Open access Review

Effects of exercise training on physical

and psychosocial health in children
with chronic respiratory disease: a
systematic review and meta-analysis
Barbara Joschtel,1 Sjaan R Gomersall,2 Sean Tweedy,1 Helen Petsky,3
Anne B Chang,4,5,6 Stewart G Trost5

To cite: Joschtel B, Abstract

Gomersall SR, Tweedy S, et al. What is already known
Introduction  Chronic disease in children is increasing,
Effects of exercise training
including the prevalence of chronic respiratory diseases ►► Exercise has been shown to be beneficial for healthy
on physical and psychosocial
health in children with such as asthma, cystic fibrosis (CF), bronchiectasis and children by improving cardiovascular fitness, mus-
chronic respiratory disease: bronchopulmonary dysplasia (BPD). The aim of this culoskeletal health, mental health and elements of
a systematic review and systematic review and meta-analysis was to evaluate the cardiometabolic risk factors.
meta-analysis. BMJ Open effects of exercise training on health outcomes in children ►► Exercise improves cardiovascular fitness and
Sport & Exercise Medicine with chronic respiratory disease.
2018;0:e000409. doi:10.1136/ quality of life (QoL) in children with asthma and
Method  Five databases were searched for randomised cystic fibrosis (CF). The effect of exercise on
bmjsem-2018-000409
controlled trials investigating the effects of exercise lung function in children is still controversial.
►► Additional material is training on children with chronic respiratory disease.
published online only. To view Following the PRISMA guidelines, eligible studies were
please visit the journal online identified and data were extracted. A meta-analysis was
(http://​dx.​doi.​org/​10.​1136/​ conducted for the outcomes cardiovascular fitness, lung
bmjsem-​2018-​000409). function and quality of life (QoL). What are the new findings
Results  The initial search returned 3688 papers. Twenty-
seven (17 in children with asthma, 10 in children with CF) ►► There are no published studies investigating the ef-
Accepted 29 August 2018 fect of exercise training in children with bronchiec-
were included in the systematic review and 24 of these
were included in the meta-analysis. No studies were tasis and bronchopulmonary dysplasia.
identified in children with bronchiectasis or BPD. Included ►► Exercise has a different effect on QoL and cardio-
papers had a total of 1009 participants aged 8–20 years. vascular fitness in children with asthma and CF.
In addition to cardiovascular fitness, lung function and
QoL, studies also assessed pulmonary function, respiratory
muscle strength, muscular strength and inflammation.
global increase in the prevalence of chronic
Meta-analysis showed a large significant effect size in
health conditions among children and adoles-
favour of exercise for cardiovascular fitness (peak VO2)
(standard mean difference (SMD)=1.16, 95%  CI 0.61 to cents. For example, between 1988 and 2006,
1.70) and QoL (SMD=1.27, 95% CI 0.72 to 1.82) as well as the prevalence of chronic disease among chil-
a small, non-significant effect size for lung function (FEV1) dren and youth in the USA increased from
(SMD=0.02, 95% CI -0.38 to 0.42). 12.6% to 26.6%,3 and it is estimated that by
Conclusion  Exercise training significantly improves 2020, non-communicable disease will be one
cardiovascular fitness and QoL in children with asthma and of the leading causes of illness, disability and
CF. Further research is needed, particularly in children with death among young people.4 In Australia, just
bronchiectasis and BPD. over 66% of children and adolescents aged 15
years or younger suffer from a chronic health
© Author(s) (or their condition.5 Chronic disease is associated with
employer(s)) 2018. Re-use ill health, disability and death and with signif-
permitted under CC BY-NC. No Introduction icant personal, social and economic impacts.1
commercial re-use. See rights
and permissions. Published by
Chronic disease is defined as long-lasting One of the major groups of chronic health
BMJ. illness that has a persistent effect on health conditions in children and adolescents is
For numbered affiliations see and quality of life (QoL).1 The WHO esti- respiratory disease. Chronic respiratory
end of article. mates that, worldwide, 38 million people diseases are a diverse group of disorders
die every year because of a non-communi- affecting the lungs and respiratory system.6 7
Correspondence to
cable disease and this number is expected to In children, these conditions include asthma,
Dr Stewart G Trost; ​s.​trost@​qut.​ increase to 52 million people by 2030.2 Coin- cystic fibrosis (CF), bronchiectasis, conse-
edu.​au cident with this increase, there has been a quences of chronic neonatal lung disease

Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409   1

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or bronchopulmonary dysplasia (BPD), sleep apnoea children have only investigated the effects of exercise
and interstitial lung disease.1 8 Asthma, a heterogeneous training in patients with asthma or CF. To our knowl-
condition consisting of reversible airway obstruction, edge, no systematic or narrative review has sought to
airway inflammation and increased airway responsive- determine the effects of exercise training in children
ness, is the most common respiratory disease, affecting with other respiratory conditions such as bronchiec-
approximately 16 million children worldwide.6 7 9 CF is tasis or BPD. Second, previous reviews have focused on
an autosomal recessive disease and is the most common a single respiratory condition and not compared the
inherited life-limiting illness in children. For 95% people effects of exercise training in different patient groups.
with CF, the cause of mortality will be respiratory failure.6 Consequently, it is unknown if the effects of exercise
Bronchiectasis is characterised by irreversible dilatation are specific to a given respiratory condition or whether
of one or more bronchi and decreased lung function10 it is possible to formulate a single evidence-based exer-
and is a major contributor to respiratory morbidity, espe- cise guideline for children with respiratory disease. Last
cially among socially and economically disadvantaged but not least, only one of the aforementioned systematic
groups. Worldwide, there are more people with bronchi- reviews conducted a meta-analysis focused exclusively
ectasis than CF.6 11 The modern and the most widely used on paediatric studies.17 Combining data from multiple
definition defines BPD as oxygen dependence at 36 weeks studies can provide a more accurate estimate of the true
of postmenstrual age (gestational age plus chronological effects of an intervention,24 and in doing so, gain a better
age). It is related to damage of the undeveloped lung understanding of health impacts of exercise training in
tissues of babies born prematurely. Children with BPD as children with respiratory disease.
infants have a greater risk of respiratory symptoms such To address these gaps, our aim was to undertake a
as coughing, wheezing and asthma than children who systematic review and meta-analysis of studies to evaluate
did not suffer from BPD after birth.12 13 These respiratory the effects of exercise training on cardiovascular fitness,
conditions are associated with poorer QoL, lung function lung function and QoL in children with respiratory
and exercise tolerance. disease related to asthma, CF, bronchiectasis or BPD.
Among healthy children, there is consistent evidence
that exercise confers numerous health benefits such as Methods
improved cardiovascular fitness, musculoskeletal health, A search for randomised controlled trials (RCTs) inves-
mental health and elements of cardiometabolic risk tigating the effects of exercise training in children with
factors such as reduced adiposity, blood lipids, blood respiratory disease was conducted adhering to the guide-
sugar levels and blood pressure.14 15 Among children with lines outlined in the Preferred Reporting Items for
respiratory disease, a burgeoning evidence base suggests Systematic Reviews and Meta-analysis (PRISMA) state-
that regular exercise improves cardiovascular fitness and ment.25
QoL.16 Nevertheless, the type, frequency, intensity and
duration of exercise required for health benefits remains Search strategy
understudied and poorly understood. The following databases were searched using the
To date, a number of systematic reviews have examined following timeframes: PubMed (1951–February 2018),
the effects of exercise training in children with asthma Web of Science (1945–February 2018), CINAHL (Cumu-
or CF.17–21 Their results indicate that exercise training lative Index to Nursing and Allied Health Literature)
improves cardiovascular fitness; however, there was no (1982–February 2018), Embase (1988–February 2018)
consensus on the effects of exercise on lung function and PsycINFO (1967–February 2018).
or QoL. Two recently published Cochrane reviews have The following key words were used and combined
examined the effects of physical training in people with with the Boolean phrase ‘OR’ within groups or ‘AND’ in
CF22 or asthma,23 but these reviews combined studies between groups:
involving both children and adults. In a meta-analysis of 1. child OR children OR adolescent OR youth OR school
exercise training studies involving asthmatic children,17 age.
swimming training was found to have a positive effect on 2. Chronic respiratory disease OR Chronic pulmonary
lung function, with significant changes in forced expira- disease OR Cystic Fibrosis OR cystic fibrosis OR cf OR
tory volume in one second (FEV1) and forced expiratory Mucoviscidosis OR bronchiectasis OR non-cf bronchi-
flow. Two other reviews in children with asthma concluded ectasis OR non-cystic fibrosis bronchiectasis OR bron-
that exercise training had a positive impact on peak expi- chopulmonary dysplasia OR asthma OR PCD OR pri-
ratory flow (PEF) but no effect on FEV1.18 19 A review of mary ciliary dyskinesia.
exercise training in children with CF on lung function 3. exercise OR exercise therapy OR physical therapy OR
outcomes concluded that exercise improves survival by physical intervention OR physical rehabilitation OR
reducing the rate of decline in lung function.21 pulmonary therapy OR pulmonary intervention OR
While these reviews have contributed to our under- pulmonary rehabilitation OR respiratory therapy OR
standing of health benefits of exercise training in respiratory intervention OR respiratory rehabilitation
children with respiratory disease, important gaps in OR rehabilitation OR aerobic OR weight training
knowledge remain. First, previous reviews focused on OR weight lifting OR resistance training OR strength

