Smoking cessation and subsequent risk of cancer: A pooled analysis of eight population-based cohort studies in Japan

BackgroundAlthough East Asia is one of the largest tobacco-epidemic regions in the world, only a few prospective studies from Asia have investigated the impact of smoking and cessation of smoking on cancer. We aimed to assess the effect of cessation of smoking on the risk of cancer using eight population-based cohort studies in Japan.MethodsWe analyzed pooled data from eight population-based prospective cohort studies in Japan with more than 320,000 participants to assess the effect of smoking cessation on the risk of total cancers and smoking-related cancers.ResultsAfter adjustment for potential confounders, cancer risks in men with >21 years of smoking cessation before baseline were found to decrease to the same level as never smokers for total cancer (never smokers: reference; former smokers with ≥21 years since smoking cessation: HR, 1.01; 95%CI: 0.91, 1.11). Even men who are heavy smokers (more than 20 pack-years) reported a reduced risk of total cancer (never smokers: reference; former smokers with ≥21 years since smoking cessation: HR, 1.06; 95%CI: 0.92, 1.23). In women, the risk of total cancer did not differ from that of never smokers after 11 years of smoking cessation before baseline (never smokers: reference; former smokers with ≥11 years since smoking cessation: HR, 0.96; 95%CI: 0.74, 1.23).ConclusionsOur study suggests that longer duration of smoking cessation may attenuate the risk of cancer in both men and women, and that even heavy smokers (more than 20 pack-years) were found to benefit from quitting smoking.     

Hospital-based tobacco treatment for inpatients with a history of cancer

ObjectiveTo describe treatment engagement and outcomes of patients who smoke with cancer and received tobacco cessation treatment during hospitalization.MethodWe analyzed treatment engagement and cessation outcomes for hospitalized patients who smoke with a current or former history of cancer receiving treatment from an inpatient tobacco treatment service between July, 2018 to October, 2019.ResultsThe service treated 407 inpatients. Patients had an overall high level of interest in quitting (7.6, 0–10 scale). One in three accepted cessation pharmacotherapies during hospitalization or at discharge (35%) and/or referral to the state tobacco quitline (37%). Of 189 patients reached at one-month post-discharge, 73 (39%) reported tobacco abstinence (18% intent to treat—ITT—quit rate); 35.5% had used cessation pharmacotherapy and 6.5% had engaged in quitline counseling. Of 151 patients reached at 6 months post-discharge, 29% reported abstinence (11%, ITT).ConclusionInpatients with a history of cancer are interested in quitting. Post-discharge quit rates and pharmacotherapy use were high but quitline use was low. Hospitalization is an under-utilized, prime treatment opportunity and teachable moment for people with a history of cancer who continue to use tobacco.     

Associations of smoking cessation with visceral fat area and prevalence of metabolic syndrome in men: the Hitachi health study

Weight gain after smoking cessation may deteriorate metabolic risk profiles, including that for metabolic syndrome. How risk profiles change according to the duration of smoking cessation and whether the visceral fat area (VFA) or the subcutaneous fat area (SFA) contributes to these changes remains uncertain. The subjects comprised 5,697 Japanese men who underwent an abdominal computed-tomography examination during a health check-up. Using never smokers as a reference group, the odds ratios of having metabolic syndrome and its components, defined using the National Cholesterol Education Program Adult Treatment Panel IIIcriteria, were calculated for each smoking category with adjustments for age, alcohol drinking, and physical activity (model 1) using a logistic regression analysis. Additional adjustments were also made for either VFA (model 2) or SFA (model 3). Current smokers had the lowest VFA (120.4 cm2) whereas ex-smokers (124.0-132.0 cm2) had a higher VFA than nonsmokers (123.1 cm2). Among the ex-smokers, VFA tended to decrease with increasing years of smoking cessation. In model 1, the odds ratios of having metabolic syndrome for current smokers and ex-smokers with smoking cessation for ≤ 4, 5-9, 10-14, and ≥ 15 years were 1.02, 1.33, 1.36, 1.40, and 1.09, respectively. The elevated odds ratios among ex-smokers (≤ 14 years) were reduced by 35-55.6% after further adjustment for VFA but not for SFA. Smoking cessation is associated with a deterioration of the metabolic risk profile, which can be ascribed, at least in part, to an increase in VFA not SFA.     

