Effects of physical exercise training on nocturnal symptoms in asthma: Systematic review
Effects of physical exercise training on nocturnal symptoms in asthma: Systematic review
Cristina de Oliveira FranciscoID 0 1
Swati Anil Bhatawadekar 0 1
Jessica Babineau 0 1
W. Darlene Reid 0 1
Azadeh Yadollahi 0 1
0 1 Toronto Rehabilitation Institute, University Health Network , Toronto, Ontario , Canada , 2 Department of Physical Therapy, University of Toronto , Toronto, Ontario , Canada , 3 Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Ontario , Canada
1 Editor: Shyamali Dharmage, The University of Melbourne , AUSTRALIA
Nocturnal worsening of asthma symptoms is a common feature of asthma. Physical exercise training improves general asthma control; however, there is no evidence showing the effects of physical exercise on nocturnal asthma symptoms. Indeed, asthma patients with daytime and nighttime symptoms are physiologically different, and thus the effects of physical exercise on asthma may also be different in these two groups. The objective of this systematic review is to explore the effects of physical exercise on nocturnal asthma symptoms.
Funding: This work was supported by grants from
Canadian Research Respiratory Network (CRRN)
and Allergen NCE. CRRN is supported by grants
from CIHR-Institute of Circulatory and Respiratory
Health and the Canadian Lung Association (CLA)/
Canadian Thoracic Society (CTS). The funders had
no role in the study design, data collection and
analysis, or preparation of the manuscript.
Searches were conducted in MEDLINE, Embase, Cochrane Central Register of Controlled
Trials, CINAHL and SPORTdiscus (last search on November 2017). Authors from studies
that did not report nocturnal symptoms but used questionnaires and/or diaries were
contacted for detailed information. Studies that provided results on nocturnal symptoms before
and after physical activity intervention were included. Prevalence of nocturnal symptoms
was calculated for each study from the percentage of study participants with nocturnal
symptoms before and after intervention.
Eleven studies were included (5 with children and 6 with adults). The prevalence of
nocturnal symptoms at baseline ranged from 0% to 63% among children and from 50–73% among
adults. In children and adults with nocturnal asthma, aerobic physical exercise reduced the
prevalence and frequency of nocturnal symptoms.
Aerobic physical exercise improves nocturnal asthma in children and adults by reducing the
prevalence and frequency of nocturnal symptoms. Physical exercise training could be used
Competing interests: C.O.F, S.A.B., J.B. and W.D.
R. report no conflicts of interest. A.Y. reports
grants from Canadian Research Respiratory
Network (CRRN) and Allergen NCE. This does not
alter our adherence to PLOS ONE policies on
sharing data and materials.
with conventional treatments to improve quality of life and asthma control in patients with
nocturnal worsening of asthma.
Asthma is a chronic inflammatory lung disorder characterized by variable and reversible
airway obstruction and airway hyper-responsiveness [1, 2]. It is associated with recurrent
episodes of wheezing, breathlessness, chest tightness and coughing . Asthma affects more than
300 million people worldwide of all ages with adverse clinical, social, and economic
consequences [4–6]. The financial burden on patients with asthma in different Western countries
ranges from $300 to $1,300 per patient per year . Moreover, asthma has a large detrimental
impact on physical, emotional, social, and professional lives of sufferers .
Nocturnal worsening of asthma symptoms is common in more than two-thirds of asthma
patients [8–11] and is associated with more severe asthma symptoms [12–15], increases in
airway hyper-responsiveness, more use of asthma medications, and declines in the lung function
[8, 16, 17]. Moreover, nocturnal asthma leads to fragmented sleep, daytime fatigue, and
impaired cognitive performance leading to poor quality of life [16, 18, 19].
The mechanisms underlying nocturnal asthma are multifactorial [16, 17, 20, 21]. During
sleep, recumbent posture causes a reduction in the lung volumes, respiratory muscle tone, and
lung compliance [22–24]. Moreover, recumbent posture also causes a shift of fluid from the
legs to the thorax (rostral fluid shift) that is associated with airway narrowing in asthma
[25, 26]. In addition, during sleep there is an overnight decrease in plasma cortisol and an
increase in airway inflammation, which in turn increases cholinergic tone [16, 17], and
enhances airway hyper-responsiveness.
