Asthma
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To cite: Liu X, Hong C, Liu Z,
et al. Association of sleep
disorders with asthma: a
meta-­analysis. BMJ Open
Respir Res 2023;10:e001661.
doi:10.1136/
bmjresp-2023-001661
► Additional supplemental
material is published online
only. To view, please visit the
journal online (http://​dx.​doi.​
org/​10.​1136/​bmjresp-​2023-​
001661).
XL and CH contributed
equally.
XL and CH are joint first
authors.
Received 15 February 2023
Accepted 8 September 2023
© Author(s) (or their
employer(s)) 2023. Re-­use
permitted under CC BY-­NC. No
commercial re-­use. See rights
and permissions. Published by
BMJ.
For numbered affiliations see
end of article.
Correspondence to
Dr Xiang Ren;
​tcszyyrenxiang@​163.​com and
Dr Xuefang Gu;
​Xxshdhua@​126.​com
Association of sleep disorders with
asthma: a meta-­analysis
Xueqian Liu,1 Cheng Hong,2 Zhiyu Liu,3 Lihua Fan,2 Moqing Yin,2 Yunhu Chen,2
Xiang Ren ‍ ‍,1 Xuefang Gu4
ABSTRACT
Background Animal experiments and clinical trials have
revealed a potential relationship between sleep disorders
and asthma. However, the associations between these
factors remain unclear.
Material and methods We searched PubMed, Embase,
Web of Science and Cochrane Library databases for
eligible studies published before 30 December 2022.
Studies investigating the association between sleep
disorders (insomnia, poor sleep quality and insufficient
sleep time) and asthma were selected. Sleep disorders
were assessed using questionnaires, interviews, or
medical records. Asthma was diagnosed based on medical
history and drug use. The Newcastle-­Ottawa Scale and
the Agency for Healthcare Research and Quality checklist
were employed for quality assessment. We used OR with
95% CI as the effect measures and forest plots to display
the results. Heterogeneity was evaluated using I2 statistics
and subgroup analyses were performed for bias analysis.
Publication bias was evaluated using the funnel plots and
Egger’s test.
Results Twenty-­three studies were included in the
primary analysis, which suggested a positive association
between sleep disorders and asthma (OR: 1.38, 95%
CI 1.10 to 1.74). Subgroup analyses were conducted
according to the study design, age, family history of
asthma and type of sleep disorders. We did not find
any association between sleep disorders and asthma in
children aged ˂12 years (OR: 1.13, 95% CI 0.97 to 1.32).
The association was insignificant in studies where the
family history of asthma was adjusted for (OR: 1.16, 95%
CI 0.94 to 1.42). Funnel plot and Egger’s test indicated a
significant publication bias.
Conclusion Sleep disorders are associated with an
increased prevalence and incidence of asthma. However,
the quality of the evidence was low because of potential
biases.
PROSPERO registration number CRD42023391989.
INTRODUCTION
Bronchial asthma is a heterogeneous disease
clinically characterised by variable airway
obstruction, with interrupted wheezing and
chest tightness being its major symptom.1
Although the pathogenesis of asthma is still
not fully understood, airway inflammation
plays a key role.2 Medication, especially gluco-
corticoids, has shown significant benefits, and
the mortality rate from asthma has decreased
Liu X, et al. BMJ Open Respir Res 2023;10:e001661. doi:10.1136/bmjresp-2023-001661
WHAT IS ALREADY KNOWN ON THIS TOPIC
⇒ Sleep disorders are highly prevalent in patients with
asthma and often result in poor asthma control.
Whether sleep disorders are associated with an in-
creased risk of asthma remains indeterminate.
WHAT THIS STUDY ADDS
⇒ Sleep disorders are associated with an increased
prevalence and incidence of asthma. However, the
quality of evidence was low because of potential
biases.
HOW THIS STUDY MIGHT AFFECT RESEARCH,
PRACTICE OR POLICY
⇒ Although more studies are required to confirm the
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current findings, sleep disorders should be serious-
ly considered in patients with asthma or in healthy
subjects.
by 26.7% from 1990 to 2015.3 However, the
prevalence has increased by 12.6%,3 bringing
huge health hazards and economic burdens.
Therefore, an increased focus on risk factors
for asthma is urgent and essential.
Sleep disorders are highly prevalent in
patients with asthma and often result in
poor asthma control.4 These findings have
led to speculation about the relationship
between sleep and asthma risk.5 Two prospec-
tive cohort studies have found that chronic
insomnia symptoms significantly increased
the risk of asthma.6 7 However, other studies
have indicated that asthma is not associated
with poor sleep quality.8–12 Moreover, several
large-­scale cross-­sectional studies8 10 13–20 have
investigated the association between insuffi-
cient sleep and asthma, with widely divergent
results. Some studies have suggested a posi-
tive association16 18 21 while others have indi-
cated that the association is not significant.8 17
A Korean study also indicated that catch-­up
sleep decreases the incidence of asthma.15
The conclusions of the observational studies
were inconsistent, and the results were easily
confounded. We hypothesised that the asso-
ciation between sleep disorders and asthma
may be subject to population specificity (eg,
  
