Engel et al.

Trials (2017) 18:282

DOI 10.1186/s13063-017-2027-z

STUDY PROTOCOL Open Access

The effect of combining manual therapy

with exercise for mild chronic obstructive
pulmonary disease: study protocol for a
randomised controlled trial
Roger M. Engel1*, Jaxson Wearing1, Peter Gonski2 and Subramanyam Vemulpad1

Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a major cause of disability and hospital admission.
Current management strategies have not been successful in altering the loss of lung function typically seen as the
disease progresses. A recent systematic review into the use of spinal manipulative therapy (SMT) in the management
of COPD concluded that there was low level evidence to support the view that a combination of SMT and exercise
had the potential to improve lung function more than exercise alone in people with moderate to severe COPD.
The aim of this study is to investigate whether the combination of exercise and manual therapy (MT) that includes
SMT produces sustainable improvements in lung function and exercise capacity in people with mild COPD.
Methods/design: The study is a randomised controlled trial of 202 people with stable mild COPD. The cohort will be
divided into two equal groups matched at baseline. The first group will receive a standardised exercise program. The second
group will receive MT that includes SMT plus the same standardised exercise program. Exercise will be administered a total
of 36 times over an 18-week period, while MT will be administered in conjunction with exercise a total of 15 times over a
6-week period. The primary outcome measure is lung function (forced expiratory volume in the 1st second: FEV1 and forced
vital capacity: FVC). The secondary outcome measures are the 6-minute walking test (6MWT), quality of life questionnaire (St
George’s Respiratory Questionnaire: SGRQ), anxiety and depression levels (Hospital Anxiety and Depression Scale: HADS),
frequency of exacerbations, chest wall expansion measurements (tape measurements) and systemic inflammatory biomarker
levels. Outcome measurements will be taken by blinded assessors on seven occasions over a 48-week period. Adverse event
data will also be gathered at the beginning of each intervention session.
Discussion: This randomised controlled trial is designed to investigate whether the combination of MT and exercise
delivers any additional benefits to people with mild COPD compared to exercise alone. The study is designed in
response to recommendations from a recent systematic review calling for more research into the effect of MT in the
management of COPD.
Trial registration: ANZCTRN, 12614000766617. Registered on 18 July 2014.
Keywords: Chronic obstructive pulmonary disease, COPD, Manual therapy, Spinal manipulative therapy, Pulmonary
rehabilitation, Exercise, Randomised controlled trial, Lung function, Trial protocol

* Correspondence: [email protected]
1
Department of Chiropractic, Macquarie University, North Ryde, Sydney, NSW
2109, Australia
Full list of author information is available at the end of the article

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Engel et al. Trials (2017) 18:282 Page 2 of 7

