Evidence relating cigarette,cigar and pipe smoking to lung cancer and chronic obstructive pulmonary disease:Meta-analysis of recent data from three regions

BACKGROUND There is a need to have up-to-date information for various diseases on the risk related to the use of different smoked products and the use of other nicotinecontaining products.Here,we contribute to the information pool by presenting up-to-date quantitative evidence for North America,Europe and Japan and for both lung cancer and chronic obstructive pulmonary disease(COPD)on the relative risk(RR)relating to current vs never product use for each of the three smoked tobacco products,cigarettes,cigars and pipes.AIM To estimate lung cancer and COPD current smoking RRs for the three products using recent data for the three regions.METHODS Publications in English from 2010 to 2020 were considered that,based on epidemiological studies in the three regions,estimated the current smoking RR of lung cancer and/or COPD for one or more of the three products.The studies should involve at least 100 cases of the disease considered,not be restricted to specific lung cancer types or populations with specific medical conditions,and should be of cohort or nested case-control study design or randomized controlled trials.Literature searches were conducted on MEDLINE separately for lung cancer and for COPD,examining titles and abstracts initially,and then full texts.Additional papers were sought from reference lists of selected papers,reviews and metaanalyses.For each study identified,the most recent available data on each product were entered on current smoking,as well as on characteristics of the study and the RR estimates.Combined RR estimates were derived using random-effects meta-analysis.For cigarette smoking,where far more data were available,heterogeneity was studied by a wide range of factors.For cigar and pipe smoking,a more limited heterogeneity analysis was carried out.Results were compared with those from previous meta-analyses published since 2000.RESULTS Current cigarette smoking:For lung cancer,44 studies(26 North American,14 European,three Japanese,and one in multiple continents),gave an overall estimate of 12.14[95%confidence interval(CI)10.30-14.30].The estimates were higher(heterogeneity P<0.001)for North American(15.15,CI 12.77-17.96)and European studies(12.30,CI 9.77-15.49)than for Japanese studies(3.61,CI 2.87-4.55),consistent with previous evidence of lower RRs for Asia.RRs were higher(P<0.05)for death(14.85,CI 11.99-18.38)than diagnosis(10.82,CI 8.61-13.60).There was some variation(P<0.05)by study population,with higher RRs for international and regional studies than for national studies and studies of specific populations.RRs were higher in males,as previously reported,the within-study male/female ratio of RRs being 1.52(CI 1.20-1.92).RRs did not vary significantly(P≥0.05)by other factors.For COPD,RR estimates were provided by 18 studies(10 North American,seven European,and one Japanese).The overall estimate of 9.19(CI 6.97-12.13),was based on heterogeneous data(P<0.001),and higher than reported earlier.There was no(P>0.1)variation by sex,region or exclusive use,but limited evidence(0.05<P<0.1)that RR estimates were greater where cases occurring shortly after baseline were ignored;where bronchiectasis was excluded from the COPD definition;and with greater confounder adjustment.Within-study comparisons showed adjusted RRs exceeded unadjusted RRs.Current cigar smoking:Three studies gave an overall lung cancer RR of 2.73(CI 2.36-3.15),with no heterogeneity,lower than the 4.67(CI 3.49-6.25)reported in an earlier review.Only one study gave COPD results,the RR(2.44,CI 0.98-6.05)being imprecise.Current pipe smoking:Four studies gave an overall lung cancer RR of 4.93(CI 1.97-12.32),close to the 5.20(CI 3.50-7.73)given earlier.However,the estimates were heterogeneous,with two above 10,and two below 3.Only one study gave COPD results,the RR(1.12,CI 0.29-4.40),being imprecise.For both diseases,the lower RR estimates for cigars and for pipes than for current smoking of cigarettes aligns with earlier published evidence.CONCLUSION Current cigarette smoking substantially increases lung cancer and COPD risk,more so in North America and Europe than Japan.Limited evidence confirms lower risks for cigars and pipes than cigarettes.

