Wong et al.
Journal of Physiological Anthropology(2024) 43:6
https://doi.org/10.1186/s40101-024-00356-5

ORIGINAL ARTICLE

Journal of
Physiological Anthropology

Open Access

Sleep and allergic diseases among young
Chinese adults from the Singapore/Malaysia
Cross‑Sectional Genetic Epidemiology Study(SMCGES) cohort
Qi Yi Ambrose Wong1, Jun Jie Lim1, Jun Yan Ng1, Yi Ying Eliza Lim1, Yang Yie Sio1 and Fook Tim Chew1*   

Abstract
Background and objective Sleep disruption has been shown to affect immune function and thus influence allergic
disease manifestation. The specific effects of sleep on allergic diseases, however, are less well-established; hence,in a unique population of young Chinese adults, we investigated the association between sleep and allergic disease.
Methods Young Chinese adults recruited from Singapore in the Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study (SMCGES) were analyzed. We used the International Study of Asthma and Allergies in Childhood(ISAAC) protocol and a skin prick test to determine atopic dermatitis (AD), allergic rhinitis (AR), and asthma status.
Information regarding total sleep time (TST) and sleep quality (SQ) was also obtained.
Results Of 1558 participants with a mean age of 25.0 years (SD = 7.6), 61.4% were female, and the mean total sleep
time (TST) was 6.8 h (SD = 1.1). The proportions of AD, AR, and asthma were 24.5% (393/1542), 36.4% (987/1551),
and 14.7% (227/1547), respectively. 59.8% (235/393) of AD cases suffered from AD-related sleep disturbances,
37.1% (209/564) of AR cases suffered from AR-related sleep disturbances, and 25.1% (57/227) of asthma cases suffered from asthma-related sleep disturbances. Only asthma cases showed a significantly lower mean TST than those
without asthma (p = 0.015). Longer TST was significantly associated with lower odds of AR (OR = 0.905, 95% CI = 0.820–
0.999) and asthma (OR = 0.852, 95% CI = 0.746–0.972). Linear regression analyses showed that lower TST was significantly associated with asthma (β =  − 0.18, SE = 0.076, p-value = 0.017), and AR when adjusted for AR-related sleep
disturbances (β =  − 0.157, SE = 0.065, p-value = 0.016). Only sleep disturbances due to AR were significantly associatedwith a poorer SQ (OR = 1.962, 95% CI = 1.245–3.089).
Conclusions We found that sleep quality, but not sleep duration was significantly poorer among AD cases,
although the exact direction of influence could not be determined. In consideration of the literature coupled with ourfindings, we posit that TST influences allergic rhinitis rather than vice versa. Finally, the association between TST
and asthma is likely mediated by asthma-related sleep disturbances, since mean TST was significantly lower
among those with nighttime asthma symptoms. Future studies could consider using objective sleep measurements
coupled with differential expression analysis to investigate the pathophysiology of sleep and allergic diseases.
Keywords Allergic rhinitis, Atopic dermatitis, Asthma, ISAAC​, Sleep*Correspondence:
Fook Tim Chew
dbscft@nus.edu.sg
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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Wong et al. Journal of Physiological Anthropology(2024) 43:6

Introduction
BackgroundThe circadian clock in humans is characterized by anapproximately 24-h period which persists in the absenceof external time cues and manifests as oscillatory patternsin physiological parameters such as body temperature,
hormone levels, and metabolism [1–3]. These rhythms
are synchronized by the master circadian clock—two
suprachiasmatic nuclei (SCN) located in the anterior
hypothalamus [3]. In turn, the master clock is entrained
to environmental cues by zeitgebers such as light, foodintake, temperature, and physical activity [4, 5]. Light, themost potent zeitgeber, acts via the intrinsically photosensitive retinal ganglion cells (ipRGC) in the eyes to entrain
the SCN to the light–dark cycle [2, 6–8]. Thus, in a circadian rhythm synchronized to the light–dark cycle, theSCN regulates the synthesis of melatonin which not only
facilitates the regulation of the circadian rhythm, but
has also been linked to various physiological functions,
including immune response [9–12]. Indeed, evidence
has been reported for the regulation of IL-2 and IL-6 bymelatonin via the retinoid-related orphan nuclear hormone receptor family (RZR/ROR) [13, 14]. Moreover, thediscovery of RZR and ROR in other immune cell types,
i.e., monocytes, B-cells, T-cells, and NK cells, has further
raised the possibility of a wider influence of melatonin
and thus the circadian rhythm on immune response [15].
Phenotypically, the circadian rhythm has been implicated in the 24-h cycle in AR symptom manifestationand severity, wherein the mechanism has yet to be determined [16]. Additionally, nocturnal bronchial asthma has
been attributed to the release of pro-inflammatory cells
in a response to daytime antigen exposure, resulting inasthma exacerbation at the end of the day [16].
The most salient effect of the circadian rhythm onhuman behavior is the sleep–wake cycle [17]. Sleep andwake states are generated by neural networks governedby circadian rhythms entrained to the light–dark cycle,
resulting in a sleep–wake cycle coinciding with the 24-h
day [18]. Importantly, sleep has been established to be abiological imperative essential to physiological and psychological well-being, the disruption of which not only
affects circadian rhythmicity, but also predisposes theindividual to an increased risk of disease, such as cardiovascular disease, diabetes, and cancer [19–22]. As isthe case with the circadian rhythm, sleep has also been
linked to immune function [23, 24]. The impairment ofeither sleep duration or sleep quality is associated with areduced antibody production and increased generationof inflammatory cytokines [18, 25]. Hence, the dual association of the circadian rhythm and sleep with immune
function has implications for the pathophysiology ofallergic disease such as atopic dermatitis (AD), allergic

