COPD, emphysema and the onset of lung cancer. A systematic review.

PubMed

Mouronte-Roibás, Cecilia; Leiro-Fernández, Virginia; Fernández-Villar, Alberto; Botana-Rial, Maribel; Ramos-Hernández, Cristina; Ruano-Ravina, Alberto

2016-11-28

Chronic Obstructive Pulmonary Disease (COPD) and emphysema have been described as possible risk factors for lung cancer. We aim to assess the relationship between COPD, emphysema and the onset of lung cancer. We have developed a systematic review of the published literature in order to systematically analyze the scientific evidence available on this association, applying predefined inclusion and exclusion criteria. 11 Studies were included. Both COPD and emphysema seem to increase the risk of developing lung cancer, being this risk higher for smokers with heavier tobacco consumption. These results emphasize the need for physicians to perform spirometries in current and former smokers and lung image tests when needed in order to identify COPD and emphysema and thus select patients at higher risk of developing lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gene expression in lung adenocarcinomas of smokers and nonsmokers.

PubMed

Powell, Charles A; Spira, Avrum; Derti, Adnan; DeLisi, Charles; Liu, Gang; Borczuk, Alain; Busch, Steve; Sahasrabudhe, Sudhir; Chen, Yangde; Sugarbaker, David; Bueno, Raphael; Richards, William G; Brody, Jerome S

2003-08-01

Adenocarcinoma (AC) has become the most frequent type of lung cancer in men and women, and is the major form of lung cancer in nonsmokers. Our goal in this paper was to determine if AC in smokers and nonsmokers represents the same genetic disease. We compared gene expression profiles in resected samples of nonmalignant lung tissue and tumor tissue in six never-smokers with AC and in six smokers with AC, who were matched for clinical staging and histologic criteria of cell differentiation. Results were analyzed using a variety of bioinformatic tools. Four times as many genes changed expression in the transition from noninvolved lung to tumor in nonsmokers as in smokers, suggesting that AC in nonsmokers evolves locally, whereas AC in smokers evolves in a field of genetically altered tissue. There were some similarities in gene expression in smokers and nonsmokers, but many differences, suggesting different pathways of cell transformation and tumor formation. Gene expression in the noninvolved lungs of smokers differed from that of nonsmokers, and multidimensional scaling showed that noninvolved lungs of smokers groups with tumors rather than noninvolved lungs of nonsmokers. In addition, expression of a number of genes correlated with smoking intensity. Our findings, although limited by small sample size, suggest that additional studies comparing noninvolved to tumor tissue may identify pathogenetic mechanisms and therapeutic targets that differ in AC of smokers and nonsmokers.

Survival among Never-Smokers with Lung Cancer in the Cancer Care Outcomes Research and Surveillance Study.

PubMed

Clément-Duchêne, Christelle; Stock, Shannon; Xu, Xiangyan; Chang, Ellen T; Gomez, Scarlett Lin; West, Dee W; Wakelee, Heather A; Gould, Michael K

2016-01-01

Differences in patient characteristics and outcomes have been observed among current, former, and never-smokers with lung cancer, but most prior studies included few never-smokers and were not prospective. We used data from a large, prospective study of lung cancer care and outcomes in the United States to compare characteristics of never-smokers and smokers with lung cancer and to examine survival among the never-smokers. Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries, with follow-up through June 2010 or later. Cox regression was used to examine the association between smoking and survival, and to identify predictors of survival among never-smokers. Among 3,410 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 who completed a baseline patient survey, there were 274 never-smokers (8%), 1,612 former smokers (47%), 1,496 current smokers or smokers who quit recently (44%), and 28 with missing information about smoking status (<1%). Never-smokers appeared more likely than former and current/recent smokers to be female and of Asian or Hispanic race/ethnicity, and to have adenocarcinoma histology, fewer comorbidities, private insurance, and higher income and education. Compared with never-smokers, the adjusted hazard of death from any cause was 29% higher among former smokers (hazard ratio, 1.29; 95% confidence interval, 1.08-1.55), and 39% higher among current/recent smokers (hazard ratio, 1.39; 95% confidence interval, 1.16-1.67). Factors predicting worse overall survival among never-smokers included Hispanic ethnicity, severe comorbidity, undifferentiated histology, and regional or distant stage. Never-smoking Hispanics appeared more likely to have regional or advanced disease at diagnosis and less likely to undergo surgical resection, although these differences were not statistically significant. Never-smokers with lung cancer are more likely than ever-smokers to be female, Asian or Hispanic, and more advantaged socioeconomically, suggesting possible etiologic differences in lung cancer by smoking status. Among never-smokers, Hispanics with lung cancer had worse survival than non-Hispanic whites.

Survival among Never-Smokers with Lung Cancer in the Cancer Care Outcomes Research and Surveillance Study

PubMed Central

Clément-Duchêne, Christelle; Stock, Shannon; Xu, Xiangyan; Chang, Ellen T.; Gomez, Scarlett Lin; West, Dee W.; Wakelee, Heather A.

2016-01-01

Rationale: Differences in patient characteristics and outcomes have been observed among current, former, and never-smokers with lung cancer, but most prior studies included few never-smokers and were not prospective. Objectives: We used data from a large, prospective study of lung cancer care and outcomes in the United States to compare characteristics of never-smokers and smokers with lung cancer and to examine survival among the never-smokers. Methods: Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries, with follow-up through June 2010 or later. Cox regression was used to examine the association between smoking and survival, and to identify predictors of survival among never-smokers. Measurements and Main Results: Among 3,410 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 who completed a baseline patient survey, there were 274 never-smokers (8%), 1,612 former smokers (47%), 1,496 current smokers or smokers who quit recently (44%), and 28 with missing information about smoking status (<1%). Never-smokers appeared more likely than former and current/recent smokers to be female and of Asian or Hispanic race/ethnicity, and to have adenocarcinoma histology, fewer comorbidities, private insurance, and higher income and education. Compared with never-smokers, the adjusted hazard of death from any cause was 29% higher among former smokers (hazard ratio, 1.29; 95% confidence interval, 1.08–1.55), and 39% higher among current/recent smokers (hazard ratio, 1.39; 95% confidence interval, 1.16–1.67). Factors predicting worse overall survival among never-smokers included Hispanic ethnicity, severe comorbidity, undifferentiated histology, and regional or distant stage. Never-smoking Hispanics appeared more likely to have regional or advanced disease at diagnosis and less likely to undergo surgical resection, although these differences were not statistically significant. Conclusions: Never-smokers with lung cancer are more likely than ever-smokers to be female, Asian or Hispanic, and more advantaged socioeconomically, suggesting possible etiologic differences in lung cancer by smoking status. Among never-smokers, Hispanics with lung cancer had worse survival than non-Hispanic whites. PMID:26730864

Association between smoking and p53 mutation in lung cancer: a meta-analysis.

PubMed

Liu, X; Lin, X J; Wang, C P; Yan, K K; Zhao, L Y; An, W X; Liu, X D

2014-01-01

To carry out a meta-analysis on the relationship between smoking and p53 gene mutation in lung cancer patients. PubMed, Web of Science, ProQest and Medline were searched by using the key words: 'lung cancer or lung neoplasm or lung carcinoma', 'p53 mutation' and 'smoking'. According to the selection criteria, 15 articles were identified and methodologically analysed by stata 12.0 software package. Crude odds ratios with 95% confidence intervals calculated using the fixed-effects model were used to assess the strength of association between smoking and p53 mutation in lung cancer. In total, 15 articles with 1770 lung cancer patients were identified; 69.6% of the patients were smokers, 30.4% were non-smokers. Overall, smokers with lung cancer had a 2.70-fold (95% confidence interval 2.04-3.59) higher risk for mutation than the non-smokers with lung cancer. In subgroup analyses, the increased risk of p53 mutation in smokers than in non-smokers was found in the non-small cell lung cancer (NSCLC) group (odds ratio = 2.38, 95% confidence interval = 1.71-3.32) and in the NSCLC and SCLC group (odds ratio = 3.82, 95% confidence interval = 2.19-6.69). This meta-analysis strongly suggests that p53 mutation is associated with smoking-induced lung cancer. Smokers with lung cancer had a higher risk for p53 mutation than non-smokers. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Prevalence and correlates of light and non-daily smoking in Brazil: Results from a nationwide representative survey.

PubMed

Formagini, Taynara Dutra Batista; Gomide, Henrique Pinto; Perales, Jaime; Colugnati, Fernando Antonio Basile

2017-09-01

The research of light (≤10 cigarettes per day) and non-daily smokers in developing countries including Brazil is scarce despite the high prevalence of these groups among smokers and health risks associated to low-level smoking. To describe health and smoking characteristics of Brazilian adult light and non-daily smokers. We analyzed data from the 2013 Brazilian National Health Research survey (n=48,282). The prevalence of current manufactured cigarette smoking in the total sample was 12.4%. Among these smokers, 12.8% were non-daily smokers (NDS), 47.4% were light smokers (LS) and 39.8% were moderate/heavy smokers (MHS). Bivariate analysis showed that non-daily smoking was associated with higher odds of poor self-rated health, binge drinking and lung diseases compared to never smokers (ORs=1.2; 5.9 and 1.9). Light smoking was associated with higher odds of poor self-rated health, binge drinking, depression, use of sleeping pills and lung diseases (ORs=1.3; 4.3; 1.4; 1.2 and 2.0). After controlling for sex and age, non-daily smoking was associated with lung disease (OR=2.2) and light smoking with depression and lung diseases (ORs=1.3 and 1.8). Smoking levels were associated with living with same-level smokers in bivariate and multivariate analyses. A large proportion of smokers in Brazil are light and non-daily smokers, carrying substantial health risks related to tobacco use. Longitudinal research is needed to provide further evidence of associations found in this study. Public health policies must take the different smoking patterns into consideration to effectively target all smokers and reduce the harmful consequences of tobacco worldwide. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic obstructive pulmonary disease among lung cancer-free smokers: The importance of healthy controls.

PubMed

Karpman, Michelle D; Eldridge, Ronald; Follis, Jack L; Etzel, Carol J; Shete, Sanjay; El-Zein, Randa A

2018-01-01

The prevalence of chronic obstructive pulmonary disease (COPD) in smokers enrolled as "healthy" controls in studies is 10-50%. The COPD status of ideal smoker populations for lung cancer case-control studies should be checked via spirometry; however, this is often not feasible, because no medical indications exist for asymptomatic smokers to undergo spirometry prior to study enrollment. Therefore, there is an unmet need for robust, cost effective assays for identifying undiagnosed lung disease among asymptomatic smokers. Such assays would help excluding unhealthy smokers from lung cancer case-control studies. We used the cytokinesis-blocked micronucleus (CBMN) assay (a measure of genetic instability) to identify undiagnosed lung disease among asymptomatic smokers. We used a convenience population from an on-going lung cancer case-control study including smokers with lung cancer (n = 454), smoker controls (n = 797), and a self-reported COPD (n = 200) contingent within the smoker controls. Significant differences for all CBMN endpoints were observed when comparing lung cancer to All controls (which included COPD) and Healthy controls (with no COPD). The risk ratio (RR) was increased in the COPD group vs. Healthy controls for nuclear buds (RR 1.28, 95% confidence interval 1.01-1.62), and marginally increased for micronuclei (RR 1.06, 0.98-1.89) and nucleoplasmic bridges (RR 1.07, 0.97-1.15). These findings highlight the importance of using truly healthy controls in studies geared toward assessment of lung cancer risk. Using genetic instability biomarkers would facilitate the identification of smokers susceptible to tobacco smoke carcinogens and therefore predisposed to either disease. Copyright © 2017 The Japanese Respiratory Society. All rights reserved.

Assessing the performance of two lung age equations on the Australian population: using data from the cross-sectional BOLD-Australia study.

PubMed

Ivey, Marsha A; Johns, David P; Stevenson, Christopher; Maguire, Graeme P; Toelle, Brett G; Marks, Guy B; Abramson, Michael J; Wood-Baker, Richard

2014-12-01

Lung age, a simple concept for patients to grasp, is frequently used as an aid in smoking cessation programs. Lung age equations should be continuously updated and should be made relevant for target populations. We observed how new lung age equations developed for Australian populations performed when utilizing the Burden of Obstructive Lung Disease (BOLD)-Australia dataset compared to more commonly used equations. Data from a cross-sectional population study of noninstitutionalized Australians aged ≥40 years with analysis restricted to Caucasians <75 years. Lung age calculated using equations developed by Newbury et al. and Morris and Temple was compared with chronological age by smoking status and within smoking status. There were 2,793 participants with a mean age of 57 (±10 SD) years. More than half (52%) ever smoked, and 10.4% were current smokers. Prevalence of chronic obstructive pulmonary disease stage I or higher was 13.4% (95% confidence interval = 12.2, 14.7). For both genders, newer Newbury equations estimated lung ages significantly higher than actual age across all smoking groups (p < .05). Morris and Temple equations resulted in lung age estimates significantly lower than chronological age for nonsmokers (p < .05) but no difference among current smokers. Both equations showed exposure to smoking had lung ages higher than never-smokers (p < .001). Lung age also increased with increased pack-years. This supports the use of updated equations suited to the population of interest. The Australian Newbury equations performed well in the BOLD-Australia dataset, providing more meaningful lung age profile compared to chronological age among smokers. Using equations not developed or ideally suited for our population is likely to produce misleading results. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Lung cancer in never smokers Epidemiology and risk prediction models

PubMed Central

McCarthy, William J.; Meza, Rafael; Jeon, Jihyoun; Moolgavkar, Suresh

2012-01-01

In this chapter we review the epidemiology of lung cancer incidence and mortality among never smokers/ nonsmokers and describe the never smoker lung cancer risk models used by CISNET modelers. Our review focuses on those influences likely to have measurable population impact on never smoker risk, such as secondhand smoke, even though the individual-level impact may be small. Occupational exposures may also contribute importantly to the population attributable risk of lung cancer. We examine the following risk factors in this chapter: age, environmental tobacco smoke, cooking fumes, ionizing radiation including radon gas, inherited genetic susceptibility, selected occupational exposures, preexisting lung disease, and oncogenic viruses. We also compare the prevalence of never smokers between the three CISNET smoking scenarios and present the corresponding lung cancer mortality estimates among never smokers as predicted by a typical CISNET model. PMID:22882894

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2014-12-01

smokers [7]. In addition, modulation of global gene expression in the normal epithelium in health smokers is similar in the large and small airways...previously shown that gene-expression profiles in cytologically normal mainstem bronchus epithelium can distinguish smokers with and without lung cancer...spatially mapping the molecular field of injury associated with smoking-related lung cancer. In smokers undergoing resection of lung lesions, high

Joint Effects of Smoking and Sedentary Lifestyle on Lung Function in African Americans: The Jackson Heart Study Cohort

PubMed Central

Campbell Jenkins, Brenda W.; Sarpong, Daniel F.; Addison, Clifton; White, Monique S.; Hickson, DeMarc A.; White, Wendy; Burchfiel, Cecil

2014-01-01

This study examined: (a) differences in lung function between current and non current smokers who had sedentary lifestyles and non sedentary lifestyles and (b) the mediating effect of sedentary lifestyle on the association between smoking and lung function in African Americans. Sedentary lifestyle was defined as the lowest quartile of the total physical activity score. The results of linear and logistic regression analyses revealed that non smokers with non sedentary lifestyles had the highest level of lung function, and smokers with sedentary lifestyles had the lowest level. The female non-smokers with sedentary lifestyles had a significantly higher FEV1% predicted and FVC% predicted than smokers with non sedentary lifestyles (93.3% vs. 88.6%; p = 0.0102 and 92.1% vs. 86.9%; p = 0.0055 respectively). FEV1/FVC ratio for men was higher in non smokers with sedentary lifestyles than in smokers with non sedentary lifestyles (80.9 vs. 78.1; p = 0.0048). Though smoking is inversely associated with lung function, it seems to have a more deleterious effect than sedentary lifestyle on lung function. Physically active smokers had higher lung function than their non physically active counterparts. PMID:24477212

Joint effects of smoking and sedentary lifestyle on lung function in African Americans: the Jackson Heart Study cohort.

PubMed

Campbell Jenkins, Brenda W; Sarpong, Daniel F; Addison, Clifton; White, Monique S; Hickson, Demarc A; White, Wendy; Burchfiel, Cecil

2014-01-28

This study examined: (a) differences in lung function between current and non current smokers who had sedentary lifestyles and non sedentary lifestyles and (b) the mediating effect of sedentary lifestyle on the association between smoking and lung function in African Americans. Sedentary lifestyle was defined as the lowest quartile of the total physical activity score. The results of linear and logistic regression analyses revealed that non smokers with non sedentary lifestyles had the highest level of lung function, and smokers with sedentary lifestyles had the lowest level. The female non-smokers with sedentary lifestyles had a significantly higher FEV1% predicted and FVC% predicted than smokers with non sedentary lifestyles (93.3% vs. 88.6%; p = 0.0102 and 92.1% vs. 86.9%; p = 0.0055 respectively). FEV1/FVC ratio for men was higher in non smokers with sedentary lifestyles than in smokers with non sedentary lifestyles (80.9 vs. 78.1; p = 0.0048). Though smoking is inversely associated with lung function, it seems to have a more deleterious effect than sedentary lifestyle on lung function. Physically active smokers had higher lung function than their non physically active counterparts.

Pairing Smoking-Cessation Services With Lung Cancer Screening: A Clinical Guideline From the Association for the Treatment of Tobacco Use and Dependence and the Society for Research on Nicotine and Tobacco

PubMed Central

Fucito, Lisa M.; Czabafy, Sharon; Hendricks, Peter S.; Kotsen, Chris; Richardson, Donna; Toll, Benjamin A.

2016-01-01

Smoking cessation is crucial for reducing cancer risk and premature mortality. The US Preventive Services Task Force (USPSTF) has recommended annual lung cancer screening with low-dose computed tomography (LDCT), and the Center for Medicare and Medicaid Services recently approved lung screening as a benefit for patients ages 55 to 77 years who have a 30 pack-year history. The Society for Research on Nicotine and Tobacco (SRNT) and the Association for the Treatment of Tobacco Use and Dependence (ATTUD) developed the guideline described in this commentary based on an illustrative literature review to present the evidence for smoking-cessation health benefits in this high-risk group and to provide clinical recommendations for integrating evidence-based smoking-cessation treatment with lung cancer screening. Unfortunately, extant data on lung cancer screening participants were scarce at the time this guideline was written. However, in this review, the authors summarize the sufficient evidence on the benefits of smoking cessation and the efficacy of smoking-cessation interventions for smokers ages 55 to 77 years to provide smoking-cessation interventions for smokers who seek lung cancer screening. It is concluded that smokers who present for lung cancer screening should be encouraged to quit smoking at each visit. Access to evidence-based smoking-cessation interventions should be provided to all smokers regardless of scan results, and motivation to quit should not be a necessary precondition for treatment. Follow-up contacts to support smoking-cessation efforts should be arranged for smokers. Evidence-based behavioral strategies should be used at each visit to motivate smokers who are unwilling to try quitting/reducing smoking or to try evidence-based treatments that may lead to eventual cessation. PMID:26916412

Lung cancer risk prediction to select smokers for screening CT--a model based on the Italian COSMOS trial.

PubMed

Maisonneuve, Patrick; Bagnardi, Vincenzo; Bellomi, Massimo; Spaggiari, Lorenzo; Pelosi, Giuseppe; Rampinelli, Cristiano; Bertolotti, Raffaella; Rotmensz, Nicole; Field, John K; Decensi, Andrea; Veronesi, Giulia

2011-11-01

Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57-18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84-16.8), and emphysema (RR = 2.36, 95% CI = 1.59-3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models.

Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer

DTIC Science & Technology

2015-07-01

AWARD NUMBER: W81XWH-14-1-0234 TITLE: Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers With Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...single cell RNA sequencing on airway epithelial cells obtained from smokers with and without lung cancer to identify cell-type dependent gene expression

CT screening for lung cancer: Importance of emphysema for never smokers and smokers.

PubMed

Henschke, Claudia I; Yip, Rowena; Boffetta, Paolo; Markowitz, Steven; Miller, Albert; Hanaoka, Takaomi; Wu, Ning; Zulueta, Javier J; Yankelevitz, David F

2015-04-01

To address the prevalence of lung cancer in high and low-risk people according to their smoking history, age, and CT findings of emphysema. We reviewed the baseline low-dose CT scans of 62,124 current, former and never smokers, aged 40-90 to determine the prevalence of lung cancer. We performed logistic regression analysis of the prevalence of lung cancer to determine the odds ratio (OR) for emphysema, conditionally on age, female gender, and ethnicity. The prevalence of lung cancer was 1.4% (95% CI: 1.3-1.6) for current smokers, 1.1% (95% CI: 1.0-1.2) for former smokers, and 0.4% (95% CI: 0.3-0.6) for never smokers. Emphysema was identified in 28.5% (6,684), 20.6% (5,422), and 1.6% (194) of current, former, and never smokers, respectively. The prevalence of lung cancer among current smokers was 1.1% for those without emphysema vs. 2.3% for those with emphysema (odds ratio [OR] 1.8; 95% confidence interval [CI]: 1.4-2.2) and the corresponding difference for former smokers was 0.9% vs. 1.8% (OR: 1.7; 95% CI: 1.3-2.2), and for never smokers, it was 0.4% vs. 2.6% (OR: 6.3; 95% CI: 2.4-16.9). Identification of emphysema in low-dose CT scans increases the risk of lung cancer and is important in determining follow-up of current, former, and never smokers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Association between environmental tobacco smoke exposure and lung cancer susceptibility: modification by antioxidant enzyme genetic polymorphisms.

PubMed

Fathy, Mona; Hamed, Mai; Youssif, Omnia; Fawzy, Nahla; Ashour, Wafa

2014-02-01

Environmental tobacco smoke (ETS) is the primary etiologic factor responsible for lung cancer. However, only 10-15 % of smokers develop lung cancer, suggesting a genetic role in modifying individual susceptibility to lung cancer. Antioxidant enzymes and genetic polymorphisms should be considered. The present study aimed to evaluate the role of antioxidant enzyme activity and genetic polymorphisms in modifying the susceptibility to lung cancer among individuals exposed to ETS. A total of 150 male subjects were divided into three groups: 50 lung cancer patients, 50 chronic smokers, and 50 passive smokers. Genotyping of microsomal epoxide hydrolase (mEH) exon 3 (Tyr(113)Hist) and exon 4 (Hist(139)Arg) polymorphisms were done by the polymerase chain reaction-restriction fragment length polymorphism technique. MnSOD (Val(16)Ala) polymorphism was detected by the real time-TaqMan assay. Erythrocyte MnSOD activity was measured spectrophotometrically. ETS-exposed individuals (both active and passive smokers) who carried the His allele of mEH exon3 have a 2.9-fold increased risk of lung cancer (odds ratio [OR] 2.9, P < 0.001). In addition, ETS-exposed carriers of the Arg allele of mEH exon 4 have a 2.1-fold increased risk of lung cancer (OR 2.1, P = 0.024). However, no association between the MnSOD Val(16)Ala polymorphism and lung cancer was detected among ETS-exposed individuals (OR 1.6, P = 0.147), although the lung cancer group had significantly lower MnSOD activity than the chronic or passive smoker groups (P = 0.03). Exons 3 and 4 polymorphisms of the mEH gene may contribute to lung cancer susceptibility through disturbed antioxidant balance. However, this was not the case with the MnSOD Val(16)Ala single-nucleotid polymorphism. Antioxidant enzymes may modulate the influence of ETS exposure on lung cancer risk.

Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

PubMed Central

2013-01-01

Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize deregulated genes and group them into gene modules by simultaneously considering gene expression level changes and gene-gene co-regulations. When applied to both simulated and empirical data, nDGE outperforms the traditional DGE method. More specifically, when applied to smoker and non-smoker lung cancer sets, nDGE results illustrate the molecular differences between smoker and non-smoker lung cancer. PMID:24341432

Attitudes towards screening for lung cancer among smokers and their non-smoking counterparts.

PubMed

Silvestri, Gerard A; Nietert, Paul J; Zoller, James; Carter, Cindy; Bradford, David

2007-02-01

There has been resurgence of interest in lung cancer screening using low-dose computed tomography. The implications of directing a screening programme at smokers has been little explored. A nationwide telephone survey was conducted. Demographics, certain clinical characteristics and attitudes about screening for lung cancer were ascertained. Responses of current, former and never smokers were compared. 2001 people from the US were interviewed. Smokers were significantly (p < 0.05) more likely than never smokers to be male, non-white, less educated, and to report poor health status or having had cancer, and less likely to be able to identify a usual source of healthcare. Compared with never smokers, current smokers were less likely to believe that early detection would result in a good chance of survival (p < 0.05). Smokers were less likely to be willing to consider computed tomography screening for lung cancer (71.2% (current smokers) v 87.6% (never smokers) odds ratio (OR) 0.48; 95% confidence interval (CI) 0.32 to 0.71). More never smokers as opposed to current smokers believed that the risk of disease (88% v 56%) and the accuracy of the test (92% v 71%) were important determinants in deciding whether to be screened (p < 0.05). Only half of the current smokers would opt for surgery for a screen-diagnosed cancer. The findings suggest that there may be substantial obstacles to the successful implementation of a mass-screening programme for lung cancer that will target cigarette smokers.

Non-small cell lung cancer in never smokers: a clinical entity to be identified.

PubMed

Santoro, Ilka Lopes; Ramos, Roberta Pulcheri; Franceschini, Juliana; Jamnik, Sergio; Fernandes, Ana Luisa Godoy

2011-01-01

It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among never-smokers with non-small cell lung cancer. All consecutive non-small cell lung cancer patients diagnosed (n = 285) between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current) were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable), gender (female vs. male), smoking status (never- vs. ever-smoker), the Karnofsky Performance Status Scale (continuous variable), histological type (adenocarcinoma vs. non-adenocarcinoma), AJCC staging (early vs. advanced staging), and treatment (chemotherapy and/or radiotherapy vs. the best treatment support). Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32%) and have adenocarcinoma (70% vs. 51%). Overall median survival was 15.7 months (95% CI: 13.2 to 18.2). The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

Smoking cessation: the potential role of risk assessment tools as motivational triggers.

PubMed

Young, Robert P; Hopkins, Raewyn J; Smith, Melinda; Hogarth, D Kyle

2010-01-01

Smoking is the most important and preventable cause of morbidity and premature mortality in developed and developing countries. To date, efforts to reduce the burden of smoking have focused on non-personalised strategies. Anxiety about ill health, especially lung cancer and emphysema, is the foremost concern for smokers and a major reason for quitting. Recent efforts in cessation management focus on behaviour change and pharmacotherapy. The '3 Ts' (tension, trigger, treatment) model of behaviour change proposes that at any one time a smoker experiences varying degrees of motivational tension, which in the presence of a trigger may initiate or enhance quitting. Smokers' optimistic bias (ie, denial of one's own vulnerability) sustains continued smoking, while increasing motivational tension (eg, illness) favours quitting. The 1 year quit rates achieved when smokers encounter a life threatening event, such as a heart attack or lung cancer, are as much as 50-60%. Utilising tests of lung function and/or genetic susceptibility personalises the risk and have been reported to achieve 1 year quit rates of 25%. This is comparable to quit rates achieved among healthy motivated smokers using smoking cessation drug therapy. In this paper we review existing evidence and propose that identifying those smokers at increased risk of an adverse smoking related disease may be a useful motivational tool, and enhance existing public health strategies directed at smoking cessation.

Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

NASA Astrophysics Data System (ADS)

Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

2015-03-01

Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, p<0.05). This paper demonstrates effectiveness of the proposed method in diagnosis and prognosis of early emphysema in CT screening for lung cancer.

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles.

EPA Science Inventory

BACKGROUND: Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease. OBJECTIVES: To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure t...

Evaluation of Vibration Response Imaging (VRI) Technique and Difference in VRI Indices Among Non-Smokers, Active Smokers, and Passive Smokers

PubMed Central

Jiang, Hongying; Chen, Jichao; Cao, Jinying; Mu, Lan; Hu, Zhenyu; He, Jian

2015-01-01

Background Vibration response imaging (VRI) is a new technology for lung imaging. Active smokers and non-smokers show differences in VRI findings, but no data are available for passive smokers. The aim of this study was to evaluate the use of VRI and to assess the differences in VRI findings among non-smokers, active smokers, and passive smokers. Material/Methods Healthy subjects (n=165: 63 non-smokers, 56 active smokers, and 46 passive smokers) with normal lung function were enrolled. Medical history, physical examination, lung function test, and VRI were performed for all subjects. Correlation between smoking index and VRI scores (VRIS) were performed. Results VRI images showed progressive and regressive stages representing the inspiratory and expiratory phases bilaterally in a vertical and synchronized manner in non-smokers. Vibration energy curves with low expiratory phase and plateau were present in 6.35% and 3.17%, respectively, of healthy non-smokers, 41.07% and 28.60% of smokers, and 39.13% and 30.43% of passive smokers, respectively. The massive energy peak in the non-smokers, smokers, and passive-smokers was 1.77±0.27, 1.57±0.29, and 1.66±0.33, respectively (all P<0.001). A weak but positive correlation was observed between VRIS and smoking index. Conclusions VRI can intuitively show the differences between non-smokers and smokers. VRI revealed that passive smoking can also harm the lungs. VRI could be used to visually persuade smokers to give up smoking. PMID:26212715

Lung dosimetry for inhaled radon progeny in smokers.

PubMed

Baias, Paul F; Hofmann, Werner; Winkler-Heil, Renate; Cosma, Constantin; Duliu, Octavian G

2010-02-01

Cigarette smoking may change the morphological and physiological parameters of the lung. Thus the primary objective of the present study was to investigate to what extent these smoke-induced changes can modify deposition, clearance and resulting doses of inhaled radon progeny relative to healthy non-smokers (NSs). Doses to sensitive bronchial target cells were computed for four categories of smokers: (1) Light, short-term (LST) smokers, (2) light, long-term (LLT) smokers, (3) heavy, short-term (HST) smokers and (4) heavy, long-term (HLT) smokers. Because of only small changes of morphological and physiological parameters, doses for the LST smokers hardly differed from those for NSs. For LLT and HST smokers, even a protective effect could be observed, caused by a thicker mucus layer and increased mucus velocities. Only in the case of HLT smokers were doses higher by about a factor of 2 than those for NSs, caused primarily by impaired mucociliary clearance, higher breathing frequency, reduced lung volume and airway obstructions. These higher doses suggest that the contribution of inhaled radon progeny to the risk of lung cancer in smokers may be higher than currently assumed on the basis of NS doses.

Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach.

PubMed

Kelsen, Steven G; Duan, Xunbao; Ji, Rong; Perez, Oscar; Liu, Chunli; Merali, Salim

2008-05-01

Cigarette smoking, which exposes the lung to high concentrations of reactive oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary disease (COPD). Recent studies indicate that ROS interfere with protein folding in the endoplasmic reticulum and elicit a compensatory response termed the "unfolded protein response" (UPR). The importance of the UPR lies in its ability to alter expression of a variety of genes involved in antioxidant defense, inflammation, energy metabolism, protein synthesis, apoptosis, and cell cycle regulation. The present study used comparative proteomic technology to test the hypothesis that chronic cigarette smoking induces a UPR in the human lung. Studies were performed on lung tissue samples obtained from three groups of human subjects: nonsmokers, chronic cigarette smokers, and ex-smokers. Proteomes of lung samples from chronic cigarette smokers demonstrated 26 differentially expressed proteins (20 were up-regulated, 5 were down-regulated, and 1 was detected only in the smoking group) compared with nonsmokers. Several UPR proteins were up-regulated in smokers compared with nonsmokers and ex-smokers, including the chaperones, glucose-regulated protein 78 (GRP78) and calreticulin; a foldase, protein disulfide isomerase (PDI); and enzymes involved in antioxidant defense. In cultured human airway epithelial cells, GRP78 and the UPR-regulated basic leucine zipper, transcription factors, ATF4 and Nrf2, which enhance expression of important anti-oxidant genes, increased rapidly (< 24 h) with cigarette smoke extract. These data indicate that cigarette smoke induces a UPR response in the human lung that is rapid in onset, concentration dependent, and at least partially reversible with smoking cessation. We speculate that activation of a UPR by cigarette smoke may protect the lung from oxidant injury and the development of COPD.

Cigarette smoke induces methylation of the tumor suppressor gene NISCH

PubMed Central

Ostrow, Kimberly Laskie; Michalidi, Christina; Guerrero-Preston, Rafael; Hoque, Mohammad O.; Greenberg, Alissa; Rom, William; Sidransky, David

2013-01-01

We have previously identified a putative tumor suppressor gene, NISCH, whose promoter is methylated in lung tumor tissue as well as in plasma obtained from lung cancer patients. NISCH was observed to be more frequently methylated in smoker lung cancer patients than in non-smoker lung cancer patients. Here, we investigated the effect of tobacco smoke exposure on methylation of the NISCH gene. We tested methylation of NISCH after oral keratinocytes were exposed to mainstream and side stream cigarette smoke extract in culture. Methylation of the promoter region of the NISCH gene was also evaluated in plasma obtained from lifetime non-smokers and light smokers (< 20 pack/year), with and without lung tumors, and heavy smokers (20+ pack/year) without disease. Promoter methylation of NISCH was tested by quantitative fluorogenic real-time PCR in all samples. Promoter methylation of NISCH occurred after exposure to mainstream tobacco smoke as well as to side stream tobacco smoke in normal oral keratinocyte cell lines. NISCH methylation was also detected in 68% of high-risk, heavy smokers without detectable tumors. Interestingly, in light smokers, NISCH methylation was present in 69% of patients with lung cancer and absent in those without disease. Our pilot study indicates that tobacco smoke induces methylation changes in the NISCH gene promoter before any detectable cancer. Methylation of the NISCH gene was also found in lung cancer patients’ plasma samples. After confirming these findings in longitudinally collected plasma samples from high-risk populations (such as heavy smokers), examining patients for hypermethylation of the NISCH gene may aid in identifying those who should undergo additional screening for lung cancer. PMID:23503203

Does cannabis smoking predispose to lung bulla formation?

PubMed

Fiorelli, Alfonso; Accardo, Marina; Vicidomini, Giovanni; Messina, Gaetana; Laperuta, Paolo; Santini, Mario

2014-01-01

The data of a consecutive series of habitual marijuana smokers were retrospectively evaluated and compared with that of non-marijuana smokers to assess differences between the 2 groups. 13 consecutive habitual marijuana smokers were referred for treatment of spontaneous pneumothorax. The demographic, clinical, radiological, and pathological findings of these patients were reviewed and compared with 140 non-marijuana smokers treated for the same pathology at the same time. Bullae were seen in 8/13 (62%) and 110/140 (78%) of marijuana smokers and non-marijuana smokers, respectively. However, when patients less than 35-years old were considered, the incidence of bulla was higher in marijuana smokers than non-marijuana smokers (7/10 vs. 3/10, p < 0.05). The pathological findings showed a greater presence of inflammatory cells in specimens from marijuana smokers than those of non-marijuana smokers (8/11 vs. 2/42, respectively, p < 0.05). No significant differences in hospital stay and clinical outcome were registered between the 2 groups. Despite the fact that we were unable to demonstrate that marijuana had a causal role in the development of emphysema, our study showed that marijuana smokers had a higher incidence of inflammatory cells in pathological specimens, which may favor lung injury, thus predisposing to bulla formation.

Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation.

PubMed

Erdogan, Bulent; Kodaz, Hilmi; Karabulut, Senem; Cinkaya, Ahmet; Tozkir, Hilmi; Tanriverdi, Ozgur; Cabuk, Devrim; Hacioglu, Muhammed Bekir; Turkmen, Esma; Hacibekiroglu, Ilhan; Uzunoglu, Sernaz; Cicin, Irfan

2016-11-10

Lung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01).The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.

Childhood pneumonia increases risk for chronic obstructive pulmonary disease: the COPDGene study.

PubMed

Hayden, Lystra P; Hobbs, Brian D; Cohen, Robyn T; Wise, Robert A; Checkley, William; Crapo, James D; Hersh, Craig P

2015-09-21

Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers. COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans. Of 10,192 adult smokers, 854 (8.4%) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95% CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1% predicted), FVC (82.7 vs. 87.4% predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95% CI 1.10-3.18). Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk. ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).

Native American Ancestry Affects the Risk for Gene Methylation in the Lungs of Hispanic Smokers from New Mexico

PubMed Central

Liu, Yushi; Thomas, Cynthia L.; Gauderman, W. James; Picchi, Maria A.; Bruse, Shannon E.; Zhang, Xiequn; Flores, Kristina G.; Van Den Berg, David; Stidley, Christine A.; Gilliland, Frank D.

2013-01-01

Rationale: Gene promoter methylation detected in sputum predicts lung cancer risk in smokers. Compared with non-Hispanic whites (NHW), Hispanics have a lower age-standardized incidence for lung cancer. Objectives: This study compared the methylation prevalence in sputum of NHWs with Hispanics using the Lovelace Smokers cohort (n = 1998) and evaluated the effect of Native American ancestry (NAA) and diet on biomarkers for lung cancer risk. Methods: Genetic ancestry was estimated using 48 ancestry markers. Diet was assessed by the Harvard University Dietary Assessment questionnaire. Methylation of 12 genes was measured in sputum using methylation-specific polymerase chain reaction. The association between NAA and risk for methylation was assessed using generalized estimating equations. The ethnic difference in the association between pack-years and risk for lung cancer was assessed in the New Mexico lung cancer study. Measurements and Main Results: Overall Hispanics had a significantly increased risk for methylation across the 12 genes analyzed (odds ratio, 1.18; P = 0.007). However, the risk was reduced by 32% (P = 0.032) in Hispanics with high versus low NAA. In the New Mexico lung cancer study, Hispanic non–small cell lung cancer cases have significantly lower pack-years than NHW counterparts (P = 0.007). Furthermore, compared with NHW smokers, Hispanic smokers had a more rapidly increasing risk for lung cancer as a function of pack-years (P = 0.058). Conclusions: NAA may be an important risk modifier for methylation in Hispanic smokers. Smoking intensity may have a greater impact on risk for lung cancer in Hispanics compared with NHWs. PMID:24032348

Enhanced perfusion defect clarity and inhomogeneity in smokers' lungs with deep-inspiratory breath-hold perfusion SPECT images.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Iwanaga, Hideyuki; Hayashi, Norio; Yamashita, Tomio; Matsunaga, Naofumi

2005-09-01

Deep-inspiratory breath-hold (DIBrH) Tc-99m-macroaggregated albumin (MAA) SPECT images were developed to accurately evaluate perfusion impairment in smokers' lungs. DIBrH SPECT was performed in 28 smokers with or without low attenuation areas (LAA) on CT images, using a triple-headed SPECT system and a laser light respiratory tracking device. DIBrH SPECT images were reconstructed from every 4 degrees projection of five adequate 360 degrees projection data sets with almost the same respiratory dimension at 20 sec DIBrH. Perfusion defect clarity was assessed by the lesion (defect)-to-contralateral normal lung count ratios (L/N ratios). Perfusion inhomogeneity was assessed by the coefficient of variation (CV) values of pixel counts and correlated with the diffusing capacity of the lungs for carbon monoxide/alveolar volume (DLCO/VA) ratios. The results were compared with those on conventional images. Five DIBrH projection data sets with minimal dimension differences of 2.9+/-0.6 mm were obtained in all subjects. DIBrH images enhanced perfusion defects compared with conventional images, with significantly higher L/N ratios (P<0.0001), and detected a total of 109 (26.9%) additional detects (513 vs. 404), with excellent inter-observer agreement (kappa value of 0.816). CV values in the smokers' lungs on DIBrH images were also significantly higher compared with those on conventional images (0.31+/-0.10 vs. 0.19+/-0.06, P<0.0001). CV values in smokers on DIBrH images showed a significantly closer correlation with DLCO/VA ratios compared with conventional images (R = 0.872, P<0.0001 vs. R=0.499, P<0.01). By reducing adverse effect of respiratory motion, DIBrH SPECT images enhance perfusion defect clarity and inhomogeneity, and provide more accurate assessment of impaired perfusion in smokers' lungs compared with conventional images.

[Evaluation of walk-in lung function service for smokers in Copenhagen--a 1-year study].

PubMed

Backer, Vibeke; Bolton, Sophie; Ehlers, Hanne D; Thomsen, Simon; Pedersen, Lars; Porsbjerg, Celeste; Lund, Thomas; Harmsen, Lotte; Harmse, Lotte; Fuglsang, Charlotte

2008-08-25

Early prevention of COPD and immediate consultation about tobacco cessation is a major issue in respiratory medicine. To evaluate if a community-based walk-in lung function service, either in a clinic or a shopping mall, could result in early detection of COPD. Early detection would facilitate prevention. In an area with 1.5 mill inhabitants, a walk-in lung function service opened in 2005/06 once a month for 3 hours at a clinic and on two full days in a mall. The staff consisted of two respiratory nurses and one chest physician. The nurses informed all participants about their lung function level and all received a preventive talk about tobacco consumption. Those with signs of COPD spoke with the doctor immediately. A total of 1169 subjects, 59% women, with a mean (SD) age of 60 years (15), visited the walk-in services, 602 (52%) of whom visited the walk-in service at the clinic. Among the participants, 826 (71%) were smokers (n=452) or former smokers (n=374). The mean tobacco consumption was 32 (18) packs a year. We found that more current smokers visited the walk-in service at the clinic (45% versus 33%), whereas more ex-smokers visited the lung function service at the mall (38% versus 25%) (p < 0.01). The mean tobacco consumption was 32 (18) packs a year, with a difference between those visiting the mall and the clinic (32 (20) versus 23 (16), p<0.05). Among smokers, 54% had normal lung function, 15% had signs of airway obstruction, whereas 31% had developed moderate to severe COPD. Despite free medical access, more that one thirds had signs of airway obstruction. As all were informed about tobacco cessation, a walk-in service in a clinic and not a supermarket is most cost effective.

Correlation between familial cancer history and epidermal growth factor receptor mutations in Taiwanese never smokers with non-small cell lung cancer: a case-control study.

PubMed

Cheng, Po-Chung; Cheng, Yun-Chung

2015-03-01

Lung cancer is a leading cause of cancer deaths in the world. Cigarette smoking remains a prominent risk factor, but lung cancer incidence has been increasing in never smokers. Genetic abnormalities including epidermal growth factor receptor (EGFR) mutations predominate in never smoking lung cancer patients. Furthermore, familial aggregations of patients with these mutations reflect heritable susceptibility to lung cancer. The correlation between familial cancer history and EGFR mutations in never smokers with lung cancer requires investigation. This was a retrospective case-control study that evaluated the prevalence of EGFR mutations in lung cancer patients with familial cancer history. Never smokers with lung cancer treated at a hospital in Taiwan between April 2012 and May 2014 were evaluated. Inclusion criteria were never smokers with non-small cell lung cancer (NSCLC). Exclusion criteria involved patients without records of familial cancer history or tumor genotype. This study included 246 never smokers with lung cancer. The study population mainly involved never smoking women with a mean age of 60 years, and the predominant tumor histology was adenocarcinoma. Lung cancer patients with familial cancer history had an increased prevalence of EGFR mutations compared to patients without family history [odds ratio (OR): 5.9; 95% confidence interval (CI): 3.3-10.6; P<0.001]. Specifically, 57 out of 85 cancer patients (67%) with familial cancer history had these mutations, while 41 out of 161 patients (25%) without family history harbored mutations. Subgroup analysis also revealed that patients with familial lung cancer history had stronger association with EGFR mutations (OR: 7.5; 95% CI: 3.4-16.3; P<0.001) compared to patients with family history of non-pulmonary cancers (OR: 5.0; 95% CI: 2.5-10.0; P<0.001). The study demonstrated an increased prevalence of EGFR mutations in Taiwanese never smoking lung cancer patients with familial cancer history. Moreover, a sizable proportion of never smoking cancer patients harbored these mutations. These observations have implications for the treatment of lung cancer in never smokers.

Which risk models perform best in selecting ever-smokers for lung cancer screening?

Cancer.gov

A new analysis by scientists at NCI evaluates nine different individualized lung cancer risk prediction models based on their selections of ever-smokers for computed tomography (CT) lung cancer screening.

[What is new in the epidemiology of lung cancer: non-smokers, women and the role of cannabis?].

PubMed

Quoix, Elisabeth

2009-09-20

Lung cancer is in France, like in other countries, the first cause of death by cancer in men. It has become the third one in women in a few years span. If smoking is the main cause of lung cancer, other causes have been quite neglected for years such as occupational risk mainly asbestos exposure. Lung cancer in non-smokers has increased during the last years. This may be a real increase or the consequence of ageing of the general population with increased incidence of lung cancer rather due to age than to tobacco. The considerable increase in women's incidence of lung cancer is partly due to the development of smoking habits since 1960 in France. The possibility of an increased suceptibility to tobacco smoke in women is biologically plausible but still very controversial. The role of cannabis smoke is also controversial since it is very difficult to isolate the effects of cannabis which is in the majority of cases smoked with tobacco. However, recent studies are in favor of an independent role of cannabis in the development of lung cancers.

Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

PubMed Central

Ostadkarampour, Mahyar; Müller, Malin; Öckinger, Johan; Kullberg, Susanna; Lindén, Anders; Eklund, Anders; Grunewald, Johan; Wahlström, Jan

2016-01-01

Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2–24 pack-years) and never-smokers (n = 15), all with normal lung function. Cells were stimulated ex vivo and key intracellular cytokines (IFNγ, IL-17, IL-10 and TNFα) and transcription factors (Foxp3, T-bet and Helios) were analyzed using flow cytometry. Our results indicate that smoking is associated with a decline in lung IL-17+ CD4+ T cells, increased IFNγ+ CD8+ T cells and these alterations relate to the history of daily cigarette consumption. There is an increased fraction of Foxp3+ regulatory T cells being Helios- in the lungs of smokers. Cytokine production is mainly confined to the Helios- T cells, both in regulatory and effector subsets. Moreover, we detected a decline of Helios+Foxp3- postulated regulatory CD8+ T cells in smokers. These alterations in the immune system are likely to increase risk for infection and may have implications for autoimmune processes initiated in the lungs among tobacco smokers. PMID:27798682

The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

2017-08-01

Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Exploring the association between perceived risks of smoking and benefits to quitting: who does not see the link?

PubMed

Lyna, Pauline; McBride, Colleen; Samsa, Greg; Pollak, Kathryn I

2002-01-01

This report explored associations between different measures of smokers' perceived risks of smoking and benefits to quitting and the extent to which these associations varied by demographic and other characteristics for 144 smokers. We hypothesized greater perceived risk of smoking would be associated with greater perceived benefits to quitting and would be strongest among smokers who were concerned about health effects of smoking and motivated to quit. Results indicated smokers' perceived themselves at risk for lung cancer regardless if they continued or quit smoking and was strongest for smokers who were older and minimized the importance of reducing lung cancer risk. There was a weak correlation between perceived risk for lung cancer when compared to nonsmokers and perception that quitting smoking would reduce lung cancer risk and was weakest for African Americans, lighters smokers, and smokers with higher intrinsic relative to extrinsic motivation for cessation. In conclusion, these subgroup differences in the relationship between perceptions of risks and benefits could be important to consider to increase the relevance and motivational potency of smoking cessation interventions.

Associations between dietary intake of choline and betaine and lung cancer risk.

PubMed

Ying, Jun; Rahbar, Mohammad H; Hallman, D Michael; Hernandez, Ladia M; Spitz, Margret R; Forman, Michele R; Gorlova, Olga Y

2013-01-01

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55-0.88) and 0.51(0.39-0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former (p(trend) = 0.002) and current (p(trend)<0.0001) smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking.

Associations between Dietary Intake of Choline and Betaine and Lung Cancer Risk

PubMed Central

Ying, Jun; Rahbar, Mohammad H.; Hallman, D. Michael; Hernandez, Ladia M.; Spitz, Margret R.; Forman, Michele R.; Gorlova, Olga Y.

2013-01-01

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55–0.88) and 0.51(0.39–0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former (ptrend = 0.002) and current (ptrend<0.0001) smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking. PMID:23383301

Body Mass Index and Waist Circumference in Relation to Lung Cancer Risk in the Women's Health Initiative

PubMed Central

Kim, Mimi; Hunt, Julie R.; Chlebowski, Rowan T.; Rohan, Thomas E.

2008-01-01

Investigators in several epidemiologic studies have observed an inverse association between body mass index (BMI) and lung cancer risk, while others have not. The authors used data from the Women's Health Initiative to study the association of anthropometric factors with lung cancer risk. Over 8 years of follow-up (1998–2006), 1,365 incident lung cancer cases were ascertained among 161,809 women. Cox proportional hazards models were used to estimate hazard ratios adjusted for covariates. Baseline BMI was inversely associated with lung cancer in current smokers (highest quintile vs. lowest: hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.42, 0.92). When BMI and waist circumference were mutually adjusted, BMI was inversely associated with lung cancer risk in both current smokers and former smokers (HR = 0.40 (95% CI: 0.22, 0.72) and HR = 0.61 (95% CI: 0.40, 0.94), respectively), and waist circumference was positively associated with risk (HR = 1.56 (95% CI: 0.91, 2.69) and HR = 1.50 (95% CI: 0.98, 2.31), respectively). In never smokers, height showed a borderline positive association with lung cancer. These findings suggest that in smokers, BMI is inversely associated with lung cancer risk and that waist circumference is positively associated with risk. PMID:18483121

Study of epidemiological risk of lung cancer in Mexico due indoor radon exposure

NASA Astrophysics Data System (ADS)

Ángeles, A.; Espinosa, G.

2014-07-01

In this work the lifetime relative risks (LRR) of lung cancer due to exposure to indoor 222Rn on the Mexican population is calculated. Cigarette smoking is the number one risk factor for lung cancer (LC), because that, to calculate the number of cases of LC due to exposure to 222Rn is necessary considers the number of cases of LC for smoking cigarette. The lung cancer mortality rates published by the "Secretaría de Salud" (SSA), the mexican population data published by the "Consejo Nacional de Población" (CONAPO), smoking data in the mexican population, published by the "Comisión Nacional Contra las Adicciones" (CONADIC), the "Organización Panamericana de la Salud" (OPS) and indoor 222Rn concentrations in Mexico published in several recent studies are used. To calculate the lifetime relative risks (LRR) for different segments of the Mexican population, firstly the Excess Relative Risk (ERR) is calculated using the method developed by the BEIR VI committee and subsequently modified by the USEPA and published in the report "EPA Assessment of Risks from Radon in Homes". The excess relative risks were then used to calculate the corresponding lifetime relative risks, again using the method developed by the BEIR VI committee. The lifetime relative risks for Mexican male and female eversmokers and Mexican male and female never-smokers were calculated for radon concentrations spanning the range found in recent studies of indoor radon concentrations in Mexico. The lifetime relative risks of lung cancer induced by lifetime exposure to the mexican average indoor radon concentration were estimated to be 1.44 and 1.40 for never-smokers mexican females and males respectively, and 1.19 and 1.17 for ever-smokers Mexican females and males respectively. The Mexican population LRR values obtained in relation to the USA and Canada LRR published values in ever-smokers for both gender are similar with differences less than 4%, in case of never-smokers in relation with Canada population the differences in LRR values are less than 2% and in never-smokers for the USA population the differences in LRR values compared with the Mexican population are about 10%.

Global perspective of tobacco habits and lung cancer: a lesson for third world countries.

PubMed

Pandey, M; Mathew, A; Nair, M K

1999-08-01

Over the past 50 years, a dominant role of tobacco smoking in lung cancer causation has been demonstrated. Almost three-quarters of the lung cancer cases can be attributed to tobacco smoking. The global variation in lung cancer incidence is thought to be directly proportional to the smoking habits prevalent in that part of the world. Lung cancer shows a greater upward trend in incidence in the USA, in central and Eastern Europe than ever before, especially in females. Japan too has recorded a 10-fold increase in incidence in both sexes since 1975. In India the problem is further compounded by absence of authentic data on time trend. The recent trend of available data suggests a more or less linear trend. At present lung cancer ranks among the top three killers in men in almost every metropolis in India. The highest incidence rate has been recorded in Bombay (14.6/ 100,000) and the lowest in Barshi (2.0/100,000). How much of these can be attributed to smoking cannot be commented on as no case-control or cohort studies have ever been undertaken in India. The situation is more alarming in other developing countries, where there is no authentic data on tobacco use or lung cancer incidences. The relationship between tobacco and cancer is both simple and complex. The majority of the cancer patients are smokers, while the cancer incidence is not proportional among smokers. To explain this, various factors such as type of smoke, duration of smoke, amount of carcinogens, presence of activation and metabolism pathways, and lately genetic environment interaction, have been put forward. It appears that the relationship is more complex than at first thought. In developing countries, it is further compounded by lack of data on usage and dependence of the economies of these countries on tobacco. The situation is alarming, with ever-increasing incidence among women and non-smokers exposed to smoke (passive smokers). Tobacco use has already become an epidemic.

Environmental tobacco smoke exposure and EGFR and ALK alterations in never smokers' lung cancer. Results from the LCRINS study.

PubMed

Torres-Durán, María; Ruano-Ravina, Alberto; Kelsey, Karl T; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Abdulkader, Ihab; Provencio, Mariano; Abal-Arca, José; Castro-Añón, Olalla; Montero-Martínez, Carmen; Vidal-García, Iria; Amenedo, Margarita; Golpe-Gómez, Antonio; Martínez, Cristina; Guzmán-Taveras, Rosirys; Mejuto-Martí, María José; Fernández-Villar, Alberto; Barros-Dios, Juan Miguel

2017-12-28

Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever-smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant. Exposure during adulthood, at home or at workplace, did not show any association with EGFR mutation. The mutation type L858R seemed the most associated with a lower probability of EGFR alterations for ETS exposure at home in adult life. There is no apparent association between ETS exposure and ALK translocation. These results might suggest that ETS exposure during childhood or at home in adult life could influence the EGFR mutations profile in lung cancer in never smokers, reducing the probability of presenting EFGR mutation. Copyright © 2017 Elsevier B.V. All rights reserved.

The Relations Between False Positive and Negative Screens and Smoking Cessation and Relapse in the National Lung Screening Trial: Implications for Public Health.