Background Manual therapy (MT) is an intervention capable of pro-

Chronic obstructive pulmonary disease (COPD) is a ducing a short-term reduction in CWR in people with
major cause of chronic morbidity and mortality. It is re- COPD. A recent systematic review which investigated the
sponsible for a substantial and increasing proportion of effect of spinal manipulative therapy (SMT), a form of
the economic and social burden of disease and is MT, in the management of COPD recommended the need
currently ranked as the fourth leading cause of death for further research into the use of SMT with exercise for
worldwide [1, 2]. The disease is characterised by pro- people with COPD [18]. While acknowledging that the
gressive loss of lung function and includes symptoms studies reviewed used small sample sizes, the reviewers
such as dyspnea, sputum production and cough [1, 2]. concluded that the quality of the evidence showing that
While lung function tests are the primary method used the combination of SMT and exercise had the potential to
to diagnose and track disease progression, COPD is as- produce clinically meaningful improvements in lung func-
sociated with other comorbidities such as depression, tion and exercise capacity compared to exercise alone was
cardiovascular disease and skeletal muscle dysfunction high [18]. This finding had not previously been reported
which also influence progression [1]. in the literature and provides an opportunity to improve
As exercise capacity is a prognostic indicator in COPD, the outcomes of PR [19, 20].
any skeletal muscle dysfunction that reduces exercise per- The primary aim of this trial is to evaluate the effect
formance can affect disease severity over time by reducing on lung function of administering MT that includes
exercise capacity [2]. In COPD, the primary source of SMT in conjunction with exercise to people with mild
exercise limitation is dyspnea, which curtails exercise per- COPD. The secondary aim is to investigate the effect of
formance before maximum capacity has been reached. Ex- this combination of interventions on exercise capacity,
ercise performance has therefore become a target for quality of life, anxiety and depression and systemic in-
therapeutic intervention with both international and flammatory biomarkers.
Australian guidelines now including exercise training as a
standard component in pulmonary rehabilitation [1, 2]. Methods/design
One of the causes of exercise-limiting dyspnea is altered Study design
chest wall mechanics which includes an increase in chest The trial is designed as a randomised controlled trial
wall rigidity (CWR) [3–6]. This increase results in a fall in and fulfils the requirements of the Standard Protocol
the efficiency of the ventilatory pumping mechanism and Items: Recommendations for Interventional Trials
an increase in the effort required to breathe [5, 7–10]. (SPIRIT) checklist [21] (Additional file 1). It will evaluate
Addressing the increase in CWR has been suggested as a 202 participants randomly allocated to two equal groups.
way of reducing or delaying the onset of exercise-limiting Participants in Group 1 (Ex) will undergo an exercise
dyspnea [11]. regime that has been modelled on an existing pulmonary
The increase in CWR typically seen in COPD is ini- rehabilitation program; participants in Group 2 (SM +
tially the result of expansionary forces exerted on the Ex) will have MT which includes SMT administered to
chest wall by the development of lung hyper-inflation their thoracic spine and ribs just prior to performing the
[12]. Over time, this increase is perpetuated by the same exercise regime as Group 1. Participants will be re-
mechanical properties of the respiratory muscles which cruited through direct referral from their respiratory
resist changes in length through a process known as specialist or general practitioner or through self-referral
thixotropy [13, 14]. The thixotropic properties of a in response to public advertisements calling for volun-
muscle are determined by the position that muscle is teers for the trial. The trial is being conducted in the
held in just prior to contraction. In the case of the pulmonary rehabilitation department at Sutherland
respiratory muscles, lung hyper-inflation places these Hospital in Sydney, Australia.
muscles in either a shortened or lengthened position
prior to contraction. Altering the resting length of Participant characteristics
these muscles would reduce CWR and therefore miti- The trial includes both males and females between
gate one of the factors responsible for producing the ages of 50 and 65 years of age with a forced ex-
exercise-limiting dyspnea. piratory volume in the 1st second (FEV1)/forced vital
While pulmonary rehabilitation (PR) has been shown to capacity (FVC) ratio of < 0.7 and an FEV1% predicted
increase exercise capacity, it has not been shown to be cap- of 60–80% (COPDX 2016: mild COPD). Participants
able of delivering any clinically meaningful increases in lung will be excluded if they are currently smoking, cannot
function [15–17]. Administering an intervention capable of complete a 6-minute walking test (6MWT) unassisted,
reducing CWR in conjunction with exercise has the poten- have a history of autoimmune disease or are contra-
tial of producing an increase in exercise capacity and lung indicated to SMT. Inclusion and exclusion criteria are
function through a synergy between interventions. described in Table 1.
Engel et al. Trials (2017) 18:282 Page 3 of 7

