Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based ... · ing body of scientific evidence....

DOI 10.1378/chest.06-2418 2007;131;4-42 Chest

Richard ZuWallack and Carla Herrerias Charles F. Emery, Donald A. Mahler, Barry Make, Carolyn L. Rochester, Andrew L. Ries, Gerene S. Bauldoff, Brian W. Carlin, Richard Casaburi,

Practice GuidelinesACCP/AACVPR Evidence-Based Clinical Pulmonary Rehabilitation: Joint

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Pulmonary Rehabilitation*

Joint ACCP/AACVPR Evidence-Based ClinicalPractice Guidelines

Andrew L. Ries, MD, MPH, FCCP (Chair);Gerene S. Bauldoff, RN, PhD, FCCP; Brian W. Carlin, MD, FCCP;Richard Casaburi, PhD, MD, FCCP; Charles F. Emery, PhD;Donald A. Mahler, MD, FCCP; Barry Make, MD, FCCP;Carolyn L. Rochester, MD; Richard ZuWallack, MD, FCCP; andCarla Herrerias, MPH

Background: Pulmonary rehabilitation has become a standard of care for patients with chronic lung diseases. Thisdocument provides a systematic, evidence-based review of the pulmonary rehabilitation literature that updates the1997 guidelines published by the American College of Chest Physicians (ACCP) and the American Association ofCardiovascular and Pulmonary Rehabilitation.Methods: The guideline panel reviewed evidence tables, which were prepared by the ACCP Clinical ResearchAnalyst, that were based on a systematic review of published literature from 1996 to 2004. This guidelineupdates the previous recommendations and also examines new areas of research relevant to pulmonaryrehabilitation. Recommendations were developed by consensus and rated according to the ACCP guidelinegrading system.Results: The new evidence strengthens the previous recommendations supporting the benefits of lower and upperextremity exercise training and improvements in dyspnea and health-related quality-of-life outcomes of pulmonaryrehabilitation. Additional evidence supports improvements in health-care utilization and psychosocial outcomes. Thereare few additional data about survival. Some new evidence indicates that longer term rehabilitation, maintenancestrategies following rehabilitation, and the incorporation of education and strength training in pulmonary rehabilitationare beneficial. Current evidence does not support the routine use of inspiratory muscle training, anabolic drugs, ornutritional supplementation in pulmonary rehabilitation. Evidence does support the use of supplemental oxygen therapyfor patients with severe hypoxemia at rest or with exercise. Noninvasive ventilation may be helpful for selected patientswith advanced COPD. Finally, pulmonary rehabilitation appears to benefit patients with chronic lung diseases otherthan COPD.Conclusions: There is substantial new evidence that pulmonary rehabilitation is beneficial for patients with COPD andother chronic lung diseases. Several areas of research provide opportunities for future research that can advance thefield and make rehabilitative treatment available to many more eligible patients in need.

(CHEST 2007; 131:4S–42S)

Key words: COPD; dyspnea; exercise training; guidelines; pulmonary rehabilitation; quality of life

Abbreviations: AACVPR � American Association of Cardiovascular and Pulmonary Rehabilitation; ACCP � AmericanCollege of Chest Physicians; ADL � activity of daily living; CRDQ � Chronic Respiratory Disease Questionnaire;DAS � distractive auditory stimuli; DEXA � dual-energy x-ray absoptiometry; ESM � education and stress management;HR � heart rate; HRQOL � health-related quality of life; IMT � inspiratory muscle training; MRC � Medical ResearchCouncil; NETT � National Emphysema Treatment Trial; NPPV � noninvasive positive-pressure ventilation;PAV � proportional assist ventilation; Pimax � maximal inspiratory pressure; RCT � randomized controlled trial;Sao2 � arterial oxygen saturation; TCEMS � transcutaneous electrical stimulation of the peripheral muscles; V̇e � minuteventilation; V̇o2 � oxygen uptake

CHEST SupplementPULMONARY REHABILITATION: JOINT ACCP/AACVPR EVIDENCE-BASED CLINICAL PRACTICE GUIDELINES

4S Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice Guidelines



P ulmonary diseases are increasingly importantcauses of morbidity and mortality in the modern

world. The COPDs are the most common chroniclung diseases, and are a major cause of lung-relateddeath and disability.1 Pulmonary rehabilitation hasemerged as a recommended standard of care forpatients with chronic lung disease based on a grow-ing body of scientific evidence. A previous set2,3 ofevidence-based guidelines was published in 1997 asa joint effort of the American College of ChestPhysicians (ACCP) and the American Association ofCardiovascular and Pulmonary Rehabilitation

(AACVPR). Since then, the published literature inpulmonary rehabilitation has increased substantially,and other organizations have published importantstatements about pulmonary rehabilitation (eg, theAmerican Thoracic Society and the European Respi-ratory Society4). The purpose of this document is toupdate the previous ACCP/AACVPR document witha systematic, evidence-based review of the literaturepublished since then.

Epidemiology of COPD

In the United States, COPD accounted for119,054 deaths in 2000, ranking as the fourth leadingcause of death and the only major disease among thetop 10 in which mortality continues to increase.5–8 Inpersons 55 to 74 years of age, COPD ranks third inmen and fourth in women as cause of death.9However, mortality data underestimate the impact ofCOPD because it is more likely to be listed as acontributory cause of death rather than the underly-ing cause of death, and it is often not listed at all.10,11

Death rates from COPD have continued to increasemore in women than in men.5 Between 1980 and2000, death rates for COPD increased 282% forwomen compared to only 13% for men. Also, in2000, for the first time, the number of women dyingfrom COPD exceeded the number of men.5

Morbidity from COPD is also substantial.5,12

COPD develops insidiously over decades and be-cause of the large reserve in lung function there is along preclinical period. Affected individuals have fewsymptoms and are undiagnosed until a relativelyadvanced stage of disease. In a population survey inTucson, AZ, Burrows13 reported that only 34% ofpersons with COPD had ever consulted a physician,36% denied having any respiratory symptoms, and30% denied dyspnea on exertion, which is the pri-mary symptom. National Health and Nutrition Ex-amination Study III data estimate that 24 million USadults have impaired lung function, while only 10million report a physician diagnosis of COPD.5There are approximately 14 million cases of chronicbronchitis reported each year, and 2 million cases ofemphysema.14 The National Center for Health Sta-tistics for 1996 reported prevalence rates of chronicbronchitis and emphysema in older adults (eg, per-sons � 65 years of age) of 82 per 1,000 men and 106per 1,000 women.15 In 2000, COPD was responsiblefor 8 million physician office visits, 1.5 millionemergency department visits, and 726,000 hospital-izations.5 COPD accounts for � 5% of physicianoffice visits and 13% of hospitalizations.16 NationalHealth and Nutrition Examination Study III datafrom 1988 to 1994 indicated an overall prevalence of

*From the University of California, San Diego, School of Medi-cine (Dr. Ries, Chair, representing both groups), San Diego, CA;The Ohio State University College of Nursing (Dr. Bauldoff,representing the AACVPR, and Dr. Emery, representing theAACVPR), Columbus, OH; Allegheny General Hospital (Dr.Carlin, ACCP Health and Science Policy Liaison, representingboth groups), Pittsburgh, PA; the Los Angeles Biomedical Re-search Institute (Dr. Casaburi, representing the ACCP), Harbor-UCLA Medical Center, Los Angeles, CA; the Department ofPulmonary and Critical Care Medicine (Dr. Mahler, representingthe ACCP), Dartmouth-Hitchcock Medical Center, Lebanon,NH; the Department of Pulmonary Rehabilitation and Emphy-sema (Dr. Make, representing the ACCP), National JewishResearch and Medical Center, Denver, CO; the Section ofPulmonary and Critical Care (Dr. Rochester, representing theACCP), Yale University School of Medicine, New Haven, CT; thePulmonary Disease Section (Dr. ZuWallack, representing theAACVPR), St. Francis Hospital, Hartford, CT; and the AmericanCollege of Chest Physicians (Ms. Herrerias), Northbrook, IL.The evidence-based practice guidelines published by The Amer-ican College of Chest Physicians (ACCP) incorporate data ob-tained from a comprehensive literature review of the most recentstudies then available. Guidelines are intended for generalinformation only, are not medical advice, and do not replaceprofessional medical care and physician advice, which alwaysshould be sought for any specific condition. Furthermore, guide-lines may not be complete or accurate because new studies thatmay have become available late in the process of guidelinedevelopment may not be incorporated into any particular guide-line before it is disseminated. The ACCP and its officers, regents,governors, executive committee, members, and employees (theACCP Parties) disclaim all liability for the accuracy or complete-ness of a guideline, and disclaim all warranties, express orimplied. Guideline users always are urged to seek out newerinformation that might impact the diagnostic and treatmentrecommendations contained within a guideline. The ACCPParties further disclaim all liability for any damages whatsoever(including, without limitation, direct, indirect, incidental, puni-tive, or consequential damages) arising out of the use, inability touse, or the results of use of a guideline, any references used in aguideline, or the materials, information, or procedures containedin a guideline, based on any legal theory whatsoever and whetheror not there was advice of the possibility of such damages.The authors have reported to the ACCP that no significantconflicts of interest exist with any companies/organizations whoseproducts or services may be discussed in this article.Manuscript received October 2, 2006; revision accepted Febru-ary 2, 2007.Reproduction of this article is prohibited without written permissionfrom the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).Correspondence to: Andrew L. Ries, MD, MPH, FCCP, Univer-sity of California, San Diego, Department of Pulmonary andCritical Care Medicine, UCSD Medical Center, 200 West ArborDr, San Diego, CA 92103-8377; e-mail: [email protected]: 10.1378/chest.06-2418

www.chestjournal.org CHEST / 131 / 5 / MAY, 2007 SUPPLEMENT 5S



COPD of 8.6% among 12,436 adults (average age forentire cohort, 37.9 years).17 In the United States,COPD is second only to coronary heart disease as areason for Social Security disability payments.

Worldwide, the burden of COPD is projected toincrease substantially, paralleling the rise in tobaccouse, particularly in developing countries. An analysisby the World Bank and World Health Organizationranked COPD 12th in 1990 in disease burden, asreflected in disability-adjusted years of life lost.10

Severity of COPD

For consistency throughout the document, thepanel used the description of severity of COPD asrecommended by the Global Initiative for ChronicObstructive Lung Disease18 and the American Tho-racic Society/European Respiratory Society Guide-lines19 based on FEV1, as follows: stage I (mild),FEV1 � 80% predicted; stage II (moderate), FEV150 to 80% predicted; stage III (severe), FEV1 30 to50% predicted; and stage IV (very severe), FEV1� 30% predicted.

Pulmonary Rehabilitation

Rehabilitation programs for patients with chroniclung diseases are well-established as a means ofenhancing standard therapy in order to control andalleviate symptoms and optimize functional capaci-ty.2,4,14,20 The primary goal is to restore the patient tothe highest possible level of independent function.This goal is accomplished by helping patients be-come more physically active, and to learn moreabout their disease, treatment options, and how tocope. Patients are encouraged to become activelyinvolved in providing their own health care, moreindependent in daily activities, and less dependenton health professionals and expensive medical re-sources. Rather than focusing solely on reversing thedisease process, rehabilitation attempts to reducesymptoms and reduce disability from the disease.

Many rehabilitation strategies have been devel-oped for patients with disabling COPD. Programstypically include components such as patient assess-ment, exercise training, education, nutritional inter-vention, and psychosocial support. Pulmonary reha-bilitation has also been applied successfully topatients with other chronic lung conditions such asinterstitial diseases, cystic fibrosis, bronchiectasis,and thoracic cage abnormalities.21 In addition, it hasbeen used successfully as part of the evaluation andpreparation for surgical treatments such as lungtransplantation and lung volume reduction sur-

gery.22–26 Pulmonary rehabilitation is appropriate forany stable patient with a chronic lung disease who isdisabled by respiratory symptoms. Patients with ad-vanced disease can benefit if they are selectedappropriately and if realistic goals are set. Althoughpulmonary rehabilitation programs have been devel-oped in both outpatient and inpatient settings, mostprograms, and most of the studies reviewed in thisdocument, pertain to outpatient programs for ambu-latory patients.

Definition

The American Thoracic Society and the EuropeanRespiratory Society have recently adopted the fol-lowing definition of pulmonary rehabilitation: Pul-monary rehabilitation is an evidence-based, multidis-ciplinary, and comprehensive intervention forpatients with chronic respiratory diseases who aresymptomatic and often have decreased daily lifeactivities. Integrated into the individualized treat-ment of the patient, pulmonary rehabilitation isdesigned to reduce symptoms, optimize functionalstatus, increase participation, and reduce health-carecosts through stabilizing or reversing systemic man-ifestations of the disease. Comprehensive pulmonaryrehabilitation programs include patient assessment,exercise training, education, and psychosocial sup-port.4

This definition focuses on three important featuresof successful rehabilitation:

1. Multidisciplinary: Pulmonary rehabilitationprograms utilize expertise from various health-care disciplines that is integrated into a com-prehensive, cohesive program tailored to theneeds of each patient.

2. Individual: Patients with disabling lung diseaserequire individual assessment of needs, individ-ual attention, and a program designed to meetrealistic individual goals.

3. Attention to physical and social function: To besuccessful, pulmonary rehabilitation pays atten-tion to psychological, emotional, and socialproblems as well as physical disability, andhelps to optimize medical therapy to improvelung function and exercise tolerance.

The interdisciplinary team of health-care profes-sionals in pulmonary rehabilitation may include phy-sicians; nurses; respiratory, physical, and occupa-tional therapists; psychologists; exercise specialists;and/or others with appropriate expertise. The spe-cific team make-up depends on the resources andexpertise available, but usually includes at least onefull-time staff member.27




Methodology and Grading of theEvidence for Pulmonary Rehabilitation

In 1997, the ACCP and the AACVPR released anevidence-based clinical practice guideline entitled“Pulmonary Rehabilitation: Joint ACCP/AACVPREvidence-Based Guidelines.”2,3 Following the ap-proved process for the review and revision of clinicalpractice guidelines, in 2002 the ACCP Health andScience Committee determined that there was aneed for reassessment of the current literature andan update of the original practice guideline. Thisnew guideline is intended to update the recommen-dations from the 1997 document and to provide newrecommendations based on a comprehensive litera-ture review. The literature review and developmentof evidence tables were conducted by Carla Herre-rias, MPH, the ACCP Clinical Research Analyst. Thejoint ACCP/AACVPR expert panel used the evi-dence to develop graded recommendations.

Expert Panel Composition

The guideline panel was organized under the jointsponsorship of the ACCP and the AACVPR. AndrewRies, MD, MPH, FCCP, Chair of the 1997 panel,served as Chair of the new panel. Panel members wereevenly distributed between and selected by the twoorganizations with a goal of making the panel multidis-ciplinary and geographically diverse. Drs. Casaburi,Mahler, Make, and Rochester represented the ACCP,and Drs. Bauldoff, Carlin, Emery, and ZuWallackrepresented the AACVPR. Five panel members (Drs.Carlin, Casaburi, Emery, Mahler, and Make) hadserved on the previous guideline panel. In addition toseveral conference calls, the panel met for one 2-daymeeting to review the evidence tables and becomefamiliar with the process of grading recommendations.Writing assignments were determined by members’known expertise in specific areas of pulmonary rehabil-itation. Each section of the guideline was assigned toone primary author and at least one secondary author.Sections were reviewed by relevant panel memberswhen topics overlapped.

