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Integrated disease management interventions for patients with chronic obstructive pulmonary disease

  1. Annemarije L Kruis1,*,
  2. Nynke Smidt2,
  3. Willem JJ Assendelft3,
  4. Jacobijn Gussekloo1,
  5. Melinde RS Boland4,
  6. Maureen Rutten-van Mölken4,
  7. Niels H Chavannes1

Editorial Group: Cochrane Airways Group

Published Online: 10 OCT 2013

Assessed as up-to-date: 12 APR 2012

DOI: 10.1002/14651858.CD009437.pub2


How to Cite

Kruis AL, Smidt N, Assendelft WJJ, Gussekloo J, Boland MRS, Rutten-van Mölken M, Chavannes NH. Integrated disease management interventions for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD009437. DOI: 10.1002/14651858.CD009437.pub2.

Author Information

  1. 1

    Leiden University Medical Center, Department of Public Health and Primary Care, Leiden, Netherlands

  2. 2

    University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen, Groningen, Netherlands

  3. 3

    Radboud University Nijmegen Medical Center, Department of Primary and Community Care, 117 ELG, Nijmegen, Netherlands

  4. 4

    Erasmus University Rotterdam, Institute of Health Policy and Management/Institute of Medical Technology Assessment, Rotterdam, Netherlands

*Annemarije L Kruis, Department of Public Health and Primary Care, Leiden University Medical Center, PO Box 9600, Leiden, 2300 RC, Netherlands. A.l.kruis@lumc.nl.

Publication History

  1. Publication Status: New
  2. Published Online: 10 OCT 2013

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Characteristics of included studies [ordered by study ID]
Aiken 2006

MethodsRCT; follow-up: unknown; control group: usual care, which means patients receiving care from managed care organizations (MCO)


ParticipantsEligible: 192 (COPD and congestive heart failure)

Randomized COPD: 61

Mean age/sex: not reported for COPD patients

Inclusion criteria: COPD or congestive heart failure patients, palliative treatment residing at home, receiving care by MCO, mean life expectancy of 2 years, saturation < 88%, oxygen usage, marked limitation of physical functioning, recent exacerbation


InterventionsPhoenix Care palliative intervention services were added to treatment services of local MCOs. Registered nurse case managers (serving 30 to 35 patients) provided the intervention service. These nurses worked with protocols and held contact with the attending physicians. Furthermore, they developed care plans, provided education to patients and tailored self management of the disease. They supported services including assessing psychological and spiritual needs. During exacerbation episodes, the nurses assessed medical status, implemented a symptom control intervention and contacted the physician

Included health care providers (HCP): GP, nurse case manager


OutcomesSF-36, medical utilization


NotesMain component of program: structured follow-up with nurses/GP


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was carried out within diagnosis, in blocks of 30 patients (15 intervention, 15 control) by a member of the project administration staff."

Allocation concealment (selection bias)Low riskQuote: "Sealed-envelopes, colour-coded by diagnosis and containing the assignment to condition, were shuffled and assigned to participants in order of shuffling (..) the enroller, blinded to condition, opened the sealed envelope that identified the patients’ study condition. "

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All participants received an interview administered by a professional interviewing firm; interviewers were blind to condition and diagnosis"

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe authors performed an attrition analysis according to the Jurs and Glass procedure

Selective reporting (reporting bias)Low riskAll outcomes reported

Bendstrup 1997

MethodsRCT; follow-up: 24 weeks; control group: no treatment


ParticipantsEligible: 47

Completed: 32

Mean age I: 64 yrs, C: 65 yrs

Sex (% male) both groups: 56%

Inclusion criteria: diagnosis of COPD according to GOLD, FEV1 of 25% to 55% of predicted value, Tiffeneau index less than 70%, stable condition for 4 weeks (no change in exercise status, sputum color/quantity, no change in medication)

Major exclusions: heart disease, musculoskeletal disease limiting exercise, intermittent claudication limiting exercise


Interventions12 week program including:

- Exercise training (strength training, backwards/sideways walking, endurance training): 3 times per week for 1 hour during 12 weeks. Patients were encouraged to train at home

- Occupational therapy: 2 group sessions

- Education: 12 sessions, including proper administration, inhalation techniques, psychological education, socioeconomic problems and nutrition

- Smoking cessation: free nicotine patches, education

Included HCP: practice nurse, physiotherapist, dietician, psychologist, occupational therapist, social worker, physician


OutcomesChronic Respiratory Disease Questionnaire (CRDQ), York Quality of Life Questionnaire (YQLQ), 6MWD, lung function, patient attendance, staff working hours


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The patients were randomly allocated to either an intervention or a control group"; no information on allocation procedure provided

Allocation concealment (selection bias)Unclear riskThe methods used to conceal the sequence of treatment group allocation were not available

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWe could not ascertain how and whether outcome assessors were blinded to treatment group assignment

Incomplete outcome data (attrition bias)
All outcomes
High riskHigh drop-out rate (31%) and no intention-to-treat analysis

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Bourbeau 2003

MethodsRCT; follow-up: 12 months; control group: usual care


ParticipantsEligible: 469

Randomized: 191

Completed: 165

Mean age: I: 69 yrs; C: 70 yrs

Sex (% male): I: 52%; C: 59%

Inclusion criteria: stable COPD with at least one hospitalisation for an exacerbation in preceding year, age ≥ 50 yrs, pack yrs ≥ 10 yrs, FEV1% predicted (post-bronchodilator): 25% to 70%, FEV1/VC < 70%

Major exclusions: no previous diagnosis of asthma or left congestive heart failure, terminal disease, dementia, uncontrolled psychiatric disease, no pulmonary rehab < 1 yrs ago, no long-term facility stays


InterventionsA disease-specific self management program (Living Well with COPD) of 7 to 8 weeks of follow-up including:

- Individual sessions of education by an experienced health professional at the patient's home

- Content of education: COPD knowledge, breathing and coughing techniques, energy conservation during day-by-day activities, relaxation exercises; preventing and controlling symptoms through inhalation techniques, understanding and using a plan of action for acute exacerbation, adopting a healthy lifestyle, leisure activities and travelling, a simple home exercise program and long-term home oxygen therapy

- An action plan for acute exacerbations was customized for each patient

Intensity: education 1 hour per week during 7 to 8 weeks, follow-up first 2 months weekly telephone calls, then once a month a telephone call. Exercise evaluation (not mandatory): 3 times per week, 30 to 45-min/session + exercise teaching

Included HCP: nurse, physiotherapist, physician, pulmonologist


OutcomesSGRQ, exacerbations, spirometry, FEV1 (L), forced vital capacity, hospital admissions, symptoms, emergency room visits, outpatients visits, 6MWT, walking distance


NotesMain component of program: self management (including action plan)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients underwent randomisation with the use of a central computer-generated list of random numbers. Randomization was stratified per centre and in blocks of 6, and patients were assigned to the self management program (intervention group) or to usual care."

Allocation concealment (selection bias)Low riskQuote: "The blocking factor was not known by the investigators or their staff in each participating centre"

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "Since a double-blind design was impossible ..."

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: ".. an independent evaluator unaware of the patient assignment was responsible for the evaluation process in each centre. The evaluator was cautioned not to ask about the workbook modules and types of contact".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "An intention to treat analysis included all available study patients".

Selective reporting (reporting bias)High riskData on the 6MWD not presented, but only stated as "not statistically significant", and authors can not provide us with additional data

Boxall 2005

MethodsRCT; follow-up 12 weeks; control group: usual care


ParticipantsEligible: not clear

Randomized: 60

Completed: 46

Mean age I: 78 yrs; C: 76 yrs

Sex (% male): I: 48%; C: 65%

Inclusion criteria: diagnosis of COPD by a respiratory specialist, age > 60 yrs, dyspnoea on exertion, live locally, motivated to exercise daily unsupervised, stable for 2 weeks, functionally housebound

Major exclusions: attending outpatient based PR, restricted shoulder movement, living in nursing home, previous lung volume surgery, pain limiting mobility


Interventions12 week program including:

- Exercise consisting of walking (level 1 to 10) and arm exercises (1 to 18) + education sessions. Patients were required to carry out exercise daily. Weekly physiotherapy visits were scheduled for the first 6 weeks, and then visits were made until week 12 of the program. Visits were used to monitor exercise performance, progress exercises, retest 6MWT at regular intervals (weeks 1, 4, 6, 8 and 12 of the program) and provide encouragement to patients

- Educational sessions for patients and carers were conducted by physiotherapists, nurses and occupational therapy staff in their homes. Those sessions covered: anatomy and physiology of the lungs, use of respiratory devices, medications, breathing techniques, secretion removal techniques, energy conservation, use of adaptive aids and stress management. Patients received on average 11 home visits during the program

Included HCP: physiotherapists, nurses, occupational therapist


OutcomesHealth status: SGRQ, 6MWD, hospital admissions, average length of stay, dyspnoea Borg Scale


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomised to equal groups using computer-generated random numbers".

Allocation concealment (selection bias)Low riskQuote: "Random number were coded into opaque envelopes by a person independent from the study, they retained the envelopes until initial assessment was completed."