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rhinitis (AR), and asthma [26–28]. Notably, the disentanglement of the effects of the circadian rhythm and sleep
on immune function is challenging given the tight intertwinement of the circadian rhythm and sleep [23].
Notwithstanding, a correlation between sleep andallergic diseases has been observed in several epidemiologic studies. Results from the National Health andNutrition Examination Survey (NHANES) showed that
impaired sleep resulting from obstructive sleep apnea
was associated with higher odds of hay fever and eczema,
while a sleep duration of 6 or fewer hours correlatedwith higher odds of allergic sensitization [29]. Studies
focusing specifically on sleep and AD-related outcomesconsistently found AD to be significantly associatedwith sleep quality, but not with sleep duration [30–32].
Interestingly, although increased AD severity was alsosignificantly associated with more sleep disruption,
there was an increased likelihood of sleep disturbanceamong those with mild or inactive AD [31]. Moreover,sleep disruptions among individuals with AD in remission were not accompanied by nighttime itching episodes [33]. Investigations of AR and sleep showed that
increased upper airway resistance and nasal discharge,
both of which are symptoms characteristic of AR, caused
microarousals during sleep [34]. Furthermore, increased
upper airway resistance associated with AR was accompanied by obstructive sleep apnea and sleep-disorderedbreathing, which also negatively impacted sleep quality[35, 36]. Conversely, a recent systematic review foundthat sleep duration was not significantly associated with
AR, while sleep quality score, sleep disturbance scores,
and sleep latency scores were higher among AR patients;
sleep efficiency was nonetheless decreased among AR
patients [37]. Finally, poor sleep patterns have beenfound to increase asthma risk [38]. While asthma has
been associated with poor sleep quality, this was likely
the result of asthma symptoms affecting sleep, or comorbid AR resulting in AR-related sleep disturbances inasthmatics [39, 40].
Despite the putative evidence for sleep influencing
allergic disease risk, the consensus that sleep can be disturbed by allergic diseases and that sleep disturbances
can be used as an indicator of allergic disease severity
introduces a dimension of confoundment to the directionality of the relationship between sleep and allergic
disease [24]. Indeed, an increased prevalence and severity of sleep disturbances were found to be associatedwith increased AD severity as determined by SCORing
Atopic Dermatitis (SCORAD) [41]. In AR, Allergic Rhinitis and its Impact on Asthma (ARIA) defines moderatesevere AR as AR which negatively impacts any aspectof quality of life, including sleep disturbances [42]. Furthermore, systematically reviewed evidence indicatesWong et al. Journal of Physiological Anthropology(2024) 43:6

that AR is associated with decreased sleep duration andquality, sleep-related disorders, and a resultant daytime
dysfunction due to sleep impairment [37]. Lastly, nighttime asthma awakening is essential for the assessment ofasthma severity, control, and remission [43–46].
Objectives

Presently, the preponderance of Asian studies assessing sleep and allergic disease originates from the Korea
National Health and Nutrition Examination Survey(KNHANES) [47–49]. As such, there is a paucity of epidemiologic studies assessing the relationship between
sleep and allergic disease among the wider Asian population. Moreover, many epidemiologic studies thus far havebeen remiss to address a chicken-and-egg dilemma: whatis the direction of the relationship between sleep andallergic disease, i.e., does sleep influence allergic disease
manifestation, or vice versa?
Here, we have selected young Chinese adults recruitedin Singapore from the Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study (SMCGES) databasewith the consideration that majority of the Singapore
subjects were Chinese (86.8%). Moreover, we note that
the Chinese population constitutes a major distinct ethnic group both in Asia and worldwide [50, 51]. Despite
the predominance of Chinese, sleep and allergic disease
have not been studied in this ethnic group in Asia. Of an
additional consideration, our focus on Chinese subjects
also aims to reduce ascertainment bias resulting from thesmall proportions of non-Chinese ethnicities and counteract potential confounding introduced by the inclusionof non-Chinese ethnicities who feature differing genetic
characteristics. Using the International Study of Asthma
and Allergies in Childhood (ISAAC) questionnaire,
which comprises utilities for collecting data on sleep
duration and sleep disturbances resulting from allergic
disease, we have performed our data collection and caseclassification according to internationally establishedstandards [52].
In summary, our present analysis focuses on a novelgroup of young Chinese adults recruited in Singapore
with three aims: (i) establish a baseline duration of sleep
among our subjects, (ii) perform an exploratory investigation of the association between sleep and allergic disease, and (iii) assign directionality to the relationshipbetween sleep and allergic disease by accounting for sleep
disturbances due to allergic disease.

