To our knowledge, this is the first study to investigate the potential relationship between sleep duration and allergen sensitization in a large population. We demonstrated not only that short sleep duration was associated with increased sensitization to food allergens and aeroallergens, but also that such an association appeared to occur in a dose-response manner and was independent of percent body fat. As compared to adults and urban or western counterparts, this is a relatively lean rural population [30
], thus, it is less likely to be confounded by obesity and obesity-associated sleep disorders, and urban factors that could adversely affect the sleep environment. Although this study is limited by its cross-sectional study design, the finding on the association between sleep duration and allergen sensitization is intriguing. It raises the possibility that short sleep duration may be a modifiable risk factor for allergic sensitization or future development of allergic diseases.
Inadequate sleep is common in modern societies [9
]. Evidence from the National Sleep Foundation Survey in the U.S. indicated that 45% of adolescents slept less than 8 hours on school nights, and 78% reported that they needed more than 8 hours of sleep to feel their best [36
]. Compared to their U.S. counterparts, Chinese adolescents reported later bedtimes, earlier rise times, and shorter sleep duration [37
]. Our previous study reported that later bedtime coupled with earlier wake-up time associated with academic demand appeared to be important contributors to sleep loss among this population, in which the majority was school-age students [12
]. Both epidemiological and experimental studies have shown that short sleep duration is associated with an increased risk of developing diabetes [14
], obesity [39
], and cardiovascular disease [13
], with evidence of influence on immune function. To our knowledge, however, no previous study has examined the relationship between short sleep duration and IgE-mediated allergen sensitization.
In the present study, we demonstrated a dose-response relationship between short sleep duration and allergen sensitization to food and aeroallergens. Allergen sensitization was more prevalent among those in the lower sleep duration tertiles compared to those in the highest sleep duration tertile. These associations were not substantially changed when we adjusted for percentage body fat and other covariates, such as age, occupation, education, cockroach at home, smoking status, and birth order. More interestingly, we found a linear relationship between short sleep duration and the number of positive SPTs.
Although the biologic mechanisms underlying this finding remain unclear, the immune alterations due to sleep deprivation may contribute to the development of allergen sensitization. Prior studies have demonstrated that sleep deprivation affects immune function, including an increased susceptibility to infections [25
]. Leeuwen et al [43
] reported that sleep restriction resulted in an elevated production of pro-inflammatory cytokines (e.g., IL-1β, IL-6, and IL-17), which play important roles in immune defense and tissue damage [44
]. So far, the results related to the effect of sleep deprivation on immunoglobulin level are not well understood in humans. One study reported that immunoglobulin level increases with sleep deprivation [47
], while another study suggested that sleep deprivation decreased the immunoglobulin level [48
]. However, most of these studies were based on short periods of sleep loss. The effects of long-term sleep deprivation on B-cell proliferation and IgE production have not yet been elucidated. It is possible that the influence of sleep duration on immune function varies according to the degree of sleep deprivation. For example, natural killer-cell activity has been reported to decrease after partial night sleep deprivation [49
] and increase during prolonged sleep deprivation [51
Our findings should be interpreted in the context of this study. Total sleep duration was calculated based on sleep questionnaires, which, we believe, reflect long-term sleep habits. Due to the cross-sectional nature of our study, we cannot determine the causal relationship between short sleep duration and allergen sensitization, which may be bi-directional. However, in this study population we speculate that short sleep duration more likely led to allergen sensitization rather than vice versa for the following reasons. Our previous report showed that there was a low prevalence of allergic diseases in this population despite a high prevalence of sensitization [25
], and thus the vast majority of sensitized subjects were clinically asymptomatic. Furthermore, we also obtained similar results when the subjects with current or prior allergic diseases or sleep disorders were excluded from the analyses.
There were several limitations in our study. Firstly, although we tested the most common food and indoor allergens among our population, we may have missed some common and important food or aeroallergens, for example, the pollens. This may lead to a misclassification of the non-sensitized group. this were the case, it would have biased the sleep-sensitization association towards null. That is, we might have underestimated the true association. Secondly, in this report we treated twins as individuals, although we corrected intra-twin correlations using GEE. We did not correct multiple comparisons because two highly correlated phenotypes were tested here. Nevertheless, the robust association and highly significant p-values suggested that the associations were unlikely due to chance alone.
In summary, we demonstrated that short sleep duration was associated with sensitization to food allergens and aeroallergens in this large sample of rural Chinese adolescents. Our findings may be generalized to the general population in the Anqing area because this twin population was enrolled from the local community, had similar demographic characteristics and lifestyle, and were comparable to the local general population with regards to age- and gender-specific weight, height, and pulmonary functions as demonstrated in our previous study [31
]. But caution is needed in generalizing our findings to other populations due to differences in demographic, environmental, dietary, and lifestyle factors. Additional longitudinal and experimental studies are needed to confirm our findings and elucidate the causality of the association between short sleep duration and allergen sensitization, and the underlying biological mechanisms, which may provide useful information and help in developing novel prevention and treatment strategies for reducing the global burden of allergic diseases.