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "Neither assessors nor participants were blinded to group assignment in this study"

Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: "Neither assessors nor participants were blinded to group assignment in this study"

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced in numbers (23/23 analyzed in both groups) across intervention and control group, with similar reasons for missing data across groups

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Cambach 1997

MethodsRCT with cross-over design; follow-up 6 months; control group: drug treatment only


ParticipantsEligible: 89 (asthma and COPD)

Analyzed: 23 (COPD)

Mean age I : 62 yrs, C: 62 yrs

Sex (% male): I: 47%, C: 75%

Diagnosis of asthma or COPD according to guidelines, evidence of dyspnoea and decreased exercise tolerance as a result of obstructive lung disease, 18 to 75 yrs, ability to travel independently to the physiotherapy practice, medication prescribed by a pulmonary physician, motivation to improve self care, informed consent

Major exclusions: 1) manifest cardiac complaints, 2) hypercapnia and/or hypoxia


Interventions12 weeks intervention including:

Exercise group sessions of 3 to 4 participants including techniques of breathing retraining and evacuation of mucus, exercise training, patient education, relaxation techniques and recreational activities. Training was 3 days a week for 90 minutes. Exercise training was performed twice a week on a cycle ergometer and by stair-walking. Recreational activities were once a week for 45 min. Education sessions were every week for 45 min

Included HCP: nurse, physiotherapist


Outcomes6MWT, incremental cycle ergometer test, CRQ


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "block randomisation procedure; four closed envelopes for condition RC and four closed envelopes for condition CR"

Allocation concealment (selection bias)Low riskQuote: "Four closed envelopes"

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
High riskOutcome assessors not likely to have been blinded to intervention, as patients were tested for exercise capacity in their practices, by their treated physiotherapist, who was probably not blinded to group allocation.

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: “Data obtained from patients who did not return for one or more of the assessments (i.e. baseline (t0), after 3 months (t3) and/or after 6 months (t6), or patients who were not measured within 3 weeks (from t0, t3 and t6) were excluded from data analysis". Comment: exclusion of non-responders may have affected outcome data

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Dheda 2004

MethodsRCT; follow-up 6 months; control group: primary care follow-up


ParticipantsEligible: 33

Completed: 25

Mean age I: 68 yrs, C: 71 yrs

Sex (% male) both groups: unknown

Diagnosis COPD according to British Thoracic Society guidelines, patients with a first admission to hospital, with progressive symptoms, a smoking history of > 20 pack-years

Major exclusions: another dominant medical condition, a mandatory reason for hospital follow-up


InterventionsIntervention program of 6 months

A respiratory nurse and/or chest physician reviewed the intervention group at least 4 times in the 6 month period (at 6, 8, 12 or 16 weeks). The following interventions were made at some or all of these visits: spirometry with reversibility, review of inhaler technique and peak flow diary, ambulatory oxygen assessment, smoking cessation advice, steroid trial, nebuliser assessments, review of medication, advice about nutrition and exercise, and introduction to a patient support group

Included HCP: nurse, chest physician


OutcomesSGRQ, SF-36


NotesMain component of program: structured follow-up with nurse/GP


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSequence generation not reported

Allocation concealment (selection bias)Unclear riskThe methods used to conceal the sequence of treatment group allocation were not available

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blind to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported and therefore unclear who scored outcome assessments (patients, caregivers, outcome assessors?)

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot clear whether the results in SGRQ were described in the total population, as well as in the patients who withdrew (n = 8) from the study

Selective reporting (reporting bias)High riskNot all outcome measurements are given in measures but only reported as "there was no significant difference at 6 months in FEV1"

Engstrom 1999

MethodsRCT; follow-up 12 months; control group: usual outpatient care


ParticipantsEligible: 58

Randomized: 55

Completed: 50

Mean age I: 66 yrs, C: 67 yrs

Sex (% male) I: 54%, C: 50%

Clinical diagnosis of COPD, developing after at least 10 yrs of smoking, FEV1 < 50%, debut of symptoms after 40 yrs of age, dyspnoea mainly elicited by exercise or infections, no allergy

Major exclusions: disabling or severe diseases, co-existence of other causes of impaired pulmonary function


Interventions12 months rehabilitation program including:

- Exercise training sessions (bicycle, arm and breathing techniques), 2/week for 6 weeks, once weekly for 6 weeks, once every second week for 6 weeks and then once a month for remaining period. Every session: 45 min. Furthermore, instructions for daily walks and an individualized daily 30-min home-training program

- Individualized educational program with outpatient team (nurse and physician) on visit every 3 months

- Occupational therapist gave 2 group sessions about energy saving techniques and 2 global education sessions

- Dietician gave information about nutrition in COPD patients and intervened in malnutrition

Included HCP: physiotherapist, nurse, physician, dietician, occupational therapist


OutcomesSGRQ, 6-MWD, W-max, days in hospital, SIP, Mood Adjective Check List (MACL)


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information reported

Allocation concealment (selection bias)High riskQuote: "Patients with COPD were recruited consecutively and, when a sufficient number had been collected, randomised to produce a rehab group and a control group of equal size."

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All the physiological and QOL assessments were blinded, except the walking test, which was performed by the nurse in the rehabilitation team"

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced in numbers across intervention and control group (2 versus 3 persons)

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Farrero 2001

MethodsRCT; follow-up 12 months; control group: usual care


ParticipantsRandomized: 122

Completed: 94

Mean age I: 69 yrs, C: 69 yrs

Clinical diagnosis of COPD, requiring oxygen for at least 6 months, with willingness to participate in a hospital based home-care program, and with residence within easy reach of the hospital


InterventionsHospital based home-care program of 12 months with the aim of combining home-care management and easy access to hospital resources. Program included:

- Monthly telephone calls and 3-monthly home visits from a nurse, working closely with a physician. Patients could also request with an immediate response, which varied according to a home visit, a hospital visit, telephone advice or a control visit.  

Included HCP: nurse and physician


OutcomesCRQ, spirometry, mortality, hospital admissions, hospital days, ED visits


NotesMain component of program: structured follow-up with nurses


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "After this initial evaluation, informed consent was obtained and patients were allocated randomly to the HCP treatment group or to the control group". Comment: unclear if patients were randomised by sequence generated or based on, for example, date of admission

Allocation concealment (selection bias)Low riskQuote: "Codes of randomisation were kept in sealed envelopes"

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: "Patients in the control group were evaluated by the HCP team at the outpatient department in the initial visit, and after 1 year." Comment: as the HCP team was the intervention team and was not blinded to which group a patient was randomised, it is likely that assessment can be influenced by no blinding of the outcome assessor

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "Quality of life was investigated in the first 40 consecutive patients included in the study (..) applied before the study and after 3 months and 12 months." Comment: reason for missing outcome data likely to be related to true outcome, with imbalance in numbers

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Fernandez 2009

MethodsRCT; follow-up 12 months; control group: education (mono-disciplinary intervention)


ParticipantsEligible: 50

Randomized: 50 (I: 30; C: 20)

Mean age: 66 yrs, C: 70 yrs

Sex: 100% male (both groups)

Inclusion criteria: GOLD 4 patients, younger than 80 yrs of age, stable COPD, defined as a period of 2 months without any exacerbations, defined as signs of acute dyspnoea requiring medical attention, changes in the quantity and characteristics of sputum, an increase in pulmonary noise or an increase in the necessity for medication, the correct administration of pharmacological treatment according to GOLD, home treatment with oxygen for at least 6 months prior to the commencement of the study

Major exclusions: severe cardiovascular pathology, unstable angina, acute myocardial infarction, cerebral vascular accident, or physical or psychological disorder that impede the practice of physical exercise


InterventionsRehab program of 11 months

At the start: 2 one-hour sessions of respiratory re-education in the hospital, where exercises at home were taught

Home-rehab program :

- 1 hour of exercise per day (respiratory reeducation, muscular inspiratory training, muscular training of upper and lower limbs)

- First 2 months: attendance of physiotherapist at home (who visited twice monthly for 1 hour)

- Month 2 to 9: single monthly visits physiotherapist, included resistance training, respiratory reeducation, isotonic training, training of respiratory muscles

- 3 respiratory education sessions by nursing staff (handling of inhalers, knowledge of the illness, what to do in the event of attack)

Included HCP: nurse, physiotherapist


OutcomesPulmonary function, SGRQ, 6MWD


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "50 patients were prospectively randomised to block of 5 patients and randomly divided into 2 groups."

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-out rates between groups comparable

Selective reporting (reporting bias)Low riskAll outcomes in methods section provided

Gottlieb 2011

MethodsRCT; follow-up: 18 months; control group: usual care


ParticipantsEligible: 133

Randomized: 61

Completed: 26

Mean age I: 74 yrs, C: 73 yrs

Sex (% male): I: 32%, C: 35%

Inclusion criteria: a diagnosis of moderate COPD, FEV1/FVC < 0.7 and 50% ≤ FEV1 < 80% with motivation for pulmonary rehabilitation

Exclusion criteria:
1. Co-morbidity contraindicating rehabilitation

2. Participation in PR within the last year

3. Cognitive disorders limiting the ability to participate in physical training and educational sessions


InterventionsProgram of intensive training for 7 weeks, with maintenance program for 6 months, including:

- Intensive 7-week physical training and educational phase led by a multidisciplinary team. Furthermore, smoking cessation counseling given on an individual basis and a dietary intervention consisted of group cookery classes and individual sessions

- Final interview following completion of the program, in which participants' achievements were compared to the original goals

- Maintenance program for 6 months, including a 90-min monthly session focusing on ways of incorporating exercise in daily life, and 2 sessions on exercise activities in the local community, and another 2 sessions on exercise as well as on repetition of relevant topics

Included HCP: multidisciplinary team, not further specified. Authors were unreachable for further information.