Methods
Participants and data collection

The Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study (SMCGES) is an ongoing largescale cross-sectional study. Utilizing email and poster

Page 3 of 12

advertisements, participants were recruited across thecampuses of the National University of Singapore (NUS),
Singapore; Universiti Tunku Abdul Rahman, Malaysia;
and Sunway University, Malaysia. Participants aged atleast 18 years old and consenting to participate in the
study completed an investigator-administered skin prick
test (SPT) and an adapted ISAAC survey.
The SPT was performed after verifying that the participant had not consumed antihistamines for at least 3 days
preceding the test; participants who had done otherwise
were rescheduled. Participants were assessed for sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus: two dust mite species selected due to their highprevalence in Singaporean homes and high rates of sensitization among the local atopic population [53, 54]. A
positive SPT result, indicating sensitization, was definedas the development of a wheal of at least 3 mm in diameter in response to any of the two allergens. In addition,a positive histamine control and negative saline control
were included, consistent with the standard SPT protocol
used for the SMCGES thus far [55]. Subjects showing a
positive SPT result were classified as atopic cases.
Our survey was adapted from the published ISAAC
Phase Three questionnaire which has been standardized
and validated for the assessment of allergic diseases internationally [56]. The survey was administered according
to established ISAAC protocol and yielded data on allergic disease symptoms, sleep disturbances due to allergic
disease, and epidemiology. Additionally, subjects werequeried for an estimate of their total sleep time (TST)and their perception of their sleep quality (SQ).
The present report concerns Chinese subjects recruitedduring data collection exercises in NUS, Singapore,
which has occurred in August annually since 2005. Subjects excluded from the current analysis fulfilled any of
the following criteria: (i) recruited in Malaysia, (ii) nonChinese ethnicity, or (iii) did not provide their estimatedtotal sleep time.
Allergic disease classification

Using data obtained via the ISAAC questionnaire, subjects’ disease statuses were determined for AD, AR, andasthma. Among atopic subjects identified by the SPT, AD
cases comprised those who had suffered from a recurrent
itchy rash for at least 6 months in any of the specified
anatomical locations: flexural region of the elbows andknees, front of the ankles, under the buttocks, aroundthe neck, cheeks, eyes, or ears. Per ARIA 2008 guidelines,
atopic subjects reporting at least two rhinitis symptoms
out of nasal blockage, nasal pruritus, sneezing, and rhinorrhea when they were not afflicted with a cold or flu
were identified as AR subjects [42]. Finally, subjects who
had ever had asthma were classified as asthma cases. The

Wong et al. Journal of Physiological Anthropology(2024) 43:6classification criteria were consistent with that of previous reports [55, 57, 58].
Sleep disturbances due to allergic disease

For AD, AR, and asthma, the respective sleep disturbances were investigated. Among AD cases, phenotypes
considered to entail sleep disturbances (AD-related sleep
disturbances) included having ever been kept awake byan itchy rash, itching in the evening or night, and itchingthat impacted sleep in general. In AR, subjects reporting
any of the four rhinitis symptoms (see the section above)
to be severe enough to interfere with sleep or indicating general sleep disturbance due to AR symptoms wereconsidered to have sleep disturbances due to AR (ARrelated sleep disturbances). Finally, asthma-afflicted subjects who had either suffered from sleep disturbances due
to wheezing, had a dry nocturnal cough not related to acold or chest infection, or experienced nighttime asthma
attacks were classified as individuals having asthmarelated sleep disturbances.
Statistical analyses

Data was compiled using Microsoft Excel. Data cleaning and statistical analyses were performed using R software, version 4.0.3 [59]. Welch’s t-tests were conducted
for continuous variables while Pearson’s chi-squared tests
were conducted for categorical variables. Finally, linear
regression models were constructed to assess the impactof allergic diseases and sleep disturbances due to allergic

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diseases on total sleep time; unadjusted and adjusted
analyses were performed, with the latter accounting forsleep disturbance due to allergic disease. Logistic regression was performed to evaluate binary outcomes, namely,
allergic disease status against total sleep time and sleep
quality, and sleep quality (very bad to moderate vs goodto very good) against allergic disease status and sleep disturbances. Statistical significance was determined where
the accompanying p-value was below 0.05 (p < 0.05).