Conflict of Interest

At several stages during the guideline develop-ment period, panel members were asked to discloseany conflict of interest. These occurred at the timethe panel was nominated, at the first face-to-facemeeting, the final conference call, and prior topublication. Written forms were completed and areon file at the ACCP.

Scope of Work

The 1997 practice guideline on pulmonary reha-bilitation focused on program component areas of

lower and upper extremity training, ventilatory mus-cle training, and various outcomes of comprehensivepulmonary rehabilitation programs, including dys-pnea, quality of life, health-care utilization, andsurvival. Psychosocial and educational aspects ofrehabilitation were examined both as program com-ponents and as outcomes.

For this review, the panel decided to focus on studiesthat had been published since the previous review,again concentrating on stable patients with COPD.Since there have been many advances and new areas ofinvestigation since the previous document was written,the panel decided to expand the scope of this reviewrather than just update the previous one. Topics cov-ered in this document include the following:

• Outcomes of comprehensive pulmonary rehabili-tation programs: lower extremity exercise training;dyspnea; health-related quality of life (HRQOL);health-care utilization and economic analysis; sur-vival; psychosocial outcomes; and long-term ben-efits from pulmonary rehabilitation;

• Duration of pulmonary rehabilitation;• Postrehabilitation maintenance strategies;• Intensity of aerobic exercise training;• Strength training in pulmonary rehabilitation;• Anabolic drugs;• Upper extremity training;• Inspiratory muscle training (IMT);• Education;• Psychosocial and behavioral components of pul-

monary rehabilitation;• Oxygen supplementation as an adjunct to pulmo-

nary rehabilitation;• Noninvasive ventilation;• Nutritional supplementation in pulmonary reha-

bilitation;• Pulmonary rehabilitation for patients with disor-

ders other than COPD; and• Summary and recommendations for future research.

Review of Evidence

The literature review was based on the scope of thework as outlined in the previous section. The literaturesearch was conducted through a comprehensive MED-LINE search from 1996 through 2004, and was sup-plemented by articles supplied by the guideline panelas well as by a review of bibliographies and referencelists from review articles and other existing systematicreviews. The literature search was limited to articlespublished in peer-reviewed journals only in the Englishlanguage, and on human subjects. Inclusion criteriaprimarily included a population of persons with adiagnosis of COPD determined either by physicalexamination or by existing diagnostic criteria; however,those with other pulmonary conditions (eg, asthma or




interstitial lung disease) were also included. The searchincluded randomized controlled trials (RCTs), meta-analyses, systematic reviews, and observational studies.The search strategy linked pulmonary rehabilitation ora pulmonary rehabilitation program with each keysubcomponent, as listed in section on “Scope of Work.”To locate studies other than RCTs, such as systematicreviews and metaanalyses, those key words were usedin searching MEDLINE and the Cochrane databases.Informal review articles were included only for handsearching additional references. For the purpose of thisreview, pulmonary rehabilitation was defined opera-tionally as studies involving exercise training plus atleast one additional component. Associated outcomesacross all components were dyspnea, exercise toler-ance, quality of life and activities of daily life, andhealth-care utilization. An initial review of 928 abstractswas conducted by the ACCP Clinical Research Analystand the Research Specialist. Full articles (a total of 202)were formally reviewed and abstracted by the ClinicalResearch Analyst, and a total of 81 clinical trials wereincluded in all evidence tables. RCTs were scored usinga simplified system that was based on methods ofrandomization, blinding, and documentation of with-drawals/loss to follow-up. This system follows a methodthat is based on a 3-point scale, which rates random-ization (and appropriateness), blinding (and appropri-ateness), and tracking of withdrawals and loss to follow-up. Studies were graded on a scale of 0 to 5.28 Noformal quantitative analysis was performed due to thewide variation in methodologies reported in studies.Given the length of time required to prepare the finalmanuscript after the conclusion of the systematic liter-ature review in December 2004, from which the tableswere constructed, the committee was allowed to in-clude reference to selected articles published in 2005and 2006 in the text if the additional informationprovided by the newer publications was felt to beimportant.

Strength of Evidence and Grading ofRecommendations

The ACCP system for grading guideline recom-mendations is based on the relationship between thestrength of the evidence and the balance of benefitsto risk and burden (Table 1).29 Simply stated, rec-ommendations can be grouped on the following twolevels: strong (grade 1); and weak (grade 2). If thereis certainty that the benefits do (or do not) outweighrisk, the recommendation is strong. If there is lesscertainty or the benefits and risks are more equallybalanced, the recommendation is weaker. Severalimportant issues must be considered when classify-ing recommendations. These include the quality ofthe evidence that supports estimates of benefit, risks,

and costs; the importance of the outcomes of theintervention; the magnitude and the precision ofestimate of the treatment effect; the risks and bur-dens of an intended therapy; the risk of the targetevent; and varying patient values.

The strength of evidence is classified, based on thequality of the data, into the following three catego-ries: high (grade A); moderate (grade B); and low(grade C). The strongest evidence comes from well-designed RCTs yielding consistent and directly ap-plicable results. In some circumstances, high-qualityevidence can be the result of overwhelming evidencefrom observational studies. Moderate-quality evi-dence is based on RCTs with limitations that mayinclude methodological flaws or inconsistent results.Studies other than RCTs that may yield strongresults are also included in the moderate-qualitycategory. The weakest type of evidence is that fromother types of observational studies. It should benoted that the ACCP Health and Science PolicyCommittee has endorsed the principle that mostrelevant clinical studies provide evidence, eventhough the quality of that evidence is varied. There-fore, the reasons for excluding studies should bedocumented.

Table 2 describes the balance of benefits to riskand burden, and the level of certainty based on thisbalance. As stated above, the more certain the

Table 2—Description of Balance of Benefits to Risks/Burdens Scale

Benefits clearly outweigh the risksand burdens

Certainty of imbalance

Risks and burdens clearlyoutweigh the benefits

Certainty of imbalance

The risks/burdens and benefitsare closely balanced

Less certainty

The balance of benefits to risksand burdens is uncertain

Uncertainty

Table 1—Relationship of Strength of the SupportingEvidence to the Balance of Benefits to Risks and

Burdens*

Strength ofEvidence

Balance of Benefits to Risks and Burdens

BenefitsOutweigh

Risks/Burdens

Risks/BurdensOutweighBenefits

EvenlyBalanced Uncertain

High 1A 1A 2AModerate 1B 1B 2BLow or very

low1C 1C 2C 2C

*1A � strong recommendation; 1B � strong recommendation;1C � strong recommendation; 2A � weak recommendation;2B � weak recommendation; 2C � weak recommendation.




balance, or lack thereof, the stronger the recommen-dation. Patient and community values are importantconsiderations in clinical decision making and arefactored into the grading process. In situations inwhich the benefits clearly do or do not outweigh therisks, it is assumed that nearly all patients would havethe same preferences. For weaker recommenda-tions, however, there may not be consistency inpatient preferences.

In addition to recommendations, the committeeincluded several statements when it thought thatthere was insufficient evidence to make a specificrecommendation. These statements are includedalong with the recommendations but are not graded.

Outcomes of Comprehensive PulmonaryRehabilitation Programs

As currently practiced, pulmonary rehabilitation typ-ically includes several different components, includingexercise training, education, instruction in various re-spiratory and chest physiotherapy techniques, and psy-chosocial support. For this review, comprehensive pul-monary rehabilitation was defined as an interventionthat includes one or more of these components beyondjust exercise training, which is considered to be anessential, mandatory component.

In addition to the clinical trials reviewed in theevidence tables in this document, several systematicreviews and metaanalyses have been publishedwithin the past decade that support the beneficialeffects from comprehensive pulmonary rehabilita-tion programs. In a Cochrane Review published in2006, Lacasse30 analyzed 31 RCTs in patients withCOPD and concluded that rehabilitation forms animportant component of the management of COPD.They reported statistically and clinically significantimprovements in important domains of quality of life(i.e., dyspnea, fatigue, emotions, and patient controlover disease). Improvement in measures of exercisecapacity were slightly below the threshold for clinicalsignificance. Similarly, after a systematic review,Cambach and colleagues31 identified 18 articlesfor inclusion in a metaanalysis of outcome mea-sures of exercise capacity and HRQOL in patientswith COPD. They found significant improvementsfor exercise measures of maximal exercise capac-ity, endurance time, and walking distance, and forHRQOL measures in all dimensions of theChronic Respiratory Disease Questionnaire(CRDQ) [ie, dyspnea, fatigue, emotion, and mas-tery]. Improvements in maximal exercise capacityand walking distance were sustained for up to 9months after rehabilitation.

Lower Extremity Exercise Training

Dyspnea: In the previous evidence-based reviewdocument2,3 the 1997 guidelines panel concludedthat the highest strength of evidence (A) supportedthe recommendation for including lower extremityexercise training as a key component of pulmonaryrehabilitation for patients with COPD. In addition,the panel concluded that there was high-grade evi-dence (A) that pulmonary rehabilitation improvesthe symptom of dyspnea in patients with COPD.This panel concluded that the evidence presented inTable 3 in this document further strengthens thoseconclusions and recommendations.

Recommendations

1. A program of exercise training of the mus-cles of ambulation is recommended as a man-datory component of pulmonary rehabilitationfor patients with COPD. Grade of recommenda-tion, 1A

2. Pulmonary rehabilitation improves thesymptom of dyspnea in patients with COPD:Grade of recommendation, 1A

HRQOL

Regarding changes in HRQOL, the previous panelconcluded that there was B level strength of evi-dence supporting the recommendation that “pulmo-nary rehabilitation improves health-related quality oflife in patients with COPD.” Based on the currentreview, this panel believes that the additional pub-lished literature now available strengthens supportfor this conclusion and upgrades the evidence tograde A. In this document, the term HRQOL will beused interchangeably with the term health status.

In one of the larger RCTs reported (200 patients),Griffiths and colleagues32 reported significant im-provements in HRQOL 1 year after a 6-week pul-monary rehabilitation program. Troosters and col-leagues33 reported sustained improvement inHRQOL over 18 months after patients participatedin a 6-month outpatient pulmonary rehabilitationprogram compared with the decline observed in thecontrol group. The study reported by Green andcolleagues34 reported improvement in HRQOL afterpulmonary rehabilitation and found that improve-ments after a 7-week intervention were greater thanthose after 4 weeks of pulmonary rehabilitation.Strijbos and colleagues35 reported significant im-provement in reported well-being after pulmonaryrehabilitation that was maintained over 18 months inrehabilitation-treated subjects, while most patientsin the control group felt unchanged or worse. Foglioand colleagues36 reported sustained improvements




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in HRQOL up to 2 years after pulmonary rehabili-tation. In a study of early pulmonary rehabilitationafter hospital discharge for an exacerbation ofCOPD, Man and colleagues reported significantimprovements in HRQOL measures. Finnerty andcolleagues37 reported marked improvements inHRQOL after pulmonary rehabilitation that persistedfor 6 months. Similar findings were reported by Bend-strup and colleagues.38 In the study reported byWedzicha and colleagues,39 which stratified patientsaccording to baseline dyspnea, improvement inHRQOL after pulmonary rehabilitation was observedin patients with moderate dyspnea (Medical ResearchCouncil [MRC] score, 3 or 4) but not in controlsubjects or patients with severe baseline dyspnea(MRC score, 5). The study by Ries and colleagues40

evaluated a maintenance program after pulmonaryrehabilitation. However, observational results after pul-monary rehabilitation that had been administered to allpatients before randomization demonstrated consistentimprovements in several different measures of bothgeneral and disease-specific measures of HRQOL.Guell and colleagues41 reported significant improve-ment in HRQOL that persisted, although diminished,for up to 2 years of follow-up after the pulmonaryrehabilitation intervention.

Of the studies reported in Table 3, only one smallstudy by White and colleagues42 reported only mod-est improvements in measured HRQOL that did notconsistently reach statistically or clinically significantlevels. In addition to the studies reported in Table 3,which generally were performed in single specializedcenters, two observational studies43,44 provide strongevidence of the effectiveness of pulmonary rehabil-itation as routinely practiced in clinical centers.Although neither of these studies43,44 was an RCT,they provide important information regarding thegeneralizability of the practice of pulmonary rehabil-itation beyond specialized centers and as currentlypracticed in the general medical community in theUnited States. A multicenter evaluation of pulmo-nary rehabilitation in 522 patients in nine centersthroughout California43 reported consistent im-provements in symptoms of dyspnea and HRQOLafter pulmonary rehabilitation. Similar findings werereported in a multicenter observational study inConnecticut.44 In this study, significant improve-ment was reported in the pulmonary functionalstatus scale in 164 patients in 10 centers and in theCRDQ in 60 patients in 3 centers. Also, in theNational Emphysema Treatment Trial (NETT),26 arandomized study that evaluated lung volume reduc-tion surgery in 1,218 patients with severe emphy-sema, all subjects were required to complete a pulmo-nary rehabilitation program as part of the eligibilityrequirements before randomization. Pulmonary reha-

bilitation was conducted at the 17 NETT centers aswell as at 539 satellite centers throughout the UnitedStates. Observational results demonstrated significantimprovements in measures of exercise tolerance, dys-pnea, and HRQOL after rehabilitation that were quitecomparable among the specialized NETT centers andthe largely community-based satellite centers.

Recommendation

3. Pulmonary rehabilitation improves HRQOLin patients with COPD. Grade of recommenda-tion, 1A

Health-Care Utilization and Economic Analysis

Regarding changes in health-care utilization re-sulting from pulmonary rehabilitation, the previouspanel concluded that there was B level strength ofevidence supporting the recommendation that “pul-monary rehabilitation has reduced the number ofhospitalizations and the number of days of hospital-ization for patients with COPD.”

In the current review, some additional informationis available about changes in health-care utilizationafter pulmonary rehabilitation. In the study by Grif-fiths and colleagues,32 over 1 year of follow-up thenumber of patients admitted to the hospital wassimilar in both the pulmonary rehabilitation groupand the control group (40 of 99 vs 41 of 101patients); however, the number of days spent in thehospital was significantly lower in the rehabilitationpatients (10.4 vs 21.0 days, respectively). In a subse-quent cost-utility economic analysis of the results inthis pulmonary rehabilitation trial, Griffiths and col-leagues45 found that the cost per quality-adjustedlife-years indicated that pulmonary rehabilitationwas, in fact, cost-effective and would likely result infinancial benefits to the health-care system (quality-adjusted life-year is a measure of effectiveness that iscommonly used in cost-effectiveness analyses, re-flecting survival adjusted for quality of life, or thevalue that individuals place on expected years of life).In the trial reported by Foglio and colleagues,36

results indicated a significant decrease in yearlyhospitalizations and exacerbations � 2 years afterpulmonary rehabilitation.

