a) 234s b) 29s, p = 0.04 Between group ∆ = 4.2, 1.4, 2.6
24 mo
a) 172s b) – 81s, p = 0.02 * values from Figure
Between group ∆ = 205s, 253s

Engstrom Outpatient + home 1,2,3 + 4 as needed RCT (Baseline- 12 mo): (Baseline- 12 mo):
1999, n = 55 52 wks; 2 sessions/wk for 6 a) PR, n = 26 6MWD SGRQ Total
Sweden44 FEV1 30.7%/ 34.1% wks; 1 session/wk next 6 wks, vs. a) 312 – 350 (38m,12%)
66/67 y 1 session/2wks for 6 wk, 1 b) usual care, n = 24 b) 308 – 306 (-2m, -1%) a) 48.6 – 48.9
session/mo for remainder intergroup ∆ = 40m, p <0.05 b) 45.3-45.8
A: High quality Maximal exercise NSD between groups
Jadad = 2 a) 60.6 W, to 70 W
b) 62.4 W, to 63.2 W

Guell 2000, Outpatient + home 1,3 RCT 6MWD CRQ


Spain45 exercise 6 mo a) PR, n = 24 6 mo: 6 mo:
n = 60 3 mo: two sessions/wk. vs. change from baseline approx. 90m in group (a) had higher scores in all
FEV1 31%/ 39% 3 mo: five sessions/wk b) usual care n = 23 group (a), 20m in group (b), p < 0.05 domains, p < 0.05
64/66y Further 6 mo supervised 24 mo: 24 mo:
breathing exercises, 1/ wk A: High quality difference between groups = 81m ∆ between groups:
Follow up: 18 mo from end of Jadad: 2 (including patients who withdrew, Dyspnea 1.0, p = 0.007
PR ITT, ∆= 95m). Approx 26% above Fatigue 1.1, p = 0.02,
baseline Mastery 1.0, p = 0.03
Emotional 1.0, p = 0.03
> MCID for all domains

Regiane Home PR 1,2,3 RCT 3MWT CRQ


Resqueti 2007, n = 38 a) 5 sessions /wk, wks 3-9, (baseline, 9wks, 6 mo)
Italy38 GOLD III or IV, 9 wks physical therapist contact, n = (baseline, 9 wks, 6mo) Dyspnea: a) 3.1,3.6,3.7
<80yFEV1 14 b) 3.2 - 3.3 - 3.6

A-35
Table A2: Studies of longer term outcomes following PR
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings
29.6%/27,5% Follow up: 15 wks from end vs. b) usual care + physical a) 148m – 167m – 167m Fatigue: a) 3.7, 4.2, 4.6
69/67 y of program exercise, unsupervised b) 4.1, 4.5,4.5
n = 15 b) 179m – 181m – 186m Emotional: a) 4.3,4.3,4.6
C: Fair quality b) 4.5, 4.5, 5
Jadad; 3 between group ∆ from baseline Mastery: a) 4.3,4 .9,4.8
6 mo: 11.4m b) 5.1,5.2, 5.1
Between groups, 9wks and 6 mo
Dyspnea: - 0.3, - 0.1
Fatigue: 0.3, - 0.1
Emotional: 0.2, 0.4
Mastery: 0.3, 0.3
Na 2005, Home 1,2,3,5? NRCT (Baseline-15 mo): Not measured
Korea35 6MWD
n = 43 12 wks, at least 5 d/ wk at a) PR, n = 20 a) 482 – 499 (17m, 4%)
FEV1 1.1/41.3%, home, hospital visit every 2 b) usual care + psychosocial, b) 497 – 509 (12m, 2%)
1.0/39.7% wks nutritional support sessions n Between group ∆ = 5 m
64/64 y = 13
Follow up: 12 mo C: Fair quality
Finnerty Outpatient 1,3 RCT Change from baseline, 6 mo Change from baseline, 6 mo
2001,UK46
n = 73 with long – PR 6 wks, 2 sessions/ wk a) PR + rec home exercise, n 6MWD SGRQ total
standing COPD = 36
Follow up at 12 and 24 wks v a) 77m b) 8m, a) – 9.3 b) – 2.2,
FEV1 0.99/ 1.06 b) Usual care, n = 29
70/ 68 y between group ∆ = 67 [- 1.6, 135.6] between group ∆ = -7.1 [- 14.7, 0.54]
B : Good quality

Jadad : 3
Griffiths 2000, Home maintenance 1,2,3, 4 (advice), 5 RCT, single blind Change from baseline, and Change from baseline
UK34 following outpatient PR SGRQ total
n = 200 PR 6 wks, 3 x 2h sessions per (a) PR + maintenance, n= ISWT
wk. 99 vs. 6wks 6 wks
FEV1 Follow up at 12 mo a) 71m, b) – 2m a) – 7.1, b) 1.3
0.91/ 0.89 (b) Usual care, n = 101,
68/68 y 12mo 12 mo
B: Good quality a) 8m, b) – 12 m a) – 3.4 b) 0.7
Jadad: 2
between group ∆ = 73, 20 Between groups :
∆ = 8.40, 4.1

A-36
Table A2: Studies of longer term outcomes following PR
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings

CRQ – between group ∆


6 wks 12 mo
Dyspnea: 5.9 1.7
Fatigue: 4.6 1.1
Emotional: 8.1 2.5
Mastery: 4.2 1.5

Fernández Home PR program 1,2,3 RCT Change from baseline, 12 mo Change from baseline, 12 mo
2009, Spain 47 6MWD
n = 50 with severe 2 hospital sessions followed a) Home PR, n = 27 a) 79m, p<0.0001 b) 13m, p>0.05 SGRQ Total
COPD and long term O2 by home PR 1h , 5d/wk.
treatment Physio home visits 2/mo for 2 vs between group ∆ = 66m a) – 14.7, p=0.0001 b) – 2.5, p>0.05
FEV1 33%/ 38% mo, then 1/mo for 9 mo
b) Usual care, n = 14
66/ 70y between group ∆ = - 12.2
B: Good quality
Jadad = 2

Du Moulin Home maintenance 1, 2?, 3, 5 RCT (0 (post PR), 3 and 6 mo): (0 (post PR), 3 and 6 mo):
2009, following 3 wk 6h sessions 5d/wk a) Home exercise program n 6MWD CRQ total
Germany50 outpatient PR Maintenance : Individualized = 10 (a) 511, 531,545 (a) 5.4; 5.7; 5.8 (∆ = 0.3, 0.4)
Moderate COPD training plan, contacted every vs. (20m, 4%; 34m, 7%) (b) 5.0; 4.9; 4.7 (.∆ = - 0.1, - 0.3)
n = 20 4 wks b) normal activities of daily b) 465, 465, 454
FEV1 41.9%/ 43.3% Follow up: 6 mo living n = 10 (0m; - 11m, - 2%) Between group ∆ = 0.4, 0.7
64/66 y Between group ∆ = 20m, 46m,
A: High quality Interaction p = 0.033 Interaction p = 0.027
Jadad: 3
Steele 2008, Home, post PR 1, 2, 3, 4, 5 RCT 6MWD SF 36
USA52 Patients with chronic a) adherence intervention – Pre PR – post PR (a +b) Physical
lung disease n = 111 8 wks (both groups); home exercise program, 365 – 410m, ∆ = 45m NSD between groups except p<0.05 in
; 85% had COPD intervention 3 mo weekly phone calls, 1 home favour intervention at wk 20
visit. n = 54, 50@20wks, 42 (∆ Post PR to 20 wks and to 52 wks): Mental
Follow up: 44 weeks post PR @ 52 wks NSD between groups except p<0.05 in
vs. a) ∆ = - 10.7, - 21.0 favour intervention, wk 20 and of
b) continuing care, recs for b) ∆ = -35.4, - 39.6 control, wk 52
continuation of exercise p = 0.023, 0.190 Seattle OLDQ
program Accelerometer activity NSD between groups except p<0.05 in

A-37
Table A2: Studies of longer term outcomes following PR
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings
n = 57, 52 @ 20 wks, 47 @ a) 164,173,170 favour of control for coping skills at
52 wks ∆ = 9, 6 wk 52
b) 154, 154, 143
A: High quality ∆ = 0, - 11
Jadad: 3 p = 0.213, 0.667
Self – reported minutes of activity
a) 30, 32, 33
∆ =2, 3
b) 28, 16, 22
∆ = -12, - 6
p = 0.015, 0.355
Moullec 2008, Home care post inpatient 1, 2, 3, 5 NRCT 6MWD SGRQ
France51 PR Baseline – end PR Baseline – end PR
All post 4 wks (20 sessions) a) self help association a) ∆ = 43m b) ∆ = 52m Symptoms a) ∆ = 6.5 b) ∆ = 6.9
n = 40, from 3 PR PR, programs + home exercise, Activities: a) ∆ = 2.9 b) ∆ = 6.7
centres Maintenance: 96 sessions n = 14, 12 @ 6mo, 11 @ 12 End PR, 6 mo & 12 moa) 471,508, Impacts: a) ∆ = 7.8 b) ∆ = 9.2
over 1 year mo 511
FEV1 52.6%/ 46.7% b) usual care + letter on (37m, 40m) End PR, 6 mo & 12 mo
63/60 y recommended home care b) 473, 436, 436
program, n = 26, 20 @ 6mo, ( - 37m, -37m) Symptoms a) 59.0, 56.2,45.5 b) 61.5,
16 @ 12 mo Between group ∆ 64.5, 65.3
6mo: 74.2m [37.7 , 110.5] Activities: a) 62.3, 46.3, 46.2
B: Good quality 12mo ; 75.8 [32.0 ,111.6] b) 63.5,67.3, 73.7
Maximal exercise Impacts: a) 29.6,19.6, 16.0
a) 78, 87, 86 b) 34.7,40.6, 50.2
b) 81,70,75
Between group ∆ Between group ∆
6mo: 19.1W [ 2.1, 36.1] Symptoms
12mo ; 13.4 W [- 1.4, 28.3] 6 mo: - 6.7 [ - 16.2 , 2.7]
12 mo: - 18.5 [-30.9 , -6.2]
Activities:
6 mo: - 20.2 [ - 33.4 , – 7.1]
12 mo: - 27.0 [- 40.0 , – 14.0]
Impacts:
6 mo: - 17.0 [ - 28.1 , – 5.8]
12 mo: - 32.4 [- 42.0 , – 22.8]

Ries 2003, Home maintenance after 1,2,3,5 RCT Baseline (post PR) to 12 mo
USA53 PR 6MWD CRQ

A-38
Table A2: Studies of longer term outcomes following PR
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings
8 wks PR then 12 mo a) Maintenance program, n =
N = 164 maintenance program. Follow 74 @ 12mo, 69@ 24 mo Baseline (post PR) to 12 mo a) 103.0 – 96.0, (-7.0) b) 105.9 – 95.9
up 24 mo post PR (- 10.0)
FEV1: 1.08 vs a) 458 – 440, (- 18) b) 473- 431 (-42)
QWB

67y b) Usual care n = 64 @ ∆ between groups 24m a) 0.665 - 0.593 (- 0.072)


12mo, 62@ 24 mo b) 0.645 – 0.580 (- 0.065)
12 mo to 24 mo
12 mo to 24 mo
A: High quality a) 451 – 416, ( - 35) b) 439 – 428 (- CRQ
11)
Jadad: 3 ∆ between groups - 24m a) 98.0 – 96.6 (- 1.4)
b) 97.5 – 94.5 (- 3.0)
QWB
a) 0.593 – 0.546 (- 0.047)
b) 0.582 – 0.535 (- 0.047)

*PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-39
Table A3: Other studies reporting longer term PR outcomes
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings
Romagnoli 2006, Inpatient 1,2,3,5 RCT 6MWD SGRQ total
Italy54 PR #1 PR #1
n = 35 18 sessions for each a) PR + 2nd and 3rd PR a) 239 – 286, b) 246 -296 a) 52 – 49, b) 51 - 50
38%/38% PR after 6 & 12 mo, n = 16 @ 6 a,b ∆ = 47, 50 a,b ∆ = -3, -1
mo, 14 @12 mo PR # 2
69/70 y vs. a) 252 -296, b) 255 PR # 2
b) PR + 2nd PR at 12mo, n a) ∆ = 44, a) 48 -46, b) 50
= 16 @ 6 mo, 15 @ 12 mo PR #3 a) ∆ = -2
a) 254 – 304, b) 258 – 308
B: Good quality a,b ∆ = 50, 50 PR #3
Jadad: 1 a) 44 – 42, b) 45 – 41
baseline vs. end PR 3 p <0.005, both groups, a,b ∆ = -2, -4
p >0.05 between groups
PR 3 values vs. baseline SS for both
groups, and above MCID