Results
Sample description

Of 13,410 subjects ascertained in the Singapore cohortof the SMCGES, a subset was administered the sleep
questions; our current analysis focuses on 1558 young
Chinese adults who provided an estimate of their sleep
duration. The mean age of our subjects was 25.0 years(SD = 7.6 years) and 61.4% were females. Overall, themean total sleep time (TST) of our sample was 6.8 h(SD = 1.1 h). Most respondents reported having a goodquality of sleep in general (43.2%). There was a significant decrease in mean TST from good, to moderate, tobad SQ (Fig. 1). Conversely, there was no significant difference between the TST of good versus very good sleep,nor bad versus very bad sleep. The proportions of AD,
AR, and asthma among the sample subjects were 25.5%(393/1542), 36.4% (987/1551), and 14.7% (227/1547),
respectively. A breakdown of sample demographics andFig. 1 Mean total sleep time and accompanying standard deviation, in hours, for each grade of sleep quality

Wong et al. Journal of Physiological Anthropology(2024) 43:6

sleep characteristics by allergic disease status is summarized in Table 1.
Associations between sleep and allergic disease

Within the disease case subsets for each allergic disease,59.8% (235/393) of AD cases suffered from AD-related
sleep disturbances, 37.1% (209/564) of AR cases suffered from AR-related sleep disturbances, and 25.1%(57/227) of asthma cases suffered from asthma-related
sleep disturbances. The mean TST of individuals afflictedwith asthma (6.7 h, SD = 1.1 h) was significantly lower
than that of those without (6.8 h, SD = 1.0 h; p = 0.015;
Table 1). Conversely, neither the mean TST of AD cases
versus controls nor AR cases versus controls were significantly different (Table 1). Among those with AD and
AR-related sleep disturbances, the mean TST was not
significantly different from that of those without sleep
disturbances (Table 2). While the mean TST of thosewith asthma-related sleep disturbance was lower thanthat of those without, the difference in mean TST was
non-significant. Accordingly, the differences in mean
TST for those experiencing AD and AR phenotypes
resulting in sleep disturbances were non-significant;mean TST was lower among those with asthma-related
sleep disturbances than those without, but this difference
was likewise non-significant (Table 3).
Among AD and asthma cases, there was a lower proportion of respondents experiencing at least a good SQ
in general as compared to non-afflicted individuals (i.e.,
56.8% of non-AD controls versus 51.8% of AD cases and55.9% of non-asthma controls versus 51.2% of asthma
cases reported having at least a good SQ in general).
Where allergic disease cases were concerned, a moderate or worse SQ was reported by 51.0% (76/149) of AD
cases suffering from AD-related sleep disturbances, 55%(66/120) of AR cases suffering from AR-related sleep disturbances, and 55.2% (16/29) of asthma cases sufferingfrom asthma-related sleep disturbances (Fig. 2).
Regression analyses for sleep and allergic diseases

Logistic regression analyses for allergic disease against
TST and SQ showed that longer TST was significantly associated with lower odds of AR (odds ratio(OR) = 0.905, 95% CI = 0.820–0.999, p-value = 0.048)
and asthma (OR = 0.852, 95% CI = 0.746–0.972,
p-value = 0.017; Fig. 3). Controlled for sleep disturbancedue to allergic disease, longer TST was significantly
associated with allergic rhinitis only (OR = 0.864, 95%
CI = 0.767–0.973, p-value = 0.016). SQ was not significantly associated with allergic disease manifestation. The
inclusion of both TST and SQ as confounding factors orinteraction terms yielded no significant findings. Linear
regression modeling of TST against allergic disease andPage 5 of 12

sleep disturbances due to allergic disease showed that
AR manifestation was significantly associated with alower TST, regardless of whether sleep disturbances were
included in the model (unadjusted: β =  − 0.11, SE = 0.055,
p-value = 0.047; adjusted: β =  − 0.157, SE = 0.065,
p-value = 0.016), while asthma was significantly associated with lower TST only when unadjusted for sleep
disturbances due to asthma (unadjusted: β =  − 0.18,
SE = 0.076, p-value = 0.017). Finally, logistic regression
analyses for SQ against allergic disease and allergic disease-related sleep disturbances showed that only sleep
disturbances due to AR were significantly associatedwith a poorer SQ (OR = 1.962, 95% CI = 1.245–3.089,
p-value = 0.004). The full results from the regression analyses are summarized in Additional file 1: Supplementary
Tables 1-4.

