Methods

Study design: prospective RCT (single blind, parallel group; trial identifier: ISRCTN05557928)

Total duration of study: 12 months

'Run in' period: none

Number of study centres and location: 2 centres; UK

Study setting: an acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital

Date of study: January 2010‐September 2012

Participants

Note: This study recruited participants with any chronic respiratory condition; Dr Greening kindly provided disaggregated data for the participants with bronchiectasis reported here.

Number randomised: 20 participants with bronchiectasis randomised (early rehabilitation: n = 8; usual care: n = 12)

Number of withdrawals: none

Number analysed: variable per outcome

Mean age (SD), years: early rehabilitation: 78 (7.8); usual care: 68.8 (11.5)

Gender, n (%) male: early rehabilitation: NA; usual care: NA

Severity of condition

Mean (SD) baseline MRC dyspnoea grade on admission: early rehabilitation: 4.9 (0.35); usual care: 4.4 (0.67)

Mean (SD) stable state MRC dyspnoea grade: early rehabilitation: 4.3 (0.46); usual care: 3.5 (0.67)

Mean (SD) stable state FEV1 (L): early rehabilitation: 0.84 (0.28); usual care: 1.18 (0.49)

Diagnostic criteria: MRC dyspnoea score; spirometry was measured to British Thoracic Society standards.

Baseline lung function: see severity of condition

Smoking history: smoker, n yes/no/ex‐smoker/missing: early rehabilitation: 1/4/2/1 ; usual care: 1/5/6/0

Inclusion criteria: the study recruited patients with a diagnosis of chronic respiratory disease, including COPD; chronic asthma, bronchiectasis or interstitial lung disease); we have considered only the subset of participants with bronchiectasis. Participants had to be aged ≥ 40 years with self‐reported breathlessness on exertion when stable (MRC dyspnoea grade 3 or worse).

Exclusion criteria: inability to provide informed consent; concomitant acute cardiac event; presence of musculoskeletal, neurological, or psychiatric comorbidities that would prevent the delivery of the rehabilitation intervention; and > 4 emergency admissions to hospital for any cause in the previous 12 months.

Interventions

Intervention: early rehabilitation (6 weeks' duration), comprising usual care plus daily, supervised volitional (strength and aerobic training) and non‐volitional (neuromuscular electrical stimulation) techniques. This complex intervention also included a self‐management programme, described by the study authors as:

"The intervention team delivered education using the SPACE (Self management programme of Activity, Coping and Education) manual for chronic obstructive pulmonary disease, a structured programme of exercise, education, and psychosocial support. Motivational interviewing techniques were used to introduce patients to the manual and to familiarise them with the content. The manual was used throughout the participants’ inpatient stay and in the subsequent discussions during telephone calls."

As this component of the complex intervention was substantial we deemed the trial to be eligible for inclusion in this review; however, we are mindful that because SPACE was included alongside other components the findings from this trial in relation to the predefined inclusion criteria for this review should be interpreted with caution. It should also be noted that SPACE was primarily designed for COPD patients and is not specifically targeted for bronchiectasis.

The pulmonary rehabilitation team, consisting of physiotherapists and nurses, delivered the intervention. The exercise programme was individually prescribed and progressed. Early rehabilitation was performed on the acute medical ward and by the participants’ bedside. After discharge, participants underwent an unsupervised home based programme, supported by telephone consultations. Those who were readmitted after the 6‐week intervention period did not receive a further early rehabilitation intervention.

Comparison: usual care (standard care from the ward clinical physiotherapy team as directed by the responsible clinical team) including physiotherapist‐delivered techniques for airway clearance, assessment and supervision of mobility, and advice on smoking cessation. Nutritional status was assessed using the malnutrition universal screening tool score in all participants, and referral for dietetic advice and nutritional support was carried out if appropriate. No supervised or progressive exercise programme was provided during the admission or immediately after discharge, but outpatient pulmonary rehabilitation was offered to all participants 3 months after discharge as part of standard care.

Concomitant medications: not stated

Excluded medications: not stated

Outcomes

Primary outcomes (pre‐specified): readmission rate at 12 months

Secondary outcomes (pre‐specified): number of hospital days, mortality, physical performance and HRQoL. Secondary functional measures were recorded at baseline, at discharge from hospital, 6 weeks, 3 months and 12 months.

Timepoints: 12 months

Outcomes collected: 1ll specified outcomes were collected

Notes

Funding: not stated

Notable author conflicts of interest: none stated/identified

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The clinical trials unit at the University of Leicester coordinated randomisation by an automated internet based service (www.sealedenvelope.com)"

Allocation concealment (selection bias)

Low risk

Quote: "The clinical trials unit at the University of Leicester coordinated randomisation by an automated internet based service (www.sealedenvelope.com)"

Blinding of participants and personnel (performance bias)
Subjective outcomes

High risk

It is not feasible to blind participants to the intervention. Knowledge of treatment group could influence self‐reporting of subjective outcomes by participants.