OutcomesSGRQ, 6MWD, MRC, Borg dyspnoea scale, Sit-to-Stand test


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Subjects were randomised 1:1 to pulmonary rehabilitation and control"

Allocation concealment (selection bias)Low riskQuote: "Randomization was performed using sealed opaque envelopes randomly assigned to participants"

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWe could not ascertain how and whether outcome assessors were blinded to treatment group assignment

Incomplete outcome data (attrition bias)
All outcomes
High riskDrop-out rate equally divided: 39% intervention group, 23% control group

Selective reporting (reporting bias)High riskResults on MRC Dyspnea Scale not reported in results section

Güell 2000

MethodsRCT; follow-up: 24 months; control group: usual care


ParticipantsEligible: 65

Randomized: 60; I: 30, C: 30

Completed (24 months): 47 (I: 23; C: 24)

Mean age I: 66 yrs, C: 64 yrs

Sex (% male) both groups: 100%

Inclusion criteria: age ≤ 75 years, FEV1 < 70%, FEV1/FVC < 65%, PaO2 > 55 mm Hg at rest with no indication for prescribing home oxygen therapy

Major exclusion criteria: clinically apparent heart disease, bone or joint disease

Exacerbation or hospitalisation in previous month


Interventions6 months intensive rehabilitation program, followed by a 6-month maintenance program

- First 3 months: 2 30-min sessions each week: breathing retraining, combined with a low-level home exercise program. If indicated, patients also received chest physiotherapy, which involved teaching effective cough and postural drainage. Patients attended educational sessions on the anatomy and basic physiology of the respiratory system as well as on the nature of their disease and of PR

- Month 3 to 6: exercise training program of 5 30-min sessions weekly on a stationary cycle ergometer. During this period, patients also began a program of home exercise with either 30 min of pedaling on a stationary cycle or 1 h of walking

- Month 6 to 12: single weekly session in groups during which they performed exercises for breathing and leg-arm co-ordination

- Month 12 to 24: instructed to do home exercises without supervision

Included HCP: nurse, physiotherapist, pulmonologist


OutcomesLung function, 6MWD, cycle ergometer, VAS, MRC, CRQ, exacerbations, hospital admissions


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Randomization was done at inclusion of consecutive patients"

Allocation concealment (selection bias)High riskQuote: "Randomization was not concealed"

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "same physician saw patients at each visit". It was unlikely that the health care professional was blinded to treatment group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The technicians, who collected data for outcome measures at every visit, as explained below, were blinded to a patient’s allocation to PR or control groups".

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Güell 2006

MethodsRCT; follow-up: 4 months; control group: usual care


ParticipantsRandomized: 40; I: 20; C: 29

Completed: 35; I: 18, C: 17

Mean age: I: 68 yrs, C: 66 yrs

Male: I: 88%, C: 100%

Inclusion criteria: age ≤ 75 years, FEV1 < 70%, FEV1/FVC < 65%, PaO2 > 55 mm Hg at rest with no indication for prescribing home oxygen therapy

Exclusion criteria: psychiatric disturbances, no heart, bone or joint disease. Exacerbation or hospitalisation in previous 2 months


InterventionsPR program of 4 months, including:

- First 2 months: 2 30-min sessions each week, including relaxation techniques, breathing retraining, and chest wall and abdominal muscle wall work. Patients attended 4 45 to 60-min educational sessions

- Month 2 to 4: 5 30-min sessions weekly exercise training on cycle ergometer

Included HCP: nurse, physiotherapist, pulmonologist


OutcomesMillon Behavior Health Inventory (MBHI), Revised Symptom Checklist (SCL-90-R), 6MWD, CRQ


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Randomization was done at inclusion of consecutive patients"

Comment: it is not clear how the sequence was generated

Allocation concealment (selection bias)High riskQuote: "Randomization was not concealed"

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "Neither patients nor clinicians were blinded to allocation"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "the technicians who collected the data were blinded to patient allocation, as were the data analysts until the analysis was deemed complete"

Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up comparable between groups (2 versus 3)

Selective reporting (reporting bias)Low riskAll outcomes reported

Koff 2009

MethodsRCT; follow-up 3 months; control group: usual care


ParticipantsEligible: 40; randomised: 40; completed 38

Mean age I: 67 yrs, C: 65 yrs

Sex (% male): I: 45%, C: 50%

Inclusion criteria: clinical diagnosis of COPD, GOLD 3+4, with a telephone land line

Exclusion criteria: active treatment for lung cancer, illiteracy, non-English speaking, inability to complete a 6MWD


Interventions3-month intervention program, including:

- Disease-specific education, by respiratory therapist at enrolment and daily by Health Buddy System (tele healthcare) Education included disease description, medications and their use, nutrition, breathing techniques

- Teaching of self management skills (use of an oximeter and increased awareness of clinical changes/problems). Patients could contact the co-ordinator in case of deterioration

- Patients were remotely monitored 5 days per week with the Health Buddy system for change in symptoms, saturation, 6MWD and lung function. The study co-ordinator reviewed these results and patients were contacted if they were at high risk for exacerbation. They started exacerbation management or had contact with respiratory physician/GP

Included HCP: physician, pulmonologist


OutcomesSGRQ, 6MWD, exacerbations, hospitalizations, ED visits, equipment satisfaction, number of calls


NotesMain component of program: self management


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients randomly selected their group assignment (by choosing a blinded envelope that contained a group indicator"

Allocation concealment (selection bias)Low riskQuote: "patients randomly selected their group assignment (by choosing a blinded envelope that contained a group indicator"

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "because of the type of intervention, it was not possible to blind the subjects or investigators as to whether they were randomised to the treatment or control arms of the trial"

Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: "primary end-point was collected by the coordinator, and analysed by R.H. Jones." The co-ordinator was also responsible for the intervention and was therefore not blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-out rates balanced in numbers across groups

Selective reporting (reporting bias)Low riskAll outcomes reported

Littlejohns 1991

MethodsRCT; follow-up 12 months; control group: usual care


ParticipantsEligible: 166

Randomized: 152; I:73, C: 79

Completed (12 months): 133; I: 68, C: 65

Mean age I: 63 yrs, C: 63 yrs

Sex (% male): I: 67, C: 63

Inclusion criteria: COPD diagnosed by spirometry, according to guidelines. Inclusion criteria: age 30 to 75 yrs, prebronchial FEV1 % < 60%, stable state, no change in medication for at least 6 weeks before recruitment, no other major disease


InterventionsIntervention group received the care of the respiratory health worker while continuing with their routine outpatient appointments during 12 months. The health worker provided:

- Health education directed at the patient and the primary care team

- Monitoring of treatment compliance and optimizing treatment by ensuring correct inhalation techniques and supervision of domiciliary oxygen

- Monitoring of the results of spirometry and the patients's symptoms to enable acute exacerbations and worsening heart failure to be detected and treated early

- Liaison between GP and hospital-based services (including domiciliary physiotherapy services and social services)

Included HCP: GP, respiratory health worker


OutcomesMortality, spirometry, 6MWD, step test, MRC chronic bronchitis questionnaire, HADS, SIP, hospital admissions, drug prescriptions, visits to GP or clinic, satisfaction


NotesMain component of program: structured follow-up with respiratory health worker


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "random numbers were generated by tables in permuted blocks of four, stratified by age and sex"

Allocation concealment (selection bias)Low riskQuote: "the groups to which successive patients were to be allocated were noted in sealed, numbered envelopes, which were kept centrally"

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "the physician was aware which group the patient was in"

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-out rates comparable between groups

Selective reporting (reporting bias)High riskThe outcomes on the MRC chronic bronchitis questionnaire are not reported

Mendes 2010

MethodsRCT; follow-up 12 weeks; 2 intervention groups (at home PR versus outpatient PR), 1 control group: usual care


ParticipantsEligible: 117

Randomized: 117 (Intervention I: 42; Intervention II: 46; Control: 29)

Analyzed: 85 (Intervention group I: 33; Intervention II: 23; Control: 29)

Mean age: Intervention I: 66 yrs, Intervention II: 71, Control: 71

Sex (% male): Intervention I: 82%, Intervention II: 83, Control: 66%

Inclusion criteria: diagnosis of COPD according to GOLD, stable at inclusion

Major exclusions: hospitalisation or COPD instability, presence of neuromuscular disease, associated respiratory disease, orthopedic or neurological disease that affected gait, recent impairment due to co-morbidities, such as myocardial infarction, heart failure, stroke or neoplasm; prior pneumonectomy or other thoracic surgery


InterventionsIntervention program of 3 months performed either at home or at the outpatient clinic:

- Both intervention groups received 1 session of education about COPD, treatment and relevance of PR

- Both intervention groups trained 3 mornings a week for 3 months, with aerobic and strengthening exercises. Patients in the outpatient clinic trained under supervision; patients who trained at home were instructed in the clinic and received support by telephone calls

Included HCP: physiotherapist, pulmonologist


Outcomes6-MWD, MRC, FEV1, BMI, all included in BODE index (body mass, obstruction, dyspnoea, exercise tolerance- index)


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were randomised electronically by a computer"

Allocation concealment (selection bias)High riskDistribution of patients was unequal: 42 in at-home group, 46 in outpatient group versus 29 in control group

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "Two duly trained health care professionals were responsible for the evaluations, which were performed by the same evaluators for all patients". Comment: not clear if these professionals were blinded to group allocation.