1
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age, sex and family history), the study design and type of
sleep disorders. Therefore, we conducted a meta-­analysis
to test the hypothesis.
MATERIALS AND METHODS
The meta-­analysis was conducted according to the recom-
mendations of the Meta-­analysis of Observational Studies
in Epidemiology (MOOSE) Group,22 and was reported
following the Preferred Reporting Items for Systematic
Reviews and Meta-­Analyses (PRISMA) statement.23 The
MOOSE checklist is provided in online supplemental
material 1.
Patient and public involvement
No patients were involved.
Literature search
Databases including PubMed, Embase, Cochrane Library
and Web of Science were searched without language
restrictions for articles published before 30 December
2022. We used the following items as keywords:
(“insomnia” OR “sleep duration” OR “sleep time” OR
“sleep restriction” OR “sleep loss” OR “lack of sleep” OR
“insufficient sleep” OR “sleep deprivation” OR “sleep
disturbances” OR “sleep quality” OR “initiate sleep” OR
“initiating sleep” OR “maintain sleep” OR “maintaining
sleep”) AND “asthma”. A complete search strategy is
provided in online supplemental material 2.
Inclusion and exclusion criteria
Observational studies (cohort, case-­ control, longitu-
dinal, or cross-­sectional) designed to evaluate the asso-
ciation between sleep disorders and the incidence (or
prevalence) of asthma were included. Sleep disorders
included insomnia, poor sleep quality and insufficient
sleep duration. Insomnia was defined as disturbance of
sleep onset or sleep maintenance, or poor sleep quality.24
Insufficient sleep was defined as sleep duration shorter
than the recommended sleep time at different ages. In
adults, sleep durations ˂7 hours were regarded as insuf-
ficient sleep.25 Sleep quality was assessed based on face-­
to-­face interviews or questionnaires from subjects. No
restrictions were imposed on the effect measures used
in the included studies. Letters, comments, conference
abstracts and studies with incomplete data were excluded.
Data extraction and risk of bias assessment
Literature search, data extraction and quality assessment
of the included studies were performed independently
by two researchers (XL and CH). When the researchers
disagreed, a third researcher (ZL.) was consulted. The
extracted information included author, region, study
design, population characteristics of each study (eg, age
and sex), diagnosis of asthma, ascertainment of sleep
disorders and adjusted covariates.
2 Liu X, et al. BMJ Open Respir Res 2023;10:e001661. doi:10.1136/bmjresp-2023-001661
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The methodological quality of the cohort or case-­
control studies was assessed using the Newcastle-­Ottawa
Scale (NOS), designed for non-­randomised controlled
trials (RCTs). It considered three parts as follows: selec-
tion bias, information bias and confounding bias. Details
of the NOS scale and grading standards are provided
in online supplemental table 1. The checklist recom-
mended by the Agency for Healthcare Research and
Quality (AHRQ)26 was employed for the quality assess-
ment of cross-­sectional studies, and the standards were
as follows: low quality, 0–3; moderate quality, 4–7; high
quality, 8–11. It consists of 11 items and the details are
provided in online supplemental table 2.
Observational studies are easily subject to confounders,
and subgroup analyses are performed. The cross-­sectional
design only describes coexistence relationships rather
than causal relationships. Patients with asthma often
experience sleep disorders. Therefore, the study design
was considered a source of bias. In the present meta-­
analysis, sleep disorders were associated with poor sleep
quality and insufficient sleep duration. The type of sleep
disorders can also lead to bias. In addition, we hypothe-
sised that the following population characteristics might
confound the relationship between sleep disorders and
asthma: (1) age, (2) race, (3) body mass index (BMI) and
(4) family history of asthma.
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Quality of evidence assessment
Two researchers (XL and CH) independently evalu-
ated the quality of evidence for all outcomes based on
the Grading of Recommendation Assessment, Develop-
ment, and Evaluation (GRADE) methodology.27 The
following factors were considered: risk of bias, inconsist-
ency in results, indirectness of evidence, imprecision and
reporting bias. The quality of the evidence was classified
as high, moderate, low or very low.
Data synthesis and analysis
All data analyses were performed using Stata V.15.0
(Stata Corp). Forest plots were used to display the indi-
vidual and pooled results for the association between
sleep disorders and asthma. OR with 95% CI were used
as effect measures. In individual studies, 19 reported
ORs, 2 reported relative risk (RR) and 2 reported HRs.
In pooled analyses of epidemiological studies, distinc-
tions among the effect measures can be ignored if the
outcomes are uncommon.28 Among studies that reported
RRs or HRs, the incidence of asthma was low (<10%).
Thus, RR and HR were regarded directly as OR in our
study. Forest plots were used to display the individual
and pooled results. Heterogeneity was assessed using I2
statistics. The random-­effect model was selected because
of the clinical heterogeneity in the definitions of asthma,
sleep quality and sleep duration. A sensitivity analysis was
conducted to assess the robustness of the results. Publi-
cation bias was evaluated using funnel plots and Egger’s
test.