NSD in intergroup t scores,


Verrill 2005, 7 hospital outpatient Intensity varied Prospective, comparative 6MWD SF 36
USA55 PR programs; between programs. non – experimental (Difference from Baseline) Physical
severe respiratory n = 590 a) n = 192, 29.6 – 35.9, effect size 0.77 ,
problems; 92% had Exercise 2/3 d/wk a) 12 wks PR 1074 – 1256 ft, effect size 0.51 ∆ = 6.3
COPD, this defined to all programs; some vs. ∆ = 182 (55.5m)
include asthma programs 3, 5 b) 24 wks of PR (b) n = 70, 27.9 – 37.1 - 36.1, effect
n = 590 b) n = 151 size > 1.0, 0.99
FEV1 1.05 C: Fair quality 1165 – 13 11 – 1366 ft ∆ = 9.2, 8.2
67y effect size 0.43, 0.60
∆ = 146, 201 ft (44 m, 61.3m) Mental
a) n = 192, 50.6 – 53.3, effect size 0.46,
∆ = 2.7
(b) n = 70, 53.7 – 56.2 - 57.2, effect
size 0.24, 0.34
∆ = 2.5, 3.5
QLI
a) n = 429, 19.4 – 21.6 effect size 0.46
(b) n = 78, 20.7 – 22.0 -22.6, effect size
0.33, 0.48
Lomundal 2007, Outpatient + home 1,3 Prospective observational (Baseline, 6 mo, 12 mo, 24 mo): (Baseline, 6 mo, 12 mo, 24 mo):
Norway56 6MWD SGRQ total
n = 28 Educational & D: Poor – fair quality 411, 414, 404, 399 58.0, 53.1, 53.5, 54.4

A-40
Table A3: Other studies reporting longer term PR outcomes
Study Setting & Patients PR program * Study design & Quality Outcomes – exercise capacity Outcomes - HRQL
ratings
exercise program: Borg score , highest during 6MWT ∆ = 4.9, 4.5, 3.6
FEV1: 41.3%, 16 sessions over 1y. 6.0, 5.8, 5.9, 5.9 p < 0.05 from baseline
67y Home exercise 30
min/d encouraged
Follow up: 1y

Lomundal 200756 Outpatient PR + home PR: 1,2,3 Prospective observational (Baseline, 6 mo, 12 mo, 24 mo, 60 mo): (Baseline, 6 mo, 12 mo, 24 mo, 60
& Steinsbekk self manage program Home: 1,3 6MWD mo):
2009, Norway57 Educational & n = 29, 26@ 5y a) 423, 466, 506, 509, 519 SGRQ total
n = 30 exercise program: (∆ = 43, 83, 86*, 96) 56.6,49.1,46.9,45.5, 44.9
16 sessions over 1y D: Poor – fair quality *At 2 y, 95% CI [63, 109] ∆ = 7.5, 6.7, 11.1*, 11.7
FEV1 40.1% Additional 3 *At 2 y, 95% CI [ 13.9 , 8.4]
63y exercise
sessions/wk over 2y p < 0.05 between all except 12 – 24 mo
Follow up: 3y
* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-41
Table A4: Studies with mental health outcomes
Study Setting & patients PR program * Study design and quality Outcomes
ratings
Haugen 2007, Inpatient clinics 1,3,5 RCT
Norway62 n = 96 4 wk; 7.5h sessions, a) PR in Norway (cold climate) n HADS
FEV1 1.4, 49%/ 1.5, 5 d/wk = 36 Anxiety
48% Follow up: 8 mo vs. a) 6.3 – 6.2 (-0.1, 2%) b) 5.9 – 4.0 (-1.9, 32%)
61/59 y after rehab b)PR in Spain (warm climate) n = p= 0.001
60
Depression
A: High quality a) 5.4 - 4.4 (-1.0, 19%) b) 4.9 – 3.7 ( -1.2, 24%)
Jadad: 3 p = 0.72
De Godoy 2005, Outpatient 1,2,3,5, RCT, single blind Beck Anxiety Inventory
Brazil65 moderate –severe 6 – physical (a)PR n=19, (a) 15.2±7 to 5±4, p<.0001 (- 10, 67%)
n = 49 exercises v b) 20±7 to 10±6, p = 0.0001 (- 10, 50%)
(b) PR without physical exercise n ( c) 13±11 to 8±9 p = 0.03 (- 5, 38%)
COPD, FEV1 34%, 12 wks = 16, ∆ = a – 10.2,, b – 10, c -5
>50y v
(c) PR without psychotherapy n = Beck Depression inventory
14 (a) 17±10 to 5±4, p=0.0003 (- 12, 71%)
(b) 20±9 to 10±9, p = 0.0014 (- 10, 50%)
B: Good quality ( c) 10±10 to 12±11, p = 0.6 (+ 2, 20%)
Jadad = 2 ∆ = a – 12,, b – 10, c +2
Distance walked – weight product, kg.km
(a) 27.4±2.5 to 32.2±4.8, p=0.007 (4.8, 18%)
(b) 22.6±8.7 to 26.4±10.2, p = 0.008 (3.8, 17%)
( c) 26.1±7.5 to 28.2 ± 6.9, p = 0.06 (2.1, 8.0)
SGRQ, %
(a) 56±21 to 40±21, p<.0001, ( - 16, 29%)
(b) 56±16 to 41±20, p = 0.0002, ( - 15, 27%)
( c) 47±19 to 43±20,p = 0.5 (- 4, 9%)
∆ = a – 16,, b – 15, c - 4

Guell 2006, Outpatient clinic, 1,3, RCT


Spain61 tertiary-care 4 mo. First 2 mo: (a) PR n = 18 Millon Behavioural Health Inventory, MBHI
respiratory service 2/wk relaxation, vs. Introversive ∆ = (a) 36 – 28 (b) 50 – 65 p ≤ 0.05 (-8, -15)
n = 40; 3 exacerb, 2 breathing control, (b) usual care n = 17 Forceful ∆ = (a) 68 – 56 (b) 54 – 61 p ≤ 0.05 (-12, +7)
withdrew activities of daily Sensitive ∆ = (a)76 – 65 (b) 67 -68, p ≤ 0.05, ( - 11, +1)
FEV1 32%/ 38% living. Second 2 mo: B: Good quality Chronic tension psychol aspects ∆ = (a)64-56 (b) 40 – 57 p ≤ 0.01 (-8, + 17)
68y/66y exercise training Jadad: 2 Hopkins Symptom Checklist (SCL-90 –R)
5/wk PR group showed SS improvement compared with control in 8 domains, trends in
that direction for a further 3
Paz Diaz 2007, Outpatient clinic 1,2,3 RCT Beck Depression Inventory

A-42
Table A4: Studies with mental health outcomes
Study Setting & patients PR program * Study design and quality Outcomes
ratings
Venezuela/ USA58 n = 24; FEV1 0.85/, (a) PR n = 10 (a) 14 ± 8 to 6 ± 2, p <0.01 (- 8, 57%)
34%/ 0.75, 30% 2 months, 3d/week vs. (b) 18 ± 8 to 16 ± 11, NSS (- 2, 11%)
67/61 y (b) usual care n = 14 Between group ∆ = - 6
State Trait Anxiety Inventory
B: Good quality Trait: a) 35 ± 26 to 19 ± 8, p = 0.06 (- 16, 46%)
Jadad: 1 (b) 18 33±25 to 35±21 NSS (+2, 6%)
State: (a) No change 9 – 8
(b) No change 19 – 21

Eaton 2009, New Inpatient and 1,2,3 RCT a1) PR attendees; a2) PR non attendees; b) Usual care
Zealand26 outpatient HADS – Anxiety
n = 97 inpatient 30 min (a) PR n = 47 Baseline: a) = 7.8, b = 8.7
exercise/ d vs. 3 months: a) = 5.6, b = 7.2
FEV1 0.8/, 36%/ 0.8, outpatient 8 wks, 2d/ (b) usual care n = 50 Between group ∆ = 0.72
35% wk HADS – Depression
70/70 y B: Good quality Baseline: a) = 6 .1, b = 6.5
follow up to 3 mo Jadad: 3 3 months: a) = 5.3 b) = 5.7
Between group ∆ = 0
Elci 2008, Hospital dept and 1,2,3 [4,5] for 3 mo; RCT
Turkey33 home 24 sessions + (a) PR HADS
community hospital exercises 2/d, 5d/wk n = 39 values at 1 & 3 mo
+ home at home (b) Usual care n = 39 (a) 17.51 – 13.54, p = 0.001 (-4, 23%)
n = 78 (b) 20.36 – 21.20, p = 0.065 (+1, 5%)
FEV1 47.8%, 46.3% B: Good quality Between group difference 4.81
60/58y Jadad: 2
O’Neill 2007, Outpatient (physio) 1,3 RCT HADS - 6 wk between group difference
UK63 + home a) 1 supervised session + 2 home – anxiety - 5.71, p = 0.92
n =91 6 wks, 3 sessions/wk sessions/ wk, n = 46 - depression - 0.18, p = 0.73
FEV1 0.91,39/ Follow up 6 mo from vs. Combined groups, ∆ from baseline, 6wk, 2 mo, 6 mo
1.1/44 start PR b) 2 supervised sessions + 1 home – anxiety - 0.77 (p>0.05)/ - 0.95/ - 0.41
69/68 y session/ wk, n = 45 - depression - 1.17/ - 0.88/ -0.61

B: Good quality
Jadad: 3
Kayahan 2006, Outpatient clinic 1,2,3,6: NRCT Hamilton Anxiety rating scale
Turkey59 bronchial hygiene, (a) 8.91±6.94 to 5.87±3.84, p=0.01 (-3, 34%)
FEV1 1.47/56% and breathing retraining, a) PR, n = 26 (b) 7.91±6.64 to 8.73±7.63, p=0.56, p = 0.04 (+ 0.8, 10%)
1.39/58% relaxation vs. Between group ∆ = 3.86

A-43
Table A4: Studies with mental health outcomes
Study Setting & patients PR program * Study design and quality Outcomes
ratings
COPD grades (a) 1 = (b) usual care n = 19 Hamilton depression rating scale
I,15 = II, 2 mo, 3d & 2.5h/wk a) 5.43±4.84 to 4.00±2.94, p=0.13 (- 2.5, 46%)
10 = III C. Fair quality (b) 7.18±6.49 to 5.55±3.96, p=0.20, p = 0.90 (-1.6, 23%)
(b) 1 = I, 11 = II , 7 Between group ∆ = - 0.21
= III.
66y
Lolak 2008, Hospital outpatient 1,2?,3,5 RCT HADS-A *(anxiety)
USA64 n = 46/37; FEV1 (a) PR n = 39 (a) 5.5 – 4, p<0.001, (- 1.5, 36% )
45%/46%, 65y/67y 8 weeks, 2d/week vs. (b) 7.0 – 4.2, reduction, p< 0.001 (- 2.8, 39%)
n = 83: 54 (65%) had (b) PR + progressive muscle between groups p = 0.22
COPD, 14 relaxation , n = 29 HADS-D (depression)
pulmonary fibrosis, (a) 4.9 – 3, p<0.001 (- 1.9, 36%)
5 asthma, 3 pulm C: Fair quality (b) 5.9 – 4.2, p< 0.001 (- 1.7, 23% )
embolism, 7 other Jadad: 3 between groups p = 0.09

Kozora 2002, Hospital clinic? 1,2?,3,5 NRCT Beck Depression inventory


USA60 (a) PR, n = 26 (a) 13.0 (1.6) to 8.3 (1.3) , p<0.001 (-4.7, 36%)
n = 46 CH PR 3 weeks, 12 vs. (b) 9.4 (1.3) to 8.2 (1.0), nsd, (- 1.2, 13%)
sessions (b) usual care n = 26, ( c) 4.8 (0.9)to 5.2 (1.0) , nsd (+ 0.4, 8%)
FEV1 39.8%, 44.4%, v Between group ∆ a) – b) = 3.5
67y (c) healthy controls, n = 20 12 neuropsychological tests
n = 29,29 &21 for neuropsych No significant interaction effects across the three groups.
tests PR patients classified as impaired had clinically significant improvement in three
tests related to visual attention, verbal retention and visuospatial ability
D: Poor – fair quality
* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-44
Table A5: Studies reporting numbers of exacerbations
Study Design/ quality Period Exacerbations per patient Statistical significance
PR Comparison
Guell 2000, Spain45 RCT 24 mo Usual care p <0.0001
a) PR, n = 24 3.7 ± 2.2 6.9 ± 3.9
v
b) usual care n = 23
A: High quality

Cote et al. 2005, Prospective cohort study 12 mo pre to 12 mo Usual care


USA48 D: Poor – fair quality post PR 1.81 - 1.45 3.71 - 4.62 p<0.005

Ambrosino 2008, RCT, double blind 12 wks PR + tiotropium relative risk reduction 31.3%,
Italy66 a) PR, n = 90 0.22 p = 0.23
vs. 0.29
b) PR + tiotropium
n = 87
A : High quality
Haugen 2007, Inpatient clinics 8 mo post PR PR, cool PR, warm p = 0.02
Norway/62 PR in Norway, n = 36 vs. PR in Spain, n = 60 climate climate
A: High quality 1.03 0.22
Maltais 2008, 8 hospital, 2 community centre outpatient clinics, n = 114 vs. self – 40 wks post PR Outpatient Home PR p > 0.05
Canada67 monitored home PR, n = 119 PR 1.55
B: Good quality 1.73