2 Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409

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training OR running OR run OR walking OR walk OR cardiovascular fitness, lung function or QoL. They
jogging OR jog OR biking OR bike OR sports OR mo- further needed to report the use of the following
tor activity OR dancing OR physical activity OR motor outcome measures: peak VO2 as measured by an incre-
skill intervention OR aerobics OR physical activity mental maximal exercise test; FEV1% for lung function
4. Intervention OR programme OR training. and QoL as measured by the Pediatric Asthma Quality of
We also scanned the references of the retrieved papers Life Questionnaire (PAQLQ) or Cystic Fibrosis Question-
for additional studies. naire (CFQ). These three outcomes were included due
to sufficient numbers of papers reporting the outcome
Selection criteria using the same outcome measure, thereby permitting a
Studies had to meet the following criteria to be included: meta-analysis of the reported data.
1. Individual and cluster RCT study design. Review-Manager (V.5.1 Cochrane Collaboration,
2. The study population included had to be children, Oxford, England) was used for data management and
adolescents or young adults between the ages of 4–21 analysis. Change scores and their corresponding SD for
years, diagnosed with asthma, CF, bronchiectsis, pri- the outcomes of interest were extracted from studies to
mary ciliary dyskinesia (PCD) or a history of BPD. calculate the standardised mean difference (SMD). If
3. The study had to report an exercise intervention with change scores were not reported, then the pre and post
a minimum duration of 2 weeks. means of the exercise programme were used to calcu-
4. The study had to report physiological, psychosocial late the change scores. SDs were calculated according
or behavioural outcomes associated with the exercise the Cochrane handbook.24 If studies reported medians,
training intervention. SEs or ranges, values were converted into means and
5. To be included in the meta-analysis the study had to SD according to the Cochrane handbook. Due to a
report data from the following outcome measures: large diversity of exercise training parameters (mode,
peak VO2, FEV1% predicted and QoL. frequency, intensity, duration and time) across all
Studies were excluded if: included studies, a randomised effects meta-analysis
1. The study population had a mean age of ≥21 years of model was employed. Subgroup analyses were performed
age. for the different patient groups (asthma and CF). For
2. The study tested interventions other than exercise, health outcomes positively impacted by exercise training,
for example, pharmacological, psychological or be- the relationships between the magnitude of the SMD and
havioural interventions. the volume, intensity and duration of exercise training
3. They were not written in English. were evaluated graphically.
The initial search results were independently assessed
for inclusion eligibility by two of the authors (BJ, ST).
Papers were first evaluated by title and abstract and when Results
they were considered eligible, the full text was obtained The PRISMA diagram (figure 1) displays the search find-
and evaluated. In the case of disagreement between the ings where 3688 papers were identified via databases and
two assessors (BJ, ST), the case was discussed between the five additional papers identified through other sources.
two assessors until consensus was reached. A total of 115 full text publications were screened and
27 articles28–54 fulfilled the inclusion criteria. A total of
Data extraction 45 papers were excluded due to study design (not an
Data were extracted by two of the authors (BJ, ST) from RCT), 23 papers were excluded because the participant
the full text of the final 27 included studies. Data extracted characteristics did not meet the inclusion criteria and
included number of participants and diagnoses, study 12 papers were excluded because the intervention was
design, type of intervention, setting of the intervention, not an exercise programme. Five of the excluded papers
outcome measurements, outcomes and effectiveness. were reviews and three were letters to a journal and
subsequently excluded. Additionally, three papers32 34 41
Quality assessment
were not included in the meta-analysis as they did not
The methodological quality of the included studies was
report peak VO2, FEV1% or scores on the PAQLQ/ CFQ.
assessed using the Physiotherapy Evidence Database Scale
Therefore, 24 papers28–31 33 35–40 42–54 were included in the
(PEDro). The PEDro scale is based on the Delphi list
meta-analysis.
and uses 11 items generating a maximum score of 11.26
Each item was assessed for being present (✔), absent (X)
or not applicable (NA). The PEDro scale is commonly Study characteristics of included studies
used to assess methodological quality of trials.27 Method- A summary of the details of the included studies can be seen
ological quality was independently assessed by two of the in online supplementary digital content 1. There were 17
authors (BJ, SG). studies in children with asthma28–30 32 33 35 36 40–43 49–54 and
10 studies in children with CF.31 34 37–39 44–48 No studies were
Meta-analysis found in children with bronchiectasis or BPD. Studies
To be included in the meta-analysis, papers needed were published between 1998 and 2015. Thirteen of
to report at least one of the following outcomes: those were published between 2000 and 2009 (9 asthma,

Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409 3

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Figure 1  Results of search strategy of randomised control trials investigating effects of exercise in children with chronic
respiratory disease.

3 CF),30 32–34 36 39 42 47–49 51–53 and 10 (5 asthma, 5 CF) were Quality assessment
published between 2010 and 2015.29 37 38 40 43–46 50 54 Table 1 provides detailed information about the quality
The remaining four studies were published before 2000 assessment for included studies. Out of the 11 criteria on
(three asthma, one CF).28 31 35 41 Studies were conducted the PEDro scale, 2 were not applicable because subject
in 13 different countries, with the majority of studies and therapist blinding was not possible. Therefore, the
conducted in Europe (9 asthma, 4 CF)28 30 33 35 37 39 40 42–45 50 51 highest score achievable was 9 out of 11 points. A score of
and South America (4 asthma, 3 CF).29 34 36 38 46 49 54 The ≥6 is equivalent to moderate to high quality,27 which was
age of the participants ranged between 8 and 20 years. In found in 1829 33 35–46 48 49 51 52 of the 27 studies. In asthma
the asthma studies, age ranged between 8 and 14 years and CF, 65%28 29 33 35 36 40–43 49 51 52 and 70%37–39 44–46 48 of
and in CF studies, age ranged between 10 and 20 years. studies, respectively, achieved a score of ≥6. A score of ≥8
Overall, sample sizes ranged between 8 and 105 partic- was found in 736 38 42 44–46 48 of the 27 studies. In asthma
ipants in asthma and CF, with a median sample size of 12%36 42 and in CF 50%39 44–46 48 of the studies achieved a
34. Only one study had a sample size of over 100 partic- score of ≥8. A score of ≤5 was found in 928 30–32 34 47 50 53 54
ipants.40 of the 27 studies. In asthma 35%28 30 32 50 53 54 and in CF

4 Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409

 Table 1  Methodological qualities of included studies: PEDro
Between- Point
group estimates and
statistical measures
Similarity >85% comparison of variability
Specified at baseline follow-up of Intention- for at least provided for at
eligibility Random Concealed on key Subject Therapist Assessor at least one to treat one key least one key
Trial criteria allocation allocation measures blinding blinding blinding key outcome analysis outcome outcome Total

Asthma
Ahmaidi et al (1993)28 ✔ ✔ x X NA NA X X X ✔ ✔ 4
29
Andrade et al (2014) ✔ ✔ ✔ ✔ NA NA X X ✔ ✔ ✔ 7
30
Basaran et al (2006) X ✔ X ✔ NA NA X ✔ X ✔ ✔ 5
Chang et al (2008)32 X ✔ X ✔ NA NA X X X ✔ ✔ 4
Counil et al (2003)33 ✔ ✔ X ✔ NA NA ✔ ✔ X ✔ ✔ 7
35
Edenbrandt et al (1990) X ✔ X ✔ NA NA X ✔ ✔ ✔ ✔ 6
36
Fanelli et al (2007) ✔ ✔ ✔ ✔ NA NA ✔ ✔ ✔ ✔ ✔ 9
40
Latorre-Román et al (2014) ✔ ✔ X ✔ NA NA X ✔ X ✔ ✔ 6
41
Matsumoto et al (1999) X ✔ X ✔ NA NA X ✔ ✔ ✔ ✔ 6
42
Moreira et al (2008) ✔ ✔ ✔ ✔ NA NA X ✔ ✔ ✔ ✔ 8
Onur et al (2011)43 ✔ ✔ X ✔ NA NA X ✔ ✔ ✔ ✔ 7
Silva et al (2006)49 ✔ ✔ X ✔ NA NA X ✔ ✔ ✔ ✔ 7

Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409

50
Silva et al. (2013) X ✔ X ✔ NA NA X ✔ X ✔ ✔ 5
51
Van Veldhoven et al. (2001) ✔ ✔ X ✔ NA NA X ✔ X ✔ ✔ 6
52
Wang et al (2009) X ✔ X ✔ NA NA X ✔ ✔ ✔ ✔ 6
53
Weisgerber et al (2003) ✔ ✔ X ✔ NA NA X X X ✔ ✔ 5
Wicher et al (2010)54 ✔ ✔ X ✔ NA NA X ✔ X X ✔ 5
Cystic fibrosis
Cerny et al (1989)31 X ✔ X X NA NA X ✔ ✔ ✔ ✔ 5
34
De Oliveira et al (2009) ✔ ✔ X ✔ NA NA X X X ✔ ✔ 5
37
Hebestreit et al (2010) ✔ ✔ X ✔ NA NA X ✔ X ✔ ✔ 6
Hommerding et al (2015)38 ✔ ✔ X ✔ NA NA X ✔ ✔ ✔ ✔ 7
Klijn et al (2004)39 ✔ ✔ ✔ ✔ NA NA ✔ ✔ X ✔ ✔ 8
44
Santana Sosa et al (2012) ✔ ✔ X ✔ NA NA ✔ ✔ ✔ ✔ ✔ 8
Santana Sosa et al (2014) ✔ ✔ X ✔ NA NA ✔ ✔ ✔ ✔ ✔ 8
Open access

Continued

5
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30%31 34 47 of the studies achieved a score of ≤5. All studies

Total
were RCTs, but only five studies concealed their rando-

8
5

8
misation (three asthma, two CF).29 36 39 42 48 Assessor

provided for at
estimates and
blinding was reported in 6 of the 27 studies.33 36 39 44–46 For

least one key

of variability
the majority of studies (25 out of 27) exercise and control

measures

outcome
Point groups exhibited similar baseline scores on primary
outcomes29 30 32–54 and 22 out of 27 studies had less than

✔
✔

✔
15% drop out.30 31 33 35–52 54 All studies reported measures
comparison
of variability and 26 out of the 27 studies described
follow-up of Intention- for at least
statistical
Between-

outcome
one key between group statistical comparisons.28–53 Intention-to-
group

treat analyses were conducted in 14 studies (8 out of 17

asthma, 6 out of 10 CF).29 31 35 36 38 41–46 48 49 52
✔
✔

✔
After excluding the three papers which were not eligible
blinding key outcome analysis

for the meta-analysis, 17 of 24 studies were found to have

Subject Therapist Assessor at least one to treat

a moderate to high quality.29 33 35–40 42–46 48 49 51 52 In asthma

✔

✔
X

67%29 33 35 36 40 42 43 49 51 52 and in CF 78%37–39 44–46 48 of

the studies achieved a score of ≥6. All studies were RCTs,
five studies concealed their randomisation29 36 39 42 48 and
assessor blinding was reported in six studies.33 36 39 44–46
>85%

Exercise and control groups exhibited similar baseline

✔
✔

scores on primary outcomes in 22 studies.29 30 33 35–40 42–54

All studies reported measures of variability and 23 of the
24 studies described between group statistical compari-
✔
X

sons.28–31 33 35–40 42–53 From the 24 studies, 21 had less than

15% drop out30 31 33 35–40 42–52 54 and 13 studies conducted
blinding blinding

intention to treat analyses.29 31 35 36 38 42–46 48 49 52

NA
NA

NA

Types of exercise training

The majority of exercise training programme were
supervised in or out of hospital.28–36 39–45 49–54 Home-
NA
NA

NA

based exercise programme were evaluated in five

at baseline

studies (CF).37 38 46–48 and 81% of the exercise training

allocation allocation measures
Similarity

programme were delivered as individual training

eligibility Random Concealed on key

sessions;28 29 31 33 34 36–39 41–48 50–54 however, five studies, all in

✔
✔

children with asthma, were conducted as group training

programme.30 32 35 40 49 A variety of exercise modes were
used. These included running,28 29 34 cycling,31 33 swim-
ming,41 52–54 circuit training,35 49 a combination of
✔
X
X

aerobic training and strength training,36–38 44–48 balance

and coordination,42 50 group exercises,37 40 51 basket-
ball,30 thai chi32 and running relays games.39 Studies in
patients with CF were limited to running,34 cycling,31
✔
✔

any exercises that raised heart rate (HR) including

Specified

ball games, skipping ropes, relays37–39 44–48 and strength

criteria

training.36 44 45 48 The duration of training ranged from 13

✔

days31 to 3 years,47 with the majority28–30 32–34 36 40–45 49–54 of

X

training programme being delivered over a time period

ranging from 6 and 16 weeks. For most studies, training
frequency was two sessions31 36 38 39 42 43 49–51 53 54 or three
Schneiderman-Walker et al