Discussion
Sleep quality, but not sleep duration, was poorer
among AD cases

While a slight majority of AD cases experienced a poorer
SQ, we found no significant difference between the mean
TST of AD cases versus that of non-AD controls. To an
extent, our findings for the lack of difference in sleep
duration between AD cases and non-AD controls echothat of previous studies. Indeed, most subjective andobjective measurements of sleep duration among pediatric AD cases and controls showed no statistically significant difference [30–32, 60–62]. Among adults, however,reports for sleep duration and AD were few and inconsistent: sleep duration was significantly shorter among
AD cases in one NHANES study but non-significantly
different elsewhere [63, 64]. Separately, our results correspond to findings that poor SQ was associated with
AD. Among both children and adults, AD cases reported
various SQ-related impairments, including longer sleeponset latency, poor sleep efficiency, and longer wakefulness after sleep onset (WASO) [41]. Finally, almost 60%
of AD cases reported AD-related sleep disturbances, ofwhich none of the phenotypes were associated with a significant difference in mean TST. These proportions were
not unusual for subjective assessments of AD-related
sleep disturbances [65, 66]. Additionally, our results provide no evidence that AD is significantly with TST, evenin the presence of AD-related sleep disturbances.
Hypotheses for the association of disrupted sleep withAD have implicated pruritus [41, 67]. Sleep disruptions
among AD patients have been attributed to scratchingmotions in response to pruritus [67]. Indeed, Il-31 which
has been established as an important mediator of pruritus has also been found to be associated with poorer sleep
quality [68, 69]. However, although movements in sleep
and worse perception of pruritus was associated with

25.0 ± 7.6

Age at collection (in years)

48

60

6.8 ± 1.1

Total sleep time (in hours)

543

389

432 (56.8%)

328 (43.2%)

6.8 ± 1.022427 (37.9%)

256 (22.7%)

315 (28.0%)

129 (11.4%)

148

127 (51.8%)

118 (48.2%)

6.8 ± 1.1

8

180 (46.8%)

80 (20.8%)

96 (24.9%)

29 (7.5%)

11

37 (9.7%)

86 (22.5%)

259 (67.8%)

2

170 (43.5%)

221 (56.5%)

24.9 ± 6.6

Yes
N = ­3931

0.170

0.480

0.010

0.010

0.023

0.769

p-value2309

375 (55.3%)

303 (44.7%)

6.9 ± 1.021366 (37.9%)

206 (21.3%)

276 (28.6%)

118 (12.2%)

44

59 (6.3%)

278 (29.5%)

606 (64.3%)

1354 (35.9%)

632 (64.1%)

25.5 ± 8.4No
N = ­9871

Allergic rhinitis

233

184 (55.6%)

147 (44.4%)

6.7 ± 1.1

9242 (43.6%)

131 (23.6%)

141 (25.4%)

41 (7.4%)

15

51 (9.3%)

129 (23.5%)369 (67.2%)

1245 (43.5%)318 (56.5%)

24.0 ± 5.7

Yes
N = ­5641

0.933

0.053

0.005

0.009

0.004

< 0.001

p-value2436494 (55.9%)

390 (44.1%)

6.8 ± 1.1

23504 (38.9%)292 (22.5%)

365 (28.1%)

136 (10.5%)

55

96 (7.6%)

346 (27.4%)

823 (65.1%)

2491 (37.3%)

827 (62.7%)

24.9 ± 7.6

No
N = ­13201

Ever asthma

Mean ± SD; n (%). Welch’s two-sample t-test was conducted for age and total sleep time. Pearson’s chi-squared test was conducted for housing type and income category

2    Unknown

1

453 (44.6%)

562 (55.4%)    Very bad to moderate    Good to very good

Sleep quality

612 (40.1%)31    ≥ SGD 6000    Unknown

418 (27.4%)

338 (22.1%)    SGD 2000—3999    SGD 4000—5999

159 (10.4%)    < SGD 2000

Income category    Unknown

408 (27.2%)

110 (7.3%)    Condo/private apartment    Landed property

321 (29.2%)
71 (6.4%)980 (65.4%)    Flats

709 (64.4%)

0

2

Housing type    Unknown

423 (36.8%)955 (61.4%)

601 (38.6%)    Female

726 (63.2%)

25.0 ± 7.9

No
N = ­11491

Atopic dermatitis    Male

GenderOverallN = ­15581

Variable

Table 1 Summary of demographic and sleep characteristics for the overall sample and by allergic disease status102

64 (51.2%)

61 (48.8%)

6.7 ± 1.0

7

107 (48.6%)

43 (19.5%)

49 (22.3%)

21 (9.5%)

5

11 (5.0%)59 (26.6%)

152 (68.5%)

0107 (47.1%)

120 (52.9%)

25.1 ± 7.5

Yes
N = ­2271

0.324

0.015

0.051

0.333

0.006

0.697

p-value2

Wong et al. Journal of Physiological Anthropology(2024) 43:6
Page 6 of 12

Wong et al. Journal of Physiological Anthropology(2024) 43:6

Table 2 Mean total sleep time and accompanying standard
deviation, in hours, by presence or absence of sleep disturbances
due to allergic disease
Allergic disease

Mean total sleep time (TST) among
those with the respective allergic
diseasep-value2

the circadian rhythm and resulting in impaired sleep [41,67]. Notwithstanding, the mechanism linking circadianrhythms, immune function and AD has yet to be comprehensively studied and elucidated.
A shorter sleep duration likely increases the risk of AR

No disease-related Diseasesleep ­disturbances1 related sleep­disturbances1
Atopic dermatitis 6.79 ± 1.00 (158)

6.77 ± 1.12 (235)0.901

Allergic rhinitis

6.70 ± 1.08 (355)