A-45
Table A6: Studies that included hospitalization data
Study Comparison and data Quality Period Hospital admissions/ patient Hospital days/ patient Other
PR Non - PR PR Non - PR
Eaton 2009, PR v usual care, patients admitted with B: Good 3 mo 0.23 0.32 1.7 4.2 NSD between groups
New Zealand26 exacerbations. COPD – related readmissions
Man 2004, Patients admitted with exacerbations. COPD – A: High 3 mo 0.35 0.59 4.8 7.7 p = 0.30, 0.21
UK24 related readmissions PR v usual care
Guell 200045 PR v usual care A: High 24 mo 0.6 1.3 p = 0.57
Griffiths 2000, PR v usual care B: Good 12 mo Respiratory – Respiratory. –
UK 34 related: 1.4 1.9 related: 9.4 18.1 p = 0.044, 0.048
All causes: All causes:
1.7 2.2 10.4 20.0 p = 0.021, 0.022
Raskin 2006, Post PR vs. pre PR, 11 centres D: Poor - 12 mo Respiratory – Respiratory – p = 0.008, 0.016
USA68 All admissions fair related: 0.18 0.35 related: 2.26 3.24
All causes: All causes:
0.40 0.65 1.98 4.16 p = 0.017, 0.150

Californian Post PR vs. pre PR, 9 centres E: Poor 12 mo 3.4 10.0 p < 0.05
PRCG 2004, All admissions, self – reported data
USA69
Lomundal Post PR vs. pre PR, maintenance study, D: Poor - 12- 36 0.3 0.7 1.4 4.3 p < 0.05, > 0.05
2007,56 admissions due to exacerbations fair mo
Steinsbekk
2009,57
Lomundal Post PR vs. pre PR, self management study, D: Poor - 24 mo 0.8 0.8 3.8 4.0 p > 0.05, > 0.05
200756 admissions due to exacerbations fair
Moullec 2008, Post PR vs. pre PR; PR + self help B: Good 12 mo Respiratory – p < 0.03
France51 associations v usual care. Self reported data related:
3.0 –0.0 2.7 – 6.4
All causes:
3.5 – 1.5 5.6 – 7.9
Cote 2005, PR v usual care, Post PR vs. pre PR D: Poor - 12 mo 0.49 – 0.26 0.56 – 0.42 1.81 – 1.45 3.71 – 4.62 p <0.005
USA48 COPD – related admissions fair
Ambrosino PR v PR + tiotropium A: High 3 mo 0.05 0.02
200866

Wittmann PR vs. PR + behaviour training. Pre PR vs. B: Good 12 mo 0.25 – 0.12 0.31 – 0.10
2007, post PR. COPD – related admissions, data
Germany70 from surveys

A-46
Table A7: Comparison of PR and pharmacological therapy
Study Setting & PR program * Study design & Outcomes
Patients Quality ratings
Ambrosino 12 pulmonary 1, 3 RCT, double blind Exercise capacity (6MWD)
2008, Italy66 units with PR 8 wks (5 wk prior a) PR, n = 90 Baseline, start PR , end PR, follow up;
n = 234 PR) vs. a) 402, 411,444, 440
FEV1 1.1, 40%/ b) PR + tiotropium b) 405, 424,451, 434
1.1/ 43% n = 87 ∆ from start PR
67/68 y Follow up 12 wks no (a) 33, 29 (b) 27, 10
PR, still treated with A : High quality NSD between groups
drug/placebo Jadad : 3 HRQL _SGRQ total
Baseline, start PR, end PR, follow up:
(a) 39.1, 37.0, 33.1, 33.1
(b) 39.1, 35.6, 30.9, 31.8
∆ from start PR
(a) - 3.9, -3.9 (b) - 4.7, -3.8,

Dyspnea, TDI
a) 2.25, b) 3.60
a) 2.1 b) 2.4

Casaburi 2005, 17 sites 1, 2? RCT, double blind


USA71 providing PR a) PR, n = 44 Maximal exercise (treadmill/cycle
8 wks (following 5 vs. ergometer),
n = 108 wks run in with drug) b) PR + tiotropium Endurance time, min-
Follow up 12 wks n = 47
FEV1 0.94/36.2/ Baseline -end PR – end follow up
0.82/32.6 A : High quality a) 10.5, 16.5,15.8
67/66 y Jadad : 3
b) 12.1, 21.9,22.4
Between group ∆
End PR: 5.35 [0.69 , 10.00]
End follow up: 6.60 [1.15 ,12.02]
HRQL _SGRQ total
Baseline - end PR – follow up
a) ∆ = - 3.41, - 1.63
b) ∆ = - 7.27, - 6.06
Between group ∆
Baseline - end PR: 3.86
End PR - end follow up: 4.43

Lindsay 2005, Outpatient 1,3,5 RCT Exercise capacity 6MWD


PRC – Hong baseline - end PR
Kong73 n = 50 a) PR + tiotropium a) ∆ = 22.98 b) ∆ = 30.80
PR 6 wks, 1d/wk 18μ/d , n = 25 baseline - 3mo
FEV1 0.9/0.8 (6wk run in prior to vs. a) ∆ = 11.28 b) ∆ = 36.68
PR) HRQL - CRQ
70/70 y b) tiotropium only baseline - end PR – 3 mo
Follow up 12 wks n = 25 Dyspnea (a) ∆ = 1.18, 0.99 ; (b) ∆ = 1.12,
(?post PR) 1.08
D : Poor to fair Fatigue (a) ∆ = 0.41, 0.51 ; b) ∆ = 0.40,
quality 0.43
Jadad: 1 Emotion (a) ∆ = 0.38, 0.42 b) ∆ = 0.28,
0.36
Mastery (a) ∆ = 0.34, 0.49 (b) 0.34, 0.41
NSD between groups

* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6.


Other

A-47
Table A8: Studies on airway therapies and PR
Study Setting & PR program * Study design
patients Outcomes
Köhnlein Inpatient, 1,2,3 Prospective,
2009, matched controls HRQL – SF-36
Germany 75 N = 80 5 d/wk, total Physical component
29 d a) PR n = 40 a) ∆ = - 0.4
FEV1: 0.69, b) ∆ = 0
25.5% // b) PR + Non Mental component
0.72/26.4% invasive positive a) ∆ = 8.0, es 0.44
pressure ventilation
57/58y n = 40 b) ∆ = 13.9, es 0.73
Exercise capacity, 6MWD
D: Poor – fair a) ∆ = 50 [35.6 – 63.1], es 0.58
quality
b) ∆ = 82 [60.6 – 101.8], es 0.89
between groups p = 0.04
Largest non stop walking distance
a) ∆ = 51 [39.5 – 82.3] es0.47
b) ∆ = 89 [60.6 – 110.6] es 0.74
between groups p = 0.03

Duiverman Hospital clinic 1,2,3 ; 4,5 if RCT


2008, necessary Start PR – 12 wks
Netherlands74 n = 72 a) PR n = 32 HRQL – CRQ total
12 wks, 3
sessions/wk + b) PR + Non a) ∆ = 8.7, b) ∆ = 15.1 , p = 0.08
12 wks run in invasive positive fatigue domain
pressure ventilation
n = 24 a) ∆ = 5.0, b) ∆ = 1.8 , p<0.05
Maugeri RFQ total
B: Good quality
Jadad: 3 ∆ = 10.7, b) ∆ = - 0.1, p<0.05
Exercise capacity 6MWD
a) 318 – 340, b) 304 – 325
between groups ∆= 0, p > 0.05

Eves 2008, Outpatient 1,2,3 RCT HRQL – SGRQ total


Canada76 6 wks, 3d/wk a) PR n = 19 a) ∆ = - 3.6
n = 19/19 vs. b) ∆ = - 7.6
FEV1 1.35/ b) PR while p = 0.049
1.37 breathing 60% He, Symptom: -a) - 5.49.4, b) -8.817
66/65y 40% O2 (HH), n = a) Activity: -3.28.3, b) -7.48.7
19 Impact: -3.39.4, b) -7.37.2
SF 36, Physical function
A: High quality a) ∆ = 5.3 b) ∆ = 6.1, p = 0.85
Jadad: 4 Mental health
a) ∆ = 0.1 b) ∆ = 5.7, p = 0.23
Constant load exercise time, min
a) 5.5 – 9.9 b) 5.3 – 14.9, diff between groups
5.2, p = 0.047
Work rate
a) ∆ = 6 (NSS)
b) ∆ = 9, p <0.001

* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6.


Other

A-48
Table A9: Studies on surgical procedures and PR
Study Setting & PR program * Study Outcomes
patients design,
quality
Pompeo 1,2?, 3. 5 RCT Exercise capacity (6MWD)
2000, Italy78 Outpatient + a) 376 – 407 (∆ = 31, 8%), p<0.0001
inpatient for 7 who At least 6 wks, 5d/wk a) PR, n = 27 b): 380 – 473 (∆ = 93, 24%),
lived too far away Follow up: vs. p<0.0001
6 mo post surgery/ b) thorascopic Mortality to 6mo
n = 60 completion PR + 24 LVRS, uni or a) 1 b) 2
±10.4 mo long term bilateral, no PR Late complications in hospital
FEV1 0.86,/ 0.83 follow up pre or post op (a) 4 (exacerbations 3, pneumonia 1)
64/62 y n = 28 b) 19 in 16 patients (53%) between
group p=0.003
B : Good Long term
quality a) 9 (4 deaths, 5 acute exacerbations)
Jadad: 3 b) 3 (2 deaths, 1 hospitalization)
(12 group a crossed over to group b for
treatment)
Dyspnea index
a) ∆ = -0.4 (-12%)
b) ∆ = - 1.52, (-46%) intergroup
p<0.0002

Mercer Outpatient 1, 3 NRCT Exercise capacity 6MWD


1999, USA79 a) 1027 – 998 (- 29, -2.8%)
n = 28 6 wks, 3d/wk a) PR, n = 13 b) 952 – 1145 ( 193+ 20.2%)
Follow up 6 mo post vs. p < 0.05
FEV1 both 0.82 surgery b) PR + LVRS
n = 12 PFSDQ
71/67 y Same 6 week PR for all, a) Baseline: 2.97; 6 mo post – trmt :
then volunteer to C : Fair quality 3.11, ∆ = 0.14
continue PR or have b)
bilateral LVRS
Baseline: 3.95; 6 mo post – trmt : 2.00,
PR group cont in mtce ∆ = - 1.95
program 2d/wk; + p < 0.05
unsupervised home Dyspnea, Borg
exercises. LVRS group: a) 5.5 – 4.5
PR instituted asap, b) 5.45 – 3.25
rehab exercise 2-3 d/wk p < 0.05
in PR centre

PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6.

A-49
Table A10: Study on electrical stimulation in PR
Study Setting & PR program * Study design & Outcomes- exercise capacity Outcomes- HRQL
Patients Quality ratings and BMI
Vivodtzev 2006 , Inpatient 1,2,3 RCT
France80 n = 17 4 wks, 4 d/wk 6MWD MRF-28
a) PR, n = 8 a) ∆ = 30 , a) ∆ = 0 ,
FEV1: 27%/, vs. b) ∆ = 63 , (p = 0.01)
p = 0.12 between groups b) ∆ = - 15%, p = 0.035
34% b) PR +
59/68y electrostimulation, n = 9 dyspnea in daily tasks domain
BMI a) ∆ = - 0.2
C : Fair quality b) ∆ = - 1.7, p = 0.05
Jadad : 1 a) ∆ = 0.3, p = 0.11 ,
b) ∆ = 0.6 , (p = 0.02)
p = 0.19 between groups

PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-50
Table A11: Studies on PR that considered patient characteristics
Study Settings and patient details * Study design, quality Outcomes
Age profile
Baltzan 2004, Canada81 Inpatient Prospective cohort Exercise capacity, 6MWD
1,2, 3, 5 a) < 80y, n = 187 a) 144 – 231, p <0.001 b) 133 – 185, p <0.001
 3 wks vs. ∆ = a) 87 b) 52
b) > 80y, n = 43 (% improvement 60 vs. 40, p = 0.17)
n = 230
C: Fair quality 2 min stair climbing test (laps)
a) 6.5 – 9.3, p < 0.001, b) 5.2 – 7.9, p<0.001
FEV1 0.72/ 0.77
intergroup p =0.040, 0.002
Global Function Score
a) 88 – 94, p<0.001 b) 85-91, p <0.001
intergroup 0.038, 0.033
Fabre 2007, France82 Outpatient Observational, cohort study
1,3, 6 = respiratory training, a) < 65y, n =18 Maximal exercise (treadmill/cycle ergometer)
7 wks, 3/wk b)  65y, n = 21 Peak power before and after training, W
a) 86.6 – 108.4 b) 75.7 – 89.2
FEV1 1.6/ 1.4 D: Poor – fair quality ∆ = a) 21.8, b) 13.5
40% of initial peak power
57/69y a) 57.1 – 70.0 b) 53.9 – 65.3
intergroup p < 0.05
Disease severity
Riario – Storza 2005, Day hospital NRCT
Italy84 1,2, 3 a) PR, no history of acute exacerbations, n = Exercise capacity, 6MWD
4 wks, 8 visits 37 a) 387 – 445 b) 370 to 401
vs. ∆ = a) 58, b) 31
FEV1 1.25/ 1.19 b) PR, at least 3 acute exacerbations in last 3
y, n = 37
75/74 y C: Fair quality p = 0.028
85
Lizak 2008, Poland, Outpatient Prospective observational Exercise capacity, ISWT
1,3 Compared outcomes for patients with MRC dyspnea score/ change, metres
6 wks, 2/wk different levels of dyspnea, & for men and 2/59.2; 3/ 65.5; 4/ 59.1; 5/64.4
women
MRC Dyspnea score 2,3,4,5: Male vs. female : -0.6 vs. -0.7, nsd
FEV1 1.19/ 1.22/ 0.99/ 0.87 C: Fair quality
70/68/70/70 y