Evidence suggests that compared to patients without nocturnal symptoms, those with
nocturnal asthma experience different physiological traits during the night [21, 27–31]. The
overnight physiological abnormalities related to nocturnal asthma include: increased airway
inflammation and decreased steroid responsiveness [21, 29, 30], increased pulmonary capillary
blood volume , functional differences in blood/air volume ratios and mechanical coupling
of the parenchyma to the airways . Anti-inflammatory treatment and bronchodilators to
relax airway smooth muscles greatly improve asthma symptoms. However, nocturnal
worsening of asthma occurs even in patients under optimal medication treatment [32, 33] suggesting
that pathophysiology of nocturnal asthma is not fully understood yet and complementary
treatments may improve asthma control in these patients.
The beneficial effects of physical exercise on general asthma control are well documented
[34–38]. Physical exercise reduces central, systemic and airway inflammation [34–37],
diminishes bronchial hyper-responsiveness, and improves aerobic fitness, exercise tolerance, asthma
control, and quality of life [37, 38]. Considering the physiological differences between asthma
patients with daytime and nighttime symptoms, the effects of physical exercise between these
two types of asthma could be distinctive. However, previous studies and systematic reviews
examining the effects of physical exercise training on asthma do not specify the effects of
exercise on night symptoms and sleep quality. The evidence of whether exercise exacerbates or
improves nocturnal symptoms needs to be synthesized so that recommendations can be made
regarding its utility in the management of patients with asthma. Therefore, the aim of this
systematic review is to explore the effects of physical exercise on nocturnal asthma symptoms.
This systematic review was conducted in accordance with Cochrane Handbook for Systematic
Reviews of Intervention and Preferred Reporting Items for Systematic Reviews and
MetaAnalyses (PRISMA) guidelines [39, 40]. The systematic literature review was performed using
the PICO strategy (Patients: Asthmatics; Intervention: Physical Exercise; Comparisons: pre
and post intervention and/or control vs intervention; Outcomes: nocturnal asthma symptoms
which included episodes of wheeze or shortness of breath at night, symptoms scores
specifically for nocturnal asthma symptoms, waking at night as result of asthma symptoms, scores of
subjective sleep quality affected specifically by asthma symptoms, number of symptom free
Comprehensive searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane
Central Register of Controlled Trials (Ovid), CINAHL (EBSCO) and SPORTdiscus (EBSCO).
In addition, a supplemental search was conducted in PubMed to identify non-MEDLINE
records. The searches were developed and executed by an expert reference librarian (JB). Search
strategies included a combination of text words and subject headings (e.g. MeSH, Emtree)
relating to: (1) physical activity or exercise (2) asthma, and (3) trials. We did not explicitly
include search terms related to nocturnal symptoms or subjective sleep quality in the search
strategies as these terms are rarely mentioned in the title, abstract, or subject headings, but are
more often embedded within the article’s full-text and thus, must be identified at the screening
level. Each database search was conducted from its respective inception until November 2017.
Searches were limited to English language papers and humans. Details of the MEDLINE search
strategy are outlined in supplementary file (S1 Text).
Study selection and data extraction
Two independent reviewers (COF and SAB) performed the screening process to determine
potential relevance. Our inclusion criteria were: 1) clinical trials with asthma patients 2)
intervention with any type of physical exercise training lasting at least 20 minutes per day,
undertaken at least two times per week for a minimum duration of four weeks (following the criteria
used in the Cochrane systematic review regarding physical activity for asthma, Carson et al
2013); 3) studies evaluating nocturnal asthma symptoms, or subjective sleep quality
affected by asthma symptoms before and after physical exercise and 4) studies in English.
Studies that did not report nocturnal symptoms, or subjective sleep quality but used instruments
(questionnaires and/or diaries) that include questions about these parameters were included.
In addition, authors of these studies were contacted to obtain information about the specific
questions related to the overnight symptoms and subjective sleep quality before and after
The exclusion criteria included studies that investigated: animals; subjects without asthma;
asthma patients combined with subjects with other diseases; other interventions besides
physical activity; only respiratory muscle training and breathing exercises; reviews, guidelines,
letters, commentaries, book chapters or published only as an abstract or poster. Studies without
extractable nocturnal symptoms and/or subjective sleep quality data were excluded if no
further information was acquired after three attempts to contact the study authors.
For each reference, the following variables were systematically extracted and entered into a
summary table: 1) authors; 2) publication year; 3) journal; 4) type of physical activity, duration,
progression and frequency; 5) nocturnal symptoms assessment tool 6) sample size; 7) age,
body mass index (BMI) and medication at baseline; 8) study design; 9) nocturnal symptoms;
Data are reported as mean ± SD or median (min-max).