Goldstein and colleagues46 conducted a cost anal-ysis that was associated with an RCT of a 2-monthinpatient pulmonary rehabilitation program (fol-lowed by 4 months of outpatient supervision) thatproduced statistically and clinically significant im-provements in measures of HRQOL and exercisecapacity. Although the cost analysis in this study wasdriven largely by the inpatient phase of the programand, as such, is not applicable to the large majority ofoutpatients programs, the authors found cost-effective-




ness ratios for the CRDQ component measures torange from $19,011 to $35,142 (in Canadian dollars)per unit difference. Even with the added costs associ-ated with the inpatient program, these cost/benefitratios are within a range that has been typically consid-ered to represent reasonable cost-effectiveness forother widely advocated health-care programs.47

In a small randomized trial of early pulmonaryrehabilitation after hospitalization for acute exacerba-tion, Man and colleagues48 reported a significant re-duction in emergency department visits and a trendtoward reduced numbers of hospital admissions anddays spent in the hospital over the 3 months afterhospital discharge in the pulmonary rehabilitationgroup compared to the usual-care group. Also, in amulticenter randomized trial of a self-managementprogram of patients with severe COPD, Bourbeau andcolleagues49 reported a significant reduction in thenumbers of hospital admissions and days spent in thehospital in the year following the intervention com-pared to the usual-care control group.

In a multicenter, observational evaluation43 of theeffectiveness of pulmonary rehabilitation in centersthroughout California (not included in Table 3),self-reported measures of health-care utilizationwere found to decrease substantially over 18 monthsof observation after the rehabilitation intervention.In the 3-month period prior to pulmonary rehabili-tation, 522 patients reported 1,357 hospital days (2.4per patient), 209 urgent care visits (0.4 per patient),2,297 physician office visits (4.4 per patient), and1,514 telephone calls to physicians (2.7 per patient).Over the 18 months after rehabilitation, the averageper patient reported health-care utilization (in thepast 3 months) was reduced approximately 60% forhospital days, 40% for urgent care visits, 25% forphysician office visits, and 30% for telephone calls. Itshould be recognized that the results of an observa-tional, noncontrolled study like this may be influ-enced by the selection of patients for pulmonaryrehabilitation shortly after an exacerbation or epi-sode of increased health-care utilization.

Recommendations

4. Pulmonary rehabilitation reduces thenumber of hospital days and other measures ofhealth-care utilization in patients with COPD.Grade of recommendation, 2B

5. Pulmonary rehabilitation is cost-effective inpatients with COPD. Grade of recommendation, 2C

Survival

The previous panel concluded that there was littleevidence (strength of evidence, C) regarding survivalafter pulmonary rehabilitation and made the recom-

mendation that “pulmonary rehabilitation may im-prove survival in patients with COPD.” Only oneRCT50 of pulmonary rehabilitation was included inthe previous review. In that study of 119 patients,Ries and colleagues50 reported 11% higher survivalover 6 years after comprehensive pulmonary reha-bilitation (67%) compared with an education controlgroup (56%). This difference was not statisticallysignificant. Other evidence for improved survival wasderived from nonrandomized and observationalstudies. This lack of evidence does not necessarilyindicate that pulmonary rehabilitation has no effecton survival, but in order to be reasonably powered todetect an effect of this magnitude the sample sizewould have to be a magnitude larger than thosefound in existing studies. The timed walk distanceand MRC-rated dyspnea do improve with pulmonaryrehabilitation, and these variables are correlated withsurvival in patients with COPD.

In the current review, few additional data werefound regarding the effect of pulmonary rehabilita-tion on survival. Similar to previous published stud-ies, the trial reported by Griffiths and colleagues32

that followed 200 patients over 1 year found fewerdeaths in the rehabilitation group (6 of 99 patients)compared with the control group (12 of 101 pa-tients).

Recommendation

6. There is insufficient evidence to deter-mine whether pulmonary rehabilitation im-proves survival in patients with COPD. No rec-ommendation is provided.

Psychosocial Outcomes

Regarding psychosocial outcomes of pulmonaryrehabilitation, the previous panel concluded that“scientific evidence was lacking” (strength of evi-dence, C). Reviews of the research literature per-taining to psychosocial outcomes of pulmonary reha-bilitation programs indicate that comprehensivepulmonary rehabilitation is generally associated withenhanced psychological well-being (ie, reduced dis-tress) and improved quality of life.51,52 In addition, ithas been found that increased self-efficacy associ-ated with exercise may mediate the effect of exerciserehabilitation on quality of life.53 Other positivepsychosocial outcomes of exercise rehabilitation in-clude improved cognitive function,54–56 reducedsymptoms of anxiety32,55 and depression,32 and im-proved patient perceptions of positive consequencesof the illness.57

In the current review of randomized studies,Griffiths and colleagues32 reported reduced symp-toms of anxiety and depression following a 6-week




pulmonary rehabilitation program, with symptoms ofdepression remaining significantly reduced at the12-month follow-up. Emery and colleagues55 foundreduced anxiety and improved cognitive functionfollowing a 10-week pulmonary rehabilitation inter-vention. In a study of 164 patients participating inpulmonary rehabilitation prior to being randomlyassigned to a long-term follow-up intervention, Riesand colleagues40 observed significant improvementsin measures of depression and self-efficacy for walk-ing immediately following the 8-week pulmonaryrehabilitation program.

Recommendation

7. There are psychosocial benefits from com-prehensive pulmonary rehabilitation programsin patients with COPD. Grade of recommenda-tion, 2B

Long-term Benefits From Pulmonary Rehabilitation

The formal component of most pulmonary reha-bilitation programs is of relatively short duration,usually ranging from 6 to 12 weeks. Regarding theissue of long-term benefits following the short-termintervention, the previous panel did not specificallyaddress this topic but recommended it as an impor-tant area for future research. Since that time, addi-tional important studies have addressed this topic.The next section discusses the issue of the durationof pulmonary rehabilitation treatment (ie, beyond 12weeks).

Several clinical trials of 6 to 12 weeks of compre-hensive pulmonary rehabilitation that have followedpatients over a longer term have found that benefitstypically persist for about 12 to 18 months after theintervention but gradually wane thereafter. In manyways, this is surprising given the severity of illness formany of these patients with chronic lung disease andthe complex set of behaviors incorporated into pul-monary rehabilitation (eg, exercise training, breath-ing control techniques, complex treatment regimenswith medications, use of supplemental oxygen, andrelaxation or panic control techniques). More recentclinical trials substantiate these findings (Table 4).

Griffiths and colleagues32 reported improvementsin measures of exercise tolerance, HRQOL, anxiety,and depression after pulmonary rehabilitation thatremained significant but declined gradually over 1year of follow-up. The study reported by Wijkstraand colleagues58 evaluated the effects of weekly vsmonthly follow-up over the 18 months after pulmo-nary rehabilitation in a small sample of patients withCOPD (n � 36). They reported no long-term im-provement in exercise tolerance in the two experi-mental groups, although this was better than the

decline observed in the control group. There were,however, more sustained improvements in dyspnea.Engstrom and colleagues59 reported sustained im-provement in exercise tolerance at 12 months afterpulmonary rehabilitation with minimal improve-ments in either a general or disease-specific measureof HRQOL (although there was a trend for worsen-ing HRQOL in the control group). Strijbos andcolleagues35 reported significant improvement inreported well-being after pulmonary rehabilitationthat was maintained over 18 months (compared tomost control subjects who reported being unchangedor worse). The study reported by Guell and col-leagues41 also found persistent, but diminished, ben-efits in measures of exercise tolerance, dyspnea, andHRQOL over the 2 years of follow-up after pulmo-nary rehabilitation.

The study reported by Ries and colleagues40 ex-amined the effects of a telephone-based mainte-nance program for 1 year after a short-term rehabil-itation intervention. The experimental effects of themaintenance program are discussed in a subsequentsection on postrehabilitation maintenance. However,as an observational study, it is notable that thecontrol group (without postprogram maintenance)demonstrated a progressive decline in benefits over2 years of follow-up. Another multicenter observa-tional evaluation of the effectiveness of pulmonaryrehabilitation in centers throughout California (notincluded in Table 3)43 found that improvements insymptoms of dyspnea, HRQOL, and indexes ofhealth-care utilization declined over 18 months butstill remained above baseline levels.

Recommendation

8. Six to twelve weeks of pulmonary rehabil-itation produces benefits in several outcomesthat decline gradually over 12 to 18 months.Grade of recommendation, 1A. Some benefits,such as HRQOL, remain above control levels at12 to 18 months. Grade of recommendation, 1C

Duration of Pulmonary Rehabilitation

There is no consensus of opinion regarding theoptimal duration of the pulmonary rehabilitationintervention. From the patient’s perspective, theoptimal duration should be that which producesmaximal effects in the individual without becomingburdensome. Significant gains in exercise tolerance,dyspnea, and HRQOL have been observed followinginpatient pulmonary rehabilitation programs as shortas 10 days60 and after outpatient programs as long as18 months.61 Shorter program duration has thepotential to reduce the cost per patient served and to




spread limited resources.62 On the other hand,longer program duration may produce greater gainsand improved maintenance of benefits. This sectionwill examine longer term pulmonary rehabilitationinterventions (ie, beyond 12 weeks of treatment).

Successful pulmonary rehabilitation requires com-plex behavioral changes for which the patients’ com-petence and adherence may be facilitated by longerexposure to treatment interventions and interactionswith staff who provide reinforcement, encourage-

Table 4—Long-term Effects of Pulmonary Rehabilitation*

Study/Year Study Type Country/Setting Patients, Total No. Outcomes Results

Wijkstra et al58/1996

RCT: home PRP vs controlgroup

Netherlands/home

45 Lung fx; endurance;6MWD; IM strengthand endurance

FEV1 improved in group B(p � 0.05 to baseline);Wmax decreased (p � 0.05for control subjects); PIP/endurance significantincrease in group A only

Engstrom etal59/1999

RCT: single blind; long-termvs conventional care

Sweden/OP 50 Lung fx and otherphysiologic factors;QOL

Walk distance/tolerancesignificantly increased in txgroup

Sickness impact profile:decreased in control group

Griffiths et al32/2000

RCT: single blind: 6-wk PRPvs conventional care

UnitedKingdom/OP

200 Exercise capacity;general health status;HRQL

Shuttle walk, SGRQ, SF-36,HAD statistically significantvs control group (6 wk)

Shuttle walk, SGRQ, CRDQ,SF-36, and HAD statisticallysignificant vs control group(12 wk)

Guell et al41/2000

RCT: single-blind; long-termvs standard care

Spain/OP 60 Dyspnea, exercise,HRQL, hospitalutilization

Treatment effects: FVC(p � 0.04); 10MWT(p � 0.0001); dyspnea(p � 0.0001); MRC scales(p � 0.0001); CRDQ scorein all domains

Exacerbations: control group,207; tx group, 111(p � 0.0001);hospitalization: controlgroup, 39; tx group, 18

Foglio et al36/2001

RCT: single-blind; repeat PRPvs no repeat

Italy/OP 61 Lung fx; symptoms;dyspnea; HRQL;health-care utilization

Lung fx/inspiratory muscle fx:NS; exercise tolerance:increased in tx group, notsustained; dyspnea/leg pain,NS; POD, short-termimprovement (NS);utilization: hospitalizationdecreased

Brooks et al71/2002

RCT: enhanced follow-up afterPRP vs standard care

Canada/OP 109 Functional exercisecapacity; HRQL

6MWD: distance, NS; time(p � 0.001); time � groupinteraction (p � 0.03);distance at 12 mo decreased(p � 0.001); HRQL:significant differences overtime

Ries et al40/2003

RCT: 12-mo maintenance vsstandard care

United States/OP

172 PFT, exercise tolerance,psychosocialmeasures, health-careutilization

At 12 mo, exercise tolerance/health status significantlyimproved in tx vs controlgroup; 6MWT decreasedboth groups

AT 24 mo, levels for allparameters were slightlyhigher than pre-PRP;utilization decreased in txgroup

*10MWT � 10-min walk test; MRC � Medical Research Council; PIP � peak inspiratory mouth pressure; 6 MWT � 6-min walk test; PFT �pulmonary function test; POD � perception of dyspnea. See Table 3 for abbreviations not used in the text.




ment, and coaching. These changes include incorpo-rating regular exercise into the patient’s lifestyle; theuse of breathing techniques, pacing and energyconservation strategies; and the use of medicationsand equipment, supplemental oxygen, and psychos-ocial adaptations. A number of external factors alsoinfluence program duration including health-caresystems and reimbursement policies, access to pro-grams, level of functional disability, health-care pro-vider referral patterns, and the ability of individualpatients to make progress toward treatment goals.

Few clinical trials have focused on the impact ofprogram duration on rehabilitation outcomes, butexisting data suggest that gains in exercise tolerancemay be greater following longer programs (Table 5).For example, two other randomized trials compared3 vs 18 months of low-intensity exercise training inpulmonary rehabilitation.63,64 Berry and colleagues63

demonstrated that the longer intervention led to a6% increase in the 6-min walk distance, a 12%reduction in self-reported disability, and faster com-pletion of stair climbing and overhead tasks. Foy andcolleagues64 showed that only male patients achievedgreater gains in CRDQ scores following the 18-month program (compared to the 3-month pro-gram). In a 2005 published prospective trial involv-ing seven outpatient programs (not in Table 5),Verrill and colleagues65 demonstrated that patientsachieved significant gains in exercise tolerance (6-min walk distance), dyspnea (University of Califor-nia, San Diego Shortness of Breath Questionnaire),and health status (Medical Outcomes Study 36-itemShort Form and the quality-of-life index) after 12weeks of pulmonary rehabilitation. Following anadditional 12 weeks of rehabilitation, exercise toler-ance but not health status or dyspnea outcomesimproved further, suggesting that program durationmay not impact all outcomes equally.

Also in support of longer term exercise training,Troosters and colleagues33 demonstrated that a6-month outpatient pulmonary rehabilitation pro-gram composed of moderate-to-high-intensity aero-bic and strength exercise training led to significantimprovements in exercise performance and qualityof life. Although this study did not compare the6-month program with a shorter one, the benefitsgained following the 6-month training program per-sisted 18 months after the completion of rehabilita-tion. This contrasts with the results of other stud-ies35,50,66 of pulmonary rehabilitation of shorter than6 months duration in which benefits tended todecline progressively over the year following reha-bilitation. Likewise, in the study by Guell and col-leagues41 (Table 4) a 12-month intervention (6months of daily rehabilitation followed by 6 monthsof weekly supervision) led to gains in exercise toler-

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ance, dyspnea, and health status that persisted overthe 1 year after rehabilitation, although even thesebenefits tended to decline gradually over the secondyear of follow-up.