6.82 ± 1.16 (209)

0.198

Asthma6.71 ± 0.95 (170)

6.50 ± 1.19 (57)

0.226

1

Page 7 of 12

2

Mean TST ± SD, in hours (N). Welch’s two-sample t-test

lower sleep quality, arousals resulting from limb movements and scratching were not significantly associatedwith sleep efficiency [33, 69]. Thus, while pruritus andscratching might be a contributory factor to poor sleep
quality among AD cases, they do not constitute the primary etiology [69]. Instead, the circadian rhythm and its
effect on immune cell expression have been proposed asa possibility: elevated cytokine and immune cell involvedin AD pathogenesis could be involved in regulating sleep[67]. Thus, increased cytokine and immune cell activity
at night could be causing AD-related itching, or the dysregulation of cytokines due to AD could be disrupting

The mean TST among AR cases was significantly lower
than that of non-AR controls. At least one-third of AR
cases suffered from AR-related sleep disturbances, but
the mean TST among sleep-disturbed individuals was
not significantly different from the non-sleep-disturbed
individuals. Moreover, a small majority of those with ARrelated sleep disturbances reported having a poorer SQwith poorer SQ being significantly associated with AR.
Concordantly, previous studies have identified a negative impact of AR on SQ assessed using different rubrics[70, 71]. Notably, we identified an association between
AR and TST, which remained significant after controlling for AR-related sleep disturbances. Taken together
with the current findings that mean TST was not significantly different between sleep-disturbed and nonsleep-disturbed AR cases, our results suggest that TST
potentially influences the manifestation of AR as opposed
to vice versa. Accordingly, the Korea National Health andNutrition Examination Survey (KNHANES) study highlighted a similar trend wherein increasing sleep duration was associated with a decrease in the prevalence ofTable 3 Mean total sleep time and accompanying standard deviation, in hours, by presence or absence of each allergic diseasephenotype resulting in sleep disturbanceAllergic disease phenotype

Mean TST among those with or without allergic disease-related sleep P-value2
disturbance phenotype
No 1

Yes 1

Kept awake by itchy rash

6.79 ± 1.05 (239)

6.77 ± 1.11 (154)0.841

Evening itch

6.76 ± 1.06 (283)

6.83 ± 1.10 (110)0.592Nighttime itch

6.80 ± 0.99 (260)6.74 ± 1.21 (133)0.660

Constant itching in the day and night

6.80 ± 1.07 (353)

6.58 ± 1.05 (40)0.199

Constant itching at night

6.75 ± 1.04 (353)

7.03 ± 1.33 (40)0.217

Sleep disturbance due to itching

6.78 ± 1.03 (297)

6.78 ± 1.19 (96)0.970

Sleep interference due to nasal blockage

6.74 ± 1.11 (420)6.77 ± 1.08 (28)0.893

Sleep interference due to nasal pruritus

6.67 ± 1.05 (412)

6.83 ± 1.53 (12)0.718

Sleep interference due to rhinorrhoea

6.73 ± 1.14 (450)

6.62 ± 0.97 (37)0.508

Sleep interference due to sneezing

6.74 ± 1.11 (467)

6.67 ± 0.98 (29)0.723

Sleep disturbances due to AR symptoms

6.68 ± 1.06 (382)

6.87 ± 1.20 (182)0.065

Sleep disturbance due to wheezing

6.98 ± 1.23 (47)

6.57 ± 1.21 (14)0.282

Dry nocturnal cough

6.71 ± 0.95 (185)

6.45 ± 1.26 (41)0.219Nighttime asthma attacks

6.80 ± 1.07 (59)

6.58 ± 1.02 (20)0.411

Atopic dermatitis

Allergic rhinitis

Asthma1

Mean ± SD (N). 2Welch’s two-sample t-test

Wong et al. Journal of Physiological Anthropology(2024) 43:6

Page 8 of 12

Fig. 2 Proportions of sleep quality among allergic disease cases denominated by the presence or absence of sleep disturbances due to eachallergic disease

Fig. 3 Odds ratios for the presence of AR, AD, and asthma. Adjusted odds ratios were obtained by controlling for the presence of sleep disturbancedue to allergic disease

AR [49, 72]. Interestingly, the present findings coupledwith KNHANES results contrast a recent meta-analysis
which found no significant differences in sleep duration
between the AR and control groups among reports published before 2019 [37].
There is a dearth of literature examining the mechanisms linking sleep duration and allergic rhinitis. Nonetheless, from studies on circadian rhythm and immune
function, disruption of the circadian rhythm precipitated by a lack of sleep has been proposed to influence
allergic rhinitis reactions [73]. Additionally, there is evidence that the circadian rhythm regulates AR symptoms,
wherein symptoms frequently worsened during the night
and in the morning, but subsided in the middle of the day[16]. Immunologically, eosinophil and basophil activities in the nasal mucosa were found to be elevated in theearly morning as compared to the afternoon, while theimmunoglobulin E (IgE)/mast cell axis has been shown tobe controlled by the circadian clock [74–77]. Despite thepossible mechanistic links, evidence for a clear pathway
between sleep and AR has yet to be clearly illustrated.
The most apparent consequence of asthma‑related sleep
disturbances is the impairment of sleep duration