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "19 out of 46 of out-patient intervention group were lost to follow up, compared to 7 out of 42."

Comment: the reasons for missing outcome data likely to be related to true outcome, with imbalance in numbers of missing data

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Rea 2004

MethodsCluster RCT; follow-up: 12 months; control: conventional care


ParticipantsEligible: 158

Randomized: 135; I: 83, C: 52

Completed: 117

Mean age of both groups: 68 yrs

Sex (% male) of both groups: 41.5%

Inclusion criteria: COPD diagnosed by ICD-9-CM codes and GP records for a clinical diagnosis of moderate to severe COPD.

Major exclusion criteria for patients: chronic asthma, bronchiectasis, comorbidity more significant than COPD, unable to give informed consent, prognosis < 12 months, long-term oxygen therapy or too unwell, deceased

Major exclusion criteria GP: no longer enrolled with participating GP practice or moved out of area, unable to contact patient, insufficient practice nurse resource


InterventionsA chronic disease management program was implemented including:

- An action plan, which was implemented by patient's own GP and practice nurse, with advice from the respiratory nurse and specialist physician. The plan comprised a timetable for regular maintenance checks and set achievable goals for lifestyle changes

- Patients visited the nurse monthly, the GP 3 monthly and at other times if worsening symptoms demanded more visits

- Patients received education about smoking cessation, medication. Annual influenza vaccination and pulmonary rehabilitation were recommended

Included HCP: GP, nurse, pulmonologist


OutcomesHealth status, SF-36, CRQ, shuttle walk test, spirometry, hospital admissions, medication, courses of oral steroids, courses of antibiotics, smoking cessation

Randomization at cluster level, analysis at patient level


NotesMain component of program: self management/action plan and structured follow-up by GP/nurse


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Practices were randomised, using a set of computer-generated numbers"

Allocation concealment (selection bias)Unclear riskNo information available

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and health care providers not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
High riskThe health care providers involved in the program administered outcome measurements at visit

Incomplete outcome data (attrition bias)
All outcomes
Low riskMissing outcome data balanced between groups, with similar reasons for missing data across groups

Selective reporting (reporting bias)Low riskAll outcomes reported

Recruitment biasLow riskQuote: "Written information about the trial was provided to patients and consent was obtained before patients knew whether they belonged to an intervention or control practice"

Baseline imbalance between groupsHigh riskNo stratified or pair-matched randomisation was used, resulting in baseline imbalance of 99 eligible patients in the intervention group and 59 patients in the control group

Loss to follow-up of clustersHigh riskQuote: "After randomisation, two practices declined to participate and in three, changes of either GP's or practice nurses prevented participation before enrolment had begun"

Adequate analysis methods for CRTHigh riskInadequate methods of analysis: randomisation done at level of GP practice, analysis performed at level of patients

Rice 2010

MethodsRCT; follow-up 12 months; control: single intervention (one page of information and telephone number)


ParticipantsEligible: 743

Randomized: 743; I: 372, C: 371

Completed: 743

Mean age I: 69 yrs, C: 71 yrs

Sex (% male) I: 98%, C: 98%

Inclusion criteria: COPD diagnosed by spirometry. Inclusion criteria: at high risk for hospitalisation as predicted by one or more of the following during the previous year: hospital admission or ED visit for COPD, chronic home oxygen use, or a course of systemic corticosteroids for COPD.

Major exclusion criteria: any condition that might preclude effective participation in the study or that would reduce life expectancy to less than a year, or no access to a telephone


InterventionsChronic disease management program of 12 months, including:

- Group session (1-1, 5-hour): general information about COPD, medication, smoking cessation, vaccinations and exercise

- All patients received an individualized written action plan including prescriptions for prednisone and antibiotics with contact information with a case manager. Participants were in possession of action plan medications at all times and were to refill prescriptions immediately upon initiating the action plan
- The case manager made monthly telephone calls

Included HCP: case manager, pharmacist


OutcomesED and hospital admissions related to COPD, SGRQ, mortality, number of telephone contacts


NotesMain component of program: self management/action plan


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "We assigned subjects in equal proportions to each of the two treatment arms by permuted Block randomisation"

Allocation concealment (selection bias)Unclear riskInformation not available

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Blinded pulmonologists independently reviewed all discharge summaries and ED reports and assigned a primary cause for each"

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll outcome data reported. Concordance between outcome observers was tested in subset and was 96.5%

Selective reporting (reporting bias)Low riskNo missing outcome data

Smith 1999

MethodsRCT; follow-up 12 months; control: usual care


ParticipantsEligible: 105

Randomized: 96; I: 48, I: 48

Completed: 36 (data only completed in Intervention group)

Mean age I: 70 yrs, C: 70 yrs

Major inclusion criteria: COPD diagnosis according to guidelines, age > 40 years, FEV1/FVC less than 60%, in a stable state, have a carer involved in their management, be able to speak and read English and give written consent

Major exclusion criteria: no other active illness


InterventionsAn intervention of 12 months including:

- Follow-up planning of in- and outpatients with a nurse in shared care approach with GP and medical staff. Goals for discharge and nurses discussed with the GP the needs and facilitated involvement of domiciliary service. Goals were inserted into patients' notes

- During 12 months every 2 to 4 weeks there was a home visit including education, spirometry, optimal medication, exacerbation management, smoking cessation and fitness advice

Included HCP: nurse, GP, social worker, hospital medical officer


OutcomesCOOP (HRQoL), mortality, hospital admissions, lung function


NotesMain component of program: structured follow-up with nurses/GP


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were randomised as they were enrolled, following discharge from hospital (..), into the HBNI or control groups from two lists of randomly computer generated numbers"

Allocation concealment (selection bias)Low riskQuote: "patients were randomised as they were enrolled, following discharge from hospital"

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "This study was unblinded"

Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: "This study was unblinded"

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "Attempts to perform questionnaires in the control subjects were unsuccessful due to a combination of (I) these subjects perceived no immediate benefit of the trial; and (ii) the burden of participating in a study"

Comment: no outcomes reported in control group

Selective reporting (reporting bias)High riskOne or more primary outcomes in the review (COOP, spirometry) are reported incompletely so that they cannot be entered in a meta-analysis

Sridhar 2008

MethodsRCT; 104 weeks; control group: usual care


ParticipantsEligible: 297

Randomized: 122 (I: 61; C: 61)

Mean age both groups: 70 yrs

Sex (% male): both groups: 49%

Inclusion criteria: diagnosis of COPD and admitted between 2000 and 2004 with an acute exacerbation of COPD

Exclusion criteria: significant comorbidity (severe heart disease or cancer, or any condition that would preclude participation in the physical therapy component of a PR program)


InterventionsIntervention program of 24 months:

- Patients started with a PR program for 4 weeks, including general education about disease and treatment, and physical training program

- After 4 weeks, patients received a home visit, including a written COPD action plan for exacerbations. The GPs provided medication

- Patients received monthly telephone calls and a home visit every 3 months until 24 months follow-up. They reinforced advice regarding treatments, smoking cessation, the need to continue their exercise therapy and reinforced the self management education

Included HCP: GP, nurse, physiotherapist


OutcomesCRQ, mortality, exacerbations, hospital admissions, lung function  


NotesMain component of program: exercise + action plan


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "122 patients were suitable and were recruited and randomised by the use of random numbers to the intervention and control group"

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-out rates comparable between groups

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Strijbos 1996

MethodsRCT; 18 months; intervention group 1: hospital based PR, intervention group 2: home based PR, control group: usual care


ParticipantsEligible: 50

Randomized: 50; I group 1: 18, I group 2: 17, C: 15

Completed: 41

Mean age I 1: 61 yrs, I 2: 60 yrs, C: 63

Sex (% male): I 1: 93%, I2: 80%, C: 80%

Inclusion criteria: diagnosis COPD as evidenced by history, physical examination, chest radiograph and pulmonary function test results, PaCO2 at rest of less than 6.5 kPa, and PaO2 at rest of more than 7.5 kPa; FEV1 < 65% predicted

Major exclusion: ischaemic heart disease, musculoskeletal disorders or other disabling diseases that could restrict the rehab therapy


Interventions12-week rehabilitation program:

- Both groups: exercise twice a week during 12 weeks, 1 hour each session

- In the hospital group exercise was administered by a physiotherapist (1 hour twice a week) and patients were instructed to practice daily exercise for at least 15 min. Patient education 3 times/1 hour by a respiratory nurse

- In the home-care group, exercise was carried out at home by the local physiotherapist and home-care nurse, under supervision of the GP. Patients received an individualized exercise program from physiotherapist of 30 minutes (24 sessions), and were instructed to exercise at least 15 to 30 min. They received 3 times education by a nurse and 3 times a visit by the physician or GP

- Both groups were intended to continue exercise daily at home, after completion of the program

Included HCP: nurse, physiotherapist and GP or pulmonologist


Outcomes4minute walking test (4MWT), cycle test (measured as maximum watts, W-max) and interviews


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomly assigned to intervention or control group". Information is insufficient to be confident that the allocation sequence was genuinely randomised

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWe were unable to ascertain whether outcome assessors were blinded to treatment group assignment

Incomplete outcome data (attrition bias)
All outcomes
Low riskComparable low drop-out rates in both groups

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Theander 2009

MethodsRCT; 3 months; control group: usual care


ParticipantsEligible: 30

Randomized: 30; I:15, C:15

Completed: 26

Mean age I: 66; C: 64 yrs

Sex (% male): I: 25%; C: 71%

Inclusion criteria: diagnosis of COPD: according to British guidelines, with FEV1 between 60% to 25% post bronchodilation, and age ≤ 75 yrs

Major exclusions: disabling or severe disease other than COPD, impaired pulmonary function due to other disease, long-term oxygen therapy, alpha1-antitrypsine deficiency, cancer disease, untreated obstructive sleep apnea syndrome and no COPD-related symptoms affecting their activities of daily life


InterventionsMultidisciplinary program:

- Physiotherapy 2 days per week (1 hour) for 12 weeks, with additional home training after q month
- Dietician support (3 sessions of 1 hour): education and, if needed, additional nutritional supplementation

- Occupational therapist: education and teaching

- Nurse (two sessions of 1 hour): education and self care advice

Included HCP: physiotherapist, dietician, occupational therapist, nurse


OutcomesBMI, FEV1, fatigue impact scale, 6MWD, grip strength, SGRQ, SF-36


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "For the randomisation we prepared 80 sealed opaque envelopes with assignment information: 40 for the rehabilitation group and 40 for the control group".

