Deaths from lung cancer and ischaemic heart disease due to passive smoking in New Zealand

Passive smoking is increasingly recognised as a public health hazard. Among New Zealanders who have never smoked, the prevalence of exposure to spousal smoking has been estimated to be 12.7% for men and 16.1% for women. The prevalence of exposure to passive smoking in the workplace has been estimated to be 33.6% and 23.4% for never smoking men and women respectively. The pooled risk estimates from epidemiological studies of the health effects of passive smoking were used to estimate the numbers of deaths from lung cancer and ischaemic heart disease attributable to passive smoking in New Zealand in 1985. The pooled relative risk estimates for lung cancer mortality were 1.3 (95% confidence interval (CI): 1.1-1.5) in both men and women exposed to passive smoking at home, and 2.2 (CI 1.4-3.0) in both men and women exposed to passive smoking at work. Using these relative risk estimates, it was calculated that 30 lung cancer deaths (range: 11-41) were attributable to involuntary smoking in New Zealand in 1985. From pooled relative risk estimates of ischaemic heart disease death of 1.3 (CI 1.1-1.6) and 1.2 (CI 1.1-1.4) for exposure to spousal smoking in men and women respectively, it was estimated that a further 91 ischaemic heart disease deaths (range: 39-177) were due to passive smoking at home. The number of ischaemic heart disease deaths due to passive smoking in the workplace was even higher, at 152 (range: 62-224), assuming relative risks of 2.3 (CI 1.4-3.4) and 1.9 (CI 1.4-2.5) for men and women respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Per capita gross national product and summarized odds ratio for epidemiologic studies on the relationship between passive smoking and lung cancer.

The summarized odds ratios of epidemiologic studies on the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer by country were recalculated, using the odds ratio values in a 1992 report entitled, "Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders" by the US Environmental Protection Agency. The relationship between the summarized odds ratio and per capita gross national product (GNP) in 1964 was studied by the country. The graphic relationship between the summarized odds ratio (ordinate) and GNP (abscissa) showed an upward convex curve. The summarized odds ratios of a developing country (China) and developed countries (USA, Western Europe) in 1964 indicated a very weak association, while those of other countries (Greece, Hong Kong, and Japan) were slightly greater than unity (1.0). This means that ETS in the developing and developed countries in 1964 hardly affected lung cancer, whereas that in the other areas affected lung cancer somewhat. Socioeconomic status in developed countries is far better than that in developing countries, and factors related to socioeconomic status may affect the summarized odds ratio. It is recognized that cancer is diagnosed clinically some years after cancer risk factors appear. If the socioeconomic status involves some risk factors which affect lung cancer, the relationship between the summarized odds ratio and the GNP may be significant. Therefore, we can forecast that the summarized odds ratio of Japan will decrease to close to unity and that that of China will increase in the future because of economic growth, making it possible for the Chinese Government to adopt a policy to reduce the influence of ETS on health.     

Interstitial lung disease in lung cancer: separating disease progression from treatment effects.

Lung cancer often develops in individuals with pre-existing pulmonary and cardiac pathology. Many of these individuals with pre-existing pathology are also at risk of occupational lung disease. New and worsening symptoms can be secondary to pre-existing pathology, progressive cancer or treatment. Pulmonary toxicity, including interstitial lung disease, following radiotherapy and conventional cytotoxic chemotherapy (e.g. cyclophosphamide, bleomycin), has been recognised for many years. Pulmonary toxicity also occurs with the newer classes of cytotoxic agents, including the deoxycytidine analogue gemcitabine. A small percentage (0.88%) of patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib have developed interstitial lung disease. This complication has been reported at a higher frequency in Japanese patients than in US patients (1.9% vs 0.34%, respectively) and in those with pre-existing pulmonary fibrosis. This review discusses the difficulties in both recognition and treatment of gefitinib-associated interstitial lung disease. Symptoms are vague, such as dyspnoea, cough and fever and can be difficult to differentiate from progressive disease, co-existing morbidity and new pulmonary pathology. Diagnosis is, therefore, by rigorous investigation to exclude all other differential diagnoses. Treatment, at present, is supportive and includes discontinuation of gefitinib, oxygen supplementation, high-dose corticosteroids and antibacterials.     

Hair analysis--a biological marker for passive smoking in pregnancy and childhood.