Evans 2009, UK86 Outpatient Retrospective cohort analysis Exercise capacity, ISWT,
1,2,3 a) before PR, Data for MRC grades 2,3,4,5:
7 wks, 2/wk vs. Difference, m: 66, 63, 59, 54
FEV1, by MRC grades b) end of PR Effect size: 0.61, 0.65, 0.58, 0.62
(2,3,4,5) : n = 450 % achieving MCID (48m): 65, 58,63,50
1.2/41%// 1.1/44%// 1.0/39%// All improved significantly, no absolute difference between groups

A-51
Table A11: Studies on PR that considered patient characteristics
Study Settings and patient details * Study design, quality Outcomes
Age profile
0.9/38% C: Fair quality
69/68/70/70 y
Carone 2007, Italy88 Inpatient clinic Multicentre observational Exercise capacity, 6MWD
1,2,3,4,5 Chronic respiratory failure vs. non– CRF a) ∆ = 48.2, 17% b) ∆ = 47.8, 13%, p > 0.05
Total wks not given, 5 outcomes after PR HRQL – SGRQ
sessions/wk a) CRF, n = 327 Total a)  = - 8.3 b)  = - 11.1, p > 0.05
n = 1130 vs.
Activity a)  = -5.9, b)  = - 12
FEV1 37.3%/ 48.6% b) non CRF, n = 730
Activity SS reduced in Non-CRF vs. CRF. No other between group
D: Poor – fair quality
differences
70/69 y
Garrod, 2006 , USA87 Outpatient clinic/combined Observational
1, 2?, 3 Mild Moderate Severe
7 wks, 2 sessions/ wk, Compared outcomes for patients with MRC grade 1/2 3/4 5
n = 74 different levels of dyspnea (MRC 1/2 n =
16, 3/4 n = 22, 5 n = 13) ∆ 6MWD 54.7 68.0 32.6
FEV1 : mild/ moderate/ severe = % > MCID 81 59 46
66%, 44%, 38% D: 6.5 Poor – fair quality ∆ SGRQ - 7.5 - 7.0 + 0.7
% > MCID 50 50 39
64/68/73 y
Plankeel 2005 , USA89 Outpatient Retrospective cohort review , data base Exercise capacity,
1, 2, 3? compared groups on 1ry limitation seen in 6MWD, % ∆
n = 290 initial exercise testing (ventilatory, a) 34.2, b) 26.7, c) 26.4 d) 35.7
4 wks, 20 sessions ventilatory & cardiovascular, cardiovascular, p = 0.12 between groups; for whole population ∆ =30.3%, p
no limitation) <0.0001
FEV1 : 0.97/ 0.99/1.52/1.26 E: Poor quality

66/67/66/67 y
Di Meo 2008, Italy90 Outpatient + home Prospective observational Exercise capacity, 6MWD
1,2, 3, 6 = Inspiratory muscle compared characteristics of patients whose Mean increase 76.2m (23.2%)
training 6MWD gain was above or below the 75th Patients with high 6MWD gain had lower baseline FEV1 (35.6% v
4 wks, 5 times/wk then at home percentile 42.6%) and lower baseline 6MWD (330m v 409m, p = 0.012) than
2/wk for 6 wks E: Poor quality those with low gain.

FEV1 35.6%/ 42.6%

74/74 y
Adherence
Fan 2008 , USA91 Outpatient, multicentre Non -random comparison using data from Duration of PR, d
1, 2, 3, 4, 5? RCT (NETT) a) 53.9, b) 52.6, p = 0.5
n = 1218 Exercise sessions
a ) medical treatment, n = 774 9.6, 11.3, p < 0.0001

A-52
Table A11: Studies on PR that considered patient characteristics
Study Settings and patient details * Study design, quality Outcomes
Age profile
6-10 wks pre surgery, 16-20 vs. Attendance at ≥ 10 post – randomization sessions
sessions b) LVRS, n =522 a) 423 (73.3%) b) 446 (85.4%), p < 0.0001
8-9 wks post
C: Fair quality
Heppner 2006, USA92 Home care after outpatient Values for post – PR ; 6mo ; 12 mo ; 24 mo:
1, 2?, 3, 5 NRCT –
Exercise capacity 6MWD
8 wk PR, 12 mo mtce a) regular walkers, n = 51 a) 470 -455-441-414 b) 470-458-443-423
24 mo follow up vs. both groups <0.01 24 mo v baseline
b) irregular walkers n = 72 Self Efficacy for Walking
COPD: n = 46/61 a) 4.6, 5.1, 4.8, 4.6 b) 4.8, 4.3, 4.1, 3.2
non – COPD: n = 5/11 C: Fair quality
HRQL QWB scale
Intergroup p<0.05 first three points, both groups declined from post
PR to 24 mo, p <0.01
Previous PR
Ries 2005 , USA93 Clinical centres Prospective observational data from RCT
1,2,3,4,5 study (NETT) Changes from baseline after PR
6- 10 wks, 16 – 20 sessions a) those who had previous PR n = 774 Exercise capacity 6MWD
vs. a) 60.7 b) 101.7, p < 0.01
FEV1 : 0.8/26.7 ; 0.8/26.8 b) no previous PR, n = 441 Maximal exercise
a) 2.4 b) 4.3, p < 0.01
67/67 y B: Good quality HRQL – SGRQ total
a) – 2.6 b) – 5.1, p = 0.01
SF 36
Physical
a) 0.9 b) 2.2
Mental
a) 1.8 b) 2.3 p < 0.01
Gender difference
Haave 2008 , Norway94 Inpatient Observational, before / after
1,2?,3,4 a) female participants Exercise capacity 6MWD (before/after PR)
4 wks b) male participants a) 506 – 630 b) 510 – 544, p = 0.35
both n = 72
FEV1 : 1.4/58.1; 0.8/26.8 HRQL – Perceived QOL scale – before/ after PR, 6 mo follow up
C: Fair quality a) 5.2,5.2, 5.3 b) 5.1, 5.5, 5.3, p = 0.54
59/59 y

Skumlien 2007, Inpatient, n = 61 NRCT 6MWD


Norway37 1,2,3,5 as needed a) PR, n = 40 (n =33 for some outcomes) Women ∆ = - 8m [-36, 21], p =0.58. Men ∆ = 33 [13, 53], p =

A-53
Table A11: Studies on PR that considered patient characteristics
Study Settings and patient details * Study design, quality Outcomes
Age profile
4 wks v 0,003.
b) Usual care Between group comparison p =0.018
FEV1 n = 20 7 of 33 (6 men, one woman) improved by ≥ 54 m
1.3, 45%/ 1.2, 46% HRQL – SGRQ total
GOLD stage II – IV C: Fair quality 12 of 18 men, 5 of 15 women had change in score ≥ MCID, p =
0.08
63/65 y
* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

Table A12: Studies on different settings for PR


Study Study design and quality Settings and patient Outcomes
numbers
Maltais 2008, Canada67 RCT – non inferiority, 8 hospital, 2 community centre Other than a better symptom score for the home PR group at 3 mo (p =
outpatient clinics, n = 114 vs. self – 0.011), NSD between groups for HRQL (CRQ, SGRQ), exercise capacity
A: High quality, Jadad: 3 monitored home PR, n = 119 (6MWD) , and maximal exercise at 3mo and 12 mo.

Guell 2008, Spain95 RCT Hospital clinic PR n = 28 vs. Improvement in exercise tolerance (6MWD) and HRQL (CRQ) similar for
A: High quality, Jadad: 3 home exercise program both groups, except hospital program gave greater benefit in emotional
(unsupervised street walking), n = 23 function domain of HRQL
Haugen 2007, Norway62 RCT Inpatient clinics At 8 mo after PR there was NSD in psychological well being (SGRQ,
A: High quality, Jadad: 3 PR in Norway, n = 36 vs. PR in HADS), exercise capacity or hospital stay between groups having
Spain, n = 60 rehabilitation in warm and cold climates.

A-54
Table A13: Studies on duration of PR
Study Setting & PR program* Study design & Quality Outcomes- exercise
patients ratings capacity Outcomes- HRQL
O’Neill 2007, Outpatient + 1,3 RCT Exercise capacity
UK63 home a) 1 supervised session + 2 Combined groups, difference from baseline, at 6 wks, 2 mo, 6 mo.
n =91 6 wks, 3 home sessions/ wk, n = 46 ∆ between groups, All SS unless shown
sessions/wk vs. baseline to end PR HRQL – CRQ total
FEV1 0.91,39/ b) 2 supervised sessions + 1 10.4, 8.2, 6.7 *
1.1/44 Follow up: home session/ wk, n = 45 ISWT 13.5 m * NSS
6 mo from B: Good quality ESWT 155 s
69/68 y start PR Jadad: 3
∆ between groups,
baseline to 2 mo
ISWT 3.9 m, ESWT 131
s

∆ between groups,
baseline to 6 mo
ISWT 0.6 m, ESWT 87s

Sewell 2006, Outpatient 1,2,3, 6 = RCT Exercise capacity


UK96 n = 100 unsupervised a) 4 wks PR + 3 wks ∆ at 4 wk, 7 wk, 6 mo HRQL - CRQ
home training unsupervised rehabilitation, ISWT Both groups SS improvement from baseline, maintained @ 6 mo, declined
FEV1 1.16/1.11 n = 41, 36 @ 6 mo a) 6.7, 56.9, 34.2 b) not from 7 wks (Fig)
2 sessions/wk, vs. measured, 52, 29 HRQL - BPQ
68/72 y 2h/ session b) 7 wks PR, n = 41, 35 @ ESWT a) 13.3±4.9 b) 13.9±4.6, p > 0.05
Follow up: 6 mo a) 115, 338, (approx 150,
6 mo from C: Fair quality from Fig) b) not
start PR Jadad: 3 measured, 217, 121
Both + home @ 7 wks p = 0.024
training between groups
exercises

A-55
Table A13: Studies on duration of PR
Study Setting & PR program* Study design & Quality Outcomes- exercise
patients ratings capacity Outcomes- HRQL
Rossi 2005, Outpatient clinic, 1,2,3 (4,5 Observational, prospective Exercise capacity, HRQL – SGRQ total
Italy98 rehab centre counsel as cohort 6MWD ∆ , 20 wks – 10 wks
nec.) 43 (% improvers (a) 20
mild – moderate a) 10 sessions PR (b) 76) - 4.8 (% improvers (a) 34 (b) 68)
CAO; n = 25 3 sessions/ wk, vs. Maximal exercise , W
(18/7 COPD/ up to 3h/ b) 20 sessions PR. max
asthma) session , 10-20 D : Poor – fair quality 4.2 (% improvers (a) 48
FEV1 64% sessions (b) 68)

65 y

Green 2001, Outpatient 1,2,3 RCT Exercise capacity, Mean CRQ total
UK difference between a)
7 wks, 2 a) 7 wk PR program and b) Mean difference between a) and b)
FEV 1: 1.03/ 1.08 sessions/ wk
vs ISWT - 0.61 [- 1.08, - 0.15]
4 wks, - 16.9 m [- 58.6, 24.81]
69, 68 y extended b) 4 wk PR program
sessions for Treadmill endurance
educational C: Fair quality test
component Jadad: 2 - 1.15 min [- 1.87, 1.39]

* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-56
Table A14: Studies on aspects of exercise training
Topic Study Setting & PR program * Study design & quality Outcomes- exercise capacity Outcomes- HRQL
patients ratings
Number of Carrieri – Outpatient a) 3, 6 = instruction to RCT Exercise capacity HRQL – CRQ
supervised Kohlman, 2005, clinic ?, home walk a) n = 36 6MWD - NSD between groups, At 4, 8 and 12 mo, all groups
sessions USA99 n = 115 b) As a) + 4 vs. and changes all less than MCID improved their mean dyspnea
supervised exercise b) n = 33 (no data given). subscale scores above MCID .
sessions vs. Endurance treadmill test NSD between groups for any
FEV1 1.09/44.8 c) As a) + 24 c) n = 34 Group c had greater improvement subscale at 12 mo
supervised exercise in performance then other groups
66 y sessions, B: Good quality At 12 mo, ∆ from baseline,
8 wks Jadad: 2 minutes: a) 1.9 [- 2.8, 6.5] b) 1.1,[-
Follow up: 3.9, 6.1] c) 8.1 [3.2, 13.0]
1 yr
Individually Sewell 2005, Outpatient 1,2,3 RCT Domestic activity monitor counts No measured
targeted training UK100 n = 180 a) PR incl. general COPM, CRQ, Exercise capacity
7 wks, 2 sessions/ wk strengthening exercises, n (ISWT, ESWT)
FEV1 0.93/ 0.97 with 1h exercise + 1h =59 NSD between groups for any
education vs. measure
69/67 y b) PR + exercises based on
individual’s daily activities,
n = 64