Figure 1 The Preferred Reporting Items for Systematic Reviews and Meta-­Analyses statement flow chart of study selection.
RESULTS
Study selection
A PRISMA statement flow chart of the study selec-
tion process is shown in figure 1. We obtained 1854
publications after eliminating duplicates. We identi-
fied 216 potentially eligible articles by reviewing titles
and abstracts. Ultimately, 23 studies6–17 19–21 29–36 met
the eligibility criteria and were included in the meta-­
analysis.
Liu X, et al. BMJ Open Respir Res 2023;10:e001661. doi:10.1136/bmjresp-2023-001661
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Characteristics of included studies
Table 1 summarises the authors, regions and population
characteristics (eg, age and sex) of each study. Five cohort
studies6 7 21 29 32 and 18 cross-­sectional studies8–17 19 20 30 31 33–36
were included in the meta-­analysis. Sleep disorders were
assessed using questionnaires, face-­to-­face interviews or
medical records. Asthma diagnosis was based on medical
records, drug use, questionnaires or interviews regarding
relevant medical history. In addition, multiple covariates
3
 4
Table 1 Characteristics of included studies
Gender, Measure of
Author Region Study design Age male (%) Diagnosis of asthma Exposure exposure OR with 95% CI Adjusted covariates
7
Brumpton et al Norway Prospective 20–65 years 55.7 Questionnaire about Insomnia Questionnaire 2.67 (1.15 to 5.45) Age, gender, BMI, education,
cohort study physician diagnosis economics, smoking, anxiety and
Open access