Allocation concealment (selection bias)Low riskQuote: "Randomization procedures were performed by an independent person from the research group, who took a random envelope from the prepared box with sealed envelopes".

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: "The data collection was performed by members of the rehabilitation group. The data collection was not blinded to the data collector"

Incomplete outcome data (attrition bias)
All outcomes
Low riskComparable drop-out rates

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Trappenburg 2011

MethodsRCT; follow-up 6 months; control group: usual care


ParticipantsEligible: 391

Randomized: 233, I: 111, C: 122

Completed (6 months): 193; I: 91, C: 102

Mean age: I 66 years, C: 65 years

Sex (% male): I: 65% C: 69%

Inclusion criteria: COPD diagnosed by spirometry, age > 40 years, smoking history of > 20 years or 15 pack-years, diagnosis of COPD as a major functionally limiting disease, current use of bronchodilator therapy

Major exclusions: primary diagnosis of asthma, primary diagnosis of cardiac disease, presence of disease that could either affect mortality or participation in the study


Interventions6-month self management/action plan program:

- Individualized action plan with treatment prescriptions related to a color-coded symptom status to enhance an adequate response to periods of symptom deterioration

- The action plan included ongoing support of a case manager, in concordance with a GP/respiratory physician. There were 2 reinforcement sessions by telephone at 1 and 4 months

Included HCP: GP, nurse, pulmonologist


OutcomesExacerbation rates and recovery time, SGRQ, HADS, courses of antibiotics, corticosteroids, ED visits for exacerbation, CCQ score during exacerbation


NotesMain component of program: self management/action plan


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomisation was carried out using the minimization technique to balance the control and intervention groups for centre and gender"

Allocation concealment (selection bias)Low riskQuote: "to conceal the assignment sequence, a central web-based service was used"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "an informed consent to postponed information procedure is used, keeping the patient unaware of the AP being the major study aim. This implies that all patients are informed about the fact that, besides the outcome assessment aiming at gaining more insight in daily symptom variations, the study has another purpose. Patients are told that they will be informed about this additional research question only after follow up because informing during recruitment would affect study results".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "investigators were blinded to allocation"

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "monthly discontinuation rates and reasons for withdrawal are comparable in both study arms"

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

van Wetering 2010

MethodsRCT; follow-up: 24 months, control group: usual care (pharmacotherapy according to guidelines, short smoking cessation advice by chest physician and recommendation to eat more in case of nutritional depletion)


ParticipantsEligible: 199

Randomized: 199; I: 102, C: 97

Completed 4 months: I: 87; C: 88

Completed 24 months: I: 77; C: 81

Mean age I: 66 yrs, C: 67 yrs

Sex: I: 71%; C: 71%

Inclusion criteria: diagnosis of COPD according to guidelines, other inclusion criteria: impaired exercise capacity, W-max < 70%, GOLD 2+3 and clinical stable at inclusion. Major exclusion criteria: prior rehabilitation and patients with serious co-morbidity that precluded exercise therapy were excluded


Interventions24-month program including:

- Intensive 4-month standardized, supervised physiotherapy 2/week (30 min), with home-based exercises

- Patients participated in an individualized education program

- All smokers were offered smoking cessation counseling

- Nutritionally depleted patients received counseling from a dietician

- During the 20-month active maintenance phase, patients were instructed to train at home and visited the physiotherapist once a month. Dietician support was continued

Included HCP: nurse, physiotherapist, dietician 


OutcomesSGRQ, total score and number of exacerbations, MRC dyspnoea scale, exercise performance (measured as maximum Watts: W-max), 6MWD, muscle strength, isometric quadriceps peak torque, maximal inspiratory mouth pressure, fat-free mass and lung function


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were randomised to INTERCOM or usual care using a computerised procedure with concealed patient allocation"

Allocation concealment (selection bias)Low riskQuote: "patients were randomised to INTERCOM or usual care using a computerised procedure with concealed patient allocation"

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "all outcome measurements were assessed single blind"

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe results were analyzed by intention-to-treat

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Wakabayashi 2011

MethodsRCT; follow-up 12 months; control group: single intervention (education)


ParticipantsEligible: 102

Randomized: 102; I: 52, C: 50

Completed: 85; I: 42, C: 43

Clinical diagnosis of COPD, > 65 years, exclusively visit the clinic with monthly scheduled appointments, have a history of cigarette smoking

Exclusion criteria: history of atopy or any apparent asthmatic features, were illiterate or had cognitive impairment score of less than 26 on MMSE, lived in a residential care facility or a nursing home, had exacerbations during preceding 3 months, or had other respiratory diseases such as bronchiectasis, any type of pulmonary fibrosis or congestive heart failure


InterventionsPatients underwent a program of educational sessions for 6 months, individually tailored according to their domain scores on the LINQ questionnaire, which was designed to assess the need for information from a patients’ perspective. The program was given by respiratory nurses and pulmonary physicians. There were six domains: 1) understanding of COPD, 2) pharmacological treatments, 3) exercise, 4) avoidance of exacerbations, including action plan with instructions in the event of exacerbations, 5) smoking cessation, 6) nutrition. All patients were provided with a booklet that was used during each session. After the intensive education period, each patient was followed up for 6 months in the same way as the patients in the usual care group

Included HCP: nurse, pulmonologist


OutcomesFEV1, MRC, SGRQ, 6MWD, Lung Information Needs Questionnaire (LINQ), BMI, BODE index (body mass index, dyspnoea, airflow obstruction, exercise capacity), Activities of Daily Living (ADL), co-morbidities, hospitalizations


NotesMain component of program: self management/action plan


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "a case manager independent of the study randomly assigned patients to either group I or group U using a computer-generated list"

Allocation concealment (selection bias)Low riskQuote: "Patients allocations were sealed in numbered envelopes by an independent evaluator, not involved in the interventions"

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "an independent evaluator, who assessed outcomes at the beginning of the study, after initial integrated education (6 months), and after follow-up period (6 months)"

Incomplete outcome data (attrition bias)
All outcomes
Low riskComparable drop-out rates between groups

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Wijkstra 1994

MethodsRCT; follow-up 12 weeks; control group: no treatment


ParticipantsRandomized: 45

Completed: 43 (I: 28; C: 15)

Mean age I: 64 yrs, C: 62 yrs

Sex (% male): I: 82%, C: 93%

Inclusion criteria: diagnosis of COPD with FEV1 % < 60%, FEV1/IVC < 50%

Exclusion criteria: evidence of ischaemic heart disease, intermittent claudication, musculoskeletal disorders or other disabling diseases that could restrict the rehab program


InterventionsIntervention program of 12 weeks:

- Patients were supervised by a multidisciplinary team: pulmonologist, physiotherapist, nurse, GP
- Patients visited physiotherapist twice a week for 12 weeks and the program consisted of conventional physiotherapy, upper limb training, inspiratory muscle training, exercise training. They had to practice twice a day for half an hour at home

- Furthermore, they received education at home from a nurse (once a month)

- They visited the GP once a month and he supervised clinical status and maintenance treatment

Included HCP: GP, physiotherapist, nurse


OutcomesLung function, CRQ, cycle ergometer test


NotesMain component of program: exercise


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were stratified for their FEV1 % predicted. After this stratification, the patients were randomly allocated"

Allocation concealment (selection bias)Low riskQuote: "(after randomisation), they were randomly allocated to one of three groups, each of 15 patients"

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants and treating therapists not likely to have been blinded to group allocation

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskWe could not ascertain how and whether outcome assessors were blinded to treatment group assignment

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 2 (out of 30) drop-outs in rehabilitation group versus no drop-outs in control group

Selective reporting (reporting bias)Low riskAll outcomes reported

Wood-Baker 2006

MethodsCluster-RCT; follow-up 12 months, control group: education + usual care


ParticipantsEligible: 218

Randomized: 138; I: 67, C: 72

Completed (12 months): 112; I: 54, C: 58

Mean age I: 69 yrs, C: 71 yrs

Sex (% male): I: 49%, C: 71%

Inclusion criteria: COPD diagnosed by spirometry, age > 50 yrs, tobacco smoking history of greater than 10 pack-years and FEV1 < 65% predicted

Exclusion criteria: nursing home residents


InterventionsControl + intervention group: COPD information booklet, individual education session with nurse. Intervention group: written self management plan, which was developed in consultation with their treating GP. Patients were encouraged to make early contact with their GP during an exacerbation