A: High quality
Jadad: 3
Interval vs. high Puhan 2006, Inpatient, rehab 1 (cycle ergometers), 3, RCT, non – inferiority ∆ Exercise capacity ∆HRQL – CRQ and Maximum
intensity Switzerland101 hospital 5, 6 = breathing a) PR, n = 46, ITT, 42 per 6MWD exercise capacity
training severe COPD, therapy protocol a) 42.3 (18.3%), b) 37.8 (13.3%) NSD between groups
GOLD ≥ 3 3wks, 12-15 sessions v Improvement clinically non-
n = 100 b) PR + strength training inferior for the interval exercise
Follow up: program, 5 exercises. n = group
FEV1 2 wks 48, ITT, 44 per protocol Unintended breaks (median) a) = 2,
0.87/34.5%// b) = 11
0.89/ 34.1% C : Fair quality Adherence to protocol
Jadad : 3 a) 47.9%, b) 23.9%
69/69 y
Hsieh 2007, Outpatient 1,3 Observational 6MWD
Taiwan104 n = 34 6 wks, 12 sessions. a) completers of program, n a) ∆ = 41.3, p = 0.003
Included high intensity = 18 b) ∆ = 40.4, p = 0.004
FEV1 1.21/52.9// training vs. between groups p = 0.90
1.30/59.6
b) non – completers, n = 16

A-57
Table A14: Studies on aspects of exercise training
Topic Study Setting & PR program * Study design & quality Outcomes- exercise capacity Outcomes- HRQL
patients ratings
71/74 y
D: Poor – fair quality

Varga 2007, Outpatient clinic 1? RCT / NRCT NSD between supervised groups in NSD between groups for Borg
Hungary103 and home 8 wks, 3/ wk, 45 High intensity n = 22 vs. peak exercise measures, p <0.05 dyspnea
n = 71 min/session interval training n = 17 between supervised and self –
FEV1 1.5/51, (RCT) training groups.
1.7/64, 1.5/52 vs.
c) self paced training, n =
61/67/60y 32
(NRCT)
C: Fair quality
Jadad: 1
Mador 2009, Outpatient clinic 1,2,3 RCT
USA 102 6MWD CRD
Interval (3 min 3 sessions/ wk for 8 a) Continuous training, n = a) ∆ = 32m a) ∆ = 9.7,
blocks 1 wks 20 b) ∆ = 48m b) ∆ = 10.4
@150%, 2@ vs NSD between groups NSD between groups
75%)) vs b) Interval training, n = 21
continuous Maximal exercise, W
training a) ∆ = 11.5
n = 48 b) ∆ = 10.0
FEV1: B: Good quality
1.39/41.7%, Jadad: 1 NSD between groups
1.54/44.6%
71/72y

Inspiratory Magadle 2007, Outpatient 1, 2, 6 = Inspiratory RCT SGRQ total


muscle training UK105 muscle training (IMT) All had general exercise for 6MWD Continuous decrease in both
FEV1 1.3, 45%/ 12 wks, 3 sessions/wk 12 wks before groups, greater in IMT group,
1.3, 46% randomization Small increase, between group p > differences became SS at the end
a) general exercise + IMT, 0.05 of the 6th mo of training, (p<0.05)
65/66y n = 14
vs.
b) general exercise + sham
IMT, n = 13
C : Fair quality
Jadad : 4
* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-58
Table A15: Studies on PR and education or counselling
Study Setting & patients PR program * Study design & quality scores Outcomes
Wittmann 2007, Inpatient clinic 1,3,5 + 4 RCT HRQL – SGRQ ∆ =
Germany70 counselling a) PR, n = 90 Total a) + 0.4 b) - 2.7
n = 212 v Activity a) + 3.1 b) 0
3 weeks b) PR + 4 x 90 min over 4d structured Stress a) + 1.9 b) - 1.8
FEV1: 1.83/1.81 behaviour training in group, and 1 x 0.5 – Symptoms a) +0.7 b) - 8.5
Follow up 12 mo 1h follow up session with doctor to discuss p < 0.01
54/54 y “action plan”. Individualized action plans
then given to patients. n = 94 Education group had 2.5 greater chance of improving than PR
Unable to work prior to PR: only group [95% CI 1.07 – 5.84]
PR grp 27%, PR + training (At 12 mo a) n =88, b) n = 92) Hospital stay
group 41%, p = 0.06 A: High quality % admitted in 1y
Jadad: 2 a) 24.7 – 11.5, p = 0.02 b) 30.8 – 9.9, p = 0.001
days in ICU
a) 4.4 – 5.7 , p>0.05 b) 11.8 – 2.2 , p = 0.02
emergency admissions, %
a) 15.5 – 11.9, p >0.05 b) 19.6 – 8.7 , p = 0.03
Per – patient days unable to work because of COPD
a) ∆ = 33% b) ∆ = 52%
intergroup p =0.12 (cf 30% pensioners)
De Blok 2006, Outpatient clinic 1, 2?, 3,4, 5, RCT
Netherlands106 n = 29 a) PR, n = 8 HRQL SGRQ, RAND 36
9 weeks vs. Between group comparison
FEV1 1.44, 52%/ 1.24/ 43% b) PR + lifestyle physical activity SGRQ total p = 0.55, all RAND modules p ≥0.14
66/63 y counselling w pedometer feedback 1 wk Exercise capacity (2MWT)
prior to PR & one wk during wk 9 of PR a) 49.3 -55.1 b) 36.6 - 57.4
n=8 between group effect size, >0.80
B : Good quality
Jadad : 2 Daily physical activity (DPA)
7RPlus (steps/day 7 days including PR)
a) ∆ = 1220 (+52%) b) ∆ =1787 (+84%), p = 0.38
4Rmin (steps/day 4 days w/out PR)
a) ∆ = 673 (+29%) b) ∆ = 1535 (+75%), p = 0.24
6Rmin (steps/day 6 days w/out PR)
a) ∆ = 455 (+19%) b) ∆ = 1430 (+ 69%), p = 0.11
Norweg 2005, Outpatient PR centre a) ETLS (exercise RCT
USA107 n = 43 training plus lecture (#s at 0,6,24 wks) HRQL – CRQ total –
series): 1,2,3, 4? Repeated measures analysis, adjusted means
70/ 74 /77 y b) ETAT (exercise a) ETLS, n = 14,11,6
training plus v a) 16.43 b) 19.99 c) 18.31

A-59
Table A15: Studies on PR and education or counselling
Study Setting & patients PR program * Study design & quality scores Outcomes
activity training): b) ETAT, n = 10,10,8
1,2,5 v mean differences ETAT > ETLS 3.56, p = 0.03
c) ETA (exercise c) ETA n = 13,12,7 ETAT vs ETA, ETLS vs ETA p > 0.05
training alone)1,2
B: Good quality Functional status
6 wks, follow up 18 Jadad: 3 PFSDQ-M
wks
Outcomes SS better at 12 wks for ETAT than ETA.(dyspnea with
activities fatigue with activities, change in activity involvement
from premorbid levels ) & for total functional status at 12 wks for
older patients (p≤0.01)
At 6 and 12 wks:, ETAT ss < ETLS for dyspnea and fatigue for
older participants
At 18 and 24 wk follow up, NSD between treatment groups
Exercise capacity (6MWD)
overall combined effect, change from baseline, all groups
905.6 ft to 1085.4 ft, p≤0.004
Self efficacy
NSD between treatment groups for self-efficacy, p=0.53
Scherer 1998, Outpatient PR 1,2 (if capable), 3, 5 NRCT, 2 group, pre-post test design
USA108 n = 59 PR: 12 wks, 3 COPD Self Efficacy Scale
66/64 y sessions/wk a) PR, n = 37 Total score - Baseline to 1 mo post program
Education: 4 wks, 1 vs.
x 2h session/wk b) education only + encouraging moderate a) 2.86 (0.88) - 3.55 (0.85), p = <0.001
exercise at home, no supervised exercise, n b) 2.85 (0.62) - 3.18 (0.72) p = 0.05
6 mo follow up = 22
- Baseline to 6 mo post program
D: Poor – fair quality
a) 2.86 (0.88) -3.33 (0.89) p = 0.03
b) 2.85 (0.62) - 2.99 (0.78) p = 0.15
* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

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Table A16: Studies on nutritional intervention
Study Setting & PR program * Study design & Quality ratings Outcomes- exercise capacity Outcomes- HRQL
Patients
Deacon Outpatient 1,2 RCT
2008, n = 100 7 wks, 21 sessions a) PR, n = 42 Exercise capacity ISWT CRQ
UK112 vs. a) ∆ = 24.3 ,
b) ∆ = 36.8 , p = 0.2 Between groups , p>0.05
FEV1: 1.1, 43%/ b) PR + creatine supplement, n = 38
1.1, 45% B : Good quality ESWT
68/68y Jadad : 3 a) ∆ = 487, ∆ = 377
Faager Outpatient 1,2,3 RCT
2006, n = 23 8 wks 2 sessions/week a) PR, n = 10 Exercise capacity ESWT, s SGRQ Total
Sweden113 vs. a) 372 – 552
b) 320 – 515 between group comparison p = 0.77
FEV1 42%/44% b) PR + creatine 0.3 g/kg for 1 wk then
0.07 g/kg for remainder, n = 13 between groups, p = 0.89
64/67 y
C: Fair quality
Jadad: 2
Fuld 2005, Outpatient 1,2,3 RCT Exercise capacity ISWT,
UK111 n = 38 8 wks, 2 sessions/wk a) PR, n = 11 a) ∆ = 76, b) ∆ = 55 SGRQ Total
vs. between groups, b vs. a a) ∆ = 1.8 b) ∆ = - 5.9
FEV1 1.12, b) PR + creatine taken 3 times/d for 14 ∆ = - 21.5 [-90.6, 47.7]
45.%/ 1.13, d, then 1/d for 10 wks., n =14 ESWT, s
45.4% a) ∆ = 275 , b) ∆= 365 between groups, b vs. a
B: Good quality between groups, b vs. a ∆ = - 7.7 [- 14.9, - 0.5]
64/62 y Jadad: 3 ∆ = 90.5 [-157.6, 339]

FFM
a) ∆ = 0.4 Kg, 0.6%
b) ∆ = 2 Kg, 2.8%
Slinde outpatient + 1,2,3 NRCT, retrospective control Body weight, kg
2002, home based Change from a) PR + dietary advice, supplements if Exercise capacity – 6MWD ∆ start – end study
Sweden114 n = 93 supervised to home necessary, n =24 Normal wgt a) 357 – 380, p < 0.05, b)
based individualised vs. Normal wgt a) + 0.3, b) – 0.8
316 – 297
FEV1: 34%/35% for each patient; 45 b) n = 63 Under wgt a) + 0.6 b) + 0.7
min, 2/ wk, for 1 y usual care; no contact with the dietician Under wgt a) 323 – 348 b) 306 – 304 Over wgt a) – 3.9 b) – 1.3
67/65 y or the physiotherapist Over wgt a)269 – 269, b) 298 – 309

D: Poor to fair quality


* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-61
Table A17: Studies on strength training in PR
Study Setting & PR program * Study design & Quality Outcomes
Patients ratings
Costi 2009, Inpatient 1,2,3,5 RCT Exercise test 6MWD
Italy117 a)  = 74.4
N = 50 3 wks, minimum of a) PR + upper extremity b) a)  = 24.2
15 sessions. exercise training, n = 25
FEV1: 6 mo follow up vs 6MRT, # rings moved
1.0/41% b) PR, n = 25 a)  = 24.8
69/ 70y (both n = 23 at 6 mo) b)  = 5.2
C: Fair quality ADL Field test, shuttles completed
Jadad = 3 a)  = 4.04
b) a)  = 0.28
between groups p < 0.001
Phillips Outpatient 1,2,3,5,6 = RCT Strength outcomes
2006, clinic breathing retraining RM chest press, lb
USA115 a) PR, n =9  = -1, -2% b)  = 9, 14%
n = 24 PR 8 wks, 2 vs. -leg press
sessions/ wk b)PR + resistance training a)  = -7, -4% b)  = 20, 9%
FEV1: 0.74, program, n = 10 both p < 0.05
32.8%/ 1.11, Group b had Exercise test 6MWD
42.0% resistance training C: Fair quality a)  = 203, 21% b)  = 223, 25%
in 13 sessions, incl Jadad = 2 Functional fitness
70/71 y 2 pre and 1 post Lift & reach test
testing  = 25% b)  = 55%, p < 0.05
Other FF tests NSD between groups
Alexander Outpatient 1,3 RCT Functional fitness
2008, clinic NSD between groups on all FF measures
USA116 8 – 10 wks, 16 PR, n = 10 Exercise test 6MWD
n = 27 sessions, 2/wk vs. a) 1071 – 1231 (14.9%) b) 1053 – 1198 (13.8%)

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Table A17: Studies on strength training in PR
Study Setting & PR program * Study design & Quality Outcomes
Patients ratings
FEV1: 1.08, Muscular strength
29.8%/ b) PR = strength training, - leg press, lb
0.86/38.6% 5 exercises, n = 10 a) 222-218 (-1.8%) b) 233 – 238 (2.1%)
73/66 y - incline bench press, lb
C: Fair quality a) 64 – 79 (9.4%) b) 74 – 78 (5.4%)
Jadad = 2 NSD between groups

* PR components: 1. aerobic training 2. strength training 3. disease education 4. nutritional 5. psychological/behavioural 6. Other

A-63
APPENDIX 6: MATERIAL FROM CLINICAL
PRACTICE GUIDELINES
Canadian Thoracic Society recommendations
The 2007 update to the Canadian Thoracic Society recommendations for management of
COPD2 includes the following recommendations related to PR:

Recommendation Evidence/ strength of recommendation


Clinically stable patients who remain dyspneic and (1A) Evidence from one or more randomized
limited in their exercise capacity despite optimal trials or meta- analyses + Good evidence to
pharmacotherapy should be referred for supervised support a recommendation for use
PR.