and prescription of depression

asthma drugs
Han et al15 Korea Cross-­sectional 12–18 years 50.2 Questionnaire about Insufficient Questionnaire ˂ 5 hours, 1.09 (1.04 Age, gender, BMI, smoking, alcohol
study physician diagnosis sleep to 1.14); 6 hours, 1.05 use, regular physical activity,
(1.00 to 1.10) economics, residence, school
type, sexual experience, drug use,
academic achievement, family
structure, stress, health status,
happiness, depression, suicidal idea,
suicidal plan and suicidal attempt
Bakour et al19 The United Cross-­sectional High school 50.3 Questionnaire about Insufficient Questionnaire 1.22 (1.07 to 1.40) Age, gender, race, smoking, alcohol
States study students physician diagnosis sleep use, marijuana use, physical activity
Bakour et al21 The United Longitudinal 12–18 years 50.1 Questionnaire about Insufficient Questionnaire 1.52 (1.11 to 2.10) Age, gender, race, BMI, smoking,
States cohort study physician diagnosis sleep alcohol, physical activity, parental
income, parental education, pubertal
development, family history of
asthma
Björnsdóttir Multicenter Cross-­sectional 39–67 years 52.3 Questionnaire about Insufficient Questionnaire 0.97 (0.62 to 1.52) Gender, age, marital status, exercise,
et al33 study physician diagnosis sleep smoking, BMI
Dashti et al20 The United Cross-­sectional ≥ 18 years 57.6 Medical record Insufficient Questionnaire 1.23 (1.09 to 1.38) Age, gender, race, BMI
States study sleep
Dai et al31 The United Cross-­sectional ≥ 18 years 43.6 Medical record Insufficient Questionnaire ˂ 5 hours, 1.7 (1.1 to Gender, age, race, education,
States study sleep 2.4); 6 hours, 1.2 (0.8 economics, employment status,
to 1.7) depression
Choi et al14 Korea Cross-­sectional 19–39 years 41.8 Questionnaire about Insufficient Questionnaire ˂ 5 hours, male, Age, BMI, smoking, alcohol use,
study physician diagnosis sleep 1.265 (0.79 to 2.206); physical activity, economics, serum
˂ 5 hours, female, 25(OH)D level, stress level
1.553 (1.023 to 2.359);
6 hours, male, 1.299
(0.959 to 1.759);
6 hours, female, 1.06
(0.757 to 1.484)
Zhang et al6 Hong Kong, Prospective Adults, 46.5 Questionnaire about Insomnia Questionnaire 17.9 (2.28 to 140) Age, gender, education, economics,
China cohort study 40.7±5.4 physician diagnosis syndrome drug use
(mean±SD)
Nutakor et al17 Multicenter Cross-­sectional ≥ 50 years 53.5 Internet interview Insufficient Internet 1.34 (0.75 to 2.40) Gender, residence, age, marital
study sleep interview status, education, economics
Stangenes et Norway Cross-­sectional ˂ 11 years NA Questionnaire about Poor sleep Questionnaire Poor sleep quality, 1.1 Gender, single parenthood, maternal
al11 study physician diagnosis quality and (0.5 to 2.5); insufficient education
and prescription of insufficient sleep, 2.6 (0.9 to 7.6)
asthma drugs sleep

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Continued
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 Table 1 Continued
Gender, Measure of
Author Region Study design Age male (%) Diagnosis of asthma Exposure exposure OR with 95% CI Adjusted covariates
8
Seow et al Singapore Cross-­sectional ≥ 18 years 49.6 Questionnaire about Poor sleep Questionnaire Poor sleep quality, Sociodemographic and lifestyle
study physician diagnosis quality and 1.011 (0.784 to 1.304); factors, physical and mental disorder
insufficient insufficient sleep, 1.174
sleep (0.899 to 1.534)
Blank et al35 The United Cross-­sectional 13–18 years 48.6 Face-­to-­face interview Insomnia Face-­to-­face 1.53 (1.19 to 1.96) Age, gender, race
States study interview
Lim et al16 Korea Cross-­sectional 12–18 years 51.6 Questionnaire about Insufficient Questionnaire ˂ 6 hours, 1.38 (1.15 to Age, genders, region, economics,
study physician diagnosis sleep 1.65); 6 to 7 hour, 1.07 smoking, physical activity, sitting
(0.9 to 1.27) time, obesity
Estanislau et Brazil Cross-­sectional 12–17 years 43.8 Questionnaire about Insufficient Questionnaire 1.17 (1.01 to 1.35) Age, gender, type of school, mental
al30 study physician diagnosis sleep disorders, excess weight
Gureje et al36 Nigeria Cross-­sectional ≥ 65 years 46.2 Face-­to-­face interview Insomnia Face-­to face 2.1 (1.4 to 3.1) Age, gender
study interview
Basnet et al34 Finland Cross-­sectional 25–74 years 47.3 Questionnaire about Poor sleep Questionnaire 1.435 (0.96 to 2.14) Age, gender, living status, education,
study physician diagnosis quality region, smoking, alcohol intake,
physical activity, BMI
Ma et al9 China Cross-­sectional 3–6 years 51.7 Questionnaire about Insufficient Questionnaire Insufficient sleep, 0.95 Age, gender, region, maternal

