Content uploaded by Mal North
Author content
All content in this area was uploaded by Mal North on Feb 07, 2018
Content may be subject to copyright.
Available via license: CC BY-NC 4.0
Content may be subject to copyright.
1
BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
AbstrAct
Objective To obtain evidence whether the online pulmonary
rehabilitation(PR) programme ‘my-PR’ is non-inferior to
a conventional face-to-face PR in improving physical
performance and symptom scores in patients with COPD.
Design A two-arm parallel single-blind, randomised
controlled trial.
Setting The online arm carried out pulmonary
rehabilitation in their own homes and the face to face arm
in a local rehabilitation facility.
Participants 90 patients with a diagnosis of chronic
obstructive pulmonary disease (COPD), modied Medical
Research Council score of 2 or greater referred for pulmonary
rehabilitation (PR), randomised in a 2:1 ratio to online (n=64)
or face-to-face PR (n=26). Participants unable to use an
internet-enabled device at home were excluded.
Main outcome measures Coprimary outcomes were
6 min walk distance test and the COPD assessment test
(CAT) score at completion of the programme.
Interventions A 6-week PR programme organised either
as group sessions in a local rehabilitation facility, or online
PR via log in and access to 'myPR’.
Results The adjusted mean difference for the 6 min walk
test (6MWT) between groups for the intention-to-treat (ITT)
population was 23.8 m with the lower 95% CI well above
the non-inferiority threshold of −40.5 m at −4.5 m with an
upper 95% CI of +52.2 m. This result was consistent in the
per-protocol (PP) population with a mean adjusted difference
of 15 m (−13.7 to 43.8). The CAT score difference in the ITT
was −1.0 in favour of the online intervention with the upper
95% CI well below the non-inferiority threshold of 1.8 at 0.86
and the lower 95% CI of −2.9. The PP analysis was consistent
with the ITT.
Conclusion PR is an evidenced-based and guideline-
mandated intervention for patients with COPD with
functional limitation. A 6-week programme of online-
supported PR was non-inferior to a conventional model
delivered in face-to-face sessions in terms of effects on
6MWT distance, and symptom scores and was safe and
well tolerated.
INTRODUCTION
Chronic obstructive pulmonary disease
(COPD) is a highly prevalent condi-
tion, which results in gradual loss of lung
function, increasing symptoms and func-
tional limitation over time.1 Pulmonary
rehabilitation (PR) is a non-pharmacolog-
ical intervention at the core of management
of COPD, aimed at reducing the burden
of symptoms by increasing exercise toler-
ance and improving self-management.
With an established evidence-base, PR has
been placed at the centre of interventions
for COPD and its provision is mandated
by the National Institute for Health and
Care Excellence (NICE) as a key pillar of
integrated care.1 The model of care for
providing PR is traditionally a face-to-face,
structured programme of exercise training
and education completed in a supervised,
centre-based setting over an established
protocol of a minimum of 6 weeks.2
While PR has been shown to improve func-
tional performance and physical activity3
and greater activity levels have themselves
been associated with reduced risk of hospi-
talisation,4 access to programmes can be
problematic for some patients and the
impact of conventional PR is limited by
Online versus face-to-face pulmonary
rehabilitation for patients with chronic
obstructive pulmonary disease:
randomised controlled trial
Simon Bourne,1,2 Ruth DeVos,1,2 Malcolm North,2 Anoop Chauhan,1 Ben Green,1
Thomas Brown,1 Victoria Cornelius,3 Tom Wilkinson2,4
To cite: BourneS, DeVosR,
NorthM, etal. Online versus
face-to-face pulmonary
rehabilitation for patients
with chronic obstructive
pulmonary disease: randomised
controlled trial. BMJ Open
2017;7:e014580. doi:10.1136/
bmjopen-2016-014580
►Prepublication history and
additional material are available.
To view these les, please visit
the journal online (http:// dx. doi.
org/ 10. 1136/ bmjopen- 2016-
014580).
Received 4 October 2016
Revised 10 May 2017
Accepted 18 May 2017
1Portsmouth Hospitals NHS
Trust, Portsmouth, UK
2myMHealth Ltd Bournemouth,
UK
3Imperial College, London, UK
4Clinical and Experimental
Sciences, Faculty of Medicine,
University of Southampton,
Southampton, UK
Correspondence to
Dr Tom Wilkinson; t. wilkinson@
soton. ac. uk
Research
Strengths and limitations of this study
►This study explored the efcacy and safety ‘myPR’, a
novel method for delivering pulmonary rehabilitation
by online support compared with conventional face-
to-face delivery in classes using a randomised
controlled trial to explore whether the online
programme was non-inferior to the standard model.
►Due to the nature of the intervention, only patients
with access to the internet at home could be
included in the study.
►Further limitations of this study include the limited
sample size,and the absence of long-term follow-
up. Larger studies are required to explore the health-
economic benets of this model and applicability in
different healthcare settings.
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
2BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
suboptimal attendance and high dropout rates.5 6 With
an ever-increasing burden on services, conventional
models of care are constantly being challenged and
alternative, cost-effective ways of delivering healthcare
to a larger cohort of patients are being sought. Indeed,
the key message and goal in the recent American
Thoracic Society/European. Respiratory Society policy
statement of the implementation and delivery of PR is
‘to expand provision of PR to suitable patients world-
wide'.7
Patients with COPD are encouraged to carry out PR
exercises in their home environment, and even unsu-
pervised exercise has been shown to be an effective
way of increasing exercise tolerance.8 More recently,
the use of Telehealth has been trialled as an alterna-
tive, and innovative way of delivering PR to individuals
in their home, with aims to increase its uptake and, in
particular access for those in isolated areas or who have
transport issues. This home-based intervention using
tele-monitoring equipment has shown some promise
in maintaining and further improving physical capacity
but hardware-related costs are high.9 10 In 2015, 86%
of patients with chronic cardiopulmonary disease had
internet access,11 and with this ever-increasing pres-
ence of technology in homes, online PR is beginning to
emerge as an alternative way of delivering PR.12 Indeed,
the current British Thoracic Society (BTS) PR guide-
lines2 recognise that ‘technology has the potential to be
used as an adjunct to rehabilitation or even provide a
"rehabilitative" service’.