Misclassification of smoking habits:An updated review of the literature

BACKGROUND Misclassification of smoking habits leads to underestimation of true relationships between diseases and active smoking, and overestimation of true relationships with passive smoking. Information on misclassification rates can be obtained from studies using cotinine as a marker.AIM To estimate overall misclassification rates based on a review and meta-analysis of the available evidence, and to investigate how misclassification rates depend on other factors.METHODS We searched for studies using cotinine as a marker which involved at least 200 participants and which provided information on high cotinine levels in selfreported non-, never, or ex-smokers or on low levels in self-reported smokers. We estimated overall misclassification rates weighted on sample size and investigated heterogeneity by various study characteristics. Misclassification rates were calculated for two cotinine cut points to distinguish smokers and nonsmokers, the higher cut point intended to distinguish regular smoking.RESULTS After avoiding double counting, 226 reports provided 294 results from 205 studies. A total of 115 results were from North America, 128 from Europe, 25 from Asia and 26 from other countries. A study on 6.2 million life insurance applicants was considered separately. Based on the lower cut point, true current smokers represented 4.96%(95% CI 4.32-5.60%) of reported non-smokers, 3.00%(2.45-3.54%) of reported never smokers, and 10.92%(9.23-12.61%) of reported exsmokers. As percentages of true current smokers, non-, never and ex-smokers formed, respectively, 14.50%(12.36-16.65%), 5.70%(3.20-8.20%), and 8.93%(6.57-11.29%). Reported current smokers represented 3.65%(2.84-4.45%) of true non-smokers. There was considerable heterogeneity between misclassification rates.Rates of claiming never smoking were very high in Asian women smokers, the individual studies reporting rates of 12.5%, 22.4%, 33.3%, 54.2% and 66.3%. False claims of quitting were relatively high in pregnant women, in diseased individuals who may recently have been advised to quit, and in studies considering cigarette smoking rather than any smoking. False claims of smoking were higher in younger populations. Misclassification rates were higher in more recently published studies. There was no clear evidence that rates varied by the body fluid used for the cotinine analysis, the assay method used, or whether the respondent was aware their statements would be validated by cotinine-though here many studies did not provide relevant information. There was only limited evidence that rates were lower in studies classified as being of good quality,based on the extent to which other sources of nicotine were accounted for.CONCLUSION It is important for epidemiologists to consider the possibility of bias due to misclassification of smoking habits, especially in circumstances where rates are likely to be high. The evidence of higher rates in more recent studies suggests that the extent of misclassification bias in studies relating passive smoking to smoking-related disease may have been underestimated.

Exclusive cigar smoking in the United States and smoking-related diseases: A systematic review

BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating exclusive cigar smoking to risk of the major smoking-related diseases.METHODS Literature searches detected studies carried out in the United States which estimated the risk of lung cancer,chronic obstructive pulmonary disease(COPD),heart disease,stroke or overall circulatory disease in exclusive cigar smokers as compared to those who had never smoked any tobacco product.Papers were identified from reviews and detailed searches on MEDLINE.For each study,data were extracted onto a study database and a linked relative risk database.Relative risks and 95%CIs were extracted,or estimated,relating to current,former or ever exclusive cigar smokers,and meta-analysed using standard methods.Sensitivity analyses were conducted including or excluding results from studies that did not quite fit the full selection criteria(for example,a paper presenting combined results from five studies,where 86%of the population were in the United States).RESULTS The literature searches identified 17 relevant publications for lung cancer,four for COPD and 12 for heart disease,stroke and circulatory disease.These related to 11 studies for lung cancer,to four studies for COPD and to eight studies for heart disease,stroke or overall circulatory disease.As some studies provided results for more than one disease,the total number of studies considered was 13,with results from four of these used in sensitivity analyses.There was evidence of significant heterogeneity in some of the meta-analyses so the random-effects estimates are summarized below.As the results from the sensitivity analyses were generally very similar to those from the main analyses,and involved more data,only the sensitivity results are summarized below.For lung cancer,relative risks(95%CI)for current,former and ever smokers were respectively,2.98(2.08 to 4.26),1.61(1.23 to 2.09),and 2.22(1.79 to 2.74)based on 6,4 and 10 individual study estimates.For COPD,the corresponding estimates were 1.44(1.16 to 1.77),0.47(0.02 to 9.88),and 0.86(0.48 to 1.54)based on 4,2 and 2 estimates.For ischaemic heart disease(IHD)the estimates were 1.11(1.04 to 1.19),1.26(1.03 to 1.53)and 1.15(1.08 to 1.23)based on 6,3 and 4 estimates,while for stroke they were 1.02(0.92 to 1.13),1.08(0.85 to 1.38),and 1.11(0.95 to 1.31)based on 5,3 and 4 estimates.For overall circulatory disease they were 1.10(1.05 to 1.16),1.11(0.84 to 1.46),and 1.15(1.06 to 1.26)based on 3,3 and 4 estimates.CONCLUSION Exclusive cigar smoking is associated with an increased risk of lung cancer,and less so with COPD and IHD.The increases are lower than for cigarettes.

