Can Lifestyle Inuence the Risk of High Nicotine Dependence?

Background: Nicotine dependence (ND) is a maladaptive pattern of tobacco smoking with withdrawal symptoms like other drug addictive disorders. It is very common in clinic that smokers always have different degree of nicotine dependence with same amount of tobacco consumption. Lifestyle may inuence cigarettes daily consumption or smoke state. So it is critical to prove the inuence of healthy or unhealthy lifestyles in high nicotine dependence smokers. This study aimed to identify behavioral correlates to high ND. Methods: 343 patients who went to clinic for smoking cessation were recruited. Participants completed a demographic questionnaire. The extent of Nicotine dependence was determined by Fagerstrom Test for Nicotine Dependence (FTND). Results: High ND patients (FTND>5) showed signicant life style compared with mild and moderate ND patients (FTND<5) is signicantly (χ 2 =36.98, P value=0.002). There is no single lifestyle index can signicantly distinguish high ND from mild and moderate ND. However, combined behaviors of caffeine drink and mental activities after dinner contribute to the risk of high ND (OR:1.939, 95%CI:1.154-3.258, P value=0.012). In addition, combined index of(sleep time < 8 hours, caffeine drink and mental activities after dinner) each signicantly distinguished patients of high ND from patients of mild and moderate ND. with high nicotine dependence(OR:2.208, 95%CI:1.032-4.737, P value=0.042 (cid:0) . Conclusion: Interact effects of mental activities after dinner and caffeine drink will increase the risk of high nicotine dependence. Sleep less than 8 hours with behaviors of mental activities after dinner and caffeine drink also have the same effect.


Introduction
Tobacco smoking is a preventable human behavior and has been identi ed to play critical role in the pathogenesis of various malignant cancers(1) and as well as pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) (2). Nicotine dependence (ND) is a maladaptive pattern of tobacco smoking with withdrawal symptoms like other drug addictive disorders and it has already been de ned by the Diagnosis and Statistical Manual of Mental Disorder-edition IV (DSM-IV) (3). Previous studies have shown that different lifestyle is closely related to smoke state change and cigarettes consumption (4).Caffeine withdrawal increase di culties in quitting smoking (5). Alcohol and nicotine dependence are likely to co-occur in the same person, which is the reason of lower likelihood of smoking cessation (6,7). People with healthy life habits, including exercise and enough time of sleep, may have less cigarettes daily consumption and lower nicotine dependence (8)(9)(10)(11). Moreover, it is very common in clinic that smokers always have different degree of nicotine dependence with same amount of tobacco consumption. Therefore, we considered that whether some relationship between lifestyle and high nicotine dependence. However, so far there is no evidence showing unhealthy factors increased the risk of high ND, vice versa. We sought to gure out the relationship between lifestyle and ND by a designed survey which recorded healthy and unhealthy life behaviors as medical history.

Methods And Procedures
A survey designed by our group members recorded patients' lifestyles from April 2010 to January 2020 in The A liated Hospital of Medical School of Ningbo University. Three hundred and forty three patients were recruited and complete the survey. All research subjects provide informed consent, and survey designation was approved by the Ethics Committee of the A liated Hospital of Medical school of Ningbo University (Ningbo, China). Informed consent contained from all patients before nish the survey. All methods were carried out in accordance with NCCN Clinical Practice Guidelines in Oncology of Smoking Cessation (12).

Survey design
Clinical characteristics and life behaviors (1)Demographic (age, gender, BMI) data were recorded as clinical characteristics. (2) Healthy lifestyles was identi ed as following: athletics(exercise more than 3 times a week and each time more than 30 minutes (8,9);sleep time ≥ 8 hours; take afternoon nap; often eat fruits. (3) Unhealthy lifestyles include: sleep time < 8 hours; alcohol consumption; caffeine drink; mental activities after dinner before sleep (13) (including gambling, overtime work, play video games, studying or other mental thinking activities).

Measurement of nicotine dependence
Nicotine dependence was measured by Fagerstrom Test for Nicotine Dependence (FTND) (14,15). FTND score > 5 was regarded as high nicotine dependence. FTND score ≤ 5 was considered as mild and moderate nicotine dependence.

Statistical analysis
The information and results questionnaire for 343 patients were included in the statistics. t-test and mean ± Standard deviation(SD) were used in age, BMI. Gender distribution and life behaviors distribution in two groups(FTND ≤ 5 and FTND > 5) were calculated by chi-square analysis. All independent or interaction effects of behaviors were analyzed by multiple logistic-regression. These analysis were calculated by IBM SPSS Statistics 21.0 and P value < 0.05 was considered as statistical difference.

Results
Demographics of the cohort are shown in Table 1, there were no differences in age, gender and BMI between the two groups. However, healthy and unhealthy lifestyles were differently distributed in the two groups ( Table 2) (χ 2 = 36.98, P value = 0.002), indicating that each behavior of athletics, sleep, sleep time ≥ 8h, fruits consumption didn't decrease the risk of high ND no matter independently or combined (Table 3). Results in Table 4 showed that caffeine drink combined with mental activities after dinner increase the risk of high nicotine dependence (OR:1.939, 95%CI:1.154,3.258, P value = 0.012). Three unhealthy interaction behaviors (sleep time < 8 hours, caffeine drink and mental activities after dinner) are associated with high nicotine dependence (OR:2.208, 95%CI:1.032,4.737, P value = 0.042).