Asthma cases reported a significantly lower mean TSTthan non-asthma individuals. Among asthma cases, aquarter suffered from asthma-related sleep disturbances,and their mean TST was significantly lower than thatof individuals without asthma. A comparison of mean
TST between asthma cases suffering from sleep disturbances and those without revealed no significant difference; evaluation of the asthma phenotypes resulting
in sleep disturbances also showed no significant difference in TST. Nonetheless, we found that there was a

Wong et al. Journal of Physiological Anthropology(2024) 43:6

consistently lower mean TST among asthma cases suffering from sleep disturbances due to wheezing, dry
nocturnal coughing, and nighttime asthma attacks. Additionally, a longer TST was significantly associated with adecreased likelihood of asthma, but this association was
not observed when adjusted for asthma-related sleep
disturbances. Indeed, shorter sleep duration and poorer
SQ among asthmatics have been reported, and having asleep duration of fewer than 5 h was significantly associated with increased asthma risk [78, 79]. Currently, we
propose that shorter TST is likely mediated by asthmarelated sleep disturbances, as opposed to TST being arisk factor for asthma.
The effects of various factors—physiological changes
and physical posture associated with sleep, circadianclock regulation of immune function, and environmental conditions—have yet to be comprehensively teased
apart [80]. Among the few studies assessing the influenceof sleep on asthma, a prospective study found that adults
with poor sleep habits had a higher risk of asthma withina follow-up period of at least 10 years, while experimental
manipulation of sleep duration among asthma patientsresulted in a decreased in peak expiratory flow rates andincreased interference of activities by asthma symptoms[38, 81]. Nonetheless, while the directionality of the relationship between sleep and asthma remains unclear, theassociation of poor sleep with asthma has been well documented, with short sleep and poor sleep quality being
associated with nocturnal respiratory symptoms [82,83]. As with AD and AR, the circadian rhythm has been
implicated: a circadian pattern of variation in airway
inflammation has been observed [84]. In fact, variableairflow and bronchial hyperresponsiveness are characteristic of asthma, and asthma exacerbations frequently
occur during the night [80, 85]. The coincidence of thecircadian rhythms of several functions, resulting in the
periodic increase in vagal tone, decreased epinephrine
levels, and change in IgE/mast cell responses might play
an important role in the manifestation and exacerbationof asthma [86, 87].

Conclusion
We have established a baseline for the characteristics of
sleep and allergic disease among young Chinese adults
in Singapore. We note, however, the limitations of gauging sleep impairment using TST which is merely participants’ estimate of their nightly time spent asleep. A
metric as precise as TST gives little detail regarding more
descriptive sleep parameters, such as sleep-onset latency(SOL), wake time after sleep onset (WASO), or sleep
fragmentation [88]. Moreover, our current analysis was
unable to account for the possible effects of medication
taken to treat allergic diseases—medications alleviating

Page 9 of 12

the effects of allergic diseases could have resulted in sleep
less impacted by allergic disease symptoms, while sedative medications could have resulted in longer total sleep
time or better sleep quality [89–92]. As such, our findingson the effect of sleep on allergic diseases or vice versa
could have been underestimates. Thus, follow-up studies
would be well-advised to consider the effect of medications on the interplay between sleep and allergic disease
by collecting the necessary information from participants
and adjusting for medication use in their analyses.
Although the sample size for each allergic disease wasrelatively small, we were able to identify associations
between sleep and allergic diseases that were supportedby the literature. Moreover, despite the cross-sectional
nature of this study, we were able to obtain an indicationof directionality by controlling for allergic disease-related
sleep disturbances. Overall, while sleep quality was associated with AD, there was a lack of evidence to discern
the direction of this relationship. Furthermore, we foundthat TST likely influences AR, and the impact of AR on
sleep is primarily on SQ as opposed to TST. Finally, we
provided evidence that the association between TST
and asthma is likely mediated by asthma-related sleep
disturbances. The present report thus constitutes thefoundation for further studies investigating the relationship between sleep and allergic diseases. Future studies
would be well-advised to use objective measurements ofsleep, such as actigraphy or polysomnography methods
which provide the capability of capturing the complexities of sleep. Furthermore, differential expression analysisof transcriptome samples obtained 12 h apart, in the day
and at night, could be considered to identify differentiallyexpressed genes which are linked to the circadian clock,immune function, or allergic disease. Functional characterization of any gene of interest could then be carriedout to determine the mechanism by which the circadianclock regulates immune response.
Abbreviations
95% CI	95% Confidence intervalAD	Atopic dermatitis
AR	Allergic rhinitis
ARIA	Allergic Rhinitis and its Impact on Asthma
IgE	Immunoglobulin E
ipRGC​	Intrinsically photosensitive retinal ganglion cells
ISAAC​	International Study of Asthma and Allergies in Childhood
NUS	National University of Singapore
OR	Odds ratio
PSG	Polysomnography
RZR/ROR	Retinoid-related orphan nuclear hormone receptor family
SCN	Suprachiasmatic nuclei
SCORAD	SCORing Atopic Dermatitis
SMCGES	Singapore/Malaysia Cross-Sectional Genetic Epidemiology Study
SOL	Sleep onset latency
SQ	Sleep quality
TST	Total sleep time
WASO	Wakefulness after sleep onset