PubMed

Clark, Melissa A; Gorelick, Jeremy J; Sicks, JoRean D; Park, Elyse R; Graham, Amanda L; Abrams, David B; Gareen, Ilana F

2016-01-01

Lung screening is an opportunity for smoking cessation and relapse prevention, but smoking behaviors may differ across screening results. Changes in smoking were evaluated among 18 840 current and former smokers aged 55-74 scheduled to receive three annual lung screenings. Participants were randomized to low-dose computed tomography or single-view chest radiography in the American College of Radiology/National Lung Screening Trial. Outcome measures included point and sustained (6-month) abstinence and motivation to quit among smokers; and relapse among smokers who quit during follow-up, recent quitters (quit < 6 months), and long-term former smokers (quit ≥ 6 months). During five years of follow-up, annual point prevalence quit rates ranged from 11.6%-13.4%; 48% of current smokers reported a quit attempt and 7% of long-term former smokers relapsed. Any false positive screening result was associated with subsequent increased point (multivariable hazard ratio HR = 1.23, 95% CI = 1.13, 1.35) and sustained (HR = 1.28, 95% CI = 1.15, 1.43) abstinence among smokers. Recent quitters with ≥1 false positive screen were less likely to relapse (HR = 0.72, 95% CI = 0.54, 0.96). Screening result was not associated with relapse among long-term former smokers or among baseline smokers who quit during follow-up. A false positive screen was associated with increased smoking cessation and less relapse among recent quitters. Consistently negative screens were not associated with greater relapse among long-term former smokers. Given the Affordable Care Act requires most health plans to cover smoking cessation and lung screening, the impact and cost-effectiveness of lung screening could be further enhanced with the addition of smoking cessation interventions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2014-12-18

that the adjacent field cancerization extends to relatively less invasive large airways and harbors markers that can detect lung cancer in smokers ; 5...profiles have been described in the normal-appearing bronchial epithelium of healthy smokers (9) including those that were diagnostic of lung cancer...10). In addition, modulation of global gene expression in the normal epithelium in health smokers is similar in the large and small airways and the

Does the Consumption of Green Tea Reduce the Risk of Lung Cancer Among Smokers?

PubMed Central

Liang, Wenbin; Binns, Colin W.; Jian, Le

2007-01-01

Experimental and epidemiological studies were reviewed to assess whether the consumption of green tea could reduce the risk of lung cancer in smokers. Articles published since 1990 were located by searching electronic databases PubMed, Ovid and Science Direct, using keywords ‘lung cancer’, ‘tea’ and ‘smoking’ without any restriction on language. After relevant articles had been located, further papers were obtained from their reference lists. Evidence from experimental studies (in vitro animal and human trials) suggested that regular intake of green tea may be protective against tobacco carcinogens. However, the mechanism behind the protective effect is only partly understood. In most of the epidemiological studies reviewed, the green tea exposure was within 5 years of the interview or follow-up, which would coincide with the induction period and latent period of lung cancer. Longer term studies are thus needed to further quantify the cancer risk. There is some evidence suggesting regular intake of green tea at high level (>3 cups per day) may reduce the risk of smokers developing lung cancer. Improvement in measuring green tea intake is required in order to confirm the evidence from epidemiological studies. PMID:17342237

Carbonaceous particulate matter on the lung surface from adults living in São Paulo, Brazil.

PubMed

Padovan, Michele Galhardoni; Whitehouse, Abigail; Gouveia, Nelson; Habermann, Mateus; Grigg, Jonathan

2017-01-01

We therefore sought to identify the exposures associated with lung surface in long-term residents of São Paulo, Brazil. Lung surface carbon were analyzed in 72 autopsy specimens by image analysis. Smoking history, measured PM10 nearest to the home, distance to main road, and distance-weighted traffic density were used as exposure variables. Data are summarized as median (IQR), and compared by Mann Whitney Test, with correlations done by Spearman's correlation. There was no association between lung surface and age or gender. There was no statistically significant association in lung surface between smokers and non-smokers 6.74 cm2 (3.47 to 10.02) versus 5.20cm2 (2.29 to 7.54), and there was no significant association between lung surface carbon and exposure to environmental PM and markers of traffic exposure. We did not find a statistically significant association between lung surface and smokers and non-smokers, and no statistically significant association between lung surface carbon and environmental exposure variables. These results suggest that lung surface carbon in long-term residents of São Paulo may predominately be from environmental PM, but the most appropriate environmental exposure marker remains unclear.

A Decade of Never-smokers Among Lung Cancer Patients-Increasing Trend and Improved Survival.

PubMed

Toh, Chee-Keong; Ong, Whee-Sze; Lim, Wan-Teck; Tan, Daniel Shao-Weng; Ng, Quan-Sing; Kanesvaran, Ravindran; Seow, Wei-Jie; Ang, Mei-Kim; Tan, Eng-Huat

2018-03-17

It is not known whether clinicopathologic characteristics, treatment, and survival of never-smokers among lung cancer incident cases have changed over time. We assessed the trend and overall survival (OS) of these patients within our institution during a 10-year period. We reviewed 2 cohorts of non-small-cell lung cancer patients with a diagnosis from 1999 to 2002 and from 2008 to 2011. The patient characteristics and OS were compared by smoking status within each cohort and between the 2 cohorts over time. Of the 992 patients in the 1999-2002 cohort and the 1318 patients in the 2008-2011 cohort, 902 and 1272 had a known smoking status, respectively. The proportion of never-smokers increased from 31% in 1999-2002 to 48% in 2008-2011 (P < .001). Within both cohorts, the differences in characteristics among never-, former-, and current-smokers have remained largely constant over time. A greater proportion of never-smokers had Eastern Cooperative Oncology Group performance status 0 to 1 and adenocarcinoma. The median OS increased from 15.5 months in 1999-2002 to 24.9 months in 2008-2011 (P = .001) for never-smokers, 12.3 to 15.9 months (P = .150) for former-smokers, and 10.5 to 13.9 months (P = .011) for current-smokers. The larger survival improvement among never-smokers was likely accounted for by the larger increase in never-smokers who were treated with tyrosine kinase inhibitors and pemetrexed over time. We found an increasing trend of never-smokers among incident lung cancer cases and improved survival for these patients during a 10-year period. The documentation of smoking status in any national cancer registry is vital to estimate the true incidence of lung cancer among never-smokers over time. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulatory T-Cell Distribution within Lung Compartments in COPD.

PubMed

Sales, Davi S; Ito, Juliana T; Zanchetta, Ivy A; Annoni, Raquel; Aun, Marcelo V; Ferraz, Luiz Fernando S; Cervilha, Daniela A B; Negri, Elnara; Mauad, Thais; Martins, Mílton A; Lopes, Fernanda D T Q S

2017-10-01

The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF + cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17 + cells only in small airways. A decrease in the density of Treg + , TGF-β + and IL-10 + in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF + cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg + cell distributions in lung compartments and the decrease in TGF-β + and IL-10 + cells in the airways may lead to the obstruction in smokers.

Smoking-Induced Upregulation of AKR1B10 Expression in the Airway Epithelium of Healthy Individuals

PubMed Central

Wang, Rui; Wang, Guoqing; Ricard, Megan J.; Ferris, Barbara; Strulovici-Barel, Yael; Salit, Jacqueline; Hackett, Neil R.; Gudas, Lorraine J.

2010-01-01

Background: The aldo-keto reductase (AKR) gene superfamily codes for monomeric, soluble reduced nicotinamide adenine dinucleotide phosphate-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that eliminates retinals, has been observed as upregulated in squamous metaplasia and non-small cell lung cancer and has been suggested as a diagnostic marker specific to tobacco-related carcinogenesis. We hypothesized that upregulation of AKR1B10 expression may be initiated in healthy smokers prior to the development of evidence of lung cancer. Methods: Expression of AKR1B10 was assessed at the mRNA level using microarrays with TaqMan confirmation in the large airway epithelium (21 healthy nonsmokers, 31 healthy smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic bronchoscopy and brushing. Results: Compared with healthy nonsmokers, AKR1B10 mRNA levels were significantly upregulated in both large and small airway epithelia of healthy smokers. Consistent with the mRNA data, AKR1B10 protein was significantly upregulated in the airway epithelium of healthy smokers as assessed by Western blot analysis and immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells. Finally, cigarette smoke extract mediated upregulation of AKR1B10 in airway epithelial cells in vitro, and transfection of AKR1B10 into airway epithelial cells enhanced the conversion of retinal to retinol. Conclusions: Smoking per se mediates upregulation of AKR1B10 expression in the airway epithelia of healthy smokers with no evidence of lung cancer. In the context of these observations and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced upregulation of AKR1B10 may be an early process in the multiple events leading to lung cancer. PMID:20705797

Lung Mass in Smokers

PubMed Central

Washko, George R.; Kinney, Gregory L.; Ross, James C.; San José Estépar, Raúl; Han, MeiLan K.; Dransfield, Mark T.; Kim, Victor; Hatabu, Hiroto; Come, Carolyn E.; Bowler, Russell P.; Silverman, Edwin K.; Crapo, James; Lynch, David A.; Hokanson, John; Diaz, Alejandro A.

2017-01-01

Rationale and Objective Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic (CT) studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers. Materials and Methods Baseline epidemiologic, clinical, and CT data (n=8,156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at five-year follow-up were available from 1,623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV1) and FEV1 decline. Results Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD had greater LM than either smokers with normal lung function or those with GOLD 2–4 COPD (P<0.001 for both comparisons). LM was predictive of rate of the decline in FEV1 (decline per 100 g, −4.7 ± 1.7 ml/yr, P=0.006). Conclusion Our cross sectional data suggest the presence of a biphasic radiologic remodeling process in smokers: the presence of such non-linearity must be accounted for in longitudinal CT studies. Baseline LM predicts the decline in lung function. PMID:27940230

Lung Cancer in Chinese Women: Evidence for an Interaction between Tobacco Smoking and Exposure to Inhalants in the Indoor Environment

PubMed Central

Tang, Li; Lim, Wei-Yen; Eng, Philip; Leong, Swan Swan; Lim, Tow Keang; Ng, Alan W.K.; Tee, Augustine; Seow, Adeline

2010-01-01

Background Epidemiologic data suggest that Chinese women have a high incidence of lung cancer in relation to their smoking prevalence. In addition to active tobacco smoke exposure, other sources of fumes and airborne particles in the indoor environment, such as cooking and burning of incense and mosquito coils, have been considered potential risk factors for lung cancer. Objectives We used a case–control study to explore effects of inhalants from combustion sources common in the domestic environment on lung cancer and their modification by active tobacco smoking. Methods We analyzed 703 primary lung cancer cases and 1,578 controls. Data on demographic background and relevant exposures were obtained by face-to-face interviews in the hospital. Results We observed a positive relationship with daily exposure to incense or mosquito coils and to cooking fumes only among smokers, and no association among lifetime nonsmokers. Interactions between smoking and frequency of cooking, or exposure to incense or mosquito coils were statistically significant and consistent with synergistic effects on lung cancer. The odds ratio (OR) comparing smokers without daily incense or mosquito coil exposure with nonsmokers without daily exposure was 2.80 [95% confidence interval (CI), 1.86–4.21], whereas the OR comparing smokers with daily exposure to the same referent group was 4.61 (95% CI, 3.41–6.24). In contrast, daily exposure to incense or mosquito coils was not associated with lung cancer among nonsmokers (OR = 0.91; 95% CI, 0.72–1.16). We observed the same pattern of associations for smokers without (OR = 2.31; 95% CI, 1.52–3.51) and with (OR = 4.50; 95% CI, 3.21–6.30) daily cooking exposure compared with nonsmokers, with no evidence of an association with daily cooking exposure among nonsmokers. Conclusion Our results suggest that active tobacco smoking not only is an important risk factor for development of lung cancer, but also may cause smokers to be more susceptible to the risk-enhancing effects of other inhalants. PMID:20472525

Plasma pro-surfactant protein B and lung function decline in smokers.

PubMed

Leung, Janice M; Mayo, John; Tan, Wan; Tammemagi, C Martin; Liu, Geoffrey; Peacock, Stuart; Shepherd, Frances A; Goffin, John; Goss, Glenwood; Nicholas, Garth; Tremblay, Alain; Johnston, Michael; Martel, Simon; Laberge, Francis; Bhatia, Rick; Roberts, Heidi; Burrowes, Paul; Manos, Daria; Stewart, Lori; Seely, Jean M; Gingras, Michel; Pasian, Sergio; Tsao, Ming-Sound; Lam, Stephen; Sin, Don D

2015-04-01

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans. Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression. Copyright ©ERS 2015.

CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations.

PubMed

Wassenaar, Catherine A; Ye, Yuanqing; Cai, Qiuyin; Aldrich, Melinda C; Knight, Joanne; Spitz, Margaret R; Wu, Xifeng; Blot, William J; Tyndale, Rachel F

2015-01-01

We investigated genetic variation in CYP2A6 in relation to lung cancer risk among African American smokers, a high-risk population. Previously, we found that CYP2A6, a nicotine/nitrosamine metabolism gene, was associated with lung cancer risk in European Americans, but smoking habits, lung cancer risk and CYP2A6 gene variants differ significantly between European and African ancestry populations. Herein, African American ever-smokers, drawn from two independent lung cancer case-control studies, were genotyped for reduced activity CYP2A6 alleles and grouped by predicted metabolic activity. Lung cancer risk in the Southern Community Cohort Study (n = 494) was lower among CYP2A6 reduced versus normal metabolizers, as estimated by multivariate conditional logistic regression [odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.26-0.73] and by unconditional logistic regression (OR = 0.62; 95% CI = 0.41-0.94). The association was replicated in an independent study from MD Anderson Cancer Center (n = 407) (OR = 0.64; 95% CI = 0.42-0.98), and pooling the studies yielded an OR of 0.64 (95% CI = 0.48-0.86). Exploratory analyses revealed a significant interaction between CYP2A6 genotype and sex on the risk for lung cancer (Southern Community Cohort Study: P = 0.04; MD Anderson: P = 0.03; Pooled studies: P = 0.002) with a CYP2A6 effect in men only. These findings support a contribution of genetic variation in CYP2A6 to lung cancer risk among African American smokers, particularly men, whereby CYP2A6 genotypes associated with reduced metabolic activity confer a lower risk of developing lung cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mortality of iron miners in Lorraine (France): relations between lung function and respiratory symptoms and subsequent mortality.

PubMed Central

Chau, N; Benamghar, L; Pham, Q T; Teculescu, D; Rebstock, E; Mur, J M

1993-01-01

An increased mortality from lung and stomach cancer was found in previous studies on Lorraine iron miners. A detailed analysis, however, was not possible due to the lack of data for survivors. In this study the cohort included 1178 workers selected at random from all the 5300 working miners aged between 35 and 55 at the start of the follow up period, which ranged from 1975 to 1985. Occupational exposures and tobacco consumption, lung function tests, and respiratory symptoms were assessed for each subject in 1975, 1980, and 1985. This study confirmed the excess of lung cancer (standardised mortality ratio (SMR) = 389, p < 0.001) and of stomach cancer (SMR = 273, p < 0.05). There was no excess of lung cancer in non-smokers and moderate smokers (< 20 pack-years) or the miners who worked only at the surface or underground for less than 20 years. A significant excess (SMR = 349, p < 0.001) was found in moderate smokers when they worked underground for between 20 and 29 years. Heavy smokers (over 30 pack-years) or subjects who worked underground for more than 30 years experienced a high risk: SMR = 478 (p < 0.001) for moderate smokers who worked underground for over 30 years; 588 (p < 0.001) for heavy smokers who worked underground for between 20 and 29 years; and 877 (p < 0.001) for heavy smokers who worked underground for over 30 years. This showed an interaction between smoking and occupational exposure. The excess mortality from lung cancer was because there were some subjects who died young (from 45 years old). Comparison with the results of a previous study showed that additional hazards produced by diesel engines and explosives increased the mortality from lung cancer. The SMR was higher than 400 (p < 0.001) from 45 years old instead of from 56 years. A relation was found between a decrease in vital capacity (VC), forced expiratory volume in one second (FEV1) and of FEV1/VC and mortality from all causes and from lung cancer in heavy smokers or men who had worked underground for more than 20 years. Respiratory symptoms were related to mortality from lung cancer among smokers (moderate and heavy) who worked underground for more than 20 years. It is considered that the risk of lung cancer in the Lorraine iron miners was mainly due to dust, diesel engines, and explosives although the role of low exposure to radon daughters could not be totally excluded. PMID:8280627

Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

PubMed

Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas

2016-05-01

Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

Cigarette smoke–induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD

PubMed Central

Dove, Rosamund E.; Leong-Smith, Pheneatia; Roos-Engstrand, Ester; Pourazar, Jamshid; Shah, Mittal; Behndig, Annelie F.; Mudway, Ian S.; Blomberg, Anders

2015-01-01

Background Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke. Methods Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13). Results Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers. Conclusions We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke–induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression. PMID:26557249

Lung cancer in never-smokers - what are the differences?

PubMed

Dias, Margarida; Linhas, Rita; Campainha, Sérgio; Conde, Sara; Barroso, Ana

2017-07-01

Characteristics of never-smokers with lung cancer are still not fully clarified. The aim of this study was to compare never-smokers and ever-smokers with non-small cell lung cancer (NSCLC) regarding patient and tumor characteristics. All consecutive newly NSCLC patients with known smoking status diagnosed between 2011 and 2015 were included in this retrospective cohort study. Clinical, histological, and molecular characteristics were compared between ever-smokers and never-smokers. Of the 558 included patients, 125 (22.4%) were never-smokers. These patients were more likely to be female (74% vs. 7%, p < .001), older (67 vs. 66 years-old, p = .019), and have adenocarcinoma (93% vs. 65%, p < .001). Never-smokers took longer to seek medical care after the symptoms onset (3 vs. 2 months, p < .001), regardless of the symptoms, histological type, or gender (OR: 1.2 [1.4-2.0]). The metastatic pattern was different in never-smokers: pleural metastases were more frequent (OR: 2.1 [1.1-4.0]), regardless of the histological type and gender. Never-smokers had a higher prevalence of ALK translocations (26% vs. 4%, p < .001) and EGFR mutations (36% vs. 8%, p < .001). The type of EGFR mutation was also significantly different between groups. Never-smokers with NSCLC present distinct demographic and clinical characteristics. The characteristics of tumor also differ between never-smokers and ever-smokers, which may suggest different carcinogenic pathways.

Cryptogenic fibrosing alveolitis and lung cancer: the BTS study.

PubMed

Harris, J M; Johnston, I D A; Rudd, R; Taylor, A J Newman; Cullinan, P

2010-01-01

The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA). Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated. 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02). These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

Linking the generation of DNA adducts to lung cancer.

PubMed

Ceppi, Marcello; Munnia, Armelle; Cellai, Filippo; Bruzzone, Marco; Peluso, Marco E M

2017-09-01

Worldwide, lung cancer is the leading cause of cancer death. DNA adducts are considered a reliable biomarker that reflects carcinogen exposure to tobacco smoke, but the central question is what is the relationship of DNA adducts and cancer? Therefore, we investigated this relationship by a meta-analysis of twenty-two studies with bronchial adducts for a total of 1091 subjects, 887 lung cancer cases and 204 apparently healthy individuals with no evidence of lung cancer. Our study shows that these adducts are significantly associated to increase lung cancer risk. The value of Mean Ratio lung-cancer (MR) of bronchial adducts resulting from the random effects model was 2.64, 95% C.I. 2.00-3.50, in overall lung cancer cases as compared to controls. The significant difference, with lung cancer patients having significant higher levels of bronchial adducts than controls, persisted after stratification for smoking habits. The MR lung-cancer value between lung cancer patients and controls for smokers was 2.03, 95% C.I. 1.42-2.91, for ex-smokers 3.27, 95% C.I. 1.49-7.18, and for non-smokers was 3.81, 95% C.I. 1.85-7.85. Next, we found that the generation of bronchial adducts is significantly related to inhalation exposure to tobacco smoke carcinogens confirming its association with volatile carcinogens. The MR smoking estimate of bronchial adducts resulting from meta-regression was 2.28, 95% Confidence Interval (C.I.) 1.10-4.73, in overall smokers in respect to non-smokers. The present work provides strengthening of the hypothesis that bronchial adducts are not simply relate to exposure, but are a cause of chemical-induced lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers: a case-control study

PubMed Central

2010-01-01

Background Inverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed. Methods We conducted a hospital-based case-control study with lung cancer cases and controls matched on smoking status, and further adjusted for smoking status, duration, and intensity in the multivariate models. A total of 948 cases and 1743 controls were included in the analysis. Results Inverse linear trends were observed between intake of fruits, total vegetables, and cruciferous vegetables and risk of lung cancer (ORs ranged from 0.53-0.70, with P for trend < 0.05). Interestingly, significant associations were observed for intake of fruits and total vegetables with lung cancer among never smokers. Conversely, significant inverse associations with cruciferous vegetable intake were observed primarily among smokers, in particular former smokers, although significant interactions were not detected between smoking and intake of any food group. Of four lung cancer histological subtypes, significant inverse associations were observed primarily among patients with squamous or small cell carcinoma - the two subtypes more strongly associated with heavy smoking. Conclusions Our findings are consistent with the smoking-related carcinogen-modulating effect of isothiocyanates, a group of phytochemicals uniquely present in cruciferous vegetables. Our data support consumption of a diet rich in cruciferous vegetables may reduce the risk of lung cancer among smokers. PMID:20423504

Lung Cancer Worry and Home Screening for Radon and Secondhand Smoke in Renters.

PubMed

Hahn, Ellen J; Hooper, Marissa; Riker, Carol; Butler, Karen M; Rademacher, Kathy; Wiggins, Amanda; Rayens, Mary Kay

2017-01-01

Lung cancer is largely preventable by eliminating tobacco smoke and radon exposure. This exploratory study assessed the relationships of demographic factors, including having one or more smokers living in the household, and a) lung cancer worry and b) completion of home screening for radon and secondhand smoke (SHS) among renters. A convenience sample of renters (N = 47) received free test kits for radon and SHS as part of a larger study. Demographic factors, lung cancer worry, and completion of home testing were assessed at baseline. The sample was mostly Caucasian (68%), female (62%), and educated beyond high school (70%). The average age was 43 years (SD = 15), and roughly half lived with at least one smoker (49%). Gender, race/ethnicity, education, and whether they had smokers in the home accounted for 35% of the variability in lung cancer worry, F(4, 42) = 5.6, p = .001. Lung cancer worry was associated with lower level of education, b = 0.77; SE(b) = 0.32, and having at least one smoker living in the home, b = 0.71; SE(b) = 0.31. Renters tested their homes for radon and SHS whether they had smokers in the home or not. Constructing and delivering educational messages that target low-educated populations may promote radon testing and smoke-free homes.

Lung Cancer Worry and Home Screening for Radon and Secondhand Smoke in Renters

PubMed Central

Hahn, Ellen J.; Hooper, Marissa; Riker, Carol; Butler, Karen M.; Rademacher, Kathy; Wiggins, Amanda; Rayens, Mary Kay

2017-01-01

Lung cancer is largely preventable by eliminating tobacco smoke and radon exposure. This exploratory study assessed the relationships of demographic factors, including having one or more smokers living in the household, and a) lung cancer worry and b) completion of home screening for radon and secondhand smoke (SHS) among renters. A convenience sample of renters (N = 47) received free test kits for radon and SHS as part of a larger study. Demographic factors, lung cancer worry, and completion of home testing were assessed at baseline. The sample was mostly Caucasian (68%), female (62%), and educated beyond high school (70%). The average age was 43 years (SD = 15), and roughly half lived with at least one smoker (49%). Gender, race/ethnicity, education, and whether they had smokers in the home accounted for 35% of the variability in lung cancer worry, F(4, 42) = 5.6, p = .001. Lung cancer worry was associated with lower level of education, b = 0.77; SE(b) = 0.32, and having at least one smoker living in the home, b = 0.71; SE(b) = 0.31. Renters tested their homes for radon and SHS whether they had smokers in the home or not. Constructing and delivering educational messages that target low-educated populations may promote radon testing and smoke-free homes. PMID:29135198

Lung Mass in Smokers.

PubMed

Washko, George R; Kinney, Gregory L; Ross, James C; San José Estépar, Raúl; Han, MeiLan K; Dransfield, Mark T; Kim, Victor; Hatabu, Hiroto; Come, Carolyn E; Bowler, Russell P; Silverman, Edwin K; Crapo, James; Lynch, David A; Hokanson, John; Diaz, Alejandro A

2017-04-01

Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers. Baseline epidemiologic, clinical, and computed tomography (CT) data (n = 8156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at 5 years' follow-up were available from 1623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV 1 ) and FEV 1 decline. Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 chronic obstructive pulmonary disease had greater LM than either smokers with normal lung function or those with GOLD 2-4 chronic obstructive pulmonary disease (P < 0.001 for both comparisons). LM was predictive of the rate of the decline in FEV 1 (decline per 100 g, -4.7 ± 1.7 mL/y, P = 0.006). Our cross-sectional data suggest the presence of a biphasic radiological remodeling process in smokers: the presence of such nonlinearity must be accounted for in longitudinal computed tomographic studies. Baseline LM predicts the decline in lung function. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Molecular Epidemiology of EGFR and KRAS Mutations in 3026 Lung Adenocarcinomas: Higher Susceptibility of Women to Smoking-related KRAS-mutant Cancers

PubMed Central

Dogan, Snjezana; Shen, Ronglai; Ang, Daphne C; Johnson, Melissa L; D’Angelo, Sandra P; Paik, Paul K; Brzostowski, Edyta B; Riely, Gregory J; Kris, Mark G; Zakowski, Maureen F; Ladanyi, Marc

2012-01-01

Purpose The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear. Experimental Design We genotyped 3026 lung adenocarcinomas for the major EGFR (exon 19 deletions and L858R) and KRAS (G12, G13) mutations and examined correlations with demographic, clinical and smoking history data. Results EGFR mutations were found in 43% of never smokers (NS) and in 11% of smokers. KRAS mutations occurred in 34% of smokers and in 6% of NS. In patients with smoking histories up to 10 pack-years, EGFR predominated over KRAS. Among former smokers with lung cancer, multivariate analysis showed that, independent of pack-years, increasing smoking-free years raise the likelihood of EGFR mutation. NS were more likely than smokers to have KRAS G>A transition mutation (mostly G12D) (58% vs. 20%, p=0.0001). KRAS G12C, the most common G>T transversion mutation in smokers, was more frequent in women (p=0.007) and these women were younger than men with the same mutation (median 65 vs. 69, p=0.0008) and had smoked less. Conclusions The distinct types of KRAS mutations in smokers vs. NS suggest that most KRAS-mutant lung cancers in NS are not due to secondhand smoke exposure. The higher frequency of KRAS G12C in women, their younger age, and lesser smoking history together support a heightened susceptibility to tobacco carcinogens. PMID:23014527

Pulmonary adenocarcinoma: A renewed entity in 2011

PubMed Central

Kadara, Humam; Kabbout, Mohamed; Wistuba, Ignacio I.

2014-01-01

Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention. PMID:22040022

Racial Differences in Tobacco Cessation and Treatment Usage After Lung Screening: An Examination of the National Lung Screening Trial.

PubMed

Kumar, Pallavi; Gareen, Ilana F; Lathan, Christopher; Sicks, JoRean D; Perez, Giselle K; Hyland, Kelly A; Park, Elyse R

2016-01-01

Black smokers have demonstrated greater lung cancer disease burden and poorer smoking cessation outcomes compared with whites. Lung cancer screening represents a unique opportunity to promote cessation among smokers; however, little is known about the differential impact of screening on smoking behaviors among black and white smokers. Using data from the National Lung Screening Trial (NLST), we examined the racial differences in smoking behaviors after screening. We examined racial differences in smoking behavior and cessation activity among 6,316 white and 497 black (median age, 60 and 59 years, respectively) NLST participants who were current smokers at screening using a follow-up survey on 24-hour and 7-day quit attempts, 6-month continuous abstinence, and the use of smoking cessation programs and aids at 12 months after screening. Using multiple regression analyses, we examined the predictors of 24-hour and 7-day quit attempts and 6-month continuous abstinence. At 12 months after screening, blacks were more likely to report a 24-hour (52.7% vs. 41.2%, p < .0001) or 7-day (33.6% vs. 27.2%, p = .002) quit attempt. However, no significant racial differences were found in 6-month continuous abstinence (5.6% blacks vs. 7.2% whites). In multiple regression, black race was predictive of a higher likelihood of a 24-hour (odds ratio [OR], 1.6, 95% confidence interval [CI], 1.2-2.0) and 7-day (OR, 1.5, 95% CI, 1.1-1.8) quit attempt; however, race was not associated with 6-month continuous abstinence. Only a positive screening result for lung cancer was significantly predictive of successful 6-month continuous abstinence (OR, 2.3, 95% CI, 1.8-2.9). Although blacks were more likely than whites to have 24-hour and 7-day quit attempts, the rates of 6-month continuous abstinence did not differ. Targeted interventions are needed at the time of lung cancer screening to promote abstinence among all smokers. Among smokers undergoing screening for lung cancer, blacks were more likely than whites to have 24-hour and 7-day quit attempts; however, these attempts did not translate to increased rates of 6-month continuous abstinence among black smokers. Targeted interventions are needed at the time of lung cancer screening to convert quit attempts to sustained smoking cessation among all smokers. ©AlphaMed Press.

Impact of long-term filter cigarette usage on lung and larnyx cancer risk: a case-control study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wynder, E.L.; Stellman, S.D.

A case-control study was conducted among 1034 white male and female hospital patients with histologically proved lung cancer (Kreyberg type I) or larynx cancer. After adjustment for duration of the smoking habit, inhalation, and butt length relative risks of developing lung or larynx cancer were consistently lower among long-term of filter cigarettes than among smokers of nonfilter cigarettes, irrespective of quantity smoked. Relative risks in all groups declined with increased years of smoking cessation. The observed risk reduction among current smokers of filter cigarettes was consistent with that expected, considering that these persons had smoked the older high-tar nonfilter cigarettesmore » for a large proportion of their lives.« less

Cost-effectiveness of implementing computed tomography screening for lung cancer in Taiwan.

PubMed

Yang, Szu-Chun; Lai, Wu-Wei; Lin, Chien-Chung; Su, Wu-Chou; Ku, Li-Jung; Hwang, Jing-Shiang; Wang, Jung-Der

2017-06-01

A screening program for lung cancer requires more empirical evidence. Based on the experience of the National Lung Screening Trial (NLST), we developed a method to adjust lead-time bias and quality-of-life changes for estimating the cost-effectiveness of implementing computed tomography (CT) screening in Taiwan. The target population was high-risk (≥30 pack-years) smokers between 55 and 75 years of age. From a nation-wide, 13-year follow-up cohort, we estimated quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures per case of lung cancer stratified by pathology and stage. Cumulative stage distributions for CT-screening and no-screening were assumed equal to those for CT-screening and radiography-screening in the NLST to estimate the savings of loss-of-QALE and additional costs of lifetime healthcare expenditures after CT screening. Costs attributable to screen-negative subjects, false-positive cases and radiation-induced lung cancer were included to obtain the incremental cost-effectiveness ratio from the public payer's perspective. The incremental costs were US$22,755 per person. After dividing this by savings of loss-of-QALE (1.16 quality-adjusted life year (QALY)), the incremental cost-effectiveness ratio was US$19,683 per QALY. This ratio would fall to US$10,947 per QALY if the stage distribution for CT-screening was the same as that of screen-detected cancers in the NELSON trial. Low-dose CT screening for lung cancer among high-risk smokers would be cost-effective in Taiwan. As only about 5% of our women are smokers, future research is necessary to identify the high-risk groups among non-smokers and increase the coverage. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

The Role of DNA Methylation in the Development and Progression of Lung Adenocarcinoma

PubMed Central

Kerr, Keith M.; Galler, Janice S.; Hagen, Jeffrey A.; Laird, Peter W.; Laird-Offringa, Ite A.

2007-01-01

Lung cancer, caused by smoking in ∼87% of cases, is the leading cause of cancer death in the United States and Western Europe. Adenocarcinoma is now the most common type of lung cancer in men and women in the United States, and the histological subtype most frequently seen in never-smokers and former smokers. The increasing frequency of adenocarcinoma, which occurs more peripherally in the lung, is thought to be at least partially related to modifications in cigarette manufacturing that have led to a change in the depth of smoke inhalation. The rising incidence of lung adenocarcinoma and its lethal nature underline the importance of understanding the development and progression of this disease. Alterations in DNA methylation are recognized as key epigenetic changes in cancer, contributing to chromosomal instability through global hypomethylation, and aberrant gene expression through alterations in the methylation levels at promoter CpG islands. The identification of sequential changes in DNA methylation during progression and metastasis of lung adenocarcinoma, and the elucidation of their interplay with genetic changes, will broaden our molecular understanding of this disease, providing insights that may be applicable to the development of targeted drugs, as well as powerful markers for early detection and patient classification. PMID:17325423

Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.

PubMed

Stang, Andreas; Schuler, Martin; Kowall, Bernd; Darwiche, Kaid; Kühl, Hilmar; Jöckel, Karl-Heinz

2015-09-18

It is now debated whether the screening of heavy smokers for lung cancer with low dose computed tomography (low dose CT) might lower their mortality due to lung cancer. We use data from the National Lung Screening Trial (NLST) in the USA to predict the likely effects of such screening in Germany. The number of heavy smokers aged 55-74 in Germany was extrapolated from survey data obtained by the Robert Koch Institute. Published data from the NLST were then used to estimate the likely effects of low dose CT screening of heavy smokers in Germany. If low dose CT screening were performed on 50% of the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would undergo such screening. If the screening were repeated annually, then, over three years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of lung cancer would be confirmed thereafter in 32 826 persons. At least one positive test result in three years would be obtained in 39.1% of the participants (519 837 persons). 4155 deaths from lung cancer would be prevented over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in Germany would fall by 2.6%. 12 449 persons would have at least one complication, and 1074 persons would die in the 60 days following screening. The screening of heavy smokers for lung cancer can lower their risk of dying of lung cancer by 20% in relative terms, corresponding to an absolute risk reduction of 0.3 percentage points. These figures can provide the background for a critical discussion of the putative utility of this type of screening in Germany.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.

PubMed

You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M; Samuel, Errol Lg; Marcano, Daniela C; Sun, Zhengzong; Sikkema, William Ka; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y; Tour, James M; Corry, David B; Kheradmand, Farrah

2015-10-05

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

[Prevalence of tobacco smoking among phthisio-pulmonological inpatients].

PubMed

Ugriumov, A I

2001-01-01

A questionnaire survey of 222 phthisiopulmonological inpatients has indicated that 21.7 of the males and 4.05% of the females are smokers. Among clinical and morphological forms of tuberculosis, fibrocavernous tuberculosis is prevalent in smokers. Tuberculoma and post tuberculous fibrosis of varying severity are common in never smokers. Smokers are at high risk for lung cancer and at less risk for sarcoidosis with the equal incidence of chronic obstructive lung disease. The paper states that hospital physicians pay little attention to smoking among their patients.

Epidemiology, radiology, and genetics of nicotine dependence in COPD.

PubMed

Kim, Deog Kyeom; Hersh, Craig P; Washko, George R; Hokanson, John E; Lynch, David A; Newell, John D; Murphy, James R; Crapo, James D; Silverman, Edwin K

2011-01-13

Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers. Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes. Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers. Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.

Lung Cancer Mortality Associated With Smoking and Smoking Cessation Among People Living With HIV in the United States.

PubMed

Reddy, Krishna P; Kong, Chung Yin; Hyle, Emily P; Baggett, Travis P; Huang, Mingshu; Parker, Robert A; Paltiel, A David; Losina, Elena; Weinstein, Milton C; Freedberg, Kenneth A; Walensky, Rochelle P

2017-11-01

Lung cancer has become a leading cause of death among people living with human immunodeficiency virus (HIV) (PLWH). Over 40% of PLWH in the United States smoke cigarettes; HIV independently increases the risk of lung cancer. To project cumulative lung cancer mortality by smoking exposure among PLWH in care. Using a validated microsimulation model of HIV, we applied standard demographic data and recent HIV/AIDS epidemiology statistics with specific details on smoking exposure, combining smoking status (current, former, or never) and intensity (heavy, moderate, or light). We stratified reported mortality rates attributable to lung cancer and other non-AIDS-related causes by smoking exposure and accounted for an HIV-conferred independent risk of lung cancer. Lung cancer mortality risk ratios (vs never smokers) for male and female current moderate smokers were 23.6 and 24.2, respectively, and for those who quit smoking at age 40 years were 4.3 and 4.5. In sensitivity analyses, we accounted for nonadherence to antiretroviral therapy (ART) and for a range of HIV-conferred risks of death from lung cancer and from other non-AIDS-related diseases (eg, cardiovascular disease). Cumulative lung cancer mortality by age 80 years (stratified by sex, age at entry to HIV care, and smoking exposure); total expected lung cancer deaths, accounting for nonadherence to ART. Among 40-year-old men with HIV, estimated cumulative lung cancer mortality for heavy, moderate, and light smokers who continued to smoke was 28.9%, 23.0%, and 18.8%, respectively; for those who quit smoking at age 40 years, it was 7.9%, 6.1%, and 4.3%; and for never smokers, it was 1.6%. Among women, the corresponding mortality for current smokers was 27.8%, 20.9%, and 16.6%; for former smokers, it was 7.5%, 5.2%, and 3.7%; and for never smokers, it was 1.2%. ART-adherent individuals who continued to smoke were 6 to 13 times more likely to die from lung cancer than from traditional AIDS-related causes, depending on sex and smoking intensity. Due to greater AIDS-related mortality risks, individuals with incomplete ART adherence had higher overall mortality but lower lung cancer mortality. Applying model projections to the approximately 644 200 PLWH aged 20 to 64 in care in the United States, 59 900 (9.3%) are expected to die from lung cancer if smoking habits do not change. Those PLWH who adhere to ART but smoke are substantially more likely to die from lung cancer than from AIDS-related causes.

Work-relatedness of lung cancer by smoking and histologic type in Korea.

PubMed

Lee, Young-Il; Lee, Sang-Gil; Kang, Dong-Mug; Kim, Jong-Eun; Kim, Young-Ki; Leem, Jong-Han; Kim, Hwan-Cheol

2014-01-01

This study investigated the distribution of causative agents related to occupational lung cancer, their relationships with work, and associations between work-relatedness and the histologic type of lung cancer. We used data from the occupational surveillance system in Korea in 2013. In addition, data from 1,404 participants diagnosed with lung cancer were collected through interviews. We included the patients' longest-held job in the analysis. Work-relatedness was categorized as "definite," "probable," "possible," "suspicious," "none," or "undetermined." Among the subjects, 69.3% were men and 30.7% were women. Regarding smoking status, current smokers were the most prevalent (35.5%), followed by non-smokers (32.3%), ex-smokers (32.2%). Regarding the causative agents of lung cancer, asbestos (1.0%) and crystalline silica (0.9%) were the most common in definite work-related cases, while non-arsenical insecticide (2.8%) was the most common in probable cases followed by diesel engine exhaust (1.9%) and asbestos (1.0%). Regarding histologic type, adenocarcinoma was the most common (41.7%), followed by squamous cell carcinoma (21.2%). Among current smokers, squamous cell carcinoma was the most common among definite and probable cases (13.4%), while non-small cell lung cancer was the least common (7.1%). Among non-smokers, squamous cell carcinoma was the most common (21.4%), while the least common was adenocarcinoma (1.6%). Approximately, 9.5% of all lung cancer cases in Korea are occupational-related lung cancer. Well-known substances associated with lung cancer, such as crystalline silica, asbestos, and diesel engine exhaust, are of particular concern. However, the histologic types of lung cancer related to smoking were inconsistent with previous studies when work-relatedness was taken into account. Future studies are required to clarify the incidence of occupational lung cancer in agricultural workers exposed to non-arsenical insecticides and the associations between work-relatedness and the histologic type of lung cancer.

Effects of cigarette smoking on diagnostic tests for work-related hypersensitivity pneumonitis: data from an outbreak of lung disease in metalworkers.

PubMed

Dangman, Kenneth H; Storey, Eileen; Schenck, Paula; Hodgson, Michael J

2004-05-01

It is widely believed that development of hypersensitivity pneumonitis (HP) is forestalled in cigarette smokers. We encountered the largest outbreak of HP in metalworkers yet reported [Hodgson et al. (2001): Am J Ind Med 39:616-628] and subsequently did a chart review of the 61 patients seen in connection with the outbreak [Dangman et al. (2002a): Am J Resp Crit Care Med 165(8):A528; Dangman et al. (2002b): Am J Ind Med 42:150-162], developing a diagnostic index for this disease. A re-examination of data from the chart review was carried out to explore possible effects of cigarette smoking on the clinical tests used to diagnose HP [Hodgson et al. (2001): Am J Ind Med 39:616-628]. Cigarette smokers with HP were less likely than non-smokers with HP to develop crackles in the lungs, elevated erythrocyte sedimentation rates (ESRs), and restrictive spirometry. Smoking habits had little effect on diffusion capacity and alveolar-arterial oxygen gradients in the patients with HP. Smokers were more likely to have abnormal gallium scans than non-smokers. It appears that cigarette smoking can affect the physical examination findings, spirometry, and ESR changes associated with HP, making these tests less sensitive and specific, and potentially obscuring the diagnosis. Such changes may contribute to the apparent "protective" effect of smoking on the development of HP.

Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study.

PubMed

Pavanello, Sofia; Fedeli, Ugo; Mastrangelo, Giuseppe; Rota, Federica; Overvad, Kim; Raaschou-Nielsen, Ole; Tjønneland, Anne; Vogel, Ulla

2012-06-01

Cytochrome P4501A2 (CYP1A2) is a key enzyme for lung carcinogen activation and lung inflammation. We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health." At enrollment (1993-1997), blood samples for genotype analyses and information on lifestyle were collected 5 (mean value) years before the onset of the disease. The study population included 425 lung cancer cases and 786 subcohort members, who were gender- and age-matched. We found that -163A carriers were at increased risk of lung cancer (P=0.035) in a multivariate COX regression model, which was adjusted for personal habits (i.e., cumulative smoking, passive smoke at home, alcohol intake, and fruit intake) and occupational exposure. Additionally, the interaction between -2467delT and smoking increases lung cancer risk in males, especially light smokers (<21.5 pack-years, P=0.004). The increased lung cancer risk found in -163C carriers, independent of smoking status, and in -2467delT male smokers, suggests that these variants could influence lung cancer development through different mechanisms (i.e. lung carcinogen activation and lung inflammation). Copyright © 2012 Elsevier Inc. All rights reserved.

Divergent epidermal growth factor receptor mutation patterns between smokers and non-smokers with lung adenocarcinoma.

PubMed

Tseng, Jeng-Sen; Wang, Chih-Liang; Yang, Tsung-Ying; Chen, Chih-Yi; Yang, Cheng-Ta; Chen, Kun-Chieh; Hsu, Kuo-Hsuan; Tsai, Chi-Ren; Chang, Gee-Chen

2015-12-01

Smoking status is an important determinant of the prevalence of epidermal growth factor receptor (EGFR) mutations in lung cancer patients. However, it is unclear whether smoking status could also influence the spectrum of EGFR mutations. We enrolled patients with lung adenocarcinoma from three medical centers in Taiwan. EGFR mutations were assessed by Sanger direct sequencing. The objective of this study was to evaluate the influence of smoking status on both the frequency and patterns of EGFR mutations. From 2001 to 2013, a total of 1175 patients with lung adenocarcinoma were enrolled for EGFR mutation analysis. The overall EGFR mutation rate was 59.6%, which was significantly higher in females than males (69.1% vs. 49.8%) and in non-smokers than current/former smokers (73.8% vs. 29.8%) (both P<0.001). Among patients harboring EGFR mutations, smokers expressed L858R mutation less frequently (35.2% vs. 50.2%, P=0.005) and exon 19 deletions more frequently (52.8% vs 38.8%, P=0.008) than non-smokers. Smokers and non-smokers also had divergent exon 19 deletions subtypes (Del E746-A750 82.5% vs. 57.6%, respectively, P<0.001). Among subgroup patients harboring the L858R mutation, smokers were associated with a higher rate of complex mutations than non-smokers (34.2% vs. 8.4%, P<0.001). Our results suggested that smoking status could influence not only the frequency but also the spectrum of EGFR mutations. These findings provide a clue for further investigation of EGFR mutagenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Smoking-related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid lung.

PubMed

Antoniou, Katerina M; Walsh, Simon L; Hansell, David M; Rubens, Michael R; Marten, Katharina; Tennant, Rachel; Hansel, Trevor; Desai, Sujal R; Siafakas, Nikolaos M; du Bois, Roland M; Wells, Athol U

2013-11-01

A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis-interstitial lung disease (RA-ILD)), and to compare the morphological features of lung fibrosis between smokers and non-smokers. Using high-resolution computed tomography, the prevalence of emphysema and the pack-year smoking histories associated with emphysema were compared between current/ex-smokers with IPF (n = 186) or RA-ILD (n = 46), and non-chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non-smokers. Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA-ILD, was associated with lower pack-year smoking histories than in control groups (P < 0.05 for all comparisons). The presence of emphysema in IPF was positively linked to the pack-year smoking history (odds ratio 1.04, 95% confidence interval (CI) 1.02-1.06, P < 0.0005). In IPF, fibrosis was coarser in smokers than in non-smokers on univariate and multivariate analysis (P < 0.01 for all comparisons). In RA-ILD, fibrosis was coarser in patients with emphysema but did not differ significantly between smokers and non-smokers. In IPF and RA-ILD, a high prevalence of concurrent emphysema, in association with low pack-year smoking histories, and an association between coarser pulmonary fibrosis and a history of smoking in IPF together provide support for possible pathogenetic linkage to smoking in both diseases. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Differences in clinical presentation of non-small cell lung cancer in never-smokers versus smokers.

PubMed

Lee, Joo Young; Na, Im Ii; Jang, Seung-Hun; Hwang, Yong Il; Choe, Du Hwan; Kim, Cheol Hyeon; Baek, Heejong

2013-12-01

This study was conducted to evaluate whether or not tumor spread and the diagnostic process in non-small cell lung cancer (NSCLC) is different based on smoking history. Associations between smoking status and clinical presentation were evaluated controlling for the effect of histology. Lung cancer with delayed diagnosis (LCDD) and incidental detection (LCID) were determined based on medical records. Of 914 patients, frequency of distant metastases was more common in never-smokers than in smokers (59% and 36%, respectively; P<0.001). Although never-smokers were more likely to have LCDD than smokers (18% and 11%, respectively; P=0.038), LCDD were not significantly associated with frequency of distant metastases [49% (LCDD) vs. 42% (non-LCDD); P=0.189] as well as tumor [29% (T3-4) vs. 24% (T1-2); P=0.134] and node [43% (N2-3) vs. 44% (N0-1); P=0.838] stage. Interestingly, never-smokers are more likely to have LCID than smokers (31% and 19%, respectively; P=0.010). In survival analysis, LCID (P=0.001; HR, 0.63) remained a prognostic factor, while LCDD did not. This study suggests distinct metastatic pattern and diagnostic processes of never-smokers. The link between survival and incidental detection was also indicated.

CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers—findings from two independent populations

PubMed Central

Wassenaar, Catherine A.; Ye, Yuanqing; Cai, Qiuyin; Aldrich, Melinda C.; Knight, Joanne; Spitz, Margaret R.; Wu, Xifeng; Blot, William J.; Tyndale, Rachel F.

2015-01-01

We investigated genetic variation in CYP2A6 in relation to lung cancer risk among African American smokers, a high-risk population. Previously, we found that CYP2A6, a nicotine/nitrosamine metabolism gene, was associated with lung cancer risk in European Americans, but smoking habits, lung cancer risk and CYP2A6 gene variants differ significantly between European and African ancestry populations. Herein, African American ever-smokers, drawn from two independent lung cancer case–control studies, were genotyped for reduced activity CYP2A6 alleles and grouped by predicted metabolic activity. Lung cancer risk in the Southern Community Cohort Study (n = 494) was lower among CYP2A6 reduced versus normal metabolizers, as estimated by multivariate conditional logistic regression [odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.26–0.73] and by unconditional logistic regression (OR = 0.62; 95% CI = 0.41–0.94). The association was replicated in an independent study from MD Anderson Cancer Center (n = 407) (OR = 0.64; 95% CI = 0.42–0.98), and pooling the studies yielded an OR of 0.64 (95% CI = 0.48–0.86). Exploratory analyses revealed a significant interaction between CYP2A6 genotype and sex on the risk for lung cancer (Southern Community Cohort Study: P = 0.04; MD Anderson: P = 0.03; Pooled studies: P = 0.002) with a CYP2A6 effect in men only. These findings support a contribution of genetic variation in CYP2A6 to lung cancer risk among African American smokers, particularly men, whereby CYP2A6 genotypes associated with reduced metabolic activity confer a lower risk of developing lung cancer. PMID:25416559

Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

PubMed Central

Boyer, Laurent; Marcos, Elisabeth; Margarit, Laurent; Le Corvoisier, Philippe; Vervoitte, Laetitia; Hamidou, Leila; Frih, Lamia; Audureau, Etienne; Covali-Noroc, Ala; Andujar, Pascal; Saakashvili, Zakaria; Lino, Anne; Ghaleh, Bijan; Hue, Sophie; Derumeaux, Geneviève; Housset, Bruno; Dubois-Randé, Jean-Luc; Boczkowski, Jorge; Maitre, Bernard; Adnot, Serge

2015-01-01

Rationale Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear. Objectives To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO). Methods Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD). Measurements and Main Results Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO. Conclusions Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening. PMID:25785739

Lung Microbiota Is Related to Smoking Status and to Development of Acute Respiratory Distress Syndrome in Critically Ill Trauma Patients.

PubMed

Panzer, Ariane R; Lynch, Susan V; Langelier, Chaz; Christie, Jason D; McCauley, Kathryn; Nelson, Mary; Cheung, Christopher K; Benowitz, Neal L; Cohen, Mitchell J; Calfee, Carolyn S

2018-03-01

Cigarette smoking is associated with increased risk of acute respiratory distress syndrome (ARDS) in patients after severe trauma; however, the mechanisms underlying this association are unknown. To determine whether cigarette smoking contributes to ARDS development after trauma by altering community composition of the lung microbiota. We studied the lung microbiota of mechanically ventilated patients admitted to the ICU after severe blunt trauma. To do so, we used 16S ribosomal RNA gene amplicon sequencing of endotracheal aspirate samples obtained on ICU admission (n = 74) and at 48 hours after admission (n = 30). Cigarette smoke exposure (quantified using plasma cotinine), ARDS development, and other clinical parameters were correlated with lung microbiota composition. Smoking status was significantly associated with lung bacterial community composition at ICU admission (P = 0.007 by permutational multivariate ANOVA [PERMANOVA]) and at 48 hours (P = 0.03 by PERMANOVA), as well as with significant enrichment of potential pathogens, including Streptococcus, Fusobacterium, Prevotella, Haemophilus, and Treponema. ARDS development was associated with lung community composition at 48 hours (P = 0.04 by PERMANOVA) and was characterized by relative enrichment of Enterobacteriaceae and of specific taxa enriched at baseline in smokers, including Prevotella and Fusobacterium. After severe blunt trauma, a history of smoking is related to lung microbiota composition, both at the time of ICU admission and at 48 hours. ARDS development is also correlated with respiratory microbial community structure at 48 hours and with taxa that are relatively enriched in smokers at ICU admission. The data derived from this pilot study suggest that smoking-related changes in the lung microbiota could be related to ARDS development after severe trauma.

Lung cancer in persons with HIV.

PubMed

Sigel, Keith; Makinson, Alain; Thaler, Jonathan

2017-01-01

Lung cancer is emerging as a leading cause of death in HIV-infected persons. This review will discuss the latest scientific evidence regarding the mechanisms driving lung cancer risk in HIV infection, the clinical presentation of lung cancer in HIV-infected persons and recent data regarding the outcomes, treatment and prevention of lung cancer in this group. Increased risk of lung cancer in HIV-infected persons is primarily due to higher smoking rates, but emerging evidence also implicates immunosuppression and inflammatory processes. Lung cancer outcomes may be worse in HIV-infected persons in the antiretroviral era, but this may stem, in part, from treatment disparities. Early detection of lung cancer using chest computed tomography (CT) is being increasingly adopted for smokers in the general population, and recent studies suggest that it may be safe and efficacious in HIV-infected smokers. Lung cancer is an important complication associated with chronic HIV infection. It is associated with unique HIV-related causal mechanisms, and may be associated with worse outcomes in some HIV-infected persons. Smoking cessation and early cancer detection with chest CT are likely to benefit HIV-infected smokers.

A prospective study of decline in lung function in relation to welding emissions.

PubMed

Christensen, Sigve W; Bonde, Jens Peter; Omland, Oyvind

2008-02-26

Numerous cross-sectional studies have reported reduced lung function among welders but limitations of exposure assessment and design preclude causal inference. The aim of this study was to investigate if long-term exposure to welding fume particulates accelerates the age-related decline in lung function. Lung function was measured by spirometry in 1987 and 2004 among 68 steel welders and 32 non-welding production workers. The decline in forced expiratory volume (FEV1) was analysed in relation to cumulated exposure to fume particulates among welders during the follow-up period. Among smokers the decline in FEV1 through follow-up period was in average 150 ml larger among welders than non-welders while the difference was negligible among non-smokers. The results did not reach statistical significance and within welders the decline in lung function was not related to the cumulated welding particulate exposure during follow-up period Long-term exposure to welding emissions may accelerate the age-related decline of lung function but at exposure levels in the range of 1.5 to 6.5 mg/m3 the average annual excess loss of FEV1 is unlikely to exceed 25 ml in smokers and 10 ml in non-smokers.

Time to First Cigarette, Physical Activity, and Pulmonary Function in Middle-aged to Older Adult Smokers.