Determinants of Smoking and Quitting in HIV-Infected Individuals

BackgroundCigarette smoking is widespread among HIV-infected patients, who confront increased risk of smoking-related co-morbidities. The effects of HIV infection and HIV-related variables on smoking and smoking cessation are incompletely understood. We investigated the correlates of smoking and quitting in an HIV-infected cohort using a validated natural language processor to determine smoking status.MethodWe developed and validated an algorithm using natural language processing (NLP) to ascertain smoking status from electronic health record data. The algorithm was applied to records for a cohort of 3487 HIV-infected from a large health care system in Boston, USA, and 9446 uninfected control patients matched 3:1 on age, gender, race and clinical encounters. NLP was used to identify and classify smoking-related portions of free-text notes. These classifications were combined into patient-year smoking status and used to classify patients as ever versus never smokers and current smokers versus non-smokers. Generalized linear models were used to assess associations of HIV with 3 outcomes, ever smoking, current smoking, and current smoking in analyses limited to ever smokers (persistent smoking), while adjusting for demographics, cardiovascular risk factors, and psychiatric illness. Analyses were repeated within the HIV cohort, with the addition of CD4 cell count and HIV viral load to assess associations of these HIV-related factors with the smoking outcomes.ResultsUsing the natural language processing algorithm to assign annual smoking status yielded sensitivity of 92.4, specificity of 86.2, and AUC of 0.89 (95% confidence interval [CI] 0.88–0.91). Ever and current smoking were more common in HIV-infected patients than controls (54% vs. 44% and 42% vs. 30%, respectively, both P<0.001). In multivariate models HIV was independently associated with ever smoking (adjusted rate ratio [ARR] 1.18, 95% CI 1.13–1.24, P <0.001), current smoking (ARR 1.33, 95% CI 1.25–1.40, P<0.001), and persistent smoking (ARR 1.11, 95% CI 1.07–1.15, P<0.001). Within the HIV cohort, having a detectable HIV RNA was significantly associated with all three smoking outcomes.ConclusionsHIV was independently associated with both smoking and not quitting smoking, using a novel algorithm to ascertain smoking status from electronic health record data and accounting for multiple confounding clinical factors. Further research is needed to identify HIV-related barriers to smoking cessation and develop aggressive interventions specific to HIV-infected patients.     

Patterns of airway inflammation and MMP-12 expression in smokers and ex-smokers with COPD

Background

Smoking activates and recruits inflammatory cells and proteases to the airways. Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema. However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown. We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago.

Methods

39 COPD outpatients – smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups. IS and BAL samples were obtained for differential and MMP-12⁺-macrophages count analysis.

Results

The number of IS neutrophils was higher in both COPD groups compared to both controls. The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers. The number of BAL MMP-12⁺-macrophages was higher in COPD smokers (1.6 ± 0.3 × 10⁶/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 10⁶/ml respectively, p < 0.05).

Conclusion

The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation. Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients.     

Cancer risk among young men with weight gain after smoking cessation: A population-based cohort study

BackgroundSmoking cessation may help the current smokers to reduce cancer risk. However, weight gain following smoking cessation may attenuate the protective association of cessation with cancer.Patients and methodsOur study included 1,278,794 men who were aged 20–39 years and underwent two consecutive health examinations by the National Health Insurance Service, without previous diagnosis of cancer. Participants were categorized into continual smokers, quitters with different degree of body weight change, and never smokers based on the biennial national health screening program (2002–2003 and 2004–2005) and were followed from January 1, 2006 to December 31, 2015. Cox proportional hazard models and restricted cubic spline model was used to evaluate the association of post-cessation weight change and cancer risk after adjustment for potential confounders.ResultsDuring the 10 years of follow-up, the analyses included 1,278,794 men with 21,494 cancer incidences. Compared to continual smokers, quitters without weight gain of 2.0 kg had significantly lower risk of obesity-related cancer (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97), smoking-related cancer (HR, 0.90; 95% CI, 0.83 to 0.98), and gastrointestinal cancer (HR, 89; 95% CI, 0.80 to 0.98). Weight gain among quitters attenuated the risk reduction of cancer compared to continual smoking. Among quitters, weight gain up to 5.0 kg with smoking cessation showed protective association with cancer risk among quitters without weight gain.ConclusionExcessive weight gain with smoking cessation among quitters was not associated with reduced risk of several cancer types. This association should be taken into account when recommending smoking cessation to prevent cancer     

The Views and Experiences of Smokers Who Quit Smoking Unassisted. A Systematic Review of the Qualitative Evidence