Green and colleagues34 also demonstrated thatpatients with severe COPD achieved greater im-provements in treadmill endurance, incrementalshuttle walk distance, and quality of life following a7-week outpatient pulmonary rehabilitation programcompared with an identical program of only 4 weeksduration. However, patients who underwent the4-week program were not reassessed at the 7-weektime point to enable the direct comparison of out-comes.

A more recent trial (not in Table 5) readdressedthis issue in a larger cohort of patients. Sewell andcolleagues67 randomized 100 patients with moder-ate-to-severe COPD (mean FEV1, 1.13 L) to receive4 vs 7 weeks of outpatient rehabilitation. All patientswere assessed at baseline, at the end of the rehabil-itation intervention, and 6 months later. Patients inthe 4-week training group were also evaluated at 7weeks. Patients in both groups had significant im-provements in exercise tolerance and health status.This study contrasts with the results of other pub-lished studies mentioned above in that it showed thatthe shorter 4-week intervention produced gains inexercise tolerance at both the 7-week and 6-monthfollow-up time periods that were comparable tothose following the longer 7-week program. Finally,in an older trial Wijkstra and colleagues61 showedthat patients who underwent 18 months of home-based rehabilitation had greater sustained improve-ments in quality of life compared with patients whoreceived twice-weekly rehabilitation over a 3-monthperiod, but no difference was noted between groupsin the magnitude of gains in the 6-min walk distance.

Overall, although some studies suggest that theduration of the pulmonary rehabilitation programimpacts exercise tolerance improvement, it is lessclear that other outcomes such as health status ordyspnea are similarly affected by program duration.Other studies60,67 have demonstrated that even pro-grams of short duration (ie, 10 days to 4 weeks) canproduce significant benefits as well. Moreover, theeffect of program duration on patient abilities toperform activities of daily living (ADLs) is uncertain.The clinical benefits of pulmonary rehabilitation maydepend as much on program site and content as onduration.62 Thus, given the variations in types ofrehabilitation programs and differences in clinicalstudy design, patient populations, health systems indifferent countries, program location, and programcontent, it is not possible at this time to draw firmconclusions regarding the optimal duration of pul-monary rehabilitation treatment.

Recommendation

9. Longer pulmonary rehabilitation pro-grams (beyond 12 weeks) produce greater sus-tained benefits than shorter programs. Grade ofrecommendation, 2C

Postrehabilitation MaintenanceStrategies

Although the benefits of pulmonary rehabilitationhave been demonstrated up to 2 years following ashort-term intervention,41 most studies suggest thatthe clinical benefits of pulmonary rehabilitation tendto wane gradually over time. This is underscored in12-month follow-up data from a cohort of patientswith COPD who had completed a 10-week compre-hensive pulmonary rehabilitation program.68 At theend of the 10-week program, participants were givena structured home exercise program to follow. At thefollow-up evaluation 1 year later, participants whohad continued with the “prescribed” exercise routinemaintained the gains that had been achieved inphysical endurance, psychological functioning, andcognitive functioning during the initial intervention.However, participants who did not maintain theexercise routine exhibited significant declines in allareas of functioning, including exercise endurance,psychological functioning, and cognitive functioning.

Interest has thus arisen in strategies to maintainthe benefits of pulmonary rehabilitation over time,such as repeated courses of rehabilitation treatmentor maintenance interventions. In the study by Foglioand colleagues,36 although repeated pulmonary re-habilitation interventions spaced 1 year apart led tosignificant short-term gains similar to those seenfollowing an initial 8-week outpatient program, noadditive, long-term physiologic benefits were noted.A study by Ries and colleagues40 demonstrated thata 12-month maintenance intervention (consisting ofmonthly supervised exercise and educational rein-forcement sessions and weekly telephone contacts)following an initial 8-week outpatient pulmonaryrehabilitation program led to modest improvementsin the maintenance of walking endurance, healthstatus, and health-care utilization compared withusual care following pulmonary rehabilitation over a1-year follow-up period. However, a gradual declinein these outcomes was noted over time in bothpatient groups, and the initial benefits of the main-tenance intervention were no longer evident at 24months of follow-up. In a separate study by Puente-Maestu and colleagues,69 a 13-month maintenanceprogram (consisting of patient self-governed walking4 km per day at least 4 days per week with supervisedsessions every 3 months) led to small gains in




tolerance of high-intensity constant-work-rate exer-cise and quality of life after an initial 8 weeks oflower extremity training (two different regimens),but the effects of the maintenance program on theability to perform lower intensity exercise or ADLswere not tested. Grosbois and colleagues70 showedthat 18 months of both self-managed, home-based,and center-based supervised exercise maintenancewere beneficial in maintaining the benefits in maxi-mal exercise tolerance following a 7-week outpatientpulmonary rehabilitation program. In this study,center-based exercise maintenance afforded no ben-efits over the patient self-managed, home-basedapproach. Other studies71 have failed to demonstrateany benefit of maintenance programs following theshort-term rehabilitation intervention. Althoughmost studies have not yet assessed how maintenanceprograms truly impact patients’ ability to performdaily activities outside of the program setting, par-ticipation after pulmonary rehabilitation in regularexercise such as walking has been associated with aslower decline in HRQOL and dyspnea duringADLs.72

Thus, the role of maintenance pulmonary rehabil-itation interventions following initial structured pro-grams remains uncertain at this time, and the bene-fits of such interventions studied to date are modest,at best. Additional research is needed to clarify therelative impact of the many factors that can impactduration benefits from short-term pulmonary reha-bilitation, such as the maintenance program struc-ture, content, and location; exacerbations of respira-tory disease; complications of other medicalcomorbidities; and the absence of reimbursementfor continued patient participation. An additionalimportant topic that must be addressed in the futureis that of long-term patient participation. A relativelysmall number of patients who are offered a commu-nity-based exercise maintenance program will acceptit and adhere to it.73 Moreover, among those personswho do enroll in maintenance programs, attrition isproblematic, resulting from factors such as diseaseexacerbations, loss of interest and/or motivation,transportation barriers, depression, program costs,and other personal issues affecting patients’ lives.Additional work is needed to evaluate the optimalmethods to incorporate short-term rehabilitationstrategies into long-term disease management pro-grams for patients with chronic lung disease.

Recommendation

10. Maintenance strategies following pulmo-nary rehabilitation have a modest effect on long-term outcomes. Grade of recommendation, 2C

Intensity of Aerobic Exercise Training

Exercise training is one of the key components ofpulmonary rehabilitation. The exercise prescriptionfor the training program is guided by the followingthree parameters: intensity; frequency; and duration.The characteristics of exercise programs in pulmo-nary rehabilitation for patients with COPD have notbeen extensively investigated.

As noted by the previous panel and a 2005 re-view,74 for most patients with COPD with limitedmaximum exercise tolerance, training intensities athigher percentages of maximum (ie, peak exercise)are well-tolerated, and physiologic training effects(eg, increase in aerobic capacity and anaerobicthreshold with reduced ventilatory demand) havebeen documented as a result of (relatively) high-intensity aerobic training. Although it has not beenconclusively demonstrated in patients with COPD,higher intensity training may result in better physi-ologic training effects, including reduced minuteventilation (V̇e) and heart rate (HR), and, thus, lessdyspnea at submaximal exercise. In this context, theterm high-intensity training for patients with COPDrefers to patients exercising close to individual peaklevels and is relative to the markedly reduced peakexercise levels in these patients. In previous studies,high-intensity training targets have been operation-ally defined to be at least 60 to 80% of the peak workrate achieved in an incremental maximum exercisetest.75,76 This should not be interpreted to representtraining at high absolute work levels.

There have only been two randomized studies77,78

published since the previous panel report that haveevaluated the intensity of exercise during pulmonaryrehabilitation in patients with COPD. Gimenez andcolleagues77 randomized 13 patients to high-intensityor moderate-intensity lower extremity exercise train-ing daily for a period of 6 weeks. High-intensityexercise was performed on a cycle ergometer using aprotocol of 1-min periods at peak oxygen uptake(V̇o2) followed by 4-min periods at 40 to 45% of peakV̇o2. The moderate-intensity exercise group pushedan oxygen cart for a similar duration of 45 min persession. High-intensity training resulted in greaterphysiologic improvements (eg, improvement in max-imum V̇o2). High-intensity exercise, but not low-intensity exercise, also resulted in decreased dyspneaat rest and during submaximal exercise, and in-creased the 12-min walk distance. Vallet and col-leagues78 randomized 24 subjects to exercise at anHR achieved at the anaerobic or gas exchangethreshold (high intensity) or at an HR of 50% ofmaximal cardiac frequency reserve (low intensity).Stationary cycle ergometry was performed for 45min 5 days per week for 4 weeks. Subjects who




trained at the higher gas exchange threshold inten-sity exhibited improvement in maximum exerciseV̇o2 and a greater decrease in V̇e compared to thosewho trained with low-intensity exercise.

The physiologic benefits of higher intensity exer-cise training with the associated reduction in V̇e atsimilar workloads may be expected to result in betteroutcomes from pulmonary rehabilitation. The fewsmall controlled randomized studies77,78 availableconfirm these expectations. However, the effects ofhigh-intensity training on other key patient-centeredoutcomes such as quality of life, shortness of breath,and ability to perform ADLs have not been investi-gated rigorously.

Moreover, the impact of exercise intensity on theimportant outcome of maintenance of exercise train-ing has not been evaluated. As in other populations,it is possible that lower intensity exercise trainingmay be associated with better long-term adherencethan higher intensity training.

Recommendations

11. Lower extremity exercise training athigher exercise intensity produces greaterphysiologic benefits than lower intensity train-ing in patients with COPD. Grade of recommen-dation, 1B

12. Both low-intensity and high-intensity ex-ercise training produce clinical benefits for pa-tients with COPD. Grade of recommendation, 1A

Strength Training in PulmonaryRehabilitation

Although always recognized as important, improv-ing the function of the muscles of the arms and legshas recently become a central focus of pulmonaryrehabilitation. In the course of everyday activities,these muscles are asked to perform two categories oftasks. Endurance tasks require repetitive actionsover an extended period of time; walking, cycling,and swimming are examples. Strength tasks requireexplosive performance over short time periods;sprinting, jumping, and lifting weights are examples.For individuals whose muscles are weak, another cat-egory of strength-related tasks may become relevant,such as maintaining balance while standing, rising froma chair, or hoisting objects above head level.

Different characteristics of skeletal muscle enablethe performance of endurance and strength tasks.Endurance is facilitated by having machinery capa-ble of the aerobic metabolism of nutrients. Predom-inance of type I fibers, dense capillarity, high con-centrations of enzymes subserving oxidativemetabolism, and high mitochondrial density all pro-

mote muscle endurance. In contrast, strength isfacilitated in muscles, the fibers of which are high innumber and large in cross-section, with high frac-tions of type II fibers.

Some work79–81 has shown that the skeletal mus-cles of patients with COPD are, in general, dysfunc-tional. Some structural and biochemical abnormali-ties would predict poor aerobic function (eg, poorcapillarization and type II fiber predominance).However, compared to age-matched healthy sub-jects, patients with COPD also have low musclemass,82,83 especially in the muscles of ambulation;this predicts poor muscle strength.83–85

In healthy subjects, strength-training programs, inwhich progressive resistance methods are used toincrease the ability to exert or resist force,86 arecapable of profoundly altering muscle structure andbiochemistry, even in older subjects.87–90 An impor-tant principle of training specificity dictates thattraining programs featuring endurance activities (eg,treadmill walking and bicycle riding) yield musclechanges that improve endurance, while training pro-grams that feature tasks requiring strength (eg, ma-chine weights, free weights, elastic resistance, andlifting the body against gravity) yield muscle changesimproving strength. However, more recent work91,92

has shown that the muscles of elderly subjects mayalso show improvements in aerobic characteristicsafter a program of strength training.

In patients with COPD, there is a strong scientificbasis for implementing endurance-training programsin regard to both design and benefits. In comparison,programs of strength training have been explored inclinical trials only in more recent years. Since the lastreview, eight randomized clinical trials relevant tostrength training have been published (Table 6),which is a considerable advance on the one studypublished prior to 1997. This older study (Simpsonand colleagues93) was not included in the previousreview and so has been included in the currentanalysis. These nine studies93–101 can be separatedinto those that allow comparison between a controlgroup (ie, either no exercise or endurance exer-cise)93–98 and a strength-trained group, and thosethat allow comparison between an endurance-trained group and a group receiving a combinedendurance-training and strength-training interven-tion.97,99–101 The latter comparison is especially rel-evant to rehabilitative practice in which the questionis whether the addition of strength training to anendurance-training program produces additionalbenefits.

The six randomized clinical trials93–98 examiningthe responses of patients with COPD to a program ofstrength training have sufficient commonality to beexamined as a group. With one exception,95 the




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average disease severity was moderately severe(FEV1 range, 38 to 48% predicted). The exception isthe study of Clark and colleagues95 in which patientswith very mild COPD were studied (average FEV1,77% predicted). Collectively, the total number ofpatients studied was moderate, with the strength-trained group in the various studies comprising 6 to26 subjects (total, 99 subjects). The training appara-tus, exercise repetition, and intensity progressionvaried among studies (see Storer102 for a review ofsuitable strength-training strategies). Program lengthranged from 8 to 12 weeks; sessions were held two orthree times per week, and session length (whenstated) ranged from 40 to 90 min. These programcharacteristics are similar to those known to beeffective in healthy subjects.103

The recorded outcomes of these studies includechanges in strength, endurance, muscle mass, anddisease-specific HRQOL. All six studies93–98 re-ported improvements in strength. A variety oftesting apparatuses were used, and it should bestressed that the measures of strength used inthese studies were effort, motivation, and practicedependent. In all studies but one,96 the change inexercise endurance was also assessed. Results weremixed. The peak exercise level in an incrementalcycle ergometer test showed a statistically signifi-cant increase in only one of five studies98; theduration of a constant-work-rate task increased inthree of five studies93,95,97; and the 6-min walkdistance increased in one of the two studies in which itwas assessed.98 In two studies in which it was mea-sured, muscle mass (assessed by MRI of a quadricepscross-section96 or dual-energy x-ray absorptiometry[DEXA] scan of lean leg mass94) increased significantly(by 4% and 3%, respectively).

Four studies97,99–101 allowed a comparison of ben-efits to COPD patients between a combinedstrength-training and endurance-training programand an endurance-training program alone. Thesestudies examined patients with, on average, moder-ately severe to severe disease (mean FEV1 range, 33to 45% predicted). The number of patients includedin the strength-training-plus-endurance-traininggroup ranged from 9 to 21 (total, 55 patients).Training programs were 8 to 12 weeks in duration;sessions were held two or three times per week; theduration of strength training per session was gener-ally not stated (it was 45 min in the study by Bernardand colleagues99). Strength-training exercises wereincluded for both the arms and the legs.

