Impact of Tobacco Smoking on Health Care Utilization and Medical Costs in Chronic Obstructive Pulmonary Disease,Coronary Heart Disease and Diabetes

Objective To determine the impact of smoking on disease-specific health care utilization and medical costs in patients with chronic non-communicable diseases(NCDs).Methods Participants were middle-aged and elderly adults with chronic NCDs from a prospective cohort in China.Logistic regressions and linear models were used to assess the relationship between tobacco smoking,health care utilization and medical costs.Results Totally,1020 patients with chronic obstructive pulmonary disease(COPD),3144 patients with coronary heart disease(CHD),and 1405 patients with diabetes were included in the analysis.Among patients with COPD,current smokers(β:0.030,95%CI:−0.032-0.092)and former smokers(β:0.072,95%CI:0.014-0.131)had 3.0%and 7.2%higher total medical costs than never smokers.Medical costs of patients who had smoked for 21-40 years(β:0.028,95%CI:−0.038-0.094)and≥41 years(β:0.053,95%CI:−0.004β0.110)were higher than those of never smokers.Patients who smoked≥21 cigarettes(β:0.145,95%CI:0.051-0.239)per day had more inpatient visits than never smokers.The association between smoking and health care utilization and medical costs in people with CHD group was similar to that in people with COPD;however,there were no significant associations in people with diabetes.Conclusion This study reveals that the impact of smoking on health care utilization and medical costs varies among patients with COPD,CHD,and diabetes.Tobacco control might be more effective at reducing the burden of disease for patients with COPD and CHD than for patients with diabetes.

When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and cancer.Although previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these outcomes.Numerous tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and diseases.This review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and functionality.We also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host health.Furthermore,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

Tobacco, air pollution, environmental carcinogenesis, and thoughts on conquering strategies of lung cancer

Each year there will be an estimated 2.1 million new lung cancer cases and 1.8 million lung cancer deaths worldwide.Tobacco smoke is the No.1 risk factors of lung cancer,accounting for>85%lung cancer deaths.Air pollution,or haze,comprises ambient air pollution and household air pollution,which are reported to cause 252,000 and 304,000 lung cancer deaths each year,respectively.Tobacco smoke and haze(hereafter,smohaze)contain fine particles originated from insufficient combustion of biomass or coal,have quite similar carcinogens,and cause similar diseases.Smohaze exert hazardous effects on exposed populations,including induction of a large amount of mutations in the genome,alternative splicing of mRNAs,abnormalities in epigenomics,initiation of tumor-promoting chronic inflammation,and facilitating immune escape of transformed cells.Tackling smohaze and development of multi-targets-based preventive and therapeutic approaches targeting smohaze-induced carcinogenesis are the key to conquer lung cancer in the future.

CONCERNING THE RELATION OF TOBACCOGLYCOPROTEIN TO BUERGER'S DISEASE

Objective To comprehend the reiation of tobacco glycoprotein (TGP) to Buerger,s disease.Metbods TGP was isolated from crude tobacco leaves by basic immunologic techniques. Serum anti- TGPantibodies were tested by Western blot analysis in 11 patients with Buerger,s disease, 15 healthy male smokers and11 nonsmoking healthy male subjects. Results 1. TGP is a dark brown protein of molecular weight 14000. It maybe a subunit of some high molecular weight protein, and exists in crude tobacco leaves. 2. Western blot analysisshowed that 81.81% of patients with Buerger’s disease (9/11), 33.33% of healthy smokers (5/15) and 27.27% ofhealthy nonsmokers (3/11) had serum anti- TGP antibodies. There was significant dtherence between patientswith Buerger,s disease and two control groups (P<0.05), and no signilicant dtherence between both control groups(P>0.05). Conclusion TGP does play an important role in the pathogenesis of Buerger’s disease. As anti - TGPantibodies are also found in some control subjects, it is speculated that other etiologic factors might coordinatelycontribute to the specifc vascular response to TGP in susceptible subjects.

Current cancer situation in China:good or bad news from the 2018 Global Cancer Statistics?

Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden,including the Global cancer statistics 2018 and Cancer statistics in China,2015,along with the GLOBCAN 2018 online database,to investigate the differences of cancer patterns between China,the United States(USA)and the United Kingdom(UK).An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018.Compared to the USA and UK,China has lower cancer incidence but a 30%and 40%higher cancer mortality than the UK and USA,among which 36.4%of the cancer-related deaths were from the digestive tract cancers(stomach,liver,and esophagus cancer)and have relatively poorer prognoses.In comparison,the digestive cancer deaths only took up≤5%of the total cancer deaths in either USA or UK.Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions.China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country,with a rapidly increase cancer burden of colorectal,prostate,female breast cancers in addition to a high occurrence of infection-related and digestive cancers.The incidence of westernized lifestyle-related cancers in China(i.e.colorectal cancer,prostate,bladder cancer)has risen but the incidence of the digestive cancers has decreased from 2000 to 2011.An estimated 40%of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries.Tobacco smoking is the single most important carcinogenic risk factor in China,contributing to~24.5%of cancers in males.Chronic infection is another important preventable cancer contributor which is responsible for~17%of cancers.Comprehensive prevention and control strategies in China should include effective tobacco-control policy,recommendations for healthier lifestyles,along with enlarg-ing the coverage of effective screening,educating,and vaccination programs to better sensitize greater awareness control to the general public.

Identification of CYP 2A6 inhibitors in an effort to mitigate the harmful effects of the phytochemical nicotine

Aim:In this study,our goal was to study the inhibition of nicotine metabolism by P4502A6,as a means for reduction in tobacco use and consequently the prevention of smoking-related cancers.Nicotine,a phytochemical,is an addictive stimulant,responsible for the tobacco-dependence in smokers.Many of the other phytochemicals in tobacco,including polycyclic aromatic hydrocarbons,N-nitrosamines,and aromatic amines,are potent systemic carcinogens.Tobacco smoking causes about one of every five deaths in the United States annually.Nicotine plasma concentration is maintained by the smokers’smoking behavior within a small range.Nicotine is metabolized by cytochrome P450s 2A6 and 2A13 to cotinine.This metabolism causes a decrease in nicotine plasma levels,which in turn leads to increased tobacco smoking,and increased exposure to the tobacco carcinogens.Methods:Using the phytochemical nicotine as a lead structure,and taking its interactions with the P4502A6 binding pocket into consideration,new pyridine derivatives were designed and synthesized as potential selective mechanism-based inhibitors for this enzyme.Results:The design and synthesis of two series of novel pyridine-based compounds,with varying substituents and substitution locations on the pyridine ring,as well as their inhibitory activities on cytochrome P4502A6 and their interactions with its active site are discussed here.Substitutions at position 3 of the pyridine ring with an imidazole or propargyl ether containing group showed the most optimal interactions with the P4502A6 active site.Conclusion:The pyridine compounds with an imidazole or propargyl ether containing substituent on position 3 were found to be promising lead compounds for further development.Hydrogen-bonding interactions were determined to be crucial for effective binding of these molecules within the P4502A6 active site.

Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer

In order to unveil ubiquitin pathway genes (UPGs) that are essential for non-small cell lung cancer (NSCLC) cell proliferation,we recently conducted a siRNA screening experiment to knockdown the expression of 696 UPGs found in the human genome in A549 and H1975 NSCLC cells.We found that silencing of one of the candidates,RFWD3 that encodes an E3 ubiquitin ligase essential for the repair of DNA interstrand cross-links inresponse to DNA damage,led to dramatic inhibition of NSCLC cell proliferation with significant Z-scores.Knockdown of RFWD3 suppressed colony forming activity of NSCLC cells.We further evaluated the significance of RFWD3 in NSCLCs and found that this gene was more elevated in tumor samples than in paired normal lung tissues and was inversely associated with the clinical outcome of patients with NSCLC.Moreover,RFWD3 expression was significantly higher in smokers than in non-smokers.These results show for the first time that RFWD3 is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.

Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%–18.5%of hospitalized adults,calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection.Here,we show that cigarette smoke extract(CSE)and carcinogen benzo(a)pyrene(BaP)increase ACE2 mRNA but trigger ACE2 protein catabolism.BaP induces an aryl hydrocarbon receptor(AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination.ACE2 in lung tissues of non-smokers is higher than in smokers,consistent with the findings that tobacco carcinogens downregulate ACE2 in mice.Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells.Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein,tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.