Table 1 Inclusion and exclusion criteria for participation

Inclusion criteria Exclusion criteria
• Male and female • Inability to complete 6-minute walking test unassisted
• 50–65 years • History of auto-immune disease, e.g. RA or SLE that may have altered
• Mild COPD (60% ≤ FEV1% < 80%: COPDX) systemic inflammatory biomarkers
• Stable COPD (no exacerbations in preceding 6 months) • Contra-indicated to thoracic spinal manipulation
• Non-smoking (for preceding 6 months) o Bone density (DEXA) scores below minimum levels (T score < –2.5
• Willingness to provide written consent and/or Z score < –1)
• Willingness to participate in and comply with the o Thoracic joint instability
study requirements o Acute pain on thoracic joint range of motion testing
o Advanced chest wall muscle wasting
o High level of anxiety related to receiving thoracic spinal manipulation
• Inability to understand English
• Inability to provide informed consent, e.g. people with a cognitive
impairment, an intellectual disability or a mental illness
• Completed a PR program in the previous 12 months
COPD chronic obstructive pulmonary disease, COPDX the COPD-X Plan. Australian and New Zealand guidelines for the management of chronic obstructive pulmonary
disease. Version 2.45. March 2016, FEV1% forced expiratory volume in the 1st second percent predicted (age-matched), RA rheumatoid arthritis, SLE systemic lupus
erythematosus, DEXA dual energy X-ray absorptiometry, PR pulmonary rehabilitation

Protocol description All MT is administered by chiropractors and/or osteo-

Volunteers who meet the inclusion criteria will be given paths with more than 5 years of experience in the manual
an information sheet and asked to provide written con- therapy protocol (MTP) used in this trial. This is the same
sent to participate in the trial. They will then undergo a MTP that was used in two previous trials on patients with
physical screening examination for the presence of COPD [22, 23]. It consists of a combination of soft tissue
contra-indications to thoracic MT. After successfully (ST) therapy and thoracic spinal manipulation (SM).
passing this screening, they will be enrolled in the trial, The ST component of the MTP consists of gentle ef-
given a trial-specific identification (ID) number and allo- fleurage and cross-fibre friction therapy applied to the
cated to a group sequentially using a computer- muscles of the posterior chest wall including the intercos-
generated random sequence list drawn up prior to the tal, serratus posterior and anterior, rhomboid, trapezius,
start of the trial by a member of the staff not involved in latissimus dorsi, erector spinae, quadratus lumborum and
any other aspect of the trial. Baseline measurements for levator scapulae muscles. The SM component consists of
each participant are then taken. These include lung two separate manipulations (Grade V mobilisation [24]).
function assessment using spirometry, exercise capacity Each manipulation involves the delivery of a high-velocity
(6MWT), chest wall expansion (tape measure), quality of low-amplitude (HVLA) posterior-to-anterior force di-
life (St George’s Respiratory Questionnaire: SGRQ), anx- rected towards the intervertebral, costovertebral and cost-
iety and depression levels (Hospital Anxiety and Depres- otransverse joints. The first manipulation is administered
sion Scale: HADS) and systemic inflammatory biomarker at the level of the upper/middle thoracic spine, while the
levels via blood sampling (C-reactive protein (CRP) and second is administered at the level of the middle/lower
leukocyte count). The study protocol flow of participants thoracic spine. All SM are administered as non-specific,
is outlined in Fig. 1. multi-joint (group) manipulations. Administering SM in
All outcome measures will be taken by staff of the hos- this way reduces the total number of manipulations
pital familiar with administering these assessments and required in a single session, as each manipulation has the
blinded to a participant’s group allocation. Lung function potential to affect several thoracic vertebrae and their
measurements are measured in the sitting position and in- associated ribs simultaneously. An MT session lasts ap-
clude FEV1 and FVC. Exercise capacity is assessed using proximately 20 minutes and is administered just prior to
the 6MWT where capacity is determined by the total dis- exercise intervention in the MT + Ex Group.
tance walked on a flat surface (hospital hallway) in a
period of 6 minutes. Quality of life (SGRQ) and anxiety Consent process
and depression (HADS) scores are calculated using the The consent process followed in this trial will be the
standard procedures for these questionnaires. Frequency same for all participants. Potential participants will re-
of exacerbations is gathered by direct questioning of a par- ceive the Patient Information and Consent Form (PICF)
ticipant. Systemic inflammatory biomarkers are measured explaining the trial’s processes and procedures, including
via blood sampling by the hospital’s pathology department consent to publish, and what is expected from them
from samples (10 mL) collected by a registered nurse who during the trial. Each participant will be given the op-
is blinded to a participant’s group allocation. The SPIRIT portunity to ask questions about their involvement in
figure showing the respective time points for enrolment, the trial and to have those questions answered by a
interventions and assessments is provided in Fig. 2. researcher associated with the trial prior to providing
Engel et al. Trials (2017) 18:282 Page 4 of 7