Included HCP: GP, nurse


OutcomesSGRQ, exacerbations (courses of antibiotics/prednisone), ED and hospital admissions, GP consultations, spirometry, mortality, physical exercise (pedometer)


NotesPrior to commencement of the randomisation process, only 50% of the included GPs attended one of a series of educational workshops on the management of COPD

Main component of program: self management/action plan


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Practices were randomised to the intervention or control group using a computer generated randomisation software package"

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskIt is not likely that participants and personnel have been blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "The baseline, 6- and 12-month assessments involved face to face contact with a research nurse at the GP's surgery or patients' home"

Incomplete outcome data (attrition bias)
All outcomes
Low risk13 intervention patients versus 14 control patients missing at 6 months, reasons similar"

Selective reporting (reporting bias)Low riskThe study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified

Recruitment biasLow riskNo information provided

Baseline imbalance between groupsHigh riskBaseline imbalance between groups

Loss to follow-up of clustersLow riskNo missing clusters

Adequate analysis methods for CRTHigh riskNo adjusting for cluster-randomized trials

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aimonino 2008Intervention duration less than 3 months

Bischoff 2012No multidisciplinary intervention

Carrieri 2005Active treatment in control group

Casas 2006Intervention duration less than 3 months

De Godoy 2003Active treatment in control group

Eaton 2009Intervention duration less than 3 months

Effing 2009Active treatment in control group

Efraimsson 2008Fewer than 2 different health care providers included

Elliott 2004Fewer than 2 different health care providers included

Garcia 2007Duration of intervention less than 3 months

Gohl 2006No multidisciplinary intervention and fewer than 2 components

Goldstein 1994Fewer than 2 components of intervention

Guell 2008Active treatment as control group

Hughes 2000No results solely for COPD

Liu 2006Not a RCT

Maltais 2008No usual care as control group

Martin 2004Fewer than 2 components of intervention

McGeoch 2006Fewer than 2 components of intervention

Monninkhof 2003No usual care as control group

Ries 2003Active treatment as control group

Soler 2006Active treatment as control group

Steele 2008Active treatment as control group

Zhou 2010COPD diagnosis was not inclusion criteria

 
Characteristics of studies awaiting assessment [ordered by study ID]
Baumann 2012

MethodsAim: to investigate whether relevant improvements in physical capabilities and quality of life in patients with chronic obstructive pulmonary disease (COPD) could be achieved by a long-term, low-intensity, once weekly rehabilitation program using limited resources. 100 patients with moderate to severe COPD were randomised to a continuous outpatient interdisciplinary
rehabilitation program or standard care

Participants100 patients with moderate to severe COPD

InterventionsPhysiotherapy-led supervised outpatient training sessions were performed once weekly in addition to educational elements

OutcomesOutcome measures at baseline and after 26 weeks were 6MWT, cycle ergometry and health-related quality of life

Notes

Fan 2012

MethodsA randomised, controlled trial comparing CCMP with guideline-based usual care
Setting: 20 Veterans Affairs hospital-based outpatient clinics

ParticipantsPatients hospitalised for COPD in the past year

InterventionsThe CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines

OutcomesThe primary outcome was time to first COPD hospitalisation. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge and self efficacy

Notes

Zwar 2012

MethodsCluster-randomized controlled trial with blinded outcome assessment of 44 general practices in south-western Sydney comprising 451 people with a diagnosis of COPD, conducted between 2006 and 2009

ParticipantsCOPD patients

InterventionsParticipants from intervention group practices were visited at their home by a registered nurse with specific training in COPD care who worked with the general practitioner, the patient and other health professionals to develop and implement an individualized care plan based on best-practice guidelines. Participants from control group practices received usual care

OutcomesThe primary outcome was disease-related quality of life measured using the St George's Respiratory Questionnaire (SGRQ) at 12-month follow-up. Other outcomes were overall quality of life, lung function, smoking status, immunization status, patient knowledge of COPD and health service use

Notes

 
Characteristics of ongoing studies [ordered by study ID]
Bower 2012

Trial name or titleA cluster randomised controlled trial of the clinical and cost-effectiveness of a 'whole systems' model of self management support for the management of long-term conditions in primary care: trial protocol

MethodsThe evaluation involves a large-scale, multi-site study of the implementation, effectiveness and cost-effectiveness of this model of self management support using a cluster-randomized controlled trial

ParticipantsPatients with 3 long-term conditions: diabetes, chronic obstructive pulmonary disease (COPD) and irritable bowel syndrome (IBS)

InterventionsThe implementation and evaluation of self management support through an evidence-based 'whole systems' model involving patient support, training for primary care teams and service re-organization, all integrated into routine delivery within primary care

OutcomesThe outcome measures include healthcare utilization and quality of life

Starting date

Contact informationTRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN90940049

Notes

Bunker 2012

Trial name or titleA pragmatic cluster randomised controlled trial of early intervention for chronic obstructive pulmonary disease by practice nurse-general practitioner teams

MethodsA pragmatic cluster-randomized trial will test the hypothesis that intervention by a practice nurse-general practitioner (GP) team leads to improved health-related quality of life and greater adherence with clinical practice guidelines for patients with newly diagnosed COPD, compared with usual care. 40 general practices in greater metropolitan Sydney Australia will be recruited to identify patients at risk of COPD and invite them to attend a case finding appointment. Practices will be randomised to deliver either practice nurse-GP partnership care, or usual care, to patients newly diagnosed with COPD

ParticipantsPatients with newly diagnosed COPD

InterventionsThe active intervention will involve the practice nurse and GP working in partnership with the patient in developing and implementing a care plan involving (as appropriate), smoking cessation, immunization, pulmonary rehabilitation, medication review, assessment and correction of inhaler technique, nutritional advice, management of psycho-social issues, patient education and management of co-morbidities

OutcomesThe primary outcome measure is health-related quality of life, assessed with the St George's Respiratory Questionnaire 12 months after diagnosis. Secondary outcome measures include validated disease-specific and general health-related quality of life measures, smoking and immunization status, medications, inhaler technique and lung function. Outcomes will be assessed by project officers blinded to patients' randomisation groups

Starting date

Contact informationTRIAL REGISTRATION: ACTRN12610000592044

Notes

Byrnes 2012

Trial name or titleCAPICHe

MethodsIntention-to-treat study applying a prospective, randomised design comparing usual care with extensive outreach to encourage use of telephone health coaching for those people identified from a risk scoring algorithm as having a higher likelihood of future health costs

ParticipantsThe trial population has been limited to people with one or more of the following selected chronic conditions: namely, low back pain, diabetes, coronary artery disease, heart failure and chronic obstructive pulmonary disease.This trial will enroll at least 64,835 sourced from the approximately 3 million Bupa Australia private health insured members located across Australia

Interventions

OutcomesThe primary outcome will be the total (non-maternity) cost per member as reported to the private health insurer (i.e. charged to the insurer) 12 months following entry into the trial for each person

Starting dateStudy recruitment will be completed in early 2012 and the results will be available in late 2013

Contact informationAustralian New Zealand Clinical Trials Registry
Reference: ACTRN12611000580976

Notes

Freund 2011

Trial name or titlePrimary care practice-based care management for chronically ill patients (PraCMan)

MethodsCluster-randomized controlled trial with primary care practices as unit of randomisation. Patients are randomised in clusters of 15 to 20 patients per practice. Each patient is assigned to a care management team consisting of 1 primary care practice and 1 healthcare assistant

ParticipantsPrimary care practices: participation of the practice in a centered care contract, at least 1 primary care practitioner, ability to perform on-site spirometry and home visits. Patients: suffering from type 2 diabetes mellitus, COPD, chronic heart failure or any combination, high risk for future hospitalisation, age 18 years or older. Major exclusions: active cancer disease, moderate to severe dementia, permanent residency in a nursing home, participation in a concurrent clinical trial, severe physical and mental disorders or other problems that hinder active participation in the intervention

InterventionsThe intervention consists of 3 elements: 1) assessment of medical/non-medical needs and resources, including for example allergies, nutritional problems, depressions, falls, physical activity, smoking status. 2) planning and setting long-term goals for care management, 3) monitoring and structured follow-up. Prior to the intervention, all case management teams will be trained

OutcomesHospitalizations, mortality, EQ-5D, SF-12, PACIC, PHQ9, MARS, RAPA, smoking status, self management, pharmacy data, healthcare costs, ADL, comorbidity, home visits, COPD exacerbations, BMI, dyspnoea, FEV

Starting dateJuly 2010

Contact informationtobias.freund@med.uni-heidelberg.de

NotesISRCTN56104508

Gomez 2006

Trial name or titleEfficacy of respiratory rehabilitation on patients with moderate COPD in primary care and maintenance of benefits at 2 years

MethodsRCT; 3 groups in parallel with blind evaluation. Control group: customary care. 56 patients per group are needed

ParticipantsPatients with a diagnosis of moderate COPD according to GOLD

Interventions3 groups: 1) pulmonary rehabilitation (educational sessions, respiratory physiotherapy, low-intensity physical exercise) for 12 weeks and program maintenance for 24 months; 2) pulmonary rehabilitation for 12 weeks without maintenance program, 3) control group

OutcomesQuality of life with Chronic Respiratory Questionnaire, 6MWD, Borg dyspnoea Scale, MRC Dyspnea Score, lung function

Starting dateFinished, results not yet published

Contact information

Notes

Jones 2009a

Trial name or titleEffect of a case management study on primary care use and prescribing for AECOPD

