Cellular senescence may predominantly drive the progression of early subclinical injury under conditions of low-dose, long-term occupational exposure. However, previous research has largely overlooked the cellular senescence induced by hexavalent chromium [Cr(VI)]. To bridge the gap, 304 workers from a chromate facility were enrolled, and a mouse model was used to confirm the effects of Cr(VI) on cellular senescence. A 2.7-fold increase in blood Cr was related to the changes of p53 [23.19 (13.06, 34.23)%], serum α-Klotho [11.45 (6.13, 17.04)%], adipsin [-14.11(-22.16, -5.24)%], leptin [-4.32(-6.99, -1.58)%] and resistin [-3.29(-5.54, -0.98)%]. There were significant correlations of blood Cr with DNA methylation of ELOVL2 and hTERT genes. Furthermore, methylation at hTERT Pos1, Pos2, Pos6, and Pos8 significantly mediated the relationship between blood Cr and p53. In the mouse model, we observed significantly higher mRNA expression levels of key genes in the p53/p21 and Rb/p16 pathways and senescence-associated β-galactosidase positive cell ratio in the exposed group. In conclusion, we found that p53 in human peripheral blood cells serves as a Cr(VI)-induced senescence biomarker, with α-Klotho upregulation and adipokines (adipsin, leptin, and resistin) downregulation indicating compensatory responses, as well as hTERT methylation partially mediating Cr(VI)-senescence association.

Tobacco smoke exposure is associated with inflammatory changes in the respiratory system including nasal mucosa. Our aim was to demonstrate nasal mucosal inflammation such as neutrophilic activation and epithelial permeability in patients with allergic rhinitis with exposure to environmental tobacco smoke (ETS) and reveal its effect on allergic rhinitis symptoms.

We enrolled 204 subjects with allergic rhinitis to this cross-sectional study. Sociodemographic and AR clinical characteristics were recorded. Urinary cotinine levels >50 ng/ml were defined as exposure to secondhand tobacco smoke. Club cell 16 (CC16) and myeloperoxidase (MPO) levels were measured in the nasal lavage fluid. Levels of these biomarkers and clinical severity were compared between ETS exposed and non-exposed children with AR.

Among 204 children enrolled, 53 (26 %) had ETS exposure. Mean age of the ETS exposed group was significantly higher than the unexposed group (12.1 ± 3.5 and 10.7 ± 3.6 years respectively, (p = 0.02). Similarly, T5SS score was significantly higher in ETS exposure group (9.3 vs 8.3, p = 0.03) but this significance was lost when corrected for age. Age and T5SS were inversely correlated with MPO levels (r = -0,24, p < 0.001 and r = -0,14, p = 0.04). Nasal lavage CC-16 and MPO levels were not found to be significantly different among subjects with and without ETS exposure (p = 0.13 and p = 0.26 respectively).

Our results demonstrated that ETS exposure is associated with more persistent AR in children. However, it is not related to severity or nasal lavage MPO or CC16 levels. Rhinitis symptoms beyond allergen period suggests isolated smoke exposure effect.

There is sufficient evidence suggesting that exposure to hexavalent chromium [Cr(VI)] can cause a decline in lung function and the onset of lung diseases. However, no studies have yet explored the underlying mechanisms of these effects from various perspectives such as systemic inflammation, oxidative stress, and cellular senescence, simultaneously. This cross-sectional study was conducted among 304 workers engaged in chromate production and processing in China. Urine was used for detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), while RNA and DNA extraction from peripheral blood cells was used for detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs). A 2.7-fold elevation in blood chromate (Cr) corresponded to a 7.86% (95% CI: 2.57%, 13.42%) rise in urinary 8-OHdG and a 4.14% (0.02%, 8.42%) increase in urinary 8-iso-PGF2α, indicating that exposure to chromates can cause oxidative stress. Furthermore, strong correlations emerged between blood Cr concentration and mRNA levels of P16, P21, TP53, and P15 in the cellular senescence pathway. Simultaneously, a 2.7-fold elevation in blood Cr associated with a -5.47% (-8.72%, -2.1%) change in telomere length, while rDNA CNs (5S, 5.8S, 18S, and 28S) changed by -3.91% (-7.99%, 0.34%), -9.4% (-15.73%, -2.6%), -8.06% (-14.01%, -1.69%), and -5.86% (-10.67%, -0.78%), respectively. Structural equation model highlighted that cellular senescence exerted significant indirect effects on Cr(VI)-associated lung function decline, with a mediation proportion of 23.3%. This study provided data supporting for 8-iso-PGF2α, telomere length, and rDNA CNs as novel biomarkers of chromate exposure, emphasizing the significant role of cellular senescence in the mechanism underlying chromate-induced lung function decline.