ACQ, Asthma Control Questionnaire; PAQLQ, Pediatric Asthma Quality of Life Questionnaire; AQLQ, Asthma Quality of Life Questionnaire.
40min 2x/wk for 8w of video game exercise
40min 2x/wk for 8w of treadmill exercise
12 wk without exercise (control)
45min 2x/wk for 5-6wk of swim classes
4-6wk without exercise (control)
At least 30min of 5–7 physical activities/wk for 6wk of
unsupervised physical activity (aerobic and strength exercises)
50min 2x/wk for 12wk of aerobic and strength exercises
1h 2x/wk for 6w of aerobic exercise (games)
10) general asthma symptoms 11) results related to the changes in asthma symptoms
(inflammatory markers, exercise capacity, lung function, etc.). Details of the full data extracted from
the papers are outlined in supplementary file (S1 Table).
Two independent reviewers (COF and SAB) assessed the risk of bias for included studies as
per The Cochrane Handbook for Systematic Reviews of Intervention criteria .
Nocturnal symptoms assessment tool
The studies included in the systematic review assessed nocturnal symptoms and subjective
sleep quality using different methods summarized in Tables 1 [41–45] and 2 [46–51]. To
evaluate asthma symptoms, seven studies used the Asthma Control Questionnaire (ACQ)
[41, 45–47, 49–51]. ACQ has been validated for adults and children [15, 52] and integrates 7
questions about asthma management, including one question about the frequency of
nocturnal asthma symptoms (ACQ-1 “On average, during the past week, how often were you woken
by your asthma during the night?”). All ACQ questions are weighed equally and the ACQ
score is the average of the responses ranging from 0 to 6 (higher ACQ score is worse asthma
control). ACQ score 1.5 is considered to be well-controlled asthma  and reduction
of 0.5 in the score is considered to be a clinically significant improvement in asthma control
Two studies used the Asthma Quality of Life Questionnaire (AQLQ) [49, 50] and other two
used the mini-AQLQ [46, 47]. These four studies used the quality of life questionnaires in
combination with ACQ. Two studies used Pediatric Asthma Quality of Life Questionnaire
(PAQLQ) [43, 45]. The mini-AQLQ is a short version of AQLQ, and the PAQLQ is the version
for children. All of these quality of life questionnaires are evaluated on scales of 1 to 7 and the
total score is the mean of all items. A higher score indicate better quality of life [55, 56] and an
increase in the score of 0.5 is considered to be a clinically significant improvement . The
PAQLQ and AQLQ have one question related to frequency of nocturnal symptoms
(PAQLQ16 “How often did your asthma wake you up during the night during the past week?” and
Data are reported as mean ± SD.
ACQ, Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire.
At least 30min 3x/wk for 10wk of aerobic exercise
1h 3x/wk for 12 wk of aerobic and strength exercise
+ 30min 5x/wk for 12wk unsupervised exercise
30min 5x/w for 12 wk of unsupervised physical
activity (aerobic and strength exercises)
12 wk without exercise (control)
Control: 10 wk without exercise
1h 3x/wk for 10wk of aerobic and strength exercise
1h 3x/wk for 10wk of aerobic and strength exercise
+ 10 wk of reduction in food intake
10wk of reduction in food intake
1h 3x/wk for 12wk of aerobic and strength exercises
AQLQ ACQ and AQLQ
AQLQ-24 “How often during the past two weeks have you been woken at night by your
asthma?”) and one question about subjective sleep quality (PAQLQ-20 “How often did you
have trouble sleeping at night because of your asthma during the past week?” and AQLQ-29
“How often during the past two weeks has your asthma interfered with getting a good night‘s
sleep?”) whereas the mini-AQLQ has only one question about subjective sleep quality
(miniAQLQ-8 “How much of the time during the last 2 weeks did you have difficulty getting a good
night‘s sleep as a result of your asthma?”).