BackgroundUnassisted cessation – quitting without pharmacological or professional support – is an enduring phenomenon. Unassisted cessation persists even in nations advanced in tobacco control where cessation assistance such as nicotine replacement therapy, the stop-smoking medications bupropion and varenicline, and behavioural assistance are readily available. We review the qualitative literature on the views and experiences of smokers who quit unassisted.MethodWe systematically searched for peer-reviewed qualitative studies reporting on smokers who quit unassisted. We identified 11 studies and used a technique based on Thomas and Harden’s method of thematic synthesis to discern key themes relating to unassisted cessation, and to then group related themes into overarching concepts.FindingsThe three concepts identified as important to smokers who quit unassisted were: motivation, willpower and commitment. Motivation, although widely reported, had only one clear meaning, that is ‘the reason for quitting’. Willpower was perceived to be a method of quitting, a strategy to counteract cravings or urges, or a personal quality or trait fundamental to quitting success. Commitment was equated to seriousness or resoluteness, was perceived as key to successful quitting, and was often used to distinguish earlier failed quit attempts from the final successful quit attempt. Commitment had different dimensions. It appeared that commitment could be tentative or provisional, and also cumulative, that is, commitment could be built upon as the quit attempt progressed.ConclusionA better understanding of what motivation, willpower and commitment mean from the smoker’s perspective may provide new insights and direction for smoking cessation research and practice.     

Smoking Habits of Men Employed in Industry,and Mortality

A study of the relation between smoking habits and lung cancer in male industrial workers over a period of three years has confirmed the earlier findings in doctors that the death-rate from lung cancer correlates closely with the number of cigarettes smoked. Of 54,460 men studied 68.7% were current cigarette smokers. The annual mortality rate from lung cancer was 0.33 per thousand in non-smokers and ex-smokers, and 1.2 per thousand for all cigarette smokers, and higher in heavy smokers.Heavy cigarette smokers who retained the cigarette in the mouth between puffs (“drooping” cigarette habit) had an annual mortality rate of 4.1 per thousand.The mortality from coronary thrombosis in smokers was nearly three times that in non-smokers. A mortality gradient with rising consumption of cigarettes was observed.Some correlation between smoking and cancer of other sites and from non-neoplastic lung disease was observed in older men, but no correlation was found with other cardiovascular diseases and cerebrovascular diseases.     

Cigarette Smoke Decreases the Maturation of Lung Myeloid Dendritic Cells

BackgroundConflicting data exist on the role of pulmonary dendritic cells (DCs) and their maturation in patients with chronic obstructive pulmonary disease (COPD). Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer.ResultsCOPD was diagnosed in 43 patients (16 current smokers and 27 former smokers), whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers). The number and maturation of DCs did not differ significantly between COPD and non-COPD patients. However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively). Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects.ConclusionsCigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung.     

Risk factors associated with head and neck cancer in former smokers: A Brazilian multicentric study

BackgroundReduced tobacco consumption in the population has not been associated with reduced incidence rates of head and neck cancer in several countries.ObjectiveTo explore the associations between HNC and sociodemographic characteristics and lifestyle of former smokers from three Brazilian cancer centers.MethodsA multicenter case-control study was conducted with 229 former smokers diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, larynx, and 318 controls (former smokers without head and neck cancer). Bivariate and multiple logistic regression analyses were conducted to estimate odds ratios (ORs) with a 95% confidence interval (CI).Results11–20 years after smoking cessation showed significant impact on HNC reduction (OR 0.22, 95% CI, 0.12–0.39), which reached 82% (95% CI, 0.09–0.35) among 20 + former smokers when compared to individuals who had stopped smoking for up to 5 years. A history of high-intensity smoking (>40 pack-years) increased HNC risk by 2.09 times (95% CI 1.13–3.89) when compared to subjects who smoked up to 20 pack-years. Past alcohol consumption (OR 1.99, 95% CI, 1.06–3.82) was also associated with head and neck cancer risk in former smokers when compared to no alcohol consumption. There was a decreased head and neck cancer risk in former smokers who had high school level of education (OR 0.38, 95% CI, 0.16–0.91) compared to illiterate former smokers; and former smokers with moderate intake of vegetables (OR 0.49, 95% CI, 0.28–0.85) and fruits (OR 0.43, 95% CI, 0.25–0.73) compared to those with low intake.ConclusionHead and neck cancer risk in former smokers decreases after 11 years after smoking cessation, former smokers with past alcohol consumption showed an increased risk of HNC. High school level of education and moderate intake of vegetables and fruits reduced HNC risk among former smokers.     