PubMed

Nye, Russell T; Mercincavage, Melissa; Branstetter, Steven A

2017-08-01

How addiction severity relates to physical activity (PA), and if PA moderates the relation between PA and lung function among smokers, is unknown. This study explored the independent and interactive associations of nicotine addiction severity and PA with lung function. The study used cross-sectional data from 343 adult smokers aged 40 to 79 participating in the 2009-10 and 2011-12 National Health and Nutrition Examination Survey. Assessed were the independent relations of nicotine addiction severity, as measured by the time to first cigarette (TTFC), and average daily minutes of moderate and vigorous PA with lung function ratio (FEV1/FVC). Additional analysis examined whether PA moderated the relationship between addiction severity and lung function. Greater lung function was independently associated with moderate PA and later TTFC, but not vigorous PA, when controlling for cigarettes per day (CPD), past month smoking, ethnicity, years smoked, and gender (P-values < .05). PA did not moderate the association between addiction severity (TTFC) and lung function (P = .441). Among middle-aged to older smokers, increased PA and lower addiction severity were associated with greater lung function, independent of CPD. This may inform research into the protective role of PA and identification of risk factors for interventions.

Acculturation matters: risk perceptions of smoking among Bosnian refugees living in the United States.

PubMed

Helweg-Larsen, Marie; Stancioff, Lucia M

2008-10-01

The relationship between acculturation and health behavior change is complex. Little research has focused on acculturation and perceptions of health-related risks. This study investigated acculturation and risk perceptions of heart attack and lung cancer among a group of refugees. Questionnaires were distributed to a sample of Bosnian refugees living in the United States (N = 55). Results indicated that smokers thought they were less at risk than other smokers and no more at risk than non-smokers, whereas non-smokers did not think they were less at risk than other non-smokers. Greater acculturation was associated with greater perception of smokers' risk of heart attack and lung cancer. Smoking cessation interventions with refugees should incorporate culturally appropriate risk information.

The clinicopathological and survival differences between never and ever smokers with non-small cell lung cancer.

PubMed

Muallaoglu, Sadik; Karadeniz, Cemile; Mertsoylu, Huseyin; Ayberk Besen, Ali; Sezer, Ahmet; Murat Sedef, Ali; Kose, Fatih; Ozyilkan, Ozgur

2014-01-01

Cigarette smoking was regarded as the most important carcinogenic factor of lung cancer, yet in recent years lung cancer in never-smokers is an increasingly prominent public health issue. The aim of this study was to assess the epidemiological and clinicopathological characteristics of never-smoker patients with non small cell lung cancer (NSCLC), focusing on clinical risk factors and survival. We retrospectively analyzed 290 NSCLC patients who presented between 2006 and 2011. Differences in clinical features and survival between never- and ever- smoker patients were analyzed. Student's t-test and Mann-Whitney U-test were used to assess the significance of the variables between the groups. Survival curves were calculated using Kaplan-Meier method. Hazard ratio (HR) for death and its 95% confidence interval (CI) were calculated by Cox regression analysis. There were 243 (83.8%) ever-smokers and 47 (16.2%) never-smokers. In never-smokers females predominated (80.9%) as well as patients with adenocarcinomas (78.7%). At the time of analysis 143 (49.3%) patients had died. The 5-year overall survival (OS) rates were not significantly different between never- and ever-smokers (p=0.410) . The median OS of all patients was 26 months (95% CI: 16.8-35.2). The median OS was 23 months (95% CI: 11.8- 34.2) for never-smokers and 30 months ∥95% CI: 19.7-40.3) for ever-smokers (p=0.410). Never-smokers tended to present with more advanced disease than ever-smokers (p<0.004) and also with more advanced age (p<0.001). The HR for death increased with poorer Eastern Cooperative Oncology Group ( ECOG ) performance status (PS) (ECOG 2=3), advanced stage (stage 3=4) and untreated patients. Slightly lower risk for death was registered in patients with adenocarcinoma vs those with squamous cell carcinoma (SCC). Although no difference in survival was seen, definite epidemiologic differences do exist between never- smokers and ever-smokers patients with NSCLC. Future efforts should focus on the underlying biological differences, and on identifying potential non-tobacco related risk factors in order to improve treatment strategies for these two groups of NSCLC patients.

Impact of spirometry feedback and brief motivational counseling on long term smoking outcomes: A comparison of smokers with and without lung impairment

PubMed Central

McClure, Jennifer B.; Ludman, Evette J.; Grothaus, Lou; Pabiniak, Chester; Richards, Julie

2009-01-01

Objective We compared long-term outcomes among smokers with and without impaired lung functioning who received brief counseling highlighting their spirometric test results. Methods Participants in this analysis all received a brief motivational intervention for smoking cessation including spirometric testing and feedback (~20 minutes), were advised to quit smoking, offered free access to a phone-based smoking cessation program, and followed for one year. Outcomes were analyzed for smokers with (n = 99) and without (n = 168) impaired lung function. Results Participants with lung impairment reported greater use of self-help cessation materials at 6 months, greater use of non-study-provided counseling services at 6 and 12 months, higher 7-day PPA rates at 6 months, and were more likely to talk with their doctor about their spirometry results. Conclusion Further research is warranted to determine if spirometry feedback has a differential treatment effect among smokers with and without lung impairment. Practice Implications It is premature to make practice recommendations based on these data. PMID:20434863

Impact of spirometry feedback and brief motivational counseling on long-term smoking outcomes: a comparison of smokers with and without lung impairment.

PubMed

McClure, Jennifer B; Ludman, Evette J; Grothaus, Lou; Pabiniak, Chester; Richards, Julie

2010-08-01

We compared long-term outcomes among smokers with and without impaired lung functioning who received brief counseling highlighting their spirometric test results. Participants in this analysis all received a brief motivational intervention for smoking cessation including spirometric testing and feedback ( approximately 20 min), were advised to quit smoking, offered free access to a phone-based smoking cessation program, and followed for one year. Outcomes were analyzed for smokers with (n=99) and without (n=168) impaired lung function. Participants with lung impairment reported greater use of self-help cessation materials at 6 months, greater use of non-study-provided counseling services at 6 and 12 months, higher 7-day PPA rates at 6 months, and were more likely to talk with their doctor about their spirometry results. Further research is warranted to determine if spirometry feedback has a differential treatment effect among smokers with and without lung impairment. It is premature to make practice recommendations based on these data. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema

PubMed Central

You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M; Samuel, Errol LG; Marcano, Daniela C; Sun, Zhengzong; Sikkema, William KA; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y; Tour, James M; Corry, David B; Kheradmand, Farrah

2015-01-01

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers. DOI: http://dx.doi.org/10.7554/eLife.09623.001 PMID:26437452

Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT.

PubMed

Gnagnarella, Patrizia; Maisonneuve, Patrick; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia

2013-06-01

The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95% CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95% CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.

Radon, smoking, and lung cancer: the need to refocus radon control policy.

PubMed

Lantz, Paula M; Mendez, David; Philbert, Martin A

2013-03-01

Exposure to radon is the second leading cause of lung cancer, and the risk is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers. The most powerful approach for reducing the public health burden of radon is shaped by 2 overarching principles: public communication efforts that promote residential radon testing and remediation will be the most cost effective if they are primarily directed at current and former smokers; and focusing on smoking prevention and cessation is the optimal strategy for reducing radon-induced lung cancer in terms of both public health gains and economic efficiency. Tobacco control policy is the most promising route to the public health goals of radon control policy.

Alcohol consumption and lung cancer risk in never smokers.

PubMed

García-Lavandeira, José Antonio; Ruano-Ravina, Alberto; Barros-Dios, Juan Miguel

2016-01-01

The main objective of this study is to analyse the role of alcohol consumption on lung cancer risk in people who have never smoked. We conducted a systematic review of the scientific literature following the PRISMA statement. We searched Medline, EMBASE and CINAHL using different combinations of MeSH terms and free text. We included cohort studies, pooled cohort studies and case-control studies comprising at least 25 anatomopathologically-confirmed diagnoses of lung cancer cases, a sample size larger than 100 individuals and more than five years of follow-up for cohort studies. We excluded studies that did not specifically report results for never smokers. We developed a quality score to assess the quality of the included papers and we ultimately included 14 investigations with a heterogeneous design and methodology. Results for alcohol consumption and lung cancer risk in never smokers are inconclusive; however, several studies showed a dose-response pattern for total alcohol consumption and for spirits. Heterogeneous results were found for wine and beer. No clear effect is observed for alcohol consumption. Due to the limited evidence, no conclusion can be drawn for beer or wine consumption. There is little research available on the effect of alcohol on lung cancer risk for people who have never smoked, and more studies are urgently needed on this topic. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

Dietary inflammatory index, Mediterranean diet score, and lung cancer: a prospective study.

PubMed

Hodge, A M; Bassett, J K; Shivappa, N; Hébert, J R; English, D R; Giles, G G; Severi, G

2016-07-01

To investigate prospectively the associations of Dietary Inflammatory Index (DII) and Mediterranean Diet Score (MDS) with lung cancer. We used data from men and women aged 40-69 years at recruitment in 1990-1994, who were participants in the Melbourne Collaborative Cohort Study (n = 35,303). A total of 403 incident lung cancer cases were identified over an average 18-year follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors, with age as the time metric. An inverse correlation was observed between the DII and MDS (ρ = -0.45), consistent with a higher DII being pro-inflammatory and less 'healthy,' while a high MDS reflects a 'healthier' diet. The DII was positively associated with risk of lung cancer in current smokers [HRQ4 vs Q1 = 1.70 (1.02, 2.82); Ptrend = 0.008] (p interaction between DII quartiles and smoking status = 0.03). The MDS was inversely associated with lung cancer risk overall [HR7-9 vs 0-3 = 0.64 (0.45, 0.90); Ptrend = 0.005] and for current smokers (HR7-9 vs 0-3 = 0.38 (0.19, 0.75); Ptrend = 0.005) (p interaction between MDS categories and smoking status = 0.31). The MDS showed an inverse association with lung cancer risk, especially for current smokers. A high DII, indicating a more pro-inflammatory diet, was associated with risk of lung cancer only for current smokers. A healthy diet may reduce the risk of lung cancer, especially in smokers.

The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients

PubMed Central

Kim, Hyun Jung; Kim, You-Sun; Kim, Kang-Hyun; Choi, Jun-Pyo; Kim, Yoon-Keun; Yun, Sunmi; Sharma, Lokesh; Dela Cruz, Charles S; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs. Subjects were matched for age and sex in all groups and for smoking levels in the COPD and healthy smoker groups. Each group included 12 men and 1 woman with the same mean age of 65.5 years. In all groups, EVs consistently showed more operational taxonomic units (OTUs) than lung tissue. In the healthy smoker and COPD groups, EVs had a higher Shannon index and a lower Simpson index than lung tissue and this trend was more prominent in the COPD group. Principal component analysis (PCA) showed clusters based on sample type rather than participants' clinical characteristics. Stenotrophomonas, Propionibacterium and Alicyclobacillus were the most commonly found genera. Firmicutes were highly present in the EVs of the COPD group compared with other samples or groups. Our analysis of the lung microbiome revealed that the bacterial communities present in the EVs and in the COPD group possessed distinct characteristics with differences in the OTUs, diversity indexes and PCA clustering. PMID:28408748

A Validated Clinical Risk Prediction Model for Lung Cancer in Smokers of All Ages and Exposure Types: A HUNT Study.

PubMed

Markaki, Maria; Tsamardinos, Ioannis; Langhammer, Arnulf; Lagani, Vincenzo; Hveem, Kristian; Røe, Oluf Dimitri

2018-05-01

Lung cancer causes >1·6 million deaths annually, with early diagnosis being paramount to effective treatment. Here we present a validated risk assessment model for lung cancer screening. The prospective HUNT2 population study in Norway examined 65,237 people aged >20years in 1995-97. After a median of 15·2years, 583 lung cancer cases had been diagnosed; 552 (94·7%) ever-smokers and 31 (5·3%) never-smokers. We performed multivariable analyses of 36 candidate risk predictors, using multiple imputation of missing data and backwards feature selection with Cox regression. The resulting model was validated in an independent Norwegian prospective dataset of 45,341 ever-smokers, in which 675 lung cancers had been diagnosed after a median follow-up of 11·6years. Our final HUNT Lung Cancer Model included age, pack-years, smoking intensity, years since smoking cessation, body mass index, daily cough, and hours of daily indoors exposure to smoke. External validation showed a 0·879 concordance index (95% CI [0·866-0·891]) with an area under the curve of 0·87 (95% CI [0·85-0·89]) within 6years. Only 22% of ever-smokers would need screening to identify 81·85% of all lung cancers within 6years. Our model of seven variables is simple, accurate, and useful for screening selection. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Cigarette smoke radioactivity and lung cancer risk.

PubMed

Karagueuzian, Hrayr S; White, Celia; Sayre, James; Norman, Amos

2012-01-01

To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.

Cruciferous Vegetable Intake Is Inversely Associated with Lung Cancer Risk among Current Nonsmoking Men in the Japan Public Health Center (JPHC) Study.

PubMed

Mori, Nagisa; Shimazu, Taichi; Sasazuki, Shizuka; Nozue, Miho; Mutoh, Michihiro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Inoue, Manami; Takachi, Ribeka; Sunami, Ayaka; Ishihara, Junko; Sobue, Tomotaka; Tsugane, Shoichiro

2017-05-01

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse. Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan. Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors). Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P -trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P -trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P -trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers. Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. © 2017 American Society for Nutrition.

Factors affecting 30-month survival in lung cancer patients.

PubMed

Mahesh, P A; Archana, S; Jayaraj, B S; Patil, Shekar; Chaya, S K; Shashidhar, H P; Sunitha, B S; Prabhakar, A K

2012-10-01

Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients.

Factors affecting 30-month survival in lung cancer patients

PubMed Central

Mahesh, P.A.; Archana, S.; Jayaraj, B.S.; Patil, Shekar; Chaya, S.K.; Shashidhar, H.P.; Sunitha, B.S.; Prabhakar, A.K.

2012-01-01

Background & objectives: Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. Methods: Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. Results: A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. Interpretation & conclusions: Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients. PMID:23168702

Regional Mapping of Gas Uptake by Blood and Tissue in the Human Lung using Hyperpolarized Xenon-129 MRI

PubMed Central

Qing, Kun; Ruppert, Kai; Jiang, Yun; Mata, Jaime F.; Miller, G. Wilson; Shim, Y. Michael; Wang, Chengbo; Ruset, Iulian C.; Hersman, F. William; Altes, Talissa A.; Mugler, John P.

2013-01-01

Purpose To develop a breath-hold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects. Materials and Methods A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue and RBC images in healthy subjects, smokers and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas and RBC-to-tissue) were calculated from the images for quantitative comparison. Results Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects. Conclusion Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breath-hold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics. PMID:23681559

[Oxidative stress in pathogenesis of COPD].

PubMed

Betsuyaku, Tomoko

2007-04-01

Cigarette smoke and aging are major risk factors of chronic obstructive pulmonary disease(COPD). It remains unsolved how long -term smoking with age affects the molecular responses in the lung. Respiratory tract is the major interface to the environment and is rich in glutathione, which protects lung from oxidative stress. We performed bronchoalveolar lavage for nonsmokers and smokers of various ages, who were further categorized according to the presence of emphysema on high-resolution computed tomography. We thus evaluated glutathione antioxidant system in BAL fluid. Characterization of older smokers with long-term smoking histories, contrasted with young recent smokers, may in part explain the predisposition of the lungs to destructive lung diseases. On the other hands, oxidative stress results from an imbalance in aerobic metabolism and poses a serious threat to cellular apoptosis, leading to emphysematous lung destruction. The therapeutic interference with targeted up-regulation of protective mechanisms might be critical for the success of future COPD therapies.

α1-antitrypsin polymerizes in alveolar macrophages of smokers with and without α1-antitrypsin deficiency.

PubMed

Bazzan, Erica; Tinè, Mariaenrica; Biondini, Davide; Benetti, Riccardo; Baraldo, Simonetta; Turato, Graziella; Fagiuoli, Stefano; Sonzogni, Aurelio; Rigobello, Chiara; Rea, Federico; Calabrese, Fiorella; Foschino-Barbaro, Maria Pia; Miranda, Elena; Lomas, David A; Saetta, Marina; Cosio, Manuel G

2018-05-12

The deficiency of α 1 -antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AM) produce AAT, however it is not known if Z-AAT can polymerize in AM, further decreasing lung AAT and promoting lung inflammation. To investigate if AAT polymerizes in human AM and to study the possible relation between polymerization and degree of lung inflammation. Immunohistochemical analysis with 2C1 monoclonal antibody specific for polymerized AAT was performed in sections of: 9 lungs from individuals with AAT deficiency (AATD) and severe COPD, 35 smokers with normal AAT levels of which 24 with severe COPD and 11 without COPD, and 13 non-smokers. AM positive for AAT polymers were counted and expressed as percentage of total AM in lung. AAT polymerization was detected in [27(4-67)%] of AM from individuals with AATD but also in AM from smokers with normal AAT with [24(0-70)%] and without [24(0-60)%] COPD, but not in AM from non-smokers [0(0-1.5)%] (p<0.0001). The percentage of AM with polymerized AAT correlated with pack-years smoked (r=0.53,p=0.0001), FEV 1 /FVC (r=-0.41,p=0.005), Small Airways Disease (r=0.44,p=0.004), number of CD8+T-cells and neutrophils in alveolar walls (r=0.51,p=0.002; r=0.31,p=0.05 respectively). Polymerization of AAT in alveolar macrophages occurs in lungs of individuals with AATD but also in smokers with normal AAT levels with or without COPD. Our findings highlight the similarities in the pathophysiology of COPD in individuals with and without AATD, adding a potentially important step to the mechanism of COPD. Copyright © 2018. Published by Elsevier Inc.

Lung Cancer Risk and Demographic Characteristics of Current 20-29 Pack-year Smokers: Implications for Screening.

PubMed

Pinsky, Paul F; Kramer, Barnett S

2015-11-01

Based on current recommendations, 30+ pack-years of smoking are required for eligibility for low-dose CT (LDCT) lung cancer screening; former smokers must have quit within 15 years. We investigated whether current smokers with 20 to 29 pack-years have similar lung cancer risks as eligible former smokers and also whether they have a different demographic profile. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was a randomly assigned screening trial of subjects age 55 to 74 years with chest radiographs (CXR) used for lung cancer. Subjects completed a baseline questionnaire containing smoking history questions. Cox proportional hazards models, adjusted for age and sex, were utilized to estimate hazard ratios (HRs) for various smoking history groups. Next, we utilized the National Health Interview Survey (NHIS), which inquired about smoking history and race/ethnicity, to analyze the demographic profiles of various high-risk smoking history categories. All statistical tests were two-sided. The PLCO cohort included 18 114 former and 12 243 current LDCT-eligible smokers, plus 2283 20- to 29-pack-year current smokers. The hazard ratio for 20- to 29-pack-year current smokers compared with eligible (30+ pack-year) former smokers was 1.07 (95% confidence interval [CI] = 0.75 to 1.5). Based on the NHIS, 10 million persons in the United States are currently LDCT eligible; an additional 1.6 million (16%, 95% CI = 13.6% to 19.0%) are 20- to 29-pack-year current smokers. The percentage increase in eligibles if 20- to 29-pack-year current smokers were included was substantially greater for women than men (22.2%, 95% CI = 17.9% to 26.7%; vs 12.2%, 95% CI = 9.3% to 15.3%, P < .001) and for minorities than non-Hispanic whites (30.0%, 95% CI = 24.2% to 36.0%; vs 14.1%, 95% CI = 11.1% to 17.0%, P < .001). The potential benefits and harms of recommending LDCT screening for 20 to 29-pack-year current smokers should be assessed. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Characteristics and Prognosis of Never-Smokers and Smokers with Asthma in the Copenhagen General Population Study. A Prospective Cohort Study.

PubMed

Çolak, Yunus; Afzal, Shoaib; Nordestgaard, Børge G; Lange, Peter

2015-07-15

Asthma is associated with complications, cardiovascular comorbidities, and higher mortality in some individuals. To test the hypothesis that, among individuals with asthma, never-smokers have different characteristics and a better prognosis than smokers. We recruited 94,079 individuals aged 20-100 years from the Copenhagen General Population Study, a prospective cohort study. Among these individuals, 5,691 (6%) had self-reported asthma (2,304 never-smokers, 2,467 former smokers, and 920 current smokers). We examined respiratory symptoms, lung function, and levels of inflammatory and allergic biomarkers in systemic circulation. Furthermore, we assessed prospectively the risk of asthma or chronic obstructive pulmonary disease (COPD) exacerbations, pneumonias, lung cancer, ischemic heart disease, ischemic stroke, and all-cause mortality during 4.5 years of follow-up. Compared with never-smokers without asthma, individuals with asthma had more respiratory symptoms and airflow limitation and higher levels of inflammatory and allergic biomarkers, which were most pronounced in smokers. Among individuals with asthma compared with never-smokers without asthma, multivariable adjusted hazard ratios for asthma exacerbations were 11 (95% confidence interval: 5.8-22) in never-smokers, 13 (6.2-29) in former smokers, and 18 (8.2-39) in current smokers. The corresponding values for other endpoints were, respectively, 8.9 (2.1-38), 23 (8.8-58), and 36 (12-105) for COPD exacerbations; 1.5 (0.9-2.2), 1.6 (1.0-2.4), and 2.4 (1.6-3.7) for pneumonias; 0.6 (0.1-5.1), 4.0 (1.3-12), and 13 (4.3-41) for lung cancer; 1.2 (0.9-1.6), 1.5 (1.2-2.0), and 2.0 (1.4-2.9) for ischemic heart disease; 1.4 (0.9-2.1), 1.2 (0.8-1.9), and 3.0 (1.7-5.3) for ischemic stroke; and 0.9 (0.6-1.3), 1.5 (1.1-2.0), and 2.7 (1.9-3.7) for all-cause mortality. Never-smokers with asthma had an increased risk of asthma and COPD exacerbations, and possibly pneumonias. Importantly, the risks for lung cancer, cardiovascular comorbidities, and death were restricted to smokers with asthma. Thus, tobacco smoking was the main explanation for poor prognosis in asthma.

Radon, Smoking, and Lung Cancer: The Need to Refocus Radon Control Policy

PubMed Central

Mendez, David; Philbert, Martin A.

2013-01-01

Exposure to radon is the second leading cause of lung cancer, and the risk is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers. The most powerful approach for reducing the public health burden of radon is shaped by 2 overarching principles: public communication efforts that promote residential radon testing and remediation will be the most cost effective if they are primarily directed at current and former smokers; and focusing on smoking prevention and cessation is the optimal strategy for reducing radon-induced lung cancer in terms of both public health gains and economic efficiency. Tobacco control policy is the most promising route to the public health goals of radon control policy. PMID:23327258

Patient-provider discussions about lung cancer screening pre- and post-guidelines: Health Information National Trends Survey (HINTS).

PubMed

Carter-Harris, Lisa; Tan, Andy S L; Salloum, Ramzi G; Young-Wolff, Kelly C

2016-11-01

In 2013, the USPSTF issued a Grade B recommendation that long-term current and former smokers receive lung cancer screening. Shared decision-making is important for individuals considering screening, and patient-provider discussions an essential component of the process. We examined prevalence and predictors of lung cancer screening discussions pre- and post-USPSTF guidelines. Data were obtained from two cycles of the Health Information National Trends Survey (2012; 2014). The analyzed sample comprised screening-eligible current and former smokers with no personal history of lung cancer (n=746 in 2012; n=795 in 2014). Descriptive and multiple logistic regression analyses were conducted; patient-reported discussion about lung cancer screening with provider was the outcome of interest. Contrary to expectations, patient-provider discussions about lung cancer screening were more prevalent pre-guideline, but overall patient-provider discussions were low in both years (17% in 2012; 10% in 2014). Current smokers were more likely to have had a discussion than former smokers. Significant predictors of patient-provider discussions included family history of cancer and having healthcare coverage. The prevalence of patient-provider discussions about lung cancer screening is suboptimal. There is a critical need for patient and provider education about shared decision-making and its importance in cancer screening decisions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Combination therapy for non-small cell lung cancer studied in new clinical trial | Center for Cancer Research

Cancer.gov

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, is slow growing and can affect smokers and non-smokers alike. David S. Schrump, M.D., Surgical Chief of the Thoracic and Gastrointestinal Oncology Branch, is leading the NCI’s participation in a multicenter trial of a combination drug therapy in patients with NSCLC. Read more...

Risk perceptions and smoking decisions of adult Chinese men.

PubMed

Lin, Wanchuan; Sloan, Frank

2015-01-01

This study analyzes effects of changes in risk perceptions of smoking's health harms on actual and attempted quits and quitting intentions of male smokers in China. Our survey of 5000+ male smokers was conducted two years after their neighbor's lung cancer diagnosis. We use proximity to a lung cancer neighbor as an exogenous determinant of individual's smoking risk perception. We show that learning of a neighbor's lung cancer diagnosis substantially affects smokers' subjective beliefs about smoking's harms, which in turn affects decisions about continued smoking and intentions to quit. Our study findings offer important public policy implications in indicating the importance of designing health-warning messages that fit smokers' personal circumstances as opposed to warnings solely based on edicts from scientific experts and/or epidemiological evidence. Copyright © 2014 Elsevier B.V. All rights reserved.

Emphysema and pulmonary impairment in coal miners: Quantitative relationship with dust exposure and cigarette smoking

NASA Astrophysics Data System (ADS)

Kuempel, E. D.; Vallyathan, V.; Green, F. H. Y.

2009-02-01

Coal miners have been shown to be at increased risk of developing chronic obstructive pulmonary diseases including emphysema. The objective of this study was to determine whether lifetime cumulative exposure to respirable coal mine dust is a significant predictor of developing emphysema at a clinically-relevant level of severity by the end of life, after controlling for cigarette smoking and other covariates. Clinically-relevant emphysema severity was determined from the association between individuals' lung function during life (forced expiratory volume in one second, FEV1, as a percentage of predicted normal values) and emphysema severity at autopsy (as the proportion of lung tissue affected). In a logistic regression model, cumulative exposure to respirable coal mine dust was a statistically significant predictor of developing clinically-relevant emphysema severity, among both ever-smokers and never-smokers. The odds ratio for developing emphysema associated with FEV1 <80% at the cohort mean cumulative coal dust exposure (87 mg/m3 x yr) was 2.30 (1.46-3.64, 95% confidence limits), and at the cohort mean cigarette smoking (among smokers: 42 pack-years) was 1.95 (1.39-2.79).

Cannabis smoking and risk of lung cancer in men: a pooled analysis of three studies in Maghreb.

PubMed

Berthiller, Julien; Straif, Kurt; Boniol, Mathieu; Voirin, Nicolas; Benhaïm-Luzon, Veronique; Ayoub, Wided Ben; Dari, Iman; Laouamri, Slimane; Hamdi-Cherif, Mokhtar; Bartal, Mohamed; Ayed, Fahrat Ben; Sasco, Annie J

2008-12-01

Cannabis is the most widely consumed illicit drug worldwide and the relation between cannabis smoking and lung cancer is suggestive, albeit inconclusive. We conducted three hospital based case-control studies in Tunisia, Morocco, and Algeria, three areas of high prevalence of cannabis consumption as well as production. This paper presents the pooled analysis of these three studies restricted to men with a total of 430 cases and 778 controls. Ninety-six percent of the cases and 67.8% of the controls were tobacco smokers and 15.3% of the cases and 5% of the controls were ever cannabis smokers. All cannabis smokers were tobacco users. Adjusting for country, age, tobacco smoking, and occupational exposure, the odds ratio (OR) for lung cancer was 2.4 (95% confidence interval [CI]: 1.6-3.8) for ever cannabis smoking. This association remained after adjustment for lifetime tobacco packyears as continuous variable, OR = 2.3 (95% CI: 1.5-3.6). The OR adjusted for intensity of tobacco smoking (cigarette/d) among current tobacco smokers and never cannabis smokers was 10.9 (95% CI: 6.0-19.7) and the OR among current tobacco users and ever cannabis smokers was 18.2 (95% CI: 8.0-41.0). The risk of lung cancer increased with increasing joint-years, but not with increasing dose or duration of cannabis smoking. Our results suggest that cannabis smoking may be a risk factor for lung cancer. However, residual confounding by tobacco smoking or other potential confounders may explain part of the increased risk.

Exhaled Breath Temperature as a Novel Marker of Future Development of COPD: Results of a Follow-Up Study in Smokers.

PubMed

Labor, Marina; Vrbica, Žarko; Gudelj, Ivan; Labor, Slavica; Jurić, Iva; Plavec, Davor

2016-12-01

Although only less than one-third of smokers develop COPD, early marker(s) of COPD development are lacking. The aim of this research was to assess the ability of an average equilibrium exhaled breath temperature (EBT) in identifying susceptibility to cigarette smoke so as to predict COPD development in smokers at risk. The study was a part of a multicenter prospective cohort study in current smokers (N = 140, both sexes, 40-65 years, ≥20 pack-years) with no prior diagnosis of COPD. Diagnostic workup includes history, physical, quality of life, hematology and highly sensitive CRP, EBT before and after smoking a cigarette, lung function with bronchodilator test, and 6-minute walk test. Patients without a diagnosis of COPD and in GOLD 1 stage at initial assessment were reassessed after 2 years. COPD was additionally diagnosed based on lower level of normal (LLN) lung function criteria. Utility of EBT for disease progression was analyzed using receiver operator curve (ROC) and logistic regression analyses. Change in EBT after smoking a cigarette at initial visit (ΔEBT) was significantly predictive for disease progression (newly diagnosed COPD; newly diagnosed COPD + severity progression) after 2 years (p < 0.05 for both). ΔEBT had an AUC of 0.859 (p = 0.011) with sensitivity of 66.7% and specificity of 98.1% for newly diagnosed COPD using LLN criteria. We conclude that EBT shows potential for predicting the future development of COPD in current smokers. This was best seen using LLN to diagnose COPD, adding further evidence to question the use of GOLD criteria for diagnosing COPD.

Differential modulation of leukotriene B4 synthesis and degradation in human bronchoalveolar lavage cells by lipopolysaccharide and tobacco smoke.

PubMed

Mao, Jenny T; Tashkin, Donald P; Tsu, I-Hsien; Serio, Kenneth J

2008-09-01

Leukotrienes have been implicated to play a prominent inductive role in carcinogenesis. We previously reported that bronchoalveolar lavage (BAL) cells from smokers manifested higher levels of leukotriene B4 (LTB4) production than ex-smokers. This study aims to elucidate the underlying mechanism(s). BAL cells from current and former smokers were exposed to lipopolysaccharide (LPS) for up to 7 days. LPS induced the release of LTB4 from BAL cells and down-regulated 5-lipoxygenase (5-LOX) mRNA expression in a dose-dependent manner, followed by a decrease in 5-LOX protein production and normalization of LTB4 levels. Exogenous LTB4 inhibited LPS-induced 5-LOX activity and accentuated the down-regulation of 5-LOX mRNA, whereas suppression of 5-LOX abrogated the LPS-induced changes, suggesting a negative feedback mechanism. LPS concomitantly induced expression and activity of the LTB4 metabolizing enzyme LTB4 omega-hydroxylase (LTB4OH) in ex-smokers' BAL cells, but not in smokers' BAL cells. In vitro smoke exposure of ex-smokers' BAL cells also abrogated the LPS-induced up-regulation of LTB4OH mRNA expression. Furthermore, ex-smokers' BAL cells expressed significantly higher LTB4OH mRNA levels than smokers' BAL cells. Such differential modulation of LTB4 synthesis and degradation by LPS in the setting of tobacco smoke exposure suggests that mechanisms responsible for sustained elevation of LTB4 levels in the lung microenvironment may contribute to the pathogenesis of tobacco-related respiratory diseases such as lung cancer. By regulating the balance of LTB4 in the lung, LTB4OH may function as a suppressor of lung carcinogenesis.

Patient's lung cancer diagnosis as a cue for relatives' smoking cessation: evaluating the constructs of the teachable moment.

PubMed

McBride, Colleen M; Blocklin, Michelle; Lipkus, Isaac M; Klein, William M P; Brandon, Thomas H

2017-01-01

To understand whether patient-reported experiences with lung cancer may create teachable moments (TM) for their relatives as evidenced by shifts in their risk perceptions, affective response, and self-image and in turn, motivation to quit smoking. Patients at a comprehensive cancer center (n = 152) completed a survey within 6 months of lung cancer diagnosis to assess their cancer-related symptoms and openness and enumerated relatives who were smokers. Relative smokers (n = 218) then completed a survey assessing their risk perceptions, affective response, and self-image as a smoker related to the patient's diagnosis (TM mechanisms), and their motivation to quit smoking. Cross-sectional mediation and moderation analyses were conducted to explore the links between patient-reported experiences, and relatives' TM mechanisms, and motivation to quit smoking. Relative-reported affect was a significant mediator of the association between patient-reported symptoms and relative smoker's desire to quit. Relatives' self-image was a significant moderator of the association between patient-reported symptoms and relative smoker's desire to quit, such that patients' reported symptoms were associated with relatives' desire to quit only when the relative smoker reported a generally positive self-image as a smoker. No evidence was found for moderated mediation. However, the link between symptoms and negative affect was moderated by perceptions of risk. Whether smokers experience a family member's lung cancer as a TM is influenced by multiple interrelated cognitive and affective factors that warrant further exploration. Clearer understanding of these factors could inform how to re-invigorate and sustain this motivation to promote concrete actions toward smoking cessation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Computerised respiratory sounds can differentiate smokers and non-smokers.

PubMed

Oliveira, Ana; Sen, Ipek; Kahya, Yasemin P; Afreixo, Vera; Marques, Alda

2017-06-01

Cigarette smoking is often associated with the development of several respiratory diseases however, if diagnosed early, the changes in the lung tissue caused by smoking may be reversible. Computerised respiratory sounds have shown to be sensitive to detect changes within the lung tissue before any other measure, however it is unknown if it is able to detect changes in the lungs of healthy smokers. This study investigated the differences between computerised respiratory sounds of healthy smokers and non-smokers. Healthy smokers and non-smokers were recruited from a university campus. Respiratory sounds were recorded simultaneously at 6 chest locations (right and left anterior, lateral and posterior) using air-coupled electret microphones. Airflow (1.0-1.5 l/s) was recorded with a pneumotachograph. Breathing phases were detected using airflow signals and respiratory sounds with validated algorithms. Forty-four participants were enrolled: 18 smokers (mean age 26.2, SD = 7 years; mean FEV 1 % predicted 104.7, SD = 9) and 26 non-smokers (mean age 25.9, SD = 3.7 years; mean FEV 1 % predicted 96.8, SD = 20.2). Smokers presented significantly higher frequency at maximum sound intensity during inspiration [(M = 117, SD = 16.2 Hz vs. M = 106.4, SD = 21.6 Hz; t(43) = -2.62, p = 0.0081, d z  = 0.55)], lower expiratory sound intensities (maximum intensity: [(M = 48.2, SD = 3.8 dB vs. M = 50.9, SD = 3.2 dB; t(43) = 2.68, p = 0.001, d z  = -0.78)]; mean intensity: [(M = 31.2, SD = 3.6 dB vs. M = 33.7,SD = 3 dB; t(43) = 2.42, p = 0.001, d z  = 0.75)] and higher number of inspiratory crackles (median [interquartile range] 2.2 [1.7-3.7] vs. 1.5 [1.2-2.2], p = 0.081, U = 110, r = -0.41) than non-smokers. Significant differences between computerised respiratory sounds of smokers and non-smokers have been found. Changes in respiratory sounds are often the earliest sign of disease. Thus, computerised respiratory sounds might be a promising measure to early detect smoking related respiratory diseases.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

PubMed

Lowry, Kathryn P; Gazelle, G Scott; Gilmore, Michael E; Johanson, Colden; Munshi, Vidit; Choi, Sung Eun; Tramontano, Angela C; Kong, Chung Yin; McMahon, Pamela M

2015-05-15

Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study limited data set. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk from COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population. © 2015 American Cancer Society.

The contribution of DNA apurinic/apyrimidinic endonuclease genotype and smoking habit to Taiwan lung cancer risk.

PubMed

Chen, Wei-Chun; Tsai, Chia-Wen; Hsia, Te-Chun; Chang, Wen-Shin; Lin, Liang-Yi; Liang, Shinn-Jye; Tu, Chih-Yen; Cheng, Wei-Erh; Chen, Hung-Jen; Wang, Shu-Ming; Bau, da-Tian

2013-06-01

To evaluate the association and interaction of genotypic polymorphism the gene for DNA-apurinic/apyrimidinic endonuclease (APEX1) with personal smoking habit and lung cancer risk in Taiwan, the polymorphic variants of APEX1, Asp(148)Glu (rs1130409), were analyzed in association with lung cancer risk, and their joint effect with personal smoking habits on lung cancer susceptibility was discussed. In this hospital-based case-control study, 358 patients with lung cancer and 716 cancer-free controls, frequency-matched by age and sex, were recruited and genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results showed that the percentages of TT, TG and GG APEX1 Asp(148)Glu genotypes were not significantly different at 43.0%, 41.1% and 15.9% in the lung cancer patient group and 39.9%, 46.1% and 14.0% in non-cancer control group, respectively. We further analyzed the genetic-lifestyle effects on lung cancer risk and found the contribution of APEX1 Asp(148)Glu genotypes to lung cancer susceptibility was neither enhanced in the cigarette smokers nor in the non-smokers (p=0.3550 and 0.8019, respectively). Our results provide evidence that the non-synonymous polymorphism of APEX1 Asp(148)Glu may not be directly associated with lung cancer risk, nor enhance the effects of smoking habit on lung cancer development.

A qualitative study of lung cancer risk perceptions and smoking beliefs among national lung screening trial participants.

PubMed

Park, Elyse R; Streck, Joanna M; Gareen, Ilana F; Ostroff, Jamie S; Hyland, Kelly A; Rigotti, Nancy A; Pajolek, Hannah; Nichter, Mark

2014-02-01

The National Comprehensive Cancer Network and the American Cancer Society recently released lung screening guidelines that include smoking cessation counseling for smokers undergoing screening. Previous work indicates that smoking behaviors and risk perceptions of the National Lung Screening Trial (NLST) participants were relatively unchanged. We explored American College of Radiology Imaging Network (ACRIN)/NLST former and current smokers' risk perceptions specifically to (a) determine whether lung screening is a cue for behavior change, (b) elucidate risk perceptions for lung cancer and smoking-related diseases, and (c) explore postscreening behavioral intentions and changes. A random sample of 35 participants from 4 ACRIN sites were qualitatively interviewed 1-2 years postscreen. We used a structured interview guide based on Health Belief Model and Self-Regulation Model constructs. Content analyses were conducted with NVivo 8. Most participants endorsed high-risk perceptions for lung cancer and smoking-related diseases, but heightened concern about these risks did not appear to motivate participants to seek screening. Risk perceptions were mostly attributed to participants' heavy smoking histories; former smokers expressed greatly reduced risk. Lung cancer and smoking-related diseases were perceived as very severe although participants endorsed low worry. Current smokers had low confidence in their ability to quit, and none reported quitting following their initial screen. Lung screening did not appear to be a behavior change cue to action, and high-risk perceptions did not translate into quitting behaviors. Cognitive and emotional dissonance and avoidance strategies may deter engagement in smoking behavior change. Smoking cessation and prevention interventions during lung screening should explore risk perceptions, emotions, and quit confidence.

A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis.

PubMed

Sun, Yanlai; Li, Zhenxiang; Li, Jianning; Li, Zengjun; Han, Jianjun

2016-03-04

Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75-0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63-1.27), 0.74 (95% CI: 0.62-0.89) and 0.86 (95% CI: 0.79-0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.

Difference in airflow obstruction between Hispanic and non-Hispanic White female smokers.

PubMed

Sood, Akshay; Stidley, Christine A; Picchi, Maria A; Celedón, Juan C; Gilliland, Frank; Crowell, Richard E; Belinsky, Steven A; Tesfaigzi, Yohannes

2008-10-01

Smoking-related respiratory diseases are a major cause of morbidity and mortality. However, the relationship between smoking and respiratory disease has not been well-studied among ethnic minorities in general and among women in particular. The objective of this cross-sectional study was to evaluate the risk of airflow obstruction and to assess lung function among Hispanic and non-Hispanic White (NHW) female smokers in a New Mexico cohort. Participants completed a questionnaire detailing smoking history and underwent spirometry testing. Outcomes studied included airflow obstruction, selected lung function parameters, and chronic mucus hyper-secretion. Chi square, logistic, and linear regression techniques were utilized. Of the 1,433 eligible women participants, 248 (17.3%) were Hispanic; and 319 had airflow obstruction (22.3%). Hispanic smokers were more likely to be current smokers, and report lower pack-years of smoking, compared to NHW smokers (p < 0.05 for all analyses). Further, Hispanic smokers were at a reduced risk of airflow obstruction compared to NHW smokers, with an O.R. of 0.51, 95% C.I. 0.34, 0.78 (p = 0.002) after adjustment for age, BMI, pack-years and duration of smoking, and current smoking status. Following adjustment for covariates, Hispanic smokers also had a higher mean absolute and percent predicted post-bronchodilator FEV(1)/FVC ratio, as well as higher mean percent predicted FEV(1) (p < 0.05 for all analyses). Hispanic female smokers in this New Mexico-based cohort had lower risk of airflow obstruction and better lung function than NHW female smokers. Further, smoking history did not completely explain these associations.

Reassessing the importance of 'lost pleasure' associated with smoking cessation: implications for social welfare and policy.

PubMed

Pechacek, Terry Frank; Nayak, Pratibha; Slovic, Paul; Weaver, Scott R; Huang, Jidong; Eriksen, Michael P

2017-11-28

Benefit-cost analyses of tobacco regulations include estimates of the informed choice of smokers to continue smoking. Few studies have focused on subjective feelings associated with continued smoking. This study estimates how smoker discontent and regret relate to risk perceptions and health concerns. We analysed data from a 2015 nationally representative, online survey of 1284 US adult current smokers. Information was collected on regret, intention to quit, perceived addiction, risk perceptions and health concerns. Multivariate logistic regression adjusting for sociodemographics and health status was used to examine factors associated with smoker discontent. More than 80% of current smokers report high (22.5%) or very high (59.8%) discontent due to inability to quit, perceived addiction and regret about having started to smoke. Higher levels of discontent did not vary significantly by sex, age, race/ethnicity, education or income (adjusted odds ratios (AORs) 0.5-1.2). Compared with the smokers expressing low (5.9%) or very low (3.6%) discontent, those expressing higher levels of discontent perceived their health status as fair/poor (AOR=2.3), worried most of the time about lung cancer (AOR=4.6) and felt they were more likely to develop lung cancer in the future (AOR=5.1). The proportion of smokers who might be characterised as having a preference to continue smoking are greatly outnumbered by addicted, discontent and concerned smokers who want to quit and regret ever having started to smoke. These discontent smokers could have a substantial net welfare gain if new regulations helped them escape their concerns about the health effects from continuing smoking. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The DNA Methyltransferase 3B -149 Genetic Polymorphism Modulates Lung Cancer Risk from Smoking

PubMed Central

Lai, Chung Yu; Huang, Chia Chen; Tsai, Chin Hung; Wang, Jiun Yao; Kerr, Chih Ling; Chen, Yi Yu; Cai, Yan Wei; Wong, Ruey Hong

2017-01-01

Background: Smoking can cause increase of DNA methylation and hypermethylation of tumor suppressor genes, this possible contributing to subsequent lung cancer development. DNA methyltransferase 3B (DNMT3B) is crucial in regulation of DNA methylation and it has been proposed that green tea might lower cancer risk through inhibiting its activity. Here, we designed a case-control study to investigate whether the DNMT3B -149 genetic polymorphism could modulate lung cancer risk due to smoking. Possible interactions of smoking and green tea consumption with this DNMT3B genetic polymorphism were also assessed. Materials and Methods: A total of 190 lung cancer patients and 380 healthy controls were recruited. Questionnaires were administered to obtain data on sociodemographic and lifestyle variables, as well as family history of lung cancer. Genotypes for DNMT3B -149 were identified by polymerase chain reaction. Results: Smoking, green tea consumption, exposure to cooking fumes, family history of lung cancer, and the DNMT3B -149 genotype (odds ratio (OR)=2.65; 95% confidence interval (CI) 1.15-6.10) were all significantly associated with the development of lung cancer. Smokers carrying the DNMT3B -149 TT genotype were at elevated risk compared to non-smokers carrying DNMT3B -149 (OR=7.69; 95% CI 2.55-23.14). Interaction of smoking with DNMT3B -149 genotypes was significant regarding lung cancer risk. However, interaction between green tea drinking and DNMT3B -149 genotypes was not. Conclusions: The DNMT3B -149 TT genotype might increase the smoking-associated lung cancer risk. PMID:29072397

Canadian individual risks of radon-induced lung cancer for different exposure profiles.

PubMed

Chen, Jing

2005-01-01

Indoor radon has been determined to be the second leading cause of lung cancer after tobacco smoking. There is an increasing need among radiation practitioners to have numerical values of lung cancer risks for men and women, ever-smokers and never-smokers exposed to radon in homes. This study evaluates individual risks for the Canadian population exposed to radon in homes at different radon concentrations and for different periods of their lives. Based on the risk model developed recently by U.S. Environmental Protection Agency (EPA), individual risks of radon-induced lung cancers are calculated with Canadian age-specific rates for overall and lung cancer mortalities (1996-2000) as well as the Canadian smoking prevalence data in 2002. Convenient tables of lifetime relative risks are constructed for lifetime exposures and short exposures between any two age intervals from 0 to 110, and for various radon concentrations found in homes from 50 to 1000 Bq/m3. The risk of developing lung cancer from residential radon exposure increases with radon concentration and exposure duration. For short exposure periods, such as 10 or 20 years, risks are higher in middle age groups (30-50) compared especially to the later years. Individuals could lower their risks significantly by reducing radon levels earlier in life. The tables could help radiation protection practitioners to better communicate indoor radon risk to members of the public.

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

PubMed Central

Meguid, Robert A.; Hooker, Craig M.; Harris, James; Xu, Li; Westra, William H.; Sherwood, J. Timothy; Sussman, Marc; Cattaneo, Stephen M.; Shin, James; Cox, Solange; Christensen, Joani; Prints, Yelena; Yuan, Nance; Zhang, Jennifer; Yang, Stephen C.

2010-01-01

Background: Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC. Methods: This investigation was a single-institution retrospective study of never and current smokers with NSCLC from 1975 to 2004. From an analytic cohort of 4,546 patients with NSCLC, we identified 724 never smokers and 3,822 current smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios (HRs) were estimated using Cox proportional hazard modeling and then further adjusted by other covariates. Results: Never smokers were significantly more likely than current smokers to be women (P < .01), older (P < .01), and to have adenocarcinoma (P < .01) and bronchioloalveolar carcinoma (P < .01). No statistically significant differences existed in stage distribution at presentation for the analytic cohort (P = .35) or for the subgroup undergoing surgery (P = .24). The strongest risk factors of mortality among patients with NSCLC who underwent surgery were advanced stage (adjusted hazard ratio, 3.43; 95% CI, 2.32-5.07; P < .01) and elevated American Society of Anesthesiologists classification (adjusted hazard ratio, 2.18; 95% CI, 1.40-3.40; P < .01). The minor trend toward an elevated risk of death on univariate analysis for current vs never smokers in the surgically treated group (hazard ratio, 1.20; 95% CI, 0.98-1.46; P = .07) was completely eliminated when the model was adjusted for covariates (P = .97). Conclusions: Our findings suggest that smoking status at time of lung cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal. PMID:20507946

Skin metastases from lung cancer: a case report.

PubMed

Pajaziti, Laura; Hapçiu, Syzana Rexhepi; Dobruna, Shkendije; Hoxha, Naim; Kurshumliu, Fisnik; Pajaziti, Artina

2015-04-11

Lung cancer is one of the most frequent malignancies, with high mortality rates. It can metastasize in almost all organs, but more often invades hilar nodes, liver, adrenal glands, bones and brain. There are various data on the incidence of lung cancer metastases in the skin. In 1-12% of patients with lung cancer are developed skin metastases. Metastases in the skin may be the first sign of lung cancer. Forty-five years old Albanian male, smoker, was admitted to our department with multiple nodules localized in the skin of the head, neck, back and chest. The nodules measuring 5-15 millimeters in greatest dimension were round and skin-colored, with telangiectasias, firm and tender. They appeared in an eruptive form about two weeks before being admitted at our hospital. In addition, the patient exhibited signs of weight loss, anorexia and fatigue. Excisional biopsy was performed to one of the lesions. Histopathology confirmed metastatic nature of the lesion namely, malignant tumor of neuroendocrine phenotype consistent with small-cell carcinoma. Chest X-ray and computed tomography revealed an expansive process in the 7(th) segment of the left lung, left hilar and mediastinal lymphadenopathy and a suspicious initial secondary deposit in the left adrenal gland. The patient was referred to the department of oncology for further treatment. After the third cycle of chemotherapy, the magnetic resonance imaging revealed brain metastases. The patient passed away four months after the diagnosis of lung cancer first presented with skin metastases. Metastases in skin may be the first sign of lung cancer. Although rare appearing, we should raise suspicion in cases of atypical lesions in the skin not only of the smokers, but also of the non-smokers. Skin metastases from small-cell lung carcinoma are a poor prognostic indicator. The appearance of multiple skin metastases with other internal metastases shorten the survival time.

MicroRNAs derived from circulating exosomes as non-invasive biomarkers for screening and diagnose lung cancer

PubMed Central

Cazzoli, Riccardo; Buttitta, Fiamma; Di Nicola, Marta; Malatesta, Sara; Marchetti, Antonio; Pass, Harvey I.

2013-01-01

Introduction Lung cancer is formerly the highest cause of mortality among tumor pathologies worldwide. There are no validated techniques for an early detection of pulmonary cancer lesions other than low-dose helical CT-scan. Unfortunately, this method have some downside effects. Recent studies have laid the basis for development of exosomes-based techniques to screen/diagnose lung cancers. As the isolation of circulating exosomes is a minimally invasive procedure, this technique opens new possibilities for diagnostic applications. Methods We used a first set of 30 plasma samples from as many patients, including 10 patients affected by Lung Adenocarcinomas, 10 with Lung Granulomas and 10 healthy smokers matched for age and sex as negative controls. Wide range microRNAs analysis (742 microRNAs) was performed by quantitative RT-PCR. Data were compared by lesion characteristics using WEKA software for statistics and modeling. Subsequently, selected microRNAs were evaluated on an independent larger group of samples (105 specimens: 50 Lung Adenocarcinomas, 30 Lung Granulomas and 25 healthy smokers). Results This analysis led to the selection of 4 microRNAs to perform a screening test (miR-378a, miR-379, miR-139-5p and miR-200b-5p), useful to divide population into 2 groups: nodule (lung adenocarcinomas+carcinomas) and non-nodule (healthy former smokers). Six microRNAs (miR-151a-5p, miR-30a-3p, miR-200b-5p, miR-629, miR-100 and miR-154-3p) were selected for a second test on the “nodule” population to discriminate between lung adenocarcinoma and granuloma. Conclusions “Screening test” has shown 97.5% sensitivity, 72.0% specificity, AUC ROC of 90.8%. “Diagnostic test” had 96.0% sensitivity, 60.0% specificity, AUC ROC of 76.0%. Further evaluation is needed to confirm the predictive power of those models on higher cohorts of samples. PMID:23945385

Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers.

PubMed

Aksoy, Mark O; Kim, Victor; Cornwell, William D; Rogers, Thomas J; Kosmider, Beata; Bahmed, Karim; Barrero, Carlos; Merali, Salim; Shetty, Neena; Kelsen, Steven G

2017-05-02

Identification of biomarkers of cigarette smoke -induced lung damage and early COPD is an area of intense interest. Glucose regulated protein of 78 kD (i.e., GRP78), a multi-functional protein which mediates cell responses to oxidant stress, is increased in the lungs of cigarette smokers and in the serum of subjects with COPD. We have suggested that secretion of GRP78 by lung cells may explain the increase in serum GRP78 in COPD. To assess GRP78 secretion by the lung, we assayed GRP78 in bronchoalveolar lavage fluid (BALF) in chronic smokers and non-smokers. We also directly assessed the acute effect of cigarette smoke material on GRP78 secretion in isolated human airway epithelial cells (HAEC). GRP78 was measured in BALF of smokers (S; n = 13) and non-smokers (NS; n = 11) by Western blotting. GRP78 secretion by HAEC was assessed by comparing its concentration in cell culture medium and cell lysates. Cells were treated for 24 h with either the volatile phase of cigarette smoke (cigarette smoke extract (CSE) or the particulate phase (cigarette smoke condensate (CSC)). GRP78 was present in the BALF of both NS and S but levels were significantly greater in S (p = 0.04). GRP78 was secreted constitutively in HAEC. CSE 15% X 24 h increased GRP78 in cell-conditioned medium without affecting its intracellular concentration. In contrast, CSC X 24 h increased intracellular GRP78 expression but did not affect GRP78 secretion. Brefeldin A, an inhibitor of classical Golgi secretion pathways, did not inhibit GRP78 secretion indicating that non-classical pathways were involved. The present study indicates that GRP78 is increased in BALF in cigarette smokers; that HAEC secrete GRP78; and that GRP78 secretion by HAEC is augmented by cigarette smoke particulates. Enhanced secretion of GRP78 by lung cells makes it a potential biomarker of cigarette smoke-induced lung injury.

Tobacco use and motivation to stop smoking among long-term smokers who are ineligible for lung cancer screening.

PubMed

Taghizadeh, Niloofar; Taylor, Kathryn L; MacEachern, Paul; Koetzler, Rommy; Dickinson, James A; Gillson, Ashley; Yang, Huiming; Tammemagi, Martin C; Penz, Erika; Pendharkar, Sachin R; Lam, Stephen C; Graham, Andrew; Culling, Jessica; Burrowes, Paul; Bédard, Eric L R; Tremblay, Alain

2017-09-01

The importance of smoking cessation interventions in lung cancer screening participants has been highlighted. This study aimed to describe the smoking habits of individuals who were ineligible for lung cancer screening and to investigate whether this encounter may represent an opportunity to reduce tobacco use. Ever smokers between the ages of 55 and 80 and ≥1.5% lung cancer risk over 6 years or having smoked ≥30 pack-years and with no more than 15 years of smoking abstinence were eligible to participate in the Alberta Lung Cancer Screening Program (ALCSP). A baseline questionnaire exploring tobacco use was administered to all interested individuals as part of the eligibility determination for the program. Among 504 individuals, 254 (50.4%) met the criteria for the ALCSP and 250 (49.6%) were non-eligible for screening. Non-eligible individuals were slightly younger (mean=60.2 vs. 63.1 years, p-value <0.001), and less likely to be current smokers (26.0% vs. 48.8%, p-value <0.001). Non-eligible smokers had a lower degree of addiction compared to eligible group, as measured by the Fagerström Test of Nicotine Dependence (Median=4.0 vs 6.0, p-value=0.001), but still in the "moderately dependent" range for this test. There were no significant differences in motivation to quit (98.5% vs. 97.6%, p-value=0.689), or motivation to receive help with their quit attempt (89.2% vs. 90.3%, p-value=0.813) between these two groups. Only 7.7% of non-eligible and 2.4% of eligible current smokers were currently in a smoking cessation program. A significant proportion of individuals applying to, but not qualifying for a lung cancer screening program are active smokers with significant nicotine dependence. Very few are currently participating in active smoking cessation programs but almost all are interested in quitting and in receiving help with quit attempts. Future studies need to investigate the most effective approaches for smoking cessation in this substantial group of older, long-term smokers, capitalizing on their motivation to receive cessation assistance. Copyright © 2017 Elsevier B.V. All rights reserved.