Two studies used their own symptom questionnaire to report the frequency of nocturnal
symptoms [42, 44]. Haines et al  had one question regarding the incidence of nightly
asthma symptoms and Weisgerber et al  had one question regarding the frequency of
coughs at night. Both questionnaires had one question about nocturnal symptoms evaluated
on a scale of 1 to 4. Higher scores indicated more nights per week with awakening due to
nocturnal symptoms. One study used a patient reported diary of daytime and nighttime symptoms
The above sources used for evaluating asthma control, nocturnal asthma and subjective
sleep quality data were related questionnaires for asthma population. The questions regarding
subjective sleep quality are specific for sleep quality affected by asthma symptoms. Global sleep
quality was not evaluated in the present study. Moreover, these questionnaires evaluate asthma
control and nocturnal asthma based on the subjective impressions of the participants
regarding the frequency of their symptoms. For this reason, these questionnaires may not be very
sensitive to mild changes in nocturnal symptoms. Thus, we calculated the prevalence of
nocturnal symptoms (percentage of participants with nocturnal symptoms) as a measurement of
presence or absence of symptoms. In the studies that used ACQ, AQLQ and PAQLQ [41, 43,
45–47, 49–51], nocturnal symptoms were considered absent when the patients reported no
nocturnal symptoms at all (any nocturnal awakening or nighttime symptoms). Studies that
used their own symptom questionnaire [42, 44] combined the patients with no nocturnal
symptoms and those with very low frequency of nocturnal symptoms. We could not reach out
to the authors to confirm the exact number of participants without any nocturnal symptoms.
For these studies, nocturnal symptoms were considered absent when patients scored 1 (lower
frequency of night symptoms available in their scale).
We calculated the changes in the scores for each of the respective single question regarding
nocturnal symptoms and subjective sleep quality from the studies where these data were
extractable [42, 44] or from the data provided by the authors [41–51]. Data are presented as
mean ± SD. The normality of data was tested using the Shapiro-Wilk test. Changes in
nocturnal symptoms scores and in subjective sleep quality from pre to post intervention were
compared with a paired t-test or Wilcoxon signed-rank test. For the studies with more than one
group, between group changes were compared using two-way ANOVA with time (pre and
post intervention) and groups (exercise and control) as factors. The prevalence of nocturnal
symptoms was calculated from the percentage of study participants with nocturnal symptoms
pre and post intervention. Statistical significance was accepted at p < 0.05. All statistical
analyses were performed using SAS (version 9.3 Institute, Cary, NC, USA).
A summary of the screening process is presented in Fig 1. The search resulted in 8902 titles
from the initial search of the above mentioned databases. After eliminating duplicates and
screening of titles and abstracts, 150 full texts were reviewed, out of which 37 were considered
to be potentially relevant [41–51, 58–83]. The authors of these 37 studies [41–51, 58–83] were
contacted to obtain the specific information about nocturnal symptoms and/or subjective
sleep quality. Three studies reported nocturnal symptoms in the published articles [42, 44, 48]
and authors of eight studies provided the specific information related to the outcomes of this
systematic review [41, 43, 45–51]. Therefore, a total of 11 studies were included in this
systematic review. Of these included studies, five studies evaluated children (7–15 years old) [41–45]
(Table 1) while six evaluated adult participants (over the age of 18 years) [46–51] (Table 2).
The detailed characteristics of the included studies with children and adults are summarized in
Tables 1 and 2, respectively. In the studies of adults, two studies compared the same control
group with unsupervised physical exercise training  and supervised physical exercise
training  and thus, these data are presented in combination. Moreover, Scott et al. published a
retrospective analysis in 2015  of the same patient cohort described previously by Scott
et al. in 2013 . For this reason, these two reports are described together.
Risk of bias in included studies
The risk of bias assessment for included studies is summarized in the Fig 2. Five out 11 studies
(45%) [41, 43, 44, 49, 50] were randomized control trials (RCT), with a low risk of bias for
allocation. However, one of these RCTs  did not provide details about the allocation
concealment, and thus was considered with an unclear risk of bias for this item. Due to the nature of
intervention in these studies (physical exercise), blinding of participants was not possible.
Additionally, blinding of outcome assessment was not performed in 3 studies [43, 49, 50]
while remaining 8 studies [41, 42, 44–48, 51] had an unclear risk of bias for this item. One
study  had evident incomplete outcome reporting data, with significant large number of
Fig 1. Flow diagram of the study inclusion.