Smoke-free policies have led to a decline in smoking prevalence. Nevertheless, as the global population grows, more non-smokers are exposed to second-hand smoke (SHS) hazards. Mitigating SHS hazards requires a systematic analysis of the global disease burden attributable to SHS.

Data on SHS was extracted from the Global Burden of Disease Study 2019. First, we measured the disease burden of SHS by the number of cases and age-standardized rates of deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) from 1990 to 2019. Second, trends in the disease burden of SHS in different periods were estimated based on the annual percentage change (APC) by joinpoint regression analysis. Finally, using histogram plots, world maps, Pearson correlation analysis, and population attributable fraction (PAF), we conducted a stratified analysis of SHS exposure by sex, age, geographic location, sociodemographic index (SDI) level, and disease.

The number of deaths caused by SHS remained stable between 1990 and 2019, and the number of YLDs more than doubled in three decades. In contrast, the number of DALYs and YLLs caused by SHS decreased. The declining trend in deaths (APC = -1.42 % [95 % UI -1.79 %, -1.05 %]), DALYs (APC = -1.91 % [95 % UI -2.15 %, -1.67 %]), and YLLs (APC = -1.28 % [95 % UI -1.93 %, -0.64 %]) had slowed down in recent years, while SHS-related YLDs were still increasing (APC = 1.84 % [95 % UI 0.74 %, 2.96 %]). From 2010 to 2019, we found that SHS exposure increased the risk of tracheal, bronchus, and lung cancer (PAF increased by 11.75 %), breast cancer (PAF increased by 5.36 %), diabetes mellitus (PAF increased by 8.24 %), and ischemic heart disease (PAF increased by 4.46 %). In addition, the disease burden caused by SHS was highest in middle SDI and low-middle SDI countries.

The global disease burden attributable to SHS is still severe, and policymakers need to implement more effective measures to reduce the harm of SHS.

Late Dr Takeshi Hirayama and his colleagues conducted a mortality follow-up of a large-scale cohort in six prefectures in Japan. This study is called the six-prefecture cohort study or Hirayama Cohort Study. The study subjects were residents aged 40 years or older at the baseline survey in 1965, which covered 94.8% of residents identified in the study area by the National Census conducted on October 1, 1965. The mortality of 264,118 cohort members was followed until the end of 1982. One of the most important findings made by this study was an association between second-hand smoke exposure and lung cancer. This finding is the origin of the worldwide spread of smoking ban in indoor public venues and workplaces. Other major findings obtained from the study are also briefly described in this article.

Background:  To present up-to-date meta-analyses of evidence from Japan relating smoking to major smoking-related diseases.  Methods:  We restricted attention to lung cancer, chronic obstructive pulmonary disease (COPD), ischemic heart disease (IHD) and stroke, considering relative risks (RRs) for current and ex-smokers relative to never smokers.  Evidence by amount smoked and time quit was also considered.  For IHD and stroke only, studies had to provide age-adjusted RRs, with age-specific results considered.  For each disease we extended earlier published databases to include more recent studies.  Meta-analyses were conducted, with random-effects RRs and tests of heterogeneity presented.  Results:  Of 40 studies, 26 reported results for lung cancer and 7 to 9 for each other disease.  For current smoking, RRs (95%CIs) were lung cancer 3.59 (3.25-3.96), COPD 3.57 (2.72-4.70), IHD 2.21 (1.96-2.50) and stroke 1.40 (1.25-1.57).  Ex-smoking RRs were lower.  Data for lung cancer and IHD showed a clear tendency for RRs to rise with increasing amount smoked and decrease with increasing time quit.  Dose-response data were unavailable for COPD and unclear for stroke, where the association was weaker.  Conclusions:  Compared to studies in other Asian and Western countries, current smoking RRs were quite similar for IHD and stroke.  The comparison is not clear for COPD, where the Japanese data, mainly from cross-sectional studies, is limited.  For lung cancer, the RRs are similar to those in other Asian countries, but substantially lower than in Western countries.  Explanations for this are unclear, but less accurate reporting of smoking by Japanese may contribute to the difference.