In all four studies, improvement in measures ofmuscle strength was superior in the group receiv-ing a strength-training component to that seenamong those receiving endurance training alone.In one study,101 measures of ADLs improved more

in the combined-training group. However, mea-sures of the increase in exercise endurance werecomparable in the two groups (with the exceptionof the study by Panton and colleagues,101 whofound a superior increase in the 12-min walkdistance in the combined-training group). Twostudies99,101 assessed muscle mass changes; neitherdetected significant changes in subjects perform-ing endurance training alone, while both showedincreases in the groups in whom a strength-training program was added (8% increase in thighcross-section by CT scan99 and 5% increase inwhole-body lean mass by DEXA scan101).

These data can be interpreted to indicate that well-designed strength-training programs increase musclestrength and mass in patients with moderate-to-severeCOPD. Strength training, when delivered as an iso-lated intervention may improve disease-specific qualityof life but does not seem to produce additional gainswhen added to a program of endurance training.Strength training does not produce endurance benefitsas consistently as does specific endurance training.

It should be emphasized that, to date, all citedtrials featuring combined programs have added astrength-training component to an endurance-train-ing program (ie, essentially doubling the time spenttraining) rather than substituting part of the endur-ance-training program with an endurance compo-nent. Therefore, whether it is wise for rehabilitationpractitioners to include a strength-training compo-nent in a session of fixed duration by reducing thetime spent in endurance activities cannot be assessedat this time. Importantly, no serious adverse effectsof strength training have been reported; these pre-liminary data suggest that strength training is safe inpatients without obvious contraindications (eg, se-vere osteoporosis). Little information is available onthe long-term benefits of strength training in thepulmonary rehabilitation patient. Whether strengthgains persist and whether adverse consequences ofweakness occur (eg, decreased mobility or injuries dueto falls) cannot be determined. Larger, longer termtrials are required to resolve these issues. Finally,muscle biopsy studies of the cellular and biochemicaladjustments following strength training have yet to bereported; such studies should help to determine theextent to which strength training ameliorates the mus-cle dysfunction seen in COPD patients.

Recommendation

13. The addition of a strength-training com-ponent to a program of pulmonary rehabilita-tion increases muscle strength and musclemass. Strength of evidence, 1A




Anabolic Drugs

Since exercise-training interventions are a corner-stone in pulmonary rehabilitation and yield benefits,at least in part, by improving the function of theexercising muscles, it seems reasonable to hypothe-size that pharmaceutical agents that improve musclefunction in similar ways might be useful adjuncts torehabilitative therapy. However, the list of drugs thatmight be suitable for clinical trials is quite limited. Inparticular, no agent that is capable of directly im-proving the aerobic characteristics of muscle hasbeen studied in a clinical trial. It is plausible thaterythropoietin might be of use in anemic patientswith COPD; increasing muscle oxygen deliverymight increase exercise endurance as it has in otherpatient groups,104,105 but this has not been tested ina clinical trial.

Drugs that produce muscle hypertrophy havebeen identified and studied to determine whetherthey elicit improvements in muscle strength. Growthhormone, generally administered by daily injection,has been shown to induce modest increases inmuscle mass. However, improved functionality hasbeen difficult to demonstrate.106,107 In the only studyin COPD, Burdet and colleagues108 studied 16 un-derweight patients with COPD who received dailygrowth hormone injections for 3 weeks. Lean bodymass (assessed by DEXA scan) increased 2.3 kg inthe growth-hormone group compared with 1.1 kg inthe placebo group. No differences in maximuminspiratory pressure, handgrip strength, or incre-mental cycle ergometer exercise capacity were de-tected between groups. The 6-min walk distancedecreased significantly in the growth-hormonegroup. Clearly, growth hormone cannot be recom-mended as an adjunct therapy for pulmonary reha-bilitation at this time.

In men, therapy with testosterone and its analogshas been shown to increase muscle mass, decreasefat mass, and improve muscle strength. Well-con-trolled trials of testosterone supplementation inhealthy young men109,110 and older men111 havedemonstrated that muscle mass and strength in-crease with a linear dose-response relationship; anappreciable hypertrophic response is seen within thephysiologic range of circulating testosterone levels.Further, hypogonadal men show increases in musclemass and strength in response to physiologic doses oftestosterone.112 The side effects of testosterone ad-ministration are of concern; lipid abnormalities,polycythemia, and liver function abnormalities havebeen reported.113 In older men who may harborsubclinical foci of prostate cancer, testosterone ad-ministration may enhance the growth of these fo-ci.114 More recent experience suggests that substan-

tially supraphysiologic doses of testosterone shouldbe avoided in older men.111 A number of formula-tions of testosterone are available; it can be admin-istered by injection, transdermal patch, transdermalgel, and orally.115 Oral administration, however, hasoften been associated with elevations in liver func-tion test results. There have also been some prelim-inary studies116 of testosterone administration inwomen. Circulating levels of testosterone in womenare roughly 10-fold lower than those in men, andhigh testosterone doses are inevitably associated withvirulization.117 Whether lower doses that are notassociated with virulization will have substantial an-abolic effects on muscle remains to be seen.

A rationale for testosterone supplementation in menwith COPD is that circulating levels have been shownto be lower than those seen in healthy young men andare often lower than those in age-matched controlsubjects.94,118,119 Since the publication of the previousrehabilitation guidelines, five RCTs94,120–123 have ap-peared in which testosterone or its analogs (collectivelyknown as anabolic steroids) have been administered topatients with COPD. These trials are similar, in thatpatients with moderately severe COPD were studied(mean FEV1 range, 34 to 49% predicted). All studieswere limited to men, except for the study of Schols andcolleagues,122 in which women received half the drugdose that men received. In three of the studies,120–122

all participants received a rehabilitation-type program.All studies used relatively low doses, and no cleardrug-related adverse reactions (with the exception of amodest increase in hematocrit94) have been reported.

Schols and colleagues122 administered nandrolonedecanoate or placebo by injection every 2 weeks for8 weeks to approximately 130 patients who alsoreceived nutritional supplementation. Although nodifferences in body weight change were observedbetween these groups, in the nandrolone groupweight gain was predominantly in lean mass, whereasin the placebo group weight gain was predominantlyfat. No difference in changes in the 6-min walkdistance or peak inspiratory pressure was detected.

Ferreira and colleagues121 administered oralstanozolol or placebo daily for 27 weeks to 23underweight patients with COPD. DEXA scan-ning revealed an increase in lean mass of approx-imately 2 kg and a 5% increase in thigh circum-ference, which are changes that were not seen inthe control group. No differences were detected in6-min walk distance or incremental cycle ergome-ter testing results.

Creutzberg and colleagues120 administered nan-drolone decanoate or placebo by IM injection every2 weeks for 8 weeks to 63 men with COPD. Fat-freemass increased by 1.7 kg in the nandrolone groupcompared to 0.3 kg in the placebo group. No signif-




icant differences were seen between groups in incre-mental cycle ergometer exercise capacity orHRQOL. Muscle strength was assessed, but nodifferences were detected in handgrip strength orisokinetic leg strength testing results.

Svartberg and colleagues123 administered testos-terone enanthate or placebo by injection every 4weeks for 26 weeks to 29 men with COPD. DEXAscanning revealed a 1.1-kg increase in lean mass and a1.5-kg decrease in fat mass in the testosterone group.No exercise outcomes were assessed. No difference inquality of life, as assessed by the St. George respiratoryquestionnaire was detected, but better sexual quality oflife and erectile function was noted.

Casaburi and colleagues94 studied 47 men withCOPD and low testosterone levels (mean total tes-tosterone level, 320 ng/dL). Subjects received 100mg of testosterone enanthate or placebo by IMinjection for 10 weeks. Half of the group receivingtestosterone also underwent a strength-training pro-gram. Testosterone therapy yielded a 2.2-kg increasein lean body mass; the group receiving both testos-terone and strength training experienced a 3.3-kgincrease in lean mass. Average leg press strengthincreased by 12% in the testosterone group and by22% in the group receiving testosterone therapy plusstrength training. No improvements in incrementalor constant-work-rate cycle ergometer exercise tol-erance were demonstrated.

In summary, anabolic steroid administration hasconsistently been shown to increase lean (presum-ably muscle) body mass in men with moderate-to-severe COPD. As expected on theoretical grounds,no improvement in endurance exercise capacitywas detected. In one study,94 but not in another,120

an increase in the strength of the muscles of ambula-tion was detected. No evidence for improvements inquality of life has been obtained. It is premature tosuggest that the administration of anabolic steroids beincorporated into rehabilitative programs for patientswith COPD. Only roughly 150 patients have receivedthis intervention and only with relatively short-termexposures; whether the benefits outweigh the risks inthe long term cannot be determined at this time.

Recommendation

14. Current scientific evidence does not sup-port the routine use of anabolic agents in pul-monary rehabilitation for patients with COPD.Grade of recommendation, 2C

Upper Extremity Training

Upper extremity exercise training specifically im-pacts the arms and has been shown to increase arm

work capacity while decreasing V̇o2 for a comparablework level. Postulated mechanisms for improvementin upper extremity function from such training inpatients with chronic lung diseases include desensi-tization to dyspnea, better muscular coordination,and metabolic adaptations to exercise.

The previous 1997 guidelines panel recommendedthat “strength and endurance training of the upperextremities improves arm function in patients withCOPD” and that “arm exercises are safe, and should beincluded in rehabilitation programs for patients withCOPD” (strength of evidence, B). This was based onfive randomized trials and one observational study.

The methodology of the earlier studies variedconsiderably. Arm training alone appeared to be lesseffective than leg training124; however, when com-bined with leg training, a significant improvement infunctional status was noted compared to either mo-dality alone.124,125 Arm training by weight liftingsignificantly improved work capacity, reduced venti-latory requirements,126 and reduced both metabolicand ventilatory requirements (ie, O2 uptake, CO2production, and V̇e) following training.127 Greaterbenefit in unsupported arm work (with reducedmetabolic cost) was seen with unsupported armexercise when compared to supported arm exercisevia ergometry.211

Since the previous guideline, one observationalstudy128 and three RCTs129–131 were identified thataddress upper extremity training (Table 7). Theyfurther support the conclusion that arm trainingpositively impacts arm activity tolerance and thatarm exercise improves ventilatory requirements byreducing ventilation and the associated V̇o2.

The study by Holland and colleagues129 comparedarm training combined with lower limb training vslower limb training alone. The combined-traininggroup reported a significant improvement in armendurance (p � 0.02) compared to the group under-going lower limb training alone. In addition, thecombined-training group demonstrated a trend to-ward reduced Borg score for perceived dyspnea(p � 0.07). No difference in perceived fatigue rat-ings was noted.

Unsupported arm exercise has been shown toincrease upper extremity activity tolerance and en-durance when compared to control subjects.130,131

Epstein and colleagues131 evaluated respiratory mus-cle strength, endurance, and exercise capacity in 26persons with severe COPD. The arm-exercise groupdemonstrated increased muscle recruitment fromthe diaphragm, reduced oxygen cost during armelevation, increased endurance time (p � 0.05), andreduced ventilation. No differences were seen be-tween groups for V̇e and mean inspiratory flow.Bauldoff and colleagues130 studied unsupported arm




Tab

le7—

Upp

erE

xtre

mit

yT

rain

ing*

Stud

y/Ye

arSt

udy

Typ

eC

ount

ry/S

ettin

gPa

tient

s,T

otal

No.

Out

com

esR

esul

ts

Bau

ldof

fet

al13

0 /19

96R

CT

:upp

erar

mvs

cont

rol

Uni

ted

Stat

es/h

ome

20E

xerc

ise

abili

ty;d

isab

ility

;fa

tigue

and

AD

LT

ime

effe

ct;N

Sfo

rtr

eatm

ent,

time

�tr

eatm

ent

Fat

igue

scor

e:tim

e�

trea

tmen

t(p

�0.

0012

);N

Sfo

rtim

eor

trea

tmen

tal

one

Bre

athl

essn

ess:

NS

Eps

tein

etal

131 /

1997

RC

T:n

otbl

inde

d;up

per

arm

vsre

spir

ator

ym

uscl

etr

aini

ngU

nite

dSt

ates

/OP

(IP

for

thos

ew

hoco

uld

not

com

mut

e)

26R

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rato

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est

reng

th,

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ranc

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erci

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sesi

gnifi

cant

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rar

mel

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ion

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cle

stre

ngth

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rted

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cise

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pons

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rin

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psE

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ance

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ease

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05vs

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oup)

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nsse

net

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olN

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ds/I

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yan

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antly

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wer

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emity

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ing:

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ifica

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ntro

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nific

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ains

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brev

iatio

nsno

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text

.




training in 20 patients with moderate-to-severeCOPD over an 8-week period. They noted signifi-cant improvement over time in ratings of perceivedfatigue (p � 0.03) and a trend toward improvementin arm endurance (p � 0.07) in the arm-traininggroup compared with control subjects. No differencewas seen for ratings of perceived dyspnea.

In a prospective, case-control observational study,Franssen and colleagues128 compared 33 stable pa-tients with COPD to 20 healthy age-matched andgender-matched control subjects. Resting energyexpenditure was significantly increased in the COPDgroup, and both lower and upper extremity testsdemonstrated significantly lower peak workload, peakV̇o2 and carbon dioxide output, respiratory exchangeratio, and end-exercise ventilation in the COPD pa-tients. There were no significant differences in me-chanical efficiency between the groups. As the me-chanical efficiency and exercise capacity did not appearto be affected uniformly in patients with COPD, therelative preservation of upper limb activities may influ-ence exercise-training prescriptions in the pulmonaryrehabilitation of patients with COPD.

In summary, the new evidence provides additionalsupport for the use of upper extremity exercisetraining in pulmonary rehabilitation for patients withCOPD by demonstrating improvement in upperlimb exercise capacity and reduced ventilation andV̇o2 cost during arm activity following unsupportedarm training. Given the lack of randomized studiescomparing unsupported vs supported arm exercise,the best type of arm training is unknown.

Recommendation

15. Unsupported endurance training of theupper extremities is beneficial in patients withCOPD and should be included in pulmonaryrehabilitation programs. Grade of recommenda-tion, 1A

IMT

In general, patients with COPD have weak in-spiratory muscles.132,133 In fact, biopsy specimensfrom patients with mild-to-moderate COPD showreduced force generation per cross-sectional area.134

The major clinical consequences of inspiratory mus-cle weakness for patients are breathlessness andexercise impairment. The rationale for IMT is thatincreasing the strength and/or endurance of therespiratory muscles has the potential to improvethese clinical outcomes. To date, clinical trials ofIMT have been performed in endurance athletes, inpatients with chronic respiratory diseases (ie, asthma,cystic fibrosis, and COPD), chronic heart failure,

chronic cervical spinal cord injury, and musculardystrophy, before cardiothoracic surgery, and toassist weaning from mechanical ventilatory support.

The 1997 guidelines panel concluded that “thescientific evidence at the present time does notsupport the routine use of ventilatory muscle trainingas an essential component of pulmonary rehabilita-tion” and that “ventilatory muscle training may beconsidered in selected patients with COPD whohave decreased respiratory muscle strength andbreathlessness” (strength of evidence, B).