Fig 2. Methodological quality graph. Review authors’ judgements about each methodological quality item presented
as percentages across all included studies.
dropouts. In addition, we identified a study with reporting bias , not presenting group
comparisons for the main outcomes. Moreover, we identified other potential source of bias in
2 studies [44, 46] and an unclear other source of bias in 1 study . Dogra et al  reported
poor adherence for unsupervised exercise protocol which may be a source of bias. Weisgerber
et al  had baseline imbalance for height and forced vital capacity between their groups
which was considered as a source of bias. Finally, Gomes et al  had an unclear other source
of bias because there was no information about adherence rate, or percentage of exercise
Nocturnal symptoms and subjective sleep quality in children
Of five studies on children, [41–45] three evaluated the effects of aerobic exercise training on
asthma symptoms [41, 44, 45] and two evaluated the effects of combined aerobic and strength
exercise training on asthma symptoms [42, 43] (Table 1). These 5 studies with children had
heterogeneous inclusion criteria. Two studies included children based on their asthma severity
(moderate persistent asthma) [42, 44], two included children based on their asthma control
(controlled asthma, i.e., no exacerbation or change in medication in the previous 30 days)
[41, 43] and one study  did not use asthma severity or level of control as an inclusion
criterion. In this study , based on the ACQ scores [15, 53], the authors included children with
well-controlled or relatively well-controlled asthma.
Table 3 shows the summary of changes in the nocturnal symptoms after physical exercise in
children. The prevalence of children with nocturnal symptoms at baseline ranged from 0% to
63%. The duration of the exercise training among the studies was between 5 and 8 weeks.
Eighty percent of the studies with children (4 studies) [41–44] showed a reduction in the
prevalence of nocturnal symptoms after physical exercise training. Only Westergren et al  did
not find changes in the prevalence of nocturnal symptoms after physical exercise training;
however, in this study there were no participants with nocturnal symptoms at baseline.
Three studies [42–44] found reductions in the prevalence of nocturnal symptoms after
physical exercise training, but did not find significant changes in the questionnaire scores
related to the frequency of nocturnal symptoms. Regarding these results, Haines et al 
included a few participants with nocturnal symptoms at baseline (30%). Moreover, using the
symptom questionnaire created by the authors, on a scale of 1 to 4, the patients without
nocturnal symptoms scored 1 and the patients with nocturnal symptoms scored 2, indicating that
Exercise group improved
asthma-related quality of life
No changes in asthma symptom
score after swimming program
Nocturnal symptoms prevalence and
changes from pre to post intervention
Prevalence: 71% to 14%
ΔACQ1: -1.4±1.4, p = 0.002
Prevalence: 54% to 15%.
ΔACQ1: -0.8±0.9, p = 0.02
Prevalence: 60% to 53%.
ΔPAQLQ-16: 0.1±0.7, p = 0.8
ΔPAQLQ-20: 0.1±0.8, p = 0.8
Prevalence: 40% to 40%
ΔPAQLQ-16: 0.5±1.9, p = 0.5
ΔPAQLQ-20: 0.0±1.4, p = 1.0
No nocturnal symptoms at baseline
ΔACQ-1: -0.3±0.5, p = 0.5
ΔPAQLQ-16: -0.0±0.6, p = 1.0
ΔPAQLQ-20: -0.3±0.5, p = 0.5
Both groups showed reduction in nocturnal
symptoms frequency with no differences
No changes in nocturnal symptoms
frequency and subjective sleep quality
Data are reported as mean ± SD.
ACQ-1, Asthma Control Questionnaire question about nocturnal asthma symptoms frequency; PAQLQ-16, Pediatric Asthma Quality of Life Questionnaire question
about nocturnal asthma symptoms frequency; PAQLQ-20, Pediatric Asthma Quality of Life Questionnaire question about subjective sleep quality.
the patients with nocturnal asthma had mild symptoms resulting in a small mean change in
the score. After 5–6 weeks of swimming twice a week, Weisgerber et al  did not find any
changes in the nocturnal symptoms scores. However, this study included only 8 children, and
they had high variability in the nocturnal symptom score (Table 3). Moreira et al 
evaluated 12 weeks of physical training (twice per week, 50 min each) in 15 children with no
changes in medications throughout the study period. They did not find any improvement in
nocturnal symptoms score but a small reduction in the prevalence of nocturnal asthma
symptoms from 60% to 53% in the exercise group. Similar to , in this study, there was also a
high variability in the nocturnal symptoms score in both exercise and control groups
Gomes et al  was the only study in which the children had significant improvements in
the nocturnal symptoms scores. They evaluated the effects of two modalities of aerobic exercise
(active video game and treadmill) for 8 weeks on asthma. There were no changes in asthma
medications throughout the study period. Both exercise interventions decreased the frequency
of nocturnal awakening (evaluated using ACQ). The reduction in nocturnal symptoms
between the two groups was similar (p = 0.1).