Liu X, et al. BMJ Open Respir Res 2023;10:e001661. doi:10.1136/bmjresp-2023-001661

study physician diagnosis sleep and (0.49 to 1.84); difficulty education, BMI, delivery mode, birth
difficulty maintaining sleep, 1.49 weight, maternal tobacco exposure
maintaining (1.05 to 2.13) during pregnancy, feeding pattern
sleep before 6 months
Chen et al10 China Cross-­sectional 12–18 years 64.4 Questionnaire about Poor sleep Questionnaire Difficulty falling asleep, Demographic characteristics,
study physician diagnosis quality 1.00 (0.77 to 1.31); family structure, gestation, delivery,
difficulty maintaining feeding, socioeconomic status,
sleep, 1.25 (0.94 to health problems, daily activity and
1.67) behaviour routine
Lin et al32 Taiwan, Prospective All ages 40.0 Medical record Insomnia Medical 1.89 (1.64 to 2.17) Age, gender, comorbidity, region,
China cohort study record economics
Chen et al29 Taiwan, Prospective 12–17 years 51.2 Questionnaire about Poor sleep Questionnaire 1.10 (1.03 to 1.17) Age, sex, parental education,
China cohort study physician diagnosis quality economics
Chen et al12 China Cross-­sectional ≤2 years 51.1 Medical record Poor sleep Face-­to-­face Difficulty falling asleep, Gender, maternal age, maternal
study quality interview 1.05 (0.89 to 1.24); education level, economics, family
difficulty maintaining history of allergy, delivery mode,
sleep, 1.06 (0.81 to household secondhand smoke
1.39)
Hu et al13 China Cross-­sectional All ages 46.5 Questionnaire about Insufficient Questionnaire 1.72 (1.32 to 2.24) Gender, age,
study physician diagnosis sleep smoking, alcohol, region, BMI

.BMI, body mass index; NA, not applicable.

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5
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 Open access
Figure 2 Forest plot of the association between insomnia and asthma.
were adjusted for in the individual studies, and the details
are presented in table 1.
All cohort studies6 7 21 29 32 were considered high
quality according to the NOS assessment (online
supplemental table 3). Eleven cross-­
sectional
studies9 10 12 13 16 17 19 20 34–36 were considered as high quality,
and seven studies8 11 14 15 30 31 33 were considered moderate
quality, according to the AHRQ 11-­item checklist (online
supplemental table 4).
Meta-analysis
Twenty-­three studies6–17 19–21 29–36 contributed to the
primary analysis, suggesting that sleep disorders were
associated with an increased incidence (or prevalence)
of asthma (OR: 1.38, 95% CI 1.10 to 1.74, figure 2).
The sensitivity analysis indicated robust results (online
supplemental figure 1). Next, subgroup analyses were
conducted according to the study design, type of sleep
disorders, race, age, BMI, and family history of asthma.
6 Liu X, et al. BMJ Open Respir Res 2023;10:e001661. doi:10.1136/bmjresp-2023-001661
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Sleep disorders were associated with asthma in the meta-­
analysis of cohort studies (OR: 1.73, 95% CI 1.16 to 2.57),
and the results were consistent in the analysis of cross-­
sectional studies (OR: 1.20, 95% CI 1.14 to 1.28; online
supplemental figure 2). Insufficient sleep duration (OR:
1.20, 95% CI 1.13 to 1.28) or poor sleep quality was
associated with asthma (OR: 1.10, 95% CI 1.05 to 1.16;
online supplemental figure 3). The association of sleep
disorders with asthma was significant in European/Amer-
ican subjects (OR: 1.34, 95% CI 1.21 to 1.48) and Asian
subjects (OR: 1.21, 95% CI 1.12 to 1.31; online supple-
mental figure 4). Sleep disorders were associated with
asthma in the meta-­analysis of studies where BMI was
adjusted (OR: 1.22, 95% CI 1.13 to 1.31), and the result
were consistent with the analysis of studies where BMI
was not adjusted (OR: 1.29, 95% CI 1.14 to 1.47; online
supplemental figure 5). Sleep disorders were associated
with increased incidence (or prevalence) of asthma in
adults (>18 years, OR: 1.36, 95% CI 1.18 to 1.57) and