Systematic review with meta-analysis of the epidemiological evidence in Europe,Israel,America and Australasia on smoking and COVID-19

BACKGROUND Previous meta-analyses related smoking to death or severe infection from coronavirus disease 2019(COVID-19)in hospitalized patients,but considered only a few studies,did not adjust for demographics and comorbidities,and inadequately defined smoking.AIM To review and meta-analyse epidemiological evidence on smoking and COVID-19,considering a range of endpoints,populations and smoking definitions and the effect of adjustment.METHODS Studies were identified from publications in English up to 30 September,2020 involving at least 100 individuals,carried out in Europe,Israel,America or Australasia,not restricted to those with specific other diseases,and providing information relating smoking to various COVID-related endpoints.Meta-analyses were carried out for combinations of population and endpoint,with variation studied by smoking definition,adjustment level and other factors.RESULTS From 96 publications,74 studies were identified,37 in the United States,10 in the United Kingdom,with up to four in the other countries.Three involved over a million individuals,and 37 involved less than a thousand.Adjusted results for smoking were available in 42 studies,with adjustment not considered in 20 studies.Results were considered by endpoint.No significant effect of smoking on COVID-19 positivity was seen in the general population,but there was a reduced risk in those tested.Best-adjusted estimates for current(vs never)smoking were 0.87(95%confidence interval:0.52-1.47)in the general population and 0.52(0.43-0.64)in those tested.For those hospitalized due to COVID-19,unadjusted rates were significantly increased in current smokers(1.20,1.01-1.42)and ever smokers(1.64,1.41-1.91),but those adjusted for comorbidities showed no increase for current(0.82,0.52-1.30)or ever smokers(1.00,0.76-1.32).There was little evidence to suggest that smoking was associated with intensive care admission.For those hospitalized with COVID-19,best-adjusted estimates were 0.88(0.72-1.08)for current smokers and 1.10(0.99-1.22)for ever smokers.In those hospitalized with COVID-19,smoking was not significantly related to subsequent mechanical ventilation,with best-adjusted estimates of 1.12(0.60-2.09)for current smokers and 1.05(0.88-1.25)for ever smokers.For those hospitalized with severe COVID-19,best-adjusted estimates were 0.74(0.49-1.12)for current smokers and 1.15(0.87-1.51)for ever smokers;few estimates were adjusted for comorbidities.While smoking was associated with increased mortality in unadjusted analyses,the association disappeared after adjustment for comorbidities.For example,in those hospitalized with COVID-19,the unadjusted estimate for ever smokers of 1.59(1.37-1.83)reduced to 1.07(0.82-1.38)when adjusted for comorbidities.Studies on those with severe COVID-19 showed that smoking tended to be associated with worsening of the disease.However,no estimate was adjusted,even for demographics.Estimates did not clearly vary by location or study size,and there was too little evidence to usefully study variations by age,amount smoked or years quit.CONCLUSION The increased COVID-19 death rate in smokers seen in unadjusted analyses disappears following adjustment for demographics and comorbidities.Among those tested,smoking is associated with lower COVID-19 infection rates.

Review with meta-analysis relating North American,European and Japanese snus or smokeless tobacco use to major smoking-related diseases

BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and stroke,far less information is available on risks from moist snuff(“snus”)or smokeless tobacco(ST)in United States/Canada,Europe or Japan.AIM To summarize data from the selected countries on risks of the four diseases associated with current ST or snus use.METHODS Publications in English in 1990-2020 were considered that,based on epidemiological studies in North America,Europe or Japan,estimated risks of lung cancer,COPD,IHD/AMI,or stroke according to use of ST or snus.The studies should involve at least 100 cases of the disease considered,and not be restricted to those with specific other diseases.Medline literature searches were conducted,selecting papers initially from examination of titles and abstracts,and then from full texts.Further papers were sought from reference lists in selected papers,reviews and meta-analyses.For each disease,relative risk estimates adjusted at least for age were extracted relating ST or snus use to risk,and combined using random-effects meta-analysis.The estimates were mainly for current vs.never or non-current use,but results for ever vs never use were also considered.RESULTS Seven publications reported results for ST use from six United States studies.The most useful results came from four studies which provided results for current vs.never use.Random-effects meta-analyses of these results showed an increased risk for each disease,clearest for lung cancer(relative risk 1.59,95%confidence interval 1.06-2.39,based on 4 estimates)and COPD(1.57,1.09-2.26,n=3),but also significant(at P<0.05)for IHD(1.26,1.10-1.45,n=4)and stroke(1.27,1.03-1.57,n=4).Also including results for ever vs.never use from two other studies increased the lung cancer estimate to 1.80(1.23-2.64,n=6),but had little effect on the other estimates.For snus,16 publications described results from 12 studies,one in Norway and the rest in Sweden.There were no results for COPD,and only three for lung cancer,with these reporting a relative risk of 0.80(0.40-1.30)for current vs never use.More extensive data were available for IHD/AMI and stroke.Using the latest results from each study,combined estimates for current vs.never use were 1.00(0.91-1.11,n=5)for IHD/AMI and 1.05(0.95-1.17,n=2)for stroke,while for current vs.non-current use they were 1.10(0.92-1.33,n=9)for IHD/AMI and 1.12(0.86-1.45,n=9)for stroke.Meta-analyses including earlier results from some studies also showed no significant association between snus use and IHD/AMI or stroke.No relevant results were found for Japan.CONCLUSION Risks of smoking-related diseases from snus use in Scandinavia are not demonstrated,while those from ST use in the United States are less than from smoking.