Nocturnal symptoms and subjective sleep quality in adults
Six studies evaluated the effects of physical activity on nocturnal symptoms in adults with
asthma [46–51]. Five of these studies evaluated the effects of combined aerobic and strength
exercise training on asthma symptoms [46, 47, 49–51] and one study evaluated the effects of
aerobic exercise training on asthma symptoms  (Table 2). The duration of the exercise
training in different studies was between 10 and 12 weeks. Moreover, these studies had a wide
range of inclusion criteria regarding level of asthma control. One study included adults with
partially controlled asthma (i.e. those who experienced asthma symptoms regularly, but
symptoms were not severe) , one study included only individuals requiring only intermittent
short-acting β2-agonists therapy 3 months preceding the study , and four studies did not
use asthma severity or level of control as an inclusion criterion [47, 49–51] but measured
patients’ asthma control using the ACQ [15, 53]. Based on the ACQ scores[15, 53], Dogra et al
 included participants with well-controlled or relatively well-controlled asthma, Turk et al
 included participants with relatively well-controlled or poorly controlled asthma, and
Scott et al [49, 50] included participants with well-controlled, relatively well-controlled or
poorly controlled asthma.
Table 4 summarizes changes in nocturnal symptoms after intervention in adults. The
prevalence of nocturnal symptoms at baseline ranged from 50 to 74%. Four of six studies with adults
[47, 49–51] showed a reduction in the prevalence of nocturnal symptoms after physical
Four studies evaluated non-obese adults with asthma [46–48, 51]. Two of these studies [47,
51] showed that supervised physical exercise for at least 12 weeks (3 times per week) reduced
the nocturnal asthma symptoms prevalence, improved subjective sleep quality and reduced
nocturnal symptoms frequency. The studies did not report if there were any changes in
medications over the study period. Dogra et al  also evaluated the effects of additional 12 weeks
of unsupervised physical exercise after the 12 weeks of supervised exercise training. They
found that subjective sleep quality and nocturnal awakening frequency scores were maintained
by unsupervised physical exercise (mean change: 0.2 ± 1.0, p = 0.7 for nocturnal symptoms
frequency and -0.3 ± 1.2, p = 0.8 for subjective sleep quality). On the other hand, a similar
duration of unsupervised exercise (12 weeks) which was not anteceded by supervised exercise did
not provide similar results . Moreover, Hallstrand et al  reported no changes in the
daytime and nocturnal symptoms and medication after 10 weeks of aerobic exercise. However,
the baseline asthma symptoms were not reported in the paper and we could not reach the
authors to get this information.
Two studies investigated the effects of physical exercise training in obese patients with
asthma [49–51]. These studies showed that in obese adults with asthma, physical exercise for at
least 10 weeks (3 times per week) reduced the prevalence of nocturnal asthma and was
associated with clinically significant improvements in nocturnal symptoms and subjective sleep
quality but they did not report if there were any changes in medication over the study period.
Turk et al  compared the effects of 12 weeks of supervised physical exercise training in
obese and non-obese patients with asthma (Table 4). In this study, the awakening frequency
score was available from 54 patients. From this sample, the percentage of patients with
nocturnal symptoms reduced from 74% at baseline to 57% after exercise training and the prevalence
of nocturnal symptoms decreased in obese and non-obese groups (Table 4). Both groups had
clinically significant reductions in the nocturnal symptoms frequency (reduction of 0.5 in
the score; Table 4) and the changes in nocturnal symptoms frequency were similar between
the two groups. However, only in non-obese patients there was a statistically significant
reduction in the scores of nocturnal symptoms frequency (p = 0.03).
Scott et al [49, 50] investigated the effects of three weight loss interventions (diet, exercise,
and diet plus exercise) on clinical outcomes of asthma. All weight loss interventions improved
asthma-related quality of life and reduced the prevalence of nocturnal symptoms (Table 4).