Discussion
Nicotine dependence is a maladaptive pattern of tobacco smoking with withdrawal symptoms like other drug addictive disorders. Many life behaviors may change cigarettes daily consumption or smoke state (4). People with healthy behaviors has lower nicotine dependence ,such as exercising, sleep enough time (8,16). Previous studies demonstrate that unhealthy lifestyles ,including sleep duration (10,16), caffeine drink consumption (5,17), alcohol dependence (6, 7), mental activities (gambling (18,19), play video games (20), overtime working (21)) increase cigarettes consumption and turn ex-smokers or nonsmokers into smokers. However, smokers with several different lifestyles is common in their daily life and there are few studies investigate the in uence of combined lifestyles on high nicotine dependence. To our knowledge, our research is the rst to study revealing the relationship between healthy or unhealthy combined lifestyles and the risk of high ND. Importantly, we revealed that interaction of mental activities after dinner, caffeine drink and sleep time less than 8 hours greatly increased the risk of high ND.
During night without smoking, decrease of nicotine level can recover nicotinic-acetylcholine receptors. It may contribute to development of withdrawal symptoms in the morning when caving for cigarettes (22).
Sleep duration further decreases positive mood and increases negative mood (10).Dopamine caused by the calming effect of nicotine relieve this bad mood (23).Therefore, smokers with high nicotine dependence will considered the rst few cigarettes as the most pleasurable of the day. We can also understand sleep duration may increase the risk of high nicotine dependence.
Mental activities after dinner(13) (including gambling, overtime work, play video games, studying or other mental thinking activities) and smoking may be related to environment factor, such as colleagues, classmates, gamblers and video game patters. Moreover, tobacco was used to make dopamine to get rid of anxious and cope with stress to focus attention in these situations (24)(25)(26).Furthermore, coffee or caffeine drink is also the choice for dealing with tiredness in that some low-cost addictive substance are available anywhere and anytime. The prevalence of drinking caffeine beverage and smoking together will happen during mental activities after dinner or morning without enough sleep time. Caffeine withdrawal symptoms increased di culties in smoking cessation (17).So,synergistict effects of mental activities after dinner, caffeine drink, sleep duration increase the risk of high nicotine dependence.
Our data proved that healthy lifestyles can't help decrease the risk of high ND. This result is different than previous studies that smokers with exercises have lower nicotine dependence and lower tobacco consumption (8,9).The main reason of differences is that we chose all range of age smokers with exercise more than 3 times a week and each time more than 30 minutes. This inclusion criteria can be wildly used in all high nicotine dependent smokers. And we also proved that afternoon snap didn't decrease the risk of high nicotine dependence. Short breaks, such as a nap, relieve stress and reduce brain fatigue during workdays. Some smokers who need nicotine for getting rid of tiredness will decrease cigarettes consumption in that enough rest help brains to focus attention. There are few studies showed the relationship between nap with nicotine dependence. Therefore, we draw a suggestion that smokers who come to clinic for cessation help with high nicotine dependence should fully consider individualized treatment no matter with healthy or unhealthy lifestyles instead of avoiding unhealthy life behaviors or developing healthy lifestyles only.
In the future, standards of unhealthy life behaviors, such and cups of caffeine drink and the sort of mental activities can obviously increase nicotine dependence in smokers. Healthy life behaviors, such as nap, should be more investigated the mechanism underlying nicotine dependence.

Conclusion
Interact effects of mental activities after dinner and caffeine drink will increase the risk of high nicotine dependence. Sleep less than 8 hours with mental activities after dinner and caffeine drink also have the same effect. Avoiding these factors may decrease likelihood for high nicotine addiction and may help increase possibility for smoking cessation. Smokes should decrease mental activities at night, caffeine drink will be take less in the meanwhile. Enough rest also makes brain relax which decrease anxious and stress. All these factors' correction may help decrease risk of high nicotine dependence. Individualized treatment for smokers should fully consider both healthy and unhealthy lifestyles.

Competing interests
The authors declare that they have no competing interests.

Ethical approval
Our study and survey designation approved by the Ethics Committee of the A liated Hospital of Medical school of Ningbo University (NBU-2020-080, Ningbo, China). Informed consent was obtained from all patients before conducted the survey.

Consent for publication
Not applicable.

Availability of data and materials
All data generated or analyzed during this study are included in this published article.

Funding
Funding for this study was provided by The A liated Hospital of Medical School of Ningbo University Youth Talent Cultivation Program (FYQM-LC-202003), and the Natural Science Foundation of Ningbo (2018A610271). The A liated Hospital of Medical School of Ningbo University Youth Talent Cultivation Program and Natural Science Foundation of Ningbo had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication.

Data availability Statement
Our data generated and analyzed during the study are available from the corresponding authors in the future research on reasonable request.

Authors' contributions
Zhongbo Chen conducted the research. Zhongbo Chen and Xuechan Yu analyzed and calculated data and wrote the rst draft of manuscript together. All authors read and approved the nal manuscript.