An urgent need exists to increase access to PR (2A) = Evidence from one or more well –
programs across Canada. designed cohort or case-control studies + Good
evidence to support a recommendation for use

A more general recommendation for persons with COPD is that “All patients should be
encouraged to maintain an active lifestyle and be cautioned about the negative consequences
of prolonged inactivity in this disease.” This is based on consensus from expert groups based
on clinical experience.

The 2008 update to the guidelines118 includes the statement: “Where formal rehabilitation
programs are not available, patients should be encouraged to undertake a home – based
exercise program to prevent progressive skeletal muscle deconditioning associated with
inactivity.” No evidence level is given.

ACCP/ AACVPR recommendations

In the guidelines from the American College of Chest Physicians (ACCP) and the American
Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) ,recommendations
are classified as strong (1) or weak (2), and strength of evidence supporting the
recommendations as high (A), moderate (B) or low (C). In the following list, 1A, 1B and 1C
refer to strong recommendations, and 2A, 2B and 2C to weak recommendations. The
document also includes statements where it was thought that there was insufficient evidence
to make a specific recommendation. These statements are not graded.
Strong recommendations
 A program of exercise training of the muscles of ambulation is recommended as a
mandatory component of PR for patients with COPD. (1A)
 PR improves health-related quality of life in patients with COPD (1A)
 Six to 12 weeks of pulmonary rehabilitation produces benefits in several outcomes
that decline gradually over 12 to 18 months. (1A)
 Some benefits, such as health-related quality of life, remain above control at 12 to 18
months. (1C)
 Lower-extremity exercise training at higher exercise intensity produces greater
physiologic benefits than lower intensity training in patients with COPD. (1B)

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 Both low- and high intensity exercise training produce clinical benefits for patients
with COPD. (1A)
 Addition of a strength training component to a program of pulmonary rehabilitation
increases muscle strength and muscle mass. (1A)
 Unsupported endurance training of the upper extremities is beneficial in patients with
COPD and should be included in PR programs. (1A)
 The scientific evidence does not support the routine use of inspiratory muscle training
as an essential component of PR. (1B)
 Education should be an integral component of PR. Education should include
information on collaborative self-management and prevention and treatment of
exacerbations. (1B)
 Supplemental oxygen should be used during rehabilitative exercise training in patients
with severe exercise-induced hypoxemia. (1C)
Weak recommendations
 PR reduces the number of hospital days and other measures of health-care utilization
in patients with COPD. (2B)
 PR is cost-effective in patients with COPD (2C)
 There are psychosocial benefits from comprehensive PR programs in patients with
COPD. (2B)
 Longer PR programs (12 weeks) produce greater sustained benefits than shorter
programs. (2B)
 Maintenance strategies following PR have a modest effect on long-term outcomes.
(2C)
 Current scientific evidence does not support the routine use of anabolic agents in PR
for patients with COPD. (2C)
 There is minimal evidence to support the benefits of psychosocial interventions as a
single therapeutic modality. (2C)
 Administering supplemental oxygen during high-intensity exercise programs in
patients without exercise-induced hypoxemia may improve gains in exercise
endurance. (2C)
 As an adjunct to exercise training in selected patients with severe COPD, non-
invasive ventilation produces modest additional improvements in exercise
performance. (2B)

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Statements
 There is insufficient evidence to determine if PR improves survival in patients with
COPD.
 Although no recommendation is provided since scientific evidence is lacking, current
practice and expert opinion support the inclusion of psychosocial interventions as a
component of comprehensive PR programs for patients with COPD.
 There is insufficient evidence to support the routine use of nutritional
supplementation in PR of patients with COPD.

Veterans Administration/ Department of Defense recommendations


The US VA/DoD clinical practice guideline for management of outpatient COPD119 includes
judgements on overall quality (quality of evidence plus link to outcomes), and net effect of
the intervention. Strength of recommendations are classified as A (A strong recommendation
that clinicians provide the intervention to eligible patients); B (A recommendation that
clinicians provide (the service) to eligible patients); C (No recommendation for or against the
routine provision of the intervention); D (Recommendation against routinely providing the
intervention to asymptomatic patients); and I (The evidence is insufficient to recommend for
or against routinely providing the intervention). The following table gives a summary of the
guideline’s recommendations on PR.

Recommendation Overall Net Effect Strength of


Quality recommendation
PR should be considered for patients with COPD Good Substantial A
who have dyspnea, reduced exercise tolerance, a
restriction in activities, or impaired health status.
Pulmonary rehabilitation should be offered to all Good Substantial A
patients who consider themselves disabled by
COPD (Level 3 and above on the dyspnea scale).
Pulmonary rehabilitation is recommended for Fair Substantial B
patients with reduced exercise tolerance and
restricted activities because of dyspnea
The exercise program should be supervised and Good Substantial A
should provide cardiovascular reconditioning with
endurance and muscle strength training
The initial exercise program should be of sufficient Fair Moderate B
length, duration, and frequency
Endurance training should be performed to improve Good Substantial A
physical endurance.
Lower limb strength training should be performed Good Moderate B
to improve exercise tolerance (walking, cycling);
upper extremity training improves arm strength
In order to maintain benefits, subsequent exercise Fair Small C
training is needed
As studies show conflicting results, respiratory Good Zero D

A-66
Recommendation Overall Net Effect Strength of
Quality recommendation
muscle training is not recommended to be part of a
rehabilitation exercise program
Patients with COPD with a prior hospitalization Fair Moderate B
should be referred for pulmonary rehabilitation
Educational components and self-management Fair Moderate B
programs should be included in rehabilitation
programs, as it can reduce COPD exacerbations,
hospital admission, and length of stay.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) statements


GOLD has used a four stage evidence level scheme in its reports - A: RCTs, rich body of
data; B: RCTs, limited body of data; C: Non – randomized trials. Observational studies; D:
Panel consensus statement. In the 2008 update of its global strategy document120 the
following benefits from PR are linked to judgments on level of evidence.

Benefits of PR in COPD Level of


evidence

Improves exercise capacity A


Reduces the perceived intensity of breathlessness A
Improves HRQL A
Reduces the number of hospitalizations and days in the hospital A
Reduces anxiety and depression associated with COPD A
Strength and endurance training of the upper limbs improves arm function B
Benefits extend well beyond the immediate period of training B
Improves survival B
Respiratory muscle training is beneficial, especially when combined with C
general exercise training
Psychosocial intervention is helpful C

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These points are informed in the text by the following additional statements:

Benefits of PR in COPD Level of


evidence

COPD patients in all stages of disease appear to benefit from exercise A


training programs, improving with respect to both exercise tolerance and
symptoms of dyspnea and fatigue
Benefit does wane after a rehabilitation program ends, but if exercise training B
is maintained at home the patient’s health status remains above pre-
rehabilitation levels.
There is no consensus on whether repeated rehabilitation courses enable N/A
patients to sustain benefits gained through the initial course
Educational and exercise training components are usually conducted in D
groups, normally with 6 – 8 individuals per class
Benefits have been seen in patients with a wide range of disability, although A
those who are chair-bound appear unlikely to respond even to home visiting
programs
Stratification by breathlessness using the MRC questionnaire may be helpful B
in selecting patients most likely to benefit. Those with MRC Grade 5 dyspnea
may not benefit
Some data indicate that continuing smokers are less likely to complete PR B
programs than non-smokers.
Use of a simple wheeled walking aid seems to improve walking distance and C
reduces breathlessness in severely disabled COPD patients.
The minimum length of an effective rehabilitation program is 6 weeks; the B
longer the program continues, the more effective the results.
A study from the UK provided evidence that an intensive, multidisciplinary B
rehabilitation program was cost – effective and decreased the use of health
services.

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APPENDIX 7: ECONOMIC STUDIES DATA
EXTRACTION FORM
Background information Results
Study name Outcomes
Year Outcome 1
Country Study group
Comparator
Significant?
Identification of interventions Outcome 2
Components of pulmonary
rehabilitation Study group
Exercise Comparator
Education Significant?
Pharmaceuticals Costs
Duration of intervention Rehab group
Intensity of intervention Rehab costs per person
Identification of alternative
intervention Hospital costs
Physician costs
Methods Drugs
Type of study Other services
N in study intervention Comparator
N in comparator Hospital costs
Time duration Physician costs
Methods of identifying costs Other services
Significant?
Cost-effectiveness ratio

Quality
Study design
Economic components
Perspective stated?
Timelines sufficiently long?
Physical sources identified?
Unit costs identified and appropriate?
All key resources included?

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APPENDIX 8: ECONOMIC STUDIES THAT COMPARED PR TO NO
REHABILITATION
Table A17: Economic studies comparing PR to no rehabilitation
128 127 125 126 7 124 129 122 130
Study Cecins Griffiths Troosters Jenkins Golmohammadi Scherer Goldstein White Clini
Year 2008 2001 2000 2001 2004 1998 1997 1997 2001
Country Australia UK Holland Australia Canada USA Canada UK Italy
Characteristics FEV1<65%, age COPD,
of enrolees FEV1<80% LFV .9L <75 years CLS (N.e.s.) COPD COPD FEV<40% COPD, FEV1<40% CAO
Location of Inpatient + Inpatient +
intervention Outpatient Outpatient Outpatient Outpatient Outpatient outpatient Outpatient Outpatient
inpat:11
daily sess.,
19 days.
3h/session//
outpat: 21
Intervention 1.25hr / 2 sess. Over
time sess. / 8 wk = 2 hr /3 sess / 6 1.5/3/12 + 1.5 / 2 1.5 / 3 / 12 = 5 days/8 w + 8 wk. 3 hrs
(hr/sess/wk 20 hrs wk = 36 hrs / 12 = 1 / 2 / 8 = 16 2.5 / 5 / 8 = 100 54 home/8 w 2.5hx2timepwx6w=30 /session
Intervention
services
Counselling No Yes No No No No Yes Yes Yes
Education Yes Yes No No Yes Yes Yes Yes Yes
Rehab /
exercise Yes Yes Yes Yes Yes Yes Yes Yes Yes
Inpatient
Start of vs.
Comparator program Standard care usual care None Pre program None usual care None outpatient
Method of
analysis Pre / post RCT RCT Pre / post Pre / post Pre / post RCT baseline / post RCT
120
questioned /
N enrolled 256 99/101 50 / 50 72 210 74 respond 45/44 42 43/43
Completers 187 92/88 37 / 33 57 Not identified 38/40 36
program
Observation (outcome); 12 To end of
duration mos (costs) 12 mos. 18 mos. 12 mos. Up to 6 years 24 weeks 24 weeks intervention
Strength,
Outcome SF36==> dyspnea,
measures CRDQ QALY CRDQ CRDQ SGRQ None Walk, CRDQ CRDQ MIP, MEP

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Table A17: Economic studies comparing PR to no rehabilitation
128 127 125 126 7 124 129 122 130
Study Cecins Griffiths Troosters Jenkins Golmohammadi Scherer Goldstein White Clini
Program
resources
include:
Operating Yes Yes Not specified Yes Yes Not specified Yes Not specified Yes
Overhead Yes Yes Not specified No Yes Not specified Yes Not specified Yes
Transport No Yes Not specified No No Not specified No Not specified Yes
Health
services
included? Yes Yes No No Yes Yes No No No
Results
1st
intervention
€ 2,720,
2nd
Program US$1,500 - intervention
costs A$292 £725 ($1,450) US$2,615 A$249 $1,092 $2,000 $12,251 £400 € 3,677
Hospital days
Health less in yrs 1 -
service costs ($397,000) £1,671 ($344) 4
Total
intervention None
Total
comparator £1,826 $663
Net
difference $11,597
Disease specific
QOL +14pts at 6 CRDQ
mos. Six minute exceeded Dyspnea, emotion, Strength >.
Outcomes CRDQ walk +52m. 90m clinically CRQ mastery: .7 mastery all increase MIP, MEP
differences significant +0.03 QALYs at 18 mos. relevant 5 pts on SG scale None difference to clin. Sign. Level same
Probabilistic
analysis. 95% Cost for
of cases below achieving a clin.
Incremental £17,000 per Impt benefit:
ratio QALY $28,993
Study quality
(0,1)
Perspective
clear? 1 1 0 0 1 0 1 1 1
Post 0 1 1 1 0 0 0 0 0