Although aspects of PR have been delivered in the
home setting, the documented attempts have, to date,
lacked the capability of administering a comprehen-
sive programme provided by conventional face-to-face
PR. The conventional model combines delivery of
educational component including information on the
condition, prescribed treatments and advice on exer-
cise and self-directed care, delivered alongside an
incremental exercise programme. The educational
component of PR is recognised by the BTS as ‘funda-
mentally integral to the format and success of the
programme’ and ‘the intention of the educational
element is to support the lifestyle and behavioural
change and assist self-management to promote self-ef-
ficacy'.2
In response to the recognised demand for alterna-
tive ways of delivering PR, a comprehensive, online
internet-based PR programme consisting of a 6-week
incremental exercise programme alongside education
sessions was developed for patients with COPD. This
online PR programme, known as myPR, was developed
by a multidisciplinary team of respiratory specialists and
is designed to mirror all of the components of a conven-
tional COPD PR programme.
We conducted a non-inferiority randomised controlled
clinical trial to compare efficacy and safety of PR
supported by the online application compared with a
face-to-face class-based PR programme.
METHODS
Study design
This was a prospective, parallel group, single-blind
randomised controlled trial conducted in a single centre
in the UK. Patients were recruited from a range of primary
and secondary care clinical settings consistent with the
route of referral for PR. The non-inferiority trial design
was to compare the clinical delivery of a 6-week online
PR programme (myPR) to the current clinical standard
of face-to-face PR programme delivered in a conventional
community setting, to patients with COPD. This study was
approved by the research ethics committee for Berkshire
B of the UK Health Research Authority (15/SC/0345).
The study was registered online as NCT02706613.
Patients were consulted and played an active role in the
development of mycopd—the online intervention plat-
form. Patients were involved in reviewing the design of
the study including the potential study burden on people
with COPD, the choice and format of patient-reported
outcome measures, the writing of the patient information
sheets and the consent form.
We randomised eligible patients with COPD using a
computerised block permutation randomise sequencer
in a ratio of 2:1 to either the online arm (myPR) or to
receive standard face-to-face PR. A 2:1 ratio was used to
reduce the number of subjects in the more costly face-
to-face arm while maintaining power. Randomisation was
stratified by severity of COPD (forced expiratory volume
in 1 s (FEV1)% predicted) to ensure equal distribution
in both arms and used an online system for concealed
allocation.
Outcomes were measured at baseline and within 1 week
of completion of either arm of the study. Due to the
nature of the intervention, blinding of participants was
not possible. Study staff carrying out the postintervention
assessments (outcome assessors) were blind to which arm
the patient had been randomised to.
Study population
Participants suitable for PR were recruited to the study
from Portsmouth Hospitals NHS Trust outpatient respi-
ratory clinics. All those participants wishing to participate
were issued with a Patient Invitation Letter and a Patient
Information Sheet. Inclusion criteria were a diagnosis of
COPD as defined by the NICE COPD guidelines with a
modified Medical Research Council (mMRC) dyspnoea
of grade 2 or greater, with access to the internet and the
ability to operate a web platform and aged 40 years or
greater. Exclusion criteria were an exacerbation requiring
additional antibiotics and/or steroids within 2 weeks prior
to screening; patients who had already undertaken a PR
programme within the last 6 months; patients who have
another respiratory disease as their main complaint other
than COPD; uncontrolled hypertension; unstable cardio-
vascular disease or significant desaturation that would
make PR exercise unsafe or prevent programme partici-
pation; patients who were unable to walk or whose ability
to walk safely and independently is significantly impaired
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
3
BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
due to non-respiratory-related conditions and/or cogni-
tive impairment; patients who are unable to read or use
an internet-enabled device or do not have access to the
internet at home and a ‘Timed Up and Go’ (TUG) test
>4 s. The TUG test was introduced as a way of assessing
safety of unsupervised exercise of patients completing the
PR programme in their homes, as it is a reliable and valid
test for quantifying functional mobility12 and has been
validated for use with COPD.13
Online PR (myPR)
After assessment, participants randomised to the online
arm were issued with unique login details to access myPR.
They were given basic instructions on the use of the
programme, in a brief 5–10 min introductory session face
to face with a member of the clinical research team. They
were instructed to access myPR at least twice and up to
five times a week. The initial start-up instructions on the
programme were designed to explain each step of myPR
to the patient, and further instructions were given as
they progressed. The physiotherapist leading the online
programme also delivered the face-to-face programmes
to ensure standardisation between the programmes.
Patients were advised to carry out exercises at a time that
was convenient to them and when they felt their energy
levels were at their best. No specific advice was given
regarding exercise modification as this is built into the
online programme itself.
The online programme is incremental in nature and
ran over 6 weeks and each week the length of each of
the 10 exercises increased by 30 s, starting from 60 s in
week 1, to 3½ min in week 6. The on-screen exercises
were designed to be carried out with the patient in real
time, with the patient following and keeping up with the
video-facilitated exercises. One minute of rest time was
given between each of the 10 exercises, with advice given
on Borg score measurement along with other tips on
managing breathlessness. During each of the 6 weeks of
exercise, patients were directed to watch three different
educational videos per week as education is a recognised
and important component of PR and helps promote
self-management. These educational sessions included
anatomy of the lungs, an explanation of COPD, manage-
ment of anxiety and depression, claiming benefits,
self-management, managing breathlessness, medications
and treatments, managing exacerbations of COPD,
sputum clearance using the Active Cycle of Breathing
Technique, nutrition, pacing, smoking cessation and
advice on travel with COPD. All of these educational
sessions are suggested in the current BTS PR guidelines,
and patients could access these videos as often as they
wished each week.
Contact details of the research team were provided so
that patients had a point of reference for any queries they
had regarding the technology or any health concerns.
Details of the online programme can be accessed via www.
mymhealth. com/ mycopd.
Face-to-face PR
Patients randomised to the conventional face-to-face PR
were given the dates and times of the next available PR
being run in a rehabilitation facility by a physiotherapist
and nurse on the research team. Patients attended two
supervised sessions for 6 weeks and were asked to carry
out exercises at home an additional three times per
week. The programme consisted of 10 exercise stations,
which were identical to the exercises carried out by the
patients using myPR. The 10 exercises included biceps
curls, squats, push ups against a wall, leg extensions in
a sitting position, upright row with weights, sit-to-stand,
arm swings with a stick, leg kicks to the side, arm punches
with weights and step-ups. Both the online and face-to-
face programmes also included warm up and cool down
sessions.