Secondhand Smoke Enhances Lung Cancer Risk in Male Smokers: An Interaction.

PubMed

Li, Wentao; Tse, Lap Ah; Au, Joseph S K; Wang, Feng; Qiu, Hong; Yu, Ignatius Tak-Sun

2016-11-01

Previous studies revealed that some indoor air pollutants and fine particle matter can interact with active smoking, enhancing lung cancer risk in smokers. Secondhand smoke (SHS), with remarkable differences from active smoking, contributes significantly to indoor air pollution and generates a considerable amount of fine particle matter, may cause a similar interaction with active smoking. Information on lifetime SHS along with active smoking and other confirmed or suspected risk factors for lung cancer was collected in this case-referent study. Odds ratios and the 95% confidence intervals (95% CIs) of smoking status in different levels of SHS were evaluated. Potential multiplicative and additive interactions were explored. Compared with never-smokers without SHS, current smokers who were exposed to a high level of SHS demonstrated the highest odds ratio (15.13, 95% CI: 8.60, 26.65), almost doubles the effect in the current smokers without SHS. Significant additive interactions between current smoking and high level of SHS were observed for all lung cancers (synergy index = 1.80, 95% CI: 1.02, 3.24) and the squamous carcinoma subgroup. High level of SHS exposure greatly enhanced lung cancer risk among current smokers, consistent with an additive interaction; while this interaction was predominant for the squamous carcinoma. The results provide new evidence to the rationale of promoting global smoking cessation. Some indoor air pollutants can interact with active smoking, yielding a synergistic effect on inducing lung cancer. SHS, with noticeable differences from active smoking, is a major source of indoor air pollution. However, little has been known about the effect of SHS in smokers and whether there is a similar interaction between SHS and active smoking. In this study, we evaluated their separate and joint effects and indeed found a more than additive interaction between them. This finding suggests a potential problem of gathering smoking aggravating by venue restriction policies and re-advocates policy efforts on smoking cessation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Red meat, Mediterranean diet and lung cancer risk among heavy smokers in the COSMOS screening study.

PubMed

Gnagnarella, P; Maisonneuve, P; Bellomi, M; Rampinelli, C; Bertolotti, R; Spaggiari, L; Palli, D; Veronesi, G

2013-10-01

To assess whether intake of selected foods and food groups and adherence to a Mediterranean diet are associated with lung cancer risk in heavy smokers. In the context of a lung cancer screening programme, we invited asymptomatic volunteers, aged 50 years or more, current smokers or recent quitters, who had smoked at least 20 pack-years, to undergo annual low-dose computed tomography. We assessed participants' diet at baseline using a self-administered food frequency questionnaire and calculated their average daily food intake using an ad hoc computer program and determined their alternate Mediterranean diet (aMED) score. We used Cox proportional hazards regression to assess the association between selected food items, beverages and the aMED score and lung cancer risk. During a mean screening period of 5.7 years, 178 of 4336 participants were diagnosed with lung cancer. At multivariable analysis, red meat consumption was associated with an increased risk of lung cancer [hazard ratio (HR) Q4 versus Q1, 1.73; 95% confidence interval (CI) 1.15-2.61; P-value for trend 0.002], while tea consumption (HR for one or more cup/day versus none, 0.56; 95% CI 0.31-0.99; P-value for trend 0.04) and adherence to a Mediterranean diet (HR for aMED ≥ 8 versus ≤ 1, 0.10; 95% CI 0.01-0.77) were significantly associated with reduced lung cancer risk. Among heavy smokers, high red meat consumption and low adherence to a Mediterranean diet are associated with increased risk of lung cancer.

Residential radon and environmental burden of disease among Non-smokers.

PubMed

Noh, Juhwan; Sohn, Jungwoo; Cho, Jaelim; Kang, Dae Ryong; Joo, Sowon; Kim, Changsoo; Shin, Dong Chun

2016-01-01

Lung cancer was the second highest absolute cancer incidence globally and the first cause of cancer mortality in 2014. Indoor radon is the second leading risk factor of lung cancer after cigarette smoking among ever smokers and the first among non-smokers. Environmental burden of disease (EBD) attributable to residential radon among non-smokers is critical for identifying threats to population health and planning health policy. To identify and retrieve literatures describing environmental burden of lung cancer attributable to residential radon, we searched databases including Ovid-MEDLINE, -EMBASE from 1980 to 2016. Search terms included patient keywords using 'lung', 'neoplasm', exposure keywords using 'residential', 'radon', and outcomes keywords using 'years of life lost', 'years of life lost due to disability', 'burden'. Searching through literatures identified 261 documents; further 9 documents were identified using manual searching. Two researchers independently assessed 271 abstracts eligible for inclusion at the abstract level. Full text reviews were conducted for selected publications after the first assessment. Ten studies were included in the final evaluation. Global disability-adjusted life years (DALYs)(95 % uncertainty interval) for lung cancer were increased by 35.9 % from 23,850,000(18,835,000-29,845,000) in 1900 to 32,405,000(24,400,000-38,334,000) in 2000. DALYs attributable to residential radon were 2,114,000(273,000-4,660,000) DALYs in 2010. Lung cancer caused 34,732,900(33,042,600 ~ 36,328,100) DALYs in 2013. DALYs attributable to residential radon were 1,979,000(1,331,000-2,768,000) DALYs for in 2013. The number of attributable lung cancer cases was 70-900 and EBD for radon was 1,000-14,000 DALYs in Netherland. The years of life lost were 0.066 years among never-smokers and 0.198 years among ever-smoker population in Canada. In summary, estimated global EBD attributable to residential radon was 1,979,000 DALYs for both sexes in 2013. In Netherlands, EBD for radon was 1,000-14,000 DALYs. Smoking population lost three times more years than never-smokers in Canada. There was no study estimating EBD of residential radon among never smokers in Korea and Asian country. In addition, there were a few studies reflecting the age of building, though residential radon exposure level depends on the age of building. Further EBD study reflecting Korean disability weight and the age of building is required to estimate EBD precisely.

Clinical and Radiographic Predictors of GOLD–Unclassified Smokers in the COPDGene Study

PubMed Central

Hokanson, John E.; Murphy, James R.; Regan, Elizabeth A.; Make, Barry J.; Lynch, David A.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Rationale: A significant proportion of smokers have lung function impairment characterized by a reduced FEV1 with a preserved FEV1/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies. Objectives: To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV1/FVC ≥ LLN and FEV1 < LLN) subjects compared to smokers with normal lung function and subjects with COPD. Methods: Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available. Measurements and Main Results: GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the “unclassified” group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema. Conclusions: Subjects with reduced FEV1 and a preserved FEV1/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764). PMID:21493737

Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study

PubMed Central

Vineis, Paolo; Hoek, Gerard; Krzyzanowski, Michal; Vigna-Taglianti, Federica; Veglia, Fabrizio; Airoldi, Luisa; Overvad, Kim; Raaschou-Nielsen, Ole; Clavel-Chapelon, Francoise; Linseisen, Jacob; Boeing, Heiner; Trichopoulou, Antonia; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Panico, Salvatore; Bueno-De-Mesquita, H Bas; Peeters, Petra H; Lund E, Eiliv; Agudo, Antonio; Martinez, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Cirera, Lluis; Quiros, J Ramon; Berglund, Goran; Manjer, Jonas; Forsberg, Bertil; Day, Nicholas E; Key, Tim J; Kaaks, Rudolf; Saracci, Rodolfo; Riboli, Elio

2007-01-01

Background Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution. Methods We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population. Results The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5–7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions. Discussion We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10–20 ug/m3, whereas levels in Italy are around 30 or 40, or higher). Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5–7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe. PMID:17302981

Alcohol consumption and lung cancer risk in never smokers: a pooled analysis of case-control studies.

PubMed

García Lavandeira, José A; Ruano-Ravina, Alberto; Kelsey, Karl T; Torres-Durán, María; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Zapata, Maruxa; Abal-Arca, José; Vidal-García, Iria; Montero-Martínez, Carmen; Amenedo, Margarita; Castro-Añón, Olalla; Golpe-Gómez, Antonio; Guzmán-Taveras, Rosirys; Martínez, Cristina; Provencio, Mariano; Mejuto-Martí, María J; García-García, Silvia; Fernández-Villar, Alberto; Piñeiro, María; Barros-Dios, Juan M

2018-06-01

Lung cancer is the deadliest cancer in developed countries but the etiology of lung cancer risk in never smokers (LCRINS) is largely unknown. We aim to assess the effects of alcohol consumption, in its different forms, on LCRINS. We pooled six multi-center case-control studies developed in the northwest of Spain. Cases and controls groups were composed of never smokers. We selected incident cases with anatomopathologically confirmed lung cancer diagnoses. All participants were personally interviewed. We performed two groups of statistical models, applying unconditional logistic regression with generalized additive models. One considered the effect of alcohol type consumption and the other considered the quantity of each alcoholic beverage consumed. A total of 438 cases and 863 controls were included. Median age was 71 and 66, years, respectively. Adenocarcinoma was the predominant histological type, comprising 66% of all cases. We found that any type of wine consumption posed an OR of 2.20 OR 95%CI 1.12-4.35), and spirits consumption had an OR of 1.90 (95%CI 1.13-3.23). Beer consumption had an OR of 1.33 (95%CI 0.82-2.14). These results were similar when women were analyzed separately, but for men there was no apparent risk for any alcoholic beverage. The dose-response analysis for each alcoholic beverage revealed no clear pattern. Wine and spirits consumption might increase the risk of LCRINSs, particularly in females. These results have to be taken with caution given the limitations of the present study.

[Clinical and radiological characteristics of pulmonary tuberculosis in tobacco smokers].

PubMed

Kombila, U D; Mbaye, F B R; Dia Kane, Y; Ka, W; Toure Badiane, N O

2018-01-27

Tobacco smoke alters lung defense mechanisms against infections and so increases the risk of mycobacterium tuberculosis infection. To determine the particular clinical features of tuberculosis in smokers and identify risk factors. We conducted a prospective, cross-sectional study over a period of nine months in Dakar, Senegal. The Chi-square test and multiple logistic regression were used to identify differences between smokers and non-smokers and to identify factors associated with clinical outcomes. We included 165 patients with active pulmonary tuberculosis (59 smokers versus 106 never-smokers). The average age of smokers was 43.8±12.7 versus 32.1±13.1 years (P<0.0001). Smokers were overwhelmingly male (98.3% versus 1.8%, P<0.0001). The average delay to consultation was longer among smokers (90 days [30-120] versus 60 days [30-90] ; P<0.0001). In multivariate analysis, alcohol abuse, increasing age, male sex, and an unknown retroviral status were independent risk factors for pulmonary tuberculosis. Haemoptysis was observed more frequently in smokers (49.1% versus 31.1%, P=0.017). With regards to chest X-ray features, smokers presented with more advanced, bilateral and cavitating lung lesions. Diagnostic delay and haemoptysis are important characteristics of the pulmonary tuberculosis in tobacco smokers. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case-control studies in Montreal.

PubMed

Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

2012-08-01

We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case-control studies were conducted in Montreal. Study I (1979-1986) included 857 cases and 1066 controls, and Study II (1996-2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9-1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8-1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7-4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3-3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.

Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case–control studies in Montreal

PubMed Central

Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

2012-01-01

We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case–control studies were conducted in Montreal. Study I (1979–1986) included 857 cases and 1066 controls, and Study II (1996–2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist–hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9–1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8–1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7–4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3–3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes. PMID:23342253

Implications of Nine Risk Prediction Models for Selecting Ever-Smokers for Computed Tomography Lung Cancer Screening.

PubMed

Katki, Hormuzd A; Kovalchik, Stephanie A; Petito, Lucia C; Cheung, Li C; Jacobs, Eric; Jemal, Ahmedin; Berg, Christine D; Chaturvedi, Anil K

2018-05-15

Lung cancer screening guidelines recommend using individualized risk models to refer ever-smokers for screening. However, different models select different screening populations. The performance of each model in selecting ever-smokers for screening is unknown. To compare the U.S. screening populations selected by 9 lung cancer risk models (the Bach model; the Spitz model; the Liverpool Lung Project [LLP] model; the LLP Incidence Risk Model [LLPi]; the Hoggart model; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 [PLCOM2012]; the Pittsburgh Predictor; the Lung Cancer Risk Assessment Tool [LCRAT]; and the Lung Cancer Death Risk Assessment Tool [LCDRAT]) and to examine their predictive performance in 2 cohorts. Population-based prospective studies. United States. Models selected U.S. screening populations by using data from the National Health Interview Survey from 2010 to 2012. Model performance was evaluated using data from 337 388 ever-smokers in the National Institutes of Health-AARP Diet and Health Study and 72 338 ever-smokers in the CPS-II (Cancer Prevention Study II) Nutrition Survey cohort. Model calibration (ratio of model-predicted to observed cases [expected-observed ratio]) and discrimination (area under the curve [AUC]). At a 5-year risk threshold of 2.0%, the models chose U.S. screening populations ranging from 7.6 million to 26 million ever-smokers. These disagreements occurred because, in both validation cohorts, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) were well-calibrated (expected-observed ratio range, 0.92 to 1.12) and had higher AUCs (range, 0.75 to 0.79) than 5 models that generally overestimated risk (expected-observed ratio range, 0.83 to 3.69) and had lower AUCs (range, 0.62 to 0.75). The 4 best-performing models also had the highest sensitivity at a fixed specificity (and vice versa) and similar discrimination at a fixed risk threshold. These models showed better agreement on size of the screening population (7.6 million to 10.9 million) and achieved consensus on 73% of persons chosen. No consensus on risk thresholds for screening. The 9 lung cancer risk models chose widely differing U.S. screening populations. However, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) most accurately predicted risk and performed best in selecting ever-smokers for screening. Intramural Research Program of the National Institutes of Health/National Cancer Institute.

Western Australian cigarette smokers have fewer small lung nodules than North Americans on CT screening for lung cancer.

PubMed

Murray, C P; Wong, P M; Louw, J; Waterer, G W

2009-08-01

To determine the prevalence of small lung nodules on low-dose helical computed tomography (CT) in a Western Australian cohort of asymptomatic long-term cigarette smokers and to compare this with a large, similarly derived cohort of North Americans from the Mayo Clinic Lung Cancer Screening Trial. Forty-nine asymptomatic long-term cigarette smokers of minimum age 50 years underwent a low-dose 64-slice helical CT of the lungs. Images were viewed on a soft copy reporting station with thin section axial and coronal images, maximum intensity projection images, and advanced image manipulation tools. The prevalence of all nodules was 39%, significantly lower than the Mayo Clinic cohort prevalence of 51% (P < 0.01, Fisher's exact test), despite the use of more advanced imaging technology and image manipulation designed to increase the sensitivity for nodules. The prevalence of small nodules in asymptomatic long-term cigarette smokers in Western Australia is high, though significantly less than that found in a large study in North America. The authors postulate this is due to the relatively low rates of mycobacterium tuberculosis and soil-derived fungal pulmonary infections in Western Australia, as well as a lower degree of urban air pollution.

The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

PubMed

Omenn, G S; Goodman, G; Thornquist, M; Grizzle, J; Rosenstock, L; Barnhart, S; Balmes, J; Cherniack, M G; Cullen, M R; Glass, A

1994-04-01

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

Noninvasive assessment of peroxidative lung damage by HIPDM lung scanning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miniati, M.; Borrelli, E.; Monti, S.

1991-03-15

The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by the lungs whence it is effluxed at a slow exponential rate. In humans (normal non smokers), the mean residence time ({bar t}) of 123I-HIPDM, assessed by external detection, averages 7.2 {plus minus} 1.1 hrs. Persistence of HIPDM in lungs is significantly increased in asymptomatic smokers and, to a greater extent, in patients with ARDS. Since production of free oxygen radicals reportedly occurs as a consequence of smoke exposure and in the course of acute lung injury, the authors hypothesized that the prolonged persistence of HIPDM in the lungs ofmore » smokers and of patients with ARDS might reflect a peroxidative damage of lung tissue. They tested this hypothesis in rabbits since their baseline HIPDM lung clearance is similar to that of nonsmoking humans. In rabbits, acute lung injury was induced by phorbol myristate acetate. Three hrs after PMA administration, the animals received an i.v. bolus of {sup 131}I-HIPDM. Radioactivity over the chest was recorded for 2 hrs by gamma camera and HIPDM mean residence time in the lungs was computed. Thereafter, the animals were sacrificed and their lungs were removed to measure wet/dry weight ratio as index of lung edema and malondialdehyde (MDA) content as index of lipid peroxidation. HIPDM mean residence time was positively correlated with MDA level in lung tissue, but not with wet/dry weight ratio. Noninvasive assessment of HIPDM lung kinetics may then serve as specific in vivo marker of peroxidative lung injury.« less

Evaluation of the Role of Invadopodia in Lung Cancer Cell Growth and Invasion

DTIC Science & Technology

2014-11-01

NSCLC cell lines. We obtained eight such lines: H1975 and H1650 ( non - smoker , mutant EGFr); H1395 and H1573 ( non - smoker , wildtype EGFr); H23 and H1792...Invadopodia are actin-based cellular protrusions found in many invasive cancer cell types. Non small cell lung cancers (NSCLCs) are highly invasive and...Abstract: Invadopodia are actin-based cellular protrusions found in many invasive cancer cell types. Non small cell lung cancers (NSCLCs) are highly

Low-dose chest computed tomography for lung cancer screening among Hodgkin lymphoma survivors: a cost-effectiveness analysis.

PubMed

Wattson, Daniel A; Hunink, M G Myriam; DiPiro, Pamela J; Das, Prajnan; Hodgson, David C; Mauch, Peter M; Ng, Andrea K

2014-10-01

Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences in regional air trapping in current smokers with normal spirometry.

PubMed

Karimi, Reza; Tornling, Göran; Forsslund, Helena; Mikko, Mikael; Wheelock, Åsa M; Nyrén, Sven; Sköld, C Magnus

2017-01-01

We investigated regional air trapping on computed tomography in current smokers with normal spirometry. It was hypothesised that presence of regional air trapping may indicate a specific manifestation of smoking-related changes.40 current smokers, 40 patients with chronic obstructive pulmonary disease (COPD), and 40 healthy never- smokers underwent computed tomography scans. Regional air trapping was assessed on end-expiratory scans and emphysema, micronodules and bronchial wall thickening on inspiratory scans. The ratio of expiratory and inspiratory mean lung attenuation (E/I) was calculated as a measure of static (fixed) air trapping.Regional air trapping was present in 63% of current smokers, in 45% of never smokers and in 8% of COPD patients (p<0.001). Current smokers with and without regional air trapping had E/I ratio of 0.81 and 0.91, respectively (p<0.001). Forced expiratory volume in 1 s (FEV 1 ) was significantly higher and emphysema less frequent in current smokers with regional air trapping.Current smokers with regional air trapping had higher FEV 1 and less emphysema on computed tomography. In contrast, current smokers without regional air trapping resembled COPD. Our results highlight heterogeneity among smokers with normal spirometry and may contribute to early detection of smoking related structural changes in the lungs. Copyright ©ERS 2017.

Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey.

PubMed

Dosemeci, M; Gokmen, I; Unsal, M; Hayes, R B; Blair, A

1997-09-01

Effects of tobacco smoking and alcohol use on risks of cancers of the larynx and lung have been evaluated extensively in industrialized countries. Few studies on the effect of these risk factors have been reported from developing countries. We conducted a case-control study to evaluate risks of laryngeal and lung cancers in men by subsite and cell type in relation to smoking and alcohol drinking in Turkey, a country where smoking and alcohol consumption patterns are different from those in industrialized countries. We identified 832 laryngeal and 1,210 lung cancer cases and 829 controls with information on smoking and alcohol use (amount and duration) and histologic cell type from an oncology treatment center of a Social Security Agency hospital in Istanbul, Turkey, admitted between 1979 and 1984. Both laryngeal and lung cancer showed significant associations with smoking and alcohol drinking, but no monotonic dose-response was obtained for alcohol drinking. Among smokers, the highest risks were observed in the supraglottis region of the larynx (odds ratio [OR] = 4.1) after adjustment for age and alcohol use. Among alcohol drinkers, the highest risks were observed in the glottis region of the larynx (OR = 1.7) after adjustment for age and smoking. In the analysis by the cell type of lung cancer among ever-smokers, small cell type showed the highest risk (OR = 5.4), while it showed no association with alcohol drinking. Cumulative cigarette use (pack-years) and number of cigarettes per day showed stronger associations than years smoked for both cancer sites. The relative risks of joint exposure to smoking and alcohol were 12.2 for laryngeal cancer and 14.1 for lung cancer among heavy smokers and heavy alcohol drinkers. This study provides epidemiologic evidence from Turkey that smoking and alcohol use are associated with risks of cancers of the larynx and lung.

Lower lung cancer rates in Jewish smokers in Israel and the USA.

PubMed

Rennert, Gad; Kremer, Ran; Rennert, Hedy S; Wollner, Mira; Agbarya, Abed; Pinchev, Mila; Lejbkowicz, Flavio; Spitz, Margaret R; Muscat, Joshua E

2015-11-01

Lung cancer rates in Israeli Jews have remained stable over the last five decades and are much lower than in most developed countries despite high historical smoking rates. We compared lung cancer risk in Jews and non-Jews in Israel and in the United States. Data were derived from a population-based, case-control study in Israel (638 cases, 496 controls) to estimate lung cancer risk associated with smoking. Data were also acquired from a case-control study in the United States with information on religious affiliation (5,093 cases, 4,735 controls). Smoking was associated with lung cancer risk in all religion/gender groups in both studies. However, major differences in risk magnitude were noted between Jews and non-Jews; ever smoking was associated with a moderately elevated risk of lung cancer in Jewish men and women in Israel (OR = 4.61, 2.90-7.31 and OR = 2.10, 1.36-3.24, respectively), and in Jewish men and women in the United States (OR = 7.63, 5.34-10.90 and OR = 8.50, 5.94-12.17) but were significantly higher in Israeli non-Jewish men (OR = 12.96, 4.83-34.76) and US non-Jewish men and women (OR = 11.33, 9.09-14.12 and OR = 12.78, 10.45-15.63). A significant interaction between smoking and religion was evident in light, moderate and heavy male and female smokers. The differences in risk level between Israeli Jews and non-Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions). Data from the two studies support the notion of a reduced risk of lung cancer in Jewish compared to non-Jewish smokers in different areas of the world. © 2015 UICC.

Single-Cell RNA Sequencing of the Bronchial Epithelium in Smokers with Lung Cancer

DTIC Science & Technology

2017-07-01

and to discuss library preparations protocols and data analysis techniques. The goal is to develop a single cell sequencing analysis toolkit . In...Research Support LUNGevity Career Development Award What other organizations were involved as partners? Organization Name: Broad Institute 19

Predictive equations for total lung capacity and residual volume calculated from radiographs in a random sample of the Michigan population.

PubMed Central

Kilburn, K H; Warshaw, R H; Thornton, J C; Thornton, K; Miller, A

1992-01-01

BACKGROUND: Published predicted values for total lung capacity and residual volume are often based on a small number of subjects and derive from different populations from predicted spirometric values. Equations from the only two large studies gave smaller predicted values for total lung capacity than the smaller studies. A large number of subjects have been studied from a population which has already provided predicted values for spirometry and transfer factor for carbon monoxide. METHODS: Total lung capacity was measured from standard posteroanterior and lateral chest radiographs and forced vital capacity by spirometry in a population sample of 771 subjects. Prediction equations were developed for total lung capacity (TLC), residual volume (RV) and RV/TLC in two groups--normal and total. Subjects with signs or symptoms of cardiopulmonary disease were combined with the normal subjects and equations for all subjects were also modelled. RESULTS: Prediction equations for TLC and RV in non-smoking normal men and women were square root transformations which included height and weight but not age. They included a coefficient for duration of smoking in current smokers. The predictive equation for RV/TLC included weight, age, age and duration of smoking for current smokers and ex-smokers of both sexes. For the total population the equations took the same form but the height coefficients and constants were slightly different. CONCLUSION: These population based prediction equations for TLC, RV and RV/TLC provide reference standards in a population that has provided reference standards for spirometry and single breath transfer factor for carbon monoxide. PMID:1412094

Worse Prognosis for Stage IA Lung Cancer Patients with Smoking History and More Severe Chronic Obstructive Pulmonary Disease.

PubMed

Yoshida, Yukihiro; Kage, Hidenori; Murakawa, Tomohiro; Sato, Yasunori; Ota, Satoshi; Fukayama, Masashi; Nakajima, Jun

2015-01-01

This retrospective study examined whether the severity of chronic obstructive lung disease (COPD) affects surgical outcomes. The subjects were 243 consecutive patients who underwent lobectomy for clinical stage IA lung cancer from 1999 to 2008 in our hospital. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system was used to classify the severity of COPD in smokers. Among the 149 smokers, 62 were diagnosed with COPD (25 as GOLD 1, 33 as GOLD 2, and 4 as GOLD 3). In univariate analysis, postoperative pulmonary complications were associated with male sex and more severe COPD. The frequencies were 17.1% in non-COPD, 24.0% in GOLD 1-COPD, and 46.0% in GOLD 2/3-COPD smokers (p = 0.0006). In univariate analysis, older age, smoking history, higher smoking pack-years and more severe COPD were associated with poor relapse-free survival. Relapse-free survival at five years was 80.7%, 66.9%, and 61.3% in non-COPD, GOLD 1-COPD, and GOLD 2/3-COPD smokers, respectively (p = 0.0005). Multivariate analyses showed that only GOLD 2/3-COPD was associated with postoperative pulmonary complications and relapse-free survival. Inhaled bronchodilators were prescribed preoperatively to 24.3% of the GOLD 2/3-COPD group. Smokers with GOLD 2/3-COPD are at high risk for pulmonary complications and have an unfavorable long-term prognosis.

Diet and lung cancer in California Seventh-day Adventists.

PubMed

Fraser, G E; Beeson, W L; Phillips, R L

1991-04-01

The Adventist Health Study, a cohort study of 34,198 California Seventh-day Adventists, identified 61 cases of new primary lung cancer over 6 years of follow-up (1977-1982). The population studied was unique in that only 4% admitted to current cigarette smoking and about half were lacto-ovovegetarians. A total of 36% of the lung tumors were adenocarcinomas, and 19% were squamous cell carcinomas. The expected associations with cigarette smoking were noted for Kreyberg group I tumors (squamous cell, large cell, and small cell carcinoma; relative risk (RR) = 53.2 for current smokers and 7.07 for past smokers), but much lesser associations were noted for Kreyberg group II tumors (adenocarcinoma and bronchoalveolar carcinoma; RR = 1.99 for current smokers and 1.59 for past smokers). In this study, fruit consumption was the dietary constituent that showed a strong, statistically significant protective association with lung cancer that was independent of smoking (fruit consumption less than 3 times/week, RR = 1.0; 3-7 times/week, RR = 0.30; greater than or equal to 2 times/day, RR = 0.26). This association was somewhat stronger for Kreyberg group II tumors, but similar trends were also noted for Kreyberg group I tumors. Confounding with smoking seems unlikely in a population with very few current smokers and where both stratification and Cox modeling methods of analysis led to similar conclusions.

Is the shape of the decline in risk following quitting smoking similar for squamous cell carcinoma and adenocarcinoma of the lung? A quantitative review using the negative exponential model.

PubMed

Fry, John S; Lee, Peter N; Forey, Barbara A; Coombs, Katharine J

2015-06-01

One possible contributor to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma of the lung may be differences in the pattern of decline in risk following quitting for the two lung cancer types. Earlier, using data from 85 studies comparing overall lung cancer risks in current smokers, quitters (by time quit) and never smokers, we fitted the negative exponential model, deriving an estimate of 9.93years for the half-life - the time when the excess risk for quitters compared to never smokers becomes half that for continuing smokers. Here we applied the same techniques to data from 16 studies providing RRs specific for lung cancer type. From the 13 studies where the half-life was estimable for each type, we derived estimates of 11.68 (95% CI 10.22-13.34) for squamous cell carcinoma and 14.45 (11.92-17.52) for adenocarcinoma. The ratio of the half-lives was estimated as 1.32 (95% CI 1.20-1.46, p<0.001). The slower decline in quitters for adenocarcinoma, evident in subgroups by sex, age and other factors, may be one of the factors contributing to the reported rise in the ratio of adenocarcinoma to squamous cell carcinoma. Others include changes in the diagnosis and classification of lung cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Index-based dietary patterns and risk of lung cancer in the NIH-AARP diet and health study.

PubMed

Anic, G M; Park, Y; Subar, A F; Schap, T E; Reedy, J

2016-01-01

Dietary pattern analysis considers combinations of food intake and may offer a better measure to assess diet-cancer associations than examining individual foods or nutrients. Although tobacco exposure is the major risk factor for lung cancer, few studies have examined whether dietary patterns, based on preexisting dietary guidelines, influence lung cancer risk. After controlling for smoking, we examined associations between four diet quality indices-Healthy Eating Index-2010 (HEI-2010), Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension (DASH)-and lung cancer risk in the NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health study. Baseline dietary intake was assessed in 460 770 participants. Over a median of 10.5 years of follow-up, 9272 incident lung cancer cases occurred. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and confidence intervals (CIs). Comparing highest to lowest quintiles, HRs (95% CIs) for lung cancer were as follows: HEI-2010=0.83 (0.77-0.89), AHEI-2010=0.86 (0.80-0.92), aMED=0.85 (0.79-0.91) and DASH=0.84 (0.78-0.90). Among the individual components of the dietary indices, higher consumption of whole grains and fruits was significantly inversely associated with lung cancer risk for several of the diet indices. Total index score analyses stratified by smoking status showed inverse associations with lung cancer for former smokers; however, only HEI-2010 was inversely associated in current smokers and no index score was inversely associated among never smokers. Although smoking is the factor most strongly associated with lung cancer, this study adds to a growing body of evidence that diet may have a modest role in reducing lung cancer risk, especially among former smokers.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

expression data was analyzed using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized...14. Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101...10143-10148 15. Spira A, Beane JE, Shah V , et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

data was analyzed using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized and log...Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101:10143...10148 15. Spira A, Beane JE, Shah V , et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat

Biochemical verification of the self-reported smoking status of screened male smokers of the Dutch-Belgian randomized controlled lung cancer screening trial.

PubMed

van der Aalst, Carlijn M; de Koning, Harry J

2016-04-01

Smoking is the main cause of lung cancer, so data linked to smoking behaviour are important in lung cancer screening trials. However, self-reporting data concerning smoking behaviour are mainly used. The aim of this study was to biochemically determine the validity and reliability of self-reported smoking status among smokers at high risk for developing lung cancer participating in the Dutch-Belgian lung cancer screening (NELSON) trial. For this sub study, a random sample of 475 men was selected who were scheduled for the fourth screening round in the NELSON trial. They were asked to complete a short questionnaire to verify the smoking behaviour for the previous seven days and a blood sample was collected to measure the cotinine level. The validity (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) and reliability (Kappa) of the self-reported smoking status compared to the cotinine level (as golden standard) were determined. Both a completed questionnaire as well as a cotinine level were available for 199 (41.9%) participants. Based on these data, Se and Sp were respectively 98% (95%-Confidence Interval (CI): 91-99) and 98% (95%-CI: 93-100). PPV and NPV were 98% and 96% and Kappa was 0.96. In conclusion, the validity of the self-reported smoking status turned out to be reliable amongst men at high risk for developing lung cancer who participate in the NELSON lung cancer screening trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HDL-cholesterol and the incidence of lung cancer in the Atherosclerosis Risk in Communities (ARIC) study

PubMed Central

Kucharska-Newton, Anna M.; Rosamond, Wayne D.; Schroeder, Jane C.; McNeill, Ann Marie; Coresh, Josef; Folsom, Aaron R.

2008-01-01

Summary This study examined prospectively the association of baseline plasma HDL-cholesterol levels with incidence of lung cancer in 14, 547 members of the Atherosclerosis Risk in Communities (ARIC) cohort. There were 259 cases of incident lung cancer identified during follow-up from 1987 through 2000. Results of this study indicated a relatively weak inverse association of HDL-cholesterol with lung cancer that was dependent on smoking status. The hazard ratio of lung cancer incidence in relation to low HDL-cholesterol, adjusted for race, gender, exercise, alcohol consumption, body mass index, triglycerides, age, and cigarette pack-years of smoking, was 1.45 (95% confidence interval 1.10, 1.92). This association was observed among former smokers (hazard ratio: 1.77, 95% confidence interval 1.05, 2.97), but not current smokers. The number of cases among never smokers in this study was too small (n=13) for meaningful interpretation of effect estimates. Excluding cases occurring within five years of baseline did not appreciably change the point estimates, suggesting lack of reverse causality. The modest association of low plasma HDL-cholesterol with greater incident lung cancer observed in this study is in agreement with existing case-control studies. PMID:18342390

Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung.

PubMed

Pavanello, Sofia; B'chir, Fatma; Pulliero, Alessandra; Saguem, Saâd; Ben Fraj, Radhia; El Aziz Hayouni, Abed; Clonfero, Erminio; Mastrangelo, Giuseppe

2007-09-01

This study aimed to identify new genetic characteristics contributing to individual susceptibility to smoke-induced lung cancer. Despite functional evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on lung cancer risk. We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design. A significant interaction between CYP1A2-T/delT or delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important role in lung carcinogenesis, especially SCC, among smokers.

Evidence that the lung Adenocarcinoma EML4-ALK fusion gene is not caused by exposure to secondhand tobacco smoke during childhood.

PubMed

Ryan, Bríd M; Wang, Yi; Jen, Jin; Yi, Eunhee S; Olivo-Marston, Susan; Yang, Ping; Harris, Curtis C

2014-07-01

The EML4-ALK fusion gene is more frequently found in younger, never smoking patients with lung cancer. Meanwhile, never smokers exposed to secondhand tobacco smoke (SHS) during childhood are diagnosed at a younger age compared with never smoking patients with lung cancer who are not exposed. We, therefore, hypothesized that SHS, which can induce DNA damage, is associated with the EML4-ALK fusion gene. We compared the frequency of the EML4-ALK fusion gene among 197 never smoker patients with lung cancer with and without a history of exposure to SHS during childhood at Mayo Clinic. The EML4-ALK fusion gene was detected in 33% of cases from never smokers with a history of SHS exposure during childhood, whereas 47% of never smoking lung cancer cases without a history of childhood SHS exposure tested positive for the fusion gene. The EML4-ALK fusion gene is not enriched in tumors from individuals exposed to SHS during childhood. These data suggest that childhood exposure to SHS is not a significant etiologic cause of the EML4-ALK fusion gene in lung cancer. ©2014 American Association for Cancer Research.

Implicit rationing criteria in non-small-cell lung cancer treatment.

PubMed Central

Arndt, K.; Coy, P.; Schaafsma, J.

1996-01-01

Data collected from lung cancer patients attending the Victoria Clinic of the British Columbia Cancer Agency are used to investigate how resources are rationed in the treatment of non-small-cell lung cancer (NSCLC). An ordered logit model is estimated to analyse empirically the relationship between treatment selection and: tumour stage, size and differentiation; the Feinstein index; Karnofsky performance status (KPS); and the patient's age, gender and marital and smoking status. Implicit rationing is found to occur with respect to all of these factors except the Feinstein index, gender and marital status. With respect to age, KPS and smoker status the main empirical results are: (a) an increase in age from 50 to 85 reduces the expected treatment expenditure by 50-70%, depending on the patient's KPS and smoker status; (b) patients with a KPS less than 80 and of 80, receive 30-46% and 75-85%, respectively, of the expected treatment expenditure for patients with a KPS of 90 or 100, depending on age and smoker status; (c) the expected treatment expenditure for active smokers is about 71-86% of the expenditure for non- or former smokers depending on age and KPS. PMID:8611380

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers

PubMed Central

Miotto, D; Hollenberg, M; Bunnett, N; Papi, A; Braccioni, F; Boschetto, P; Rea, F; Zuin, A; Geppetti, P; Saetta, M; Maestrelli, P; Fabbri, L; Mapp, C

2002-01-01

Background: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. Methods: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. Results: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9–5.8) and 1.4 (1.07–3.4) respectively); glands (33.3 (18.2–43.8) and 16.2 (11.5–22.2), respectively); and bronchial vessels (54.2 (48.7–56.8) and 40.0 (36–40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. Conclusions: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD. PMID:11828045

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles

PubMed Central

2013-01-01

Background Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease. Objectives To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure to concentrated ambient fine particles (CAFP) with MMAD ≤ 2.5 microns in ex-smokers and lifetime smokers. Methods Eleven subjects, aged 35–74 years, came to the laboratory 5 times; a training day and two exposure days separated by at least 3 weeks, each with a post-exposure visit 22 h later. Double-blind and counterbalanced exposures to “clean air” (mean 1.5 ± 0.6 μg/m3) or CAFP (mean 108.7 ± 24.8 μg/m3 ) lasted 2 h with subjects at rest. Results At 3 h post-exposure subjects’ DTPA clearance half-time significantly increased by 6.3 min per 100 μg/m3 of CAFP relative to “clean air”. At 22 h post-exposure they showed significant reduction of 4.3% per 100 μg/m3 in FEV1 and a significant DLCO decrease by 11.1% per 100 μg/m3 of CAFP relative to “clean air”. At both 3 h and 22 h the HDL cholesterol level significantly decreased by 4.5% and 4.1%, respectively. Other blood chemistries and markers of lung injury, inflammation and procoagulant activity were within the normal range of values at any condition. Conclusions The results suggest that an acute 2 h resting exposure of smokers and ex-smokers to fine ambient particulate matter may transiently affect pulmonary function (spirometry and DLCO) and increase DTPA clearance half-time. Except for a post exposure decrease in HDL no other markers of pulmonary inflammation, prothrombotic activity and lung injury were significantly affected under the conditions of exposure. PMID:24245863

The impact of BMI on non-malignant respiratory symptoms and lung function in arsenic exposed adults of Northern Chile.

PubMed

Nardone, Anthony; Ferreccio, Catterina; Acevedo, Johanna; Enanoria, Wayne; Blair, Alden; Smith, Allan H; Balmes, John; Steinmaus, Craig

2017-10-01

Elevated body mass index (BMI) and arsenic are both associated with cancer and with non-malignant lung disease. Using a unique exposure situation in Northern Chile with data on lifetime arsenic exposure, we previously identified the first evidence of an interaction between arsenic and BMI for the development of lung cancer. We examined whether there was an interaction between arsenic and BMI for the development of non-malignant lung disease. Data on lifetime arsenic exposure, respiratory symptoms, spirometry, BMI, and smoking were collected from 751 participants from cities in Northern Chile with varying levels of arsenic water concentrations. Spirometry values and respiratory symptoms were compared across subjects in different categories of arsenic exposure and BMI. Adults with both a BMI above the 90th percentile (>33.9kg/m 2 ) and arsenic water concentrations ≥11µg/L exhibited high odds ratios (ORs) for cough (OR = 10.7, 95% confidence interval (CI): 3.03, 50.1), shortness of breath (OR = 14.2, 95% CI: 4.79, 52.4), wheeze (OR = 14.4, 95% CI: 4.80, 53.7), and the combined presence of any respiratory symptom (OR = 9.82, 95% CI: 4.22, 24.5). In subjects with lower BMIs, respiratory symptom ORs for arsenic water concentrations ≥11µg/L were markedly lower. In never-smokers, reductions in forced vital capacity associated with arsenic increased as BMI increased. Analysis of the FEV 1 /FVC ratio in never-smokers significantly increased as BMI and arsenic concentrations increased. Similar trends were not observed for FEV 1 alone or in ever-smokers. This study provides preliminary evidence that BMI may increase the risk for arsenic-related non-malignant respiratory disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Cellular morphometry of the bronchi of human and dog lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, E.S.

1991-03-01

One hundred and thirty-one bronchial samples from 62 patients have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. Complete patient records including occupational and smoking histories, as well as possible exposure to radon, are obtained. In addition, one hundred and sixty-two mongol dog bronchi dissected from different lobes of 23 dog lungs have also been similarly prepared. Ninety-four human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 532 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurementmore » of the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 240 micrographs of dog epithelium from 31 bronchial samples have been entered into COSAS. We have, using the COSAS planimetry program, established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the epithelial cell types of dog bronchi. The data are being used to develop weighting factors for dosimetry and radon risk analysis. 26 refs., 7 figs., 4 tabs.« less

Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer.

PubMed

Russo, Andrea L; Thiagalingam, Arunthathi; Pan, Hongjie; Califano, Joseph; Cheng, Kuang-hung; Ponte, Jose F; Chinnappan, Dharmaraj; Nemani, Pratima; Sidransky, David; Thiagalingam, Sam

2005-04-01

Promoter DNA methylation status of six genes in samples derived from 27 bronchial epithelial cells and matching blood samples from 22 former/current smokers and five nonsmokers as well as 49 primary non-small cell lung cancer samples with corresponding blood controls was determined using methylation-specific PCR (MSP). Lung tumor tissues showed a significantly higher frequency of promoter DNA methylation in p16, MGMT, and DAPK (P < 0.05; Fisher's exact test). p16 promoter DNA methylation in tumors was observed at consistently higher levels when compared with all the other samples analyzed (P = 0.001; Fisher's exact test). ECAD and DAPK exhibited statistically insignificant differences in their levels of DNA methylation among the tumors and bronchial epithelial cells from the smokers. Interestingly, similar levels of methylation were observed in bronchial epithelial cells and corresponding blood from smokers for all four genes (ECAD, p16, MGMT, and DAPK) that showed smoking/lung cancer-associated methylation changes. In summary, our data suggest that targeted DNA methylation silencing of ECAD and DAPK occurs in the early stages and that of p16 and MGMT in the later stages of lung cancer progression. We also provide preliminary evidence that peripheral lymphocytes could potentially be used as a surrogate for bronchial epithelial cells to detect altered DNA methylation in smokers.

Cigarette smoking decreases dynamic inspiratory capacity during maximal exercise in patients with type 2 diabetes.

PubMed

Kitahara, Yoshihiro; Hattori, Noboru; Yokoyama, Akihito; Yamane, Kiminori; Sekikawa, Kiyokazu; Inamizu, Tsutomu; Kohno, Nobuoki

2012-06-01

To investigate the influence of cigarette smoking on exercise capacity, respiratory responses and dynamic changes in lung volume during exercise in patients with type 2 diabetes. Forty-one men with type, 2 diabetes without cardiopulmonary disease were recruited and divided into 28 non-current smokers and 13 current smokers. All subjects received lung function tests and cardiopulmonary exercise testing using tracings of the flow-volume loop. Exercise capacity was compared using the percentage of predicted oxygen uptake at maximal workload (%VO2max). Respiratory variables and inspiratory capacity (IC) were compared between the two groups at rest and at 20%, 40%, 60%, 80% and 100% of maximum workload. Although there was no significant difference in lung function tests between the two groups, venous carboxyhemoglobin (CO-Hb) levels were significantly higher in current smokers. %VO2max was inversely correlated with CO-Hb levels. Changing patterns in respiratory rate, respiratory equivalent and IC were significantly different between the two groups. Current smokers had rapid breathing, a greater respiratory equivalent and a limited increase in IC during exercise. Cigarette smoking diminishes the increase in dynamic IC in patients with type 2 diabetes. As this effect of smoking on dynamic changes in lung volume will exacerbate dynamic hyperinflation in cases complicated by chronic obstructive pulmonary disease, physicians should consider smoking habits and lung function when evaluating exercise capacity in patients with type 2 diabetes.

Frequency of breast cancer, lung cancer, and tobacco use articles in women's magazines from 1987 to 2003.

PubMed

Tobler, Kyle J; Wilson, Philip K; Napolitano, Peter G

2009-01-01

The objective of this study was to compare the frequency of articles in women's magazines that address breast cancer, lung cancer, and tobacco use from 1987-2003 and to ascertain whether the annual number of articles reflected corresponding cancer mortality rates from breast cancer and lung cancer and the number of female smokers throughout this time period. We reviewed 13 women's magazines published in the United States from 1987-2003 using the search terms breast cancer, lung cancer, smoking, and tobacco. We reviewed the abstracts or entire articles to determine relevance. A total of 1044 articles addressed breast cancer, lung cancer, or tobacco use: 681 articles related to breast cancer, 47 related to lung cancer, and 316 related to tobacco use. The greater number of breast cancer articles compared to lung cancer articles was statistically significant (P value < .0001). The greater number of breast cancer articles compared to lung cancer articles combined with tobacco use articles was also statistically significant (P = .0012). The annual number breast cancer articles compared to the breast cancer mortality rate demonstrated a negative relationship. The annual number of lung cancer articles compared to the lung cancer mortality rate demonstrated no relationship. The annual number of tobacco use articles compared to the annual number of female smokers demonstrated no relationship. Breast cancer was more frequently represented than lung cancer or tobacco use in women's magazines from 1987-2003 despite the increase in lung cancer mortality, a decrease in breast cancer mortality, and an insignificant change in the number of female smokers.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

PubMed

Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

2011-03-10

Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a.

PubMed

Hedström, Anna Karin; Ryner, Malin; Fink, Katarina; Fogdell-Hahn, Anna; Alfredsson, Lars; Olsson, Tomas; Hillert, Jan

2014-04-01

Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy. The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ, in the treatment of multiple sclerosis (MS). This report is based on 695 MS patients treated with IFNβ-1a, included in two Swedish case-control studies that collected information on smoking habits. Using logistic regression, the development of NAbs to IFNβ-1a among current smokers was compared with that of non-smokers, by calculating the odds ratio (OR) with a 95% confidence interval (CI). Current smokers showed an increased risk of developing NAbs to IFNβ-1a, compared with non-smokers (OR 1.9; 95% CI 1.3-2.8; p = 0.002). There were no gender differences. We observed no association between past smoking and the risk of developing NAbs to IFNβ-1a. The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.

Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers.

PubMed

Li, Chenguang; Fang, Rong; Sun, Yihua; Han, Xiangkun; Li, Fei; Gao, Bin; Iafrate, A John; Liu, Xin-Yuan; Pao, William; Chen, Haiquan; Ji, Hongbin

2011-01-01

We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations. We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing. 152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5' partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected. The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor.

Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers

PubMed Central

Han, Xiangkun; Li, Fei; Gao, Bin; Iafrate, A. John; Liu, Xin-Yuan; Pao, William; Chen, Haiquan; Ji, Hongbin

2011-01-01

Purpose We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations. Experimental Design We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing. Results 152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5′ partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected. Conclusion The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor. PMID:22140546

Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

PubMed

Gupta, Pawan; Dash, Devijyoti; Mittal, Richa; Chhabra, Sunil K

2017-05-01

The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking. © 2015 John Wiley & Sons Ltd.

Impact of Lung Cancer Screening Results on Smoking Cessation

PubMed Central

Berg, Christine D.; Riley, Thomas L.; Cunningham, Christopher R.; Taylor, Kathryn L.

2014-01-01

Background Lung cancer screening programs may provide opportunities to reduce smoking rates among participants. This study evaluates the impact of lung cancer screening results on smoking cessation. Methods Data from Lung Screening Study participants in the National Lung Screening Trial (NLST; 2002–2009) were used to prepare multivariable longitudinal regression models predicting annual smoking cessation in those who were current smokers at study entry (n = 15489, excluding those developing lung cancer in follow-up). The associations of lung cancer screening results on smoking cessation over the trial period were analyzed. All hypothesis testing used two sided P values. Results In adjusted analyses, smoking cessation was strongly associated with the amount of abnormality observed in the previous year’s screening (P < .0001). Compared with those with a normal screen, individuals were less likely to be smokers if their previous year’s screen had a major abnormality that was not suspicious for lung cancer (odds ratio [OR] = 0.811; 95% confidence interval [CI] = 0.722 to 0.912; P < .001), was suspicious for lung cancer but stable from previous screens (OR = 0.785; 95% CI = 0.706 to 0.872; P < .001), or was suspicious for lung cancer and was new or changed from the previous screen (OR = 0.663; 95% CI = 0.607 to 0.724; P < .001). Differences in smoking prevalence were present up to 5 years after the last screen. Conclusions Smoking cessation is statistically significantly associated with screen-detected abnormality. Integration of effective smoking cessation programs within screening programs should lead to further reduction in smoking-related morbidity and mortality. PMID:24872540

[Study on smoking attributed death and effects of smoking cessation in residents aged 35-79 years in Tianjin, 2016].

PubMed

Li, W; Wang, D Z; Zhang, H; Xu, Z L; Xue, X D; Jiang, G H

2017-11-10

Objective: To analyze the influence of smoking on deaths in residents aged 35-79 years and the effects of smoking cessation in Tianjin. Methods: The data of 39 499 death cases aged 35-79 years in 2016 in Tianjin were collected, the risks for deaths caused by smoking related diseases and excess deaths as well as effects of smoking cessation were analyzed after adjusting 5 year old age group, education level and marital status. Results: Among the 39 499 deaths cases, 1 589 (13.56%) were caused by smoking, the percentage of the excess mortality of lung cancer caused by smoking was highest (47.60%); the risk of death due to lung cancer in smokers was 2.75 times higher than that in non-smokers (95 %CI : 2.47-3.06). Among the female deaths, 183 (7.29%) were caused by smoking, the percentage of the excess mortality of lung cancer was highest (28.90%); and the risk of death of lung cancer in smokers was 4.04 times higher than that in non-smokers (95 %CI : 3.49-4.68). The OR for disease in ex-smokers was 0.80 compared with 1.00 in smokers (95 %CI : 0.72-0.90). The OR in males who had quitted smoking for ≥10 years was lower (0.74, 95 %CI : 0.63-0.86) than that in those who had quitted smoking for 1-9 years (0.85, 95 %CI : 0.74-0.98), but the difference was not significant. Conclusion: Smoking is one of the most important risk factors for deaths in residents in Tianjin. Smoking cessation can benefit people's health.

Factor Structure and Stability of Smoking-Related Health Beliefs in the National Lung Screening Trial

PubMed Central

Koblitz, Amber R.; Persoskie, Alexander; Ferrer, Rebecca A.; Klein, William M. P.; Dwyer, Laura A.; Park, Elyse R.

2016-01-01

Introduction: Absolute and comparative risk perceptions, worry, perceived severity, perceived benefits, and self-efficacy are important theoretical determinants of tobacco use, but no measures have been validated to ensure the discriminant validity as well as test-retest reliability of these measures in the tobacco context. The purpose of the current study is to examine the reliability and factor structure of a measure assessing smoking-related health cognitions and emotions in a national sample of current and former heavy smokers in the National Lung Screening Trial. Methods: A sub-study of the National Lung Screening Trial assessed current and former smokers’ (age 55–74; N = 4379) self-reported health cognitions and emotions at trial enrollment and at 12-month follow-up. Items were derived from the Health Belief Model and Self-Regulation Model. Results: An exploratory factor analysis of baseline responses revealed a five-factor structure for former smokers (risk perceptions, worry, perceived severity, perceived benefits, and self-efficacy) and a six-factor structure for current smokers, such that absolute risk and comparative risk perceptions emerged as separate factors. A confirmatory factor analysis of 12-month follow-up responses revealed a good fit for the five latent constructs for former smokers and six latent constructs for current smokers. Longitudinal stability of these constructs was also demonstrated. Conclusions: This is the first study to examine tobacco-related health cognition and emotional constructs over time in current and former heavy smokers undergoing lung screening. This study found that the theoretical constructs were stable across time and that the factor structure differed based on smoking status (current vs. former). PMID:25964503

[Helping smoking cessation in COPD, asthma, lung cancer, operated smokers].

PubMed

Perriot, J; Underner, M; Peiffer, G; Dautzenberg, B

2018-06-01

Smoking is the cause of addictive behavior. Tobacco addiction is a chronic disease that makes difficult to stop smoking and leads to further use. Smoking is a risk factor for COPD, asthma and lung cancer; it may be the cause of severe perioperative complications. This finding justifies that smokers benefit from advice of stopping smoking and smoking cessation assistance. Helping patients to stop smoking increases the chances of quitting, improves the prognosis of tobacco-related diseases, the effectiveness of their treatments and the quality of life of the patients. This article updates the modalities of smoking cessation assistance in smokers with COPD, asthma and lung cancer in operated patients. The goal of the management must be the complete cessation of tobacco smoke intoxication, which alone reduces tobacco mortality. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Risk factors of Lung Cancer in nonsmoker.

PubMed

Akhtar, Nahid; Bansal, Jeena Gupta

Generally, the cause of lung cancer is attributed to tobacco smoking. But many of the new lung cancer cases have been reported in nonsmokers. Apart from smoking; air pollution, environmental exposure, mutations, and single-nucleotide polymorphisms are known to be associated with lung cancer. Improper diet, alcohol consumption, marijuana smoking, estrogen, infections with human papillomavirus (HPV), HIV, and Epstein-Barr virus are suggested to be linked with lung cancer but clear evidences to ascertain their relation is not available. This article provides a comprehensive review of various risk factors and the underlying molecular mechanisms responsible for increasing the incidence of lung cancer. The pathologic, histologic, and genetic differences exist with lung cancer among smokers and nonsmokers. A better understanding of the risk factors, differences in pathology and molecular features of lung cancer in smokers and nonsmokers and the mode of action of various carcinogens will facilitate the prevention and management of lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Lung cancer risk comparison among male smokers between the "six-prefecture cohort" in Japan and the British physicians' cohort.