In the current review, six investigations of IMTwere identified (Table 8)137,206–210 that met thefollowing criteria: randomized trial involving patientswith COPD and a treatment and a control group; useof a resistance, threshold, or flow device for IMT;and inclusion of appropriate physiologic (ie, inspira-tory muscle strength [maximal inspiratory pressure(Pimax)] and/or endurance and exercise perfor-mance) and clinical (ie, dyspnea ratings and/or healthstatus) outcome measures. These six studies includeda total of 169 patients with COPD (range, 17 to 32subjects per study) who completed the trials, whichlasted from 2 months to 1 year in duration. Inaddition, a metaanalysis by Lotters and colleagues135

and a review article by Lisboa and Borzone136 werealso considered.

The 1997 guidelines panel raised various concernsabout the methodology of studies evaluating IMT.For example, one question regarding the previousstudies was: “Is the training stimulus adequate toinduce an expected physiologic response?” All of thesix new studies that were reviewed (Table 8) pro-vided subjects with an appropriate training stimulussuch that the respective IMT group achieved im-provement in respiratory muscle function comparedwith the control group.

Another key concern is the type of IMT. Themajor training methods are threshold loading, resis-tive breathing, and targeted flow. Five of the six newstudies206–210 used threshold loading, which has theadvantage of being independent of inspiratory flowrate but requires a build up of negative pressurebefore flow begins. In addition, threshold loadingenhances the velocity of inspiratory muscle contrac-tion, which appears favorable by shortening inspira-tory time, thus allowing more time for exhalation andlung emptying. The sixth study137 trained subjectswith an incentive flowmeter that provided visualfeedback.

One of the most important questions relates to thetypes of patients with COPD (ie, phenotypes) con-cerns who should be considered for IMT. In the sixnew trials (Table 8), 137,206–210 patients were re-cruited based on a diagnosis of COPD and a willing-ness to participate in the study. No specific patient




Tab

le8

—In

spir

ator

yM

usc

leT

rain

ing*

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y/Ye

arSt

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Typ

eC

ount

ry/S

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ts

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oaet

al20

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tion:

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phenotypes, such as stage of COPD, evidence ofinspiratory muscle weakness, degree of hyperinfla-tion, severity of breathlessness, level of exerciseimpairment, and/or reduced health status, were con-sidered for inclusion or exclusion criteria in thesestudies. In a metaanalysis, Lotters and colleagues135

found that neither the degree of severity of COPDnor hyperinflation had any effect on the efficacy ofIMT. However, subgroup analysis revealed thatthose patients with inspiratory muscle weakness (ie,Pimax, � 60 cm H2O) improved Pimax significantlymore with IMT combined with exercise trainingcompared to patients without inspiratory muscleweakness.

The consideration of outcome measures is alsoimportant to assess the benefits of IMT. Overall, thesix investigations summarized in Table 8137,206–210

show consistent improvements in inspiratory musclefunction, increases in exercise performance, andreductions in dyspnea. These data generally supportthe findings of the metaanalysis by Lotters andcolleagues135 that IMT by itself significantly in-creased inspiratory muscle strength and endurance,significantly improved dyspnea related to ADLs andduring exercise, and showed a nonsignificant trendfor an increase in exercise capacity.

Collectively, the positive results of the six newstudies137,206–210 (Table 8) provide further supportfor the efficacy (both physiologic and patient-cen-tered outcomes) of IMT. However, each study wasperformed at a single institution and included rela-tively small numbers of patients with COPD. Basedon this information, the panel continues to recom-mend that IMT be considered in selected patientswith COPD who have decreased inspiratory musclestrength and breathlessness despite receiving opti-mal medical therapy. The panel believes that alarge-scale, multicenter RCT should be performedwith appropriate statistical power to more com-pletely examine the role of IMT in treating patientswith COPD. Appropriate patient characteristics,training methodologies, and outcome measures areimportant considerations.

Recommendation

16. The scientific evidence does not supportthe routine use of IMT as an essential compo-nent of pulmonary rehabilitation. Grade of rec-ommendation, 1B

Education

The 1997 guidelines panel agreed that “educationis generally considered to be a necessary, but notsufficient, part of pulmonary rehabilitation” but didnot review the topic independent of the other com-

ponents because it could not identify a sufficientnumber of studies that were focused solely oneducation. The panel reviewed education along withthe psychosocial and behavioral components andrecommended that “although scientific evidence islacking, expert opinion supports the inclusion ofeducational and psychosocial interventions as com-ponents of comprehensive pulmonary rehabilitationprograms for patients with COPD” (strength ofevidence, C).

Patient education is a central component of mostpulmonary rehabilitation programs. Educationclasses are generally conducted in a lecture/discus-sion format and may cover a wide variety of topicsregarding the management of chronic lung disease.The scientific evidence for education in the 1997guidelines was based on four randomized studies andone observational study.138–142 Three of these stud-ies138–140 demonstrated mild improvement in dys-pnea. One of these studies140 compared dyspneaself-management to health education as the control,finding that the self-management group reporteddeceased dyspnea on baseline dyspnea index/transi-tional dyspnea index. In addition, both forms ofeducation resulted in significant improvement indyspnea. Conflicting results were reported in the twoadditional studies reviewed.141,142 One study141

found that education imparted no benefit on copingskills, while the second study142 reported increasedpsychological distress following an education inter-vention.

In the current review, four new RCTs were iden-tified.49,55,143,144 The results of all of these studiesdemonstrate that education alone has no indepen-dent benefit (Table 9).

In the study by Emery and colleagues,55 a three-group design tested comprehensive pulmonary reha-bilitation vs education and stress management(ESM) vs a waiting-list group in 79 stable patientswith COPD using blinded data collectors. The find-ings were that the pulmonary rehabilitation groupdemonstrated significant improvements in endur-ance exercise, maximum V̇o2, psychological well-being, and illness-related impairment when com-pared to the education group (p � 0.05). Significantimprovement was seen over time for anxiety as wellas cognitive function in the pulmonary rehabilitationgroup vs the education group (p � 0.05). However,all groups achieved significant improvement in men-tal efficiency over time. The authors concluded thatcomprehensive pulmonary rehabilitation producedsignificant improvements in endurance exercise, anx-iety, and cognitive performance when compared toeither the education-alone group or to the waiting-list group.

The study by Stulbarg and colleagues144 also used




Tab

le9

—E

duca

tion

inP

ulm

onar

yR

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ilit

atio

n*

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y/Ye

arSt

udy

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mes

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a three-group design evaluating education in theform of (1) dyspnea self-management alone vs (2)dyspnea self-management with minimal exercisetraining (4 sessions) vs (3) dyspnea self-managementwith extensive exercise training (24 sessions) in 115patients with moderate-to-severe COPD with singleblinding. Significant improvement was seen in thetraining group for 6-min walk distance (p � 0.001).Both the program-exposure group and the exercise-training group reported significant improvement inshortness of breath that was not seen in the self-management group (p � 0.04). Improvements inCRDQ subscales were seen primarily in the exercise-training group (p � 0.003), supporting the hypothe-sis that improvement in dyspnea was related to thenumber of exercise sessions undertaken. No im-provements in dyspnea or function were seen in theself-management group.

In the third study by Ringbaek and colleagues,143

an 8-week pulmonary rehabilitation program pluseducation was compared to conventional care in 45stable patients with moderate COPD without theblinding of either the participants or the researchstaff. No significant differences were seen betweenthe group receiving pulmonary rehabilitation pluseducation compared to the control group. Of note,the authors concluded that the absence of significantdifferences might be due to the brevity of theprogram (8 weeks), the selection of patients withmoderate COPD, or type II error.

In the final study by Bourbeau and colleagues,49 aself-management program was compared to usualcare in 191 patients with COPD. The 2-monthprogram was composed of weekly visits by nurses orallied health professionals including exercise evalua-tion and home-based instruction in an exercise-training program. Monthly telephone calls were con-ducted in months 3 to 12. The number of hospitaladmissions related to COPD exacerbations was re-duced significantly in the intervention group vs theusual-care group (40%), as well as the number ofhospital admissions related to other problems (57%).In addition, significant reductions in the numbers ofemergency department visits (41%) and unsched-uled physician visits (59%) were seen. These resultssuggest that a self-management program provided byhealth professionals reduced health-care service uti-lization.

In summary, there continues to be limited re-search that is specific to the impact of education onthe key outcomes of pulmonary rehabilitation inpatients with COPD. Nevertheless, current practiceand expert opinion suggest that there are importantbenefits of patient education, independent of pulmo-nary rehabilitation, including active patient partici-pation in a partnership with health-care providers to

achieve collaborative self-management and patientadherence to health-enhancing behaviors. Patienteducation is included as an important recommenda-tion in current clinical practice guidelines forCOPD.18,145

Patient education remains an integral componentof comprehensive pulmonary rehabilitation, possiblylimiting the ability to differentiate the benefits ofeducation alone. Discriminating the effect of educa-tional topics vs exercise is difficult as they aregenerally administered together and appear to behighly related. The previous 1997 guidelines panelthought that education outside of a comprehensivepulmonary rehabilitation program was not sufficientto improve the well-being of patients with COPD.The new evidence on using education and self-management education supports this conclusion,since none of the studies found a benefit for educa-tion alone in the absence of exercise training.

Recommendation

17. Education should be an integral compo-nent of pulmonary rehabilitation. Educationshould include information on collaborativeself-management, and the prevention and treat-ment of exacerbations. Grade of recommendation,1B

Psychological and Behavioral Componentsof Pulmonary Rehabilitation

Based on little published evidence, the 1997guidelines panel concluded that “Evidence to datedoes not support the benefits of short-term psycho-social interventions as single therapeutic modalities,but longer term interventions may be beneficial” andthat “expert opinion supports the inclusion of edu-cation and psychosocial interventions as componentsof comprehensive pulmonary rehabilitation pro-grams for patients with COPD.”

Psychological Distress in COPD

Some studies146,147 have confirmed that there is arelatively high prevalence of psychological distressamong patients with COPD. Depression and anxietyare the most commonly reported psychological con-cerns. However, due to the variety of methodsutilized in measuring depression and anxiety, preva-lence estimates for clinically significant depressionvary from 7 to 57%,148 and estimates for clinicallysignificant anxiety vary from 10 to 96%.149,150 Dataindicate that clinical depression may not be associ-ated with mortality among patients with COPD.151

However, no studies have evaluated the influence of




depressive symptoms on survival among patientswith COPD, despite evidence among patients withcardiac disease that mortality is associated withdepressive symptoms. Studies54,152,153 also have doc-umented changes in cognitive functioning amongpatients with COPD, including impairments inmemory performance and higher cognitive skills (eg,attention and complex visual-motor processes, ab-straction ability, and verbal tasks).

Overall, psychological distress is an importantclinical feature of COPD because patients withCOPD are more likely than age-matched peers toreport symptoms of distress, especially depressionand anxiety. In addition, psychological distressamong patients with COPD predicts impaired qual-ity of life and restricted ADLs.154 Functional capac-ity is more strongly associated with emotional/psy-chosocial factors (eg, depression, anxiety,somatization, low self-esteem, attitudes toward treat-ment, and social support) than with traditional phys-iologic indicators.155 Although psychological factorsare associated with functional performance, the in-fluence of psychological factors on disease progres-sion and mortality is unknown.

Psychosocial Interventions

During the past decade, there have been very fewstudies evaluating nonexercise psychosocial interven-tions among patients with COPD. Rose and col-leagues156 reviewed studies evaluating psychosocialinterventions to treat anxiety and panic. They de-scribed only one study55 published since 1995 with arandomized control group. Participants in this studywere randomly assigned to one of the following threegroups: exercise with ESM (designed to provide thestandard of care in pulmonary rehabilitation); ESM(designed to provide participants with the psychoso-cial components of rehabilitation minus any exercisetraining); and a nonintervention waiting list. Out-comes from participants in the ESM group reflectedthe effects of a psychosocial intervention. The resultsindicated that ESM participants achieved significantincreases in their knowledge about and treatment ofCOPD, but there were no effects of ESM onindicators of anxiety, depression, or quality of life. Inaddition, ESM participants did not exhibit changesin cognitive function. Thus, the data indicate thatESM alone in the absence of exercise had a minimalimpact on psychosocial functioning. These data areconsistent with the results of a 2005 study157 indicat-ing that patients with COPD who attended aneducational lecture series in addition to undergoingexercise training did not experience any benefitsbeyond those experienced by participants in exercisetraining without education or those who underwent

exercise training with activity training. Despite theabsence of any apparent benefit from educationaltraining in the latter study, it is noteworthy that theretention of participants assigned to the educationalgroup was 100% at 12 weeks compared to 64% and84%, respectively, in the other two groups. Thus, theeducational intervention may have facilitated aspectsof program adherence that the other regimens didnot.

Health Behavior Interventions

Behavioral factors are important in the preventivecare and rehabilitation of patients with COPD. Spe-cifically, smoking is well known to be the primaryrisk factor for the onset of COPD. Diagnosis withCOPD is not always a sufficient health threat tomotivate smokers to quit. Data regarding smokingcessation interventions among pulmonary rehabilita-tion patients are sparse. In a 2005 study158 of patientswith COPD who were smoking, participants wererandomly assigned to either a smoking cessationeducational intervention or to usual care. Partici-pants were recruited at various primary care sitesthroughout the Netherlands. The results indicatedthat quit rates in the intervention group were ap-proximately double those in the usual-care group(16% vs 9%, respectively). These data confirm that adiagnosis of COPD is not a sufficient stimulus toinitiate the process of smoking cessation, but educa-tional information may facilitate quitting in somepatients.

Conclusions

The data suggest that depression and anxiety aremore common among patients with COPD than inthe public at large. Data indicate that psychosocialintervention may facilitate behavioral changes, suchas smoking cessation, as well as the management ofsymptoms, including dyspnea. However, psychoso-cial interventions alone may not lead to reducedpsychological distress.

Recommendations

18. There is minimal evidence to support thebenefits of psychosocial interventions as a sin-gle therapeutic modality. Grade of recommenda-tion, 2C

19. Although no recommendation is pro-vided, since scientific evidence is lacking, cur-rent practice and expert opinion support theinclusion of psychosocial interventions as acomponent of comprehensive pulmonary reha-bilitation programs for patients with COPD.




Oxygen Supplementation as an Adjunct toPulmonary Rehabilitation

It was demonstrated � 25 years ago that long-termoxygen supplementation prolongs survival in patientswith COPD and severe resting hypoxemia.159,160

More recently, the usefulness of oxygen therapy inimproving outcomes from pulmonary rehabilitationin patients with COPD has been evaluated in severalRCTs. A distinction must be made between theimmediate effect of oxygen on exercise performanceand its usefulness in the exercise-training componentof pulmonary rehabilitation.161 This section will re-view the latter.

As an adjunct to exercise training, supplementaloxygen therapy has been studied in the following twosituations: (1) patients who are severely hypoxemic atrest or with exercise; and (2) patients who do nothave severe hypoxemia. The rationale for thesestudies is that supplemental oxygen therapy im-proves dyspnea and exercise capacity in patients withCOPD and hypoxemia,162,163 and even in thosewithout exercise-induced hypoxemia,164 possibly al-lowing them to train at higher intensities. Thesestudies, which evaluated exercise performance and,in some instances, HRQOL, are summarized inTable 10.