sessions per week.28–30 32–34 37 40 44–47 52 Exercise duration

Selvadurai et al (2002)48

ranged between 10 and 90 min per session. The dura-

Schindel et al (2015)46
Table 1  Continued

tion of exercise in children with asthma (50–60 min

per session) was typically longer than the one reported
for children with CF (20–30 min per session). Exer-
cise intensity monitoring was reported in 12 studies (7
(2000)47

asthma,28 29 33 36 41 43 52 5 CF34 44 45 47 48). Eleven out of

the 12 studies used HR monitoring to monitor exercise
Trial

intensity,28 29 33 36 41 43–45 47 48 52 and the remaining study

6 Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409

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used treadmill slope and velocity.34 To define the HR walk test,29 40 PWC 170,30 work capacity via cycle and
for the optimal training intensity 7 of 11 studies used swimming ergometer,35 41 9 min run distance49 and the
a percentage of HR max or submaximal HR (65%– 3 min step test.34 Cardiovascular fitness significantly
80%),28 29 33 43 47 48 52 2 studies used the HR at ventilatory improved in 16 out of 19 studies (9 asthma,28–30 33 36 40 41 49
threshold,44 45 1 at lactate threshold41 and 1 at two-thirds 7 CF31 34 37 39 44 45 48).
of the difference between the anaerobic threshold and
the respiratory compensation point.36 Meta-analysis
Eleven studies reported data for peak VO2, four in chil-
Outcome measures and findings dren with asthma28 33 36 51 and seven in children with
Across the 27 trials included in the qualitative synthesis, CF.37–39 44 45 47 48 Across all studies, the mean effect size was
12 different outcomes were assessed, including cardio- large (SMD=1.16, 95% CI 0.61 to 1.70) and significant in
vascular fitness, pulmonary function, respiratory muscle favour of the intervention. Subgroup analyses showed a
strength, QoL, muscular strength, inflammation param- large and significant effect size favouring the intervention
eters, anaerobic fitness, physical activity, psychosocial among children with asthma (SMD=1.97, 95% CI 0.61 to
indices, asthma control, broncho-hyper-responsiveness 3.32) and a medium but significant effect size in favour
(BHR) and posture. In this review, six of these outcomes of the intervention among children with CF (SMD=0.77,
(cardiovascular fitness, pulmonary function, respiratory 95% CI 0.25 to 1.29). The corresponding forest plot can
muscle strength, QoL, strength and inflammation) were be found in figure 2. There was no relationship between
included in the qualitative synthesis and discussed in the SMD and the volume, intensity and duration of the
detail. The remaining outcomes were excluded because exercise training programme (r=0.02–0.10). See figures
they were assessed in only a few studies. From the 27 studies included in online supplementary file 2.
included in the quantitative synthesis, 24 were included
in the meta-analysis (15 asthma,28–30 33 35 36 40 42 43 49–54 9 Lung function
CF31 37–39 44–48). Using these studies, there were suffi- Pulmonary function was assessed in 23 studies, with 13
cient data to conduct a meta-analysis on the following studies in children with asthma29 30 32 33 35 40 42 43 49 51–54 and
outcomes: cardiovascular fitness (peak VO2), lung func- 10 studies in children with CF.31 34 37–39 44–48 FEV1 was used
tion (FEV1%) and QoL (PAQLQ or CFQ). in all 23 studies,28 30–35 37–40 42–49 51–53 with 16 reporting
per cent predicted values and four studies reporting
Cardiovascular fitness absolute values (litres (L)). Forced vital capacity (FVC)
Cardiovascular fitness was assessed in 19 studies, 10 of those was the second most evaluated outcome, reported in 17
studies were in children with asthma28–30 33 35 36 40 41 49 51 studies (9 asthma,29 30 32 35 43 51–54 8 CF31 34 37–39 44–46). PEF
and 9 in children with CF.31 34 37–39 44 45 48 Peak VO2 was was measured in eight studies29 30 32 40 42 51–53 in children
the most common measure of cardiovascular fitness and with asthma. Four studies assessed maximal inspiratory
was used in four studies in children with asthma28 33 36 51 and expiratory pressure (two asthma,29 54 two CF44 45) as
and seven studies in children with CF.37–39 44 45 47 48 Other outcomes. Eight29–32 40 43 48 52 out of 23 studies reported
measurements of cardiovascular fitness were the 6 min improvements in lung function. Six of those studies

Figure 2  Forest plot: cardiovascular fitness (peak VO2). CF, cystic fibrosis.

Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409 7

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Figure 3  Forest plot: lung function (FEV1). CF, cystic fibrosis.

reported a significant increase in FEV1 or FVC (four favour of the intervention. Subgroup analyses revealed
asthma,32 40 43 52 two CF31 48) and five studies reported an large and significant effect sizes in favour of the inter-
increase in PEF.29 30 32 40 52 vention in both children with asthma (SMD=1.33, 95%
CI 0.65 to 2.01) and children with CF (SMD=1.10, 95%
Meta-analysis CI 0.16 to 2.04). The corresponding forest plot can be
Fifteen studies reported changes in FEV1% predicted, 10 found in figure 4. There was no correlation between
in children with asthma29 30 33 35 42 43 49 52–54 and 5 in chil- the SMD and the volume, intensity and duration of the
dren with CF.31 38 46–48 Across all studies, the mean effect exercise training programme (r=−0.5 to 0.06) (online
size was small and non-significant (SMD=0.02, 95% CI - supplementary file 2).
0.38 to 0.42). Effect sizes for change in FEV1 were similar
for children with asthma (SMD=0.06, 95% CI - 0.52 to Muscular strength
0.65) and CF (SMD=0.01, 95% CI - 0.44 to 0.47). The Muscular strength was measured in six studies (two
corresponding forest plot can be found in figure 3. asthma,40 49 four CF39 44 45 48), using a variety of protocols
Quality of life and indices including grip strength,40 countermove-
QoL was assessed in 12 studies (6 asthma,29 30 36 40 42 50 6 ment jumps,40 number of sit ups,49 isometric muscle
CF37–39 44 45 48). All studies in children with asthma used force,39 maximum weight for five repetitions (five RM)
the PAQLQ.29 30 36 40 42 50 In children with CF, the CFQ37–39 for bench press, leg press and seated row44 45 and isoki-
or CFQ Revised (CFQ-R)44 45 were used, with one excep- netic muscle strength of the quadriceps and hamstring.48
tion (Quality of Wellbeing Scale).48 QoL improved in Five studies (two asthma,40 49 three CF44 45 48) reported
8 out of 12 studies (4 in asthma,29 30 36 40 4 CF37 39 45 48). significant increases in muscular strength by measuring
The four studies in asthma showed statistically significant grip strength,40 countermovement jumps,40 number of
improvement,29 30 36 40 two studies in CF showed domain sit-ups,49 maximum weight for five repetitions (five RM)
specific significant improvement,37 39 one study in CF for bench press, leg press and seated row44 45 or isokinetic
showed significant improvement in the aerobic exercise muscle strength of the quadriceps and hamstring.48 Of
group but not in the resistance exercise groups48 and one note, four additional studies assessed respiratory muscle
study in CF had a borderline non-significant statistical strength (two asthma,29 54 two CF44 45), by determining
improvement.45 maximal inspiratory and/or expiratory pressure. Respira-
tory muscle strength improved significantly in three out
Meta-analysis of the four studies (two asthma,29 54 one CF45).
The PAQLQ or the CFQ was used in eight studies, six
in children with asthma29 30 36 40 42 50 and two in children Inflammation
with CF.44 45 Across all studies, the mean effect size was Inflammatory markers were measured in four studies
large and significant (SMD=1.27, 95% CI 0.72 to 1.82) in (three asthma,29 42 43 one CF34). C reactive protein34 42 was

8 Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409

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Figure 4  Forrest plot: quality of life.