Several studies have shown a relationship between cigarette smoking and general diseases of the nose in a large Asian population. The current study was conducted to better understand the effect of cigarette smoke exposure on rhinologic diseases in Koreans.

Data were obtained from the 2008-2011 Korea National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized population in Korea. Of the 37,753 people surveyed, 11,589 adult participants had completed questionnaires on rhinologic symptoms and smoking behaviors, had undergone nasal endoscopy, and had provided urine collection were enrolled. Rhinologic diseases investigated in this study included subjective olfactory dysfunction, rhinitis symptoms, chronic rhinosinusitis (CRS), and nasal septal deviation with obstructive symptoms. The relationship between disease and cigarette smoking was evaluated using multivariate regression analyses.

In South Korea, the weighted prevalence of subjective olfactory dysfunction, rhinitis symptoms, CRS, and nasal septal deviation with obstructive symptoms was 4.6%, 27.2%, 6.2%, and 4.0%, respectively. The only disease significantly associated with active smoking was CRS in participants 40 years of age and older after adjusting for age, sex, residency, house income, education, and occupation (adjusted odds ratio = 1.427, 95% confidence interval = 1.050 to 1.938). For each year of active smoking, CRS prevalence increased by 1.5%. None of the rhinologic diseases examined were associated with passive smoking.

Our study showed that CRS seems to be associated with active smoking in older participants. Considering the relatively high prevalence of CRS in Korea, further longitudinal researches for their association and prevention are required.

In non-smokers, haemoglobin adducts from 3- and 4-aminobiphenyl have been reported to arise mainly from exposure to environmental tobacco smoke (ETS). Therefore, the impact of self-reported smoking (n = 27) and exposure of non-smokers to ETS (n = 78) on haemoglobin adducts was studied in pregnant women from Homburg, Germany. In addition to 3- and 4-aminobiphenyl, adducts from seven monocyclic aromatic amines (aniline, o -, m -, and p -toluidine, 2,4-dimethylaniline, 2-ethylaniline and o -anisidine) and the adduct from tobacco-specific nitrosamines (4-hydroxy-1-(3-pyridyl)1-butanone) were determined. Five of 78 self-reported non-smoking women had plasma cotinine levels and urinary cotinine/creatinine ratios indicative of active smoking. In the remaining 73 non-smokers cotinine/creatinine ratios correlated significantly with self reported exposure to ETS. However, none of the haemoglobin adducts increased with increasing exposure to ETS or increasing cotinine/creatinine ratios. Although significantly elevated in smoking compared with non-smoking women, the mean haemoglobin adduct levels formed by tobacco-specific nitrosamines (54 7 8 9 vs 26 7 4 1 fmol g-1, p &lt; 0 001), 3-aminobiphenyl (3 0 0 5 vs 1 4 0 1 pg g-1, p &lt; 0 001), 4-aminobiphenyl (27 9 3 4 vs 10 2 0 7 pg g-1, p &lt; 0 001), o -toluidine (289 25 vs 237 65 pg g-1, p &lt; 0 001), p -toluidine (315 32 vs 197 13 pg g-1; p &lt; 0 001), 2,4-dimethylaniline (25 5 2 9 vs 18 6 1 6 pg g-1, p &lt; 0 05), had considerable overlappings ranges indicating lack of specificity as biomarkers to tobacco smoke exposure. Exposure to other as yet unknown environmental sources appearsto be more significant than previously thought.

National smoking-specific lung cancer mortality rates are unavailable, and studies presenting estimates are limited, particularly by histology. This hinders interpretation. We attempted to rectify this by deriving estimates indirectly, combining data from national rates and epidemiological studies.

We estimated study-specific absolute mortality rates and variances by histology and smoking habit (never/ever/current/former) based on relative risk estimates derived from studies published in the 20th century, coupled with WHO mortality data for age 70-74 for the relevant country and period. Studies with populations grossly unrepresentative nationally were excluded. 70-74 was chosen based on analyses of large cohort studies presenting rates by smoking and age. Variations by sex, period and region were assessed by meta-analysis and meta-regression.