Rooyackers and colleagues165 randomized 24 pa-tients with severe COPD who were referred topulmonary rehabilitation and who experienced hy-poxemia during exercise testing (arterial oxygen sat-uration [Sao2] at maximum exercise, � 90%) intothe following two groups: (1) exercise training withroom air; and (2) exercise training with supplementaloxygen administered at a rate of 4 L/min. Theexercise-training intensity was increased as tolerated,but the work rate was adjusted to keep Sao2 at

� 90% in all patients. Health status was measuredusing the CRDQ. In prerehabilitation testing, com-pared with breathing room air, the use of supple-mental oxygen was associated with greater maximalcycle exercise performance and 6-min walk dis-tances. However, exercise training with supplemen-tal oxygen did not enhance the benefits of exercisetraining with respect to exercise performance mea-sured while breathing room air or on health statusmeasurements. These negative results might be ex-plained by the fact that the mean work rate duringinterval cycle exercise training during the last 6weeks was not significantly different between thetwo groups (p � 0.12).

Garrod and Wedzicha166 randomized 25 patientswith severe COPD and exercise-hypoxemia into 18sessions of exercise training breathing room air orsupplemental oxygen (4 L/min) over 6 weeks. Pa-tients were instructed to exercise as long as possibleat a high intensity. In the short term, supplementaloxygen therapy improved the shuttle walk distanceand symptoms of dyspnea in test results beforerehabilitation. However, supplemental oxygen ther-apy with exercise training did not enhance thepostrehabilitation gains in exercise performance,health status, or questionnaire-measured functionalstatus. These results might be explained by the factthat the group receiving oxygen supplementation didnot have significantly higher oxygen saturation levelsthan the nonsupplemented group. There was a smallimprovement in exertional dyspnea following reha-bilitation with oxygen therapy.

Wadell and colleagues167 randomized 20 patientswith COPD and exercise-induced hypoxemia intotraining with or without supplemental oxygen (at arate of 5 L/min). Training involved 30-min sessions

Table 10—Oxygen Supplementation as an Adjunct to Exercise Training*

Study/Year Design Hypoxia Patients, No. DurationBetween-Group Differences After Exercise

Training†

Rooyackers et al165/1997

RCT; O2 vs RA; Sao2

kept at � 90%;blinding not stated

Yes 24 50 sessions over10 wk

No differences in peak work rate, peak V̇o2,6MWT, or health status

Garrod et al166/2000

RCT; double blind; O2

vs RAYes 25 18 sessions over

6 wkNo difference in shuttle walk test, health

status, ADL scale; less postrehabilitationdyspnea with O2 treatment

Wadell et al167/2001

RCT; O2 vs RA; Sao2

kept at � 90%,patient blinded to txgroup

Yes 20 24 sessions over8 wk

No difference in exercise performance orhealth status

Emtner et al168/2003

RCT; double-blind; O2

vs RA groupNo 29 21 sessions over

7 wkO2 group achieved higher levels of exercise

training and greater increases in constantwork rate testing

*RA � room air. See Tables 3 and 4 for abbreviations not used in the text.†Testing conducted with patients breathing room air.




on a treadmill three times weekly for 8 weeks.Training intensity was individualized to target dys-pnea and perceived exertion ratings and to maintainSao2 at � 90%. Oxygen supplementation led tolonger walk test distances before and after rehabili-tation. However, there were no significant between-group differences in exercise-training effects at theend of the rehabilitation period, when patients weretested either while breathing room air or supplemen-tal oxygen. In fact, there was a trend for greaterimprovement in those patients who trained whilebreathing room air.

The studies described above evaluated the effectof oxygen in patients who experienced hypoxemiaduring exercise. More recently, Emtner and col-leagues168 evaluated the use of supplemental oxygenas an adjunct to exercise training in patients withCOPD who did not meet the standard criteria foroxygen supplementation. Unlike previous studies,this randomized trial was double-blinded. Twenty-nine patients without significant exercise-inducedoxygen desaturation were randomized to receivecompressed air or oxygen (at a rate of 3 L/min)during high-intensity exercise training. Patients weretrained in 21 sessions over a 7-week period with atarget intensity of 75% of the baseline peak work rateon a cycle ergometer, which was progressively ad-justed according to the patient’s perceived level ofdyspnea and fatigue. The results indicated that pa-tients receiving oxygen were able to train at higherintensities. After exercise training, endurance time ata constant work rate improved more in the groupreceiving supplemental oxygen therapy (14.5 min)compared with the group breathing room air (10.5min; p � 0.05). This improvement in exercise per-formance was accompanied by a reduction in respi-ratory rate at isotime during the tests. A recentmetaanalysis169 of these trials concluded that therewas a trend toward greater improvement in constant-work-rate test results and health status with oxygensupplementation, but the opposite effect was presentwith the 6-min walk test distance.

In summary, the use of continuous supplementaloxygen for patients with COPD and severe restinghypoxemia is clearly indicated and recommended asa part of routine clinical practice. From a safetyperspective, there is a strong rationale to administersupplemental oxygen during exercise training forpatients with severe resting or exercise hypoxemia.However, while oxygen use improves maximal exer-cise performance acutely in the laboratory, studiestesting its effect in enhancing the exercise-trainingeffect have produced inconsistent results. This mayreflect differences in methodology among the stud-ies, especially with respect to intensity targets fortraining. Of note, most of the studies reviewed

evaluated supplemental oxygen administered at arate of 3 to 5 L/min, which is higher than that usedin the typical clinical setting. As described above, onewell-designed study168 of supplemental oxygen ther-apy for nonhypoxemic patients with COPD whotrained at high intensity showed greater improve-ment in exercise capacity with oxygen therapy. Thelong-term benefit when supplemental oxygen is dis-continued and the effect on other outcomes such asHRQOL remain to be determined.

Recommendations

20. Supplemental oxygen should be usedduring rehabilitative exercise training in pa-tients with severe exercise-induced hypoxemia.Grade of recommendation, 1C

21. Administering supplemental oxygen dur-ing high-intensity exercise programs in patientswithout exercise-induced hypoxemia may im-prove gains in exercise endurance. Grade ofrecommendation, 2C

Noninvasive Ventilation

Noninvasive positive-pressure ventilation (NPPV)includes the techniques of continuous positive air-way pressure, pressure support, and proportionalassist ventilation (PAV). A metaanalysis170 of noctur-nal NPPV in stable hypercapneic patients withCOPD, which included four eligible trials, showedthat this therapy did not improve lung function, gasexchange, or sleep efficiency, but may have led to anincreased walk distance. The rationale for NPPV asan adjunct to exercise training is that through un-loading the respiratory muscles, the decreased workof breathing might allow for improved tolerance ofexercise training and the ability to achieve higherlevels of exercise intensity.171 In a systematic reviewof NPPV in seven trials that met specified inclusioncriteria (describing a total of 65 patients withCOPD), van’t Hul and colleagues172 concluded thatdyspnea and exercise endurance were significantlyimproved in the short term with the application ofthis therapy. However, these short-term effects ondyspnea and exercise performance must be differen-tiated from the ability of repeated NPPV use toenhance outcomes from pulmonary rehabilitation.

In this evidence-based review, we were able toidentify several trials that evaluated NPPV as anadjunct to an exercise training or pulmonary rehabil-itation program (Table 11). Garrod and colleagues173

randomized 45 patients with severe COPD to 12weeks of exercise training with or without nocturnalNPPV via nasal mask. The median settings for NPPVwere 16 cm H2O inspiratory and 4 cm H2O expira-




tory bilevel pressure ventilation. Compared with theexercise-training-only group, those patients usingnocturnal NPPV as an adjunct to exercise traininghad a significantly increased shuttle walk distance(72 m) and greater improvement in health status.

Two trials174,175 evaluated the adjunctive effect ofNPPV during supervised exercise training. Bianchiand colleagues174 randomized 33 men with moder-ate-to-severe COPD (mean FEV1, 44% predicted)beginning a 6-week pulmonary rehabilitation pro-gram into receiving mask PAV or spontaneousbreathing during exercise training. Five of the 18patients in the PAV group dropped out because oflack of compliance with the equipment. There wereno between-group differences in dyspnea, leg fa-tigue, exercise performance, or health status. In asimilar trial, but including patients with more severedisease (mean FEV1, 27% predicted), Hawkins andcolleagues175 found that PAV during 6 weeks ofhigh-intensity cycle exercise training led to betteroutcomes. Compared to those patients breathingwithout assistance during exercise training, the PAVgroup had a 15.2% higher training intensity, higherpeak work rate, and a trend (p � 0.09) of lower lactatelevels at the isowork rate. There was no significantbetween-group difference in exercise endurance.

Johnson and colleagues176 randomized 39 patientswith severe COPD (mean FEV1, 34% predicted)who were undergoing 6 weeks of pulmonary reha-bilitation into the following three groups: (1) helioxbreathing; (2) nasal NPPV therapy; and (3) spontane-ous breathing during exercise training. Bilevel pressureventilation was administered via nasal mask, with in-spiratory positive airway pressure at 8 to 12 cm H2O (astolerated) and expiratory positive airway pressure at 2cm H2O. NPPV allowed for a longer exercise timeduring training, but there were no between-groupdifferences in the percentage change in peak workload.

Costes and colleagues177 randomized 14 patientswith severe COPD into NPPV or spontaneous-breathing groups. Bilevel pressure ventilation set-tings were adjusted to tolerance. All were given 24sessions of exercise training over 8 weeks. The NPPVgroup demonstrated greater improvement in peakV̇o2 following exercise training compared to thegroup trained conventionally.

More recently, van’t Hul and colleagues178 ran-domized 29 patients with COPD into the followingtwo groups: (1) inspiratory pressure support (10 cmH2O) as an adjunct to an 8-week high-intensity cycleexercise-training program; and (2) sham therapy(inspiratory support at 5 cm H2O) with exercisetraining. Although both the patients and the investi-gator assessing the outcomes were blinded to thetreatment group, the physiotherapists supervising exer-cise training were not. Significant between-group im-provements in favor of the treatment group were seenin shuttle walk distance and cycle endurance time.

In summary, several randomized trials have com-pared spontaneous breathing with NPPV as an ad-junct to exercise in patients with COPD. Obviousmethodological issues exist with respect to blindingpatients and investigators, differences in exercisetraining and outcome assessments, and the smallnumbers of subjects. However, it appears that thistherapy does confer an immediate postrehabilitationbenefit in improving exercise tolerance in selectedpatients with more advanced disease.

Recommendation

22. As an adjunct to exercise training in se-lected patients with severe COPD, noninvasiveventilation produces modest additional im-provements in exercise performance. Grade ofrecommendation, 2B

Table 11—Noninvasive Ventilation as an Adjunct to Exercise Training*

Study/Year Design Patients, No. Duration Between-Group Differences After Exercise Training

Garrod et al173/2000

Nocturnal NPPV vs SB 45 16 sessions over8 wk

The nocturnal NPPV group had increased shuttlewalk distance and health status compared to thecontrol group

Bianchi et al174/2002

PAV vs SB 33 18 sessions over6 wk

No significant differences in exercise tolerance,dyspnea, leg fatigue, or health status

Hawkins et al175/2002

PAV vs SB 19 18 sessions over6 wk

Higher training intensity with PAV, higher peak workrate, trend for lower lactate at iso-work rate

Johnson et al176/2002

NPPV vs heliox vs SB 39 12 sessions over6 wk

NPPV allowed for longer exercise training duration;no difference in peak workload

Costes et al177/2003

NPPV vs SB 14 24 sessions over8 wk

The NPPV group had a greater increase in peak V̇o2;no differences in exercise endurance or lactatemeasured at isotime

van’t Hul et al178/2006

Inspiratory pressure supportvs SB

29 24 sessions over8 wk

Inspiratory pressure support group had greaterimprovement in shuttle walk distance and cycleendurance time

*SB � spontaneous breathing.




Nutritional Supplementation inPulmonary Rehabilitation

Poor nutritional status is associated with increasedmorbidity and mortality in patients with moderate-to-severe COPD.179 Prior studies have investigatedthe effects of dietary supplementation on patientswith COPD, as summarized in a relatively recentmetaanalysis.180 Summary data indicate that nutri-tional support/supplementation does not have a clin-ically significant effect on lung function or functionalabilities. No studies have evaluated the effects ofbehavioral weight management (gain or loss) amongpatients with COPD.

There remains very little information regardingthe effects of nutritional supplementation used inconjunction with a comprehensive pulmonary reha-bilitation program. Only one study181 has investi-gated the effects of nutritional supplementation ad-ministered during a comprehensive pulmonaryrehabilitation program. In this double blind, ran-domized trial, 85 patients with chronic lung diseasewere randomized to receive either (1) carbohydratesupplementation or (2) a nonnutritive placebo dur-ing a 7-week pulmonary rehabilitation program. Theaim was to augment exercise performance with theuse of carbohydrate supplementation. Outcomesmeasured included physical performance, health sta-tus, and body weight and composition. Twenty-fivepatients were unable to complete the study and werenot included in the final analysis. Significant in-creases in shuttle walk distance and HRQOL (asmeasured by the CRDQ) were noted in both groups.In well-nourished patients (ie, body mass index � 19kg/m2), improvement in shuttle walk performancewas significantly greater in the nutritionally supple-mented group (mean difference between groups,27 m; 95% confidence interval, 1 to 53 m; p � 0.05).The increase in shuttle walk performance correlatedwith increases in total carbohydrate intake.

The overall effects of nutritional supplementationin this single study are difficult to determine giventhe significant number of patients who did notcomplete the study and the fact that improvementwas noted in both experimental groups. This studysuggests that exercise-training results in a negativeenergy balance that can be overcome by supplemen-tation, and in selected patients, may improve theoutcome of training.

Recommendation

23. There is insufficient evidence to supportthe routine use of nutritional supplementationin the pulmonary rehabilitation of patients withCOPD. No recommendation is provided.

Pulmonary Rehabilitation for PatientsWith Disorders Other Than COPD

Although they have not been studied as well todate, patients with respiratory disorders other thanCOPD can also benefit substantially from pulmonaryrehabilitation. Indeed, the scientific rationale forproviding pulmonary rehabilitation to patients withnon-COPD diagnoses is the same as that for patientswith COPD. General principles of rehabilitationtreatment emphasize the adaptation of multidisci-plinary treatment strategies to the needs of individ-ual patients. Pulmonary rehabilitation programs pro-vide an ideal setting to address both common andindividual concerns for patients with a variety ofdifferent chronic lung diseases.