MethodsRCT

ParticipantsPatients admitted to hospital with an exacerbation of COPD

InterventionsIntensive case management (including hospital and home visits), exercise, education and access to support 7 days a week (phone line) and nurse/doctor review 5 days a week. Control group: usual care

OutcomesData on all GP and practice nurse visits to either surgery or home and prescriptions for antibiotics and steroids (including all primary and secondary care prescriptions) were collected during the 12-month study period

Starting date

Contact information

NotesResults submitted, not accepted yet

Kruis 2013

Trial name or titleRECODE

MethodsRECODE is a cluster-randomized trial with 2 years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomised to IDM or usual care

ParticipantsCOPD patients

InterventionsThe intervention started with a 2-day multidisciplinary course in which health care providers are trained as a team in essential components of effective COPD IDM in primary care. During the course, the team redesigns the care process and defines responsibilities of different caregivers. They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare. Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months. The team learns the details of an ICT program that supports recording of process and outcome measures. Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice. After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other's experience

OutcomesHealth status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ) Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnoea, costs of healthcare utilization and productivity loss

Starting date1 September 2010

Contact informationa.l.kruis@lumc.nl; Netherlands Trial Register (NTR): NTR2268

Notes

Murphy 2011

Trial name or titleThe effectiveness of a structured education pulmonary rehabilitation programme for improving the health status of people with Chronic Obstructive Pulmonary Disease (COPD): The PRINCE study

MethodsThis study evaluated the effectiveness of a structured education pulmonary rehabilitation program (SEPRP), delivered at the level of the general practice, on the health status of people with COPD. A cluster-randomized controlled trial was employed with the General Practice as the unit of randomisation

ParticipantsAll adults with a diagnosis of COPD were eligible to participate

InterventionsThe experimental group received a SEPRP, designed in consultation with people with COPD, experts, general practitioners and practice nurses. It was delivered 2 hours per week over 8 weeks by practice nurses and physiotherapists. The control group received 'usual care'

OutcomesThe primary outcome measure was health status measured by the Chronic Respiratory Questionnaire (CRQ) at 12 to 14 weeks

Starting date

Contact information

Notes

Roman 2013

Trial name or titleEfficacy of pulmonary rehabilitation in patients with moderate chronic obstructive pulmonary disease: a randomised controlled trial

MethodsThis study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and
usual care in improving the quality of life of patients with moderate COPD. The authors conducted a parallel-group, randomised clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups

ParticipantsModerate COPD

InterventionsSee above

OutcomesHealth outcomes were quality of life, exercise capacity, pulmonary function and exacerbations

Starting date

Contact informationISRCTN94514482

Notes

 
Comparison 1. Integrated disease management versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 SGRQ: short-term (3 to 12 months)13Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 SGRQ: Total
131425Mean Difference (IV, Random, 95% CI)-3.71 [-5.83, -1.59]

    1.2 SGRQ: Symptoms
111377Mean Difference (IV, Random, 95% CI)-2.39 [-5.31, 0.53]

    1.3 SGRQ: Activity
111352Mean Difference (IV, Random, 95% CI)-2.70 [-4.84, -0.55]

    1.4 SGRQ: Impact
111355Mean Difference (IV, Random, 95% CI)-4.04 [-5.96, -2.11]

 2 SGRQ: long-term (> 12 months)2Mean Difference (IV, Random, 95% CI)Subtotals only

    2.1 SGRQ: Total
2189Mean Difference (IV, Random, 95% CI)-0.22 [-7.43, 6.99]

    2.2 SGRQ: Symptoms
2191Mean Difference (IV, Random, 95% CI)5.65 [-8.88, 20.18]

    2.3 SGRQ: Activity
2191Mean Difference (IV, Random, 95% CI)-2.13 [-7.89, 3.63]

    2.4 SGRQ: Impact
2182Mean Difference (IV, Random, 95% CI)-1.62 [-5.50, 2.25]

 3 Subgroup analysis SGRQ (total score) based on type of setting131425Mean Difference (IV, Random, 95% CI)-3.77 [-5.90, -1.64]

    3.1 Primary care
6456Mean Difference (IV, Random, 95% CI)-4.68 [-8.80, -0.56]

    3.2 Secondary care
7969Mean Difference (IV, Random, 95% CI)-3.41 [-5.97, -0.85]

 4 Subgroup analysis SGRQ (total score) based on type of study design131425Mean Difference (IV, Random, 95% CI)-3.71 [-5.83, -1.59]

    4.1 RCTs
121304Mean Difference (IV, Random, 95% CI)-4.22 [-6.14, -2.30]

    4.2 CRCTs
1121Mean Difference (IV, Random, 95% CI)2.3 [-1.62, 6.22]

 5 Subgroup analysis SGRQ (total score) based on type of control group131425Mean Difference (IV, Random, 95% CI)-3.71 [-5.83, -1.59]

    5.1 Control group: usual care
9744Mean Difference (IV, Random, 95% CI)-4.09 [-6.35, -1.84]

    5.2 Control group: mono-disciplinary treatment
4681Mean Difference (IV, Random, 95% CI)-2.98 [-7.69, 1.74]

 6 Subgroup analysis SGRQ (total score) based on dominant component of intervention111315Mean Difference (IV, Random, 95% CI)-3.61 [-5.67, -1.55]

    6.1 Dominant component self management
5942Mean Difference (IV, Random, 95% CI)-2.76 [-5.88, 0.36]

    6.2 Dominant component exercise
6373Mean Difference (IV, Random, 95% CI)-4.74 [-7.05, -2.43]

 7 CRQ: short-term (3 to 12 months)4Mean Difference (IV, Random, 95% CI)Subtotals only

    7.1 CRQ: Dyspnea
4160Mean Difference (IV, Random, 95% CI)1.02 [0.67, 1.36]

    7.2 CRQ: Fatigue
4161Mean Difference (IV, Random, 95% CI)0.82 [0.46, 1.17]

    7.3 CRQ: Emotion
4161Mean Difference (IV, Random, 95% CI)0.61 [0.26, 0.95]

    7.4 CRQ: Mastery
4161Mean Difference (IV, Random, 95% CI)0.75 [0.38, 1.12]

 8 CRQ: Long-term (> 12 months)2Mean Difference (IV, Random, 95% CI)Subtotals only

    8.1 CRQ: Dyspnea
2151Mean Difference (IV, Random, 95% CI)0.47 [-0.31, 1.25]

    8.2 CRQ: Fatigue
2151Mean Difference (IV, Random, 95% CI)0.45 [0.05, 0.85]

    8.3 CRQ: Emotion
2151Mean Difference (IV, Random, 95% CI)0.53 [0.10, 0.95]

    8.4 CRQ: Mastery
2151Mean Difference (IV, Random, 95% CI)0.80 [0.37, 1.23]

 9 General health QoL: SIP mean difference2Mean Difference (IV, Random, 95% CI)Subtotals only

    9.1 SIP total
2183Mean Difference (IV, Random, 95% CI)-1.06 [-3.00, 0.89]

    9.2 SIP: physical
2183Mean Difference (IV, Random, 95% CI)-2.63 [-5.55, 0.30]

    9.3 SIP: psychosocial
2183Mean Difference (IV, Random, 95% CI)-0.86 [-3.17, 1.44]

 10 Functional exercise capacity: 6MWD mean difference14Mean Difference (IV, Random, 95% CI)Subtotals only

    10.1 6MWD: short-term (3 to 12 months)
14871Mean Difference (IV, Random, 95% CI)43.86 [21.83, 65.89]

    10.2 6MWD: long-term (> 12 months)
2184Mean Difference (IV, Random, 95% CI)16.84 [3.01, 30.67]

 11 Subgroup analysis 6MWD based on type of setting14Mean Difference (IV, Random, 95% CI)Subtotals only

    11.1 Primary care
7427Mean Difference (IV, Random, 95% CI)45.16 [8.65, 81.67]

    11.2 Secondary care
7438Mean Difference (IV, Random, 95% CI)49.18 [14.28, 84.08]

    11.3 Tertiary care
135Mean Difference (IV, Random, 95% CI)85.0 [30.43, 139.57]

 12 Subgroup analysis 6MWD based on type of control group14871Mean Difference (IV, Random, 95% CI)43.86 [21.83, 65.89]

    12.1 Control group: mono disciplinary treatment
4180Mean Difference (IV, Random, 95% CI)35.99 [-5.34, 77.31]

    12.2 Control group: usual care
10691Mean Difference (IV, Random, 95% CI)46.59 [19.68, 73.51]

 13 Subgroup analysis 6MWD based on dominant component of intervention14871Mean Difference (IV, Random, 95% CI)43.86 [21.83, 65.89]

    13.1 Dominant component: exercise
12653Mean Difference (IV, Random, 95% CI)51.47 [26.53, 76.40]

    13.2 Dominant component: structured follow-up
1133Mean Difference (IV, Random, 95% CI)3.50 [-28.31, 35.31]

    13.3 Dominant component: individually tailored education program
185Mean Difference (IV, Random, 95% CI)0.4 [-39.64, 40.44]

 14 Maximal exercise capacity: cycle test (W-max)4298Mean Difference (IV, Random, 95% CI)6.99 [2.96, 11.02]

 15 Number of patients experiencing at least one exacerbation: short-term (3-12 months)2407Odds Ratio (M-H, Random, 95% CI)1.21 [0.77, 1.91]