Blinding of participants and personnel (performance bias)
Objective outcomes

Low risk

Quote: "Single blind". It is not feasible to blind participants to the treatment group. However, knowledge of treatment group would be unlikely to influence objective outcomes.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: “..all investigators performing the outcome measures were blinded to treatment allocation..”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

During trial: 14/196 withdrew from intervention group; 10/193 withdrew from control group. Missing data imputed

Selective reporting (reporting bias)

Low risk

All pre‐specified outcomes reported

Other bias

High risk

Baseline imbalances in age and disease severity in the subset of participants with bronchiectasis; participants in the control group appeared to have less severe disease. Higher mortality with intervention in bronchiectasis subgroup (intervention: 4/8; control: 2/12)

Methods

Study design: proof‐of‐concept RCT (NCT01117493).

Total duration of study: 6 months

'Run in' period: none

Number of study centres and location: single regional respiratory centre, Belfast, Northern Ireland, UK.

Study setting: Tertiary care

Date of study: September 2006‐October 2007

Participants

Number randomised: 64 (32/32)

Number of withdrawals: 4 (2/2)

Number analysed: 60 (30/30)

Mean age (SD), years: intervention: 60 (9); control: 60 (8)

Gender, % m/f: intervention: 44/56; control: 47/53

Diagnostic criteria: assessment by respiratory clinician

Baseline lung function ‐ mean (SD) % predicted FEV1: intervention: 59 (20); control: 65 (23)

Smoking history: not stated

Inclusion criteria: adults (aged ≥ 18 years) with a primary diagnosis of bronchiectasis based on a respiratory physician’s assessment, including a CT scan

Exclusion criteria: primary diagnosis of CF, MRSA infection, or a condition that would have an impact on the assessment procedures (e.g. sensory impairment, pregnancy, language barrier, or a factor that would prevent adherence to the self‐management programme)

Interventions

Intervention: usual care plus EPP: disease‐specific EPP was delivered in a group format during 1 session/week (2.5 h) for 8 weeks in total (2 weeks of disease‐specific education; 6 weeks of standardised EPP). The disease‐specific component included causes of bronchiectasis, disease process, medical investigations, dealing with symptoms, airway clearance techniques, exacerbations, health promotion and support available. The format of the disease‐specific EPP was delivered by a physiotherapist and a nurse with specialist expertise in the management of bronchiectasis who were trained and followed a scripted manual to standardise delivery. The format of the EPP was developed and piloted before this RCT. Topics included general health education, education on self‐management treatment strategies, action planning, and problem solving.

Comparison: usual care: reviews at a specialist respiratory clinic on a 3‐monthly basis to monitor spirometry results, inflammatory blood marker levels, and sputum microbiologic assessment. Inhaled therapy and antibiotics were prescribed if required, and treatment was adjusted to the needs of the participant as necessary, including hospital admission.

Concomitant medications: not stated

Excluded medications: not stated

Outcomes

Primary outcomes (pre‐specified): CDSS ‐ comprises 10 scales as follows: exercise, disease information, obtaining help, communication with physician, managing disease, doing cores, social activity, managing symptoms, managing breathlessness, managing depression. Responses are measured using a 1‐10 Likert scale where higher scores indicate greater self‐efficacy. There is no Minimum Clinically Important Difference value for these scales.

Secondary outcomes (pre‐specified): revised Illness Perception Questionnaire, SGRQ, FEV1, frequency of oral and/or intravenous antibiotic therapy prescribed at respiratory clinics

Timepoints: baseline, post‐intervention (8 weeks), 3 and 6 months postintervention

Outcomes collected: all specified outcomes were collected

Notes

Funding: supported by the Health and Social Care Research and Development Division, Public Health Agency, Belfast, Northern Ireland

Notable author conflicts of interest: none

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “…computer generated concealed randomisation process conducted by an independent person...”

Allocation concealment (selection bias)

Low risk

Quote “..an envelope corresponding to the patient’s number was opened to reveal if they were assigned to the intervention or control group.”

Blinding of participants and personnel (performance bias)
Subjective outcomes

High risk

Not blinded and lack of blinding may have influenced outcome (1 withdrew who ‘wanted intervention’)

Blinding of participants and personnel (performance bias)
Objective outcomes

Low risk

It is not feasible to blind participants or personnel to the intervention. However, knowledge of treatment group would be unlikely to influence objective outcomes.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: “Data were collected by trained health professionals who were blinded to participants’ groups and had no other contact with the participants. Study participants were requested not to disclose their group assignment.”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

6 months: 2/32 missing from intervention group (1 illness, 1 did not complete outcome measures); 2/32 missing from control group (1 wanted intervention, 1 disliked questionnaire). Even balance between groups

Selective reporting (reporting bias)

Low risk

All planned outcomes were reported. Subjective outcomes were well‐reported but objective outcomes poorly reported.

Other bias

High risk

This was a proof‐of‐concept study so there was no power calculation. There is therefore a risk that negative findings were influenced by an inadequate sample size