PubMed

Mizuno, S; Akiba, S; Hirayama, T

1989-12-01

We estimated the effective duration of cigarette smoking using the data of lung cancer mortality among male smokers of a large-scale cohort study in Japan and evaluated its role in the lung cancer risk difference between male smokers of the Japanese cohort and the British physicians' cohort. By selecting male cohort members who answered that they had started smoking at ages 18-22 (average = 20.3), the subjects of our analysis, which numbered 49,013, were made relatively homogeneous in terms of age at which smoking was started. Assuming lung cancer mortality to be proportional to the 4.5th power of the effective duration of cigarette smoking, i.e., (age-theta)4.5, as was proposed on the basis of the British cohort study by Doll and Peto, the parameter theta was estimated to be 29.4 for male smokers aged 40-64 in 1966; therefore, the estimated duration of cigarette smoking was, on average, 9.1 years (95% confidence interval = 5.8-11.6) shorter than that calculated from the reported age at which smoking was started. Our findings suggested that the low lung cancer mortality relative to daily cigarette consumption in Japan resulted from the shorter duration of cigarette smoking in the Japanese cohort, possibly due to the severe shortage of cigarettes during and shortly after World War II. Once the effective duration of cigarette smoking was adjusted, lung cancer mortality in the range of 5-34 cigarettes per day was fairly comparable to that observed among the cohort of male British physicians.

Respiratory function in healthy ever-smokers is impaired by smoking habits in a dose-dependent manner.

PubMed

Osanai, Shinobu; Ogasa, Toshiyuki; Sumitomo, Kazuhiro; Hasebe, Naoyuki

2018-01-01

There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials

PubMed Central

Correa, Candace; Duane, Frances K.; Aznar, Marianne C.; Anderson, Stewart J.; Bergh, Jonas; Dodwell, David; Ewertz, Marianne; Gray, Richard; Jagsi, Reshma; Pierce, Lori; Pritchard, Kathleen I.; Swain, Sandra; Wang, Zhe; Wang, Yaochen; Whelan, Tim; Peto, Richard; McGale, Paul

2017-01-01

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk. PMID:28319436

Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials.

PubMed

Taylor, Carolyn; Correa, Candace; Duane, Frances K; Aznar, Marianne C; Anderson, Stewart J; Bergh, Jonas; Dodwell, David; Ewertz, Marianne; Gray, Richard; Jagsi, Reshma; Pierce, Lori; Pritchard, Kathleen I; Swain, Sandra; Wang, Zhe; Wang, Yaochen; Whelan, Tim; Peto, Richard; McGale, Paul

2017-05-20

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.

Surgery for lung adenocarcinoma with smokers' polycythemia: a case report.

PubMed

Sugiura, Yasoo; Nemoto, Etsuo; Shinoda, Hiromi; Nakamura, Naoya; Kaseda, Shizuka

2013-02-01

Smoking is a cause of cancer and polycythemia. Therefore, surgeons who treat patients with cancer may also encounter patients with polycythemia. However, few cases of surgical patients with polycythemia have been reported; in particular, a surgical case involving smokers' polycythemia has never been reported. We herein report a patient with lung cancer and smokers' polycythemia who successfully underwent lobectomy with control of hematocrit based on a modified formula in the perioperative period. A 67-year-old man underwent abdominoperineal resection for rectal carcinoma in June 2008. A ground glass opacity had been identified in the upper lobe of the right lung and was gradually enlarging. In March 2012, bronchoscopic cytology for investigation of the mass revealed non-small cell lung cancer, suggesting primary lung non-small cell carcinoma (T1bN0M0, Stage IA). When he was referred to our hospital for surgery, his complete blood count showed a red blood cell level of 6.50×106/μL, hemoglobin of 21.0 g/dL, and hematocrit of 60.1%. The hematologists' diagnosis was secondary polycythemia due to heavy smoking (smokers' polycythemia) because the white blood cell and platelet counts were within normal limits and the erythropoietin was not increased. We calculated the appropriate phlebotomy and infusion volumes based on a formula that we modified. After 550 g of blood was phlebotomized to reduce the hematocrit to approximately 55%, video-assisted right lung upper lobectomy with lymph node dissection was performed in April 2012. The hematocrit was maintained at <50% postoperatively, and the patient was uneventfully discharged on postoperative day 7. The predictive hematocrit and measured hematocrit were very closely approximated in this case. We experienced a patient with smokers' polycythemia who underwent right upper lobectomy for adenocarcinoma. The findings in this case report are meaningful for surgeons treating cancer patients because there are few reports discussing the perioperative care of surgical patients with polycythemia.

Pulmonary 3He Magnetic Resonance Imaging Biomarkers of Regional Airspace Enlargement in Alpha-1 Antitrypsin Deficiency.

PubMed

Lessard, Eric; Young, Heather M; Bhalla, Anurag; Pike, Damien; Sheikh, Khadija; McCormack, David G; Ouriadov, Alexei; Parraga, Grace

2017-11-01

Thoracic x-ray computed tomography (CT) and hyperpolarized 3 He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (L m ) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers. We enrolled patients with AATD (n = 8; 57 ± 7 years), ex-smokers with COPD (n = 8; 77 ± 6 years), and a control group of never-smokers (n = 5; 64 ± 2 years) who underwent thoracic CT, MRI, spirometry, plethysmography, the St. George's Respiratory Questionnaire, and the 6-minute walk test during a single 2-hour visit. MRI-derived ADC, L m , surface-to-volume ratio, and ventilation defect percent were generated for the apical, basal, and whole lung as was CT lung area ≤-950 Hounsfield units (RA 950 ), low attenuating clusters, and airway count. In patients with AATD, there was a significantly different MRI-derived ADC (P = .03), L m (P < .0001), and surface-to-volume ratio (P < .0001), but not diffusing capacity of carbon monoxide, residual volume or total lung capacity, or CT RA 950 (P > .05) compared to COPD ex-smokers with a significantly different St. George's Respiratory Questionnaire. In this proof-of-concept demonstration, we evaluated CT and MRI lung emphysema measurements and observed significantly worse MRI biomarkers of emphysema in patients with AATD compared to patients with COPD, although CT RA 950 and diffusing capacity of carbon monoxide were not significantly different, underscoring the sensitivity of MRI measurements of AATD emphysema. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

“Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health”

PubMed Central

McEvoy, Cindy T.; Spindel, Eliot R.

2016-01-01

Summary Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking. PMID:27639458

Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers | Division of Cancer Prevention

Cancer.gov

This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. |

Lung Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Screening with chest x-ray or sputum cytology does not reduce lung cancer mortality. Get detailed information about lung cancer screening in this clinician summary.

Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

PubMed Central

Leng, Shuguang; Stidley, Christine A.; Liu, Yushi; Edlund, Christopher K.; Willink, Randall P.; Han, Younghun; Landi, Maria Teresa; Thun, Michael; Picchi, Maria A.; Bruse, Shannon E.; Crowell, Richard E.; Van Den Berg, David; Caporaso, Neil E.; Amos, Christopher I.; Siegfried, Jill M.; Tesfaigzi, Yohannes; Gilliland, Frank D.; Belinsky, Steven A.

2011-01-01

The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here we identified genetic determinants for this epigenetic process and examined their biological effects on gene regulation. A two-stage approach involving discovery and replication was employed to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and DNA damage response in members of the Lovelace Smokers Cohort (n=1434). Molecular validation of three identified variants was conducted using primary bronchial epithelial cells. Association of study-wide significance (P<8.2×10−5) was identified for rs1641511, rs3730859, and rs1883264 in TP53, LIG1, and BIK, respectively. These SNPs were significantly associated with altered expression of the corresponding genes in primary bronchial epithelial cells. In addition, rs3730859 in LIG1 was also moderately associated with increased risk for lung cancer among Caucasian smokers. Together, our findings suggest that genetic variation in DNA replication and apoptosis pathways impacts the propensity for gene promoter hypermethylation in the aerodigestive tract of smokers. The incorporation of genetic biomarkers for gene promoter hypermethylation with clinical and somatic markers may improve risk assessment models for lung cancer. PMID:22139380

Validation of Protein Markers for Lung Cancer Using CARET Sera and Proteomics Techniques — EDRN Public Portal

Cancer.gov

1.1 To validate the finding from pilot studies with CARET sera of autoantibodies to annexins I and II and PGP9.5 as potential biomarkers for lung cancers before the clinical diagnosis, evaluating sensitivity and specificity by time before diagnosis, treatment arm, gender, histologic type, and smoking status. 1.2 To determine whether a pattern of occurrence of autoantibodies in lung cancer sera may be diagnostic of lung cancer that is not dependent on the occurrence of any particular autoantibody. 1.3 To compare the findings for individual biomarker candidates and combinations of biomarker candidates in participants who were current smokers versus former smokers.

DJ-1 Modulates Nuclear Erythroid 2-Related Factor-2-Mediated Protection in Human Primary Alveolar Type II Cells in Smokers.

PubMed

Bahmed, Karim; Messier, Elise M; Zhou, Wenbo; Tuder, Rubin M; Freed, Curt R; Chu, Hong Wei; Kelsen, Steven G; Bowler, Russell P; Mason, Robert J; Kosmider, Beata

2016-09-01

Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2-related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases.

DJ-1 Modulates Nuclear Erythroid 2–Related Factor-2–Mediated Protection in Human Primary Alveolar Type II Cells in Smokers

PubMed Central

Bahmed, Karim; Messier, Elise M.; Zhou, Wenbo; Tuder, Rubin M.; Freed, Curt R.; Chu, Hong Wei; Kelsen, Steven G.; Bowler, Russell P.; Mason, Robert J.

2016-01-01

Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2–related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases. PMID:27093578

Human papilloma virus in non-small cell lung cancer in never smokers: a systematic review of the literature.

PubMed

Hasegawa, Yoshikazu; Ando, Masahiko; Kubo, Akihito; Isa, Shun-Ichi; Yamamoto, Satomi; Tsujino, Kazuyuki; Kurata, Takayasu; Ou, Sai-Hong I; Takada, Minoru; Kawaguchi, Tomoya

2014-01-01

Non-small cell lung cancer (NSCLC) in never smokers has emerged as a global public health issue. The cause is still unclear, and few studies have focused on the prevalence of human papillomavirus (HPV) in the never smokers. We performed a systematic search of PubMed for articles of HPV infection in human subjects with NSCLC up to September 2012. Although smoking status was not fully reported in all studies, we contacted the authors by e-mail to supplement this information. Differences in the distribution of patients with and without HPV infection were tested with the Chi squared test. We identified 46 eligible articles, including 23 from Asian countries (N=2337 NSCLC cases), 19 from European countries (N=1553) and 4 from North and South America (N=160). The HPV prevalence was 28.1% (95% confidence interval (CI) 26.6-30.3%), 8.4% (95% CI 7.1-9.9%) and 21.3% (95% CI 15.2-28.4%), respectively. Eleven studies from East Asia (N=1110) and 4 from Europe (N=569) provided information on smoking status. The number of never smoker was 392 patients (33.9%) in East Asia and 54 patients (14.8%) in Europe. The HPV prevalence in East Asian countries was similar between never and ever smokers (33.9% vs 39.2%, P=0.080). Based on the literature confirming the presence of HPV in lung cancer in never smokers, the virus plays a role in carcinogenesis in the disease. There were different patterns of HPV prevalence between Asian and European countries in the never smokers as well as in ever smokers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Lung Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Lung cancer screening with low-dose spiral CT scans has been shown to decrease the risk of dying from lung cancer in heavy smokers. Learn more about tests to detect lung cancer and their potential benefits and harms in this expert-reviewed summary.

Risk Profiling May Improve Lung Cancer Screening

Cancer.gov

A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

Urban air carcinogens and their effects on health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lechner, J.F.

1994-11-01

Airborne carcinogens may be relevant especially in metropolitan regions with extreme smog as a primary cause of lung cancer. Lung cancer is most common in urban environs and the incidence directly correlates with the size of the city. In addition, several, but not all formal epidemiological studies also suggest a positive correlation between lung cancer incidence and the intensity of air pollution exposure. There is further support for a role of air pollution; as of 1993, 4.4% of all of the bronchogenic adenocarcinoma cancer cases among Mexicans living in industrialized cities are under 40 years of age. It is plausiblemore » that chronic inhalation of automobile combustion products, factory emissions, and/or radon is at least partially responsible for the higher incidence of lung cancer exemplified by the never-smoking urban residents. The exceptionally high incidence of lung cancer cases among never-smokers living in highly industrialized Mexican cities offers a unique opportunity to use molecular epidemiology to test whether chronic inhalation of atmospheric pollutants increases the risk for this disease. Overall, the analysis of the genetic alterations in two cancer genes, and possibly the hprt locus should give new insight as to whether the urban never-smokers developed their cancers because of exposure to environmental pollutants.« less

Signs of Gas Trapping in Normal Lung Density Regions in Smokers.

PubMed

Bodduluri, Sandeep; Reinhardt, Joseph M; Hoffman, Eric A; Newell, John D; Nath, Hrudaya; Dransfield, Mark T; Bhatt, Surya P

2017-12-01

A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known. To identify subthreshold structural disease in normal-appearing lung regions in smokers. We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity. The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV 1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV 1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001). Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Proportion and clinical features of never-smokers with non-small cell lung cancer.

PubMed

Cho, Jaeyoung; Choi, Sun Mi; Lee, Jinwoo; Lee, Chang-Hoon; Lee, Sang-Min; Kim, Dong-Wan; Yim, Jae-Joon; Kim, Young Tae; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

2017-02-08

The proportion of never-smokers with non-small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never-smokers with NSCLC in a large single institution. We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014. Of the 1860 NSCLC patients, 707 (38.0%) were never-smokers. The proportions of women (83.7% vs. 5.6%) and adenocarcinoma (89.8% vs. 44.9%) were higher among never-smokers than among ever-smokers. Significantly more never-smokers were diagnosed at a younger median age (65 vs. 68 years, P < 0.001) and earlier stage (stage I-II, 44.5% vs. 38.9%, P = 0.015) compared with ever-smokers. Epidermal growth factor receptor mutations (57.8% vs. 24.4%, P < 0.001) and anaplastic lymphoma kinase rearrangements (7.8% vs. 2.8%, P < 0.001) were more common in never-smokers, whereas Kirsten rat sarcoma viral oncogene homolog mutations (5.8% vs. 9.6%, P = 0.021) were less frequently encountered in never-smokers than in ever-smokers. Never-smokers showed longer survival after adjusting for the favorable effects of younger age, female sex, adenocarcinoma histology, better performance status, early stage disease, being asymptomatic at diagnosis, received antitumor treatment, and the presence of driver mutations (hazard ratio, 0.624; 95% confidence interval, 0.460-0.848; P = 0.003). More than one-third of the Korean patients with NSCLC were never-smokers. NSCLC in never-smokers had different clinical characteristics and major driver mutations and resulted in longer overall survival compared with NSCLC in ever-smokers.

Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers

PubMed Central

Fang, Xue; Yin, Zhihua; Li, Xuelian; Xia, Lingzi; Zhou, Baosen

2016-01-01

MicroRNA biosynthesis genes can affect the regulatory effect of global microRNAs to target mRNA and hence influence the genesis and development of human cancer. Here, we selected five single nucleotide polymorphisms (SNPs) (rs7813, rs2740349, rs2291778, rs910924, rs595961) in two key microRNA biosynthesis genes (GEMIN4 and AGO1) and systematically evaluated the association between these SNPs, the gene-environment interaction and lung cancer risk. To control the impact of cigarette smoking on lung cancer, we recruited Chinese female non-smokers for the study. The total number of lung cancer cases and cancer-free controls were 473 and 395 in the case-control study. Four SNPs showed statistically significant associations with lung cancer risk. After Bonferroni correction, rs7813 and rs595961 were evidently still associated with lung cancer risk. In the stratified analysis, our results revealed that all five SNPs were associated with the risk of lung adenocarcinoma; after Bonferroni correction, significant association was maintained for rs7813, rs910924 and rs595961. Haplotype analysis showed GEMIN4 haplotype C-A-G-T was a protective haplotype for lung cancer. In the combined unfavorable genotype analysis, with the increasing number of unfavorable genotypes, a progressively increased gene-dose effect was observed in lung adenocarcinoma. We also found that individuals exposed to cooking oil fumes showed a relatively high risk of lung cancer, but no interactions were found between cooking oil fume exposure or passive smoking exposure with these SNPs, either on an additive scale or a multiplicative scale. Overall, this is the first study showing that rs7813 and rs595961 could be meaningful as genetic markers for lung cancer risk. PMID:27669275

Anti-p-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD.

PubMed

Banerjee, Santanu; Bhattacharyya, Parthasarathi; Mitra, Subhra; Kundu, Somenath; Panda, Samiran; Chatterjee, Indu B

2017-01-01

Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p -benzoquinone ( p -BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p -BQ is also derived from CS in smokers and it elicits the production of anti- p -BQ antibody in humans. We therefore hypothesized that anti- p -BQ antibody might have a protective role against COPD and could be used as a predictive biomarker for COPD in smokers. The objective of this study was to compare the serum anti- p -BQ antibody level between smokers with and without COPD for the evaluation of the hypothesis. Serum anti- p -BQ antibody concentrations of current male smokers with (n=227) or without (n=308) COPD were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA) developed in our laboratory. COPD was diagnosed by spirometry according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. A significant difference was observed in the serum anti- p -BQ antibody level between smokers with and without COPD (Mann-Whitney U -test =4,632.5, P =0.000). Receiver operating characteristic (ROC) curve analysis indicated that the ELISA had significant precision (area under the curve [AUC] =0.934, 95% confidence interval [CI]: 0.913-0.935) for identifying smokers with COPD from their low antibody level. The antibody cutoff value of 29.4 mg/dL was constructed from the ROC coordinates to estimate the risk for COPD in smokers. While 90.3% of smokers with COPD had a low antibody value (≤29.4 mg/dL), the majority (86.4%) of smokers without COPD had a high antibody value (≤29.4 mg/dL); 13.6% of current smokers without COPD having an antibody level below this cutoff value (odds ratio [OR] =59.3, 95% CI: 34.15-101.99) were considered to be at risk for COPD. Our results indicate that serum anti- p -BQ antibody level may be used as a biomarker to identify asymptomatic smokers at risk for COPD for early intervention of the disease.

Anti-p-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD

PubMed Central

Banerjee, Santanu; Bhattacharyya, Parthasarathi; Mitra, Subhra; Kundu, Somenath; Panda, Samiran; Chatterjee, Indu B

2017-01-01

Background and objective Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p-benzoquinone (p-BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p-BQ is also derived from CS in smokers and it elicits the production of anti-p-BQ antibody in humans. We therefore hypothesized that anti-p-BQ antibody might have a protective role against COPD and could be used as a predictive biomarker for COPD in smokers. The objective of this study was to compare the serum anti-p-BQ antibody level between smokers with and without COPD for the evaluation of the hypothesis. Methods Serum anti-p-BQ antibody concentrations of current male smokers with (n=227) or without (n=308) COPD were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA) developed in our laboratory. COPD was diagnosed by spirometry according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Results and discussion A significant difference was observed in the serum anti-p-BQ antibody level between smokers with and without COPD (Mann–Whitney U-test =4,632.5, P=0.000). Receiver operating characteristic (ROC) curve analysis indicated that the ELISA had significant precision (area under the curve [AUC] =0.934, 95% confidence interval [CI]: 0.913–0.935) for identifying smokers with COPD from their low antibody level. The antibody cutoff value of 29.4 mg/dL was constructed from the ROC coordinates to estimate the risk for COPD in smokers. While 90.3% of smokers with COPD had a low antibody value (≤29.4 mg/dL), the majority (86.4%) of smokers without COPD had a high antibody value (≤29.4 mg/dL); 13.6% of current smokers without COPD having an antibody level below this cutoff value (odds ratio [OR] =59.3, 95% CI: 34.15–101.99) were considered to be at risk for COPD. Conclusion and future directions Our results indicate that serum anti-p-BQ antibody level may be used as a biomarker to identify asymptomatic smokers at risk for COPD for early intervention of the disease. PMID:28684907

A genome-wide gene–environment interaction analysis for tobacco smoke and lung cancer susceptibility

PubMed Central

Zhang, Ruyang; Chu, Minjie; Zhao, Yang; Wu, Chen; Guo, Huan; Shi, Yongyong; Dai, Juncheng; Wei, Yongyue; Jin, Guangfu; Ma, Hongxia; Dong, Jing; Yi, Honggang; Bai, Jianling; Gong, Jianhang; Sun, Chongqi; Zhu, Meng; Wu, Tangchun; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing; Chen, Feng

2014-01-01

Tobacco smoke is the major environmental risk factor underlying lung carcinogenesis. However, approximately one-tenth smokers develop lung cancer in their lifetime indicating there is significant individual variation in susceptibility to lung cancer. And, the reasons for this are largely unknown. In particular, the genetic variants discovered in genome-wide association studies (GWAS) account for only a small fraction of the phenotypic variations for lung cancer, and gene–environment interactions are thought to explain the missing fraction of disease heritability. The ability to identify smokers at high risk of developing cancer has substantial preventive implications. Thus, we undertook a gene–smoking interaction analysis in a GWAS of lung cancer in Han Chinese population using a two-phase designed case–control study. In the discovery phase, we evaluated all pair-wise (591 370) gene–smoking interactions in 5408 subjects (2331 cases and 3077 controls) using a logistic regression model with covariate adjustment. In the replication phase, promising interactions were validated in an independent population of 3023 subjects (1534 cases and 1489 controls). We identified interactions between two single nucleotide polymorphisms and smoking. The interaction P values are 6.73 × 10− 6 and 3.84 × 10− 6 for rs1316298 and rs4589502, respectively, in the combined dataset from the two phases. An antagonistic interaction (rs1316298–smoking) and a synergetic interaction (rs4589502–smoking) were observed. The two interactions identified in our study may help explain some of the missing heritability in lung cancer susceptibility and present strong evidence for further study of these gene–smoking interactions, which are benefit to intensive screening and smoking cessation interventions. PMID:24658283

Chemoprevention of Lung Cancer

PubMed Central

Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

2013-01-01

Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

Telomerase and the Genetics of Emphysema Susceptibility. Implications for Pathogenesis Paradigms and Patient Care

PubMed Central

Stanley, Susan E.; Merck, Samantha J.

2016-01-01

In the past five decades, alpha-1 antitrypsin deficiency has been the only known genetic cause of emphysema, yet it explains the genetics in only 1–2% of severe cases. Recently, mutations in telomerase genes were found to induce susceptibility to young-onset, severe, and familial emphysema at a frequency comparable to that of alpha-1 antitrypsin deficiency. Telomerase mutation carriers with emphysema report a family history of idiopathic pulmonary fibrosis, and both lung phenotypes show autosomal dominant inheritance within families. The data so far point to a strong gene–environment interaction that determines the lung disease type. In never-smokers, pulmonary fibrosis predominates, while smokers, especially females, are at risk for developing emphysema alone or in combination with pulmonary fibrosis. The telomere-mediated emphysema phenotype appears to have clinically recognizable features that are distinct from alpha-1 antitrypsin deficiency, and patients are prone to developing short telomere syndrome comorbidities that influence clinical outcomes. In animal models, telomere dysfunction causes alveolar epithelial stem cell senescence, which is sufficient to drive lung remodeling and recruit inflammation. Here, we review the implications of these discoveries for understanding emphysema biology as well as for patient care. PMID:28005428

Effect of cigar smoking on carboxyhaemoglobin and plasma nicotine concentrations in primary pipe and cigar smokers and ex-cigarette smokers

PubMed Central

Turner, J A McM; Sillett, R W; McNicol, M W

1977-01-01

Five ex-cigarette smokers and five primary pipe and cigar smokers each smoked a large cigar. Carboxyhaemoglobin (COHb) and plasma nicotine levels were measured. In the ex-cigarette smokers mean COHb rose from 2·9% to 9·6% and plasma nicotine from 79·0 nmol/l to 281 nmol/l (12·8-45·6 ng/ml). This response was similar to that of cigarette smokers smoking cigarettes, which indicated that the subjects had inhaled and absorbed significant amounts of nicotine. In the primary pipe and cigar smokers the mean COHb rose from 0·8% to 1·0% and the plasma nicotine from 21 nmol/l to 32 nmol/l (3·4-5·2 ng/ml), indicating neither significant inhalation nor significant nicotine absorption. Since ex-cigarette smokers do not seem to lose their habit of inhaling when they change to cigars, measures aimed at persuading smokers to switch to cigars will have little effect on their health. Pipe and cigar smokers who have never smoked cigarettes do not inhale, which probably accounts for their reduced incidence of coronary heart disease and lung cancer. But they also appear not to absorb nicotine, which suggests that nicotine is absorbed largely from the lung and that the buccal mucosa is unimportant. It also raises the interesting question of why primary pipe and cigar smokers do smoke. PMID:589225

Rapamycin prevents the development and progression of mutant epidermal growth factor receptor lung tumors with the acquired resistance mutation T790M.

PubMed

Kawabata, Shigeru; Mercado-Matos, José R; Hollander, M Christine; Donahue, Danielle; Wilson, Willie; Regales, Lucia; Butaney, Mohit; Pao, William; Wong, Kwok-Kin; Jänne, Pasi A; Dennis, Phillip A

2014-06-26

Lung cancer in never-smokers is an important disease often characterized by mutations in epidermal growth factor receptor (EGFR), yet risk reduction measures and effective chemopreventive strategies have not been established. We identify mammalian target of rapamycin (mTOR) as potentially valuable target for EGFR mutant lung cancer. mTOR is activated in human lung cancers with EGFR mutations, and this increases with acquisition of T790M mutation. In a mouse model of EGFR mutant lung cancer, mTOR activation is an early event. As a single agent, the mTOR inhibitor rapamycin prevents tumor development, prolongs overall survival, and improves outcomes after treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI). These studies support clinical testing of mTOR inhibitors in order to prevent the development and progression of EGFR mutant lung cancers. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Nonuniformity of diffusing capacity from small alveolar gas samples is increased in smokers.

PubMed

Cotton, D J; Mink, J T; Graham, B L

1998-01-01

Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSM manoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer. To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity. Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates. Both smokers and nonsmokers performed SBWSM manoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix). For SBWSM, DI was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DI with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVC manoeuvres, there were no differences due to smoking in Sn or Emix, but DI was increased in smokers and correlated with age and smoking pack-years, but not with Sn. For SBWSM manoeuvres the increase in DI in smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DI reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVC manoeuvres, the increase in DI in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DI during this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

Lung Cancer Occurrence in Never-Smokers: An Analysis of 13 Cohorts and 22 Cancer Registry Studies

PubMed Central

Thun, Michael J; Hannan, Lindsay M; Adams-Campbell, Lucile L; Boffetta, Paolo; Buring, Julie E; Feskanich, Diane; Flanders, W. Dana; Jee, Sun Ha; Katanoda, Kota; Kolonel, Laurence N; Lee, I-Min; Marugame, Tomomi; Palmer, Julie R; Riboli, Elio; Sobue, Tomotaka; Avila-Tang, Erika; Wilkens, Lynne R; Samet, Jon M

2008-01-01

Background Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions. Methods and Findings We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40–69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking. Conclusions These comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries. PMID:18788891

Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection.

PubMed

Pavel, Ana B; Campbell, Joshua D; Liu, Gang; Elashoff, David; Dubinett, Steven; Smith, Kate; Whitney, Duncan; Lenburg, Marc E; Spira, Avrum

2017-11-01

We have previously shown that gene expression alterations in normal-appearing bronchial epithelial cells can serve as a lung cancer detection biomarker in smokers. Given that miRNAs regulate airway gene expression responses to smoking, we evaluated whether miRNA expression is also altered in the bronchial epithelium of smokers with lung cancer. Using epithelial brushings from the mainstem bronchus of patients undergoing bronchoscopy for suspected lung cancer (as part of the AEGIS-1/2 clinical trials), we profiled miRNA expression via small-RNA sequencing from 347 current and former smokers for which gene expression data were also available. Patients were followed for one year postbronchoscopy until a final diagnosis of lung cancer ( n = 194) or benign disease ( n = 153) was made. Following removal of 6 low-quality samples, we used 138 patients (AEGIS-1) as a discovery set to identify four miRNAs (miR-146a-5p, miR-324-5p, miR-223-3p, and miR-223-5p) that were downregulated in the bronchial airway of lung cancer patients (ANOVA P < 0.002, FDR < 0.2). The expression of these miRNAs is significantly more negatively correlated with the expression of their mRNA targets than with the expression of other nontarget genes (K-S P < 0.05). Furthermore, these mRNA targets are enriched among genes whose expression is elevated in cancer patients (GSEA FDR < 0.001). Finally, we found that the addition of miR-146a-5p to an existing mRNA biomarker for lung cancer significantly improves its performance (AUC) in the 203 samples (AEGIS-1/2) serving an independent test set (DeLong P < 0.05). Our findings suggest that there are miRNAs whose expression is altered in the cytologically normal bronchial epithelium of smokers with lung cancer, and that they may regulate cancer-associated gene expression differences. Cancer Prev Res; 10(11); 651-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Risk perception and intention to quit among a tri-ethnic sample of nondaily, light daily, and moderate/heavy daily smokers.

PubMed

Savoy, Elaine; Reitzel, Lorraine R; Scheuermann, Taneisha S; Agarwal, Mohit; Mathur, Charu; Choi, Won S; Ahluwalia, Jasjit S

2014-10-01

Although the relationship between risk perceptions and quit intentions has been established, few studies explore the potential impact of smoking level on these associations, and none have done so among diversely-aged samples of multiple ethnicities. Participants, ranging in age from 25 to 81, were 1133 nondaily smokers (smoked ≥1 cigarette on 4 to 24days in the past 30days), 556 light daily smokers (≤10 cigarettes per day), and 585 moderate to heavy daily smokers (>10 cigarettes per day). Each smoking level comprised approximately equal numbers of African Americans, Latinos, and Whites. A logistic regression analysis, adjusted for sociodemographics, self-rated health, time to the first cigarette of the day and smoking level, was used to examine the association between risk perception (perceived risk of acquiring lung cancer, lung disease, and heart disease) and intention to quit (≤6months versus >6months/never). A second adjusted model tested moderation by smoking level with an interaction term. Greater risk perception was associated with a higher odds of planning to quit within 6months (AOR=1.34, CI.95=1.24, 1.45). Smoking level did not moderate this association (p=.85). Results suggest that educating all smokers, irrespective of their smoking level, about increased risk of developing smoking-related diseases might be a helpful strategy to enhance their intention to make a smoking quit attempt. Copyright © 2014 Elsevier Ltd. All rights reserved.

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wattson, Daniel A., E-mail: dwattson@partners.org; Hunink, M.G. Myriam; DiPiro, Pamela J.

2014-10-01

Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs.more » LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit.« less

The effect of inhaled corticosteroids on the development of emphysema in smokers assessed by annual computed tomography.

PubMed

Shaker, Saher B; Dirksen, Asger; Ulrik, Charlotte S; Hestad, Marianne; Stavngaard, Trine; Laursen, Lars C; Maltbaek, Niels; Clementsen, Paul; Skjaerbaek, Nanna; Nielsen, Lars; Stoel, Berend; Skovgaard, Lene T; Tonnesen, Philip

2009-04-01

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

Medical follow-up of workers exposed to lung carcinogens: French evidence-based and pragmatic recommendations.

PubMed

Delva, Fleur; Margery, Jacques; Laurent, François; Petitprez, Karine; Pairon, Jean-Claude

2017-02-14

The aim of this work was to establish recommendations for the medical follow-up of workers currently or previously exposed to lung carcinogens. A critical synthesis of the literature was conducted. Occupational lung carcinogenic substances were listed and classified according to their level of lung cancer risk. A targeted screening protocol was defined. A clinical trial, National Lung Screnning Trial (NLST), showed the efficacy of chest CAT scan (CT) screening for populations of smokers aged 55-74 years with over 30 pack-years of exposure who had stopped smoking for less than 15 years. To propose screening in accordance with NLST criteria, and to account for occupational risk factors, screening among smokers and former smokers needs to consider the types of occupational exposure for which the risk level is at least equivalent to the risk of the subjects included in the NLST. The working group proposes an algorithm that estimates the relative risk of each occupational lung carcinogen, taking into account exposure to tobacco, based on available data from the literature. Given the lack of data on bronchopulmonary cancer (BPC) screening in occupationally exposed workers, the working group proposed implementing a screening experiment for bronchopulmonary cancer in subjects occupationally exposed or having been occupationally exposed to lung carcinogens who are confirmed as having high risk factors for BPC. A specific algorithm is proposed to determine the level of risk of BPC, taking into account the different occupational lung carcinogens and tobacco smoking at the individual level.

An epidemiological study on occupation and cancer risk.

PubMed

Kato, I; Tominaga, S; Ikari, A

1990-06-01

The relation between occupation and cancer risk was examined on the basis of 17,164 male and 6,835 female cancer patients aged 30 years or over who were entered in the Aichi Cancer Registry during the period, 1979-1987. Controlling for age, the risk of developing lung cancer was significantly high in sales, transport-and-communications, mental, ceramics and construction workers in men, and service workers in women. The risk of developing liver cancer was significantly high in transport-and-communications and service workers in men. The risk of developing colon cancer was significantly high in professional people of both sexes and in clerical workers in men. The risk of developing female breast cancer was significantly high in professional women, administrative and clerical workers and hairdressers. The risk of developing stomach cancer was significantly high in male and female agricultural workers, while that of developing cancer of the mouth-and-pharynx was significantly high in construction workers in men and filature-and-spinning workers in women. Analysis of smoking and alcohol drinking habits, by occupation, suggested the increased risk of developing lung cancer to be associated with a greater percentage of smokers and the increased risks of developing cancers of the liver and mouth-and-pharynx to be associated with a greater percentage of daily alcohol drinkers. When the analysis was limited to smokers, the risk of developing lung cancer was still significantly high in metal, ceramics and construction workers in men.

Lung cancer incidence attributable to residential radon exposure in Alberta in 2012

PubMed Central

Grundy, Anne; Brand, Kevin; Khandwala, Farah; Poirier, Abbey; Tamminen, Sierra; Friedenreich, Christine M.; Brenner, Darren R.

2017-01-01

Background: Radon is carcinogenic, and exposure to radon has been shown to increase the risk of lung cancer. The objective of this study was to quantify the proportion and number of lung cancer cases in Alberta in 2012 that could be attributed to residential radon exposure. Methods: We estimated the population attributable risk of lung cancer for residential radon using radon exposure data from the Cross-Canada Survey of Radon Concentrations in Homes from 2009-2011 and data on all-cause and lung cancer mortality from Statistics Canada from 2008-2012. We used cancer incidence data from the Alberta Cancer Registry for 2012 to estimate the total number of lung cancers attributable to residential radon exposure. Estimates were also stratified by sex and smoking status. Results: The mean geometric residential radon level in Alberta in 2011 was 71.0 Bq/m3 (geometric standard deviation 2.14). Overall, an estimated 16.6% (95% confidence interval 9.4%-29.8%) of lung cancers were attributable to radon exposure, corresponding to 324 excess attributable cancer cases. The estimated population attributable risk of lung cancer due to radon exposure was higher among those who had never smoked (24.8%) than among ever smokers (15.6%). However, since only about 10% of cases of lung cancer occur in nonsmokers, the estimated total number of excess cases was higher for ever smokers (274) than for never smokers (48). Interpretation: With about 17% of lung cancer cases in Alberta in 2012 attributable to residential radon exposure, exposure reduction has the potential to substantially reduce Alberta's lung cancer burden. As such, home radon testing and remediation techniques represent important cancer prevention strategies. PMID:28663187

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.

PubMed

Hopkins, Raewyn J; Duan, Fenghai; Chiles, Caroline; Greco, Erin M; Gamble, Greg D; Aberle, Denise; Young, Robert P

2017-03-01

Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group). Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less. In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer.

Prevalence of chronic obstructive pulmonary disease in asymptomatic smokers

PubMed Central

Sansores, Raúl H; Velázquez-Uncal, Mónica; Pérez-Bautista, Oliver; Villalba-Caloca, Jaime; Falfán-Valencia, Ramcés; Ramírez-Venegas, Alejandra

2015-01-01

Background Physicians do not routinely recommend smokers to undergo spirometry unless they are symptomatic. Objective To test the hypothesis that there are a significant number of asymptomatic smokers with chronic obstructive pulmonary disease (COPD), we estimated the prevalence of COPD in a group of asymptomatic smokers. Methods Two thousand nine hundred and sixty-one smokers with a cumulative consumption history of at least 10 pack-years, either smokers with symptoms or smokers without symptoms (WOS) were invited to perform a spirometry and complete a symptom questionnaire. Results Six hundred and thirty-seven (21.5%) smokers had no symptoms, whereas 2,324 (78.5%) had at least one symptom. The prevalence of COPD in subjects WOS was 1.5% when considering the whole group of smokers (45/2,961) and 7% when considering only the group WOS (45/637). From 329 smokers with COPD, 13.7% were WOS. Subjects WOS were younger, had better lung function and lower cumulative consumption of cigarettes, estimated as both cigarettes per day and pack-years. According to severity of airflow limitation, 69% vs 87% of subjects were classified as Global Initiative for Chronic Obstructive Lung Disease stages I–II in the WOS and smokers with symptoms groups, respectively (P<0.001). A multivariate analysis showed that forced expiratory volume in 1 second (mL) was the only predictive factor for COPD in asymptomatic smokers. Conclusion Prevalence of COPD in asymptomatic smokers is 1.5%. This number of asymptomatic smokers may be excluded from the benefit of an “early” intervention, not just pharmacological but also from smoking cessation counseling. The higher forced expiratory volume in 1 second may contribute to prevent early diagnosis. PMID:26586941

Prevalence of chronic obstructive pulmonary disease in asymptomatic smokers.

PubMed

Sansores, Raúl H; Velázquez-Uncal, Mónica; Pérez-Bautista, Oliver; Villalba-Caloca, Jaime; Falfán-Valencia, Ramcés; Ramírez-Venegas, Alejandra

2015-01-01

Physicians do not routinely recommend smokers to undergo spirometry unless they are symptomatic. To test the hypothesis that there are a significant number of asymptomatic smokers with chronic obstructive pulmonary disease (COPD), we estimated the prevalence of COPD in a group of asymptomatic smokers. Two thousand nine hundred and sixty-one smokers with a cumulative consumption history of at least 10 pack-years, either smokers with symptoms or smokers without symptoms (WOS) were invited to perform a spirometry and complete a symptom questionnaire. Six hundred and thirty-seven (21.5%) smokers had no symptoms, whereas 2,324 (78.5%) had at least one symptom. The prevalence of COPD in subjects WOS was 1.5% when considering the whole group of smokers (45/2,961) and 7% when considering only the group WOS (45/637). From 329 smokers with COPD, 13.7% were WOS. Subjects WOS were younger, had better lung function and lower cumulative consumption of cigarettes, estimated as both cigarettes per day and pack-years. According to severity of airflow limitation, 69% vs 87% of subjects were classified as Global Initiative for Chronic Obstructive Lung Disease stages I-II in the WOS and smokers with symptoms groups, respectively (P<0.001). A multivariate analysis showed that forced expiratory volume in 1 second (mL) was the only predictive factor for COPD in asymptomatic smokers. Prevalence of COPD in asymptomatic smokers is 1.5%. This number of asymptomatic smokers may be excluded from the benefit of an "early" intervention, not just pharmacological but also from smoking cessation counseling. The higher forced expiratory volume in 1 second may contribute to prevent early diagnosis.

Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women's Health Study.

PubMed

Cutler, Gretchen J; Nettleton, Jennifer A; Ross, Julie A; Harnack, Lisa J; Jacobs, David R; Scrafford, Carolyn G; Barraj, Leila M; Mink, Pamela J; Robien, Kim

2008-08-01

Flavonoids, which are found in certain plant foods, are thought to lower cancer risk through their antioxidant, antiestrogenic and antiproliferative properties. We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung, colorectal, breast, pancreatic and upper aerodigestive cancer among women in a large prospective cohort study. Study participants were 34,708 postmenopausal women in the Iowa Women's Health Study who completed a food frequency questionnaire and were followed for cancer occurrence from 1986 through 2004. Flavonoid intake was estimated from 3 databases developed by the USDA Nutrient Data Laboratory (NDL). Hazard ratios (HR) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories. Interactions between smoking history and flavonoid intake were also examined. After multivariable adjustment, lung cancer incidence was inversely associated with intakes of flavanones (HR = 0.68; 95% CI: 0.53-0.86, all results highest vs. lowest quintile) and proanthocyanidins (HR = 0.75; 95% CI: 0.57-0.97). Among current and past smokers, those with intakes in the highest quintile for flavanones (HR = 0.66; 95% CI: 0.50-0.86), and proanthocyanidins (HR = 0.66; 95% CI; 0.49-0.89) had significantly lower lung cancer incidence than those in the lowest quintile. Similar associations were not seen in never smokers. Isoflavone intake was inversely associated with overall cancer incidence (HR = 0.93, 95% CI: 0.86-1.00). This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk, especially among current and past smokers.

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities

PubMed Central

Richter, Patricia; Faroon, Obaid; Pappas, R. Steven

2017-01-01

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs. PMID:28961214

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities.

PubMed

Richter, Patricia; Faroon, Obaid; Pappas, R Steven

2017-09-29

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs.

Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers.

PubMed

Castaldi, Peter J; San José Estépar, Raúl; Mendoza, Carlos S; Hersh, Craig P; Laird, Nan; Crapo, James D; Lynch, David A; Silverman, Edwin K; Washko, George R

2013-11-01

Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.

Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths

PubMed Central

Liu, Bo-Qi; Peto, Richard; Chen, Zheng-Ming; Boreham, Jillian; Wu, Ya-Ping; Li, Jun-Yao; Campbell, T Colin; Chen, Jun-Shi

1998-01-01

Objective To assess the hazards at an early phase of the growing epidemic of deaths from tobacco in China. Design Smoking habits before 1980 (obtained from family or other informants) of 0.7 million adults who had died of neoplastic, respiratory, or vascular causes were compared with those of a reference group of 0.2 million who had died of other causes. Setting 24 urban and 74 rural areas of China. Subjects One million people who had died during 1986-8 and whose families could be interviewed. Main outcome measures Tobacco attributable mortality in middle or old age from neoplastic, respiratory, or vascular disease. Results Among male smokers aged 35-69 there was a 51% (SE 2) excess of neoplastic deaths, a 31% (2) excess of respiratory deaths, and a 15% (2) excess of vascular deaths. All three excesses were significant (P<0.0001). Among male smokers aged ⩾70 there was a 39% (3) excess of neoplastic deaths, a 54% (2) excess of respiratory deaths, and a 6% (2) excess of vascular deaths. Fewer women smoked, but those who did had tobacco attributable risks of lung cancer and respiratory disease about the same as men. For both sexes, the lung cancer rates at ages 35-69 were about three times as great in smokers as in non-smokers, but because the rates among non-smokers in different parts of China varied widely the absolute excesses of lung cancer in smokers also varied. Of all deaths attributed to tobacco, 45% were due to chronic obstructive pulmonary disease and 15% to lung cancer; oesophageal cancer, stomach cancer, liver cancer, tuberculosis, stroke, and ischaemic heart disease each caused 5-8%. Tobacco caused about 0.6 million Chinese deaths in 1990 (0.5 million men). This will rise to 0.8 million in 2000 (0.4 million at ages 35-69) or to more if the tobacco attributed fractions increase. Conclusions At current age specific death rates in smokers and non-smokers one in four smokers would be killed by tobacco, but as the epidemic grows this proportion will roughly double. If current smoking uptake rates persist in China (where about two thirds of men but few women become smokers) tobacco will kill about 100 million of the 0.3 billion males now aged 0-29, with half these deaths in middle age and half in old age. Key messagesOf the Chinese deaths now being caused by tobacco, 45% are from chronic lung disease, 15% from lung cancer, and 5-8% from each of oesophageal cancer, stomach cancer, liver cancer, stroke, ischaemic heart disease, and tuberculosisTobacco now causes 13% (and will probably eventually cause about 33%) of deaths in men but only 3% (and perhaps eventually about 1%) of deaths in women as the proportion of young women who smoke has become smallTwo thirds of men now become smokers before age 25; few give up, and about half of those who persist will be killed by tobacco in middle or old ageIf present smoking patterns continue about 100 million of the 0.3 billion Chinese males now aged 0-29 will eventually be killed by tobaccoTobacco caused 0.6 million deaths in 1990 and will cause at least 0.8 million in 2000 (0.7 million in men) and about 3 million a year by the middle of the century on the basis of current smoking patterns PMID:9822393

[Smoking fewer cigarettes per day may determine a significant risk reduction in developing smoking attributable diseases? Is there a risk reduction for e-cigarette users?].

PubMed

Pieri, Luca; Chellini, Elisabetta; Gorini, Giuseppe

2014-01-01

Among Italian smokers--about 10 millions in 2013--about 600,000 began using electronic cigarettes (e-cigs) in last years. About 10% of e-cig users quitted smoking tobacco, whereas the 90% was dual users. Among them, about three out of four decreased the number of cigarettes smoked per day (cig/day), but did not quit. How many fewer cigarettes a smoker has to smoke to obtain significant health benefits? Is there a threshold? In order to observe a significant 27% reduction in the risk of developing lung cancer, a smoker must reduce the number of cig/day by at least 50%, while for the other smoking-related diseases (acute myocardial infarction - AMI, stroke, chronic obstructive pulmonary diseases), halving the number of cig/day did not drive to a significant risk reduction. Even smoking 5 cig/day increases the risk of AMI, whereas it significantly lowers the risk of lung cancer. Obviously, quitting smoking is the best choice to highly reduce risks for all smoking-related diseases. Therefore, in order to achieve significant risk reductions, e-cig users should quit smoking as first choice, or, if they feel it is impossible to them, reduce the consumption of traditional cigarettes to less than 5 cig/day.

Impaired lung function in individuals chronically exposed to biomass combustion.

PubMed

da Silva, Luiz Fernando Ferraz; Saldiva, Silvia Regina Dias Médici; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa

2012-01-01

The use of biomass for cooking and heating is considered an important factor associated with respiratory diseases. However, few studies evaluate the amount of particulate matter less than 2.5 μm in diameter (PM2.5), symptoms and lung function in the same population. To evaluate the respiratory effects of biomass combustion and compare the results with those of individuals from the same community in Brazil using liquefied petroleum gas (Gas). 1402 individuals in 260 residences were divided into three groups according to exposure (Gas, Indoor-Biomass, Outside-Biomass). Respiratory symptoms were assessed using questionnaires. Reflectance of paper filters was used to assess particulate matter exposure. In 48 residences the amount of PM2.5 was also quantified. Pulmonary function tests were performed in 120 individuals. Reflectance index correlated directly with PM2.5 (r=0.92) and was used to estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor-Biomass and Outside-Biomass, compared to Gas. There was a significantly increased odds ratio (OR) for cough, wheezing and dyspnea in adults exposed to Indoor-Biomass (OR=2.93, 2.33, 2.59, respectively) and Outside-Biomass (OR=1.78, 1.78, 1.80, respectively) compared to Gas. Pulmonary function tests revealed both Non-Smoker-Biomass and Smoker-Gas individuals to have decreased %predicted-forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) as compared to Non-Smoker-Gas. Pulmonary function tests data was inversely correlated with duration and ePM2.5. The prevalence of airway obstruction was 20% in both Non-Smoker-Biomass and Smoker-Gas subjects. Chronic exposure to biomass combustion is associated with increased prevalence of respiratory symptoms, reduced lung function and development of chronic obstructive pulmonary disease. These effects are associated with the duration and magnitude of exposure and are exacerbated by tobacco smoke. Copyright © 2011 Elsevier Inc. All rights reserved.

Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

PubMed

Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

2016-03-01

It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

Asbestos-related lung cancers: A retrospective clinical and pathological study.

PubMed

Uguen, Marie; Dewitte, Jean-Dominique; Marcorelles, Pascale; Loddé, Brice; Pougnet, Richard; Saliou, Philippe; De Braekeleer, Marc; Uguen, Arnaud

2017-07-01

Exposure to asbestos results in serious risks of developing mesothelioma and lung cancer. The link between asbestos exposure and lung carcinoma is well established. Nevertheless, precise histopathological data are poorly considered when investigating the asbestos-cancer link in a compensatory approach. In the present study, we aim to describe the features of individuals with compensated lung cancer who were referred to an occupational disease center, regarding occupational exposure to asbestos, smoking history and pathological data. We led a retrospective study of compensated ARLC cases seen in our occupational disease center between 2003 and 2013. A total of 146 men were included (mean age at diagnosis, 63.2 years) of whom approximately 90% were heavy current or former smokers (mean value, 30.4 packs/year). The major industries associated with the lung cancer cases were shipbuilding (69.9%), and building construction (7.5%) in this harbor region. The results of the present study showed that lung upper lobe was most prevalent (61.6%) and an excess of adenocarcinoma was found (45.9%), followed by squamous cell carcinoma (38.4%) as well as thoracic sarcomas (2.1%). Neoplasm was not histologically proven in 6.8% of the cases. Subsequent pathology examinations also reclassified 2 tumors as metastases from esophageal and laryngeal origins. In conclusion, smoking prevention should be encouraged in asbestos-exposed workers as reflected by the number of smokers with asbestos-related lung cancer. Thus, histological data should be considered further to evaluate the potent relationship between asbestos exposure and lung malignancy, especially in a compensatory approach.

Legalizing Cannabis: A physician's primer on the pulmonary effects of marijuana.

PubMed

Lutchmansingh, Denyse; Pawar, Leena; Savici, Dana

2014-01-01

Habitual smoking of marijuana is associated with multiple respiratory symptoms such as cough, sputum production, and wheezing .These symptoms are not significantly different from those exhibited by tobacco smokers. Furthermore, endobronchial biopsies of habitual smokers of marijuana and /or tobacco have shown that both marijuana and cigarette smoking cause significant bronchial mucosal histopathology and that these effects are additive. Although marijuana smokers have minimal changes in pulmonary function studies as compared to tobacco smokers, they may develop bullous disease and spontaneous pneumothoraces. The relationship between marijuana smoking and lung cancer remains unclear due to design limitations of the studies published so far. These findings should warn individuals that marijuana smoking may result in serious short-term and long-term respiratory complications, and habitual marijuana use should be viewed with caution. The medical literature so far does not support routine evaluation by pulmonary function tests or imaging studies; until more definitive data is available, we do not recommend the regular use of these tests in the evaluation of habitual marijuana smokers.

Smoking Cessation in COPD Causes a Transient Improvement in Spirometry and Decreases Micronodules on High-Resolution CT Imaging

PubMed Central

Dhariwal, Jaideep; Tennant, Rachel C.; Hansell, David M.; Westwick, John; Walker, Christoph; Ward, Simon P.; Pride, Neil; Barnes, Peter J.; Kon, Onn Min

2014-01-01

Background: Smoking cessation is of major importance for all smokers; however, in patients with COPD, little information exists on how smoking cessation influences lung function and high-resolution CT (HRCT) scan appearances. Methods: In this single-center study, we performed screening spirometry in a group of heavy smokers aged 40 to 80 years (N = 358). We then studied the effects of smoking cessation in two groups of selected subjects: smokers with COPD (n = 38) and smokers with normal spirometry (n = 55). In parallel to subjects undergoing smoking cessation, we studied a control group of nonsmokers (n = 19). Results: Subjects with COPD who quit smoking had a marked, but transient improvement in FEV1 at 6 weeks (184 mL, n = 17, P < .01) that was still present at 12 weeks (81 mL, n = 17, P < .05) and only partially maintained at 1 year. In contrast, we saw improvement in the transfer factor of lung for carbon monoxide at 6 weeks in both subjects with COPD who quit smoking (0.47 mmol/min/kPa, n = 17, P < .01) and subjects who quit smoking with normal spirometry (0.40 mmol/min/kPa, n = 35, P < .01). An upper-zone single HRCT image slice reliably identified emphysema at baseline in 74% of smokers with COPD (28 of 38) and 29% of healthy smokers (16 of 55). Smoking cessation had no significant effect on the appearances of emphysema but decreased the presence of micronodules on HRCT imaging. Conclusions: Cigarette smoking causes extensive lung function and HRCT image abnormalities, even in patients with normal spirometry. Smoking cessation has differential effects on lung function (FEV1 and gas transfer) and features on HRCT images (emphysema and micronodules). Cessation of smoking in patients with COPD causes a transient improvement in FEV1 and decreases the presence of micronodules, offering an opportunity for concomitant therapy during smoking cessation to augment these effects. Smoking cessation at the earliest possible opportunity is vital to minimize permanent damage to the lungs. PMID:24522562

ALK-rearranged squamous cell lung carcinoma responding to crizotinib: A missing link in the field of non-small cell lung cancer?