148 studies provided estimates (Europe 59, America 54, China 22, other Asia 13), 54 providing estimates by histology (squamous cell carcinoma, adenocarcinoma). For all smoking habits and lung cancer types, mortality rates were higher in males, the excess less evident for never smokers. Never smoker rates were clearly highest in China, and showed some increasing time trend, particularly for adenocarcinoma. Ever smoker rates were higher in parts of Europe and America than in China, with the time trend very clear, especially for adenocarcinoma. Variations by time trend and continent were clear for current smokers (rates being higher in Europe and America than Asia), but less clear for former smokers. Models involving continent and trend explained much variability, but non-linearity was sometimes seen (with rates lower in 1991-99 than 1981-90), and there was regional variation within continent (with rates in Europe often high in UK and low in Scandinavia, and higher in North than South America).

The indirect method may be questioned, because of variations in definition of smoking and lung cancer type in the epidemiological database, changes over time in diagnosis of lung cancer types, lack of national representativeness of some studies, and regional variation in smoking misclassification. However, the results seem consistent with the literature, and provide additional information on variability by time and region, including evidence of a rise in never smoker adenocarcinoma rates relative to squamous cell carcinoma rates.

An objective assessment of exposure to tobacco smoke may be accomplished by means of examining particular biomarkers in body fluids. The most common biomarker of tobacco smoke exposure is urinary, or serum, cotinine. In order to distinguish non-smokers from passive smokers and passive smokers from active smokers, it is necessary to estimate cotinine cut-off points. The objective of this article was to apply statistical distribution of urinary cotinine concentration to estimate cut-off points distinguishing the three above-mentioned groups. The examined group consisted of 327 volunteers (187 women and 140 men) who were ethnically homogenous inhabitants of the same urban agglomeration (Sosnowiec, Poland). The values which enabled differentiation of the examined population into groups and subgroups were as follows: 50 microg l(-1) (differentiation of non-smokers from passive smokers), 170 microg l(-1) (to divide the group of passive smokers into two subgroups: minimally and highly exposed to environmental tobacco smoke), 550 microg l(-1) (differentiation of passive smokers from active smokers), and 2100 microg l(-1) (to divide group of active smokers into two subgroups: minimally and highly exposed to tobacco smoke). The results suggest that statistical distribution of urinary cotinine concentration is useful for estimating urinary cotinine cut-off points and for assessing the smoking status of persons exposed to tobacco smoke.

Since 1996, the tobacco industry has used the 16 Cities Study conclusions that workplace secondhand tobacco smoke (SHS) exposures are lower than home exposures to argue that workplace and other smoking restrictions are unnecessary.

Our goal was to determine the origins and objectives of the 16 Cities Study through analysis of internal tobacco industry documents and regulatory agency and court records, and to evaluate the validity of the study's conclusions.

The tobacco industry's purpose in conducting the 16 Cities Study was to develop data showing that workplace SHS exposures were negligible, using these data to stop smoking restrictions by the U.S. Occupational Safety and Health Administration. The extensive involvement of R.J. Reynolds Tobacco Company and the tobacco industry's Center for Indoor Air Research in controlling the study was not fully disclosed. The study's definition of "smoking workplace" included workplaces where smoking was restricted to designated areas or where no smoking was observed. This definition substantially reduced the study's reported average SHS concentrations in "smoking workplaces" because SHS levels in unrestricted smoking workplaces are much greater than in workplaces with designated smoking areas or where no smoking occurred. Stratifying the data by home smoking status and comparing exposures by workplace smoking status, however, indicates that smoke-free workplaces would halve the total SHS exposure of those living with smokers and virtually eliminate SHS exposure for most others.

Data in the 16 Cities Study reveal that smoke-free workplaces would dramatically reduce total SHS exposure, providing significant worker and public health benefits.

To analyse the statements given by tobacco industry defence witnesses during trial testimonies and depositions in second-hand smoke cases and in parallel, to review criticisms of epidemiology in industry-funded publications in order to identify strategies for discrediting epidemiologic evidence on passive smoking health effects.

A collection of depositions and trial testimony transcripts from tobacco industry-related lawsuits filed in the United States during the 1990s, was compiled and indexed by the Tobacco Deposition and Trial Testimony Archive (DATTA). Statements in DATTA made by expert witnesses representing the tobacco industry relating to the health effects of passive smoking were identified and reviewed. Industry-supported publications within the peer-reviewed literature were also examined for statements on exposure misclassification, meta-analysis, and confounding.