The same educational sessions as on myPR were then
delivered, but were presented and discussed orally rather
than in video format as in myPR, which offered patients
the opportunity to address questions.
Primary and secondary outcomes
The primary outcome measures were to compare best
performance 6 min walk distance (6MWD) test over a
30 m course on completion of the online and conven-
tional PR programmes using the 6 min walk test (6MWT)
performed according to national standards,2 and impact
on health status using the COPD assessment test (CAT)
score. Secondary outcome measures included the St
Georges Respiratory Questionnaire (SGRQ) to assess
respiratory quality of life, and the Hospital Anxiety and
Depression Scale (HADS) to assess anxiety and depres-
sion. Safety was assessed by the incidence of adverse
events (AEs) in each arm at study completion.
Adverse events
AEs were captured in the face-to-face group at the start
of each session (twice a week) during the 6-week inter-
vention and at final assessment. In the online arm, AEs
were captured during a weekly phone call to the partici-
pant from the study clinical team and at final assessment.
Causality and severity was assessed by the clinical study
team.
STATISTICAL ANALYSES
Sample size calculation
The size of the study was chosen with consideration to
provision of preliminary evidence for the non-inferiority
of online PR as compared with gold standard face-to-face
PR. As a result, the primary focus was to obtain an esti-
mate for the lower bound of the 95% CI for the 6MWD
test, and upper bound of the 90% CI for the CAT. In a
fully powered study, it is common that the non-inferiority
margin is set to be half the clinically important minimum
difference. As this is the first examination of the interven-
tion the non-inferiority margin was chosen to be less than
the minimum important clinical difference but not as
high as the commonly used criteria of half the difference.
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
4BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
Figure 1 CONSORT diagram patient ow in study. COPD, chronic obstructive pulmonary disease; ITT, intention to treat; PR,
pulmonary rehabilitation.
From the published literature and practice guidelines
on the 6MWD test, 54 m was a widely accepted minimum
value of a meaningful increase in patient’s perception of
exercise performance.14 15 This level was originally used to
establish power and calculate the appropriate sample size.
Assuming no difference between intervention arms and a
SD of 100,17 we required 75 participants (2:1 ratio) to esti-
mate the lower 95% CI bound for the mean difference to
be no more than 40.5 m. Subsequent to the study design,
an update minimally clinically important difference of 30
m has been proposed and adopted.16 17 Consideration of
both cut-offs was undertaken in the analysis.
An accepted clinically important minimum difference
of the CAT score is estimated to be 1.8 with a SD of 6.4.20
Assuming no difference between intervention arms and a
SD of 6.4, we required 94 participants (2:1 ratio) to esti-
mate the upper 90% CI bound for the mean difference
to be no more than 1.8. We took the larger of these two
values (n=94: 63:32 per arm).
Randomisation
Participants were randomised using permuted blocks via
an online randomisation system hosted by myMHealth in
a ratio of 2:1 with more participants being randomised
to the online myPR arm. A concealed allocation was
performed. Randomisation was stratified by disease
severity defined by the global initiative for obstructive
lung disease (GOLD) classification of COPD severity.18
Blinding
To ensure the study team remained blind as to which arm
of the study each participant was on, they were divided
into two teams. One team was responsible for the assess-
ment and randomisation of participants onto the study
and the other team provided the after-intervention assess-
ment. A separate team member, who was not involved in
the prestudy or poststudy assessments, was not blinded,
to ensure availability to answer any questions participants
had throughout the study, and deal with any potential
adverse events. All subjects were asked in advance not to
discuss their PR programme during assessments.
Statistical methods
Statistical analysis was performed for both the inten-
tion-to-treat (ITT) population and per-protocol (PP)
population. ITT analysis included all participants in the
arms they were randomised to regardless of adherence to
either intervention. The frequency, patterns and predic-
tors of missing data were explored. Data at follow-up was
imputed regardless of the reason for missing. Multiple
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
5
BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
Table 1 Baseline characteristics of randomised patients by
intervention arm
Baseline variables
Face-to-face
PR (n=26)
Online PR
(n=64)
Age (years), mean (SD) 71.4 (8.6) 69.1 (7.9)
Gender (male), n (%) 18 (69) 41 (62)
Smoking, n (%)
Current smoker 6 (23) 9 (14)
Ex-smoker 20 (76.9) 55 (85.9)
COPD severity, n (%)
Mild 5 (19) 15 (23)
Moderate 13 (50) 26 (41)
Severe 7 (27) 17 (27)
Very severe 1 (4) 6 (9)
FEV1, mean (SD) 1.66 (0.67) 1.63 (0.71)
FEV1% predicted, mean (SD) 60.5 (20.1) 58.0 (23.6)
FVC, mean (SD) 2.97 (1.03) 3.03 (0.99)
FVC predicted, mean (SD) 83.2 (21.2) 88.4 (22.0)
COPD, chronic obstructive pulmonary disease; FEV1, forced
expiratory volume in 1 s; FVC, forced vital capacity; PR, pulmonary
rehabilitation.
Table 2 Comorbidities by intervention arm
Comorbidities
Face-to-face
n (%) Online n (%)
Hypertension 7 (26.9%) 23 (35.9%)
Cardiovascular disease 13 (50%) 22 (34.3%)
Cerebrovascular disease 1 (3.8%) 5 (7.8%)
Dermatological 0 7 (10.9%)
Diabetes and endocrine 6 (23.1%) 14 (21.9%)
Gastroenterological 5 (19.2%) 21 (32.8%)
Haematological 1 (3.8%) 1 (1.6%)
Neurological and psychiatric 3 (11.5%) 11 (17.2%)
History of malignancy 3 (11.5%) 4 (6.3%)
Musculoskeletal 7 (25.9%) 9 (14.1%)
Renal 2 (7.7%) 2 (3.1%)
Other respiratory 1 (3.8%) 3 (4.7%)
None 3 (11.5%) 4 (6.3%)
imputation was implemented based on chained equation
model and using age, gender, baseline scores and COPD
severity assuming unobserved measurements were missing
at random (100 datasets).19 Analyses were repeated for
participants with complete data only and compared with
analyses where missing data were imputed.