PubMed

Vergne, Florence; Quéré, Gilles; Andrieu-Key, Sophie; Descourt, Renaud; Quintin-Roué, Isabelle; Talagas, Matthieu; De Braekeleer, Marc; Marcorelles, Pascale; Uguen, Arnaud

2016-01-01

ALK-rearrangements are mainly encountered in lung adenocarcinomas and allow treating patients with anti-ALK targeted therapy. ALK-rearranged squamous cell lung carcinomas are rare tumors that can also respond to anti-ALK-targeted therapy. Nevertheless, ALK screening is not always performed in patients with squamous cell lung carcinomas making the identification and treatment of this molecular tumor subtype challenging. We intend to report a rare case of ALK-rearranged lung squamous cell carcinoma with response to crizotinib therapy. We report clinical, pathological, immunohistochemical and fluorescent in situ hybridization data concerning a patient having an ALK-rearranged squamous cell lung cancer diagnosed in our institution. The patient was a 58-year old woman with a metastatic-stage lung cancer. Histopathological and immunohistochemical analyses were performed on a bronchial biopsy sample and concluded in a non-keratinizing squamous cell lung carcinoma expressing strongly cytokeratin 5/6, p63 and p40, which are classic hallmarks of lung squamous cell carcinomas, but also cytokeratin 7 which is more commonly expressed in lung adenocarcinomas. The tumor did not express thyroid transcription factor-1. ALK rearrangement was searched because of the never-smoker status of the patient and resulted in strong positive fluorescent in situ hybridization test and ALK/p80 immunohistochemistry. The patient responded to crizotinib therapy during 213 days. Our observation points out the interest of considering ALK screening in patients with metastatic lung squamous cell carcinomas, especially in patients lacking a usual heavy-smoker clinical history. The histopathological and immunohistochemical features of this particular tumor highlighting the overlapping criteria between lung adenocarcinomas and rare ALK-rearranged squamous cell lung carcinomas could also be relevant to extend ALK screening to tumors with intermediate phenotypes between squamous cell carcinomas and adenocarcinomas and/or arising in non-smokers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Qualitative Study of Lung Cancer Risk Perceptions and Smoking Beliefs Among National Lung Screening Trial Participants

PubMed Central

2014-01-01

Introduction: The National Comprehensive Cancer Network and the American Cancer Society recently released lung screening guidelines that include smoking cessation counseling for smokers undergoing screening. Previous work indicates that smoking behaviors and risk perceptions of the National Lung Screening Trial (NLST) participants were relatively unchanged. We explored American College of Radiology Imaging Network (ACRIN)/NLST former and current smokers’ risk perceptions specifically to (a) determine whether lung screening is a cue for behavior change, (b) elucidate risk perceptions for lung cancer and smoking-related diseases, and (c) explore postscreening behavioral intentions and changes. Methods: A random sample of 35 participants from 4 ACRIN sites were qualitatively interviewed 1–2 years postscreen. We used a structured interview guide based on Health Belief Model and Self-Regulation Model constructs. Content analyses were conducted with NVivo 8. Results: Most participants endorsed high-risk perceptions for lung cancer and smoking-related diseases, but heightened concern about these risks did not appear to motivate participants to seek screening. Risk perceptions were mostly attributed to participants’ heavy smoking histories; former smokers expressed greatly reduced risk. Lung cancer and smoking-related diseases were perceived as very severe although participants endorsed low worry. Current smokers had low confidence in their ability to quit, and none reported quitting following their initial screen. Conclusions: Lung screening did not appear to be a behavior change cue to action, and high-risk perceptions did not translate into quitting behaviors. Cognitive and emotional dissonance and avoidance strategies may deter engagement in smoking behavior change. Smoking cessation and prevention interventions during lung screening should explore risk perceptions, emotions, and quit confidence. PMID:23999653

Air pollution and fuel vapour induced changes in lung functions: are fuel handlers safe?

PubMed

Chawla, Anuj; Lavania, A K

2008-01-01

Automobile exhaust derived air pollutants have become a major health hazard. Coupled with the inhalation of fuel vapour, as occurs in petrol station workers, this may lead to significant impairment of lung function. Spirometric lung functions were studied in 58 petrol station workers to examine this possibility. The forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow 25%-75% (FEF25-75) and peak expiratory flow (PEF) were recorded and analysed separately for smokers and non-smokers. The workers were divided into 5 groups for analysis of data based on the number of years of work in the petrol pumps. Outdoor air analysis was also carried out. The FVC, FEV1 and PEF declined significantly with increasing years of work in petrol stations in both smokers and non-smokers. Smoking as an independent variable was found to affect the FEV1 significantly but not FVC or PEF. The FEF25-75 was found to be the most affected spirometric value with a significant reduction with increasing years of work. Smoking as such did not affect it. Oxides of nitrogen (NOx), suspended particulate matter (SPM) and particulate matter less than 10 microns (PM10) in outdoor air were higher than the national ambient air quality standards. Exposure to automobile exhaust and fuel vapour impairs lung function in a time-dependent manner. Cigarette smoking appears to accelerate the decline.

Development and application of pulmonary structure-function registration methods: towards pulmonary image-guidance tools for improved airway targeted therapies and outcomes

NASA Astrophysics Data System (ADS)

Guo, Fumin; Pike, Damien; Svenningsen, Sarah; Coxson, Harvey O.; Drozd, John J.; Yuan, Jing; Fenster, Aaron; Parraga, Grace

2014-03-01

Objectives: We aimed to develop a way to rapidly generate multi-modality (MRI-CT) pulmonary imaging structurefunction maps using novel non-rigid image registration methods. This objective is part of our overarching goal to provide an image processing pipeline to generate pulmonary structure-function maps and guide airway-targeted therapies. Methods: Anatomical 1H and functional 3He MRI were acquired in 5 healthy asymptomatic ex-smokers and 7 ex-smokers with chronic obstructive pulmonary disease (COPD) at inspiration breath-hold. Thoracic CT was performed within ten minutes of MRI using the same breath-hold volume. Landmark-based affine registration methods previously validated for imaging of COPD, was based on corresponding fiducial markers located in both CT and 1H MRI coronal slices and compared with shape-based CT-MRI non-rigid registration. Shape-based CT-MRI registration was developed by first identifying the shapes of the lung cavities manually, and then registering the two shapes using affine and thin-plate spline algorithms. We compared registration accuracy using the fiducial localization error (FLE) and target registration error (TRE). Results: For landmark-based registration, the TRE was 8.4±5.3 mm for whole lung and 7.8±4.6 mm for the R and L lungs registered independently (p=0.4). For shape-based registration, the TRE was 8.0±4.6 mm for whole lung as compared to 6.9±4.4 mm for the R and L lung registered independently and this difference was significant (p=0.01). The difference for shape-based (6.9±4.4 mm) and landmark-based R and L lung registration (7.8±4.6 mm) was also significant (p=.04) Conclusion: Shape-based registration TRE was significantly improved compared to landmark-based registration when considering L and R lungs independently.

Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study.

PubMed

Tan, W C; Sin, D D; Bourbeau, J; Hernandez, P; Chapman, K R; Cowie, R; FitzGerald, J M; Marciniuk, D D; Maltais, F; Buist, A S; Road, J; Hogg, J C; Kirby, M; Coxson, H; Hague, C; Leipsic, J; O'Donnell, D E; Aaron, S D

2015-09-01

There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population. To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers. We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA). The prevalence of COPD (FEV1/FVC

Perceived Risks of Certain Types of Cancer and Heart Disease among Asian American Smokers and Non-Smokers.

ERIC Educational Resources Information Center

Ma, Grace X; Tan, Yin; Feeley, Rosemary M.; Thomas, Priya

2002-01-01

Assessed Asian Americans' knowledge levels regarding the health risks of tobacco use. Surveys of Korean, Chinese, Vietnamese, and Cambodian smokers and nonsmokers indicated that most respondents recognized the association between smoking and increased risk for lung, mouth, throat, and esophageal cancer and heart disease. There were significant…

Arsenic, asbestos and radon: emerging players in lung tumorigenesis

PubMed Central

2012-01-01

The cause of lung cancer is generally attributed to tobacco smoking. However lung cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic, asbestos and radon are three prominent non-tobacco carcinogens strongly associated with lung cancer. Exposure to these agents can lead to genetic and epigenetic alterations in tumor genomes, impacting genes and pathways involved in lung cancer development. Moreover, these agents not only exhibit unique mechanisms in causing genomic alterations, but also exert deleterious effects through common mechanisms, such as oxidative stress, commonly associated with carcinogenesis. This article provides a comprehensive review of arsenic, asbestos, and radon induced molecular mechanisms responsible for the generation of genetic and epigenetic alterations in lung cancer. A better understanding of the mode of action of these carcinogens will facilitate the prevention and management of lung cancer related to such environmental hazards. PMID:23173984

Marijuana and Lung Disease.

PubMed

Tashkin, Donald P

2018-05-17

As marijuana smoking prevalence increases in the U.S. concern regarding its potential risks to lung health has also risen, given the general similarity in the smoke contents between marijuana and tobacco. Most studies have found a significant association between marijuana smoking and chronic bronchitis symptoms after adjustment for tobacco. While reports are mixed regarding associations between marijuana smoking and lung function, none has shown a relationship to decrements in forced expired volume in 1 sec (FEV1) and few have found a relationship to a decreased ratio of FEV1 to forced vital capacity (FVC), possibly related to an association between marijuana and an increased FVC. A few studies have found a modest reduction in specific airway conductance in relation to marijuana, probably reflecting endoscopic evidence of bronchial mucosal edema among habitual marijuana smokers. Diffusing capacity in marijuana smokers has been normal and two studies of thoracic high-resolution computed tomography (HRCT) have not shown any association of marijuana smoking with emphysema. Although bronchial biopsies from habitual marijuana smokers have shown precancerous histopathological changes, a large cohort study and a pooled analysis of six well-designed case-control studies have not found evidence of a link between marijuana smoking and lung cancer. The immunosuppressive effects of delta-9 tetrahydrocannabinol raise the possibility of an increased risk of pneumonia, but further studies are needed to evaluate this potential risk. Several cases series have demonstrated pneumothoraces/pneumomediastinum, as well as bullous lung disease, in marijuana smokers, but these associations require epidemiologic studies for firmer evidence of possible causality. Copyright © 2018. Published by Elsevier Inc.

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

PubMed

Kubík, A; Zatloukal, P; Tomásek, L; Pauk, N; Havel, L; Dolezal, J; Plesko, I

2007-01-01

The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial.

PubMed

Sluyter, John D; Camargo, Carlos A; Waayer, Debbie; Lawes, Carlene M M; Toop, Les; Khaw, Kay-Tee; Scragg, Robert

2017-12-13

Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50-84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; range = 0.9-1.5 years), either (1) vitamin D₃ 200,000 IU, followed by monthly 100,000 IU doses ( n = 226); or (2) placebo monthly ( n = 216). At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome). Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group. There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants. However, among ever-smokers ( n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL ( p = 0.03). FEV1 increases were larger among vitamin D-deficient ever-smokers ( n = 54): 122 (8, 236) mL ( p = 0.04). FEV1 improvements were largest among ever-smokers with asthma/COPD ( n = 60): 160 (53, 268) mL ( p = 0.004). Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD.

Post-9/11/2001 lung function trajectories by sex and race in World Trade Center-exposed New York City emergency medical service workers.

PubMed

Vossbrinck, Madeline; Zeig-Owens, Rachel; Hall, Charles B; Schwartz, Theresa; Moir, William; Webber, Mayris P; Cohen, Hillel W; Nolan, Anna; Weiden, Michael D; Christodoulou, Vasilios; Kelly, Kerry J; Aldrich, Thomas K; Prezant, David J

2017-03-01

To determine whether lung function trajectories after 9/11/2001 (9/11) differed by sex or race/ethnicity in World Trade Center-exposed Fire Department of the City of New York emergency medical service (EMS) workers. Serial cross-sectional study of pulmonary function tests (PFTs) taken between 9/11 and 9/10/2015. We used data from routine PFTs (forced expiratory volume in 1 s (FEV 1 ) and FEV 1 % predicted), conducted at 12-18 month intervals. FEV 1 and FEV 1 % predicted were assessed over time, stratified by sex, and race/ethnicity. We also assessed FEV 1 and FEV 1 % predicted in current, former and never-smokers. Among 1817 EMS workers, 334 (18.4%) were women, 979 (53.9%) self-identified as white and 939 (51.6%) were never-smokers. The median follow-up was 13.1 years (IQR 10.5-13.6), and the median number of PFTs per person was 11 (IQR 7-13). After large declines associated with 9/11, there was no discernible recovery in lung function. In analyses limited to never-smokers, the trajectory of decline in adjusted FEV 1 and FEV 1 % predicted was relatively parallel for men and women in the 3 racial/ethnic groups. Similarly, small differences in FEV 1 annual decline between groups were not clinically meaningful. Analyses including ever-smokers were essentially the same. 14 years after 9/11, most EMS workers continued to demonstrate a lack of lung function recovery. The trajectories of lung function decline, however, were parallel by sex and by race/ethnicity. These findings support the use of routine, serial measures of lung function over time in first responders and demonstrate no sex or racial sensitivity to exposure-related lung function decline. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO)

PubMed Central

Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; McNallan, Sheila R; Cote, Michele L; Lim, Wei-Yen; Chang, Shen-Chih; Kim, Jin Hee; Ugolini, Donatella; Chen, Ying; Liloglou, Triantafillos; Andrew, Angeline S; Onega, Tracy; Duell, Eric J; Field, John K; Lazarus, Philip; Le Marchand, Loic; Neri, Monica; Vineis, Paolo; Kiyohara, Chikako; Hong, Yun-Chul; Morgenstern, Hal; Matsuo, Keitaro; Tajima, Kazuo; Christiani, David C; McLaughlin, John R; Bencko, Vladimir; Holcatova, Ivana; Boffetta, Paolo; Brennan, Paul; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Lissowska, Jolanta; Mates, Dana; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Mukeria, Anush; Zaridze, David; Seow, Adeline; Schwartz, Ann G; Yang, Ping; Zhang, Zuo-Feng

2014-01-01

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention. PMID:24615328

Fried meat intake is a risk factor for lung adenocarcinoma in a prospective cohort of Chinese men and women in Singapore

PubMed Central

Butler, Lesley M.; Yu, Mimi C.

2013-01-01

Probable human carcinogens are generated during Chinese-style high-temperature cooking of meat and have been detected in the ambient air and on the meat surface. Although the inhalation of these compounds is an established risk factor for lung cancer, exposure via fried meat consumption has not yet been prospectively evaluated as a risk factor. The relationship between fried meat intake and lung cancer risk was investigated using data from a prospective cohort study among Chinese in Singapore. Lung cancer cases (n = 1130) were identified from 61 321 men and women, 70% of whom were lifetime never smokers. Proportional hazards regression methods were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, there was no association between fried meat intake and risk of all lung cancers combined. For lung adenocarcinoma, fried meat intake had a statistically significant association with increased risk. The association between fried meat intake and risk of lung adenocarcinoma became stronger when analyses were restricted to lifetime never smokers. Compared with the lowest tertile of fried meat intake, the HRs (95% CIs) for the second and third tertiles were 1.43 (0.98, 2.08) and 1.51 (1.03, 2.22), respectively (P for trend = 0.04). The positive association was present among both men and women. There was no association between fried meat intake and risk of non-adenocarcinomas of the lung. Our prospective results for fried meat intake support consumption as an important route of exposure to compounds from Chinese-style high-temperature cooking for the development of lung adenocarcinoma. PMID:23568952

Automated identification of patients with pulmonary nodules in an integrated health system using administrative health plan data, radiology reports, and natural language processing.

PubMed

Danforth, Kim N; Early, Megan I; Ngan, Sharon; Kosco, Anne E; Zheng, Chengyi; Gould, Michael K

2012-08-01

Lung nodules are commonly encountered in clinical practice, yet little is known about their management in community settings. An automated method for identifying patients with lung nodules would greatly facilitate research in this area. Using members of a large, community-based health plan from 2006 to 2010, we developed a method to identify patients with lung nodules, by combining five diagnostic codes, four procedural codes, and a natural language processing algorithm that performed free text searches of radiology transcripts. An experienced pulmonologist reviewed a random sample of 116 radiology transcripts, providing a reference standard for the natural language processing algorithm. With the use of an automated method, we identified 7112 unique members as having one or more incident lung nodules. The mean age of the patients was 65 years (standard deviation 14 years). There were slightly more women (54%) than men, and Hispanics and non-whites comprised 45% of the lung nodule cohort. Thirty-six percent were never smokers whereas 11% were current smokers. Fourteen percent of the patients were subsequently diagnosed with lung cancer. The sensitivity and specificity of the natural language processing algorithm for identifying the presence of lung nodules were 96% and 86%, respectively, compared with clinician review. Among the true positive transcripts in the validation sample, only 35% were solitary and unaccompanied by one or more associated findings, and 56% measured 8 to 30 mm in diameter. A combination of diagnostic codes, procedural codes, and a natural language processing algorithm for free text searching of radiology reports can accurately and efficiently identify patients with incident lung nodules, many of whom are subsequently diagnosed with lung cancer.

Dietary acrylamide intake and the risk of cancer among Finnish male smokers

PubMed Central

Hirvonen, T; Kontto, J; Jestoi, M; Valsta, L; Peltonen, K; Pietinen, P; Virtanen, SM; Sinkko, H; Kronberg-Kippilä, C; Albanes, D; Virtamo, J

2012-01-01

Objective To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. Methods The study consisted of 27,111 male smokers, aged 50–69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. Results During an average 10.2 year follow-up 1703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest vs. the lowest quintile in the multivariate-adjusted model was 1.18 ((95% confidence interval (CI) 1.01–1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. Conclusions High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers. PMID:20859673

Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424).

PubMed

Cheng, Ting-Yuan David; Darke, Amy K; Redman, Mary W; Zirpoli, Gary R; Davis, Warren; Payne Ondracek, Rochelle; Bshara, Wiam; Omilian, Angela R; Kratzke, Robert; Reid, Mary E; Molina, Julian R; Kolesar, Jill M; Chen, Yuhchyau; MacRae, Robert M; Moon, James; Mack, Philip; Gandara, David R; Kelly, Karen; Santella, Regina M; Albain, Kathy S; Ambrosone, Christine B

2018-01-13

To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = -15.8, P = .003) and nuclear ER-β (β = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = -42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort.

PubMed

Mirabelli, Maria C; Preisser, John S; Loehr, Laura R; Agarwal, Sunil K; Barr, R Graham; Couper, David J; Hankinson, John L; Hyun, Noorie; Folsom, Aaron R; London, Stephanie J

2016-04-01

Interpretation of longitudinal information about lung function decline from middle to older age has been limited by loss to follow-up that may be correlated with baseline lung function or the rate of decline. We conducted these analyses to estimate age-related decline in lung function across groups of race, sex, and smoking status while accounting for dropout from the Atherosclerosis Risk in Communities Study. We analyzed data from 13,896 black and white participants, aged 45-64 years at the 1987-1989 baseline clinical examination. Using spirometry data collected at baseline and two follow-up visits, we estimated annual population-averaged mean changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by race, sex, and smoking status using inverse-probability-weighted independence estimating equations conditioning-on-being-alive. Estimated rates of FEV1 decline estimated using inverse-probability-weighted independence estimating equations conditioning on being alive were higher among white than black participants at age 45 years (e.g., male never smokers: black: -29.5 ml/year; white: -51.9 ml/year), but higher among black than white participants by age 75 (black: -51.2 ml/year; white: -26). Observed differences by race were more pronounced among men than among women. By smoking status, FEV1 declines were larger among current than former or never smokers at age 45 across all categories of race and sex. By age 60, FEV1 decline was larger among former and never than current smokers. Estimated annual declines generated using unweighted generalized estimating equations were smaller for current smokers at younger ages in all four groups of race and sex compared with results from weighted analyses that accounted for attrition. Using methods accounting for dropout from an approximately 25-year health study, estimated rates of lung function decline varied by age, race, sex, and smoking status, with largest declines observed among current smokers at younger ages. Published by Elsevier Ltd.

Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers.

PubMed

Baker, Julie A; McCann, Susan E; Reid, Mary E; Nowell, Susan; Beehler, Gregory P; Moysich, Kirsten B

2005-01-01

Although cigarette smoking is a clear risk factor for lung cancer, the other determinants of lung cancer risk among smokers are less clear. Tea and coffee contain catechins and flavonoids, which have been shown to exhibit anticarcinogenic properties. Conversely, caffeine may elevate cancer risk through a variety of mechanisms. The current study investigated the effects of regular consumption of black tea and coffee on lung cancer risk among 993 current and former smokers with primary incident lung cancer and 986 age-, sex-, and smoking-matched hospital controls with non-neoplastic conditions. Results indicated that lung cancer risk was not different for those with the highest black tea consumption (>or=2 cups/day) compared with nondrinkers of tea [adjusted odds ratio (aOR)=0.90; 95% confidence interval (CI)=0.66-1.24]. However, elevated lung cancer risk was observed for participants who consumed 2-3 cups of regular coffee daily (aOR=1.34; 95% CI=0.99-1.82) or >or=4 cups of regular coffee daily (aOR=1.51, 95% CI=1.11-2.05). In contrast, decaffeinated coffee drinking was associated with decreased lung cancer risk for both participants who consumed or=2 cups/day (aOR=0.64; 95% CI=0.51-0.80). These results suggest that any chemoprotective effects of phytochemicals in coffee and tea may be overshadowed by the elevated risk associated with caffeine in these beverages.

Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers

PubMed Central

2014-01-01

Background Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, a comprehensive somatic mutation analysis of EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers has not been conducted. Methods We analyzed whole exome sequencing data from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas and additional 54 tumors in two expansion cohort sets. Candidate loci were validated by target capture and Sanger sequencing. Gene set analysis was performed using Ingenuity Pathway Analysis. Results We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. These included targetable genes involved in PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase signaling (ERBB4) and genes not previously highlighted in lung adenocarcinomas, such as SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response). In the expansion cohort (N = 70), TP53 was the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, the majority of altered genes were involved in cell cycle/DNA repair (P <0.001) and cAMP-dependent protein kinase signaling (P <0.001). Conclusions The genomic makeup of EGFR/KRAS/ALK-negative lung adenocarcinomas in never-smokers is remarkably diverse. Genes involved in cell cycle regulation/DNA repair are implicated in tumorigenesis and represent potential therapeutic targets. PMID:24576404

Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

PubMed

Mohamed Hoesein, Firdaus A A; de Jong, Pim A; Lammers, Jan-Willem J; Mali, Willem P Th M; Mets, Onno M; Schmidt, Michael; de Koning, Harry J; Aalst, Carlijn van der; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Ginneken, Bram van; van Rikxoort, Eva M; Zanen, Pieter

2014-09-01

Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (β) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (β = -0.46), while for the FEV1/FVC this was emphysema (β = -0.55). For the residual volume (RV) air trapping was most contributing (β = -0.35). Lung diffusion capacity was most influenced by emphysema (β = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.

Leukocyte telomere length in relation to risk of lung adenocarcinoma incidence: Findings from the Singapore Chinese Health Study.

PubMed

Yuan, Jian-Min; Beckman, Kenneth B; Wang, Renwei; Bull, Caroline; Adams-Haduch, Jennifer; Huang, Joyce Y; Jin, Aizhen; Opresko, Patricia; Newman, Anne B; Zheng, Yun-Ling; Fenech, Michael; Koh, Woon-Puay

2018-06-01

Telomeres are crucial in the maintenance of chromosome integrity and genomic stability. Critically short telomeres can trigger programed cell death while cells with longer telomeres may have increased likelihood of replicative errors, resulting in genetic mutations and chromosomal alterations, and ultimately promoting oncogenesis. Data on telomere length and lung cancer risk from large prospective cohort studies are spare. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction (qPCR) method in 26,540 participants of the Singapore Chinese Health Study. After a follow-up of 12 years, 654 participants developed lung cancer including 288 adenocarcinoma, 113 squamous cell carcinoma and 253 other/unknown histological type. The Cox proportional hazard regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI). HR of lung adenocarcinoma for individuals in the highest comparing the lowest 20 percentile of telomere length was 2.84 (95% CI 1.94-4.14, p trend  < 0.0001). This positive association was present in never smokers (p trend  < 0.0001), ever smokers (p trend  = 0.0010), men (p trend  = 0.0003), women (p trend  < 0.0001), and in shorter (p trend  = 0.0002) and longer (p trend  = 0.0001) duration of follow-up. There was no association between telomere length and risk of squamous cell carcinoma or other histological type of lung cancer in all or subgroups of individuals. The agreement of results from this prospective cohort study with those of previous prospective studies and Mendelian randomization studies suggest a possible etiological role of telomere length in the development of lung adenocarcinoma. © 2018 UICC.

Individualized prediction of lung-function decline in chronic obstructive pulmonary disease

PubMed Central

Zafari, Zafar; Sin, Don D.; Postma, Dirkje S.; Löfdahl, Claes-Göran; Vonk, Judith; Bryan, Stirling; Lam, Stephen; Tammemagi, C. Martin; Khakban, Rahman; Man, S.F. Paul; Tashkin, Donald; Wise, Robert A.; Connett, John E.; McManus, Bruce; Ng, Raymond; Hollander, Zsuszanna; Sadatsafavi, Mohsen

2016-01-01

Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being −124 to −15 mL/yr for smokers and −83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study — ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study — ClinicalTrials.gov, no. NCT00751660 PMID:27486205

Reduction of physical activity in daily life and its determinants in smokers without airflow obstruction.

PubMed

Furlanetto, Karina Couto; Mantoani, Leandro Cruz; Bisca, Gianna; Morita, Andrea Akemi; Zabatiero, Juliana; Proença, Mahara; Kovelis, Demétria; Pitta, Fabio

2014-04-01

In smokers without airflow obstruction, detailed, objective and controlled quantification of the level of physical inactivity in daily life has never been performed. This study aimed to objectively assess the level of physical activity in daily life in adult smokers without airflow obstruction in comparison with matched non-smokers, and to investigate the determinants for daily physical activity in smokers. Sixty smokers (aged 50 (39-54) years) and 50 non-smokers (aged 48 (40-53) years) matched for gender, age, anthropometric characteristics, educational level, employment status and seasons of the year assessment period were cross-sectionally assessed regarding their daily physical activity with a step counter, besides assessment of lung function, functional exercise capacity, quality of life, anxiety, depression, self-reported comorbidities carbon monoxide level, nicotine dependence and smoking habits. When compared with non-smokers, smokers walked less in daily life (7923 ± 3558 vs 9553 ± 3637 steps/day, respectively), presented worse lung function, functional exercise capacity, quality of life, anxiety and depression. Multiple regression analyses identified functional exercise capacity, Borg fatigue, self-reported motivation/physical activity behaviour and cardiac disease as significant determinants of number of steps/day in smokers (partial r(2)  = 0.10, 0.12, 0.16 and 0.05; b = 15, -997, 1207 and -2330 steps/day, respectively; overall fit of the model R(2)  = 0.38; P < 0.001). Adult smokers without airflow obstruction presented reduced level of daily physical activity. Functional exercise capacity, extended fatigue sensation, aspects of motivation/physical activity behaviour and self-reported cardiac disease are significant determinants of physical activity in daily life in smokers. © 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.

Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.

PubMed

Moazed, Farzad; Burnham, Ellen L; Vandivier, R William; O'Kane, Cecilia M; Shyamsundar, Murali; Hamid, Umar; Abbott, Jason; Thickett, David R; Matthay, Michael A; McAuley, Daniel F; Calfee, Carolyn S

2016-12-01

Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Combined pulmonary fibrosis and emphysema: an increasingly recognized condition* **

PubMed Central

Dias, Olívia Meira; Baldi, Bruno Guedes; Costa, André Nathan; Carvalho, Carlos Roberto Ribeiro

2014-01-01

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis. PMID:25029654

Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers

PubMed Central

San José Estépar, Raúl; Mendoza, Carlos S.; Hersh, Craig P.; Laird, Nan; Crapo, James D.; Lynch, David A.; Silverman, Edwin K.; Washko, George R.

2013-01-01

Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than −950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures. PMID:23980521

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD

PubMed Central

Naz, Shama; Kolmert, Johan; Yang, Mingxing; Reinke, Stacey N.; Kamleh, Muhammad Anas; Snowden, Stuart; Heyder, Tina; Levänen, Bettina; Erle, David J.; Sköld, C. Magnus; Wheelock, Åsa M.; Wheelock, Craig E.

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD. Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform. Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung. These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence. PMID:28642310

Lung cancer in never smokers--a review.

PubMed

Couraud, Sébastien; Zalcman, Gérard; Milleron, Bernard; Morin, Franck; Souquet, Pierre-Jean

2012-06-01

An estimated 10-25% of lung cancers worldwide occur in never smokers, i.e. individuals having smoked less than 100 cigarettes in their lifetime. Lung cancer in never smokers (LCINS) is more frequent in women, although large geographic variations are found. Histologically, adenocarcinomas predominate. The mere existence of LCINS suggests that risk factors other than smoking must be present. Exposure to environmental tobacco smoke (particularly in women) and exposure to workplace carcinogens (particularly in men) are the two most important alternative risk factors. However, a history of either is absent in more than a third of LCINS. The large proportion of women in LCINS suggest a hormonal element that may interact with other identified factors such as hereditary risks, a history of respiratory infections or disease, exposure to air pollution, cooking and heating fumes, or exposure to ionising radiation. The study of genomic polymorphisms finds constitutive DNA variations across subjects according to their smoking status, particularly in genes coding for enzymes that participate in the metabolism of certain carcinogens, in those coding for DNA repair enzymes, or in genes associated with tobacco addiction, or inflammatory processes. The type of molecular mutation in p53 or KRAS varies with smoking status. EGFR mutations are more frequent in never smokers, as are EML4-ALK fusions. The mutually exclusive nature of certain mutations is a strong argument in favour of separate genetic paths to cancer for ever smokers and never smokers. In the present paper we review current clinical and molecular aspects of LCINS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Radioactivity of cigarettes and the importance of (210)Po and thorium isotopes for radiation dose assessment due to smoking.

PubMed

Kubalek, Davor; Serša, Gregor; Štrok, Marko; Benedik, Ljudmila; Jeran, Zvonka

2016-05-01

Tobacco and tobacco smoke are very complex mixtures. In addition to various chemical and organic compounds they also contain natural radioactive elements (radionuclides). In this work, the natural radionuclide activity concentrations ((234)U, (238)U, (228)Th, (230)Th, (232)Th, (226)Ra, (210)Pb and (210)Po) of nine different cigarette samples available on the Slovenian market are reported. In addition to (210)Po, the transfer of thorium isotopes from a cigarette to a smoker's body and lungs have been determined for the first time. Cigarette smoke and exhaled air from smokers' lungs were collected from volunteer smokers (C-4 brand) to determinate what quantity of (210)Po and thorium isotopes is transferred from the tobacco to the smoker's lungs. Cigarette ash and smoked filters were also collected and analysed. Among the determined isotopes, (210)Pb and (210)Po showed the highest activity concentrations. During the smoking of one cigarette approximately 22% of (210)Po (and presumably its predecessor (210)Pb), 0.6% of (228)Th, 24% of (230)Th, and 31% of (232)Th are transferred from the cigarette and retained in the smoker's body. The estimated annual effective dose for smokers is 61 μSv/year from (210)Po; 9 μSv/year from (210)Pb; 6 μSv/year from (228)Th; 47 μSv/year from (230)Th, and 37 μSv/year from (232)Th. These results show the importance of thorium isotopes in contributing to the annual effective dose for smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative health impact of indoor radon in France.

PubMed

Ajrouche, Roula; Roudier, Candice; Cléro, Enora; Ielsch, Géraldine; Gay, Didier; Guillevic, Jérôme; Marant Micallef, Claire; Vacquier, Blandine; Le Tertre, Alain; Laurier, Dominique

2018-05-08

Radon is the second leading cause of lung cancer after smoking. Since the previous quantitative risk assessment of indoor radon conducted in France, input data have changed such as, estimates of indoor radon concentrations, lung cancer rates and the prevalence of tobacco consumption. The aim of this work was to update the risk assessment of lung cancer mortality attributable to indoor radon in France using recent risk models and data, improving the consideration of smoking, and providing results at a fine geographical scale. The data used were population data (2012), vital statistics on death from lung cancer (2008-2012), domestic radon exposure from a recent database that combines measurement results of indoor radon concentration and the geogenic radon potential map for France (2015), and smoking prevalence (2010). The risk model used was derived from a European epidemiological study, considering that lung cancer risk increased by 16% per 100 becquerels per cubic meter (Bq/m 3 ) indoor radon concentration. The estimated number of lung cancer deaths attributable to indoor radon exposure is about 3000 (1000; 5000), which corresponds to about 10% of all lung cancer deaths each year in France. About 33% of lung cancer deaths attributable to radon are due to exposure levels above 100 Bq/m 3 . Considering the combined effect of tobacco and radon, the study shows that 75% of estimated radon-attributable lung cancer deaths occur among current smokers, 20% among ex-smokers and 5% among never-smokers. It is concluded that the results of this study, which are based on precise estimates of indoor radon concentrations at finest geographical scale, can serve as a basis for defining French policy against radon risk.

Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

PubMed

Tao, Meng-Hua; Dai, Qi; Chen, Shande; Freudenheim, Jo L; Rohan, Thomas; Wakelee, Heather; Datta, Mridul; Wactawski-Wende, Jean

2017-08-01

Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women's Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial. The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50-79 years, recruited at 40U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models. After 11 years' cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71-1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment (p=0.04 for interaction). Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers. Copyright © 2017 Elsevier B.V. All rights reserved.

[Epidemiology and incidence of primary lung cancer in a region with low tobacco consumption: Guadeloupe (French West Indies). Data from the cancer registry 2008-2009].

PubMed

Cadelis, G; Kaddah, S; Bhakkan, B; Quellery, M; Deloumeaux, J

2013-09-01

Few data are available about primary lung cancer in the Caribbean. The purpose of this study was to provide, for the first time, the epidemiological and clinical characteristics of primary lung cancer in the archipelago of Guadeloupe (French West Indies). From the cancer registry, we identified in this retrospective study, all incident cases of primary lung cancer that had occurred between 1st January 2008 and 31st December 2009 in Guadeloupe. Over the period from 2008 to 2009, 106 patients with primary lung cancer were identified. Males accounted for 72.6% and the women for 27.4%. Mean incidence rate over the 2 years was estimated at 13.4/100000 persons-years (95% CI: [6.0-20.8]) in men (world standardized) and 4.2/100000 persons-years (95% CI: [0.3-8.1]) in women. The median age at initial diagnosis was 65 years for men and 66 years for women. We noted a proportion of 61.3% of current smokers, 4.7% of passive smokers and 34% of non-smokers. The comorbidities were present in 41% of patients. Non-small cell lung cancer (NSCLC) accounted for 88.7% of lung cancers and small cell lung cancer for 7.5%. The most common histological type was adenocarcinoma (43%) followed by squamous cell (24%). Stage III and IV patients accounted for 64.1% of individuals with NSCLC. The incidence of primary lung cancer in Guadeloupe is relatively low compared to metropolitan France. Guadeloupe is also a French department where the rate of tobacco consumption is one of the lowest. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Differences in chronic obstructive pulmonary disease phenotypes between non-smokers and smokers.

PubMed

Ji, Wonjun; Lim, Myoung Nam; Bak, So Hyeon; Hong, Seok-Ho; Han, Seon-Sook; Lee, Seung-Joon; Kim, Woo Jin; Hong, Yoonki

2018-02-01

Although tobacco smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), more than one-fourth of COPD patients are non-smokers. In this cross-sectional study, the differences in COPD phenotypes between non-smokers and smokers in male subjects were investigated and were focused on structural lung changes using a quantitative assessment of computed tomography (CT) images. They divided male participants with COPD, from a Korean cohort near a cement plant, into non-smokers and smokers by a cutoff of a 5 pack-year smoking history. Clinical characteristics, including age, body mass index (BMI), spirometry results, history of biomass smoke exposure, and CT measurements, were compared between the two groups. Emphysema index (EI) and mean wall area percentage (MWA %) were used to evaluate the structural lung changes on volumetric CT scans. The non-smoker group (n = 49) had younger patients and had a greater BMI than the smoker group (n = 113) (P < .05). Spirometry results, including post-bronchodilator forced expiratory volume in 1 s, were comparable between the two groups. More smokers had emphysema than non-smokers (EI 10.0 vs. 6.5, P < .001), but after accounting the potential confounders in model analysis, the difference was borderline significance (P = .051). In the subgroup of biomass smoke-exposed subjects, MWA% was significantly greater in smokers than in non-smokers (MWA 69.1 vs. 65.3, P = .03), while EI was not statistically different (EI 7.1 vs. 10.4, P = .52). Non-smoker males with COPD were younger and had a greater BMI than the smokers. Tobacco smoke exposure seemed to be associated with an emphysema-predominant phenotype, while biomass smoke exposure exhibited a significant interaction with tobacco smoking in an airway-predominant phenotype. © 2016 John Wiley & Sons Ltd.

Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis.

PubMed

Kärkkäinen, Miia; Kettunen, Hannu-Pekka; Nurmi, Hanna; Selander, Tuomas; Purokivi, Minna; Kaarteenaho, Riitta

2017-08-22

Cigarette smoking has been associated with the risk of idiopathic pulmonary fibrosis (IPF). Certain comorbidities have been associated with reduced survival although some studies have indicated that current smokers have a longer survival than ex-smokers. Comorbidities in relation to smoking history have not been previously analyzed. Retrospective data was collected and patients were categorized according to gender and smoking habits. Comorbidities and medications were collected. Predictive values for mortality were identified by COX proportional hazard analyses. We examined 45 non-smokers (53.3% female), 66 ex-smokers (9.1% female) and 17 current smokers (17.6% female) with IPF. Current smokers were younger at baseline (58.1 ± 8.74 years) compared to non-smokers (71.4 ± 8.74, p < 0.001) and ex-smokers (72.5 ±7.95, p <0.001). Median survival of non-smokers and current smokers was longer (55.0 and 52.0 months, respectively) than that of ex-smokers (36.0 months) (p=0.028 and 0.034, respectively). In age and severity adjusted analyses, smoking was not related to survival. Cardiovascular diseases (CVD) (72.7 %) were the most common comorbidities, current smokers had more chronic obstructive pulmonary disease (COPD) and lung cancer compared to ex-smokers (p<0.001). CVD, COPD and use of insulin were related to poorer survival in adjusted analyses. Smoking seems to influence the course of disease in IPF since current smokers developed the disease at a younger age in comparison to non-smokers and ex-smokers. No significant differences in the major comorbidities were detected between IPF patients with different smoking histories. The mechanism through which smoking influences IPF progression requires further investigation.

Occupational risk factors of lung cancer: a hospital based case-control study

PubMed Central

Droste, J. H.; Weyler, J. J.; Van Meerbeeck, J. P.; Vermeire, P. A.; van Sprundel, M. P.

1999-01-01

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex- smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.   PMID:10472306

Consumer awareness and attitudes related to new potential reduced-exposure tobacco product brands.

PubMed

Parascandola, Mark; Augustson, Erik; O'Connell, Mary E; Marcus, Stephen

2009-07-01

In recent years, there has been a proliferation of potential reduced-exposure tobacco products (PREPs) marketed that claim to be less harmful or less addictive, compared with conventional cigarettes. Tobacco control scientists have raised concerns about the potential adverse impact of marketing of these products for smoking prevention and cessation efforts. Although these products have not been widely used among smokers, there are few data available on consumers' awareness and attitudes toward these products. Data were obtained from the 2003 and 2005 Health Information National Trends Survey, a nationally representative telephone survey of adults 18 years and older regarding health communication and associated beliefs and behaviors. Our study population consisted of 6,369 respondents in 2003 and 5,586 respondents in 2005, of whom 19% were current smokers and 28% were former smokers. In 2005, 45% of respondents had heard of at least one PREP product, while only 4.8% had actually tried one. Awareness and use were substantially higher among current smokers (55.6% and 12.7%). Awareness was highest for Marlboro Ultra Smooth (MUS) (30.2%), Eclipse (18.2%), Quest (7.8%), and Ariva (5.4%), while less than 2% for any other product. Of respondents who had tried a PREP, 50% cited harm reduction or assistance in quitting as a reason for trying the product and 30% believed that the product was less harmful than their usual brand. In the combined 2003 and 2005 dataset, 54.4% of current smokers stated that they would be "very" or "somewhat" interested in trying a cigarette advertised as less harmful, while only 3.2% of former smokers and 1.1% of never-smokers were interested. Among current smokers, interest was higher in females and non-Hispanic Whites, and among daily smokers, those who smoked 20 or more cigarettes per day and those who were not considering quitting. Smokers interested in PREPs were substantially more likely to rate their perceived lung cancer risk as high (40.3% vs. 8.3%) and to worry frequently about developing lung cancer (19.7% vs. 4%). These results suggest that there is a substantial level of interest among current smokers in cigarettes marketed with claims of reduced exposure or harm. Of particular concern is that "health conscious" smokers and heavy smokers not planning to quit may be especially vulnerable to PREP marketing messages and view such products as an alternative to smoking cessation.

Consumer awareness and attitudes related to new potential reduced-exposure tobacco product brands

PubMed Central

Augustson, Erik; O’Connell, Mary E.; Marcus, Stephen

2009-01-01

Introduction: In recent years, there has been a proliferation of potential reduced-exposure tobacco products (PREPs) marketed that claim to be less harmful or less addictive, compared with conventional cigarettes. Tobacco control scientists have raised concerns about the potential adverse impact of marketing of these products for smoking prevention and cessation efforts. Although these products have not been widely used among smokers, there are few data available on consumers’ awareness and attitudes toward these products. Methods: Data were obtained from the 2003 and 2005 Health Information National Trends Survey, a nationally representative telephone survey of adults 18 years and older regarding health communication and associated beliefs and behaviors. Our study population consisted of 6,369 respondents in 2003 and 5,586 respondents in 2005, of whom 19% were current smokers and 28% were former smokers. Results: In 2005, 45% of respondents had heard of at least one PREP product, while only 4.8% had actually tried one. Awareness and use were substantially higher among current smokers (55.6% and 12.7%). Awareness was highest for Marlboro Ultra Smooth (MUS) (30.2%), Eclipse (18.2%), Quest (7.8%), and Ariva (5.4%), while less than 2% for any other product. Of respondents who had tried a PREP, 50% cited harm reduction or assistance in quitting as a reason for trying the product and 30% believed that the product was less harmful than their usual brand. In the combined 2003 and 2005 dataset, 54.4% of current smokers stated that they would be “very” or “somewhat” interested in trying a cigarette advertised as less harmful, while only 3.2% of former smokers and 1.1% of never-smokers were interested. Among current smokers, interest was higher in females and non-Hispanic Whites, and among daily smokers, those who smoked 20 or more cigarettes per day and those who were not considering quitting. Smokers interested in PREPs were substantially more likely to rate their perceived lung cancer risk as high (40.3% vs. 8.3%) and to worry frequently about developing lung cancer (19.7% vs. 4%). Discussion: These results suggest that there is a substantial level of interest among current smokers in cigarettes marketed with claims of reduced exposure or harm. Of particular concern is that “health conscious” smokers and heavy smokers not planning to quit may be especially vulnerable to PREP marketing messages and view such products as an alternative to smoking cessation. PMID:19541949

MMP12, lung function, and COPD in high-risk populations.

PubMed

Hunninghake, Gary M; Cho, Michael H; Tesfaigzi, Yohannes; Soto-Quiros, Manuel E; Avila, Lydiana; Lasky-Su, Jessica; Stidley, Chris; Melén, Erik; Söderhäll, Cilla; Hallberg, Jenny; Kull, Inger; Kere, Juha; Svartengren, Magnus; Pershagen, Göran; Wickman, Magnus; Lange, Christoph; Demeo, Dawn L; Hersh, Craig P; Klanderman, Barbara J; Raby, Benjamin A; Sparrow, David; Shapiro, Steven D; Silverman, Edwin K; Litonjua, Augusto A; Weiss, Scott T; Celedón, Juan C

2009-12-31

Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups. We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [-82A-->G]) was positively associated with FEV(1) in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2x10(-6)). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P=0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.005) and among participants in a family-based study of early-onset COPD (P=0.006). The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers. 2009 Massachusetts Medical Society

Lung, Laryngeal and Other Respiratory Cancer Incidence among Japanese Atomic Bomb Survivors: An Updated Analysis from 1958 through 2009

DOE PAGES

Cahoon, Elizabeth K.; Preston, Dale L.; Pierce, Donald A.; ...

2017-03-21

The Life Span Study (LSS) of Japanese atomic bomb survivors is comprised of a large, population-based cohort offering one of the best opportunities to study the relationship between exposure to radiation and incidence of respiratory cancers. Risks of lung, laryngeal and other cancers of the respiratory system were evaluated among 105,444 LSS subjects followed from 1958 to 2009. During this period, we identified 2,446 lung, 180 laryngeal and 115 other respiratory (trachea, mediastinum and other ill-defined sites) first primary incident cancer cases. Ten additional years of follow-up, improved radiation dose estimates, revised smoking data, and updated migration information were thenmore » used to investigate the joint effects of radiation and smoking using Poisson regression methods. For nonsmokers, the sexaveraged excess relative risk per Gy (ERR/Gy) for lung cancer (at age 70 after radiation exposure at age 30) was estimated as 0.81 (95% CI: 0.51, 1.18) with a female-to-male ratio of 2.83. There was no evidence of curvature in the radiation dose-response relationship overall or by sex. Lung cancer risks increased with pack-years of smoking and decreased with time since quitting smoking at any level of radiation exposure. Similar to the previously reported study, which followed cohort members through 1999, the ERR/Gy for lung cancer was significantly higher for low-to-moderate smokers than for heavy smokers, with little evidence of any radiation-associated excess risk in heavy smokers. Of 2,446 lung cancer cases, 113 (5%) could be attributed to radiation exposure. Of the 1,165 lung cancer cases occurring among smokers, 886 (76%) could be attributed to smoking. While there was little evidence of a radiation effect for laryngeal cancer, a nonsignificantly elevated risk of other respiratory cancers was observed. However, significant smoking effects were observed for both laryngeal (ERR per 50 pack-years ¼ 23.57; 95% CI: 8.44, 71.05) and other respiratory cancers (ERR per 50 pack-years¼1.21; 95% CI: 0.10, 3.25)« less

Lung, Laryngeal and Other Respiratory Cancer Incidence among Japanese Atomic Bomb Survivors: An Updated Analysis from 1958 through 2009

PubMed Central

Cahoon, Elizabeth K.; Preston, Dale L.; Pierce, Donald A.; Grant, Eric; Brenner, Alina V.; Mabuchi, Kiyohiko; Utada, Mai; Ozasa, Kotaro

2017-01-01

The Life Span Study (LSS) of Japanese atomic bomb survivors is comprised of a large, population-based cohort offering one of the best opportunities to study the relationship between exposure to radiation and incidence of respiratory cancers. Risks of lung, laryngeal and other cancers of the respiratory system were evaluated among 105,444 LSS subjects followed from 1958 to 2009. During this period, we identified 2,446 lung, 180 laryngeal and 115 other respiratory (trachea, mediastinum and other ill-defined sites) first primary incident cancer cases. Ten additional years of follow-up, improved radiation dose estimates, revised smoking data, and updated migration information were used to investigate the joint effects of radiation and smoking using Poisson regression methods. For nonsmokers, the sex-averaged excess relative risk per Gy (ERR/Gy) for lung cancer (at age 70 after radiation exposure at age 30) was estimated as 0.81 (95% CI: 0.51, 1.18) with a female-to-male ratio of 2.83. There was no evidence of curvature in the radiation dose-response relationship overall or by sex. Lung cancer risks increased with pack-years of smoking and decreased with time since quitting smoking at any level of radiation exposure. Similar to the previously reported study, which followed cohort members through 1999, the ERR/Gy for lung cancer was significantly higher for low-to-moderate smokers than for heavy smokers, with little evidence of any radiation-associated excess risk in heavy smokers. Of 2,446 lung cancer cases, 113 (5%) could be attributed to radiation exposure. Of the 1,165 lung cancer cases occurring among smokers, 886 (76%) could be attributed to smoking. While there was little evidence of a radiation effect for laryngeal cancer, a nonsignificantly elevated risk of other respiratory cancers was observed. However, significant smoking effects were observed for both laryngeal (ERR per 50 pack-years = 23.57; 95% CI: 8.44, 71.05) and other respiratory cancers (ERR per 50 pack-years = 1.21; 95% CI: 0.10, 3.25). PMID:28323575

Lung, Laryngeal and Other Respiratory Cancer Incidence among Japanese Atomic Bomb Survivors: An Updated Analysis from 1958 through 2009.

PubMed

Cahoon, Elizabeth K; Preston, Dale L; Pierce, Donald A; Grant, Eric; Brenner, Alina V; Mabuchi, Kiyohiko; Utada, Mai; Ozasa, Kotaro

2017-05-01

The Life Span Study (LSS) of Japanese atomic bomb survivors is comprised of a large, population-based cohort offering one of the best opportunities to study the relationship between exposure to radiation and incidence of respiratory cancers. Risks of lung, laryngeal and other cancers of the respiratory system were evaluated among 105,444 LSS subjects followed from 1958 to 2009. During this period, we identified 2,446 lung, 180 laryngeal and 115 other respiratory (trachea, mediastinum and other ill-defined sites) first primary incident cancer cases. Ten additional years of follow-up, improved radiation dose estimates, revised smoking data, and updated migration information were used to investigate the joint effects of radiation and smoking using Poisson regression methods. For nonsmokers, the sex-averaged excess relative risk per Gy (ERR/Gy) for lung cancer (at age 70 after radiation exposure at age 30) was estimated as 0.81 (95% CI: 0.51, 1.18) with a female-to-male ratio of 2.83. There was no evidence of curvature in the radiation dose-response relationship overall or by sex. Lung cancer risks increased with pack-years of smoking and decreased with time since quitting smoking at any level of radiation exposure. Similar to the previously reported study, which followed cohort members through 1999, the ERR/Gy for lung cancer was significantly higher for low-to-moderate smokers than for heavy smokers, with little evidence of any radiation-associated excess risk in heavy smokers. Of 2,446 lung cancer cases, 113 (5%) could be attributed to radiation exposure. Of the 1,165 lung cancer cases occurring among smokers, 886 (76%) could be attributed to smoking. While there was little evidence of a radiation effect for laryngeal cancer, a nonsignificantly elevated risk of other respiratory cancers was observed. However, significant smoking effects were observed for both laryngeal (ERR per 50 pack-years = 23.57; 95% CI: 8.44, 71.05) and other respiratory cancers (ERR per 50 pack-years = 1.21; 95% CI: 0.10, 3.25).

Lung, Laryngeal and Other Respiratory Cancer Incidence among Japanese Atomic Bomb Survivors: An Updated Analysis from 1958 through 2009

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cahoon, Elizabeth K.; Preston, Dale L.; Pierce, Donald A.

The Life Span Study (LSS) of Japanese atomic bomb survivors is comprised of a large, population-based cohort offering one of the best opportunities to study the relationship between exposure to radiation and incidence of respiratory cancers. Risks of lung, laryngeal and other cancers of the respiratory system were evaluated among 105,444 LSS subjects followed from 1958 to 2009. During this period, we identified 2,446 lung, 180 laryngeal and 115 other respiratory (trachea, mediastinum and other ill-defined sites) first primary incident cancer cases. Ten additional years of follow-up, improved radiation dose estimates, revised smoking data, and updated migration information were thenmore » used to investigate the joint effects of radiation and smoking using Poisson regression methods. For nonsmokers, the sexaveraged excess relative risk per Gy (ERR/Gy) for lung cancer (at age 70 after radiation exposure at age 30) was estimated as 0.81 (95% CI: 0.51, 1.18) with a female-to-male ratio of 2.83. There was no evidence of curvature in the radiation dose-response relationship overall or by sex. Lung cancer risks increased with pack-years of smoking and decreased with time since quitting smoking at any level of radiation exposure. Similar to the previously reported study, which followed cohort members through 1999, the ERR/Gy for lung cancer was significantly higher for low-to-moderate smokers than for heavy smokers, with little evidence of any radiation-associated excess risk in heavy smokers. Of 2,446 lung cancer cases, 113 (5%) could be attributed to radiation exposure. Of the 1,165 lung cancer cases occurring among smokers, 886 (76%) could be attributed to smoking. While there was little evidence of a radiation effect for laryngeal cancer, a nonsignificantly elevated risk of other respiratory cancers was observed. However, significant smoking effects were observed for both laryngeal (ERR per 50 pack-years ¼ 23.57; 95% CI: 8.44, 71.05) and other respiratory cancers (ERR per 50 pack-years¼1.21; 95% CI: 0.10, 3.25)« less

Early Detection of Lung Cancer Using Nano-Nose - A Review

PubMed Central

Fernandes, M. P.; Venkatesh, S; Sudarshan, B. G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer. PMID:26628933

Early Detection of Lung Cancer Using Nano-Nose - A Review.

PubMed

Fernandes, M P; Venkatesh, S; Sudarshan, B G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer.

Tobacco Smoking: Patterns, Health Consequences for Adults, and the Long-term Health of the Offspring

PubMed Central

Maritz, Gert S.; Mutemwa, Muyunda

2012-01-01

Tobacco use started several centuries ago and increased markedly after the invention of the cigarette making machine. Once people start smoking they find it difficult to quit the habit. This is due to the addictive effect of nicotine in tobacco smoke. Various epidemiologic and laboratory studies clearly showed that smoking is associated with various diseases such as heart diseases, asthma and emphysema and the associated increase in morbidity and mortality of smokers. Several studies implicate nicotine as the causative factor in tobacco smoke. Apart from nicotine, various carcinogens also occur in tobacco smoke resulting in an increase in the incidence of cancer in smokers. While the smoking habit is decreasing in developed countries, tobacco use increases in the developing countries. Smoking prevalence is also highest in poor communities and amongst those with low education levels. It is important to note that, although ther is a decline in the number of smokers in the developed countries, there is a three to four decades lag between the peak in smoking prevalence and the subsequent peak in smoking related mortality. It has been shown that maternal smoking induces respiratory diseases in the offspring. There is also evidence that parental smoking may program the offspring to develop certain diseases later in life. Various studies showed that maternal nicotine exposure during pregnancy and lactation via tobacco smoke of nicotine replacement therapy (NRT), program the offspring to develop compromised lung structure later in life with the consequent compromised lung function. This implies that NRT is not an option to assist pregnant or lactating smokers to quit the habit. Even paternal smoking may have an adverse effect on the health of the offspring since it has been shown that 2nd and 3rd hand smoking have adverse health consequences for those exposed to it. PMID:22980343

Relative Importance of Different Attributes of Graphic Health Warnings on Tobacco Packages in Viet Nam.

PubMed

Giang, Kim Bao; Chung, Le Hong; Minh, Hoang Van; Kien, Vu Duy; Giap, Vu Van; Hinh, Nguyen Duc; Cuong, Nguyen Manh; Manh, Pham Duc; Duc, Ha Anh; Yang, Jui-Chen

2016-01-01

Graphic health warnings (GHW) on tobacco packages have proven to be effective in increasing quit attempts among smokers and reducing initial smoking among adolescents. This research aimed to examine the relative importance of different attributes of graphic health warnings on tobacco packages in Viet Nam. A discrete choice experimental (DCE) design was applied with a conditional logit model. In addition, a ranking method was used to list from the least to the most dreadful GHW labels. With the results from DCE model, graphic type was shown to be the most important attribute, followed by cost and coverage area of GHW. The least important attribute was position of the GHW. Among 5 graphic types (internal lung cancer image, external damaged teeth, abstract image, human suffering image and text), the image of lung cancer was found to have the strongest influence on both smokers and non-smokers. With ranking method, the image of throat cancer and heart diseases were considered the most dreadful images. GHWs should be designed with these attributes in mind, to maximise influence on purchase among both smokers and non-smokers.