Passive smoking has been shown to adversely affect the health of infants and children. We used hair analysis for nicotine and its metabolite cotinine as a biological marker for exposure to smoking in these two groups. Using radioimmunoassay we measured maternal and fetal hair concentrations of nicotine and cotinine in the mother-infant pairs belonging to three different groups based on the mother's smoking habits. The three groups were: active smokers, passive smokers and nonsmokers. There was a significant correlation between maternal and neonatal hair concentration for both, nicotine and cotinine. Mothers and infants in the smoking groups, both active and passive, had significantly higher hair concentrations of both, nicotine and cotinine than in the control, nonsmoking group. In an older cohort, we compared two groups: 78 asthmatic children were compared to 86 healthy children exposed to similar degrees of passive smoking. By using objective, biological markers, our study aimed at verifying whether asthmatic children are different from nonasthmatic children in the way their bodies handle nicotine. Our results show, that, despite the fact that parents of asthmatic children tend to smoke a lower number of cigarettes per day, their children had an average twofold higher concentrations of cotinine in their hair then the control, nonasthmatic children. These studies document the importance of hair analysis as a tool for measuring exposure to cigarette smoke.     

p16、RASSF1A基因甲基化与中国人群肺癌发生 及被动吸烟关系的研究

目的探讨p16、RASSF1A基因甲基化与肺癌发生及被动吸烟的关系。方法采用Meta分析法研究p16、RASSF1A基因甲基化与中国人群肺癌发生与香烟烟雾暴露的关系;采用焦磷酸测序法检测被动吸烟对小鼠肺组织中p16、RASSF1A基因甲基化程度的影响。结果 (1) Meta分析结果显示,中国肺癌吸烟患者中p16基因甲基化频率显著高于肺癌不吸烟患者(OR=3.77,95%CI:1.88～7.58),差异具有统计学意义(P <0.05);RASSF1A基因甲基化频率显著高于肺癌不吸烟患者(OR=4.59,95%CI:1.39～15.15),差异具有统计学意义(P <0.05);(2)被动吸烟小鼠不同剂量组均未检测出p16和RASSF1A基因甲基化。结论中国人群肺癌患者中p16和RASSF1A基因甲基化高度相关,吸烟造成p16和RASSF1A基因甲基化与肺癌易感性相关;被动吸烟对小鼠p16、RASSF1A基因甲基化的程度未造成影响。     

吸烟及非吸烟肺癌患者的尿液代谢组学比较研究

目的探讨吸烟对肺癌患者体内代谢物质变化的影响。方法收集唐山市人民医院2012年9月-2017年9月诊治的60例肺癌患者尿液样本,其中发现数据集包括吸烟史20例,无吸烟史20例,验证数据集包括吸烟史10例,无吸烟史10例。采用LC-MS法对肺癌尿液样本进行非靶向代谢组学研究,利用主成分分析法(PCA)和偏最小二乘判别分析法(PLS-DA)进行多元统计学分析。结果本研究发现有吸烟史肺癌组与无吸烟史肺癌组患者的尿液代谢图谱存在显著差异,并检测到17个差异有统计学意义(P<0.05)的代谢特征离子。与无吸烟史肺癌组患者相比,有吸烟史肺癌组患者尿液中3种代谢特征离子含量显著上升,14种代谢特征离子含量显著下降,基于KEGG代谢通路富集分析并发现吸烟会影响肺癌患者体内的酪氨酸代谢通路。此外,本研究还采用独立验证数据集对发现的17个差异有统计学意义的代谢特征离子进行验证,发现这些差异代谢特征能够较好地区分吸烟与非吸烟肺癌患者组,其预测准确度达75%,灵敏度为80%和特异性为70%。结论吸烟肺癌患者呈现出不同于非吸烟肺癌患者的尿液代谢谱图特征,尿液中多种代谢物的含量显著改变表明吸烟会影响肺癌患者体内物质代谢,这为进一步实验与临床研究提供了一定的参考依据,并为实现吸烟与非吸烟肺癌患者的个体化精准医疗提供一定的指导。     

基因多态性与吸烟交互作用致肺癌易感性的研究进展

肺癌是人类最常见的癌症之一。目前,肺癌的发病率和病死率在恶性肿瘤中居首位,致癌环境在肺癌的发病因素中起到重要的作用,但肿瘤的发生并不单纯取决于致癌环境,个体易感性在肿瘤的发生发展过程中有不可忽视的作用。越来越多的研究表明,肺癌的发生是遗传因素和环境因素交互作用的结果。本文对近年来基因多态性与吸烟交互作用与肺癌易感性的研究进行阐述,并对存在不同结果的原因及研究发展进行讨论。     

Work in the metal industry and nasopharyngeal cancer mortality among formaldehyde-exposed workers