A-71
Table A17: Economic studies comparing PR to no rehabilitation
128 127 125 126 7 124 129 122 130
Study Cecins Griffiths Troosters Jenkins Golmohammadi Scherer Goldstein White Clini
program
outcomes?
Program
fully costed? 1 1 0 0 1 0 1 0 1
Post
program
utilization? 1 1 0 0 1 1 1 0 0
Physical
resources
id'd? 1 1 0 1 0 0 1 0 1
Unit costs
id'd? 1 1 0 1 1 1 1 0 0

Effectiveness -
- appropriate
control? 0 1 1 0 0 0 1 0 1
Incremental? 1 1 1 1 0 0 1 0 1
Uncertainty? 1 1 1 1 1 1 0 1 1
Quality score
(/9) 7 9 4 5 5 3 7 2 6

A-72
APPENDIX 9: BUDGET IMPACT ANALYSIS MODEL RESULTS
Table A18: Budget impact analysis model results
Increase
Prevalence Number in Total Cumulative
COPD COPD COPD at end of Target of persons currently numbers served amount
prevalence incidence mortality year served served served in year served Total cost per year

Assumptions Incidence = .079 Mortality=.011 Target = 25% of cases

Year 1 775,000 61,225 -8,525 827,700 206,925 8,927 0 8,927 8,927 $0

Year 2 827,700 65,388 -9,932 883,156 220,789 8,927 0 8,927 17,854 $0


Model 1. Year 3 883,156 69,769 -10,598 942,327 235,582 8,927 0 8,927 26,781 $0
NICE
guidelines, Year 4 942,327 74,444 -11,308 1,005,463 251,366 8,927 0 8,927 35,708 $0
no
program Year 5 1,005,463 79,432 -12,066 1,072,829 268,207 8,927 0 8,927 44,635 $0
expansion Year 6 1,072,829 84,754 -12,874 1,144,709 286,177 8,927 0 8,927 53,562 $0

Year 7 1,144,709 90,432 -13,737 1,221,404 305,351 8,927 0 8,927 62,489 $0

Year 8 1,221,404 96,491 -14,657 1,303,238 325,810 8,927 0 8,927 71,416 $0

Year 9 1,303,238 102,956 -15,639 1,390,555 347,639 8,927 0 8,927 80,343 $0

Year 10 1,390,555 109,854 -16,687 1,483,723 370,931 8,927 0 8,927 89,270 $0

Assumptions Incidence = .079 Mortality=.011 Target = 25% of cases

Year 1 775,000 61,225 -8,525 827,700 206,925 8,927 28,000 36,927 36,927 $33,908,000

Year 2 827,700 65,388 -9,932 883,156 220,789 8,927 28,000 36,927 73,854 $33,908,000

Year 3 883,156 69,769 -10,598 942,327 235,582 8,927 28,000 36,927 110,781 $33,908,000
Model 2.
NICE Year 4 942,327 74,444 -11,308 1,005,463 251,366 8,927 28,000 36,927 147,708 $33,908,000
guidelines, Year 5 1,005,463 79,432 -12,066 1,072,829 268,207 8,927 28,000 36,927 184,635 $33,908,000
100%
uptake Year 6 1,072,829 84,754 -12,874 1,144,709 286,177 8,927 28,000 36,927 221,562 $33,908,000

Year 7 1,144,709 90,432 -13,737 1,221,404 305,351 8,927 28,000 36,927 258,489 $33,908,000

Year 8 1,221,404 96,491 -14,657 1,303,238 325,810 8,927 28,000 36,927 295,416 $33,908,000

Year 9 1,303,238 102,956 -15,639 1,390,555 347,639 8,927 28,000 36,927 332,343 $33,908,000

Year 10 1,390,555 109,854 -16,687 1,483,723 370,931 8,927 28,000 36,927 369,270 $33,908,000
Model 3.
NICE
guidelines,
67% Mortality Target = 25% of
uptake Values Incidence = .079 =.011 cases, 67% uptake

Year 1 775,000 61,225 -8,525 827,700 138,640 8,927 15,900 24,827 24,827 $19,254,900

A-73
Table A18: Budget impact analysis model results
Increase
Prevalence Number in Total Cumulative
COPD COPD COPD at end of Target of persons currently numbers served amount
prevalence incidence mortality year served served served in year served Total cost per year

Year 2 827,700 65,388 -9,932 883,156 147,929 8,927 15,900 24,827 49,654 $19,254,900

Year 3 883,156 69,769 -10,598 942,327 157,840 8,927 15,900 24,827 74,481 $19,254,900

Year 4 942,327 74,444 -11,308 1,005,463 168,415 8,927 15,900 24,827 99,308 $19,254,900

Year 5 1,005,463 79,432 -12,066 1,072,829 179,699 8,927 15,900 24,827 124,135 $19,254,900

Year 6 1,072,829 84,754 -12,874 1,144,709 191,739 8,927 15,900 24,827 148,962 $19,254,900

Year 7 1,144,709 90,432 -13,737 1,221,404 204,585 8,927 15,900 24,827 173,789 $19,254,900

Year 8 1,221,404 96,491 -14,657 1,303,238 218,292 8,927 15,900 24,827 198,616 $19,254,900

Year 9 1,303,238 102,956 -15,639 1,390,555 232,918 8,927 15,900 24,827 223,443 $19,254,900

Year 10 1,390,555 109,854 -16,687 1,483,723 248,524 8,927 15,900 24,827 248,270 $19,254,900

Mortality Target = all COPD


Assumptions Incidence = .079 =.011 cases

Year 1 775,000 61,225 -8,525 827,700 827,700 8,927 139,300 148,227 148,227 $168,692,300

Year 2 827,700 65,388 -9,932 883,156 883,156 8,927 139,300 148,227 296,454 $168,692,300

Year 3 883,156 69,769 -10,598 942,327 942,327 8,927 139,300 148,227 444,681 $168,692,300
Model 4. Year 4 942,327 74,444 -11,308 1,005,463 1,005,463 8,927 139,300 148,227 592,908 $168,692,300
Canadian
Guidelines Year 5 1,005,463 79,432 -12,066 1,072,829 1,072,829 8,927 139,300 148,227 741,135 $168,692,300

Year 6 1,072,829 84,754 -12,874 1,144,709 1,144,709 8,927 139,300 148,227 889,362 $168,692,300

Year 7 1,144,709 90,432 -13,737 1,221,404 1,221,404 8,927 139,300 148,227 1,037,589 $168,692,300

Year 8 1,221,404 96,491 -14,657 1,303,238 1,303,238 8,927 139,300 148,227 1,185,816 $168,692,300

Year 9 1,303,238 102,956 -15,639 1,390,555 1,390,555 8,927 139,300 148,227 1,334,043 $168,692,300

Year 10 1,390,555 109,854 -16,687 1,483,723 1,483,723 8,927 139,300 148,227 1,482,270 $168,692,300
Model 5.
Am. Resp.
Society
moderate / Mortality Target = 7% of COPD
severe Assumptions Incidence = .079 =.011 cases
cases
Year 1 775,000 61,225 -8,525 827,700 57,939 8,927 1,500 10,427 10,427 $1,816,500

Year 2 827,700 65,388 -9,932 883,156 61,821 8,927 1,500 10,427 20,854 $1,816,500

Year 3 883,156 69,769 -10,598 942,327 65,963 8,927 1,500 10,427 31,281 $1,816,500

Year 4 942,327 74,444 -11,308 1,005,463 70,382 8,927 1,500 10,427 41,708 $1,816,500

Year 5 1,005,463 79,432 -12,066 1,072,829 75,098 8,927 1,500 10,427 52,135 $1,816,500

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Table A18: Budget impact analysis model results
Increase
Prevalence Number in Total Cumulative
COPD COPD COPD at end of Target of persons currently numbers served amount
prevalence incidence mortality year served served served in year served Total cost per year

Year 6 1,072,829 84,754 -12,874 1,144,709 80,130 8,927 1,500 10,427 62,562 $1,816,500

Year 7 1,144,709 90,432 -13,737 1,221,404 85,498 8,927 1,500 10,427 72,989 $1,816,500

Year 8 1,221,404 96,491 -14,657 1,303,238 91,227 8,927 1,500 10,427 83,416 $1,816,500

Year 9 1,303,238 102,956 -15,639 1,390,555 97,339 8,927 1,500 10,427 93,843 $1,816,500

Year 10 1,390,555 109,854 -16,687 1,483,723 103,861 8,927 1,500 10,427 104,270 $1,816,500

A-75
APPENDIX 10: EXCLUDED PUBLICATIONS
Clinical publications
Narrative reviews, commentaries
50440 Alimoglu Sendrom 2007;19(10):51-7
50405 Anon Cardiopulm Phys Ther J 2006; 17: 38
50448 J Natl Med Assoc 2008;100(1):150-1
50620 J Cardiopulm Rehabil Prev 2007;27(1):57-8
50511 Anthonisen Can Respir J 2005;12(4):185-6
50618 Bartels et al Arch Phys Med Rehabil 2006;87(3):Suppl-90-, S103-5
50378 Bateman South African Med J 1998 (8):999-1002
Bekkering, KNGF 2003 Available: https://www.cebp.nl/vault_public/cms/?ID=63
50363 British Thoracic Society Thorax 2001;56(11):827-34
50417 Britto et al Revista de Fisioterapia da USP (Sao Paulo) 2002;9(1):9-16
Brooks D Chron Resp Dis 2006; 3: 1-3
50620 Carlin. J Cardiopulm Rehabil Prev 2007;27(5):311-3.
Casaburi NEJM 2009;360:1329-35.
50628 Court-Fortune et al Nutrition Clinique et Metabolisme 2006;20(4):196-201
37963 Crowe J Chron Obst Pulmonary Disease 2005;2(3):319-29.
50473 Fischer Pneumologie 2007;61(4):233-48
50430 Fromer et al Int J Clin Pract 2008;62(8):1219-36
50445 Gilbert J Natl Med Assoc 2008;100(2):266
50500 Goldstein Chest 2005;128(6):3783-4
50391 Halpin Thorax 2004;59(3):181-2
51784 Hernandez Chest 2000;118:106
50454 Huijsmans et al Respir Med 2008;102(1):162-71
50514 Kurosawa et al Respiration and Circulation 2005;53(5):501-7
50407 Lee BMJ 2005;330(7489):480
50642 Leuppi Dis Manag Health Outcomes 2004;12(5):281-4
McBride Wessex Institute; 1999
50617 Milani et al J Cardiopulm Rehabil 1998;18(1):17-22
Ministry of Health, Singapore. Clinical Practice Guidelines. COPD 2006
50369 Moreno et al Rev Med Chil 1999;127(2):229-34
50392 NICE Thorax 2004;59(Suppl 1):1-232
50480 Nici et al Eur Respir J 2006;28(3):461-2

A-76
50450 Nici et al J Cardiopulm Rehabil 2007;27(6):355-8
50485 Nici et al Am J Respir Crit Care Med 2006;173(12):1390-413
50407 Pasqua Rass Patol Appar Respir 2007;22(4-5):264-84
50432 Puhan International Journal of Respiratory Care 2007;3(3):90-3
50354 Puhan et al Praxis 2003;92(4):111-6
50401 Qaseem A et al Ann Intern Med 2007;147(9):633-8-, I41
50404 Reid et al Physiother Can 2007;59(3):218-28
50416 Reishstein Evid Based Nurs 2004;7(1):22.
50377 Resnikoff et al Respir Care Clin N Am 1998;4(3):475-92
50464 Ries J Cardiopul Rehab & Prev 2007;27:233-6
50383 Ries Respir Care 2008;53(9):1203-7
50386 Ries Chest 2005
50436 Ries et al Proc Am Thorac Soc 2008;5(4):524-9
50471 Ries et al Chest 2007;131(5 Suppl):1S-3S
50517 Sivori et al Medicina 2004;64(4):357-67
50428 Sivori et al Medicina 2008;68(4):325-44
51923 Societe de Pneumologie de Langue Francaise Rev Mal Respir 2005;22(4):696-704
50344 SPLF Rev Mal Respir 2005;22(5 C3):7S8-7S14
37958 Spruit et al Sports Med 2007;37(6):501-18
50476 Su Chin J Clin Rehabil 2006;10(32):141-3
50708 Tiep et al Dis Manag Health Outcomes 2008;16(5):305-13
50410 Troosters et al Am J Respir Crit Care Med 2005;172(1):19-38
50426 Vincent et al Crit Rev Phys Rehabil Med 2008;20(2):127-58
50390 Wedzicha Thorax 2004;59(3):183,
50434 Zuwallack Am J Med 2008;121(7 Suppl 1):S25-S32

Insufficient information
50466 Abholz HH, Z Allgemeinmed 2007;83(7):292-307.
53296 Baicus C, Eur J Intern Med 2009;20(5):e124-e125.
44247 Bausewein C, Cochrane Database Syst Rev 2008;(2):CD005623.
53294 Bulley C, Physiother Res Int 2009;14(3):181-92.
50524 Cambach W, Arch Phys Med Rehabil 1999;80(1):103-11.
50623 Chang AT, Contemporary Clinical Trials 2008;29(5):796-800.
50460 Coventry PA, J Psychosom Res 2007;63(5):551-65.
50327 Effing T Cochrane Database Syst Rev 2007;(4).