Planning elective operations on patients who smoke: survey of North American plastic surgeons.

Patient smoking status affects many aspects of plastic surgery, including patient selection, counseling, management, and outcomes. No specific recommendations for performing elective procedures on patients who smoke are available. The goal of this study was to determine the current practice standards and attitudes toward this often controversial topic. In September of 2000, 1600 members of the American Society for Aesthetic Plastic Surgery were sent questionnaires, 955 of which were returned. Questions elicited categorical answers, either dichotomous or multiple choice. Data were evaluated using logistic regression and the chi-square and binomial tests. Our results show that 60 percent (p < 0.01) of plastic surgeons routinely perform a less than optimal procedure on their patients who smoke. The survey measured willingness to perform various operative procedures on patients who smoke and types of smoking cessation aids offered. Of those physicians who require patients to quit smoking before surgery, only 16.7 percent (p < 0.01) would perform a nicotine test if they suspected noncompliance. Interestingly, 28.6 percent (p < 0.01) of the physicians responding admit to a smoking history, whereas only 1.5 percent (p < 0.01) continue to smoke, compared with the national smoking rate of almost 25 percent. Physicians who are previous smokers are less likely to offer smoking cessation aids than those who have never smoked, and the proportion not offering aids increases as the amount of previous smoking increases (p = 0.02). This study shows that a wide range of opinions exists on which elective surgical procedures should be performed on patients who smoke. Furthermore, the physician's prior smoking history influences this decision. No clear consensus exists on how best to treat patients who smoke who request elective surgeries. Although surgeons would prefer to operate on nonsmokers, they are faced with a significant population of patients who use tobacco. No clear consensus exists on how best to treat these individuals. Advancements in wound healing research and smoking cessation aids will provide more insight into this treatment dilemma.     

Smoking enhances the expression of angiotensin-converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection

Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers. The ACE2 expression level of ex-smokers who smoked cigarettes until recently (cessation period shorter than 6 months) was higher than that of nonsmokers and ex-smokers with a long history of nonsmoking (cessation period longer than 6 months). We also showed that the efficiency of SARS-CoV-2 infection was enhanced in a manner dependent on the angiotensin-converting enzyme 2 (ACE2) expression level. Using RNA-seq analysis on the lungs of smokers, we identified that the expression of inflammatory signaling genes was correlated with ACE2 expression. Notably, with increasing duration of smoking cessation among ex-smokers, not only ACE2 expression level but also the expression levels of inflammatory signaling genes decreased. These results indicated that smoking enhances the expression levels of ACE2 and inflammatory signaling genes. Our data suggest that the efficiency of SARS-CoV-2 infection is enhanced by smoking-mediated upregulation of ACE2 expression level.     

Cotinine levels and self-reported smoking status in patients attending a bronchoscopy clinic.

The reliability of self-reported smoking behaviour can vary and may result in bias if errors in misclassification vary with outcome. We examined whether self-report was an accurate measure of current smoking status in patients with malignant or non-malignant respiratory disease. Smoking behaviour was assessed by self-report and by analysis of whole blood for cotinine, a biomarker of exposure to cigarette smoke, in 166 patients attending a bronchoscopy clinic. Cotinine levels ranged from 2.5 to >400 ng ml(-1) blood and were higher in self-reported current smokers (173+/-123 ng ml(-1)) than in never smokers (3.7+/-8.7 ng ml(-1)) or ex-smokers (20.5+/-49.0 ng ml(-1)). Cotinine levels in self-reported current smokers increased with the numbers of cigarettes smoked (p=0.06), and levels in smokers and ex-smokers decreased with the reported length of time since the last cigarette (p=0.001). Using a cotinine level of 20 ng ml(-1) and self-report as the gold standard, the sensitivity and specificity for defining current smoking status were 90.2% and 82.4%, respectively. Out of a total of 125 self-reported current non-smokers, 23 (18.4%) had cotinine levels greater than 20 ng ml(-1). Smoking prevalence was significantly underestimated by self-report (24.7%) when compared with that defined using blood cotinine levels (36.1%: p<0.001). Misclassification of current smoking status was particularly high in ex-smokers, in patients without malignant respiratory disease, in men, and in those below the median age. Such differential misclassification may result in bias in studies examining associations between current smoking habits and disease risk.     