In the gold standard care arm, participants were
invited to two face-to-face sessions per week. In the
intervention arm, participants could access rehabilita-
tion programme as much as they wanted to per week,
although they were requested to access the programme
at least five times per week, on different days. The PP
analysis population was defined as participants who, on
average, took up the offer of at least one face-to-face
session per week or accessed the online programme at
least once per week.
Baseline characteristics were summarised by randomi-
sation group as means and SDs (continuous normally
distributed variables), medians and IQRs (non-normally
distributed variables) and frequencies and percentages
(categorical variables). The mean differences in the
outcomes between the intervention and control arms and
95% and 90% CIs were estimated using linear regression
adjusted for disease severity measured by FEV1% predicted
and baseline functional capacity (6MWT) as both factors
are measurable and may impact on the response to exer-
cise training. Residual analysis was performed to examine
model assumptions.
RESULTS
Recruitment and baseline characteristics
Overall, 143 subjects were screened for eligibility. The
trial ran from September 2015 to March 2016. Figure 1
shows the subject flow for screening, randomisation and
follow-up in the study. Table 1 illustrates the personal
characteristics and baseline measures for the randomised
90 patients. No important imbalances were identified for
these variables between the two intervention groups. The
90 participants with COPD had a mean age of 70 years
(8.2) and moderate airflow obstruction with a mean
FEV1% predicted of 59% (22). Patients in intervention
arms were well matched prior to rehabilitation. Comor-
bidities for each intervention arm are illustrated in
table 2.
Primary outcomes
The baseline 6MWT distance was 416.5 (118.3) m in the
face-to-face group and 388.7 (104.4) m in the online
intervention group and rose to 445.1 (124.9) and 433.6
(102.9) m, respectively after the intervention.
The adjusted mean difference for the 6MWT between
groups for the ITT population was 23.8 m with the lower
95% CI well above the non-inferiority threshold of −40.5
m at −4.5 m with an upper 95% CI of +52.2 m. This result
was consistent in the PP population with a mean adjusted
difference of 15 m (−13.7 to 43.8). Non-inferiority of
intervention was seen whether the minimally clinically
important difference (MCID) of 54 or 30 m was used (see
figure 2A).
The CAT score difference in the ITT was −1.0 in favour
of the online intervention with the upper 95% CI well
below the non-inferiority threshold of 1.8 at 0.86 and a
lower 95% CI of −0.2.9. The PP analysis was consistent
with the ITT with a mean CAT score difference of −0.64
(95% CI −2.5 to 1.2) (figure 2B).
Secondary outcomes
HADS recorded at baseline demonstrated a reduction
indicative of improvement in both intervention arms. The
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
6BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
Figure 2A Adjusted mean difference and 95% CI for 6 min walk test (6MWT) in the intention-to-treat (ITT) and per-protocol
(PP) population.
Figure 2B Adjusted mean difference and 95% CI for COPD assessment test (CAT) score in the intention-to-treat (ITT) and per-
protocol (PP) population.
adjusted mean difference for HADS for the ITT popula-
tion was −0.74 (95% CI −3.5 to 0.9) in favour of online
PR. Similarly, COPD health-related quality of life (SGRQ)
scores and mMRC dyspnoea scores suggested non-inferi-
ority for the online intervention group (see table 3).
PP analysis
Fifteen (23%) participants withdrew or were lost to
follow-up from the online group and 5 (19%) in the
face-to-face treatment groups. A breakdown of the
non-completer participants is summarised in the online
supplementary Table S1. A further three participants had
an exacerbation in the online group and were unable to
complete the final study assessments. A PP analysis of all
outcome measures recorded demonstrated differences
well outside the clinically important difference for infe-
riority for all stipulated MCID values. All intervention
effect estimates were in the direction of favour for the
online intervention (see table 4).
Safety
Adverse events are summarised in table 5. Overall, both
interventions were well tolerated with no safety issues
identified.
Adherence to rehabilitation training and education
Adherence in both study arms was incomplete. Table 6
summarises the exercise sessions completed: a) atten-
dance at the face-to-face group and b) participation
with the online sessions. Overall, 72% of the two face-
to-face sessions were attended, compared with 62% of
the suggested five sessions recorded as accessed online
over the 6-week intervention period. The attendance at
the face-to-face sessions was relatively stable with a mean
1.6 sessions per participant in week 1 and 1.4 in week 6,
while there was a decline in participation in the online
arm from a mean of 3.9 sessions per participant in week
1 to 2.5 in week 6.
DISCUSSION
We report a single-blinded, randomised clinical trial of
a novel and newly designed online pulmonary rehabili-
tation programme compared with the usual standard
of care PR, delivered by face-to-face supervised patient
sessions. The trial was designed to provide preliminary
evidence for the use of online PR by examining the
performance with respect to non-inferiority on validated
clinical measures namely the 6MWT and the CAT score.
The results are supportive of the hypothesis that there
is no difference in either coprimary outcomes between
these two approaches to delivering PR. In addition,
non-inferiority was demonstrated between the impacts of
online and conventional PR on validated clinical scores
for breathlessness or health-related quality of life between
the groups after the 6-week intervention period.
A predetermined PP analysis confirmed that for
compliers the online PR was non-inferior with a direction
of estimate in favour of online PR for all measures.
Clinical improvements with pulmonary rehabilitation and
comparison with other studies
Pulmonary rehabilitation is part of standard care for
patients with COPD who are functionally limited.1 2 It has
been demonstrated to improve exercise tolerance and
functional independence.3 The majority of studies of PR
in COPD have demonstrated benefits through delivery
of the model of a complex intervention of graded exer-
cise and education over a 6-week course, which has now
formed part of guideline-based treatment.2 The impact
of conventional PR on key outcomes such as 6MWD test
and CAT score has been assessed by a number of groups.