A-77
53234 Fischer MJ Respir Med 2009;103(10):1564-71.
50403 Gallucci MA. (Teachers College, Columbia University).
50641 Garrod R Cochrane Database of Systematic Reviews 2008 Issue 1. 2008. CD006906.
50475 Gomez A, Aten Primaria 2006;38(4):230-3.
51785 Guyatt GH, J Clin Epidemiol 1999;52(3):187-92.
HAS 2007 Available:
http://www.hassante.fr/portail/upload/docs/application/pdf/rapport_reentrainement_a_lexercice_s
50402 Hassanein 2006 Case Western Reserve University
ICSI Jan 2009 Available:
http://www.icsi.org/chronic_obstructive_pulmonary_disease/chronic_obstructive_pulmonary_disease
_2286.html
50639 Ilnitskii AN. Ter Arkh 2003;75(3):50-3. 50357?
53295 Kagaya H, Tohoku J Exp Med 2009;218(3):215-9. Available:
http://www.jstage.jst.go.jp/article/tjem/218/3/215/_pdf
50372 Lewczuk J, Pneumonol Alergol Pol 1998;66(9-10):464-7.
50374 Lewczuk J Pol Arch Med Wewn 1998;100(4):331-6.
50521 Liu Chin J Clin Rehabil 2002;6(21):3170-1.
51924 Lopez Varela MV, Arch Bronconeumol 2006;42(9):434-9.
50408 McCarroll ML. (The Ohio State University).
53298 Menadue C, Cochrane Database Syst Rev 2009;(2).
50330 Milenkovic B, Srp Arh Celok Lek 2007;135(7-8):419-24.
NIHR 2008 Available:
http://www.hta.ac.uk/project/1316.asp?SearchText=chronic+bronchitis%2FCOPD&PjtId=1316&PjtT
ypeWebsite=HTA-STD
37961 Nonoyama ML, Cochrane Database Syst Rev 2007;(2):CD005372. Ref ID:
50335 Oh H, J Clin Nurs 2007;16(1):3-15.
50384 Oh HS. Taehan Kanho Hakhoe Chi 2003;33(6):743-52.
50395 Ong KC, Annals Academy of Medicine Singapore 2001;30(1):15-21.
50420 Peters ML. State University of New York at Albany.
50359 Piszko Pneumonol Alergol Pol 2002;70(11-12):566-72.
50351 Piszko Pol Arch Med Wewn 2004;111(1):57-62.
50348 Puhan MA, Respir Res 2005;6:54. Available:
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1164434&blobtype=pdf
Registered Nurses' Association of Ontario March 2005 Available:
http://www.rnao.org/Page.asp?PageID=924&ContentID=807
50637 Romagnoli M, Eur Respir J 2005;26(Suppl 49).
50399 Salman GF, JGIM 1999;14(Suppl 2):68.

A-78
50531 Salman GF, J Gen Intern Med 2003;18:213-21.
50385 Subramanaim V, Chest 2007;132(4 Suppl S):536S.
50313 Titova ON, Vopr Kurortol Fizioter Lech Fiz Kult 2008;(4):17-20.
50396 Tregonning M, Thorax 2000;55(Supplement 3):A7.
50493 Varga J, Orv Hetil 2005;146(44):2249-55.
WHO 2001 Available: http://www.who.int/respiratory/publications/WHO_MNC_CRA_02.1.pdf
50149 Wijkstra PJ, Monaldi Arch Chest Dis 2000;55(2):130-4.
50423 Zhang ZQ, Chinese Critical Care Medicine 2008;20(10):607-10.

Did not relate to full PR programs


50412 Alexander JL Arizona State University
53077 Allan et al Respir Care 2009;54(9):1175-82
50365 Carrieri-Kohlman et al Nurs Res 2001;50(3):136-46.
50361 Cegla et al Pneumologie 2002;56(7):418-24
Garrod R, Chartered Soc of Physiotherapists E05 March 2003 Available: http://www.csp.org.uk
50499 Chen et al Chin J Clin Rehabil 2005;9(43):17-9
53233 Dourado Braz J Med Biol Res 2009;42(3):263-71
50609 Franssen et al Chest 2004;125(6):2021-8
50483 Garcia-Aymerich et al Thorax 2006;61(9):772-8
50398 Lum et al J Am Geriatr Soc 1999;47(9):S105
50508 Murphy et al Respir Med 2005;99(10):1297-302
NZHTA 1998 Available: http://nzhta.chmeds.ac.nz/publications/nzhta2.pdf
50443 O'Brien et al J Cardiopulm Rehabil Prev 2008;28(2):128-41
50615 O'Donnell et al Am J Respir Crit Care Med 1998;157(5 Pt 1):1489-97
37987 Puhan Thorax 2005;60(5):367-75
50526 Shioya et al Eur Respir J 2007;30(Suppl 51):188s
50373 Sivori et al Medicina (B Aires) 1998;58(6):717-27
50449 Skumlien et al Respir Med 2008;102(3):422-9
50406 Smidt et al Ned Tijdschr Fysiother 2005;115(4):86-95
50424 van Wetering Int J Chron Obstruct Pulmon Dis 2008;3(3):443-51.
50634 Vogiatzis et al Chest 2005;128(6):3838-45
50604 Vogiatzis et al Thorax 2007;62(11):950-6
50621 Wadell et al Adv Physiother 2005;7(2):51-9
2956 Weiner et al Chest 2000;118(3):672-8
50414 Whitsel 1998, Syracuse University

A-79
Inappropriate study design
50341 Alexopoulos et al Am J Geriatr Psychiatry 2006;14(5):466-75
50371 Ando et al Nihon Kokyuki Gakkai Zasshi 1999;37(9):680-7
50418 Arena et al Cardiopulm Phys Ther J 2003;14(3):3-6
50490 Arnold et al Patient Educ Couns 2006;61(1):99-108
50520 Barakat International Journal of COPD 2007;2(4):585-91
50636 Belza et al J Cardiopulm Rehabil Prev 2005;25(2):107-14
50478 Biscione et al Eur Respir J 2006;27(6):1320-1
50367 Buchi et al Schweiz Med Wochenschr 2000;130(5):135-42
50468 Carr et al Chest 2007;132(1):127-34
53334 Carr J Cardiopulm Rehabil Prev 2009;29(5):318-24
50319 Cecins et al Aust Health Rev 2008;32(3):415-22
50329 Drozdowski et al Pneumonol Alergol Pol 2007;75(2):147-52
51779 Duren-Winfield et al West J Nurs Res 2000;22(4):460-74
50415 Faager et al Nordisk Fysioterapi 1999;3(4):146-52
50630 Ferreira et al J Cardiopulm Rehabil Prev 2006;26(1):54-60
50463 Foglio et al Respir Med 2007;101(9):1961-70
50427 Garcia-Aymerich et al Ann Epidemiol 2008;18(10):775-83
50608 Garrod et al Physiother Res Int 2004;9(3):111-20
50619 Geddes et al Cardiopulm Phys Ther J 2007;18(4):3-13
50456 Georgiadou et al Eur Respir J 2007;29(2):284-91
50387 Hillerdal Chest 2005;128;3489-3499
50316 Haave et al Chron Respir Dis 2008; 5(2):69-73
50453 Haave Int J COPD 2007;2(3):355-9
53231 Hassenein J Mol Signal 2009;29(4):255-60.
50518 Holland et al J Cardiopulm Rehabil Prev 2004;24(6):422-7
50376 Inoue et al Nihon Kokyuki Gakkai Zasshi 1998;36(9):756-62
50488 Koppers et al Chest 2006;129(4):886-92
50336 Kubo Asia Pac J Clin Nutr 2006;15(4):551-5.
50515 Lange et al Ugeskr Laeger 2005;167(3):274-9
50447 Laviolette et al Thorax 2008;63(2):115-21
50498 Leleu et al Rev Pneumol Clin 2005;61(6):359-64
50616 Leuppi et al Dtsch Med Wochenschr 1998;123(7):174-8
50364 Lisboa et al Rev Med Chil 2001;129(4):359-66
50626 Lotshaw et al J Cardiopulm Rehabil Prev 2007;27(4):247-51

A-80
50612 Mador Chest 2005;128(3):1216-24
50422 Mann et al Can J Respir Ther 1998;34(4):123-7
50366 Miyahara et al Acta Med Okayama 2000;54(4):179-84
50419 Mok et al Asian J Nursing Stud 2003;6(2):58-64
50519 Ngaage et al Heart Lung 2004;33(6):381-9
50431 Ninot et al Disabil Rehabil 2007;29(22):1671-8
50503 Nishiyama et al Qual Life Res 2005;14(10):2315-21
50395 Ong Annals Academy of Medicine Singapore 2001;30(1):15-21, January, 2001
50347 Pande et al Indian J Chest Dis Allied Sci 2005;47(3):217-9
50352 Panton et al Eur J Appl Physiol 2004;91(4):443-9
50625 Pitta et al Chest 2008;134(2):273-80
50644 Rae et al Prim Care Respir J 2008; 17
50497 Riario-Sforza et al Rass Patol Appar Respir 2005;20(6):284-90
50315 Ringbaek et al Chron Respir Dis 2008;5(2):75-80.
50333 Ringbaek et al Ugeskr Laeger 2007;169(17):1572-6
50613 Rajendran et al Indian Heart J 1998;50(5):531-4
50353 Schaanning Tidsskr Nor Lægeforen 2000;120(5):551-5
50375 Scherer et al J N Y State Nurses Assoc 1998;29(3-4):16-20
50340 Schultz et al Dtsch Med Wochenschr 2006;131(33):1793-8
50643 Solanes et al Respir Med 2008;
50506 Trappenburg et al Arch Phys Med Rehabil 2005;86(9):1788-92
50370 Vogiatzis et al Chest 1999;116(5):1200-7
51771 Von Leupoldt Lung 2008;186(6):387-91
50492 Zhao et al Chinese Journal of Rehabilitation Medicine 2006;21(2):127-31
50631 Zuwallack et al Chron Respir Dis 2006;3(1):11-8

Not relevant to PR for COPD


42046 Adams Drug Benefit Trends 2006; 259 - 265
AHRQ 2001 Available: http://www.ahrq.gov/clinic/epcsums/copdsum.htm
50388 Baggott Chest 2004;126(4 Suppl S):739S, OCT
32813 Chumillas et al Arch Phys Med Rehabil 1998;79(1):5-9
50611 Clini et al Thorax 2001;56(7):519-23
50504 Coultas et al Chest 2005;128(4):2017-24
50458 Garrod et al Respir Med 2007;101(12):2429-36
50633 Harpa et al Respir Med 2006;100(1):130-9

A-81
Health Council of the Netherlands 2003 Available:
http://www.gezondheidsraad.nl/nl/adviezen/oefentherapie
50516 Hendriksen et al Ugeskr Laeger 2005;167(3):269-72
50389 Kujala Scand J Med Sci Sports 2004;14(6):339-45
50640 Lenz et al Dtsch Z Sportmed 2001;52(7/8):S16
50635 Mercken et al Am J Respir Crit Care Med 2005;172(8):994-1001
50331 Montgomery et al Prev Chronic Dis 2007;4(3):A62, 2007
50413 Migliore. New York University 2003
50421 Muth. Union Institute, 2001.
50610 Ortega et al Am J Respir Crit Care Med 2002;166(5):669-74
50462 O'Shea et al Chron Respir Dis 2007;4(3):135-42
50438 Peytremann-Bridevaux et al Am J Med 2008;121(5):433-43
SBU 2000. Available: http://www.sbu.se/en/Published/Yellow/Treating-asthma-and-COPD/
50527 Sugawara et al Eur Respir J 2007;30(Suppl 51):514s
50409 Wang et al Chinese Nursing Research 2004;18(9B):1608-9

Duplicates or support material related to selected publications


50530 Lacasse Y Lancet 1996;348:1115-9.
50323 Lacasse Y Eur Medicophys 2007;43(4):475-85.
Sillen Chest 2009;136(1):44-61
49112 Wilt et al Ann Intern Med 2007;147(9):639-53

Economic publications
31498 Ashworth Cochrane Database Syst Rev 2005;(1):CD004017
50153 Barandun Schweiz Rundsch Med Prax 1997;86:1979-83
50144 California Pulmonary Rehabilitation Collaborative Group. J Cardiopulm Rehabil 2004;24(1):52-
62
51779 Duren-Winfield West J Nurs Res 2000;22(4):460-74
50632 Eaton Respirology 2009;14(2):230-8.
50147 Fan Int J Chron Obstruct Pulmon Dis 2008;5(2):105-16
53169 Goldstein Chest 1997;112(2):370-9
53465 Haggerty Chest 1991;100: 607-12.
50146 Hanaoka Respirology 2008;13(6):919-22
50145 Hessel Pneumologie 2000;54(7):289-95
51858 Motegi Nihon Kokyuki Gakkai Zasshi 2006;44(11):787-94

A-82
50151 Parker Respir Care 1998;43(3):177-82
51291 Roselle Respir Care 1982;27(10):1194-9
50379 Scherer Rehabil Nurs 1998;23(2):71-7
53461 Strijbos Chest 1996;109(2):366-72
51860 Troosters Am J Med 2000;109(3):207-12
50149 Wijkstra Monaldi Arch Chest Dis 2000;55(2):130-4

A-83

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