Effects of radon mitigation vs smoking cessation in reducing radon-related risk of lung cancer.

PubMed Central

Mendez, D; Warner, K E; Courant, P N

1998-01-01

OBJECTIVES: The purpose of this paper is to provide smokers with information on the relative benefits of mitigating radon and quitting smoking in reducing radon-related lung cancer risk. METHODS: The standard radon risk model, linked with models characterizing residential radon exposure and patterns of moving to new homes, was used to estimate the risk reduction produced by remediating high-radon homes, quitting smoking, or both. RESULTS: Quitting smoking reduces lung cancer risk from radon more than does reduction of radon exposure itself. CONCLUSIONS: Smokers should understand that, in addition to producing other health benefits, quitting smoking dominates strategies to deal with the problem posed by radon. PMID:9585753

Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy?

PubMed

Diaz, Alejandro A; Estépar, Raul San José; Washko, George R

2016-01-01

Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial–American College of Radiology Imaging Network Cohort

PubMed Central

Hopkins, Raewyn J.; Duan, Fenghai; Chiles, Caroline; Greco, Erin M.; Gamble, Greg D.; Aberle, Denise

2017-01-01

Rationale: Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. Objectives: We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1–4. Methods: In the National Lung Screening Trial–ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group). Measurements and Main Results: Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less. Conclusions: In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer. PMID:28076701

Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

PubMed Central

Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

Genetic Contribution to Non-Squamous, Non-Small Cell Lung Cancer in Non-Smokers.

PubMed

Carr, Shamus R; Akerley, Wallace; Cannon-Albright, Lisa

2018-04-04

Lung carcinogenesis is strongly influenced by environmental and heritable factors. The genetic contribution to the different histologies is unknown. A population-based computerized genealogy resource linked to a statewide cancer registry of lung cancer cases (n=5408) was analyzed to evaluate the heritable contribution to lung cancer histology in smoking (n=1751) and non-smoking cases (n=818). Statistical methods were used to test for significant excess relatedness of lung cancer cases. Significant excess distant relatedness was observed for all lung cancer histology subgroups analyzed except the small cell lung cancer subset (p=0.213). When smoking and non-smoking histologic subsets of lung cancer were considered, excess relatedness was observed only in non-smoking NSCLC (n=653; p=0.026) and, particularly, in those non-smokers with non-squamous histology (n=561; p=0.036). Sixty one pedigrees were identified which demonstrated a significant excess risk of non-smoking, non-squamous lung cancer cases; and an excess of female cases was observed among the cases in these high-risk pedigrees. This analysis supports a genetic predisposition to lung cancer carcinogenesis in non-smoking, non-squamous NSCLC cases. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Diminished Disease-Free Survival After Lobectomy: Screening Implications.

PubMed

Reich, Jerome M; Kim, Jong S; Asaph, James W

2015-09-01

The aim of this study was to estimate the effect of lobectomy on life expectancy in healthy smokers and consider the implications for lung cancer screening. In a retrospective cohort study that provided a minimum of 15 years of follow-up, we analyzed lung cancer survival, all-cause survival, and fatality (1-survival) of 261 persons with stage I non-small-cell lung cancer who underwent lobectomy at Portland Providence Medical Center between 1978 and 1994. We: (1) compared 5-year disease-free fatality (non-lung-cancer fatality) with lung cancer fatality; and (2) based on actuarial data that demonstrated life expectancy equivalence of the healthiest smokers (whom we assumed would be comparable with subjects judged eligible for lobectomy) in the US population, we compared their long-term, disease-free survival (our primary end point) with actuarial expectations by computing the Kaplan-Meier survival function of the differences between lifetimes since surgery in disease-free persons versus matched, expected remaining lifetimes in the US population. (1) Five-year disease-free fatality (16.1%) was 58% as high as 5-year lung cancer fatality (27.6%); (2) disease-free survival was reduced by 6.9-years (95% confidence interval, 5.5-8.3), 41% of actuarial life expectancy (17 years). The divergence from expected survival took place largely after 6 years of follow-up. Lobectomy materially diminishes long-term disease-free survival in the healthiest smokers--persons judged healthy enough to tolerate major surgery and to have sufficient pulmonary reserve to sustain loss of one-fifth of their lung tissue. In screened populations, diminished survival in overdiagnosed persons will offset, to an undetermined extent, the mortality benefit imparted by preemption of advanced lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Alcoholic beverage intake and risk of lung cancer: the California Men's Health Study.

PubMed

Chao, Chun; Slezak, Jeff M; Caan, Bette J; Quinn, Virginia P

2008-10-01

We investigated the effect of alcoholic beverage consumption on the risk of lung cancer using the California Men's Health Study. The California Men's Health Study is a multiethnic cohort of 84,170 men ages 45 to 69 years who are members of the Kaiser Permanente California health plans. Demographics and detailed lifestyle characteristics were collected from surveys mailed between 2000 and 2003. Incident lung cancer cases were identified by health plan cancer registries through December 2006 (n=210). Multivariable Cox's regression was used to examine the effects of beer, red wine, white wine (including rosé), and liquor consumption on risk of lung cancer adjusting for age, race/ethnicity, education, income, body mass index, history of chronic obstructive pulmonary disease/emphysema, and smoking history. There was a significant linear decrease in risk of lung cancer associated with consumption of red wine among ever-smokers: hazard ratio (HR), 0.98; 95% confidence interval (95% CI), 0.96-1.00 for increase of 1 drink per month. This relationship was slightly stronger among heavy smokers (>or=20 pack-years): HR, 0.96; 95% CI, 0.93-1.00. When alcoholic beverage consumption was examined by frequency of intake, consumption of >or=1 drink of red wine per day was associated with an approximately 60% reduced lung cancer risk in ever-smokers: HR, 0.39; 95% CI, 0.14-1.08. No clear associations with lung cancer were seen for intake of white wine, beer, or liquor. Moderate red wine consumption was inversely associated with lung cancer risk after adjusting for confounders. Our results should not be extrapolated to heavy alcohol consumption.

LIFETIME PHYSICAL INACTIVITY IS ASSOCIATED WITH LUNG CANCER RISK AND MORTALITY.

PubMed

Cannioto, Rikki; Etter, John Lewis; LaMonte, Michael J; Ray, Andrew D; Joseph, Janine M; Al Qassim, Emad; Eng, Kevin H; Moysich, Kirsten B

2018-01-01

Investigations of the independent associations of physical inactivity with cancer endpoints have been mounting in the epidemiological literature, in part due to the high prevalence of physical inactivity among cancer patients and to evidence that inactivity associates with carcinogenesis via pathways independent of obesity. Yet, physical inactivity is not currently recognized as a well-established risk or prognostic factor for lung cancer. As such, we examined the associations of lifetime physical inactivity with lung cancer risk and mortality in a hospital-based, case-control study. Materials and Methods: The analyses included data from 660 lung cancer patients and 1335 matched cancer-free controls. Multivariable logistic regression analyses were utilized to assess the association between lifetime physical inactivity and lung cancer risk, and Cox proportional hazards models were utilized to estimate the association between lifetime physical inactivity and mortality among lung cancer cases. Results: We observed a significant positive association between lifetime physical inactivity and lung cancer risk: [Odds ratio (OR)=2.23, 95% confidence interval (CI): 1.77-2.81]; the association remained significant among never smokers (OR=3.00, 95% CI:1.33-6.78) and non-smokers (OR=2.33, 95% CI: 1.79-3.02). We also observed a significant positive association between lifetime physical inactivity and lung cancer mortality [Hazard ratio (HR)=1.40, 95% CI: 1.14-1.71]; the association remained significant in non-smokers (HR=1.51, 95% CI: 1.16-1.95). These data add to the body of evidence suggesting that physical inactivity is an independent risk and prognostic factor for cancer. Additional research utilizing prospectively collected data is needed to substantiate the current findings.

Risk Factors for Lung Cancer in Iowa Women: Implications for Prevention

PubMed Central

Neuberger, John S.; Mahnken, Jonathan D.; Mayo, Matthew S.; Field, R. William

2007-01-01

Background Multiple risk factors possibly associated with lung cancer were examined as part of a large-scale residential radon case-control study conducted in Iowa between 1994 and 1997. We were particularly interested in stratifying risk factors by smoking status. Relatively little risk factor information is available for Midwestern rural women. Methods Four hundred thirteen female lung cancer cases and 614 controls aged 40-84, who were residents of their current home for at least 20 years, were included. Risk factors examined included cigarette smoking, passive smoking, occupation, chemical exposure, previous lung disease, family history of cancer, and urban residence. Multiple logistic regression analysis was conducted after adjusting for age, education, and cumulative radon exposure. Results As expected, active cigarette smoking was the major risk factor for lung cancer. While cessation of smoking was significantly associated with a reduced risk for lung cancer, the risk remained significantly elevated for 25 years. Among all cases, asbestos exposure was a significant risk. Among ex-smokers, pack-year history predominated as the major risk. Among never smokers, a family history of kidney or bladder cancer were significant risk factors (OR= 7.34, 95% CI = 1.91 - 28.18; and 5.02, 95% CI = 1.64-15.39, respectively), as was a history of previous lung disease (OR=2.28, 95% CI=1.24-4.18) and asbestos exposure. No statistically significant increase in lung cancer risk was found for occupation or urban residence. Conclusions Smoking prevention activities are urgently needed in rural areas of the United States. Relatives of individuals with smoking-related cancers are potentially at increased risk. Genetic risk factors should be more fully investigated in never smokers. PMID:16581199

Lung function profiles and aerobic capacity of adult cigarette and hookah smokers after 12 weeks intermittent training.

PubMed

Koubaa, Abdessalem; Triki, Moez; Trabelsi, Hajer; Masmoudi, Liwa; Zeghal, Khaled N; Sahnoun, Zouhair; Hakim, Ahmed

2015-01-01

Introduction Pulmonary function is compromised in most smokers. Yet it is unknown whether exercise training improves pulmonary function and aerobic capacity in cigarette and hookah smokers and whether these smokers respond in a similar way as do non-smokers. Aim To evaluate the effects of an interval exercise training program on pulmonary function and aerobic capacity in cigarette and hookah smokers. Methods Twelve cigarette smokers, 10 hookah smokers, and 11 non-smokers participated in our exercise program. All subjects performed 30 min of interval exercise (2 min of work followed by 1 min of rest) three times a week for 12 weeks at an intensity estimated at 70% of the subject's maximum aerobic capacity ([Formula: see text]). Pulmonary function was measured using spirometry, and maximum aerobic capacity was assessed by maximal exercise testing on a treadmill before the beginning and at the end of the exercise training program. Results As expected, prior to the exercise intervention, the cigarette and hookah smokers had significantly lower pulmonary function than the non-smokers. The 12-week exercise training program did not significantly affect lung function as assessed by spirometry in the non-smoker group. However, it significantly increased both forced expiratory volume in 1 second and peak expiratory flow (PEF) in the cigarette smoker group, and PEF in the hookah smoker group. Our training program had its most notable impact on the cardiopulmonary system of smokers. In the non-smoker and cigarette smoker groups, the training program significantly improved [Formula: see text] (4.4 and 4.7%, respectively), v [Formula: see text] (6.7 and 5.6%, respectively), and the recovery index (7.9 and 10.5%, respectively). Conclusions After 12 weeks of interval training program, the increase of [Formula: see text] and the decrease of recovery index and resting heart rate in the smoking subjects indicated better exercise tolerance. Although the intermittent training program altered pulmonary function only partially, both aerobic capacity and life quality were improved. Intermittent training should be advised in the clinical setting for subjects with adverse health behaviors.

Lung function profiles and aerobic capacity of adult cigarette and hookah smokers after 12 weeks intermittent training.

PubMed

Koubaa, Abdessalem; Triki, Moez; Trabelsi, Hajer; Masmoudi, Liwa; Zeghal, Khaled N; Sahnoun, Zouhair; Hakim, Ahmed

2015-01-01

Pulmonary function is compromised in most smokers. Yet it is unknown whether exercise training improves pulmonary function and aerobic capacity in cigarette and hookah smokers and whether these smokers respond in a similar way as do non-smokers. To evaluate the effects of an interval exercise training program on pulmonary function and aerobic capacity in cigarette and hookah smokers. Twelve cigarette smokers, 10 hookah smokers, and 11 non-smokers participated in our exercise program. All subjects performed 30 min of interval exercise (2 min of work followed by 1 min of rest) three times a week for 12 weeks at an intensity estimated at 70% of the subject's maximum aerobic capacity (VO2max). Pulmonary function was measured using spirometry, and maximum aerobic capacity was assessed by maximal exercise testing on a treadmill before the beginning and at the end of the exercise training program. As expected, prior to the exercise intervention, the cigarette and hookah smokers had significantly lower pulmonary function than the non-smokers. The 12-week exercise training program did not significantly affect lung function as assessed by spirometry in the non-smoker group. However, it significantly increased both forced expiratory volume in 1 second and peak expiratory flow (PEF) in the cigarette smoker group, and PEF in the hookah smoker group. Our training program had its most notable impact on the cardiopulmonary system of smokers. In the non-smoker and cigarette smoker groups, the training program significantly improved VO2max (4.4 and 4.7%, respectively), v VO2max (6.7 and 5.6%, respectively), and the recovery index (7.9 and 10.5%, respectively). After 12 weeks of interval training program, the increase of VO2max and the decrease of recovery index and resting heart rate in the smoking subjects indicated better exercise tolerance. Although the intermittent training program altered pulmonary function only partially, both aerobic capacity and life quality were improved. Intermittent training should be advised in the clinical setting for subjects with adverse health behaviors.

Cumulative exposure to dust and gases as determinants of lung function decline in tunnel construction workers

PubMed Central

Bakke, B; Ulvestad, B; Stewart, P; Eduard, W

2004-01-01

Aims: To study the relation between lung function decrease and cumulative exposure to dust and gases in tunnel construction workers. Methods: A total of 651 male construction workers (drill and blast workers, tunnel concrete workers, shotcreting operators, and tunnel boring machine workers) were followed up by spirometric measurements in 1989–2002 for an average of six years. Outdoor concrete workers, foremen, and engineers served as a low exposed referent population. Results: The between worker component of variability was considerably reduced within the job groups compared to the whole population, suggesting that the workers within job groups had similar exposure levels. The annual decrease in FEV1 in low-exposed non-smoking workers was 21 ml and 24 ml in low-exposed ever smokers. The annual decrease in FEV1 in tunnel construction workers was 20–31 ml higher than the low exposed workers depending on job group for both non-smokers and ever smokers. After adjustment for age and observation time, cumulative exposure to nitrogen dioxide showed the strongest association with a decrease in FEV1 in both non-smokers, and ever smokers. Conclusion: Cumulative exposure to nitrogen dioxide appeared to be a major risk factor for lung function decreases in these tunnel construction workers, although other agents may have contributed to the observed effect. Contact with blasting fumes should be avoided, diesel exhaust emissions should be reduced, and respiratory devices should be used to protect workers against dust and nitrogen dioxide exposure. PMID:14985522

Ethical analysis of the justifiability of labelling with COPD for smoking cessation.

PubMed

Kotz, D; Vos, R; Huibers, M J H

2009-09-01

Spirometry for early detection of chronic obstructive pulmonary disease (COPD) and smoking cessation is criticised because of the potential negative effects of labelling with disease. To assess the effects of opinions of smokers with mild to moderate COPD on the effectiveness of spirometry for smoking cessation, the justification of early detection of airflow limitation in smokers and the impact of confrontation with COPD. Qualitative study with data from a randomised controlled trial. General population of Dutch and Belgian Limburg. Semistructured ethical exit interviews were conducted with 205 smokers who were motivated to quit smoking and had no prior diagnosis of COPD but were detected with airflows limitation by means of spirometry. They received either (1) counselling, including labelling with COPD, plus with nortriptyline for smoking cessation, (2) counselling excluding labelling with COPD, plus nortriptyline for smoking cessation or (3) care as usual for smoking cessation by the general practitioner, without labelling with COPD. Of the participants, 177 (86%) agreed or completely agreed that it is justified to measure lung function in heavy smokers. These participants argued that measuring lung function raises consciousness of the negative effects of smoking, helps to prevent disease or increases motivation to stop smoking. Most of the 18 participants who disagreed argued that routinely measuring lung function in smokers would interfere with freedom of choice. Labelling with disease is probably a less important issue in the discussion about the pros and cons of early detection of COPD.

Acute post cessation smoking. A strong predictive factor for metabolic syndrome among adult Saudis.

PubMed

Al-Daghri, Nasser M

2009-02-01

To determine the influence of tobacco exposure in the development of metabolic syndrome (MS) in the adult Saudi population. Six hundred and sixty-four adults (305 males and 359 females) aged 25-70 years were included in this cross-sectional study conducted at the King Abdul-Aziz University Hospital, between June 2006 and May 2007. We classified the participants into non-smokers, smokers, and ex-smokers (defined as complete cessation for 1-2 years). All subjects were screened for the presence of MS using the modified American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI), International Diabetes Federation (IDF) and World Health Organization (WHO) definitions. Metabolic syndrome was highest among ex-smokers regardless of definition used. Relative risk for ex-smokers (95% CI: 2.23, 1.06-4.73) was more than twice in harboring MS as compared to non-smokers (95% CI: 2.78, 1.57-4.92) (p=0.009). Acute post-cessation smoking is a strong predictor for MS among male and female Arabs. Smoking cessation programs should include a disciplined lifestyle and dietary intervention to counteract the MS-augmenting side-effect of smoking cessation.

Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions

PubMed Central

Suehara, Yoshiyuki; Arcila, Maria; Wang, Lu; Hasanovic, Adnan; Ang, Daphne; Ito, Tatsuo; Kimura, Yuki; Drilon, Alexander; Guha, Udayan; Rusch, Valerie; Kris, Mark G.; Zakowski, Maureen F.; Rizvi, Naiyer; Khanin, Raya; Ladanyi, Marc

2014-01-01

Background The mutually exclusive pattern of the major driver oncogenes in lung cancer suggests that other mutually exclusive oncogenes exist. We performed a systematic search for tyrosine kinase (TK) fusions by screening all TKs for aberrantly high RNA expression levels of the 3′ kinase domain (KD) exons relative to more 5′ exons. Methods We studied 69 patients (including 5 never smokers and 64 current or former smokers) with lung adenocarcinoma negative for all major mutations in KRAS, EGFR, BRAF, MEK1, and HER2, and for ALK fusions (termed “pan-negative”). A NanoString-based assay was designed to query the transcripts of 90 TKs at two points: 5′ to the KD and within the KD or 3′ to it. Tumor RNAs were hybridized to the NanoString probes and analyzed for outlier 3′ to 5′ expression ratios. Presumed novel fusion events were studied by rapid amplification of cDNA ends (RACE) and confirmatory RT-PCR and FISH. Results We identified 1 case each of aberrant 3′ to 5′ ratios in ROS1 and RET. RACE isolated a GOPC-ROS1 (FIG-ROS1) fusion in the former and a KIF5B-RET fusion in the latter, both confirmed by RT-PCR. The RET rearrangement was also confirmed by FISH. The KIF5B-RET patient was one of only 5 never smokers in this cohort. Conclusion The KIF5B-RET fusion defines an additional subset of lung cancer with a potentially targetable driver oncogene enriched in never smokers with “pan-negative” lung adenocarcinomas. We also report for the first time in lung cancer the GOPC-ROS1 fusion previously characterized in glioma. PMID:23052255

Indirectly estimated absolute lung cancer mortality rates by smoking status and histological type based on a systematic review

PubMed Central

2013-01-01

Background 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. Methods 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. Results 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). Conclusions 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. PMID:23570286

Idiopathic pulmonary fibrosis and lung cancer: a clinical and pathogenesis update.

PubMed

Antoniou, Katerina M; Tomassetti, Sara; Tsitoura, Eliza; Vancheri, Carlo

2015-11-01

About one out of 10 patients with idiopathic pulmonary fibrosis (IPF) develop lung cancer. This review provides an epidemiology and clinical update of the association of these two lethal diseases. In addition, we focus on the emerging overlapping epigenetic mechanisms in both diseases. In a vast majority of cases, lung cancer is diagnosed during the clinical and radiological follow-up for the fibrosis. The risk of development of lung cancer in IPF is higher for older male smokers and there is a significantly higher prevalence of lung cancer in the combined IPF and emphysema syndrome compared with fibrosis only. The association of two lethal diseases, such as IPF and lung cancer, carries a very poor outcome and the correct treatment strategy, particularly for advanced forms of lung cancer, is still unclear. The two novel drugs approved for IPF, pirfenidone and nintedanib, open a new scenario in which treated patients with fibrosis will live longer, and possibly have a lower incidence of lung cancer. However, prospective studies are urgently needed to definitively clarify the role of lung cancer treatment in the management of IPF patients. Furthermore, common epigenetic alterations may represent a promising target for therapeutic approaches in the near future.

Polonium in cigarette smoke and radiation exposure of lungs

NASA Astrophysics Data System (ADS)

Carvalho, Fernando P.; Oliveira, João M.

2006-01-01

Polonium (210Po), the most volatile of naturally-occurring radionuclides in plants, was analysed in three common brands of cigarettes produced in Portugal. The analyses were carried out on the unburned tobacco contained in cigarettes, on the ashes and butts of smoked cigarettes and on the mainstream smoke. 210Po in tobacco displays concentrations ranging from 3 to 37 mBq g-1, depending upon the cigarette brand. The 210Po activity remaining in the solid residue of a smoked cigarette varied from 0.3 to 4.9 mBq per cigarette, and the 210Po in the inhaled smoke varied from 2.6 to 28.9 mBq. In all brands of cigarettes tested, a large fraction of the 210Po content is not inhaled by the smoker and it is released into the atmosphere. Part of it may be inhaled by passive smokers. Depending upon the commercial brand and upon the presence or absence of a filter in the cigarette, 5 to 37 % of the 210Po in the cigarette can be inhaled by the smoker. Taking into account the average 210Po in surface air, the smoker of one pack of twenty cigarettes per day may inhale 50 times 210Po than a non smoker. Cigarette smoke contributes with 1.5 % to the daily rate of 210Po absorption into the blood, 0.39 Bq d-1, and, after systemic circulation it gives rise to a whole body radiation dose in the same proportion. However, in the smoker the deposition of 210Po in the lungs is much more elevated than normal and may originate an enhanced radiation exposure. Estimated dose to the lungs is presented and radiobiological effects of cigarette smoke are discussed.

Lung injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR.

PubMed

Wang, Chengbo; Mugler, John P; de Lange, Eduard E; Patrie, James T; Mata, Jaime F; Altes, Talissa A

2014-01-01

To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as "smokers" indicating an elevation of the ADC AUC. Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage. Copyright © 2013 Wiley Periodicals, Inc.

COPD in Never Smokers

PubMed Central

McBurnie, Mary Ann; Vollmer, William M.; Gudmundsson, Gunnar; Welte, Tobias; Nizankowska-Mogilnicka, Ewa; Studnicka, Michael; Bateman, Eric; Anto, Josep M.; Burney, Peter; Mannino, David M.; Buist, Sonia A.

2011-01-01

Background: Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined. Methods: We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio. Results: Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations. Conclusion: This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. PMID:20884729

Effects of Smoking on Cost of Hospitalization and Length of Stay among Patients with Lung Cancer in Iran: a Hospital-Based Study.

PubMed

Sari, Ali Akbari; Rezaei, Satar; Arab, Mohammad; Majdzadeh, Reza; Matin, Behzad Karami; Zandian, Hamed

2016-01-01

Smoking is recognized as a main leading preventable cause of mortality and morbidity worldwide. It is responsible for a considerable nancial burden both on the health system and in society. This study aimed to examine the effect of smoking on cost of hospitalization and length of stay (LoS) among patients with lung cancer in Iran in 2014. A total of 415 patients were included in the study. Data on age, sex, insurance status, type of hospitals, type of insurance, geographic local, length of stay and cost of hospitalization was extracted by medical records and smoking status was obtained from a telephone survey. To compare cost of hospitalization and LoS for different smoking groups, current smokers, former smokers, and never smokers, a gamma regression model and zero-truncated poisson regression were used, respectively. Compared with never smokers, current and former smokers showed a 48% and 35% increase in hospitalization costs, respectively. Also, hospital LoS for current and former smokers was 72% and 31% higher than for never smokers, respectively. Our study indicated that cigarette smoking imposes a signi cant nancial burden on hospitals in Iran. It is, however, recommended that more research should be done to implement and evaluate hospital based smoking cessation interventions to better increase cessation rates in these settings.

Epidemiology of Lung Cancer

PubMed Central

Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

2013-01-01

Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

Beta-cryptoxanthin protection against cigarette smoke-induced inflammatory responses in the lung is due to the action of its own molecule

USDA-ARS?s Scientific Manuscript database

Higher intake of the dietary xanthophyll, beta-cryptoxanthin (BCX), has been associated with a lower risk of lung cancer death in smokers. We have previously shown that BCX feeding was effective in reducing both cigarette smoke (CS)-induced lung inflammation in ferrets and carcinogen-induced lung tu...

Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

NASA Astrophysics Data System (ADS)

Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

2014-03-01

Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

Characterisation of smoking behaviour across the life course and its impact on decline in lung function and all-cause mortality: evidence from a British birth cohort

PubMed Central

Clennell, S; Kuh, D; Guralnik, J M; Patel, K V; Mishra, G D

2008-01-01

Objectives: To describe smoking trajectories from early adolescence into mid-life and to examine the effects of these trajectories on health and all-cause mortality. Methods: A nationally representative birth cohort study including 3387 men and women followed up since their birth in 1946 in England, Scotland and Wales. The main outcome measure is all-cause mortality by age 60 years and rate of decline in forced expiratory volume in 1 second (FEV1). Results: Eighteen per cent of the sample were categorised as lifelong smokers (smokers at all six waves at ages 20, 25, 31, 36, 43, 53 years), of whom 90% had begun smoking by age 18 years. By age 60 years, 10% of all lifelong smokers had died. They had a threefold increase in mortality rate compared with never smokers (hazard ratio (HR) 3.2, 95% confidence interval (CI) 2.1 to 4.8). For predominantly smokers (smokers for at least four of the six data collections), mortality rate remained higher than never smokers (HR 1.6, 95% CI 1.0 to 2.5). Predominantly non-smokers did not differ from those who never smoked (HR 1.3, 95% CI 0.9 to 2.0). Using the most recent smoking status available, current smokers had more than double the risk of mortality compared with never smokers (HR 2.4, 95% CI 1.6 to 3.5). Lifelong smokers and predominantly smokers had a greater rate of decline in lung function than never smokers (regression coefficients −18 ml/year, 95% CI −22 to −13; −6, 95% CI −10.3 to −1.7 respectively). For current smokers, the decline was 8.4 ml/year (95% CI −12.0 to −5.0) faster than never smokers. Conclusions: The strength and differentiation of adverse effects identified by using simplified smoking behaviours has highlighted the advantages of obtaining further information on lifelong smoking behaviour from former smokers, rather than just current smoking status. PMID:18450766

Lung cancer risk in welders and foundry workers with a history of heavy smoking in the USA: The National Lung Screening Trial.

PubMed

Wong, Jason Y Y; Bassig, Bryan A; Seow, Wei Jie; Hu, Wei; Ji, Bu-Tian; Blair, Aaron; Silverman, Debra T; Lan, Qing

2017-06-01

Foundry work is a risk factor for lung cancer; however, the association with welding is unclear, as smoking is common among metalworkers and may mask the relationship. We evaluated whether history of welding and foundry work, independently and jointly, and employment duration were associated with lung cancer risk in heavy smokers. We analysed data from the National Lung Screening Trial, a prospective randomised trial of 53 454 heavy smokers (>30 pack-years) in the USA. Cox regression models were used to estimate the HRs and 95% CIs of medically/histologically confirmed incident lung cancer during the follow-up period (2002-2009) in relation to history and duration of welding and foundry work assessed via questionnaires, adjusted for screening arm, component study, sex, age, race/ethnicity, education, smoking status and pack-years, body mass index and personal/family medical history. There were 2034 incident lung cancer cases throughout the follow-up. Increasing years of employment in welding (p-trend =0.039) and foundry work (p-trend =0.005) were related to increased lung cancer risk among heavy smokers. Having ever been employed (≥1 yr) as either a welder or foundry worker alone was associated with non-significant increased risks of lung cancer (HR=1.12 (95% CI 0.91 to 1.37) and HR=1.09 (95% CI 0.85 to 1.39), respectively). Further, there was a joint-effect in that those who were ever employed in both occupations had significantly increased risks (HR=1.48 (95% CI 1.08 to 2.04)). Our findings provide further evidence that exposure to welding/metal fumes may be associated with elevated lung cancer risk. NCT00047385. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Public spirometry for primary prevention of COPD.

PubMed

Zirlik, Sabine; Wich, Christina; Frieser, Markus; Hildner, Kai; Kleye, Christin; Neurath, Markus F; Fuchs, Florian S

2014-02-01

The most effective action for primary prevention of chronic obstructive lung disease is smoking cessation early enough. In secondary prevention, smokers with airway obstruction were more likely to quit smoking. The aim of this study was to evaluate the impact of a public spirometry on smoking habits in terms of primary prevention. Spirometry with its medical analysis was offered to visitors of a local public event called 'Lange Nacht der Wissenschaften' ('Long night of sciences'). The impact of results on smoking habits was evaluated in all smokers with an anonymized questionnaire afterwards. Two hundred fifty-seven people with the median age of 30 years (interquartile range 22-46) were examined. Out of 44 current smokers (17.1%), only two individuals showed a prebronchodilator FEV1/forced vital capacity-value <0.7. Fourteen smokers stated to have an increased motivation to quit smoking whereas 28 smokers declared that their motivation to quit smoking was independent of spirometry result. These smokers were significantly younger (median age 28 vs. 40 years, P = 0.025) without differences in spirometry results or smoking habits. In an unselected population with a high amount of younger adults, normal spirometry did not show a short-term benefit for primary prevention of chronic obstructive lung disease in terms of increasing motivation to quit smoking. © 2013 John Wiley & Sons, Ltd.

Neutrophilic infiltration within the airway smooth muscle in patients with COPD

PubMed Central

Baraldo, S; Turato, G; Badin, C; Bazzan, E; Beghe, B; Zuin, R; Calabrese, F; Casoni, G; Maestrelli, P; Papi, A; Fabbri, L; Saetta, M

2004-01-01

Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation. PMID:15047950

Aspergillus sensitisation in bidi smokers with and without chronic obstructive lung disease.

PubMed

Agarwal, Ritesh; Bhogal, Sumita; Choudhary, Hansraj; Aggarwal, Ashutosh N; Sehgal, Inderpaul S; Dhooria, Sahajal; Behera, Digambar; Chakrabarti, Arunaloke

2017-06-01

Recent studies have described fungal sensitisation in patients with chronic obstructive pulmonary disease (COPD). However, no study has evaluated fungal sensitisation specifically in bidi smokers. Herein, we evaluate the prevalence of Aspergillus sensitisation in bidi smokers. Bidi smokers with and without COPD underwent chest radiography, spirometry, Aspergillus skin test, A. fumigatus precipitins, A. fumigatus-specific IgE and total IgE. Aspergillus sensitisation was defined as the presence of either immediate cutaneous hyperreactivity to Aspergillus antigen or raised A. fumigatus-specific IgE level >0.35 kUA/L. Bidis were obtained from a subset of cases and controls and cultured for the growth of any fungus. Two hundred subjects with COPD and 72 chronic bidi smokers without COPD were included in the study (258 men; mean age, 56.8 years). Aspergillus sensitisation was found to be significantly higher in bidi smokers without COPD (27.8%) compared to the COPD cases (16%). Age, COPD, lung function, severity of smoking and current smoking were not associated with Aspergillus sensitisation, on a multivariate logistic regression analysis. We found a high prevalence of Aspergillus sensitisation in bidi-smoking subjects. More studies are required to confirm the findings of our study. © 2017 Blackwell Verlag GmbH.

[The consequences of passive smoking in adults].

PubMed

Trédaniel, J; Savinelli, F; Vignot, S; Bousquet, G; Le Maignan, C; Misset, J-L

2006-04-01

Passive smoking is the involuntary inhalation by a non-smoker of smoke generated in his neighbourhood by one or more smokers. The effect of this exposure is already generally recognised in children. In adults the induction of chronic obstructive lung disease has not been demonstrated. This is no longer the case for ischaemic heart disease and lung cancer where the effect of passive exposure of non-smokers to cigarette smoke is recognised. The biological plausibility together with the concordance of results obtained over successive years, as well as the large numbers of patients included in the studies, lead to a confident conclusion that the risks in adult non-smokers are increased by the order of 25%. There is no evidence that bias affects the conclusions reached and the World Health Organisation has recently classified passive smoking as being carcinogenic in man. As a result of these data prevention of passive exposure to cigarette smoke should be part of a larger framework of smoking prevention, especially among the young.

Smokers who use internet and smokers who don't: data from the Health Information and National Trends Survey (HINTS).

PubMed

Stoddard, Jacqueline L; Augustson, Erik M

2006-12-01

Web-assisted tobacco interventions (WATI) have proliferated in recent years, but little is known about those such sites are reaching and those who might be reached in the future. A better understanding of factors that differentiate smokers who do and do not use the Internet could help developers of smoking cessation resources optimize the content and dissemination of resources to these two groups. Using the 2003 Health Information National Trends Survey (HINTS), a nationally representative survey of U.S. adults, we compared smokers using the Internet (n=728) with smokers not using the Internet (n=516) on demographics, smoking history, healthcare (status, care, access, and use), beliefs about lung cancer risks, and media preferences. Our results showed that compared with smokers not on the Internet, those using the Internet had a higher income and were more likely to be employed, despite having a younger age. Internet-connected smokers also reported less psychological distress, fewer barriers to healthcare, and a greater interest in quitting smoking. Preferences for media also differed by Internet status: Those on the Internet spent less time on television and more time with newspapers and magazines than those not on the Internet. These and other differences may assist the public health community with both the design and dissemination of resources to help smokers quit.

Lung cancer-A global perspective.

PubMed

McIntyre, Amanda; Ganti, Apar Kishor

2017-04-01

Lung cancer is the leading cause of cancer deaths worldwide. While tobacco exposure is responsible for the majority of lung cancers, the incidence of lung cancer in never smokers, especially Asian women, is increasing. There is a global variation in lung cancer biology with EGFR mutations being more common in Asian patients, while Kras mutation is more common in Caucasians. This review will focus on the global variations in lung cancer and its treatment. © 2017 Wiley Periodicals, Inc.

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.

Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed usingmore » data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

DOE PAGES

Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.; ...

2015-09-15

Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed usingmore » data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study.

PubMed

Barrow, Timothy M; Klett, Hagen; Toth, Reka; Böhm, Jürgen; Gigic, Biljana; Habermann, Nina; Scherer, Dominique; Schrotz-King, Petra; Skender, Stephanie; Abbenhardt-Martin, Clare; Zielske, Lin; Schneider, Martin; Ulrich, Alexis; Schirmacher, Peter; Herpel, Esther; Brenner, Hermann; Busch, Hauke; Boerries, Melanie; Ulrich, Cornelia M; Michels, Karin B

2017-11-01

Smoking tobacco is a known risk factor for the development of colorectal cancer and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never-smokers, 47 former smokers, and 13 active smokers, and in adjacent mucosa from 49 never-smokers, 64 former smokers, and 18 active smokers. Our analyses identified 15 CpG sites within the APC 1A promoter that were significantly hypermethylated and 14 CpG loci within the NFATC1 gene body that were significantly hypomethylated (pLIS < 1 × 10 -5 ) in the tumours of active smokers. The APC 1A promoter was hypermethylated in 7 of 36 tumours from never-smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%). Promoter hypermethylation was positively associated with duration of smoking (Spearman rank correlation, ρ = 0.26, p = 0.03) and was confined to tumours, with hypermethylation never being observed in adjacent mucosa. Further analysis of adjacent mucosa revealed significant hypomethylation of four loci associated with the TNXB gene in tissue from active smokers. Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis. Further work is required to establish the validity of our observations in independent cohorts. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marmorstein, J.

This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Criticalmore » support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.« less

Cigarettes, lung cancer, and coronary heart disease: the effects of inhalation and tar yield.

PubMed

Higenbottam, T; Shipley, M J; Rose, G

1982-06-01

Ten-year mortality rates for lung cancer and coronary heart disease have been related to cigarette smoking habits in 17 475 male civil servants aged 40-64 and in sample of 8089 male British residents aged 35-69. Both diseases were more frequent in smokers. Lung cancer rates were higher overall for "non-inhalers", particularly in heavy smokers. Tar yield correlated with the risk of lung cancer in non-inhalers but less so in inhalers. Conversely, coronary deaths were more common among inhalers, and the effect of tar/nicotine yield (such as it was) was confined to inhalers. It appears that there are subtle interactions between the amount smoked, the tar/nicotine yield of the cigarette, and the style of smoking. Thus the effects of a change in cigarette characteristics are hard to predict, and they may be different for respiratory and cardiovascular disease.

Plasma Chemokine signature correlates with lung goblet cell hyperplasia in smokers with and without chronic obstructive pulmonary disease.

PubMed

Kim, Victor; Cornwell, William D; Oros, Michelle; Durra, Heba; Criner, Gerard J; Rogers, Thomas J

2015-09-30

Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung and systemic inflammation as well as airway goblet cell hyperplasia (GCH). Mucin production is activated in part by stimulation of the epidermal growth factor (EGF) receptor pathway through neutrophils and macrophages. How circulating cytokine levels relate to GCH is not clear. We performed phlebotomy and bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, and eight COPD subjects FEV1 30-60 %). Six endobronchial biopsies per subject were performed. GCH was measured by measuring mucin volume density (MVD) using stereological techniques on periodic acid fast-Schiff stained samples. We measured the levels of chemokines CXCL8/IL-8, CCL2/MCP-1, CCL7/MCP-3, CCL22/MCD, CCL3/MIP-1α, and CCL4/MIP-1β, and the cytokines IL-1, IL-4, IL-6, IL-9, IL-17, EGF, and vascular endothelial growth factor (VEGF). Differences between groups were assessed using one-way ANOVA, t test, or Chi squared test. Post hoc tests after ANOVA were performed using Bonferroni correction. MVD was highest in healthy smokers (27.78 ± 10.24 μL/mm(2)) compared to COPD subjects (16.82 ± 16.29 μL/mm(2), p = 0.216) and nonsmokers (3.42 ± 3.07 μL/mm(2), p < 0.0001). Plasma CXCL8 was highest in healthy smokers (11.05 ± 8.92 pg/mL) compared to nonsmokers (1.20 ± 21.92 pg/mL, p = 0.047) and COPD subjects (6.01 ± 5.90 pg/mL, p = 0.366). CCL22 and CCL4 followed the same trends. There were no significant differences in the other cytokines measured. When the subjects were divided into current smokers (healthy smokers and COPD current smokers) and non/ex-smokers (nonsmokers and COPD ex-smokers), plasma CXCL8, CCL22, CCL4, and MVD were greater in current smokers. No differences in other cytokines were seen. Plasma CXCL8 moderately correlated with MVD (r = 0.552, p = 0.003). In this small cohort, circulating levels of the chemokines CXCL8, CCL4, and CCL22, as well as MVD, attain the highest levels in healthy smokers compared to nonsmokers and COPD subjects. These findings seem to be driven by current smoking and are independent of airflow obstruction. These data suggest that smoking upregulates a systemic pattern of neutrophil and macrophage chemoattractant expression, and this correlates significantly with the development of goblet cell hyperplasia.

Dynamic hyperinflation after metronome-paced hyperventilation in COPD--a 2 year follow-up.

PubMed

Hannink, Jorien; Lahaije, Anke; Bischoff, Erik; van Helvoort, Hanneke; Dekhuijzen, Richard; Schermer, Tjard; Heijdra, Yvonne

2010-11-01

In contrast to the decline in FEV(1), the behavior of dynamic hyperinflation (DH) over time is unknown in patients with COPD. Metronome-paced hyperventilation (MPH) is a simple applicable surrogate for exercise to detect DH. To evaluate changes in MPH-induced DH during two years follow-up in mild-to-severe COPD patients. Additionally, influence of smoking status on DH and the relation between DH and other lung function parameters were assessed. Patients were recruited from a randomized controlled trial conducted in general practice. Measurements of lung function and DH were performed at baseline and after 12 and 24 months. DH was assessed by MPH with breathing frequency set at twice the baseline rate. Change in inspiratory capacity after MPH was used to reflect change in end-expiratory lung volume and therefore DH, presuming constant total lung capacity. During follow-up, 68 patients completed all measurements. DH increased by 0.23±0.06L (p≤0.001). No significant changes in FEV(1) %pred were seen. Smokers had lower FEV(1) and a more rapid decline than non-smokers. DH in smokers increased more over time compared to non-smokers. The amount of DH correlated positively with resting inspiratory capacity. After two years, a significant increase in MPH-induced DH in COPD patients was demonstrated, which was not accompanied by a decline in FEV(1). It might be that DH is a sensitive measure to track consequences of changes in airflow obstruction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Are Systemic Manifestations Ascribable to COPD in Smokers? A Structural Equation Modeling Approach.

PubMed

Boyer, Laurent; Bastuji-Garin, Sylvie; Chouaid, Christos; Housset, Bruno; Le Corvoisier, Philippe; Derumeaux, Geneviève; Boczkowski, Jorge; Maitre, Bernard; Adnot, Serge; Audureau, Etienne

2018-06-05

Whether the systemic manifestations observed in Chronic Obstructive Pulmonary Disease (COPD) are ascribable to lung dysfunction or direct effects of smoking is in debate. Structural Equations Modeling (SEM), a causal-oriented statistical approach, could help unraveling the pathways involved, by enabling estimation of direct and indirect associations between variables. The objectives of the study was to investigate the relative impact of smoking and COPD on systemic manifestations, inflammation and telomere length. In 292 individuals (103 women; 97 smokers with COPD, 96 smokers without COPD, 99 non-smokers), we used SEM to explore the pathways between smoking (pack-years), lung disease (FEV 1 , K CO ), and the following parameters: arterial stiffness (aortic pulse wave velocity, PWV), bone mineral density (BMD), appendicular skeletal muscle mass (ASMM), grip strength, insulin resistance (HOMA-IR), creatinine clearance (eGFR), blood leukocyte telomere length and inflammatory markers (Luminex assay). All models were adjusted on age and gender. Latent variables were created for systemic inflammation (inflammatory markers) and musculoskeletal parameters (ASMM, grip strength, BMD). SEM showed that most effects of smoking were indirectly mediated by lung dysfunction: e.g. via FEV 1 on musculoskeletal factor, eGFR, HOMA-IR, PWV, telomere length, CRP, white blood cells count (WBC) and inflammation factor, and via K CO on musculoskeletal factor, eGFR and PWV. Direct effects of smoking were limited to CRP and WBC. Models had excellent fit. In conclusion, SEM highlighted the major role of COPD in the occurrence of systemic manifestations while smoking effects were mostly mediated by lung function.

Proactive recruitment of cancer patients’ social networks into a smoking cessation trial

PubMed Central

Bastian, Lori A.; Fish, Laura J.; Peterson, Bercedis L.; Biddle, Andrea K.; Garst, Jennifer; Lyna, Pauline; Molner, Stephanie; Bepler, Gerold; Kelley, Mike; Keefe, Francis J.; McBride, Colleen M.

2011-01-01

Background This report describes the characteristics associated with successful enrollment of smokers in the social networks (i.e., family and close friends) of patients with lung cancer into a smoking cessation intervention. Methods Lung cancer patients from four clinical sites were asked to complete a survey enumerating their family members and close friends who smoke, and provide permission to contact these potential participants. Family members and close friends identified as smokers were interviewed and offered participation in a smoking cessation intervention. Repeated measures logistic regression model examined characteristics associated with enrollment. Results A total of 1,062 eligible lung cancer patients were identified and 516 patients consented and completed the survey. These patients identified 1,325 potentially eligible family and close friends. Of these, 496 consented and enrolled in the smoking cessation program. Network enrollment was highest among patients who were white and had late-stage disease. Social network members enrolled were most likely to be female, a birth family, immediate family, or close friend, and live in close geographic proximity to the patient. Conclusions Proactive recruitment of smokers in the social networks of lung cancer patients is challenging. In this study, the majority of family members and friends declined to participate. Enlisting immediate female family members and friends, who live close to the patient as agents to proactively recruit other network members into smoking cessation trials could be used to extend reach of cessation interventions to patients’ social networks. Moreover, further consideration should be given to the appropriate timing of approaching network smokers to consider cessation. PMID:21382509

Beta-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage and squamous metaplasia in ferrets

USDA-ARS?s Scientific Manuscript database

In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung ...

PPARγ in emphysema: blunts the damage and triggers repair?

PubMed Central

Kelly, Neil J.; Shapiro, Steven D.

2014-01-01

Cigarette smoke is the most common cause of pulmonary emphysema, which results in an irreversible loss of lung structure and function. Th1 and Th17 immune responses have been implicated in emphysema pathogenesis; however, the drivers of emphysema-associated immune dysfunction are not fully understood. In this issue of the JCI, Shan and colleagues found that peroxisome proliferator–activated receptor γ (PPARγ) is downregulated in APCs isolated from the lungs of emphysematous chronic smokers and mice exposed to cigarette smoke. Furthermore, treatment with a PPARγ agonist prevented emphysema development and appeared to reduce emphysema-associated lung volume expansion in mice exposed to cigarette smoke. Further work will need to be done to evaluate the potential of PPARγ agonists to restore lung capacity in emphysematous patients. PMID:24569365

Cost-effectiveness of Lung Cancer Screening in Canada.

PubMed

Goffin, John R; Flanagan, William M; Miller, Anthony B; Fitzgerald, Natalie R; Memon, Saima; Wolfson, Michael C; Evans, William K

2015-09-01

The US National Lung Screening Trial supports screening for lung cancer among smokers using low-dose computed tomographic (LDCT) scans. The cost-effectiveness of screening in a publically funded health care system remains a concern. To assess the cost-effectiveness of LDCT scan screening for lung cancer within the Canadian health care system. The Cancer Risk Management Model (CRMM) simulated individual lives within the Canadian population from 2014 to 2034, incorporating cancer risk, disease management, outcome, and cost data. Smokers and former smokers eligible for lung cancer screening (30 pack-year smoking history, ages 55-74 years, for the reference scenario) were modeled, and performance parameters were calibrated to the National Lung Screening Trial (NLST). The reference screening scenario assumes annual scans to age 75 years, 60% participation by 10 years, 70% adherence to screening, and unchanged smoking rates. The CRMM outputs are aggregated, and costs (2008 Canadian dollars) and life-years are discounted 3% annually. The incremental cost-effectiveness ratio. Compared with no screening, the reference scenario saved 51,000 quality-adjusted life-years (QALY) and had an incremental cost-effectiveness ratio of CaD $52,000/QALY. If smoking history is modeled for 20 or 40 pack-years, incremental cost-effectiveness ratios of CaD $62,000 and CaD $43,000/QALY, respectively, were generated. Changes in participation rates altered life years saved but not the incremental cost-effectiveness ratio, while the incremental cost-effectiveness ratio is sensitive to changes in adherence. An adjunct smoking cessation program improving the quit rate by 22.5% improves the incremental cost-effectiveness ratio to CaD $24,000/QALY. Lung cancer screening with LDCT appears cost-effective in the publicly funded Canadian health care system. An adjunct smoking cessation program has the potential to improve outcomes.

Single Nucleotide Polymorphism in ATM Gene, Cooking Oil Fumes and Lung Adenocarcinoma Susceptibility in Chinese Female Non-Smokers: A Case-Control Study

PubMed Central

Shen, Li; Yin, Zhihua; Wu, Wei; Ren, Yangwu; Li, Xuelian; Zhou, Baosen

2014-01-01

Background The ataxia-telangiectasia mutated (ATM) gene plays an important role in the DNA double-strand breaks repair pathway. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ATM -111G>A (rs189037) polymorphism, environmental risk factors and the risk of lung adenocarcinoma in Chinese female non-smokers. Methods A hospital-based case-control study of 487 lung cancer patients and 516 matched cancer-free controls was conducted. Information concerning demographic and environmental risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, 10 ml venous blood was collected from each subject for biomarker testing. Single nucleotide polymorphism was determined by using TaqMan method. Results This study showed that the individuals with ATM rs189037 AA genotype were at an increased risk for lung adenocarcinoma compared with those carrying the GA or GG genotype (adjusted odds ratios (OR) 1.44, 95% confidence interval (CI) 1.02–2.02, P = 0.039). The stratified analysis suggested that increased risk associated with ATM rs189037 AA genotype in individuals who never or seldom were exposed to cooking oil fumes (adjusted OR 1.89, 95%CI 1.03–3.49, P = 0.040). Conclusions ATM rs189037 might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, ATM rs189037 AA genotype might be a risk factor of lung adenocarcinoma among female non-smokers without cooking oil fume exposure. PMID:24819391

Household air pollution and lung cancer risk among never-smokers in Nepal.

PubMed

Raspanti, Greg A; Hashibe, Mia; Siwakoti, Bhola; Wei, Mei; Thakur, Binay Kumar; Pun, Chin Bahadur; Al-Temimi, Mohammed; Lee, Yuan-Chin Amy; Sapkota, Amir

2016-05-01

More than half of the global population relies on biomass fuels (wood, charcoal, crop residue, dung) for cooking and/or heating purposes. Household air pollution (HAP) resulting from the use of these solid fuels is of particular concern, given the overall prevalence as well as the intensity of exposure and the range of potential adverse health outcomes. Long term exposure to HAP is a major public health concern, particularly among women and children in low and middle income countries. In this study, we investigated the association between exposure to HAP resulting from combustion of biomass and lung cancer risk among Nepalese population. Using a hospital-based case-control study (2009-2012), we recruited 606 lung cancer cases and 606 healthy controls matched on age (±5 years), gender, and geographical residence. We used unconditional logistic regression to compute odds ratios (ORs) and 95% Confidence Intervals (95% CI) for lung cancer risk associated with HAP exposures, adjusting for potential confounders (tobacco use, TB status, SES, age, gender, ethnicity, and exposure to second hand smoke. In our overall analysis, we observed increased risk of lung cancer among those who were exposed to HAPs (OR: 1.77, 95% CI: 1.00-3.14). A more detailed analysis stratified by smoking status showed considerably higher risk of lung cancer associated with increasing duration of exposure to HAP from biomass combustion, with evidence of a borderline exposure-response relationship (Ptrend=0.05) that was more pronounced among never-smokers (Ptrend=0.01). Our results suggest that chronic exposure to HAP resulting from biomass combustion is associated with increased lung cancer risk, particularly among never-smokers in Nepal. Copyright © 2016 Elsevier Inc. All rights reserved.

Connective Tissue Growth Factor Promotes Pulmonary Epithelial Cell Senescence and Is Associated with COPD Severity.

PubMed

Jang, Jun-Ho; Chand, Hitendra S; Bruse, Shannon; Doyle-Eisele, Melanie; Royer, Christopher; McDonald, Jacob; Qualls, Clifford; Klingelhutz, Aloysius J; Lin, Yong; Mallampalli, Rama; Tesfaigzi, Yohannes; Nyunoya, Toru

2017-04-01

The purpose of this study was to determine whether expression of connective tissue growth factor (CTGF) protein in chronic obstructive pulmonary disease (COPD) is consistent in humans and animal models of COPD and to investigate the role of this protein in lung epithelial cells. CTGF in lung epithelial cells of ex-smokers with COPD was compared with ex-smokers without COPD by immunofluorescence. A total of twenty C57Bl/6 mice and sixteen non-human primates (NHPs) were exposed to cigarette smoke (CS) for 4 weeks. Ten mice of these CS-exposed mice and eight of the CS-exposed NHPs were infected with H3N2 influenza A virus (IAV), while the remaining ten mice and eight NHPs were mock-infected with vehicle as control. Both mRNA and protein expression of CTGF in lung epithelial cells of mice and NHPs were determined. The effects of CTGF overexpression on cell proliferation, p16 protein, and senescence-associated β-galactosidase (SA-β-gal) activity were examined in cultured human bronchial epithelial cells (HBECs). In humans, CTGF expression increased with increasing COPD severity. We found that protein expression of CTGF was upregulated in lung epithelial cells in both mice and NHPs exposed to CS and infected with IAV compared to those exposed to CS only. When overexpressed in HBECs, CTGF accelerated cellular senescence accompanied by p16 accumulation. Both CTGF and p16 protein expression in lung epithelia are positively associated with the severity of COPD in ex-smokers. These findings show that CTGF is consistently expressed in epithelial cells of COPD lungs. By accelerating lung epithelial senescence, CTGF may block regeneration relative to epithelial cell loss and lead to emphysema.

Dietary Flavonoid Intake and Lung Cancer—A Population-based Case-control Study

PubMed Central

Cui, Yan; Morgenstern, Hal; Greenland, Sander; Tashkin, Donald P.; Mao, Jenny T.; Cai, Lin; Cozen, Wendy; Mack, Thomas M.; Lu, Qing-Yi; Zhang, Zuo-Feng

2017-01-01

BACKGROUND Laboratory studies suggest that flavonoids are antimutagenic and anticarcinogenic. To investigate the associations between commonly consumed flavonoid compounds and lung cancer, the authors conducted a population-based case–control study of 558 lung cancer cases and a group of 837 controls. METHODS Dietary intakes of flavonoids were estimated by combining the intake frequency (collected by a food frequency questionnaire), portion size, and food composition data. Unconditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence limits (95% CLs) with an adjustment for potential confounders, including age, sex, race-ethnicity, years of schooling, smoking status, pack-years of tobacco smoking, and daily energy intake. RESULTS Lung cancer was associated inversely with the consumption of epicatechin (in 10 mg per day increment: OR, 0.64; 95% CL, 0.46–0.88), catechin (4 mg per day increment: OR, 0.49; 95% CL, 0.35–0.70), quercetin (9 mg per day increment: OR, 0.65; 95% CL, 0.44–0.95), and kaempferol (2 mg per day increment: OR, 0.68; 95% CL, 0.51–0.90) among tobacco smokers. There was little association between lung cancer and the flavonoid compounds mentioned above among nonsmokers. Regardless of smoking status, there was little association with total flavonoids: thearubigins, hesperetin, naringenin, and myricetin. In addition, consumption of vegetables, tea, and wine, all of which are rich sources of flavonoids, was associated inversely with lung cancer among tobacco smokers. CONCLUSIONS Certain flavonoid compounds, including epicatechin, catechin, quercetin, and kaempferol, were associated inversely with lung cancer among tobacco smokers, but not among nonsmokers. Further studies of these associations may be warranted. PMID:18327817

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study.