As in COPD, persons with other forms of chronicrespiratory disease commonly experience decondi-tioning and exercise intolerance, disabling symptomsof dyspnea and fatigue, impaired health status andquality of life, systemic inflammation, nutritionalimpairments, and/or muscle dysfunction (related todeconditioning, loss of fat-free mass, and/or cortico-steroid use) that collectively impair functional statusalong with abnormalities of pulmonary function.These comorbidities that are associated with chronicrespiratory disease can potentially be addressed andcorrected with rehabilitation strategies including ex-ercise training and other interventions such as nutri-tional support, despite the presence of irreversibleabnormalities of lung function. Moreover, pulmo-nary rehabilitation programs provide the opportunityto educate and train patients in adapting to complextreatment interventions such as immunosuppressivemedications, oxygen therapy, noninvasive ventila-tion, tracheostomy, lung volume reduction surgery,or lung transplantation. Optimal outcomes fromthese depend on patient understanding and compli-ance with therapeutic recommendations, but there isminimal time typically available in the routine clini-cal care setting for patient education, training, andcoaching for the complex behavioral changes in-cluded in treatment recommendations. Pulmonaryrehabilitation can assist patients in adjusting complexinterventions such as the technical requirements foroxygen supplementation or noninvasive ventilation.Patients undergoing lung transplantation or lungvolume reduction surgery are frequently required toparticipate in preoperative and postoperative pulmo-nary rehabilitation, in part, to provide needed edu-cation and support.

Modification of the relative emphasis on the coreprogram components and overall program content ofpulmonary rehabilitation may be required to main-tain patient safety and to meet individual patientneeds and goals.182 The goals of pulmonary rehabil-




itation for patients with chronic lung diseases otherthan COPD may differ from the standard goals forpatients with COPD. Education of the rehabilitationprogram staff regarding the pathophysiology, symp-toms, mechanisms of exercise limitation, naturalcourse, and signs of disease destabilization as well asthe therapeutic interventions specific for each of thevarious respiratory disorders is essential, as is closecommunication with referring physicians and theprogram medical director. Pulmonary rehabilitationstaff must be familiar with the recommended meth-ods of assessing patient exercise capacity, must beable to develop and safely implement the exerciseprogram, and to identify situations in which special-ized equipment or room setup may be required.Additional specific expertise may be needed in de-veloping appropriate rehabilitation programs fornon-COPD patients with disease-specific input fromphysical, occupational, and respiratory therapists,nurses, health psychologists, dieticians, respiratoryphysicians, and, when necessary, physiatrists or neu-rologists. Disease-appropriate and age-appropriatetools for the assessment of exercise capacity, healthstatus, and quality of life should be utilized, andefforts must be made to integrate topics relating tonon-COPD diagnoses in situations in which thepatient group is composed predominantly of COPDpatients. Individual patient education sessions andadditional written and/or video materials may beneeded.

Although most of the studies conducted and pub-lished to date investigating the outcomes of pulmo-nary rehabilitation for disorders other than COPDare uncontrolled trials or case series, RCTs arebeginning to emerge.183,184 The strength of existingevidence supporting the use of pulmonary rehabili-tation varies across the different diseases. Thus far,existing data suggest that, as in COPD, exercisetraining and rehabilitation improve exercise toler-ance and/or health status/quality of life for personswith asthma,183,185,186 bronchiectasis,187cystic fibro-sis,184,188,189 interstitial lung disease and restrictivechest wall disease,21,190,191 pulmonary hyperten-sion,192 obesity-related respiratory disease,193,194 andlung cancer,195,196 and selected patients with respi-ratory impairment from neuromuscular diseases.197–

200 For some patients with neuromuscular disease,pulmonary rehabilitation may not include traditionalexercise training, but may instead focus on acclima-tization to NPPV, optimization of functional status,and maintenance of the ability to live independentlythrough the use of adaptive/assistive equipment (eg,walkers or sock reachers). Caution must be taken toavoid excess muscle fatigue, especially among per-sons with degenerative neuromuscular disorders.Further research is needed to identify optimal train-

ing regimens, program structures, and outcome mea-surement tools that are useful in pulmonary rehabil-itation for patients with respiratory disorders otherthan COPD.

Recommendations

24. Pulmonary rehabilitation is beneficial forpatients with some chronic respiratory diseasesother than COPD. Grade of recommendation, 1B

25. Although no recommendation is providedsince scientific evidence is lacking, the currentpractice and expert opinion suggest that pulmo-nary rehabilitation for patients with chronicrespiratory diseases other than COPD shouldbe modified to include treatment strategiesspecific to individual diseases and patients, inaddition to treatment strategies common toboth COPD and non-COPD patients.

Summary and Recommendations for FutureResearch

The field of pulmonary rehabilitation has contin-ued to develop and mature substantially since thepublication of the previous evidence-based guide-lines in 1997. Additional published literature hasadded substantially to the scientific basis of pulmo-nary rehabilitation interventions as well as outcomes.The new data that have been examined furtherstrengthen the evidence that supports the benefits oflower extremity exercise training in pulmonary reha-bilitation and the improvement expected in symp-toms of dyspnea from comprehensive pulmonaryrehabilitation programs. The evidence supportingimportant changes in HRQOL has also beenstrengthened in new studies. Although there is someadditional evidence, there is still a need for moresystematic studies of the effect of pulmonary reha-bilitation on health-care costs and utilization. Thequestion is still open about whether pulmonaryrehabilitation improves survival in patients withCOPD. Trends observed in existing studies suggestthat pulmonary rehabilitation may have a modesteffect on survival, but a larger study powered toaddress survival would add important new informa-tion to the field and would have a significant impacton future health policy decisions. There is also aneed for more studies about psychosocial outcomesand interventions. New evidence adds support forthe inclusion of psychosocial components in compre-hensive pulmonary rehabilitation programs and theimportant beneficial effects of such programs onpsychosocial health, but more is clearly needed.Several promising studies lend continued support forupper extremity training as a means of achieving




important benefits in ADLs for many patients withdisabling chronic lung diseases. There remains littleevidence to support the routine inclusion of specificventilatory muscle training in pulmonary rehabilita-tion. There is little evidence that education alone,outside the context of comprehensive pulmonaryrehabilitation treatment, is beneficial. However,there have been no systematic studies evaluatingeducational delivery, topic selection, and reinforce-ment of information. Investigation may be warrantedregarding patient-specific learning styles, the dura-tion of educational sessions, topic selection, and theuse of educational reinforcement. Finally, emergingdata have demonstrated that exercise training andpulmonary rehabilitation are beneficial for patientswith respiratory disorders other than COPD.

An important area for future research relates tothe duration of pulmonary rehabilitation treatmentand strategies to help patients sustain benefits over alonger period of time. The existing literature stronglyindicates that the typical 6-week to 12-week compre-hensive pulmonary rehabilitation program producesbenefits that are sustained for approximately 12 to 18months. This, in itself, is remarkable in the face ofprogressive chronic lung diseases. However, it islikely that new treatment strategies could be devel-oped to help patients maintain the benefits frompulmonary rehabilitation over longer periods of time.Changes in the typical program structure, the periodof intervention, the more efficient use of limitedresources, as well as the tailoring of the rehabilitationintervention to different clinical phenotypes ofCOPD (eg, with or without peripheral or respiratorymuscle weakness, and depleted or nondepleted fat-free mass) may allow principles of pulmonary reha-bilitation to be adapted to longer term chronicdisease management, improve postprogram mainte-nance of benefits, and allow many more patients whoare in need to benefit from pulmonary rehabilitation.The development of better postprogram strategies tohelp patients adhere to rehabilitative treatments andto better maintain the complex behavior changesacquired in pulmonary rehabilitation might extendthe duration of benefits.

Interesting new evidence in the literature high-lights several areas for fruitful future research inrelation to pulmonary rehabilitation, and the treat-ment of patients with chronic lung diseases. Possibletopics include strength training in addition to endur-ance exercise training (and optimal methods for suchstrength-training protocols), better definition of op-timal exercise-training regimens, supplemental oxy-gen therapy for patients with less severe restinghypoxemia or hypoxemia specific to exercise orsleep, use of noninvasive ventilatory assistance as anadjunct to exercise training, nutritional supplemen-

tation, and use of rehabilitation strategies for pa-tients with chronic lung diseases other than COPD.

One interesting new area for future research is tofurther define the role for the transcutaneous elec-trical stimulation of the peripheral muscles(TCEMS) as a rehabilitative strategy for patientswith COPD and other forms of chronic respiratorydisease. Studies published thus far have demon-strated that TCEMS in the muscles of ambulationcan lead to significant improvements in musclestrength, exercise endurance, dyspnea,201,202 andV̇o2 max201 among stable patients with moderate-to-severe COPD, as well as in severely deconditionedpatients with severe airflow obstruction and low bodymass index who are recovering from acute COPDexacerbations.203 TCEMS also may facilitate im-provement in mobility among bed-bound patientswith COPD and respiratory failure requiring me-chanical ventilation.204 This safe, well-tolerated tech-nique can even be performed COPD exacerbationsand may help to prevent functional decline duringCOPD exacerbations.201 Further work is needed toclarify which subpopulations of patients benefit mostfrom this technique, to define the role of TCEMS asa routine component of pulmonary rehabilitation,and to understand the mechanisms by whichTCEMS confers its benefits among patients withchronic lung disease.

One novel approach to encouraging adherence isthrough the use of distractive auditory stimuli(DAS). A 2002 RCT205 of the effects of DAS (ie,listening to music while exercising) on exercise ad-herence and exercise outcomes among patients withCOPD who had completed a pulmonary rehabilita-tion program found no differences in amount ofexercise, velocity of exercise, or physical symptomsduring the study period between DAS participantsand control subjects receiving standard care. How-ever, participants in the DAS group experiencedreductions in dyspnea during ADLs and a significantincrease in exercise endurance (as determined by the6-min walk distance). Thus, DAS may help to dis-tract participants from exercise-related dyspnea andmay help patients to increase exercise durationduring individual bouts.

Finally, an important area of research in COPDrelates to the importance of exacerbations in influ-encing the natural history of the disease, and inaccelerating the subsequent morbidity and mortality.Preliminary evidence48 suggests that pulmonary re-habilitation after an exacerbation could improvemortality in these high-risk patients. Additional workin this area would be very important.

In summary, this is an exciting time that is full ofopportunities in the field of pulmonary rehabilita-tion. Pulmonary rehabilitation has now become well




established as a recommended treatment that canprovide important benefits to substantial numbers ofdisabled patients with chronic lung diseases. A re-view of the various components of pulmonary reha-bilitation also highlights opportunities, and chal-lenges, for future research that have the potential toimprove and broaden the scope of pulmonary reha-bilitation practice for the large population of patientswith chronic lung diseases, most of whom do notcurrently have access to such programs.

Summary of Recommendations

1. A program of exercise training of the mus-cles of ambulation is recommended as amandatory component of pulmonary reha-bilitation for patients with COPD.Grade of Recommendation: 1A

2. Pulmonary rehabilitation improves thesymptom of dyspnea in patients with COPD.Grade of Recommendation: 1A

3. Pulmonary rehabilitation improves health-related quality of life in patients with COPD.Grade of Recommendation: 1A

4. Pulmonary rehabilitation reduces the num-ber of hospital days and other measures ofhealth-care utilization in patients withCOPD.Grade of Recommendation: 2B

5. Pulmonary rehabilitation is cost-effective inpatients with COPD.Grade of Recommendation: 2C

6. There is insufficient evidence to determine ifpulmonary rehabilitation improves survivalin patients with COPD. No recommendationis provided.

7. There are psychosocial benefits from com-prehensive pulmonary rehabilitation pro-grams in patients with COPD.Grade of Recommendation: 2B

8. Six to 12 weeks of pulmonary rehabilitationproduces benefits in several outcomes thatdecline gradually over 12 to 18 months.(Grade of Recommendation: 1A)Some benefits, such as health-related qualityof life, remain above control at 12 to 18months.

(Grade of Recommendation: 1C)

9. Longer pulmonary rehabilitation pro-grams (12 weeks) produce greater sus-tained benefits than shorter programs.Grade of Recommendation: 2C

10. Maintenance strategies following pul-monary rehabilitation have a modesteffect on long-term outcomes.Grade of Recommendation: 2C

11. Lower-extremity exercise training athigher exercise intensity produces greater-physiologic benefits than lower-intensitytraining in patients with COPD.Grade of Recommendation: 1B

12. Both low- and high-intensity exercise train-ing produce clinical benefits for patientswith COPD.Grade of Recommendation: 1A

13. Addition of a strength training componentto a program of pulmonary rehabilitationincreases muscle strength and muscle mass.Strength of evidence: 1A

14. Current scientific evidence does not sup-port the routine use of anabolic agents inpulmonary rehabilitation for patientswith COPD.Grade of Recommendation: 2C

15. Unsupported endurance training of theupper extremities is beneficial in patientswith COPD and should be included inpulmonary rehabilitation programs.Grade of Recommendation: 1A

16. The scientific evidence does not supportthe routine use of inspiratory muscletraining as an essential component of pul-monary rehabilitation.Grade of Recommendation: 1B

17. Education should be an integral compo-nent of pulmonary rehabilitation. Educa-tion should include information on collab-orative self-management and preventionand treatment of exacerbations.Grade of Recommendation: 1B

18. There is minimal evidence to support thebenefits of psychosocial interventions as asingle therapeutic modality.Grade of Recommendation: 2C




19. Although no recommendation is providedsince scientific evidence is lacking, currentpractice and expert opinion support theinclusion of psychosocial interventions as acomponent of comprehensive pulmonaryrehabilitation programs for patients withCOPD.

20. Supplemental oxygen should be used dur-ing rehabilitative exercise training in pa-tients with severe exercise-induced hypox-emia.Grade of Recommendation: 1C

21. Administering supplemental oxygen duringhigh-intensity exercise programs in patientswithout exercise-induced hypoxemia mayimprove gains in exercise endurance.Grade of Recommendation: 2C

22. As an adjunct to exercise training in se-lected patients with severe COPD, noninva-sive ventilation produces modest additionalimprovements in exercise performance.Grade of Recommendation: 2B

23. There is insufficient evidence to supportthe routine use of nutritional supplemen-tation in pulmonary rehabilitation of pa-tients with COPD. No recommendation isprovided.

24. Pulmonary rehabilitation is beneficial forsome patients with chronic respiratorydiseases other than COPD.Grade of Recommendation: 1B

25. Although no recommendation is providedsince scientific evidence is lacking, cur-rent practice and expert opinion suggestthat pulmonary rehabilitation for patientswith chronic respiratory diseases otherthan COPD should be modified to in-clude treatment strategies specific to in-dividual diseases and patients in additionto treatment strategies common to bothCOPD and non-COPD patients.

ACKNOWLEDGMENT: This clinical practice guideline hasbeen endorsed by the American Thoracic Society, The EuropeanRespiratory Society, the US COPD Coalition and also theAmerican Association of Cardiovascular and Pulmonary Rehabil-itation (by way of collaboration on the project).

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DOI 10.1378/chest.06-2418 2007;131;4-42 Chest

Richard ZuWallack and Carla Herrerias Charles F. Emery, Donald A. Mahler, Barry Make, Carolyn L. Rochester, Andrew L. Ries, Gerene S. Bauldoff, Brian W. Carlin, Richard Casaburi,

Clinical Practice GuidelinesPulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based

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