Fig. 1 Flow of participants through the trial. MT manual therapy, Ex exercise

consent. A trial-specific ID number will be used when Statistical analysis

gathering and recording all information about a partici- Data will be reported as group means, standard deviations
pant. A list containing the contact details of all partici- and 95% confidence intervals. Analysis will be performed
pants and their corresponding ID numbers will be kept as an analysis of covariance (ANCOVA) for differences be-
separate from all other data. All paper copy forms will tween groups with baseline as a covariate. Standard errors
be stored in a locked filing cabinet in the hospital facility will be calculated using a non-parametric bootstrap to
during the trial. Once the intervention phase of the trial allow for the different error variances for each group. A p
has been completed (week 26), all data from these files value of < 0.05 has been set for statistical significance. For
will be transferred to a password-protected encrypted outcomes found to be statistically significant, the propor-
file and stored on the chief investigator’s university com- tion of participants with a change greater than the
puter located in his locked university office. These files minimum clinically important difference will be calculated
will be backed up on an external hard drive and stored for each outcome. The number needed to treat will be
in a locked filing cabinet in the university office of an- calculated using Bender’s method for confidence intervals.
other investigator. The trial was approved by the South Missing data will be accounted for by using an intention-
Eastern Sydney Local Health District - Human Research to-treat analysis with data from subjects lost to follow-up
Ethics Committee (HREC): approval number 13/004. imputed using the multiple imputation method.
Two interim analyses are planned before the final ana-
Sample size calculation lysis. They are mid-trial following the second blood test
The sample size calculation was based on FVC. The (week 24) and 6 weeks after completion of all interven-
minimum clinically important difference for FVC is tions (week 32). The conduct of the trial will not be
200 mL with the standard deviation obtained from pre- affected by the results of these interim analyses.
vious studies [22, 23]. With a power of 0.8 (80%) and an
alpha of 0.05, the minimum sample size per group is 92. Data monitoring
Assuming a drop-out rate of 10%, the minimum cohort A Data Safety Monitoring Board (DSMB) has been
size would be 202 (two groups of 101). appointed to oversee the study. It consists of a
Engel et al. Trials (2017) 18:282 Page 5 of 7

STUDY PERIOD
Enrolment Allocation Post-allocation (weeks)

TIMEPOINT -1 0 1 4 8 16 24 25 26 32 48

ENROLMENT:

Eligibility screen X

Informed consent X
Physical
examination
X

Allocation X

INTERVENTIONS:

Exercise (Ex)

Manual Therapy
(MT)

ASSESSMENTS:

Vitals:
heart rate, blood X X
pressure, height,
X X X X X
weight
Six minute
walking test X X X X X X X
(6MWT)
Spirometry: X X X X X X X
FEV1, FVC
Chest wall X X
expansion
X X X X X
Quality of life: X X X X X X X
SGRQ, HAD
Blood test:
CRP, leukocytes
X X X X X
Adverse event
monitoring
Fig. 2 SPIRIT figure showing time points for enrolment, interventions and assessments. FEV1 Forced expiratory volume in the 1st second, FVC Forced
vital capacity, SGRQ St George’s Respiratory Questionnaire, HAD Hospital Anxiety and Depression (scale), CRP C-reactive protein