The witnesses challenged causation of adverse health effects of passive smoking by citing limitations of epidemiologic research, raising methodological and statistical issues, and disputing biological plausibility. Though not often cited directly by the witnesses, the defence tactics mirrored the strategies used in industry-funded reports in the peer-reviewed literature.

The tobacco industry attempted to redirect the focus and dialogue related to the epidemiologic evidence on passive smoking. This approach, used by industry experts in trial testimony and depositions, placed bias as a certain alternative to causation of diseases related to passive smoking and proposed an unachievable standard for establishing the mechanism of disease.

To provide a participant's account of the development of a paper commissioned by the tobacco industry examining the reliability of self reported smoking status; to redress the distorted report of this Japanese spousal smoking study which evaluated the reliability and validity of self reported smoking status, and estimated confounding by diet and lifestyle factors.

Repeated interviews on smoking status and its verification by environmental and biological markers for environmental tobacco smoke (ETS) exposure.

Urban wives in Osaka City and Sizuoka City, Japan

Semi-random sampling of 200 wives in each city. From the Osaka subjects, 100 non-smoking wives were selected for the validity study.

Kappa coefficient for reliability of self reported smoking status. Correlation coefficients between environmental nicotine concentration, cotinine in saliva and urine, and self reported smoking status.

The kappa coefficient for the repeated interview was high suggesting sufficient reliability of the response. The proportion of self reported current smokers misclassified as non-smokers was equivalent to the misclassified self reported non-smokers. Ambient concentration of nicotine and personal exposure to nicotine correlated with each other and also with salivary cotinine and self reported ETS exposure but not with urinary cotinine/creatinine ratio (CCR). There was no major difference in diet and lifestyle related to husband's smoking status.

Self reported smoking status by Japanese wives shows high reliability. It also shows high validity when verified by both nicotine exposure and salivary cotinine, but not by CCR. A previous report questioning the credibility of self reported smoking status, based on questionable CCR, could thus be of dubious validity. In addition, possible dietary and lifestyle confounding factors associated with smoking husbands were not demonstrable, a finding not reported previously. Using all the data from this project changes the conclusion of the previous published report. In addition to the distortion of scientific findings by a tobacco industry affiliated researcher, anti-smoking campaigners made attempts to intimidate and suppress scientific activities. These distortions of science should be counteracted.

Cigarette smoking during pregnancy affects the unborn fetus. This study aimed to investigate: (1) the smoking status of pregnant women before, during and after pregnancy in the Yamato and Ayase municipalities, Kanagawa, Japan; (2) the characteristics that differentiate successful spontaneous smoking quitters from continuous smokers during pregnancy; and (3) the awareness of risks of smoking that may influence smoking cessation during pregnancy. A community-based, cross-sectional survey of 420 postpartum women, who delivered their babies from July 2002 to October 2002, was performed. Out of 420 respondents, 275 (65.4%) did not smoke before and during pregnancy. Of the 145 women who smoked before pregnancy, 101 (69.3%) quit successfully while pregnant. Smoking prevalence during pregnancy was 10.4%. Out of 101 successful quitters during pregnancy, 22 (21.8%) women resumed smoking after childbirth. A multiple regression analysis showed that the independent predictors of smoking cessation during pregnancy were primiparous women and women living with non-smokers in the household. Although maternal age predicted smoking cessation in a simple regression analysis, this predictive value was lost in the multiple analysis. A simple analysis showed no significant association between the awareness of smoking risks and smoking cessation during pregnancy. It is suggested that Japanese smokers are more likely to quit while pregnant than women in other countries. In the future, smoking cessation programmes should be designed to help multiparous women and women living with smokers to give up smoking.

The examination of a single scientific manuscript seldom alerts scientists, reviewers, editors, and scientific administrators to the fabrication and falsification of data and information. This review shows that most documented cases of scientific fraud involve falsification (altering truthful information) and fabrication (inventing information where none previously existed). Plagiarism is much less frequent. The review of published accounts also shows that the publication of scientific papers containing recognizable fraudulent material is very low, probably less than 0.02% and extremely difficult to detect. Because most reported cases of fraud have involved research done at prestigious organizations with distinguished co-authors, and that is published in journals with exacting review processes, it becomes evident that some unscrupulous scientists are adept at fabricating and falsifying data. However, "significant" scientific fraud is detected when scientists repeatedly report results that cannot be independently verified, when colleagues report suspicious behavior, or scientific audits are performed. This review documents and compares many of the better-known cases of scientific fraud. Fraudulent behavior has served as the impetus for the scientific community to develop publication procedures and guidelines that help to guard against not only fraudulent behavior but also against other types of unethical or undesirable behaviors. A companion paper reviews the non-fraudulent issues associated with scientific publication.