the most common blood parameter assessed and frac- bronchiectasis, BPD or other respiratory conditions and
tional exhaled nitric oxide (FeNO),42 43 the most common whether generalised clinical guidelines for therapeutic
asthma biomarker. Other parameters were plasma cyto- exercise in children with respiratory disease are justified.
kines,29 immunoglobulin E (IgE),42 malondialdehyde,43 In studies investigating children with asthma and CF,
glutathione peroxidase (GSH-Px)43 and superoxide there was considerable heterogeneity with respect to
dismutase.43 An improvement in inflammation was found the mode, frequency, intensity and duration of exercise
in two42 43 of the three studies in children with asthma, training. Frequency ranged from 1 to 7 sessions per week,
which was shown by a statistically significant decrease in duration from 13 days to 3 years and the length of training
FeNO43 and mite-specific IgE42 and significant increase ranged from 10 to 90 min per session. The majority were
in GSH-Px.43 individually supervised sessions. The mode ranged from
single exercise modes such as running or cycling to ball
Discussion games, strength training and coordination. Some studies
The aim of this systematic review and meta-analysis was to offered strictly just one mode, while others combined
synthesise the available research investigating the effects different modes and some studies offered a wide variety
of exercise training in children with respiratory disease of modes from which the patient could choose the most
related to asthma, CF, bronchiectasis or BPD. A total of favourable for him or her. The majority of sessions were
27 RCT’s were included in the systematic review; 17 were prescribed with little to no consideration for motivational
on children with asthma and 10 studies involved chil- strategies appropriate for children, such as games. Even
dren with CF. Eighteen of those studies were moderate though studies meeting the inclusion criteria consistently
to high quality. Importantly, no exercise training studies reported significant improvements in cardiovascular
involving children and adolescents with bronchiectasis fitness and QoL, no relationship between intensity,
(or PCD) or BPD were identified. From these 27 studies, duration and volume of exercise training was observed.
24 were included in the meta-analysis. A large signifi- The reasons for this may be the small number of studies
cant mean effect size in favour of exercise was found for included in this analysis, the wide range of exercise mode
cardiovascular fitness (VO2 peak) (SMD=1.16, 95% CI and inconsistency in frequency, duration and intensity.
0.61 to 1.70) and QoL (SMD=1.27, 95% CI 0.72 to 1.82) Across studies, there was little consistency in the
as well as a small, non-significant mean effect size in lung primary outcomes and the methods used to assess the
function. outcomes, making it difficult to combine results in the
A key finding from the present review was the absence meta-analyses and to draw conclusions. For example,
of studies evaluating exercise training in children with five different measurement protocols were used to assess
respiratory diseases other than asthma or CF. Although cardiovascular fitness, resulting in five different metrics.
clinical guidelines for the treatment and manage- Due to this lack of consistency, it was not possible to
ment of respiratory disease recommend exercise,55 the include all RCTs investigating cardiovascular fitness in
results highlight the need for exercise training studies the meta-analysis. It would be preferable for the field to
for other respiratory conditions, such as bronchiectasis adopt a consensus approach in relation to the preferred
and BPD. Further research is needed to determine if metrics and measurement protocols for assessing cardio-
exercise training is equally beneficial for children with vascular fitness and other health outcomes in children

Joschtel B, et al. BMJ Open Sport Exerc Med 2018;0:e000409. doi:10.1136/bmjsem-2018-000409 9

 Open access
5
with respiratory disease. This would improve compara- Institute of Health and Biomedical Innovation, Centre for Children’s Health
bility between studies and strengthen the conclusions of Research, Queensland University of Technology, Brisbane, Queensland, Australia
6
Department of Respiratory Medicine, Lady Cilento Children’s Hospital, Children’s
future systematic reviews. Health Queensland, Brisbane, Queensland, Australia
Muscular strength and endurance are important
outcomes of exercise training as they facilitate physical Contributors  BJ devised the research question, completed the search, screened
function and improve QoL.56 Six studies that evaluated papers, extracted and analysed data and wrote the paper. ST was a major
contributor in designing the research question, screening papers, analysing data
muscular strength were included, but because different
and writing the paper. SRG contributed to the quality assessment and writing the
outcomes were measured, it was not possible to include paper. HP assisted in devising the research question and writing the paper. SGT
them in the meta-analysis. An earlier review of exercise and ABC contributed to manuscript development. All authors read and approved the
training studies conducted in patients with CF concluded final manuscript.
that significant improvements in strength can be achieved Funding  Professor Chang is supported by an Australian National Health and
Medical Research Council (NHMRC) Practitioner Fellowship (Grant APP1058213).
through regular exercise training.21 The conclusions
of our qualitative synthesis are in agreement with this Competing interests  None declared.
finding. Patient consent  Not required.
There is growing evidence that exercise has a positive Provenance and peer review  Not commissioned; externally peer reviewed.
effect on inflammation.57–59 Inflammation is a major Data sharing statement  Data are available from the corresponding author on
contributor to disease in respiratory diseases. In patients request ​s.​trost@​qut.​edu.​au.
with CF, it leads to damage of lung tissue resulting in Open access  This is an open access article distributed in accordance with the
higher susceptibility for new infections.60 In asthma, Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
ongoing inflammation is associated with poorer clin- and license their derivative works on different terms, provided the original work is
ical outcomes.61 Therefore, investigating the effect of properly cited, appropriate credit is given, any changes made indicated, and the
exercise on inflammatory parameters in children with use is non-commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/
respiratory disease is an important area of research.
The effect of exercise on inflammation was investigated
in only three studies, and although two reported an References
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