Cigarette smoking in male patients with chronic schizophrenia in a Chinese population: prevalence and relationship to clinical phenotypes

The high prevalence of smoking in schizophrenia of European background may be related to smoking's reducing clinical symptoms and medication side effects. Because smoking prevalence and its associations with clinical phenotypes are less well characterized in Chinese than European patients with schizophrenia, we assessed these smoking behaviors using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND) in 776 Chinese male schizophrenia and 560 control subjects. Patients also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). We found that the schizophrenia patients had a higher lifetime incidence of smoking (79% vs 63%), were more likely to be heavy smokers (61% vs 31%), and had lower smoking cessation rates (4% vs 9%) (all p<0.0001) than controls. Among the schizophrenia patients smoking prevalence increased with age, with the largest difference from controls in the age cohort of 55-75 years: 75% vs 46% (p<0.0001). Among the schizophrenia smokers 73% started to smoke before the onset of their illness by an average of 7.6 years. The patients with schizophrenia who were current smokers scored significantly lower on the PANSS negative symptom subscore (p<0.005), and on the SAES symptom scale (p<0.04; Bonferroni corrected p>0.05) than the non-smoking patients. These results suggest that Chinese males with schizophrenia smoke more frequently than the general population. Further, smokers with schizophrenia may display fewer negative symptoms and possibly less parkinsonism than non-smokers with schizophrenia.     

Cotinine levels and self-reported smoking status in patients attending a bronchoscopy clinic

The reliability of self-reported smoking behaviour can vary and may result in bias if errors in misclassification vary with outcome. We examined whether self-report was an accurate measure of current smoking status in patients with malignant or non-malignant respiratory disease. Smoking behaviour was assessed by self-report and by analysis of whole blood for cotinine, a biomarker of exposure to cigarette smoke, in 166 patients attending a bronchoscopy clinic. Cotinine levels ranged from 2.5 to &gt;400 ng ml^?1 blood and were higher in self-reported current smokers (173±123 ng ml^?1) than in never smokers (3.7±8.7 ng ml^?1) or ex-smokers (20.5±49.0 ng ml^?1). Cotinine levels in self-reported current smokers increased with the numbers of cigarettes smoked (p=0.06), and levels in smokers and ex-smokers decreased with the reported length of time since the last cigarette (p=0.001). Using a cotinine level of 20 ng ml^?1 and self-report as the gold standard, the sensitivity and specificity for defining current smoking status were 90.2% and 82.4%, respectively. Out of a total of 125 self-reported current non-smokers, 23 (18.4%) had cotinine levels greater than 20 ng ml^?1. Smoking prevalence was significantly underestimated by self-report (24.7%) when compared with that defined using blood cotinine levels (36.1%: p&lt;0.001). Misclassification of current smoking status was particularly high in ex-smokers, in patients without malignant respiratory disease, in men, and in those below the median age. Such differential misclassification may result in bias in studies examining associations between current smoking habits and disease risk.     

早期戒烟大鼠肺病理及炎性介质变化

目的观察早期戒烟后大鼠肺组织病理及炎性介质表达变化规律。方法选用Wistar雄性大鼠80只,随机分为对照组及早期戒烟后0天、1周、2周、4周、6周、8周、12周组。采用酶联免疫吸附方法测定各组大鼠血清中IL-8的蛋白质含量,S-P免疫组化学方法检测肺组织NF-κB p65的表达,并光镜下观察HE染色切片、对大鼠气道炎症进行病理学评分。结果早期戒烟组大鼠可见气道上皮细胞纤毛发生粘连、倒伏,上皮细胞空泡变形、坏死、增生,炎症细胞浸润;其血清IL-8浓度、肺组织NF-κB的表达及气道炎症病理评分在戒烟后各时相点较未吸烟对照组明显升高,有统计学意义（P〈0.05）。早期戒烟组大鼠血清IL-8的浓度、肺组织NF-κB的表达及肺组织病理炎症评分在戒烟后略有上升、且在戒烟后8周达到高峰,但随后在戒烟12周时可见IL-8的浓度有下降趋势,肺组织病理炎症反应有所减轻。结论早期戒烟大鼠在戒烟早期虽可见炎症反应略有加重,但随戒烟时间延长,仍可见炎症反应有所减轻。因此,提倡及早且坚持戒烟。     

Emotional and Affective Temperaments in Smoking Candidates for Bariatric Surgery

Introduction

The prevalence of smoking habits in severe obesity is higher than in the general population. There is some evidence that smokers have different temperaments compared to non-smokers. The aim of this study is to evaluate the associations between smoking status (smokers, ex-smokers and non-smokers) and temperament characteristics in bariatric surgery candidates.