Prenatal and postnatal exposure to tobacco smoke adversely affects maternal and child health. Secondhand smoke (SHS) has been linked causally with sudden infant death syndrome (SIDS) in major health reports. In 1992, the US Environmental Protection Agency (EPA) first noted an association between SHS and SIDS, and both prenatal exposure and postnatal SHS exposure were listed as independent risk factors for SIDS in a 1997 California EPA report (republished in 1999 by the National Cancer Institute) and a 2004 US Surgeon General report. The tobacco industry has used scientific consultants to attack the evidence that SHS causes disease, most often lung cancer. Little is known about the industry's strategies to contest the evidence on maternal and child health. In 2001, a review was published on SIDS that acknowledged funding from the Philip Morris (PM) tobacco company. Tobacco industry documents related to this review were examined to identify the company's influence on the content and conclusions of this review.

Tobacco industry documents include 40 million pages of internal memos and reports made available to the public as a result of litigation settlements against the tobacco industry in the United States. Between November 2003 and January 2004, we searched tobacco industry document Internet sites from the University of California Legacy Tobacco Documents Library and the Tobacco Documents Online website. Key terms included "SIDS" and names of key persons. Two authors conducted independent searches with similar key terms, reviewed the documents, and agreed on relevancy through consensus. Thirty documents were identified as relevant. Two drafts (an early version and a final version) of an industry-funded review article on SIDS were identified, and 2 authors independently compared these drafts with the final publication. Formal comments by PM executives made in response to the first draft were also reviewed. We used Science Citation Index in July 2004 to determine citation patterns for the referenced SIDS reviews.

PM executives feared that SHS and maternal and child health issues would create a powerful and emotional impetus for smoke-free areas in the home, public areas, and the workplace. In response to the 1992 US EPA report on SHS, the Science and Technology Department of PM's Switzerland subsidiary, Fabriques de Tabac Reunies, searched for "independent" consultants to publish articles addressing SHS. The first industry-funded article was a literature review focusing on smoking and SIDS, conducted by consultant Peter Lee and co-author Allison Thornton, which stated that the association between parental smoking and SIDS could have been attributable to the failure to control fully for confounders. That first review has only been cited once, in the subsequent industry-funded review. In 1997, PM commissioned a consultant, Frank Sullivan, to write a review, with coauthor Susan Barlow, of all possible risk factors for SIDS. The first draft concluded that prenatal and postnatal smoking exposures are both independent risk factors for SIDS. After receiving comments and meeting with PM scientific executives, Sullivan changed his original conclusions on smoking and SIDS. The final draft was changed to emphasize the effects of prenatal maternal smoking and to conclude that postnatal SHS effects were "less well established." Changes in the draft to support this new conclusion included descriptions of Peter Lee's industry-funded review, a 1999 negative but underpowered study of SIDS risk and urinary cotinine levels, and criticisms of the conclusions of the National Cancer Institute report that SHS was causally associated with SIDS. In April 2001, the Sullivan review was published in the United Kingdom journal Paediatric and Perinatal Epidemiology, with a disclosure statement that acknowledged financial support from PM but did not acknowledge contributions from PM executives in the preparation of the review. By 2004, the Sullivan SIDS review had been cited at least 19 times in the medical literature.

PM executives responded to corporate concerns about the possible adverse effects of SHS on maternal and child health by commissioning consultants to write review articles for publication in the medical literature. PM executives successfully encouraged one author to change his original conclusion that SHS is an independent risk factor for SIDS to state that the role of SHS is "less well established." These statements are consistent with PM's corporate position that active smoking causes disease but only public health officials conclude the same for SHS. The author's disclosure of industry funding did not reveal the full extent of PM's involvement in shaping the content of the article. This analysis suggests that accepting tobacco industry funds can disrupt the integrity of the scientific process. The background of this SIDS review is relevant for institutions engaged in the debate about accepting or eschewing funding from the tobacco industry. Those who support acceptance of tobacco industry funds argue that academic authors retain the right to publish their work and maintain final approval of the written product, but this argument fails to recognize that the tobacco industry funds work to ensure that messages favorable to the industry are published and disseminated. Clinicians, parents, and public health officials are most vulnerable to the changed conclusions of the SIDS review. The national SIDS "Back to Sleep" campaign has been very successful in reducing SIDS rates. However, estimates of SIDS risk from SHS (odds ratios range from 1.4 to 5.1) have considerable overlap with estimates of risk from prone sleep positioning (odds ratios range from 1.7 to 12.9). With the Back to Sleep campaign well underway, efforts to address parental smoking behavior in both the prenatal and postnatal periods should be intensified. The tobacco industry's disinformation campaign on SHS and maternal and child health can be counteracted within clinicians' offices.