Figure 3 Forest plot of the association between insomnia and asthma in adults (>18 years), adolescent (12–18 years) and
children (˂12 years).
adolescents (12–18 years, OR: 1.15, 95% CI 1.08 to 1.21),
but not in children (˂12 years, OR: 1.13, 95% CI 0.97 to
1.32; figure 3). The association between sleep disorders
and asthma was significant in studies where family history
of asthma was not adjusted (OR: 1.27, 95% CI 1.18 to
1.36), while the association was not significant in those
where family history of asthma was adjusted (OR: 1.16,
95% CI 0.94 to 1.42; figure 4). Additional details of the
subgroup analyses are presented in table 2. Funnel plots
(figure 5) and Egger’s test (p=0.001) also indicated a
significant publication bias.
Quality of evidence
In the overall analysis, the quality of evidence was
regarded as very low. In the subgroup analyses, the grade
levels of evidence ranged from low to very low. The
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classification of the GRADE evidence for all outcomes is
presented in table 3.
DISCUSSION
To our knowledge, this is the first meta-­analysis evaluating
the relationship between sleep disorders and asthma.
After a comprehensive review of the current literature,
we found that sleep disorders were positively associated
with asthma. However, this association was insignifi-
cant in studies in which a family history of asthma was
adjusted. In addition, this relationship was not significant
in children.
Several subgroup analyses were performed to interpret
the high heterogeneity observed in the primary analysis.
Our meta-­analysis included 23 studies, most of which
were cross-­sectional. Such a study design cannot describe
7
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Figure 4 Forest plot of the association between insomnia and asthma in studies where family history of asthma was
adjusted and not adjusted.
a causal relationship; however, a pooled analysis of
cohort studies indicated that sleep disorders significantly
increased the incidence of asthma. Similarly, another
7-­
year prospective cohort study that recruited 7655
individuals discovered that healthy-­long sleep duration,
compared with short sleep time, decreased the incidence
of asthma in adults.37 Moreover, two Mendelian rando-
misation studies demonstrated the causality between
insomnia and asthma from a genetic perspective. These
findings suggest that sleep disorders may be a risk factor
for asthma.
We also speculate that an association between sleep
disorders and asthma might exist in a partial popula-
tion owing to the contradictory results of individual
studies. Obesity is believed to play a role in the devel-
opment of asthma. A cross-­sectional survey by Bakour et
al,19 including 16 728 participants in Florida, concluded
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that short sleep duration was related to asthma only in
adolescents with obesity. However, our subgroup anal-
yses indicated that sleep disorders were associated with
asthma, regardless of whether BMI was adjusted. We also
found that the association between sleep disorders and
asthma was insignificant in children aged ˂12 years. In
these studies, the measurements of sleep disorders were
mainly based on questionnaires completed by parents
rather than on self-­ reported results, which may have
led to bias. It should also be noted that the incidence
of asthma could have been underestimated because the
diagnosis was mainly based on relevant symptoms such as
wheezing.38 Therefore, this result should be interpreted
with caution. In addition, the present meta-­ analysis
suggests that the association between sleep disorders
and asthma is modified by genetic factors since this asso-
ciation was not significant in studies that adjusted for a
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Table 2 Subgroup analyses according to possible factors that may modify the association between insomnia and asthma
Heterogeneity
Characteristics of studies Number of studies OR with 95% CI (%)
Cohort studies6 7 21 29 32 5 1.73 (1.16 to 2.57) 93.3
Cross-­sectional studies8–17 19 20 30 31 33–36 18 1.20 (1.14 to 1.28) 54.9
Insufficient sleep duration8 9 11 13–17 19–21 30 31 33 14 1.20 (1.13 to 1.28) 56.1
Poor sleep quality8–12 29 34 7 1.10 (1.05 to 1.16) 0
6–8 14 17 20 31 33 34 36
Adults 10 1.36 (1.18 to 1.57) 56.4
10 15 16 19 21 29 30 35
Adolescents 8 1.15 (1.08 to 1.21) 59.8
Children9 11 12 3 1.13 (0.97 to 1.32) 14.7
7 11 19–21 31 34 35
Studies conducted in Europe and America 8 1.34 (1.21 to 1.48) 22.2
Studies conducted in Asia6 8–10 12–16 29 32 11 1.21 (1.12 to 1.31) 79.8
7 9 13–16 20 21 30 33 34
Studies in which BMI was adjusted 11 1.22 (1.13 to 1.31) 62.7
6 8 10–12 17 19 29 31 32 35 36
Studies in which BMI was not adjusted 12 1.29 (1.14 to 1.47) 79.4
Studies in which family history of asthma was adjusted12 21 2 1.16 (0.94 to 1.42) 53.1
Studies in which family history of asthma was not adjusted6–11 21 1.27 (1.18 to 1.36) 76.1
13–17 19 20 29–36

