Our meta-analysis has quantitatively examined the association between smoking and sleep disorder. The pooled analysis included six cohort studies including about 13 thousand people. The results showed that smoking was significantly associated with incidence of sleep disorder. Sensitivity analysis revealed heterogeneity was mainly from one study [25]. After review the whole article, we noticed in this study, pool sleepers at the baseline who developed insomnia at the endpoint were also included in the analysis while in other included studies, this part of participants were excluded. Besides, PSG was used to diagnose insomnia in this study, which might detected potential insomnia in other included studies. All these factors might cause the heterogeneity.
The stratified analysis according to smoking status found significant association between current smokers and incidence of sleep disorder, both for regular smokers and occasional smokers. Many previous studies reported similar association[7, 30]. The association between occasional smokers and incidence of sleep disorder was more significant than regular smokers. This point was the first time to be reported. The main cause of smoking’ negative effects on sleep is associated with chemicals in it, so after quitting or decreasing, the impact should reduce. However, one study demonstrated that sleep architecture disturbances among current smokers were not influenced by the amount of smoking quantified by pack-years [31], which indicated there might be other mechanisms of smoking’ impact on sleep. Because the effects were associated with nicotine-acetylcholine receptors in our brain[31], as the daily amount of smoking increased, this kind of receptors might be saturated at some point and the effects of smoking might reach the maximum. The effects of nicotine on our brain were nonspecific, so while its concentration in the blood reached a certain value, other effects might gradually emerge which might alleviate the effects of nicotine on sleep health. There is still no better explanation according to existing researches. More works on the association between the amount of smoking quantified by pack-years and sleep disorder were needed to be done. To better understand the etiology, concentration of nicotine and other chemicals in cigarette needed to be tested among insomnia population so their effects on sleep could be analyzed.
The pooled analysis didn’t indicate a positive association in ex-smokers. It was also reported that there were not significant differences between former smokers and never smokers for the prevalence of trouble sleeping[32]. Another study has shown that longer sleep duration was associated with successful smoking cessation[33]. Besides, insomnia symptoms were also risk factors for cessation failure following smoking treatment[34]. The effects were mutual and might create a vicious circle between smoking and insomnia. This suggested that quitting smoking might be beneficial to sleep health and current smokers might improve sleep quality by quitting smoking.
The region-specific analysis found significant association between smoking and incidence of sleep disorder in North America and Asia. Epidemiological investigations and cross-sectional studies in these places reported similar conclusion[6, 18]. The association was not significant in Europe. This point was consistent with previous studies[35, 36], which in Europe didn’t suggest that smoking was an independent risk factor for sleep disorder or insomnia either. The different results between areas might due to differences in living habits, social atmosphere and gene. We noticed that Mediterranean diet, which was popular in Europe, was possibly beneficial factor for sleep health[37]. The pace of life in Europe was much slower than in other areas and lifestyle has been reported to related to sleep disorder[5]. Besides, genetic diversity might also have an influence on how human organism reacted to smoking[38]. These factors might decrease the effect of smoking on sleep, but couldn’t offset it. One included study[29] showed that excessive daytime sleepiness was related to smoking for females while nightmares and disturbing dreams were related to smoking among males. More work needed to be done to reveal the substantial association between smoking and sleep disorder. Cross-sectional studies and epidemiological researches in other areas revealed the negative effect of smoking on sleep health[7, 30]. Sleep disorder and smoking are both worldwide problems. Our study showed the conclusion that prohibiting smoking was beneficial to sleep health was widely applicable.
The subgroup analysis based on age suggested significant association both in adults (> 18) and juveniles (≤ 18).Similar results were reported by other studies[7, 39, 40]. Considering only one included study focused on juveniles, more works needed to be done in the future. A cohort study of the unborn reported the adverse influence of in utero exposure to smoking on sleep patterns in preterm neonates[41]. These studies suggested that smoking might contribute to incidence of sleep disorder at all ages. Comparatively, the earlier people smoked, the greater effect smoke caused on sleep. Juveniles, especially children ‘respiratory system and nervous system are immature, which might be more sensitive to chemicals in cigarettes.