respiratory physician, a unit nurse manager, the hospital’s does not include any neck manipulation. The MTP used
governance officer and an experienced manual therapist in this trial is the same protocol as the one used in two
clinician. The DSMB will meet every 4 months or as previous trials on people with COPD [22, 23]. There
needed to review the study data. were no major or moderate AEs reported in either of
those trials. Mild AEs associated with MT intervention
Adverse events were reported at a rate of 15% (18 out of 112) in the trial
The risks of harm or discomfort to participants in this on patients with moderate COPD (average age 56.1 years)
project primarily relate to the potential for adverse [22] and at a rate of less than 1% (2 out of 403) in the
events (AEs) resulting from MT intervention. The ma- trial on patients with moderate to severe COPD (average
jority of reported AEs associated with MT are mild age 65.5 years) [23].
(muscle soreness and local discomfort), self-limiting, re- As the MTP used in the trial being reported here is
quire no further medical attention and resolve within the same as the one used in the two previous Australian
48 hours [25]. Moderate AEs such as fracture, have also trials, it is reasonable to predict that the risk of harm or
been reported following SMT and have been estimated discomfort to participants will be at a similar rate to
to occur at a rate of 1 in 40,000 [26]. Reports of major those of the previous trials.
or catastrophic AEs resulting from spinal manipulation
have appeared in the literature with nearly all associated Discussion
with neck (cervical) manipulation. This trial involves In COPD, disease progression is marked by declining
manipulation of the thoracic spine and ribs only and lung function and includes predictors of morbidity and
Engel et al. Trials (2017) 18:282 Page 6 of 7