OBJECTIVE: To investigate further the possibility that the large nasopharyngeal cancer (NPC) mortality excess among a cohort of formaldehyde-exposed workers may be related to occupational factors external to the study plant. METHODS: Subjects were 7345 workers employed at a plastics-producing plant (1941-1984) in Wallingford, Connecticut evaluated independently as part of a National Cancer Institute cohort study. Vital status for 98% of the cohort and cause of death for 95% of 2872 deaths were determined through 2003. Reconstructed worker exposures to formaldehyde were used to compute unlagged and lagged exposure measures. We computed standardized mortality ratios (SMRs) based on US and local county rates. In a nested case-control study we evaluated mortality risks from NPC and from all other pharyngeal cancers combined (AOPC) in relation to formaldehyde exposure while accounting for potential confounding or effect modification by smoking or external (non-Wallingford) employment. Job applications, Connecticut commercial city directories and a previous survey were used to assign subjects to three external job groups. RESULTS: We observed no new deaths from NPC and one additional AOPC death (pharynx unspecified) yielding, respectively, SMRs of 4.43 (7 deaths, 95% CI=1.78-9.13) and 1.71 (16 deaths, 95% CI=1.01-2.72). Five of seven NPC cases worked in silver smithing (including brass plating and other jobs related to silver or brass) or other metal work (including steel working and welding), and this type of work was relatively rare in the remaining study population (OR=14.41, 95% CI=1.08-82.1). For AOPC, we found a moderate increase in risk for other metal work (OR=1.40, 95% CI=.31-5.1). Interaction models suggested that NPC and AOPC risks were not elevated in subjects exposed only to formaldehyde. CONCLUSIONS: The results of our nested case-control study suggest that the large nasopharyngeal cancer mortality excess in the Wallingford cohort may not be due to formaldehyde exposure, but rather reflects the influence of external employment in the ferrous and non-ferrous metal industries of the local area that entailed possible exposures to several suspected risk factors for upper respiratory system cancer (e.g., sulfuric acid mists, mineral acid, metal dusts and heat). Our findings may also help to explain why the associations with formaldehyde and nasopharyngeal cancer reported in the 1994 update of the 10-plant NCI formaldehyde cohort study were unique to the Wallingford plant (Plant 1 in NCI study). Further updates of the NCI formaldehyde cohort study should include co-exposure data on silver smithing and other metal work for all study plants to help explain the unique findings for nasopharyngeal cancer in Plant 1 compared with the other nine plants.     

Mediators of passive lung anaphylaxis in the rat.

Passive lung anaphylaxis (PLA) was investigated in rats sensitized by the intravenous injection of high titre reaginic antiserum prepared in rats. 2 The effect of various pharmacological antagonists on anaphylactic bronchoconstriction in vivo were examined. An antihistamine (mepyramine), a kallikrein inactivator (aprotinin) or a prostaglandin synthesis inhibitor (aspirin) did not inhibit PLA, whereas an anti-5-hydroxytryptamine agent (methysergide) and an anti-slow reacting substance-A agent (FPL 55712) significantly reduced the response. 3 Isolated perfused lungs taken from sensitized rats released, on challenge with the sensitizing antigen, histamine, 5-hydroxytryptamine, slow reacting substance of anaphylaxis (SRS-A) and prostaglandins, but no rabbit aorta contracting substance (RCS). 4 Disodium cromoglycate inhibited both anaphylactic bronchoconstriction in vivo and the anaphylactic release of mediators in vitro. Inhibition in vivo was dose-related. 5 Mediators from the intestine, the primary shock organ of anaphylaxis in the rat, did not contribute to the lung response. 6 Vagal reflex pathways were found not to be important in PLA in vivo. 7 The relationship between the mediators released following antigen challenge of passively sensitized rat lung in vitro and passive lung anaphylaxis in vivo is discussed.     

Risks and benefits of nicotine to aid smoking cessation in pregnancy.

Cigarette smoking during pregnancy is the single largest modifiable risk for pregnancy-related morbidity and mortality in the US. Addiction to nicotine prevents many pregnant women who wish to quit smoking from doing so. The safety and efficacy of nicotine replacement therapy (NRT) for smoking cessation during pregnancy have not been well studied. Nicotine is classified by the US Food and Drug Administration as a Pregnancy Category D drug. Animal studies indicate that nicotine adversely affects the developing fetal CNS, and nicotine effects on the brain may be involved in the pathophysiology of sudden infant death syndrome (SIDS). It has been assumed that the cardiovascular effects of nicotine resulting in reduced blood flow to the placenta (uteroplacental insufficiency) is the predominant mechanism of the reproductive toxicity of cigarette smoking during pregnancy. Short term high doses of nicotine in pregnant animals do adversely affect the maternal and fetal cardiovascular systems. However, studies of the acute effects of NRT in pregnant humans indicate that nicotine alone has minimal effects upon the maternal and fetal cardiovascular systems. Cigarette smoking delivers thousands of chemicals, some of which are well documented reproductive toxins (e.g. carbon monoxide and lead). A myriad of cellular and molecular biological abnormalities have been documented in placentas, fetuses, and newborns of pregnant women who smoke. The cumulative abnormalities produced by the various toxins in cigarette smoke are probably responsible for the numerous adverse reproductive outcomes associated with smoking. It is doubtful that the reproductive toxicity of cigarette smoking is primarily related to nicotine. We recommend the following. Efficacy trials of NRT as adjunctive therapy for smoking cessation during pregnancy should be conducted. The initial dose of nicotine in NRT should be similar to the dose of nicotine that the pregnant woman received from smoking. Intermittent-use formulations of NRT (gum, spray, inhaler) are preferred because the total dose of nicotine delivered to the fetus will be less than with continuous-use formulations (transdermal patch). A national registry for NRT use during pregnancy should be created to prospectively collect obstetrical outcome data from NRT efficacy trials and from individual use. The goal of this registry would be to determine the safety of NRT use during pregnancy, especially with respect to uncommon outcomes such as placental abruption. Finally, our review of the data indicate that minimal amounts of nicotine are excreted into breast milk and that NRT can be safely used by breast-feeding mothers.     