Methods

We analyzed data on temperament of 420 bariatric surgery candidates, as assessed by the AFECTS scale, in an exploratory cross-sectional survey of bariatric surgery candidates who have been grouped into smokers, ex-smokers and non-smokers.

Results

We detected significant statistical differences in temperament related to the smoking status in this population after controlling the current use of psychiatric medication. Smokers had higher anxiety and lower control than non-smokers. Ex-smokers with BMI >50 kg/m² presented higher coping and control characteristics than smokers.

Conclusions

Smoking in bariatric surgery candidates was associated with lower control and higher anxious temperament, when controlled by current use of psychiatric medication. Smokers with BMI >50 kg/m² presented lower coping and control than ex-smokers. Assessment of temperament in bariatric surgery candidates may help in decisions about smoking cessation treatment and prevention of smoking relapse after surgery.     

Chronic Bronchitis and Current Smoking Are Associated with More Goblet Cells in Moderate to Severe COPD and Smokers without Airflow Obstruction

BackgroundGoblet cell hyperplasia is a classic but variable pathologic finding in COPD. Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described. We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.MethodsWe recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers. Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue. Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane. Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.ResultsHealthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects. COPD subjects had a greater GCD than nonsmokers. When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD. When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD. This finding was also seen in those with CB in the COPD group alone. In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates. All other covariates were not significant predictors of GCD or MVD.ConclusionsCurrent smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction. This provides clinical and pathologic correlation for smokers with and without COPD.     

Cigarette smoking and KRAS oncogene mutations in sporadic colorectal cancer: results from the Netherlands Cohort Study

Since a KRAS oncogene mutation is an early event in colorectal cancer development and cigarette smoking is thought to have an effect on early stages of colorectal tumorigenesis, smoking, especially long-term smoking, may be associated with the risk for colorectal cancer with KRAS oncogene mutations. In the Netherlands Cohort Study on diet and cancer (n=120,852 men and women), using a case-cohort design, adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed for colorectal tumors with wild-type and with mutated KRAS gene, and with specific G:C-->T:A or G:C-->A:T point mutations in KRAS, according to cigarette smoking status, frequency, duration, pack years, age at first exposure, years since cessation, inhalation and filter usage. After 7.3 years and excluding the first 2.3 years, 648 cases and 4083 sub-cohort members were included in the analyses. Ex-smokers, but not current smokers, were at increased risk for colorectal cancer with wild-type KRAS gene tumors when compared with never smokers, albeit not statistically significant (RR 1.26, 95% CI 0.96-1.66). This was not observed for KRAS mutated tumors when comparing ex-smokers with never smokers (RR 1.15, 95% CI 0.79-1.66). The highest category of smoking frequency (>20 cigarettes/day) and inhalation of smoke were associated with an increased risk for colorectal cancer with wild-type KRAS gene tumors, though not statistically significant, when compared with never smoking (frequency: RR 1.24, 95% CI 0.90-1.71 and inhalation: RR 1.25, 95% CI 0.94-1.67). These associations were strongest in men (ex-smokers: RR 1.79, 95% CI 1.00-3.20; frequency: RR 1.91, 95% CI 1.03-3.52; inhalation: RR 1.69, 95% CI 0.94-3.04). No associations were observed between any of the smoking characteristics and the risk for colorectal cancer with mutated KRAS gene tumors, nor where there any clear associations with tumors with specific G:C-->A:T transitions or G:C-->T:A transversions. These results suggest that, in contrast to the hypothesis, smoking does not increase the risk for colorectal tumors with a mutated KRAS gene. Some smoking characteristics, i.e. being an ex-smoker, frequency and inhalation, may be associated with risk for colorectal cancer characterized by the wild-type KRAS gene, especially in men.     

Demographic characteristics of cigarette smokers in the United States.

This research uses a multivariate log-linear examination of a national data set to analyze the combined influences of ethnicity, age, and sex on cigarette smoking status, not only for smokers but for former smokers and current nonsmokers as well. In general, we find that demographic differences in smoking vary across several dimensions. For instance, compared to females, males are more likely to smoke and to smoke heavily. The differences between male and female cessation rates vary with ethnicity; also, males and females tend to have different ratios of former smokers to light, moderate, and heavy smokers. Mexican-Americans who smoke generally smoke small quantities of cigarettes. And Blacks are as likely as other groups not to smoke at all, and less likely than Anglos to smoke heavily. This article discusses potential future mortality effects, intervention strategies, and directions for future research.