In this study, we used a large-scale survey data, which was part of the NSPGDC, to investigate the association of sleep problems with asthma/wheeze and allergic rhinitis among children aged 0-6 years in Guangzhou. The results revealed the prevalence of asthma/wheeze and allergic rhinitis among children aged 0-6 years was 2.8%, and 4.6% respectively. The findings also suggested that frequent nocturnal awakenings but not short sleep duration and late bedtime, was significant associated with asthma/wheeze and allergic rhinitis. However, these associations differed by children’ age.
Comparison with other studies
In the present study, we found that the prevalence of asthma/wheeze and allergic rhinitis were lower than previous studies conducted both in China and western countries. For example, a study conducted in six representative cities in China, found that the prevalence of asthma and allergic rhinitis were 8.0% and 16.6%, respectively [26]. A population-based birth cohort study conducted in Sweden reported that the prevalence of wheeze episodes before 2 years of age was 25% [27]. A nationwide study conducted in Portugal reported that the prevalence of current rhinitis was 43.4% among child aged 3-5 years [28]. The discrepancies might be related to different characteristics of study participants, apart from the different measurements for asthma/wheeze and allergic rhinitis. However, our findings were similar to a study conducted in Shanghai, which reported that the prevalence of wheeze and allergic rhinitis were 3.7% and 2.5%, respectively [9].
Our findings suggest that frequent nocturnal awakening was associated with asthma/wheeze (OR=1.53, 1.20-1.94) and allergic rhinitis (OR=1.39, 1.14-1.71), which were similar to previous studies that investigated the association of sleep problems with allergic diseases among children under 6 years [9, 10]. Wang et al conducted a study to examine the associations of sleep disorders with the risk of wheeze and allergic rhinitis among 566 Chinese toddlers and found that having more than 2 times of nocturnal awaking per night was associated with a higher risk of wheeze (OR=6.16, 1.28~29.74) [9]. Kozyrskyj et al analyzed the conditions of 2398 children from on a community-based birth cohort in Australia and found that persistent nocturnal awakening before 3 years of age was associated with an increased risk of nonatopic asthma at age 6 (OR=1.87, 1.08~3.25), after adjusting for other risk factors of asthma, including co-sleeping, wheeze and family stress [10]. In this study, we also found that the associations of frequent nocturnal awakening with asthma/wheeze and allergic rhinitis were differed by age, which was not reported in previous studies [9, 10]. This age differences may be due to age difference prevalence rate of asthma/wheeze and allergic rhinitis, which had low diagnosis rate among children aged 0-3 years. To reduce the harmful of asthma/wheeze and allergic rhinitis to the child, parent need detect the early symptoms of the disease as early as possible [29], although age difference on association of frequent nocturnal awakening with asthma/wheeze and allergic rhinitis need to be verified in different population.
Possible explanations of the association of frequent nocturnal awaking with asthma/wheeze and allergic rhinitis
The association between frequent nocturnal awaking and asthma/wheeze and allergic rhinitis could be explained by several plausible biological mechanisms. Firstly, frequent nocturnal awakening may increase the levels of pro-inflammatory cytokines and decrease the immunologic tolerance to allergen [9, 10], shifting the balance between Th1 and Th2 cytokines towards an allergy related (Th2) pattern [30], which are known factors contributing to allergic diseases such as asthma/wheeze and allergic rhinitis. Secondly, frequent nocturnal awakening could disrupt the regulation of the hypothalamic–pituitary–adrenal (HPA) axis [31, 32] and the circadian rhythms of melatonin [33, 34]. Children with impaired HPA-axis regulation showed a blunted cortisol awakening response and lower cortisol levels [31, 32], which lacks suppression of airway inflammation that could increase the risk of asthma and rhinitis [35, 36]. Additionally, melatonin may also play a very important role in anti-inflammatory and immunomodulatory functions [35, 37], thus a decline in the level of melatonin could reduce the suppression of inflammation and airway hyper-responsiveness, which in turn could trigger asthma and allergic rhinitis [38, 39].
Strengths and limitations
The major strength of this study is the sample size. For this large-scale cross-sectional study, we recruited 13376 representative participants from rural and urban Guangzhou by using a well-designed protocol, which makes our results more generalized. The other major strength of this study is that we have adjusted for several important confounders, such as region and maternal smoking and children’s passive smoking, which was not adjusted in previous studies, making our results more robust. Additionally, this is the first investigation on the association of sleep problems with asthma/wheeze and allergic rhinitis among Chinese child aged 0-6 years, which also filled in the age gap in this area of research.
There were several limitations in our study. First, asthma/wheeze and allergic rhinitis were not determined by objective measures, but rather parent reported ISAACQ, which although was highly recognized for its reliability and validity and was used in previous studies [30, 17]. Second, sleep problems were assessed through questionnaires based on the parents’ reports, instead of objective measurement, thus recall bias may exist. On balance, previous studies have demonstrated that information regarding sleep garnered from parents is likely to be reliable [40]. Third, although we have adjusted for various potential confounders, we did not adjust for family allergy history of the parents or mother’s stress during pregnancy, which are risk factors for allergenic diseases [10]. Fourth, this study is a cross-sectional study, which deduces a weak association in the exploration of the causal relationship of sleep problems and asthma/wheeze and allergic rhinitis. Future prospective research studies are needed to validate these findings, since asthma/wheeze and allergic rhinitis are significant clinical and public concerns.
Sleep problems including shortened sleep duration, late bedtime and frequent nocturnal awaking are common among children aged 0-6 years, which have a broad impact on children’s development and physical health. In the present study, we used data from the NSPGDC to investigate the association of sleep problems with asthma/wheeze and allergic rhinitis among Chinese children 0-6 years and found that frequent nocturnal awakening was associated with asthma/wheeze and allergic rhinitis. Although this is a cross-sectional study and the association of frequent nocturnal awakening with asthma/wheeze and allergic rhinitis differed by age, the results suggests that pediatricians should consider evaluating sleep problems when evaluating the risk factors for asthma/wheeze and allergic rhinitis, and that parents should help their children develop good sleeping habits to reduce the risk of asthma/wheeze and allergic rhinitis.