mortality such as exercise capacity and exacerbations. and Consent Form; PR: Pulmonary rehabilitation; RA: Rheumatoid arthritis;
While pulmonary rehabilitation has demonstrated im- RCT: Randomised controlled trial; SGRQ: St George’s Respiratory
Questionnaire; SLE: Systemic lupus erythematous; SM: Spinal manipulation;
provements in exercise capacity and quality of life SMT: Spinal manipulative therapy; ST: Soft tissue
measures, it has yet to show any clinically meaningful
improvements in lung function. Administering a com- Acknowledgements
In-kind support for the trial was provided by Sutherland Hospital and
bination of MT and exercise has been shown to have the Macquarie University.
potential to deliver improvements in lung function and
exercise capacity by reducing CWR and delaying the Funding
This trial is supported by a 2014 ‘Industry Grant’ (reference number not
onset of exercise-limiting dyspnea, thereby facilitating an available) from the Chiropractic Association of Australia (New South Wales)
increase in exercise performance. We hypothesize that and a 2015 ‘Establishment Grant’ (reference number not available) from the
over time this would have a cumulative beneficial effect St George and Sutherland Medical Research Foundation.
on exercise capacity.
Availability of data and materials
For this approach to reach its maximum potential, the Not applicable.
combination of interventions would need to be adminis-
tered earlier in the disease cycle (i.e. in the mild COPD Authors’ contributions
RE, PG and SV designed the study. JW and RE prepared and edited the
stage) before a greater proportion of lung function and manuscript. All authors read and approved the final manuscript.
exercise capacity has been lost. Administering an inter-
vention that improves the long-term prognosis of COPD Authors’ information
Roger Engel, Jaxson Wearing and Subramanyam Vemulpad are with the
through increasing exercise capacity may also help to Department of Chiropractic, Macquarie University, Sydney, Australia. Peter
improve the uptake of exercise as a possible preventative Gonski is with Southcare, Sutherland Hospital, Sydney, Australia.
measure against disease progression.
The current Australian guidelines recommend PR for Competing interests
The authors declare that they have no competing interests.
people with all stages of COPD [2]. However, figures
show that only 5—10% of Australians with moderate to Consent for publication
severe COPD access PR services [27]. While there are a Written informed consent was obtained from each participant for publication
of their individual details and accompanying images in this manuscript.
number of reasons for such a low uptake, including poor
service availability, compliance has been identified as Ethics approval and consent to participate
one of the reasons. Including MT intervention in PR The study conforms to the Declaration of Helsinki. The study has been approved
by the South Eastern Sydney Local Health District - Human Research Ethics
programs may help remedy this if it is shown to enhance Committee (HREC): approval number 13/004. All participants give written
the benefits of PR. informed consent.
The randomised controlled trial being reported in this
manuscript is designed to examine the effect of a combin- Publisher’s Note
ation of MT and exercise on lung function and exercise Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
capacity in people with mild COPD. The trial’s design
satisfies the recommendations of a recent systematic Author details
1
review into the use of SMT in the management of COPD Department of Chiropractic, Macquarie University, North Ryde, Sydney, NSW
2109, Australia. 2Southcare, Sutherland Hospital, Sydney, Australia.
[18] in that it is adequately powered, configured to have a
low risk of bias and has the potential to deliver meaningful Received: 7 November 2016 Accepted: 30 May 2017
data for the use of MT in the management of COPD.
References
Trial status 1. Global strategy for the diagnosis, management and prevention of COPD
Recruitment for the trial is ongoing at the time of submission. 2017 (GOLD). http://goldcopd.org/gold-2017-global-strategy-diagnosis-
management-prevention-copd/. Accessed 15 June 2017.
2. The COPD-X Plan: Australian and New Zealand guidelines for the
Additional file management of chronic obstructice pulmonary disease 2017. Version 2.49.
http://copdx.org.au/. Accessed 15 June 2017.
Additional file 1: SPIRIT 2013 checklist. Recommended items to address 3. Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R.
in a clinical trial protocol and related documents. (PDF 168 kb) Characteristics of physical activities in daily life in chronic obstructive
pulmonary disease. Am J Respir Crit Care Med. 2005;171(9):972–7.
4. Theander K, Jakobsson P, Jörgensen N, Unosson M. Effects of pulmonary
Abbreviations rehabilitation on fatigue, functional status and health perceptions in
6MWT: 6-Minute walking test; AE: Adverse event; ANCOVA: Analysis of patients with chronic obstructive pulmonary disease: a randomized
covariates; COPD: Chronic obstructive pulmonary disease; CRP: C-reactive controlled trial. Clin Rehabil. 2009;23(2):125–36.
protein; CWR: Chest wall rigidity; DEXA: Dual energy X-ray absorptiometry; 5. O’Donnell DE, Ora J, Webb KA, Laveneziana P, Jensen D. Mechanisms of
DSMB: Data Safety Monitoring Board; Ex: Exercise; FEV1: Forced expiratory activity-related dyspnea in pulmonary diseases. Respir Physiol Neurobiol.
volume in the 1st second; FVC: Forced vital capacity; HADS: Hospital Anxiety 2009;167(1):116–32.
and Depression Scale; HVLA: High-velocity low-amplitude; ID: Identification; 6. Pride N, Macklem PT. Lung mechanics in disease. Chapter 1.1: Chronic
MT: Manual therapy; MTP: Manual therapy protocol; PICF: Patient Information Obstructive Pulmonary Disease. Compr Physiol. 1986.
Engel et al. Trials (2017) 18:282 Page 7 of 7