In a meta-analysis of 14 studies which measured changes
in the 6MWD test, the beneficial impact of PR was 55.7 m
(27.8–92.8),20 with an MCID modelled at an improvement
of 54 m for a patient to detect a benefit.14 Subsequent
studies have identified 30 m as an appropriate value.16 17
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
7
BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
Table 3 Between-group differences in primary and secondary outcomes
Mean value (SD), n
Regression
analysis(ITT
population)
Regression
analysis(PP
population)
Face-to-face PR
(n=26) Online PR (n=64)
Adjusted difference
(95% CI) p Value
Adjusted difference
(95% CI) p Value
6 min walk test (m)
Baseline 416.5 (118.3) 388.7 (104.4) 23.8 (−4.5 to 52.2) 0.098 15.0 (−13.7 to 43.8) 0.300
7 weeks 445.1 (124.9) 433.6 (102.9)
COPD assessment test score
Baseline 17.3 (6.7) 18.1 (7.9) −1.0 (−2.9 to 0.86) 0.373 −0.64 (−2.5 to 1.2) 0.569
7 weeks 16.2 (6.7) 14.9 (7.0)
Hospital Anxiety and Depression Scale
Baseline 10.0 (6.0–18.0) 10.0 (6.0–16.5) −0.74 (−3.5 to 0.9) 0.263 −1.2 (−3.5 to 1.2) 0.320
7 weeks 10.5 (5.0–13.0) 7.0 (4.0–15.0)
St Georges Respiratory Questionnaire
Baseline 37.7 (17.2) 42.4 (18.6) −3.72 (−10.7 to 3.3) 0.291 −2.5 (−9.3 to 4.4) 0.474
7 weeks 39.3 (18.5) 39.3 (18.5)
Modied Medical Research Council Dyspnoea score
Baseline 2.0 (1.0–2.0) 2.0 (1.0–3.0) 0.03 (−0.56 to 0.63) 0.909 0.04 (−0.54 to 0.63) 0.885
7 weeks 1.5 (1.0, 2.0) 1.0 (1.0, 2.0)
ITT, intention to treat; PP, per -protocol; PR, pulmonary rehabilitation.
Table 4 Number of participants with missing outcome data and summary by intervention arm for completers only
Mean value (SD), n
Face-to-face PR Online PR Regression p Value Direction of estimate
6 min walk test
Baseline 416.5 (118.3), 26 388.7 (104.4), 62 26.1 (−1.0 to 53.2) 0.06 In favour of online PR
7 weeks 457.3 (122.1), 21 449.4 (99.0), 46
COPD assessment test score
Baseline 17.3 (6.7), 26 18.1 (7.9), 64 −1.2 (−3.4 to 0.9) 0.260 In favour of online PR
7 weeks 15.2 (6.9), 21 15.2 (7.6), 44
Hospital Anxiety and Depression Scale
BaselineII 10.0 (6.0–18.0), 26 10.0 (6.0–16.5), 64 −1.2 (−3.3 to 1.0) 0.267 In favour of online PR
7 weeks 10.0 (4.5–12.5), 20 6.5 (4.0–14.5), 44
St Georges Respiratory Questionnaire
Baseline 37.7 (17.2), 26 42.4 (18.6), 64 −4.2 (−10.9 to 2.5) 0.215 In favour of online PR
7 weeks 38.1 (15.5), 21 39.3 (19.9), 44
Modied Medical Research Council Dyspnoea score
Baseline 2.0 (1.0–2.0), 26 2.0 (1.0–3.0), 64 −0.03 (−0.55 to 0.49) 0.912 In favour of online PR
7 weeks 1.0 (1.0, 2.0), 21 1.0 (1.0–2.0), 44
PR, pulmonary rehabilitation
The improvements in exercise capacity seen in this study
in both treatment arms were within range of those in
published analysis, demonstrated non-inferiority with
both MCID values and were similar to small studies in
comparable clinical groups.21
While the evidence for safety and benefit of PR for
patients with stable COPD is well established, the evidence
behind the best methods to deliver this intervention is
much less strong. The optimal duration of intervention
has been established by clinical studies comparing length
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
8BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
Table 5 Intervention emergent adverse events by treatment
groups
Adverse event
Face-to-face
PR, n
Online
PR, n
Back pain 1 1
Muscular skeletal chest pain 0 1
Inguinal pain 1 0
Common cold 1 0
PR, pulmonary rehabilitation
Table 6 Exercise sessions completed by face-to-face (n=26) and online groups (n=64)
Week 1 Week 2 Week 3 Week 4 Week 5 Week 6
Face-to-face(n=26)
0 sessions 3 (11) 8 (31) 5 (19) 6 (23) 6 (23) 7 (27)
One session 3 (11) 3 (11) 4 (15) 1 (4) 5 (19) 1 (4)
Two sessions 20 (77) 15 (58) 17 (65) 19 (73) 15 (58) 18 (69)
Mean 1.6 1.3 1.5 1.5 1.3 1.4
online groups (n=64)
0 sessions 9 (14) 12 (19) 13 (20) 14 (22) 18 (28) 18 (28)
One session 2 (3) 2 (3) 4 (6) 6 (9) 2 (3) 4 (6)
Two sessions 6 (9) 5 (8) 7 (11) 8 (13) 6 (9) 11 (17)
Three sessions 4 (6) 7 (11) 5 (8) 8 (13) 11 (17) 8 (13)
Four sessions 11 (17.2) 6 (9) 9 (14) 5 (8) 6 (9) 9 (14)
Five sessions 17 (27) 25 (39) 18 (28) 17 (27) 17 (27) 9 (14)
Six sessions 11 (17) 6 (9) 8 (13) 4 (6) 3 (5) 5 (8)
Seven sessions 4 (6) 1 (2) 0 (0) 2 (3) 1 (2) 0 (0)
Mean 3.9 3.5 3.2 3.0 2.8 2.5
All numbers are n (%)
of PR exposure,22 23 but the current design and delivery
of education and exercise interventions is based largely
on best practice and expert opinion.2 Indeed, the recent
BTS guidelines on P R highlight the need for funda-
mental research in this area: ‘The optimal structure of PR
remains unknown. More robust studies are required to
determine quality, cost-effectiveness and greater choice
of delivery. To improve accessibility to PR, such research
may include technologies’.