To describe how the transnational tobacco industry has collaborated with local Asian tobacco monopolies and companies to promote a scientific and regulatory agenda.

Analysis of previously secret tobacco industry documents.

Transnational tobacco companies began aggressively entering the Asia market in the 1980s, and the current tobacco industry in Asia is a mix of transnational and local monopolies or private companies. Tobacco industry documents demonstrate that, in 1996, Philip Morris led an organisation of scientific representatives from different tobacco companies called the Asian Regional Tobacco Industry Science Team (ARTIST), whose membership grew to include monopolies from Korea, China, Thailand, and Taiwan and a company from Indonesia. ARTIST was initially a vehicle for PM's strategies against anticipated calls for global smoke-free areas from a World Health Organization secondhand smoke study. ARTIST evolved through 2001 into a forum to present scientific and regulatory issues faced primarily by Philip Morris and other transnational tobacco companies. Philip Morris' goal for the organisation became to reach the external scientific and public health community and regulators in Asia.

The Asian tobacco industry has changed from an environment of invasion by transnational tobacco companies to an environment of participation with Philip Morris' initiated activities. With this participation, tobacco control efforts in Asia face new challenges as Philip Morris promotes and integrates its scientific and regulatory agenda into the local Asian tobacco industry. As the local Asian tobacco monopolies and companies can have direct links with their governments, future implementation of effective tobacco control may be at odds with national priorities.

Tobacco smoke is one of the causes of oxidative stress that is leading to attenuation of the antioxidative body protective barrier by means of decreasing the levels of intra- and extracellular antioxidants. The effect of tobacco smoke on plasma levels of two main forms of Vitamin E, alpha- and gamma-tocopherol, in passive smokers (urinary cotinine concentration 50-500 microg/L) and active smokers (urinary cotinine concentration >500 microg/L) were studied. Slight, but statistically significant decreases in plasma alpha-tocopherol level in passive and active smokers in comparison with non-smokers (by 5.7% and 9.2%, respectively) were found. The plasma gamma-tocopherol levels remained unchanged. The Pearson's correlation coefficient for the plasma alpha-tocopherol level and the urinary cotinine concentration in passive and active smokers was -0.431, P = 0.004 and -0.534, P < 0.001, respectively, and for gamma-tocopherol in similar conditions -0.190, P = 0.217 and 0.346, P = 0.027, respectively. The obtained results indicate the secondary role that alpha- and gamma-tocopherol play in the process of tobacco smoke free radical scavenge, or they may also reflect the body increased anti-oxidative mobilization in response to oxidative stress evoked by tobacco smoke.

Studies of the health effects of environmental tobacco smoke (ETS) using measured air concentrations are subject to bias. Cotinine, a nicotine metabolite detected in urine, has been recommended as a quantitative measure of nicotine intake and thus as a marker for ETS exposure in humans. The aim of this study was to correlate home indoor ETS levels with passive smokers' urinary cotinine levels. The urinary cotinine concentrations of 57 non-smoking women who spend >19 h a day at home and the nicotine levels in their living room air were measured over a period of 24 h. Nicotine and urinary cotinine levels were analyzed using GC/MS and HPLC/UV, respectively. In addition, information was collected regarding the smoking habits of the subjects' families. A significant correlation was found between the nicotine levels in indoor air and the urinary cotinine to creatinine ratio of the passive smokers. The smoking habits of the subjects' family members were also correlated to the urinary cotinine levels of the passive smokers.

To review the epidemiological evidence for the association between passive smoking and lung cancer.

Primary studies and meta-analyses examining the relationship between passive smoking and lung cancer were identified through a computerised literature search of Medline and Embase, secondary references, and experts in the field of passive smoking. Primary studies meeting the inclusion criteria were meta-analysed.