Because included studied didn’t divide participants into males and females, we couldn’t conduct a subgroup analysis based on gender. To explore whether gender was associated with sleep disorder in smokers, we divided included studies into subgroups by gender ratio (women/men). The result suggested significant association in population with gender ratio (women/men) < 1, but not in population with gender ratio(women/men) ≥ 1, that is, smoke has a negative influence on sleep in population which males are in the majority. The result was reported for the first time. Prior research suggested that females were more likely to have insomnia[42]. After discussion, we concluded that as male smokers were more than female smokers, the sample size of female smokers was not enough in included studies, which might contribute to bias. Wetler et al (1994)[43] suggested that both for males and females, current smoking was associated with some kinds of insomnia symptoms. The association was not significant when we changed the endpoints to other insomnia symptoms. Besides, the frequency of insomnia symptoms had an influence on the association. The pooled result in population with gender ratio (woman/man) ≥ 1 showed a high heterogeneity and one reported significant association between smoke and incident sleep disorder, the other didn’t. As there were only two studies in the subgroup, different religion, mental disorder and social status may all contribute to the high heterogeneity. Passive smoking has also been found to associate with sleep disturbance among pregnant women[44]. To better understand the interaction between gender, smoking and sleep disorder, more works with female smokers and comprehensive analysis of all-cause insomnia incidence remained to be done.
4.1 Biological mechanisms
A large amount of studies have revealed that smoke, especially long-time smoke, could promote the occurrence of sleep difficulties. Compared with no smoker, the population with smoking experience has a higher incidence of sleep disorder and associated diseases. The specific biological mechanism of smoking to particulate matters is still evolving. So far, researchers mainly focused on nicotine, the primary addictive component of cigarettes or tobacco. Nicotine has a known potential for enhancing attention and maintaining a certain level of arousal. These effects are obtained by the central release of dopamine, norepinephrine, serotonin, acetylcholine, all of which have been implicated in the regulation of wakefulness, and by the stimulant effect nicotine has on cholinergic neurotransmission in the basal forebrain responsible for cortical arousal[45]. In relation to sleep disorder, nicotine can regulate and change the normal neurotransmitter and disturb sleep architecture both in the early[46] and later stages of the sleep[43]. The changes have been detected by sleep parameters analysis (polysomnography, PSG). Furthermore, nicotine could generate a dose-dependent reduction in sleep efficiency, slow-wave-sleep, REM (rapid eyes movement) sleep and total sleep time[47, 48].
Besides, several psychosocial and physiological factors may account for the association between smoking and incident insomnia. Depression and obesity might be underlying factors in the biopsychosocial domain. Cigarette use has been linked to adverse life events and work stress, which are also associated with insomnia symptoms[5]. Future studies are needed to investigate these multiple associations and reveal the biochemical relationship between smoking and sleep disorder.
4.2 Strengths and limitations
There are several strengths in our study. Firstly, the six studies we included for meta-analysis and one for systematic review were all cohort studies. We did not include cross-sectional studies, because they couldn’t reveal the sequence of smoking and sleep disorder. Though there were several reviews of this topic, none of them included meta-analysis. So this article was the first systematic review and meta-analysis in the recent 20 years. Secondly, the quality of included studies were high or moderate, which might contribute to the reliability. Besides, we systematically analyzed the association between smoking status and sleep disorder, which provided extra basis for the public policy of promoting anti-smoking.
We admitted limitations in the following aspects. Firstly, the number of included studies is not enough, especially for the incidence of excessive daytime sleep and subgroup-analysis. Secondly, the pooled result of smoking and incident insomnia in population with gender ratio (woman/man) ≥ 1 showed a high heterogeneity. There were two studies in this subgroup and one suggested significant association and the other didn’t. Excluding any one of them showed different consequences. Thirdly, sleep disorder or insomnia includes different kinds of symptoms. We didn’t find enough studies on specific insomnia symptoms to conduct subgroup analysis while studies focused on different insomnia symptoms might have different results. Lastly, alcohol, tea, social status, depression and other factors might also have an interaction with smoking and sleep disorder, which was not discussed in the study.
4.3 Recommendations for future research
4.3.1 Study design
We suggest high-quality longitudinal studies and cohort studies with detailed baseline information and regular health examination as ideal study method. Population with different features, such as a specific job or different age groups and gender composition, should be recorded and synthesized by stratified analysis. Mental health, geographical region and other potential factors should be taken into account to improve the representativeness of the study.
4.3.2 Smoking status
Future studies should record daily cigarettes that participants smoke and divide them into different groups. The association between smoke and sleep disorder need more quantification.
4.3.3 Adjustment by covariates
During the review of eligible studies, we found various covariates which may exert unstable impact on the summary. We recommend standardized covariates included at least age, sex, BMI, smoking status, alcohol consumption, chronic respiratory diseases, mental disorder, socioeconomic status at an individual level. Further adjustment can be performed by personal habits (such as physical activities, diet) and health status (such as diabetes, family history of disorder). This work requires detailed and elaborate baseline information.
4.3.4 Definition of endpoints
Though all studies provided definition and diagnostic criteria, some studies lacked preciseness when describing sleep disorder or insomnia. We recommend future studies definite sleep disorder or insomnia according to DSM. And more studies are needed to discuss the relationship between smoking and specific insomnia symptoms.