This study has established the potential for delivery
of PR via an online platform in demonstrating non-in-
feriority of all measured outcomes compared with
conventional PR.
Despite the widespread use of online technologies to
manage almost every aspect of daily life, there are surpris-
ingly few well-conducted clinical trials in this field. A
small pilot study explored the use of online PR in COPD
and found the intervention to hold possible merit with
improvements in quality of life and a favourable cost-ben-
efit model.24 Our approach supports this preliminary
finding and offers new evidence that online-supported
PR may benefit a range of patients with COPD who may
be able to access this important intervention through the
use of this technology for the first time.
Within the limitations of the sample size, our study
demonstrated that online PR demonstrated no significant
safety concerns and similarly to conventional PR appears
to be an appropriate intervention if careful clinical
measures are taken to mitigate risk.1 2 Significant numbers
of patients were excluded due to exercise-induced oxygen
desaturation. In face-to-face PR, supplemental oxygen
can be administered and saturations monitored so for
this subset of patients further work is required to ascer-
tain the suitability of online-supported models and best
practice therein.
Access and adherence—key issues for delivery of PR
Access to high-quality PR for patients with COPD is variable
in the UK.25 Resource limitations, geographical distance
from treatment centres and availability of classes which
suit time commitments for participants have all been cited
as key reasons why PR is currently ineffectively delivered
to a large proportion of patients who may benefit.25 This
national audit of PR services identified that over 37% of
patients wait over 3 months for access to classes. Working
patients are particularly disadvantaged as classes are often
only provided during office hours. Consequently, atten-
dance at PR is uniformly low and completion of courses
similarly suboptimal with only 69% of patients referred
attending for assessment. Capacity for delivery is currently
limited— the UK National Audit estimates that 81 000
referrals are made for PR each year—the great majority
for COPD. This is in comparison to the estimated 900 000
patients with an established diagnosis in the UK with a
significant number of patients having no access to local
services within a reasonable travelling time.2 25
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
9
BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
The majority of patients in high-income countries
have access to the internet—a recent study established
that over 86% of patients with cardiopulmonary disease
have direct access.11 Indeed, the majority of subjects (161
of 163) assessed for eligibility for the study had access
to the internet. Furthermore, study of regular internet
use in patients with long-term conditions has identified
that the majority with access (68%), use the internet
regularly to understand more about their disease.26
Currently, disease relevant information is often avail-
able from charities and patient group sites and users
seldom have access to prescribed interventions to date.
This situation will undoubtedly change rapidly in the UK
with the announcement that the National Health Service
(NHS) will support prescription of digital health tech-
nologies from April 2017. However, even with improving
patterns of internet access it is important that most if
not all patients can use digital platforms effectively and
with minimum requirements for training and support
The ‘myCOPD’ web app was designed with patients and
extensive usability assessments were carried out in the
development process. Inevitably, even with a user-friendly
system implementation to all patients with a chronic
condition will be challenging, further studies to define
optimal models to ensure equity of access are required
and resources to ensure support considered in health
economic assessments.
Adherence to PR is another barrier to its overall impact
in this patient group. In 1998, Singh et al found less than
half of patients referred to PR completed the course.27
Adherence rates reported in clinical trials such as this
tend to be higher and our completion rates of over 70%
for this trial are in line with these. There is minimal
published evidence regarding the factors that lead to
non-adherence to PR in patients with COPD. Young et
al identified a number of patient factors including social
isolation and active smoking which predicted poor adher-
ence to PR, suggesting that the necessity for patients to
participate in group sessions may be a barrier for certain
patients.28 In our study, adherence to the intervention in
both arms was as expected, incomplete. Although there
was an attrition over the 6-week intervention period to the
use of online PR, in terms of supported sessions accessed
each week, the mean was still greater than the face-to-
face arm. Very little additional support from the trial or
technical team was required in this study by patients in
the online arm, with most issues resolved remotely. It is
possible a more intensive online or telephone mentoring
approach may improve adherence yet further. We suggest
further studies are required to determine the patient’s
preference for the model of access to PR and the impacts
of this ‘patient-centred’ approach on access and adher-
ence.
Comparison with digital health interventions in other
disease areas
In other disease areas or aspects of COPD care,
there is a richer evidence base to support the role of
digitally supported interventions. In the management of
dyspnoea, a comparison of internet-based versus face-to-
face supported self- management in COPD was assessed
in a small randomised controlled trial.29 This study was
published over 8 years ago and was troubled by tech-
nical challenges; however, its findings demonstrated that
both online and face-to-face programmes were useful in
improving dyspnoea. Cardiac rehabilitation is another
evidence-based facet of the management of a long-term
condition. Patients with cardiac conditions demonstrate a
high level of interest in the concept of technology-enabled
home rehabilitation.30 Clinical studies of internet-based
interventions suggest clinical benefit for patients with
ischaemic heart disease, although overall conclusions
are limited by poor trial quality and the data to support
improvements in activity was stronger.31
The data from our study is aligned with the avail-
able data from existing trials across a range of diseases
suggesting that online supported management and reha-
bilitation may offer clinical benefits. Considering the
range of comorbidities that a large proportion of patients
with long-term conditions suffer from it is vital that a coor-
dinated approach to enable an overall improvement in
health rather than just single disease relevant outcomes is
the goal for the emerging use of mobile health technol-
ogies. This will require close working between clinicians,
technologists and commissioners to ensure that a coordi-
nated and patient friendly approach is developed along
with rigorous testing to establish clinical benefit and
cost-effectiveness.
Limitations of this study
We acknowledge a number of limitations to the interpre-
tation of this trial. It is a relatively small study, which was
designed to explore the non-inferiority of online PR inter-
vention. While we report that all clinical outcomes were
non- inferior, we accept that a larger randomised controlled
trial fully powered to demonstrate health economic benefits
is required to explore the potential to change the model of
PR delivery and hence clinical practice. The study was rela-
tively short—in line with the current clinical model of 6-week
to 12-week clinical PR courses. As extending the online
intervention is not limited by resource implications, it will
be possible to explore the role of long-term programmes
including maintenance classes and the duration of impacts
using this model. Our study was also delivered at a single
centre; we recognise practice may differ across providers
and regions and hence a multicentred pragmatic study is
indicated to understand the place for online PR in compli-
menting current practice in a range of clinical settings.