From 1981 to the end of 1999 there have been 76 primary epidemiological studies of passive smoking and lung cancer, and 20 meta-analyses. There were 43 primary studies that met the inclusion criteria for this meta-analysis; more studies than previous assessments. The pooled relative risk (RR) for never-smoking women exposed to environmental tobacco smoke (ETS) from spouses, compared with unexposed never-smoking women was 1.29 (95% CI 1.17-1.43). Sequential cumulative meta-analysed results for each year from 1981 were calculated: since 1992 the RR has been greater than 1.25. For Western industrialised countries the RR for never-smoking women exposed to ETS compared with unexposed never-smoking women, was 1.21 (95% CI 1.10-1.33). Previously published international spousal meta-analyses have all produced statistically significant RRs greater than 1.17.

The abundance of evidence in this paper, and the consistency of findings across domestic and workplace primary studies, dosimetric extrapolations and meta-analyses, clearly indicates that non-smokers exposed to ETS are at increased risk of lung cancer.

The recommended public health policy is for a total ban on smoking in enclosed public places and work sites.

To validate a detailed questionnaire for assessment of environmental tobacco smoke (ETS) exposure by the biomarker cotinine in various media, a population-based study in the urban area of Malmö, Sweden was performed in children aged 8-13 years with and without asthmatic symptoms. There were strong correlations between urinary and saliva cotinine concentrations and also, though to a lesser extent, between these media and plasma. Even a detailed questionnaire gave only a rough picture of the ETS exposure, as indicated by the biomarkers. In a multivariate model, the most significant questionnaire-derived predictor of the cotinine levels was the maternal smoking habits; other questionnaire variables gave only a minimal explained variance. Children with a history of asthmatic symptoms had statistically significantly lower median cotinine levels in urine and saliva compared to referent children, most likely because of the antismoking information to their parents. This should be considered in epidemiological studies of ETS risks.

Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population.

Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke.

When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure.

A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).

Lung cancer in younger people is uncommon and has characteristics that distinguish it from cancer in older patients. The percentage of smokers among younger patients ranges from 40% to 50% in Asia to 90% in Western countries. The prognosis for young patients with this disease is controversial.

Medical records of 91 young (40 years of age or younger) and 3,221 older (more than 40 years of age) Japanese patients with lung cancer were reviewed to compare smoking habits, distribution of histopathologic types, clinical stage, and survival.

Among female patients, only 39% were smokers in both age groups, whereas smokers were less common among the young male patients (84%) than the older male patients (95%) (p < 0.0001). Adenocarcinomas were diagnosed in 92% of the young and 73% of the older female patients (p = 0.021) versus only 71% and 42% of the corresponding male patients (p < 0.0001). There was no difference in tumor extent or survival between the two groups of female patients. In the male groups, advanced disease (stages IIIB and IV) was more common in the young patients (75%) than in the older patients (54%) (p = 0.0031), but there was no survival difference between the two groups.

Young male and female lung cancer patients in Japan have different characteristics from each other and from older patients of the same sex. Their survival did not differ from that of older patients.

Since 1981, numerous epidemiological studies have investigated the relationship between passive smoking and lung cancer in nonsmokers. The overall evidence, predominantly relating to women, indicates a weak association with the husband's smoking and many reviewers have concluded that this demonstrates a causal effect of exposure to environmental tobacco smoke (ETS). Interpreting weak associations is notoriously difficult, however, and this paper reviews problems specific to the ETS-lung cancer relationship. After describing how to select relevant studies and appropriate data, the methods for combining evidence together ('meta-analysis') are discussed, and the need to investigate sources of heterogeneity is emphasized. Separate consideration is given to various forms of bias that may affect overall relative risk estimates, including misclassification of active smoking status, confounding, systematic case-control differences, recall bias, diagnostic bias and publication bias. Sections on dose-response, multiple ETS exposure sources and other issues follow. The problems are illustrated from the available literature. It is shown there is no significant association of lung cancer with workplace, childhood or social ETS exposure or with smoking by the wife. Though statistically significant, the association with husband's smoking is weak and heterogeneous and varies widely according to various study characteristics. The association is markedly weakened by the adjustment for smoking misclassification bias and is likely to be affected by confounding and other sources of bias. While the precise extent of all the biases remains unclear, it seems impossible to conclude with any certainty that ETS causes lung cancer.