Wong et al. Journal of Physiological Anthropology(2024) 43:6

Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s40101-​024-​00356-5.
Additional file 1: Supplementary Table 1. Results from the logistic
regression analyses for allergic disease manifestation against total sleep
time only (model 1), sleep quality only (model 2), TST and sleep quality(model 3), and TST and sleep quality as interaction terms (model 4).
Supplementary Table 2. Results from the logistic regression analyses
for allergic disease manifestation against total sleep time only (model1), sleep quality only (model 2), TST and sleep quality (model 3), and TST
and sleep quality as interaction terms (model 4). In all models, allergic
disease cases experiencing sleep disturbance due to allergic disease were
excluded. Supplementary Table 3. Results from the logistic regression
analyses for total sleep time against allergic disease only (model 1) andallergic disease and sleep disturbances due to allergic disease (model 2).
Supplementary Table 4. Results from the logistic regression analyses forsleep quality against allergic disease only (model 1) and allergic disease
and sleep disturbances due to allergic disease (model 2).
Acknowledgements
We extend our sincerest gratitude to all participants for their contributions tothis study. We also thank the student volunteers whose valuable help madethe large-scale data collection possible.
Authors’ contributions
F.T.C. conceived and supervised the current research study. Q.Y.A.W. conducted
the literature review, analyzed and interpreted the data, and wrote the manuscript. Q.Y.A.W., J.J.L., J.Y.N., P.M., Y.Y.E.L., and Y.Y.S. assisted in recruiting study participants and data collation. All authors read and approved the final manuscript.
Funding
F.T.C. received grants from the National University of Singapore (N-154–000038–001), Singapore Ministry of Education Academic Research Fund (R-154–
000-191–112; R-154–000-404–112; R-154–000-553–112; R-154–000-565–112;
R-154–000-630–112; R-154–000-A08-592; R-154–000-A27-597; R-154–
000-A91-592; R-154–000-A95-592; R154-000-B99-114), Biomedical ResearchCouncil (BMRC) (Singapore) (BMRC/01/1/21/18/077; BMRC/04/1/21/19/315;
BMRC/APG2013/108), Singapore Immunology Network (SIgN-06–006;
SIgN-08–020), National Medical Research Council (NMRC) (Singapore)(NMRC/1150/2008), National Research Foundation (NRF) (Singapore) (NRFMP-2020–0004), Singapore Food Agency (SFA) (SFS_RND_SUFP_001_04;
W22W3D0006), and the Agency for Science Technology and Research(A*STAR) (Singapore) (H17/01/a0/008; and APG2013/108). The funding agencies had no role in the study design, data collection, data analysis, decision to
publish, or preparation of the manuscript.
Availability of data and materials
All data used and included in this study are available from the corresponding
author (F.T.C.).

Declarations
Ethics approval and consent to participate
Ethical approval for this study was granted by the NUS Institutional Review
Board (IRB reference code: NUS-07–023, NUS-09–256, NUS-10–445, NUS-13–
075, NUS-14–150, and NUS-18–036). This study was performed in compliancewith the Declaration of Helsinki, Good Clinical Practice, and local regulatory
guidelines. Before participation, each subject was informed of this study’s
details via a Participant Information Sheet and provided written informed
consent to participation through the signature of a Consent Form.
Consent for publication
All authors have read and consented to the publication of this manuscript.
Competing interests
F.T.C. reports grants from the Singapore Ministry of Education Academic
Research Fund, Singapore Immunology Network, National Medical Research

Page 10 of 12

Council (Singapore), Biomedical Research Council (Singapore), National
Research Foundation (NRF) (Singapore), Singapore Food Agency (SFA), and the
Agency for Science Technology and Research (Singapore), during the conductof the study, and has received consultancy fees from Sime Darby Technology
Centre, First Resources Ltd, Genting Plantation, Olam International, and Syngenta Crop Protection, outside the submitted work. The other authors declare
no other competing interests.
Author details
1
Department of Biological Sciences, Faculty of Science, National Universityof Singapore, Allergy and Molecular Immunology Laboratory, Lee Hiok Kwee
Functional Genomics Laboratories, Block S2, Level 5, 14 Science Drive 4, Lower
Kent Ridge Road, Singapore 117543, Singapore.
Received: 28 June 2023 Accepted: 19 January 2024

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