BMI, body mass index.

family history of asthma. Nevertheless, only two studies balance.39–41 These immune responses are critical for the
were included in the secondary analysis, which may have onset of asthma.42 Moreover, sleep disorders can result

been underpowered to reach a definitive conclusion.
Several mechanisms may contribute to the association
between asthma and insufficient sleep. In both animal
models and human trials, sleep restriction upregulated
the levels of inflammatory markers, increased the expres-
sion of interleukin subfamily genes, and resulted in an
evident shift in the T helper lymphocyte 1/2 cytokine
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in endocrine and metabolic disorders, such as abnormal
lip and glucose metabolism, hormone changes, and
insulin resistance.43 44 These abnormalities may interact
with chronic inflammation ultimately promoting asthma
development.45 46
In patients with asthma, nocturnal symptoms often
lead to poor sleep.47 Even among healthy individuals,

Figure 5 Funnel plot for publication bias assessment.

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Table 3 Quality of evidence for overall and subgroup analyses
Number
Overall and subgroup analyses of studies OR 95% CI Quality of evidence
6–17 19–21 29–36
Overall 23 1.38 1.10 to 1.74 ⨁〇〇〇
Very Low
Cohort studies6 7 21 29 32 5 1.73 1.16 to 2.57 ⨁〇〇〇
Very Low
Cross-­sectional studies8–17 19 20 30 31 33–36 18 1.20 1.14 to 1.28 ⨁〇〇〇
Very Low
Insufficient sleep duration8 9 11 13–17 19–21 30 31 33 14 1.20 1.13 to 1.28 ⨁〇〇〇
Very Low
Poor sleep quality8–12 29 34 7 1.10 1.05 to 1.16 ⨁⨁〇〇
Low
Adults6–8 14 17 20 31 33 34 36 10 1.36 1.18 to 1.57 ⨁〇〇〇
Very Low
Adolescents10 15 16 19 21 29 30 35 8 1.15 1.08 to 1.21 ⨁〇〇〇
Very Low
Children9 11 12 3 1.13 0.97 to 1.32 ⨁〇〇〇
Very Low
Studies conducted in Europe and America7 11 19–21 31 34 35 8 1.34 1.21 to 1.48 ⨁⨁〇〇
Low
Studies conducted in Asia6 8–10 12–16 29 32 11 1.21 1.12 to 1.31 ⨁〇〇〇
Very Low

Protected by copyright.
Studies in which BMI was adjusted7 9 13–16 20 21 30 33 34 11 1.22 1.13 to 1.31 ⨁〇〇〇
Very Low
Studies in which BMI was not adjusted6 8 10–12 17 19 29 31 32 35 36 12 1.29 1.14 to 1.47 ⨁〇〇〇
Very Low
Studies in which family history of asthma was adjusted12 21 2 1.16 0.94 to 1.42 〇〇〇〇
Very Low
Studies in which family history of asthma was not adjusted6–11 13–17 19 21 1.27 1.18 to 1.36 ⨁〇〇〇
20 29–36
Very Low
BMI, body mass index.