7. O’Donnell DE, Laveneziana P. Dyspnea and activity limitation in COPD:

mechanical factors. COPD: J Chron Obstruct Pulmon Dis. 2007;4(3):225–36.
8. Pepin V, Saey D, Laviolette L, Maltais F. Exercise capacity in chronic
obstructive pulmonary disease: mechanisms of limitation. COPD: J Chron
Obstruct Pulmon Dis. 2007;4(3):195–204.
9. Ranieri V, Giuliani R, Mascia L, Grasso S, Petruzzelli V, Bruno F, et al. Chest
wall and lung contribution to the elastic properties of the respiratory
system in patients with chronic obstructive pulmonary disease. Eur Respir
J. 1996;9(6):1232–9.
10. Aliverti A, Kayser B, Macklem PT. A human model of the pathophysiology of
chronic obstructive pulmonary disease. Respirology. 2007;12(4):478–85.
11. Engel R, Vemulpad S. The role of spinal manipulation, soft-tissue therapy,
and exercise in chronic obstructive pulmonary disease: a review of the
literature and proposal of an anatomical explanation. J Altern Complement
Med. 2011;17(9):797–801.
12. Brashers VL, Davey S. Alterations of pulmonary function. In:
Pathophysiology: the biologic basis for disease in adults and children.
London: Elsevier; 2006. p. 1205–45.
13. Izumizaki M, Iwase M, Ohshima Y, Homma I. Acute effects of thixotropy
conditioning of inspiratory muscles on end-expiratory chest wall and lung
volumes in normal humans. J Appl Physiol. 2006;101(1):298–306.
14. Proske U, Morgan DL, Gregory JE. Thixotropy in skeletal muscle and in
muscle spindles: a review. Prog Neurobiol. 1993;41(6):705–21.
15. Bestall J, Paul E, Garrod R, Garnham R, Jones P, Wedzicha J. Longitudinal
trends in exercise capacity and health status after pulmonary rehabilitation
in patients with COPD. Respir Med. 2003;97(2):173–80.
16. Pitta F, Troosters T, Probst VS, Langer D, Decramer M, Gosselink R. Are
patients with COPD more active after pulmonary rehabilitation? Chest J.
2008;134(2):273–80.
17. Laviolette L, Bourbeau J, Bernard S, Lacasse Y, Pepin V, Breton M-J, et al.
Assessing the impact of pulmonary rehabilitation on functional status in
COPD. Thorax. 2008;63(2):115–21.
18. Wearing J, Beaumont S, Forbes D, Brown B, Engel R. The use of spinal
manipulative therapy in the management of chronic obstructive pulmonary
disease: a systematic review. J Altern Complement Med. 2016;22(2):108–14.
19. Garcia-Aymerich J, Agustí À, Barberà JA, Belda J, Farrero E, Ferrer A, et al.
Phenotypic heterogeneity of chronic obstructive pulmonary disease. Arch
Bronconeumol (English Edition). 2009;45(3):133–42.
20. Celli B, MacNee W, Agusti A, Anzueto A, Berg B, Buist A, et al. Standards for
the diagnosis and treatment of patients with COPD: a summary of the ATS/
ERS position paper. Eur Respir J. 2004;23(6):932–46.
21. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K,
Hróbjartsson A, Mann H, Dickersin K, Berlin J, Doré C, Parulekar W,
Summerskill W, Groves T, Schulz K, Sox H, Rockhold FW, Rennie D, Moher D.
SPIRIT 2013 Statement: Defining standard protocol items for clinical trials.
Ann Intern Med. 2013;158:200–7.
22. Engel RM, Vemulpad SR, Beath K. Short-term effects of a course of manual
therapy and exercise in people with moderate chronic obstructive pulmonary
disease: a preliminary clinical trial. J Manip Physiol Ther. 2013;36(8):490–6.
23. Engel RM, Gonski P, Beath K, Vemulpad S. Medium term effects of including
manual therapy in a pulmonary rehabilitation program for chronic
obstructive pulmonary disease (COPD): a randomized controlled pilot trial. J
Man Manip Ther. 2014;24:80–9.
24. Maitland GD. Maitland’s vertebral manipulation. 8th ed. Eds: Hengeveld E,
Banks K, editors. Edinburgh: Elsevier; 2014.
25. Carnes D, Mars TS, Mullinger B, Froud R, Underwood M. Adverse events and
manual therapy: a systematic review. Man Ther. 2010;15(4):355–63.
26. Ernst E. Adverse effects of spinal manipulation: a systematic review. J R Soc Submit your next manuscript to BioMed Central
Med. 2007;100(7):330–8.
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