被动吸烟鼠肺超微结构和表面活性蛋白A表达的变化

目的探讨被动吸烟鼠肺早期超微结构和表面活性蛋白A(SPA)表达的变化。方法健康昆明小鼠被动吸烟4周,通过电镜观察鼠肺早期的超微结构改变;应用免疫组织化学技术(SABC法),观察鼠肺SPA表达的变化。结果透射电镜下实验组小鼠Ⅱ型肺泡上皮细胞线粒体空泡变性,板层小体数量增多,部分脱颗粒,肺泡巨噬细胞内有大量吞噬颗粒,血管内皮细胞核染色质边聚成块状,核固缩,核周隙增宽。随着被动吸烟时间的延长,实验组SPA表达逐渐减弱。实验组SPA表达与对照组比较有显著性差异(P<0.05)。结论被动吸烟鼠肺早期即有超微结构改变,Ⅱ型肺泡上皮细胞和终末细支气管黏膜上皮SPA表达减弱,表明表面活性物质功能降低,形成细支气管及肺泡慢性炎症反应。     

Cigarette smoking and pressure-volume characteristics of the lung.

This study was done to identify the immediate changes induced by cigarette smoking on the mechanical properties of the lung. Static compliance (C stat), static pressure-volume (Stat P-V) hysteresis, vital capacity (VC), frequency dependence of dynamic compliance (C dyn) and collateral ventilation (Coll V) of the lung were studied in six mongrel dogs. The smoking of one cigarette induced a fall in VC and static P-V hysteresis of the lungs. These changes indicate an increase in elastic recoil of the lung probably caused by inactivation of pulmonary surfactant. Frequency dependence of C dyn did not develop after smoking. Extensive collateral ventilation was seen in the lungs of all the experimental animals and in those of five other normal dogs, who had not been exposed to cigarette smoke. The significance of these findings are discussed.     

When risk factors combine: the interaction between alcohol and smoking for aerodigestive cancer, coronary heart disease, and traffic and fire injury

BACKGROUND: Alcohol and tobacco are responsible for a significant amount of burden of disease, but some diseases may be a result of the interaction between these two risk factors. METHODS: Systematic literature review identified articles on the interaction of alcohol and smoking on a number of outcomes related to both risk behaviours. RESULTS: The interaction of smoking and alcohol significantly increases risk for aerodigestive cancers, and may increase risk for traffic injury and fire injury, but there were very few quality studies on injury. The indication that the cardioprotective effect of alcohol on coronary heart disease is only valid for smokers, but this result is inconclusive because of small evidence base. CONCLUSIONS: The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Unfortunately, little is known on the mechanisms and details of this interaction on disease outcomes. Future studies, especially for coronary heart disease and injury outcomes, are warranted.     

A review of the evidence on smoking bans and incidence of heart disease

We update an earlier review of smoking bans and heart disease, restricting attention to admissions for acute myocardial infarction. Forty-five studies are considered. New features of our update include consideration of non-linear trends in the underlying rate, a modified trend adjustment method where there are multiple time periods post-ban, comparison of estimates based on changes in rates and numbers of cases, and comparison of effect estimates according to post-ban changes in smoking restrictiveness. Using a consistent approach to derive ban effect estimates, taking account of linear time trends and control data, the reduction in risk following a ban was estimated as 4.2% (95% confidence interval 1.8–6.5%). Excluding regional estimates where national estimates are available, and studies where trend adjustment was not possible, the estimate reduced to 2.6% (1.1–4.0%). Estimates were little affected by non-linear trend adjustment, where possible, or by basing estimates on changes in rates. Ban effect estimates tended to be greater in smaller studies, and studies with greater post-ban changes in smoking restrictiveness. Though the findings suggest a true effect of smoking bans, uncertainties remain, due to the weakness of much of the evidence, the small estimated effect, and various possibilities of bias.