the prevalence of insomnia is continuously increasing.48
Therefore, sleep disorders should be considered. Devel-
oping proper sleep patterns is important for preventing
and controlling asthma. Moreover, our findings provide
opportunities for new asthma treatment strategies (ie,
sleep-­related interventions). Several RCTs have found
that hypnotic treatment can improve bronchial hyper-­
responsiveness.49–51 However, RCTs with small sample
sizes may be underpowered to reach definitive conclu-
sions. More well-­designed multicentre trials are required
to confirm these findings. Although sleeping pills may
be a potential pharmacological treatment, the risk of
adverse events should be fully evaluated in future studies.
This meta-­analysis was based on aggregate rather than
individual data. As a result, heterogeneity among the
studies was significant for all outcomes. This is an obvious
limitation of this study. Another limitation was the poten-
tial bias in our meta-­analysis, which reduced confidence
in our results. There are several possible reasons for
this discrepancy. In most studies, asthma is diagnosed
based on questionnaires rather than secure records (eg,
medical records or drug prescriptions). Thus, the inci-
dence and prevalence of asthma can be inaccurately
evaluated. Similarly, the ascertainment of sleep disor-
ders was mainly based on self-­reported results, which are
susceptible to recall bias. Thus, improved measurements
(eg, home polysomnography) are necessary for future
studies. However, despite adjusting for numerous covari-
ates, residual confounders were inevitable. For example,
obstructive sleep apnoea, a common sleep disorder,
has been associated with the development of asthma in
previous studies.52 53 However, they are also common in
patients with insomnia.54 Thus, it may confound the asso-
ciation between asthma and sleep disorders investigated
in this meta-­analysis.
CONCLUSIONS
We found a positive association between sleep disorders
and the increased prevalence and incidence of asthma.
However, the quality of evidence is not high and the
association between sleep disorders and asthma may be

10 Liu X, et al. BMJ Open Respir Res 2023;10:e001661. doi:10.1136/bmjresp-2023-001661


subject to confounding factors (eg, age and family history
of asthma). Further studies are required to confirm these
findings.
Author affiliations
1 with atopic disease: a cross-­sectional study among Chinese
Emergency Department, Taicang TCM Hospital Affiliated to Nanjing University
of Chinese Medicine, Taicang, Jiangsu, China
2
Cardiovascular Medicine Department, Taicang TCM Hospital Affiliated to
Nanjing University of Chinese Medicine, Taicang, Jiangsu, China
3
Department of Gastroenterology, The Second Affiliated Hospital of Nanjing
University of Chinese Medicine, Nanjing, Jiangsu, China
4 first 2 years of life with sleep outcomes among Chinese toddlers.
Outpatient Department, Taicang TCM Hospital Affiliated to Nanjing University
of Chinese Medicine, Taicang, Jiangsu, China
Contributors XR and XG are responsible for the overall content as the guarantors.
XL and CH managed literature search, data extraction and quality assessment.
XL and MY contributed to manuscript writing. ZL and LF were in charge of data
analysis. YC helped with the language polishing. All authors have read and
approved the final manuscript.
Funding This study was supported by the 2022 Suzhou (Taicang) Science
and Technology Development Plan (Application Number: SKYD2022059), and
the 2021 Taicang City Basic Research Program Projects (Application Number:
TC2021JCYL05 and TC2021JCYL23).
Competing interests None declared.
Patient consent for publication Not applicable.
Ethics approval Not applicable.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access
repository.
Supplemental material This content has been supplied by the author(s). It has
not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been
peer-­reviewed. Any opinions or recommendations discussed are solely those
of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and
responsibility arising from any reliance placed on the content. Where the content
includes any translated material, BMJ does not warrant the accuracy and reliability
of the translations (including but not limited to local regulations, clinical guidelines,
terminology, drug names and drug dosages), and is not responsible for any error
and/or omissions arising from translation and adaptation or otherwise.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-­commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the
use is non-­commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
ORCID iD
Xiang Ren http://orcid.org/0009-0000-4458-865X
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