As with all studies of exercise-related interventions,
double blinding was not possible; however, this will have
impacted on both groups. Every effort was made to ensure
assessments were made in a blinded fashion in both arms.
As many of the barriers to delivery of face-to-face PR—
access, geography and capacity—are overcome within the
conduct of a randomised controlled trial, it is likely that the
real test of online technologies such as this will be against
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
10 BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
the usual standard of care and so ‘real-world’ data will be
key to explore the potential uptake and impacts in this situ-
ation. Therefore, further work is needed—not to establish
comparative efficacy of models but to establish a real-world
evidence base and to understand the long-term utility of
scalable digital platforms across healthcare settings.
Comparison with current guidelines
National and international guidelines recommend PR for
patients with COPD with functional limitation.1 2 Current
models for delivering PR are based on best practice
advice and rely on a model of face-to-face delivery, which
has been established over a number of years. Our study
was designed and delivered in this context and provides
important evidence that a new model of internet-enabled
delivery for this vital intervention may be considered by
clinicians.
Conclusions and policy implementations
COPD is a disease of global health importance with a
limited array of clinically proven interventions available
to clinicians or patients to improve outcomes, PR is one
of these interventions and has become part of the stan-
dard of care for this disease. Recent national audits have
identified significant inadequacies in accessing PR and
recent UK guidelines identify the need for novel studies
to explore new models of delivering PR to patients with
COPD to overcome this unmet need.
We have conducted a significant study to explore
non-inferiority of the role of internet-enabled PR to
improve clinical outcomes compared with the standard
model of clinical delivery. We have demonstrated for
the first time that in all clinical measures studied, online
PR using the myMHealth platform is non-inferior to
usual care and suggest that this modality of delivery be
explored widely in the delivery of this important inter-
vention in this common disease. There is now a potential
opportunity for the online provision of PR to compli-
ment currently available face-to-face services in order to
increase capacity, reduce costs and broaden availability to
socially or geographically isolated groups, which requires
exploration in future studies across wide populations to
establish optimal implementation of strategies and to
assess health economic benefits.
Acknowledgements We thank the clinical trials team at Queen Alexandra
Hospitals NHS trust and the staff of myMHealth. We are grateful to the patients who
contributed to the design and conduct of the study.
Contributors RDV, MN, SCB, VC and TW contributed to the study design. BG was
principal investigator. RDV, MN, BG, TB and AJC contributed to the study delivery.
VC analysed the data. All authors contributed to data interpretation and manuscript
preparation and reviewed the nal draft. TW is guarantor for the data.
Funding The study was funded by a Small Business Research Initiative (SBRI)
grant from NHS England.
Competing interests Dr Bourne reports grants and personal fees from myMHealth
(a medical software company) during the conduct of the study; other from
myMHealth, outside the submitted work. He is CEO, co-founder and part owner
of this company. Mrs De Vos reports personal fees from myMHealth, during the
conduct of the study; and is a partner in the rehabilitation facility that hosted some
of the clinical trial activity. Dr Green reports grants to Portsmouth Hospitals NHS
Trust from myMHealth, during the conduct of the study. Mr North has nothing to
disclose. Dr Cornelius reports personal fees from myMHealth, during the conduct of
the study. Professor Chauhan has nothing to disclose. Dr Brown reports grants from
myMHealth, during the conduct of the study. Professor Wilkinson reports grants and
personal fees from myMHealth during the conduct of the study. He is co-founder
and part owner of this company.
Patient consent Detail has been removed from this case description/these case
descriptions to ensure anonymity. The editors and reviewers have seen the detailed
information available and are satised that the information backs up the case the
authors are making.
Ethics approval This study was approved by the research ethics committee for
Berkshire B of the UK Health Research Authority (15/SC/0345).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All anonymised trial data are available on application to
the senior author.
Open Access This is an Open Access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work is
properly cited and the use is non-commercial. See: http:// creativecommons. org/
licenses/ by- nc/ 4. 0/
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2017. All rights reserved. No commercial use is permitted unless otherwise
expressly granted.
references
1. National Institute for Health and Care Excellence. Chronic obstructive
pulmonary disease;. 2013 https://www. nice. org. uk/ guidance/
conditions- and- diseases/ respiratory- conditions/ chronic- obstructive-
pulmonary- disease.
2. Society BT. British thoracic society quality standards for pulmonary
rehabilitation in adults, 20146https://www. brit- thoracic. org. uk/
document- library/ clinical- information/ pulmonary- rehabilitation/ bts-
quality- standards- for- pulmonary- rehabilitation- in- adults/.
3. McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for
chronic obstructive pulmonary disease. Cochrane Database Syst Rev
2015:CD003793.
4. Garcia-Aymerich J, Lange P, Benet M, et al. Regular physical activity
reduces hospital admission and mortality in chronic obstructive
pulmonary disease: a population based cohort study. Thorax
2006;61:772–8.
5. Fischer MJ, Scharloo M, Abbink JJ, et al. Drop-out and attendance
in pulmonary rehabilitation: the role of clinical and psychosocial
variables. Respir Med 2009;103:1564–71.
6. Arnold E, Bruton A, Ellis-Hill C. Adherence to pulmonary
rehabilitation: a qualitative study. Respir Med 2006;100:1716–23.
7. Vogiatzis I, Rochester CL, Spruit MA, et al. Increasing implementation
and delivery of pulmonary rehabilitation: key messages from the new
ATS/ERS policy statement. Eur Respir J 2016;47:1336–41 http://
www. ncbi. nlm. nih. gov/ pubmed/ 27132269.
8. Mendes de Oliveira JC. Studart Leitao Filho FS, Malosa Sampaio LM,
Negrinho de Oliveira AC, Hirata R, Costa D, Donner CF, de Oliveira
LV. outpatient vs. Home-based pulmonary rehabilitation in COPD: a
randomized controlled trial. Multidisciplinary Respiratory Medicine
2010;5:401.
9. Holland AE, Hill CJ, Rochford P, et al. Telerehabilitation for people
with chronic obstructive pulmonary disease: feasibility of a simple,
real time model of supervised exercise training. J Telemed Telecare
2013;19:222–6.