Clinically significant improvements in subjective sleep quality (increase of 0.5 in the score,
Asthma quality of life and asthma control
improved after supervised and unsupervised
No changes in asthma symptom scores after
All three interventions improved
asthmarelated quality of life. Asthma control
improved in diet group and combined
Prevalence: 71% to 51%
ΔACQ-1: -0.6±1.5, p = 0.03
Prevalence: 79% to 68%
ΔACQ-1: -0.6±1.7, p = 0.1
A clinically and statistically significant
improvement in subjective sleep quality and a
clinically significant reduction in nocturnal
symptoms frequency were observed in the
supervised exercise group
Compared to the control group, in the
supervised exercise group, subjective sleep
quality improved and frequency of nocturnal
There were no significant changes in the
nocturnal symptoms frequency within each
A clinically significant improvement in
subjective sleep quality was observed in exercise
and exercise + diet group
Within each group, there were no significant
changes in the nocturnal awakening frequency
Reduction in nocturnal awakening frequency
was clinically significant in both groups, but
statistically significant only in the non-obese
Data are reported as mean ± SD.
ACQ-1, Asthma Control Questionnaire question about nocturnal asthma symptoms frequency; AQLQ-24, Asthma Quality of Life Questionnaire question about
of Life Questionnaire question about subjective sleep quality.
Table 4) were found only in the groups that performed exercise (exercise plus diet and exercise
groups). However, subjective sleep quality improvement was statistically significant only in the
diet plus exercise group (Table 4). In all three groups, there were no statistically significant
changes in the nocturnal symptoms frequency. However, in the diet plus exercise group,
reduction in the nocturnal symptoms frequency was borderline significant (p = 0.06) and also
This is the first systematic review to explore the effects of physical exercise on nocturnal
asthma symptoms. We included 11 studies and our main finding is that aerobic physical
exercise may improve nocturnal asthma in children and adults by reducing the prevalence and
frequency of nocturnal symptoms.
In the studies with children, physical exercise for at least 6 weeks, twice a week, reduces the
prevalence of nocturnal symptoms [41–44]. Moreover, supervised aerobic physical exercise for
8 weeks (2 times per week) improves nocturnal symptoms and aerobic fitness and reduces
pulmonary inflammation . The prevalence of children with nocturnal symptoms at baseline
ranged from 0–63%. However, some studies included controlled asthma, possibly excluding
patients with severe nocturnal symptoms. Thus, the heterogeneity in the inclusion criteria
among the studies could contribute to the discrepancy in the prevalence of nocturnal
In studies with non-obese adults with asthma, supervised physical exercise for at least
12 weeks reduced the nocturnal asthma prevalence, improved subjective sleep quality, and
reduced nocturnal symptoms frequency [47, 51]. Unsupervised exercise training for the same
period (12 weeks) did not improve nocturnal symptoms , but was effective to control
nocturnal symptoms frequency after the supervised exercise period . The improvements in
general asthma control after aerobic physical exercise training were associated with the
improvements in aerobic fitness and dyspnea index [47, 51]. However, based on the included
studies, it is not possible to determine the mechanisms by which physical exercise can improve
nocturnal asthma in non-obese patients.
In obese adults with asthma, physical exercise for at least 10 weeks reduced the prevalence
of nocturnal asthma and was associated with clinically significant reduction in nocturnal
symptoms and enhanced subjective sleep quality [49–51]. Scott el at [49, 50] investigated the
effects of three weight loss interventions (diet, exercise, and diet plus exercise) on clinical
outcomes of asthma. In this study, all interventions led to a significant weight loss in all groups.
However, the authors found clinically significant improvements in subjective sleep quality
only in the groups that performed physical exercise. Thus, it is not clear whether in obese
patients with asthma, weight loss plays an additional role in reducing nocturnal symptoms
frequency and improving asthma control. In Scott el at studies [49, 50], the diet group had a few
participants with nocturnal symptoms at baseline (38% of the participants), and the symptoms
were mild (mean score of subjective sleep quality at baseline of 6.4 ± 0.6 in a scale of 7).
The same study  showed that physical exercise reduced eosinophilic airway
inflammation independent of the weight loss. On the other hand, neutrophilic airway inflammation
reduction was associated with adipose tissue diminution . Together, these results indicate
that in obese asthma patients, the combination of eosinophilic and neutrophilic inflammation
pathways may be related to the nocturnal asthma [84, 85]. Because the prevalence of nocturnal
symptoms was variable between the intervention groups and we did not have enough
information about inflammation or weight loss from other included studies, it was not possible to
determine which inflammatory pathway may be more important in the pathophysiology of
nocturnal asthma or which intervention (exercise or weight management) is more effective in
reducing the prevalence of nocturnal asthma in obese patients. Despite that, based on these
studies [49–51] we may conclude that both weight management and physical exercise could be
beneficial to reduce nocturnal asthma prevalence and frequency in obese patients with asthma.