 16 Number of patients experiencing at least one exacerbation: long-term (> 12 months)2301Odds Ratio (M-H, Fixed, 95% CI)1.53 [0.90, 2.60]

 17 All hospital admissions: short-term (3 to 12 months)2266Odds Ratio (M-H, Random, 95% CI)0.62 [0.36, 1.07]

 18 All hospital admissions: long-term (> 12 months)2283Odds Ratio (M-H, Random, 95% CI)0.78 [0.38, 1.57]

 19 Respiratory-related hospital admissions: short-term (3 to 12 months)71470Odds Ratio (M-H, Random, 95% CI)0.68 [0.47, 0.99]

 20 Respiratory-related hospital admissions: long-term (> 12 months)1179Odds Ratio (M-H, Random, 95% CI)0.59 [0.28, 1.22]

 21 Hospital days per patient (all causes): short-term (3 to 12 months)6741Mean Difference (IV, Random, 95% CI)-3.78 [-5.90, -1.67]

 22 Hospital days per patient: long-term (> 12 months)1Mean Difference (IV, Random, 95% CI)Totals not selected

 23 ED visits41161Odds Ratio (M-H, Random, 95% CI)0.64 [0.33, 1.25]

 24 Number of patients using at least one course of oral steroids3348Odds Ratio (M-H, Random, 95% CI)1.13 [0.64, 2.01]

 25 Number of patients using at least one course of antibiotics2236Odds Ratio (M-H, Random, 95% CI)1.43 [0.24, 8.48]

 26 MRC dyspnea score3345Mean Difference (IV, Random, 95% CI)-0.30 [-0.48, -0.11]

 27 Borg score3145Mean Difference (IV, Random, 95% CI)0.14 [-0.70, 0.98]

 28 Mortality51235Odds Ratio (M-H, Random, 95% CI)0.85 [0.49, 1.46]

    28.1 Short-term (3 to 12 months)
41113Odds Ratio (M-H, Random, 95% CI)0.96 [0.52, 1.74]

    28.2 Long-term (> 12 months)
1122Odds Ratio (M-H, Random, 95% CI)0.45 [0.16, 1.28]

 29 FEV1 (liter)3Mean Difference (IV, Random, 95% CI)Subtotals only

    29.1 FEV1 (liter): short-term
2234Mean Difference (IV, Random, 95% CI)0.00 [-0.14, 0.14]

    29.2 FEV1 (liter): long-term
1104Mean Difference (IV, Random, 95% CI)-0.11 [-0.28, 0.06]

 30 FEV1 (% predicted)9Mean Difference (IV, Random, 95% CI)Subtotals only

    30.1 FEV1 (% predicted): short-term
4280Mean Difference (IV, Random, 95% CI)-0.57 [-3.54, 2.39]

    30.2 FEV1 (% predicted; mean change): short-term
4514Mean Difference (IV, Random, 95% CI)2.15 [0.38, 3.91]

    30.3 FEV1 (% predicted): long-term
1104Mean Difference (IV, Random, 95% CI)-4.60 [-11.26, 2.06]

 31 Anxiety and depression (HADS)2Mean Difference (IV, Random, 95% CI)Subtotals only

    31.1 HADS: depression
2316Mean Difference (IV, Random, 95% CI)0.21 [-0.39, 0.81]

    31.2 HADS: anxiety
2316Mean Difference (IV, Random, 95% CI)0.22 [-0.41, 0.85]

 
Summary of findings for the main comparison. Integrated disease management compared to control for patients with chronic obstructive pulmonary disease

Integrated disease management compared to control for patients with chronic obstructive pulmonary disease

Patient or population: patients with chronic obstructive pulmonary disease
Settings: 8 studies in primary care, 12 studies in secondary care, 1 study in tertiary care, 5 studies in both primary and secondary care
Intervention: integrated disease management
Comparison: control

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlDisease management

Quality of life measured on the SGRQ (St George's Respiratory Questionnaire) total score. Scale from: 0 to 100. Lower score indicates improvement
Follow-up: 3 to 12 months
The mean change in the SGRQ (total score) ranged from 3.4 lower to 6.24 higherThe mean SGRQ (total score) in the intervention groups was
3.71 lower
(5.83 to 1.59 lower)
MD -3.71 (-5.83 to -1.59)1425
(13 studies)
⊕⊕⊕⊕
high2
MCID = -4 points, lower score means improvement

Quality of life measured on the CRQ dyspnoea domain
Scale from: 0 to 7. Higher score indicates improvement
Follow-up: 3 to 12 months
The mean change in the CRQ (dyspnoea domain) ranged from 0 to 0.2 lowerThe mean CRQ dyspnoea domain in the intervention groups was
1.02 higher
(0.67 to 1.36 higher)
MD 1.02 (0.67 to 1.36)160
(4 studies)
⊕⊕⊕⊝
moderate1
MCID = 0.5 points

Results on the other domains of the CRQ (fatigue, emotion, mastery) were also all statistically and clinically relevant

Functional exercise capacity
6-minute walking distance (6MWD)
Follow-up: 3 to 12 months
The mean change in the 6MWD ranged from 38 lower to 36 higherThe mean functional exercise capacity in the intervention groups was
43.86 higher
(21.83 to 65.89 higher)
MD 43.86 (21.83 to 65.89)838
(14 studies)
⊕⊕⊕⊝
moderate3
MCID = 35 meters. Sensitivity analysis did show there was inconsistency in the effect. After removing low-quality studies, the MD was 15.15 meters (95% CI 6.37 to 23.93, P < 0.001)

Respiratory-related hospital admissions
Follow-up: 3 to 12 months
27 per 10020 per 100
(15 to 27)
OR 0.68
(0.47 to 0.99)
1470
(7 studies)
⊕⊕⊕⊕
high

Hospital days per patient (all causes)
Follow-up: 3 to 12 months
The mean change in hospital days ranged from 1.6 to 11.9 higherThe mean number of hospital days per patient (all causes) in the intervention groups was
3.78 lower
(5.9 to 1.67 lower)
MD -3.78

(-5.9 to -1.67)
741
(6 studies)
⊕⊕⊕⊕
high

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; IDM: integrated disease management; MCID: minimal clinically important difference; MD: mean difference; OR: odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1We downgraded one as there was considerable risk of bias in two studies on allocation concealment and two studies did not blind the outcome assessor.
2We did not downgrade due to risk of bias, as studies contributing more than 2.7% to the meta-analysis had a low risk of bias. Sensitivity analysis on high-risk studies did not change the effect or significance of the effect.
3We downgraded one as all included studies were of moderate to low quality. If we removed studies which had high or unclear risk of bias on allocation concealment, the effect decreased to 15 meters.
 
Table 1. Characteristics of included studies

StudyCountryN (randomised)N (completed)Number of components interventionNumber of health care providersMain component interventionSettingControl group

Aiken 2006US411852SFPRIMU

Bendstrup 1997Denmark423247ESECU

Bourbeau 2003Canada19116544SMSECU

Boxall 2005Australia604623EPRIMU

Cambach 1997Netherlands432322EPRIMDRUG

Dheda 2004UK332542SFSECU

Engstrom 1999Sweden555045ESECU

Farrero 2001Spain1229422SFSECU

Fernandez 2009Spain504122EPRIMEDU

Gottlieb 2011Denmark61264Multidisciplinary team, not specifiedEPRIMU

Güell 2000Spain604733ESECU

Güell 2006Spain402524ETERTDRUG

Koff 2009US403842SMPRIMU

Littlejohns 1991UK15213343SFSECU

Mendes 2010Brazil1178522EPRIM/SECU

Rea 2004New Zealand13511754SM/SFPRIM/SECU

Rice 2010US74374332SMSECEDU

Smith 1999Australia963683SFPRIM/SECU

Sridhar 2008UK12210443E/SMPRIM/SECU

Strijbos 1996Netherlands504133EPRIM/SECU

Theander 2009Sweden302644ESECU

TrappenburgNetherlands23319333SMSECU

Wakabayashi 2011Japan1028542IT EDUSECEDU

Wetering 2010Netherlands19917543ESECU

Wijkstra 1995Netherlands454323EPRIMU

Wood-Baker 2006Australia13511232SMPRIMEDU

 Main component: SF: structural follow-up; SM: self management; E: exercise; IT EDU: individually tailored education
Setting: PRIM: primary care; SEC: secondary care; TERT: tertiary care
Control group: U: usual care; DRUG: optimization of drug treatment; EDU: education
 
Table 2. Components of IDM in each included study

AuthorEducationSelf managementExacerbation/action planExercisePsychosocial/occupationalSmokingOptimal medicationNutritionFollow-upCase managementMultidisciplinary

Aiken 2006xxxxx

Bendstrup 1997xxxx

Bourbeau 2003xxxx

Boxall 2005xx

Cambach 1997xx

Dheda 2004xxxx

Engstrom 1999xxxx

Farrero 2001xx

Fernandezxx

Gottlieb 2011xxxx

Güell 2000xxx

Güell 2006xx

Koff 2009xxxx

Littlejohns 1991xxxx

Mendes 2010xx

Rea 2004xxxxx

Rice 2010xxx

Smith 1999xxxxxxxx

Sridhar 2008xxxx

Strijbos 1996xxx

Theander 2009xxxx

Trappenburg 2011xxx

Wakabayashi 2011xxxx

Wetering 2010xxxx

Wijkstra 1995xx

Wood-Baker 2006xxx