10. Cruz J, Brooks D, Marques A. Home telemonitoring effectiveness in
COPD: a systematic review. Int J Clin Pract 2014;68:369–78.
11. Disler RT, Inglis SC, Newton PJ, et al. Patterns of technology use in
patients attending a cardiopulmonary outpatient clinic: a self-report
survey. Interact J Med Res 2015;4:e5.
12. Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic
functional mobility for frail elderly persons. J Am Geriatr Soc
1991;39:142–8.
13. Mesquita R, Wilke S, Smid D, et al. Timed up & go test in COPD:
changes over time. validity and responsiveness to pulmonary
rehabilitation. 1.2 Rehabilitation and Chronic Care 2014;44(Suppl
58):3037. Sep.
14. Redelmeier DA, Bayoumi AM, Goldstein RS, et al. Interpreting small
differences in functional status: the six Minute walk test in chronic
lung disease patients. Am J Respir Crit Care Med 1997;155:1278–82.
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
11
BourneS, etal. BMJ Open 2017;7:e014580. doi:10.1136/bmjopen-2016-014580
Open Access
15. Troosters T, Gosselink R, Decramer M, et al. Six minute walking
distance in healthy elderly subjects. Eur Respir J 1999;14:270–4.
16. Puhan MA, Chandra D, Mosenifar Z, et al. The minimal important
difference of exercise tests in severe COPD. Eur Respir J
2011;37:784–90.
17. Holland AE, Hill CJ, Rasekaba T, et al. Updating the minimal
important difference for six-minute walk distance in patients with
chronic obstructive pulmonary disease. Arch Phys Med Rehabil
2010;91:221–5.
18. GOLD- Global Initiative for Chronic Obstructive lung disease. https://
www. guidelines. co. uk/ gold/ copd.
19. Royston P. Multiple imputation of missing values: update. The Stata
Journal 2005;5:1–14.
20. Lacasse Y, Wong E, Guyatt GH, et al. Meta-analysis of respiratory
rehabilitation in chronic obstructive pulmonary disease. Lancet
1996;348:1115–9.
21. Laviolette L, Bourbeau J, Bernard S, et al. Assessing the impact
of pulmonary rehabilitation on functional status in COPD. Thorax
2008;63:115–21.
22. Beauchamp MK, Janaudis-Ferreira T, Goldstein RS, et al. Optimal
duration of pulmonary rehabilitation for individuals with chronic
obstructive pulmonary disease - a systematic review. Chron Respir
Dis 2011;8:129–40.
23. Green RH, Singh SJ, Williams J, et al. A randomised controlled
trial of four weeks versus seven weeks of pulmonary
rehabilitation in chronic obstructive pulmonary disease. Thorax
2001;56:143–5.
24. Burkow TM, Vognild LK, Johnsen E, et al. Comprehensive pulmonary
rehabilitation in home-based online groups: a mixed method pilot
study in COPD. BMC Res Notes 2015;8:766.
25. Steiner M, Holzhauer-Barrie J, Lowe D, et al; Pulmonary
Rehabilitation: time to breath better. Resources and organisation of
Pulmonary Rehabilitation services in England and Wales: National
Chronic Obstructive Pulmonary Disease (COPD) Audit Programme,
2015. www. rcplondon. ac. uk/ COPD.
26. Martinez CH, St Jean BL, Plauschinat CA, et al. Internet access
and use by COPD patients in the National Emphysema/COPD
Association survey. BMC Pulm Med 2014;14:66.
27. Singh SJ, Smith DL, Hyland ME, et al. A short outpatient pulmonary
rehabilitation programme: immediate and longer-term effects on
exercise performance and quality of life. Respir Med
1998;92:1146–54.
28. Young P, Dewse M, Fergusson W, et al. Respiratory rehabilitation in
chronic obstructive pulmonary disease: predictors of nonadherence.
Eur Respir J 1999;13:855–9.
29. Nguyen HQ, Donesky-Cuenco D, Wolpin S, et al. Randomized
controlled trial of an internet-based versus face-to-face dyspnea
self-management program for patients with chronic obstructive
pulmonary disease: pilot study. J Med Internet Res
2008;10:e9.
30. Buys R, Claes J, Walsh D, et al. Cardiac patients show high interest
in technology enabled cardiovascular rehabilitation. BMC Med Inform
Decis Mak 2016;16:95.
31. Devi R, Singh SJ, Powell J, et al. Internet-based interventions for the
secondary prevention of coronary heart disease. Cochrane Database
Syst Rev 2015;22:CD009386.
32. Cote CG, Casanova C, Marín JM, et al. Validation and comparison
of reference equations for the 6-min walk distance test. Eur Respir J
2008;31:571–8.
33. Kon SS, Canavan JL, Jones SE, et al. Minimum clinically important
difference for the COPD Assessment Test: a prospective analysis.
Lancet Respir Med 2014;2:195–203.
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from
controlled trial
obstructive pulmonary disease: randomised
rehabilitation for patients with chronic
Online versus face-to-face pulmonary
Green, Thomas Brown, Victoria Cornelius and Tom Wilkinson
Simon Bourne, Ruth DeVos, Malcolm North, Anoop Chauhan, Ben
doi: 10.1136/bmjopen-2016-014580
2017 7: BMJ Open
http://bmjopen.bmj.com/content/7/7/e014580
Updated information and services can be found at:
These include:
References http://bmjopen.bmj.com/content/7/7/e014580#ref-list-1
This article cites 28 articles, 8 of which you can access for free at:
Open Access
http://creativecommons.org/licenses/by-nc/4.0/non-commercial. See:
provided the original work is properly cited and the use is
non-commercially, and license their derivative works on different terms,
permits others to distribute, remix, adapt, build upon this work
Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
This is an Open Access article distributed in accordance with the Creative
service
Email alerting box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
Collections
Topic Articles on similar topics can be found in the following collections
(363)Respiratory medicine
Notes
http://group.bmj.com/group/rights-licensing/permissions
To request permissions go to:
http://journals.bmj.com/cgi/reprintform
To order reprints go to:
http://group.bmj.com/subscribe/
To subscribe to BMJ go to:
group.bmj.com on February 7, 2018 - Published by http://bmjopen.bmj.com/Downloaded from