Moreover, studies in children and adults with asthma show improvements in airway
inflammation after physical training [41, 49, 72, 86, 87], that can lead to improved asthma control
during the day and overnight. However, just 3 of the included studies evaluated the effects of
physical exercise on inflammatory markers [41, 43, 49], and nocturnal symptoms were not the
main outcome in these studies.
The mechanisms related to nocturnal worsening of asthma remain unclear. Nevertheless,
the circadian changes in lung function as well as supine posture are known to contribute to the
nocturnal worsening of asthma [16, 88]. Eight of the included studies evaluated the effects of
physical training on daytime lung function [41–44, 46–49]. Seven of these studies [41, 43, 44,
46–49] as well as a previous systematic review  did not find changes in lung function
related to physical exercise training. Although, the included studies did not evaluate overnight
changes in lung function, it is unlikely that exercise training will cause overnight changes if it
did not change daytime lung function. Another factor that may be associated with the
nocturnal worsening of asthma is the overnight rostral fluid shift from the legs to the thorax which
can increase fluid accumulation in the lower airway wall, narrow airway lumen, and worsen
asthma symptoms [25, 26]. Previous studies in patients with sleep apnea have shown that
physical training during the day can reduce overnight fluid shift out of the legs and improve sleep
apnea severity  and snoring . However, no study has evaluated the effect of exercise
training on overnight rostral fluid shift and nocturnal asthma symptoms in patients with
Our systematic review has limitations that are important to address. First of all, we included
a small number of studies. This was because many potentially relevant studies did not report
nocturnal symptoms and subjective sleep quality data. Of 38 full text studies where authors
were contacted, 71% of the authors could not be reached or did not have the requested data.
Second, the majority of the included studies had a small number of participants and 50% of
the studies had a high risk of bias for allocation, increasing the risk of type I error (false
positive). Third, asthma medication was not reported in 3 studies [42, 49, 50] and 73% of the
included studies did not report changes in asthma medications over the study period.
Medication use may be an important potential confounder because it is related to both the ability to
exercise and to asthma symptoms control, including nocturnal asthma symptoms. Fourth, our
measurements of the frequency of nocturnal symptoms and subjective sleep quality were each
based on a single subjective question. There is no standardized questionnaire to evaluate
nocturnal symptoms in asthma. Sleep quality is impacted by a wide number of factors  but
specific questionnaires or objective measurements such as polysomnography indices are not
usually evaluated in asthma patients. Moreover, in our study we evaluated subjective sleep
quality affected specifically by asthma symptoms. Lastly, the heterogeneous physical exercise
routines and durations are also a limitation. We could not define minimum requirements for
exercise regimens to optimize management of patients with nocturnal asthma based on our
results. Additionally, the small number of randomized controlled trials (n = 5) and
heterogeneity among them did not allow a meta-analysis. Despite the limited evidence, our review
confirmed the high prevalence of nocturnal asthma in children and adults and the efficacy of
physical exercise to improve nocturnal asthma control.
In conclusion, our systematic review demonstrated that aerobic physical exercise may improve
nocturnal asthma in children and adults by reducing the prevalence and frequency of
nocturnal symptoms. The mechanisms by which physical activity improves nocturnal asthma remain
unclear. For this reason, there is a need for more studies to evaluate the potential mechanisms
of nocturnal worsening of asthma and how physical exercise might affect different asthma
phenotypes. Such studies could lead to develop effective exercise routines as alternative or
complementary treatments to improve asthma symptoms and quality of life in patients with nocturnal
Conceptualization: Cristina de Oliveira Francisco, W. Darlene Reid, Azadeh Yadollahi.
Data curation: Cristina de Oliveira Francisco, Azadeh Yadollahi.
Formal analysis: Cristina de Oliveira Francisco, Swati Anil Bhatawadekar, Jessica Babineau.
Methodology: Cristina de Oliveira Francisco, Swati Anil Bhatawadekar, Jessica Babineau, W.
Darlene Reid, Azadeh Yadollahi.
Supervision: Azadeh Yadollahi.
Writing – original draft: Cristina de Oliveira Francisco.
Writing – review & editing: Cristina de Oliveira Francisco, Swati Anil Bhatawadekar, Jessica
Babineau, W. Darlene Reid, Azadeh Yadollahi.
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