PubMed

Maisonneuve, Patrick; Shivappa, Nitin; Hébert, James R; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia; Gnagnarella, Patrizia

2016-04-01

To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants' diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01-1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk.

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study

PubMed Central

Shivappa, Nitin; Hébert, James R.; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia; Gnagnarella, Patrizia

2016-01-01

Purpose To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. Methods In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants’ diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. Results In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01–1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Conclusions Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk. PMID:25953452

Deaf patient-provider communication and lung cancer screening: Health Information National Trends survey in American Sign Language (HINTS-ASL).

PubMed

Kushalnagar, P; Engelman, Alina; Sadler, G

2018-07-01

To assess whether mode of communication and patient centered communication (PCC) with physicians were associated with the likelihood of deaf smokers inquiring about lung cancer screening. An accessible health survey including questions about PCC, modes of communication, smoking status and lung cancer screening was administered in American Sign Language (HINTS-ASL) to a nationwide sample of deaf adults from February to August 2017. Of 703 deaf adults who answered the lung screening question, 188 were 55-80 years old. The odds ratio of asking about a lung cancer screening test was higher for people with lung disease or used ASL (directly or through an interpreter) to communicate with their physicians. PCC was not associated with asking about a lung cancer screening test. Current or former smokers who are deaf and use ASL are at greater risk for poorer health outcomes if they do not have accessible communication with their physicians. Optimal language access through interpreters or directly in ASL is critical when discussing smoking cessation or lung cancer screening tests. Counseling and shared decision-making will help improve high-risk deaf patients' understanding and decision-making about lung cancer screening. Copyright © 2018 Elsevier B.V. All rights reserved.

MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner.

PubMed

Andriani, Francesca; Majorini, Maria Teresa; Mano, Miguel; Landoni, Elena; Miceli, Rosalba; Facchinetti, Federica; Mensah, Mavis; Fontanella, Enrico; Dugo, Matteo; Giacca, Mauro; Pastorino, Ugo; Sozzi, Gabriella; Delia, Domenico; Roz, Luca; Lecis, Daniele

2018-03-20

Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibroblasts towards a tumor-supporting phenotype. We employed a co-culture-based high-throughput screening to identify specific miRNAs modulating the pro-tumorigenic potential of lung fibroblasts. Multiplex assays and ELISA were instrumental to study the effect of miRNAs on the secretome of both primary and immortalized lung fibroblasts from lung cancer patients and to evaluate plasmatic levels of HGF in heavy smokers. Direct mRNA targeting by miRNAs was investigated through dual-luciferase reporter assay and western blot. Finally, the pro-tumorigenic activity of fibroblasts and their conditioned media was tested by employing in vitro migration experiments and mouse xenografts. We identified miR-16 as a master regulator of fibroblast secretome and showed that its upregulation reduces HGF secretion by fibroblasts, impairing their capacity to promote cancer cell migration. This effect is due to a pleiotropic activity of miR-16 which prevents HGF expression through direct inhibition of FGFR-1 signaling and targeting of HGF mRNA. Mechanistically, miR-16 targets FGFR-1 downstream mediator MEK1, thus reducing ERK1/2 activation. Consistently, chemical or genetic inhibition of FGFR-1 mimics miR-16 activity and prevents HGF production. Of note, we report that primary fibroblast cell lines derived from lungs of heavy smokers express reduced miR-16 levels compared to those from lungs not exposed to smoke and that HGF concentration in heavy smokers' plasma correlates with levels of tobacco exposure. Finally, in vivo experiments confirmed that restoration of miR-16 expression in fibroblasts reduced their ability to promote tumor growth and that HGF plays a central role in the pro-tumorigenic activity of fibroblasts. Overall, these results uncover a central role for miR-16 in regulating HGF production by lung fibroblasts, thus affecting their pro-tumorigenic potential. Correlation between smoking exposure and miR-16 levels could provide novel clues regarding the formation of a tumor-proficient milieu during the early phases of lung cancer development.

Synergistic effect of air pollution and habitual smoking on the retention of inorganic fibers identified as ferruginous bodies in autopsy cases in Mexico City.

PubMed

Salazar-Flores, Margarita; Rivera-Rodríguez, Rosa María; Vázquez-Manriquez, María Eugenia; Arenas-Huertero, Francisco

2009-08-01

In order to evaluate the synergistic effect of habitual smoking and air pollution in Mexico City on the retention of inorganic fibers, ferruginous bodies (FB) were quantified as markers of exposure to inorganic fibers in lung digests from 426 autopsy cases. FB were isolated from 426 lung digests from cases with several lung diseases. The results revealed more retention of FB in the smokers group than in non-smokers: 38 FB per gram (FB/g) versus 11.2 FB/g, respectively (p < 0.05). Male smokers living in Mexico City increased their median to 54 FB/g. This contrasts with the median of outside residents: 11.2 FB/g (p < 0.002). Housewives and manual laborers increased their medians when the smoking habit was positive: from 11 to 14 FB/g, and from 16 to 21.5 FB/g, respectively. There is an effect of tobacco smoke on the retention of more fibers identified as FB when the individuals are males and Mexico City residents.

Smoking cessation results in a clinical lung cancer screening program.

PubMed

Borondy Kitts, Andrea K; McKee, Andrea B; Regis, Shawn M; Wald, Christoph; Flacke, Sebastian; McKee, Brady J

2016-07-01

Lung cancer screening may provide a "teachable moment" for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012(®) high-risk criteria and had an order for CT lung screening. A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715-1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143-0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477-0.877). Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates. A positive exam result correlated with reduced relapse rates among smokers recently quit smoking.

Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma.

PubMed

Schuller, Hildegard M; Al-Wadei, Hussein A N; Majidi, Mourad

2008-10-01

Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulated by cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein and transactivation of the epidermal growth factor receptor and that this pathway is activated by beta-1-adrenoreceptors (beta(1)-ARs) and the non-genomic estrogen receptor beta. Our current in vitro studies with HPL1D and NCI-H322 cells showed that signaling via the gamma-amino butyric acid receptor (GABA(B)R) strongly inhibited base level and isoproterenol-induced cAMP, p-CREB, cyclic adenosine monophosphate response element-luciferase activity and p-extracellular regulated kinase-1 (ERK1)/2 and effectively blocked DNA synthesis and cell migration. The inhibitory effects of gamma-amino butyric acid (GABA) were disinhibited by the GABA(B)R antagonist CGP-35348 or GABA(B)R knockdown. Immunohistochemical investigation of hamster lungs showed significant underexpression of GABA in animals with small airway-derived PACs induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These findings suggest that GABA may have tumor suppressor function in small airway epithelia and the PACs derived from them and that downregulation of GABA by NNK may contribute to the development of this cancer in smokers. Our findings suggest that marker-guided treatment with GABA or a GABA(B)R agonist of individuals with downregulated pulmonary GABA may provide a novel targeted approach for the prevention of PAC in smokers.

Awareness of blindness and other smoking-related diseases and its impact on motivation for smoking cessation in eye patients.

PubMed

Handa, S; Woo, J H; Wagle, A M; Htoon, H M; Au Eong, K G

2011-09-01

Cigarette smoking is a major cause of morbidity and mortality. The association between smoking and eye diseases is less widely recognised relative to other better-known smoking-related conditions. This study aims to assess the awareness and fear of known smoking-related diseases among current smokers attending an ophthalmology outpatient clinic and to evaluate their relative impact on the likelihood of smoking cessation. A cross-sectional survey using a structured interview of randomly selected current smokers attending an eye clinic was conducted. The knowledge of six smoking-related diseases (lung cancer, heart attack, stroke, blindness, other cancers, and other lung diseases) was assessed. The fear of smoking-related conditions and the relative impact of each smoking-related condition on the smoker's motivation to quit smoking were evaluated. Out of 200 current smokers aged from 14 to 83 years, only 42.5% (85 patients) were aware that smoking causes blindness. Smokers' perception of harm caused by smoking was 6.53±3.21 (mean±SD) on a visual analogue scale of 0 to 10. Patients placed blindness as the second most important motivating factor to quit smoking immediately, within 1 year and 5 years, after lung cancer. The awareness of the risk of blindness from smoking was lowest compared with five other smoking-related diseases among eye patients who smoke. However, blindness remains a key motivational factor in smoking cessation and hence should be emphasised as an important negative health consequence of smoking in public health education and anti-smoking campaigns.

Profiling over 1500 lipids in induced lung sputum and the implications in studying lung diseases.

PubMed

t'Kindt, Ruben; Telenga, Eef D; Jorge, Lucie; Van Oosterhout, Antoon J M; Sandra, Pat; Ten Hacken, Nick H T; Sandra, Koen

2015-01-01

Induced lung sputum is a valuable matrix in the study of respiratory diseases. Although the methodology of sputum collection has evolved to a point where it is repeatable and responsive to inflammation, its use in molecular profiling studies is still limited. Here, an in-depth lipid profiling of induced lung sputum using high-resolution liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS) is described. An enormous complexity in lipid composition could be revealed. Over 1500 intact lipids, originating from 6 major lipid classes, have been accurately identified in 120 μL of induced sputum. By number and measured intensity, glycerophospholipids represent the largest lipid class, followed by sphingolipids, glycerolipids, fatty acyls, sterol lipids, and prenol lipids. Several prenol lipids, originating from tobacco, could be detected in the lung sputum of smokers. To illustrate the utility of the methodology in studying respiratory diseases, a comparative lipid screening was performed on lung sputum extracts in order to study the effect of Chronic Obstructive Pulmonary Disease (COPD) on the lung barrier lipidome. Results show that sphingolipid expression in induced sputum significantly differs between smokers with and without COPD.

TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice

PubMed Central

Foronjy, Robert F.; Salathe, Matthias A.; Dabo, Abdoulaye J.; Baumlin, Nathalie; Cummins, Neville; Eden, Edward

2016-01-01

The expression of Toll-like receptor (TLR)-9, a pathogen recognition receptor that recognizes unmethylated CpG sequences in microbial DNA molecules, is linked to the pathogenesis of several lung diseases. TLR9 expression and signaling was investigated in animal and cell models of chronic obstructive pulmonary disease (COPD). We observed enhanced TLR9 expression in mouse lungs following exposure to cigarette smoke. Tlr9−/− mice were resistant to cigarette smoke-induced loss of lung function as determined by mean linear intercept, total lung capacity, lung compliance, and tissue elastance analysis. Tlr9 expression also regulated smoke-mediated immune cell recruitment to the lung; apoptosis; expression of granulocyte-colony stimulating factor (G-CSF), the CXCL5 protein, and matrix metalloproteinase-2 (MMP-2); and protein tyrosine phosphatase 1B (PTP1B) activity in the lung. PTP1B, a phosphatase with anti-inflammatory abilities, was identified as binding to TLR9. In vivo delivery of a TLR9 agonist enhanced TLR9 binding to PTP1B, which inactivated PTP1B. Ptp1b−/− mice had elevated lung concentrations of G-CSF, CXCL5, and MMP-2, and tissue expression of type-1 interferon following TLR9 agonist administration, compared with wild-type mice. TLR9 responses were further determined in fully differentiated normal human bronchial epithelial (NHBE) cells isolated from nonsmoker, smoker, and COPD donors, and then cultured at air liquid interface. NHBE cells from smokers and patients with COPD expressed more TLR9 and secreted greater levels of G-CSF, IL-6, CXCL5, IL-1β, and MMP-2 upon TLR9 ligand stimulation compared with cells from nonsmoker donors. Although TLR9 combats infection, our results indicate that TLR9 induction can affect lung function by inactivating PTP1B and upregulating expression of proinflammatory cytokines. PMID:27288485

Identification of biomarkers for lung cancer in never smokers — EDRN Public Portal

Cancer.gov

The overall goal of this project is to identify, verify and apply biomarkers for the early diagnosis or risk assessment of lung cancer in never smokers. The first year will be regarded as a year of discovery. After successful demonstration of the feasibility of the approach for novel marker discovery, funding will be applied for to perform confirmation and preclinical studies on the biomarkers and validation studies (specific aims 2 and 3, to be performed in years two and three). Year two can be regarded as the year of confirmation and year three as the year of validation.

[The role of spirometry in encouraging smoking cessation in general practice. A pilot study using "lung age"].

PubMed

Lorenzo, A; Noël, F; Lorenzo, M; Van Den Broucke, J

2017-09-01

Our aim was to investigate whether spirometry, performed in general practitioners' offices would change non-motivated smokers' attitudes toward smoking cessation. We performed an interventional, prospective, before-after single-center study, approved by a research ethics committee. We included 74 smokers older than 18years old, who reported no intention to quit smoking, whatever they were visiting general practitioners for. We performed spirometry and gave them their results, FEV 1 /FVC and lung age together with a comment on it. Nine months later, we called them for another assessment. Fifty-six percent were women with an average-age of 46.5, who smoked 26.3 pack-years. Eighty-two percent of them had normal FEV 1 /FVC but lung age was pathological among 38% of them. Nine months later, 61.1% reported an increased motivation to quit smoking. They smoked 10.9 cigarettes per day versus 13,3 at baseline (P=0.0254). Increase in motivation was not statistically related to age, gender, previous smoking cessations, daily smoking, nicotine dependence or an abnormal FEV 1 /VC ratio (P>0.75) but was significantly related to the presence of an abnormal lung age status (P<0.03). This study suggests that spirometry in general practice, combined with the determination of the lung age, may increase motivation towards smoking cessation in smokers who lack motivation. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Beta-cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cell motility by downregulating nicotinic acetylcholine receptor alpha7 signaling

USDA-ARS?s Scientific Manuscript database

Despite the consistent association between a higher intake of the provitamin A carotenoid beta-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-...

Nicotine prevents the apoptosis induced by menadione in human lung cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Tao; Lu Heng; Shang Xuan

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on lung cancer and other illnesses. Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer. However, the mechanism of nicotine action in the development of lung cancer remains largely unknown. In the present study, we designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung cancer cell A549 to be in a physiological nicotine environment, and observed that nicotine promoted cell proliferation and prevented the menadione-induced apoptosis, and exerts its role ofmore » anti-apoptosis by shift of apoptotic stage induced by menadione from late apoptotic stage to early apoptotic stage, in which NF-{kappa}B was up-regulated. Interference analysis of NF-{kappa}B in A549 cells showed that knock down of NF-{kappa}B resulted in apoptosis promotion and counteracted the protective effect of nicotine. The findings suggest that nicotine has potential effect in lung cancer genesis, especially in patients with undetectable early tumor development and development of specific NF-{kappa}B inhibitors would represent a potentially exciting new pharmacotherapy for tobacco-related lung cancer.« less

Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.

PubMed Central

Wiencke, John K; Kelsey, Karl T

2002-01-01

Cigarette smoking by children and adolescents continues to be prevalent, and this fact represents a major public health problem and challenge. Epidemiologic work has previously suggested that exposure of the lung to tobacco carcinogens at an early age may be an independent risk factor for lung cancer. Recent studies at the molecular and cellular levels are consistent with this, now suggesting that early exposure enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. In this paper we hypothesize that adolescence, which is known to be the period of greatest development for the lung, may constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking. The fact that lung development differs by sex might also contribute to apparent gender differences in lung cancer susceptibility. Because this hypothesis has important implications for health policy and tobacco control, additional resources need to be devoted to its further evaluation. Targeted intervention in adolescent smoking may yield even greater reductions in lung cancer occurrence than otherwise anticipated. PMID:12055044

Future initiatives to reduce lung cancer incidence in the United Kingdom: smoking cessation, radon remediation and the impact of social change.

PubMed

Denman, Antony R; Rogers, Stephen; Timson, Karen; Phillips, Paul S; Crockett, Robin Gm; Groves-Kirkby, Christopher J

2015-03-01

Smoking and radon cause lung cancer, with smoking being the more significant risk factor. Although programmes to identify UK houses with raised radon levels and to encourage remedial action started in 1990, uptake has been limited and those most at risk, smokers and young families, are not being reached. The risks from smoking and radon are multiplicative. Public health campaigns have reduced smoking prevalence significantly. Since most radon-induced lung cancers occur in smokers, reducing the number of smokers will reduce the number of radon-induced lung cancers. This article considers the impact of reducing smoking prevalence on the effectiveness of radon remediation programmes, combining this with demographic trends and regional variations to assess implications for future public health. Results on cost-effectiveness of smoking cessation and radon remediation programmes were combined with government figures for smoking prevalence to estimate the number of cancers averted and the cost-effectiveness of such programmes, taking into account demographic changes, including increasing life expectancy. Regional variations in smoking prevalence and smoking cessation programmes were reviewed, comparing these to the geographic variation of radon. The continuing impact of smoking cessation programmes in reducing smoking prevalence will reduce the number of radon-induced lung cancers, but with a lag. Smoking cessation programmes are more cost-effective than radon remediation programmes, presenting an additional opportunity to reduce radon risk to smokers. Regional data show no correlation between smoking prevalence and radon levels. Reduced smoking prevalence reduces the effectiveness of radon remediation programmes. This, coupled with limited uptake of radon remediation, suggests that radon remediation programmes should be targeted, and that an integrated public health policy for smoking and radon is appropriate. Lack of correlation between smoking prevalence and radon suggests that local assessment of relative priorities for public health strategies, such as the 'Total Place' initiative, is appropriate. © Royal Society for Public Health 2014.

Patient navigation for lung cancer screening among current smokers in community health centers a randomized controlled trial.

PubMed

Percac-Lima, Sanja; Ashburner, Jeffrey M; Rigotti, Nancy A; Park, Elyse R; Chang, Yuchiao; Kuchukhidze, Salome; Atlas, Steven J

2018-03-01

Annual chest computed tomography (CT) can decrease lung cancer mortality in high-risk individuals. Patient navigation improves cancer screening rates in underserved populations. Randomized controlled trial was conducted from February 2016 to January 2017 to evaluate the impact of a patient navigation program on lung cancer screening (LCS) among current smokers in five community health centers (CHCs) affiliated with an academic primary care network. We randomized 1200 smokers aged 55-77 years to intervention (n = 400) or usual care (n = 800). Navigators contacted patients to determine LCS eligibility, introduce shared decision making about screening, schedule appointments with primary care physicians (PCPs), and help overcome barriers to obtaining screening and follow-up. Control patients received usual care. The main outcome was the proportion of patients who had any chest CT. Secondary outcomes were the proportion of patients contacted, proportion receiving LCS CTs, screening results and number of lung cancers diagnosed. Of the 400 intervention patients, 335 were contacted and 76 refused participation. Of the 259 participants, 124 (48%) were ineligible for screening; 119 had smoked <30 pack-years, and five had competing comorbidities. Among the 135 eligible participants in the intervention group, 124 (92%) had any chest CT performed. In intention-to-treat analyses, 124 intervention patients (31%) had any chest CT versus 138 control patients (17.3%, P < 0.001). LCS CTs were performed in 94 intervention patients (23.5%) versus 69 controls (8.6%, P < 0.001). A total of 20% of screened patients required follow-up. Lung cancer was diagnosed in eight intervention (2%) and four control (0.5%) patients. A patient navigation program implemented in CHCs significantly increased LCS among high-risk current smokers. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients.

PubMed

Garassino, Marina Chiara; Gelibter, Alain Jonathan; Grossi, Francesco; Chiari, Rita; Soto Parra, Hector; Cascinu, Stefano; Cognetti, Francesco; Turci, Daniele; Blasi, Livio; Bengala, Carmelo; Mini, Enrico; Baldini, Editta; Quadrini, Silvia; Ceresoli, Giovanni Luca; Antonelli, Paola; Vasile, Enrico; Pinto, Carmine; Fasola, Gianpiero; Galetta, Domenico; Macerelli, Marianna; Giannarelli, Diana; Lo Russo, Giuseppe; de Marinis, Filippo

2018-05-03

Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians' request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation-positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Lung function, atopy, specific hypersensitivity, and smoking of workers in the enzyme detergent industry over 11 years.

PubMed

Flood, D F; Blofeld, R E; Bruce, C F; Hewitt, J I; Juniper, C P; Roberts, D M

1985-01-01

A study of 2800 workers employed in three factories of the two major manufacturers of enzymatic products in the United Kingdom covering 11 years of operation from 1969 to 1980 showed that 2344 workers had sufficient lung function data to meet the operational criteria and these were analysed in three separate groups by factory locations. Spirometry and prick tests for specific skin reactions to standardised enzyme were performed at six monthly intervals for the first six years of the study and then annually. Factory enzyme dust and total dust measurements were made to determine the degree of dust exposure of the subjects. The lung function of the factory groups was analysed for the effects of working in the detergent industry, the degree of exposure to enzymes, skin prick test positivity to enzymes, atopicity, and smoking. The 4.5% of workers who had experienced respiratory effects from enzymes were analysed separately. Exposure to the enzyme allergen has had no significant long term effect on the lung function of the detergent workers. A higher proportion of atopics than non-atopics became skin test positive to the allergen and more smokers than non-smokers were sensitised. The overall lung function of detergent workers showed 39 ml/year loss in FEV1 on the 11 year longitudinal study and 51 ml/year loss on the lateral (cross sectional) analysis with better lung function in the south east than the north west of England. In the development of the methodology for the study several potential problems were discovered that could remain unrecognised in a cross sectional analysis performed in isolation.

Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.

PubMed

Kelsen, Steven G; Aksoy, Mark O; Georgy, Mary; Hershman, Richard; Ji, Rong; Li, Xiuxia; Hurford, Matthew; Solomides, Charalambos; Chatila, Wissam; Kim, Victor

2009-05-01

The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1-4) by immunohistochemistry. CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3-4 (P < 0.01 for GOLD 3-4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV(1) (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells.

Lymphoid Follicle Cells in Chronic Obstructive Pulmonary Disease Overexpress the Chemokine Receptor CXCR3

PubMed Central

Kelsen, Steven G.; Aksoy, Mark O.; Georgy, Mary; Hershman, Richard; Ji, Rong; Li, XiuXia; Hurford, Matthew; Solomides, Charalambos; Chatila, Wissam; Kim, Victor

2009-01-01

Rationale: The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. Objectives: We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. Methods: CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1–4) by immunohistochemistry. Measurements and Main Results: CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3–4 (P < 0.01 for GOLD 3–4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV1 (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. Conclusions: These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells. PMID:19218194

Cannabis, tobacco smoking, and lung function: a cross-sectional observational study in a general practice population

PubMed Central

Macleod, John; Robertson, Roy; Copeland, Lorraine; McKenzie, James; Elton, Rob; Reid, Peter

2015-01-01

Background Health concerns around cannabis use have focused on the potential relationship with psychosis but the effect of cannabis smoking on respiratory health has received less attention. Aim To investigate the association between tobacco-only smoking compared with tobacco plus cannabis smoking and adverse outcomes in respiratory health and lung function. Design and setting The design was cross-sectional with two groups recruited: cigarette smokers with tobacco pack-years; cannabis smokers with cannabis joint-years. Recruitment occurred in a general practice in Scotland with 12 500 patients. Method Exposures measured were tobacco smoking (pack-years) and cannabis smoking (joint-years). Cannabis type (resin, herbal, or both) was recorded by self-report. Respiratory symptoms were recorded using NHANES and MRC questionnaires. Lung function was measured by spirometry (FEV1/FVC ratio). Results Participants consisted of 500 individuals (242 males). Mean age of tobacco-only smokers was 45 years; median tobacco exposure was 25 pack-years. Mean age of cannabis and tobacco smokers was 37 years; median tobacco exposure was 19 pack-years, rising to 22.5 when tobacco smoked with cannabis. Although tobacco and cannabis use were associated with increased reporting of respiratory symptoms, this was higher among those who also smoked cannabis. Both tobacco and cannabis users had evidence of impaired lung function but, in fully adjusted analyses, each additional joint-year of cannabis use was associated with a 0.3% (95% confidence interval = 0.0 to 0.5) increase in prevalence of chronic obstructive pulmonary disease. Conclusion In adults who predominantly smoked resin cannabis mixed with tobacco, additional adverse effects were observed on respiratory health relating to cannabis use. PMID:25624312

Cannabis, tobacco smoking, and lung function: a cross-sectional observational study in a general practice population.

PubMed

Macleod, John; Robertson, Roy; Copeland, Lorraine; McKenzie, James; Elton, Rob; Reid, Peter

2015-02-01

Health concerns around cannabis use have focused on the potential relationship with psychosis but the effect of cannabis smoking on respiratory health has received less attention. To investigate the association between tobacco-only smoking compared with tobacco plus cannabis smoking and adverse outcomes in respiratory health and lung function. The design was cross-sectional with two groups recruited: cigarette smokers with tobacco pack-years; cannabis smokers with cannabis joint-years. Recruitment occurred in a general practice in Scotland with 12 500 patients. Exposures measured were tobacco smoking (pack-years) and cannabis smoking (joint-years). Cannabis type (resin, herbal, or both) was recorded by self-report. Respiratory symptoms were recorded using NHANES and MRC questionnaires. Lung function was measured by spirometry (FEV1/FVC ratio). Participants consisted of 500 individuals (242 males). Mean age of tobacco-only smokers was 45 years; median tobacco exposure was 25 pack-years. Mean age of cannabis and tobacco smokers was 37 years; median tobacco exposure was 19 pack-years, rising to 22.5 when tobacco smoked with cannabis. Although tobacco and cannabis use were associated with increased reporting of respiratory symptoms, this was higher among those who also smoked cannabis. Both tobacco and cannabis users had evidence of impaired lung function but, in fully adjusted analyses, each additional joint-year of cannabis use was associated with a 0.3% (95% confidence interval = 0.0 to 0.5) increase in prevalence of chronic obstructive pulmonary disease. In adults who predominantly smoked resin cannabis mixed with tobacco, additional adverse effects were observed on respiratory health relating to cannabis use. © British Journal of General Practice 2015.

Expression of GULP1 in bronchial epithelium is associated with the progression of emphysema in chronic obstructive pulmonary disease.

PubMed

Datta, Sayantan; Nam, Hae-Seong; Hayashi, Masamichi; Maldonado, Leonel; Goldberg, Rachel; Brait, Mariana; Sidransky, David; Illei, Peter; Baras, Alex; Vij, Neeraj; Hoque, Mohammad O

2017-03-01

GULP1 functions as a cytoplasmic adaptor protein involved in the engulfment of apoptotic cells. The aim of this study was to investigate the expression and/or promoter methylation of GULP1 in the bronchial tissue and the lung parenchyma of chronic obstructive pulmonary disease (COPD) patients and control subjects without COPD (non-smokers and smokers). Using a case-control design, we selected a group of 15 subjects with non-small cell lung carcinoma (NSCLC), 15 subjects with COPD, 9 subjects of without COPD (4 non-smokers and 5 smokers) as controls. We studied the expression of GULP1 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry (IHC). To understand the mechanistic aspect of GULP1 expression in COPD and NSCLC, we performed quantitative methylation specific PCR (QMSP) in cases and controls of COPD and NSCLC. Our IHC analysis revealed that GULP1 was not expressed in pneumocytes or alveolar macrophages of COPD patients, however, GULP1 expression was detected at different levels in bronchial epithelium. GULP1 expression statistically correlated with severity of COPD-emphysema (p = 0.001, χ 2 test). GULP1 promoter methylation was not observed by QMSP assay in any of the samples thereby excluding the role of promoter methylation in differential expression of GULP1 in COPD and NSCLC. This study provides preliminary observations on the differences in GULP1 expression in different cellular components of lung tissues from COPD and control subjects. Our findings suggest a potential role for GULP1 in the pathogenesis and progression of COPD-emphysema that warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Loss of heterozygosity patterns provide fingerprints for genetic heterogeneity in multistep cancer progression of tobacco smoke-induced non-small cell lung cancer.

PubMed

Pan, Hongjie; Califano, Joseph; Ponte, Jose F; Russo, Andrea L; Cheng, Kuang-hung; Thiagalingam, Arunthathi; Nemani, Pratima; Sidransky, David; Thiagalingam, Sam

2005-03-01

Dilution end point loss of heterozygosity (LOH) analysis, a novel approach for the analysis of LOH, was used to evaluate allelic losses with the use of 21 highly polymorphic microsatellite markers at nine chromosomal sites most frequently affected in smoking-related non-small cell lung cancers. Allelotyping was done for bronchial epithelial cells and matching blood samples from 23 former and current smokers and six nonsmokers as well as in 33 adenocarcinomas and 25 squamous cell carcinomas (SCC) and corresponding matching blood from smokers. Major conclusions from these studies are as follows: (a) LOH at chromosomal sites 8p, 9p, 11q, and 13q (P >0.05, Fisher's exact test) are targeted at the early stages, whereas LOH at 1p, 5q, 17p, and 18q (P <0.05, Fisher's exact test) occur at the later stages of non-small cell lung cancer progression; (b) LOH at 1p, 3p, 5q, 8p, 9p, 11q, 13q, 17p, and 18q occurs in over 45% of the tobacco smokers with SCC and adenocarcinoma; (c) compared with bronchial epithelial cells from smokers, there is a significantly higher degree of LOH at 1p, 5q, and 18q in adenocarcinoma and at 1p, 3p, and 17p in SCC (P <0.05, Fisher's exact test). We propose that lung cancer progression induced by tobacco smoke occurs in a series of target gene inactivations/activations in defined modules of a global network. The gatekeeper module consists of multiple alternate target genes, which is inclusive of but not limited to genes localized to chromosomal loci 8p, 9p, 11q, and 13q.

Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.

PubMed

McEvoy, Cindy T; Schilling, Diane; Clay, Nakia; Jackson, Keith; Go, Mitzi D; Spitale, Patricia; Bunten, Carol; Leiva, Maria; Gonzales, David; Hollister-Smith, Julie; Durand, Manuel; Frei, Balz; Buist, A Sonia; Peters, Dawn; Morris, Cynthia D; Spindel, Eliot R

2014-05-01

Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. clinicaltrials.gov Identifier: NCT00632476.

Lung cancer in patients with lung transplants.

PubMed

Espinosa, D; Baamonde, C; Illana, J; Arango, E; Carrasco, G; Moreno, P; Algar, F J; Alvarez, A; Cerezo, F; Santos, F; Vaquero, J M; Redel, J; Salvatierra, A

2012-09-01

The aim of our study was to describe the incidence of lung cancer in patients after lung transplantation (LT). We performed an observational, retrospective, descriptive study based on data from 340 patients undergoing lung transplantation between October 1993 and December 2010. We collected data about the donors, recipients, intra- and postoperative periods, and survivals. We identified 9 (2.6%) patients who developed lung cancer after LT. Their average age was 56 ± 9.3 years (range, 18-63). All cases were men with 8/9 (88.8%) having received a single lung transplant. All cancers developed in the native lung. The indications for transplantation were: emphysema type chronic obstructive pulmonary disease (COPD; n = 5), idiopathic pulmonary fibrosis (n = 3), or cystic fibrosis (n = 1); 77% of them were former smokers. All of the COPD patient were affected. The interval from transplantation to diagnosis was 53.3 ± 12 months (range 24-86). Survival after cancer diagnosis was 49.3 ± 6.3 (range = 0-180) months. LT was associated with a relatively high incidence of lung cancer, particularly in the native lung. In our series, lung cancer was related more to patients with emphysema-type COPD and a history of smoking. We believe that these patients should be closely followed to establish the diagnosis and apply early treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

MMP12, Lung Function, and COPD in High-Risk Populations

PubMed Central

Hunninghake, Gary M.; Cho, Michael H.; Tesfaigzi, Yohannes; Soto-Quiros, Manuel E.; Avila, Lydiana; Lasky-Su, Jessica; Stidley, Chris; Melén, Erik; Söderhäll, Cilla; Hallberg, Jenny; Kull, Inger; Kere, Juha; Svartengren, Magnus; Pershagen, Göran; Wickman, Magnus; Lange, Christoph; Demeo, Dawn L.; Hersh, Craig P.; Klanderman, Barbara J.; Raby, Benjamin A.; Sparrow, David; Shapiro, Steven D.; Silverman, Edwin K.; Litonjua, Augusto A.; Weiss, Scott T.; Celedón, Juan C.

2010-01-01

BACKGROUND Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups. METHODS We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV1]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV1 and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. RESULTS The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [−82A→G]) was positively associated with FEV1 in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2×10−6). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P = 0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P = 0.005) and among participants in a family-based study of early-onset COPD (P = 0.006). CONCLUSIONS The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers. PMID:20018959

Will chronic e-cigarette use cause lung disease?

PubMed

Rowell, Temperance R; Tarran, Robert

2015-12-15

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. Copyright © 2015 the American Physiological Society.

Will chronic e-cigarette use cause lung disease?

PubMed Central

Rowell, Temperance R.

2015-01-01

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. PMID:26408554

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

PubMed

Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang; Lynch, David A; Strand, Matthew J; van Beek, Edwin J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

2018-02-01

Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruano-Ravina, Alberto, E-mail: alberto.ruano@usc.es; CIBER de Epidemiología y Salud Pública CIBERESP, Barcelona; García-Lavandeira, José Antonio

We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjustedmore » also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78–2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93–5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. - Highlights: • Some leisure time activities are associated with the exposure to carcinogenic substances. • These activities are model-making, painting (artistic or not), furniture refinishing or wood working. • Few studies have assessed lung cancer risk due to these hobbies and none in never-smokers. • Leisure activities related to exposure to carcinogenic substances present higher lung cancer risk. • The risk is higher when these activities are performed for more than 10 years.« less

Association Between Environmental Tobacco Smoke Exposure and the Occurrence of EGFR Mutations and ALK Rearrangements in Never-smokers With Non-Small-cell Lung Cancer: Analyses From a Prospective Multinational ETS Registry.

PubMed

Soo, Ross A; Kubo, Akihito; Ando, Masahiko; Kawaguchi, Tomoya; Ahn, Myung-Ju; Ou, Sai-Hong Ignatius

2017-09-01

Molecular studies have demonstrated actionable driver oncogene alterations are more frequent in never-smokers with non-small-cell lung cancer (NSCLC). The etiology of these driver oncogenes in patients with NSCLC remains unknown, and environmental tobacco smoke (ETS) is a potential cause in these cases. We assembled clinical and genetic information for never-smoker patients with NSCLC accrued in Japan, Korea, Singapore, and the United States. To determine an association between cumulative ETS and activating EGFR mutations or ALK rearrangements, the Mantel extension test was used. Multivariate analysis on activating EGFR and ALK gene rearrangements was performed using the generalized linear mixed model with nations as a random effect. From July 2007 to December 2012, 498 never-smokers with pathologically proven NSCLC were registered and tested for the association between ETS and EGFR and ALK status. EGFR mutations were more frequent in the ever-ETS cohort (58.4%) compared with the never-ETS cohort (39.6%), and the incidence of EGFR mutations was significantly associated with the increment of cumulative ETS (cETS) in female never-smokers (P = .033), whereas the incidence of ALK rearrangements was not significantly different between the ever-ETS and never-ETS cohorts. Odds ratio for EGFR mutations for each 10-year increment in cETS was 1.091 and 0.89 for female and male never-smokers (P = .031 and P = .263, respectively). Increased ETS exposure was closely associated with EGFR mutations in female never-smokers with NSCLC in the expanded multinational cohort. However, the association of ETS and ALK rearrangements in never-smokers with NSCLC was not significant. Copyright © 2017 Elsevier Inc. All rights reserved.

Smokers' responses to television advertisements about the serious harms of tobacco use: pre-testing results from 10 low- to middle-income countries.

PubMed

Wakefield, Melanie; Bayly, Megan; Durkin, Sarah; Cotter, Trish; Mullin, Sandra; Warne, Charles

2013-01-01

While television advertisements (ads) that communicate the serious harms of smoking are effective in prompting quitting-related thoughts and actions, little research has been conducted among smokers in low- to middle-income countries to guide public education efforts. 2399 smokers aged 18-34 years in 10 low- to middle-income countries (Bangladesh, China, Egypt, India, Indonesia, Mexico, Philippines, Russia, Turkey and Vietnam) viewed and individually rated the same five anti-smoking ads on a standard questionnaire and then engaged in a structured group discussion about each ad. Multivariate logistic regression analysis, with robust SEs to account for the same individual rating multiple ads, was performed to compare outcomes (message acceptance, perceived personalised effectiveness, feel uncomfortable, likelihood of discussing the ad) across ads and countries, adjusting for covariates. Ads by country interactions were examined to assess consistency of ratings across countries. Three ads with graphic imagery performed consistently highly across all countries. Two of these ads showed diseased human tissue or body parts, and a third used a disgust-provoking metaphor to demonstrate tar accumulation in smokers' lungs. A personal testimonial ad performed more variably, as many smokers did not appreciate that the featured woman's lung cancer was due to smoking or that her altered physical appearance was due to chemotherapy. An ad using a visual metaphor for lung disease was also more variable, mostly due to lack of understanding of the term 'emphysema'. Television ads that graphically communicate the serious harms of tobacco use are likely to be effective with smokers in low- to middle-income countries and can be readily translated and adapted for local use. Ads with complex medical terms or metaphors, or those that feature personal testimonials, are more variable and at least require more careful pre-testing and adaptation to maximise their potential.

Residential Radon Exposure and Lung Cancer: Evidence of an Inverse Association in Washington State.

ERIC Educational Resources Information Center

Neuberger, John S.; And Others

1992-01-01

Presents results of a descriptive study of lung cancer death rates compared to county levels of radon in Washington State. Age-specific death rates were computed for white female smokers according to radon exposure. A significant lung cancer excess was found in lowest radon counties. No significant difference was found between the proportion of…

Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers.

PubMed

Seo, Takayuki; Pahwa, Punam; McDuffie, Helen H; Yurube, Keigo; Egoshi, Masayoshi; Umemoto, Yuichiro; Ghosh, Sunita; Fukushima, Yumi; Nakagawa, Kazuko

2008-06-01

The activity of the enzymes that metabolize tobacco smoke may affect the susceptibility to chronic obstructive pulmonary disease (COPD). Cytochrome P450 (CYP) 3A5 is expressed selectively over CYP3A4 in human lung, but the association between the CYP3A5 polymorphisms and the airway injury is unknown. Two hundred and six male Saskatchewan grain workers participated in this longitudinal study, and their lung function values of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), respiratory symptoms, smoking status, and the occupational history were analyzed. A significant interactive effect was observed between the CYP3A5 genotype and current smoking status on FEV1, and the annual decline rates of FEV1 and FVC in current smokers were greater among CYP3A5*1/*3 carriers than CYP3A5*3/*3 carriers (-48.7+/-16.4 vs. -31.5+/-4.7 ml/years, P=0.02; -27.4+/-18.9 vs. -5.8+/-6.5 ml/years, P=0.04). The incidences of chronic cough and COPD were also higher in current smokers with CYP3A5*1/*3 than in nonsmokers and current smokers with CYP3A5*3/*3. The adjusted odds ratios for chronic cough and COPD current smokers with CYP3A5*1/*3 versus nonsmokers with the CYP3A5*3/*3 genotype were 11.4 (P=0.009) and 4.3 (P=0.13), respectively. The results suggest that CYP3A5*1 may be a novel genetic risk factor for airway injury in smokers, and that CYP3A5 may play a role in airway injury owing to the bioactivation of chemicals in tobacco smoke.

A Review of Pulmonary Toxicity of Electronic Cigarettes in the Context of Smoking: A Focus on Inflammation.

PubMed

Shields, Peter G; Berman, Micah; Brasky, Theodore M; Freudenheim, Jo L; Mathe, Ewy; McElroy, Joseph P; Song, Min-Ae; Wewers, Mark D

2017-08-01

The use of electronic cigarettes (e-cigs) is increasing rapidly, but their effects on lung toxicity are largely unknown. Smoking is a well-established cause of lung cancer and respiratory disease, in part through inflammation. It is plausible that e-cig use might affect similar inflammatory pathways. E-cigs are used by some smokers as an aid for quitting or smoking reduction, and by never smokers (e.g., adolescents and young adults). The relative effects for impacting disease risk may differ for these groups. Cell culture and experimental animal data indicate that e-cigs have the potential for inducing inflammation, albeit much less than smoking. Human studies show that e-cig use in smokers is associated with substantial reductions in blood or urinary biomarkers of tobacco toxicants when completely switching and somewhat for dual use. However, the extent to which these biomarkers are surrogates for potential lung toxicity remains unclear. The FDA now has regulatory authority over e-cigs and can regulate product and e-liquid design features, such as nicotine content and delivery, voltage, e-liquid formulations, and flavors. All of these factors may impact pulmonary toxicity. This review summarizes current data on pulmonary inflammation related to both smoking and e-cig use, with a focus on human lung biomarkers. Cancer Epidemiol Biomarkers Prev; 26(8); 1175-91. ©2017 AACR . ©2017 American Association for Cancer Research.

Knowledge of the signs and symptoms and risk factors of lung cancer in Australia: mixed methods study.

PubMed

Crane, Melanie; Scott, Nicola; O'Hara, Blythe J; Aranda, Sanchia; Lafontaine, Mayanne; Stacey, Ingrid; Varlow, Megan; Currow, David

2016-06-13

Lung cancer is the leading cause of cancer death in Australia. There is potential that health promotion about the risks and warning signs of lung cancer could be used to reduce delays in symptom presentation when symptoms are first detected. This study investigated knowledge, attitudes and beliefs which might impact help-seeking behaviour and could provide insight into possible public health interventions in New South Wales (NSW). A convergent mixed method study design was used wherein data from 16 qualitative focus groups of residents (40+ years), purposefully recruited and stratified by smoking status, age and geography (metropolitan/regional), were compared with a CATI administered population-wide telephone survey (n = 1,000) using the Cancer Research UK cancer awareness measure (LungCAM). Qualitative findings were analysed thematically using NVIVO. Logistic regression analysis was used to investigate predictors of symptom knowledge in STATA. Findings were integrated using triangulation techniques. Across focus groups, haemoptysis was the only symptom creating a sense of medical urgency. Life experiences evoked a 'wait and see' attitude to any health deterioration. Perceived risk was low amongst those at risk with current smokers preferring to deny their risk while former smokers were generally unaware of any ongoing risk. The quantitative sample consisted of females (62 %), 40-65 years (53 %), low SES (53 %), former (46 %) and current smokers (14 %). In quantitative findings, haemoptysis and dyspnoea were the most recognised symptoms across the sample population. Age (<65 years), sex (female) and high socio-economic status contributed to a higher recognition of symptoms. Smoking was recognised as a cause of lung cancer, yet ever-smokers were less likely to recognise the risk of lung cancer due to second-hand smoke (OR 0.7 95 % CI 0.5-0.9). While there was some recognition of risk factors and symptoms indicative of lung cancer, there was disparity across the sample population. The qualitative findings also suggest that knowledge may not lead to earlier presentation; a lack of urgency about symptoms considered trivial, and smoking-related barriers such as stigma may also contribute to time delays in presentation. Public health interventions may be required to increase awareness of risk and emphasise the importance of seeking medical attention for ongoing symptoms.

A cross-sectional survey investigating the desensitisation of graphic health warning labels and their impact on smokers, non-smokers and patients with COPD in a London cohort

PubMed Central

Ratneswaran, Culadeeban; Chisnall, Ben; Drakatos, Panagis; Sivakumar, Sukhanthan; Sivakumar, Bairavie; Barrecheguren, Miriam; Douiri, Abdel; Steier, Joerg

2014-01-01

Objectives There is a lack of evidence regarding the effectiveness of graphic health warning labels (GHWL) in different individuals, including patients with chronic obstructive pulmonary disease (COPD). Investigating knowledge and attitudes may allow better implementation of future public health policies. We hypothesised that differences in the impact of GHWL exist between non-smokers, smokers and patients with COPD, with decreased efficacy in those groups who are longer and more frequently exposed to them. Participants and setting 163 participants (54% male, aged 21–80) including 60 non-smokers, 53 smokers and 50 patients with COPD (Gold stage II–IV), attending London respiratory outpatient clinics, participated in case-controlled surveys (50 items). Outcome measures Ten different GHWL were shown and demographics, smoking history, plans to quit, smoking-risk awareness, emotional response, processing and impact of GHWL on behaviour were recorded. Patients were further asked to prioritise the hypothetical treatment or prevention of five specific smoking-related diseases. Results Smokers, in particular those with COPD, were less susceptible to GHWL than non-smokers; 53.4% of all participants expressed fear when looking at GHWL, non-smokers (71.9%) more so than smokers (39.8%, p<0.001). COPD participants were less aware of the consequences than non-COPD participants (p<0.001), including an awareness of lung cancer (p=0.001). Lung cancer (95%), oral cancer (90.2%), heart disease (84.7%) and stroke (71.2%) were correctly associated with smoking, whereas blindness was least associated (23.9%). However, blindness was prioritised over oral cancer, stroke and in patients with COPD also over heart disease when participants were asked about hypothetical treatment or prevention. Conclusions GHWL are most effective in non-smokers and a desensitisation effect was observed in smokers and patients with COPD. As a consequence, a tailored and concerted public health approach to use such messages is required and ‘blindness’ deserves to be mentioned in this context because of an unexpectedly high-deterring impact. PMID:24996914

Body mass index modulates aromatic DNA adduct levels and their persistence in smokers.

PubMed

Godschalk, Roger W L; Feldker, Dorien E M; Borm, Paul J A; Wouters, Emiel F M; van Schooten, Frederik-Jan

2002-08-01

Smokers with a low body mass index (BMI; weight/height(2)) have a higher risk for developing lung malignancies as compared with smokers of average weight, but there is no mechanistic explanation for this observation. Carcinogens in cigarette smoke are thought to elicit cancer by the formation of DNA adducts, which give the opportunity to additionally investigate the biological link between BMI and lung cancer. DNA adduct levels in peripheral blood lymphocytes of 24 healthy smoking volunteers (0.76 +/- 0.41 adducts per 10(8) nucleotides) positively correlated with cigarette consumption (r = 0.51; P = 0.01) and were inversely related with BMI (r = -0.48; P = 0.02). A significant overall relationship was observed when both parameters were included in multiple regression analysis (r = 0.63; P = 0.007). Moreover, body composition may affect DNA adduct persistence, because lipophilic tobacco smoke-derived carcinogens accumulate in adipose tissue and can be mobilized once exposure ceases. Therefore, DNA adduct levels and BMI were reassessed in all of the subjects after a nonsmoking period of 22 weeks. Adduct levels declined to 0.44 +/- 0.23 per 10(8) nucleotides (P = 0.002), and the estimated half-life was 11 weeks on the basis of exponential decay to background levels in never-smoking controls (0.33 +/- 0.18 per 10(8) nucleotides). Overweight subjects (BMI >25) with little weight gain after smoking cessation (

Smoking-related interstitial lung diseases.

PubMed

Caminati, A; Graziano, P; Sverzellati, N; Harari, S

2010-12-01

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

Epidermal growth factor receptor mutations in lung adenocarcinoma in Malaysian patients.

PubMed

Liam, Chong-Kin; Wahid, Mohamed Ibrahim A; Rajadurai, Pathmanathan; Cheah, Yoke-Kqueen; Ng, Tiffany Shi-Yeen

2013-06-01

Despite available data from other Asian countries, the prevalence of epidermal growth factor receptor (EGFR) mutations among lung adenocarcinoma patients has not been reported in Malaysia. This study sought to determine the frequency of EGFR mutations among multiethnic Malaysian patients diagnosed with lung adenocarcinoma. Demographic and clinical information of patients whose lung adenocarcinoma biopsy specimens were submitted for EGFR mutation testing at Sime Darby Medical Center from 2009 to 2011 were analyzed. EGFR mutations at exons 18, 19, 20, and 21 were detected either through bidirectional sequencing or real-time polymerase chain reaction. Among 812 patients in the study, 49% were female, 63.7% were ethnic Chinese, 29.4% Malay, 4.8% Indian, and 2.1% other ethnic groups. Mutations were present in the tumors of 321 patients (39.5%), with mutations at exons 19 (23.5%) and 21 (14.9%) being the most common. Mutations were significantly more frequent among women than in men (52.5% versus 27.8%, p < 0.001). Although mutations were more common among Chinese (40.8%) compared with Malay (37.2%) or Indian (33.3%) patients, the difference was not statistically significant (p = 0.591). Of 211 patients with smoking history records, never-smokers had a higher mutation rate compared with ever-smokers (54.8% versus 20.7%, p < 0.001). EGFR mutations were present in 39.5% of patients. Mutations were more common in women and never-smokers with no differences in mutation frequency between different ethnicities. Because of the high mutation rates, reflex testing for EGFR mutation should be a routine practice for advanced lung adenocarcinoma patients in Malaysia.

Clinical Validation of a miRNA Blood Test to Identify High-Risk Individuals Eligible for Low-Dose Computed Tomography Screening for Lung Cancer Early Detection

DTIC Science & Technology

2015-10-01

screening. The project requires the use of serum samples obtained from at-risk subjects (heavy smokers with defined characteristics) undergoing...screening. The project requires the use of serum samples obtained from at-risk subjects (heavy smokers with defined characteristics) that were collected

Pulmonary function response in smokers and patients with chronic obstructive lung diseae (COPD) following exposure to concentrated fine (PM2.5) particles

EPA Science Inventory

Population-based studies strongly suggest that smokers and patients with COPD may be susceptible to particulate matter (PM). The reported associations were stronger with fine than coarse PM .These findings, however, have not been supported by laboratory or clinical data. We stu...

Childhood-Onset Asthma in Smokers. Association between CT Measures of Airway Size, Lung Function, and Chronic Airflow Obstruction

PubMed Central

Hardin, Megan E.; Come, Carolyn E.; San José Estépar, Raúl; Ross, James C.; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K.; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K.; Crapo, James D.; Lynch, David A.; Make, Barry; Barr, R. Graham; Hersh, Craig P.; Washko, George R.

2014-01-01

Rationale and Objectives: Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. Methods: We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Measurements and Main Results: Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. Conclusion: In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764). PMID:25296268

Base damage, local sequence context and TP53 mutation hotspots: a molecular dynamics study of benzo[a]pyrene induced DNA distortion and mutability

PubMed Central

Menzies, Georgina E.; Reed, Simon H.; Brancale, Andrea; Lewis, Paul D.

2015-01-01

The mutational pattern for the TP53 tumour suppressor gene in lung tumours differs to other cancer types by having a higher frequency of G:C>T:A transversions. The aetiology of this differing mutation pattern is still unknown. Benzo[a]pyrene,diol epoxide (BPDE) is a potent cigarette smoke carcinogen that forms guanine adducts at TP53 CpG mutation hotspot sites including codons 157, 158, 245, 248 and 273. We performed molecular modelling of BPDE-adducted TP53 duplex sequences to determine the degree of local distortion caused by adducts which could influence the ability of nucleotide excision repair. We show that BPDE adducted codon 157 has greater structural distortion than other TP53 G:C>T:A hotspot sites and that sequence context more distal to adjacent bases must influence local distortion. Using TP53 trinucleotide mutation signatures for lung cancer in smokers and non-smokers we further show that codons 157 and 273 have the highest mutation probability in smokers. Combining this information with adduct structural data we predict that G:C>T:A mutations at codon 157 in lung tumours of smokers are predominantly caused by BPDE. Our results provide insight into how different DNA sequence contexts show variability in DNA distortion at mutagen adduct sites that could compromise DNA repair at well characterized cancer related mutation hotspots. PMID:26400171

Childhood-onset asthma in smokers. association between CT measures of airway size, lung function, and chronic airflow obstruction.

PubMed

Diaz, Alejandro A; Hardin, Megan E; Come, Carolyn E; San José Estépar, Raúl; Ross, James C; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K; Crapo, James D; Lynch, David A; Make, Barry; Barr, R Graham; Hersh, Craig P; Washko, George R

2014-11-01

Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Implication of a chromosome 15q15.2 locus in regulating UBR1 and predisposing smokers to MGMT methylation in lung

PubMed Central

Leng, Shuguang; Wu, Guodong; Collins, Leonard B.; Thomas, Cynthia L.; Tellez, Carmen S.; Jauregui, Andrew R.; Picchi, Maria A.; Zhang, Xiequn; Juri, Daniel E.; Desai, Dhimant; Amin, Shantu G.; Crowell, Richard E.; Stidley, Christine A.; Liu, Yushi; Swenberg, James A.; Lin, Yong; Wathelet, Marc G.; Gilliland, Frank D.; Belinsky, Steven A.

2015-01-01

O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that protects cells from carcinogenic effects of alkylating agents; however, MGMT is silenced by promoter hypermethylation during carcinogenesis. A single nucleotide polymorphism (SNP) in an enhancer in the MGMT promoter was previously identified to be highly significantly associated with risk for MGMT methylation in lung cancer and sputum from smokers. To further genetic investigations, a genome-wide association and replication study was conducted in two smoker cohorts to identify novel loci for MGMT methylation in sputum that were independent of the MGMT enhancer polymorphism. Two novel trans-acting loci (15q15.2 and 17q24.3) that were identified acted together with the enhancer SNP to empower risk prediction for MGMT methylation. We found that the predisposition to MGMT methylation arising from the 15q15.2 locus involved regulation of the ubiquitin protein ligase E3 component UBR1. UBR1 attenuation reduced turnover of MGMT protein and increased repair of O6-methylguanine in nitrosomethylurea-treated human bronchial epithelial cells (HBEC), while also reducing MGMT promoter activity and abolishing MGMT induction. Overall, our results substantiate reduced gene transcription as a major mechanism for predisposition to MGMT methylation in the lungs of smokers, and support the importance of UBR1 in regulating MGMT homeostasis and DNA repair of alkylated DNA adducts in cells. PMID:26183928

[Factors predictive of good motivation to quit smoking among Moroccan smokers attending a lung disease outpatient clinic in 2008].

PubMed

Bouaïti, E; Mzouri, M; Sbaï-Idrissi, K; Razine, R; Kassouati, J; Lamrabet, M; Hassouni, F; Ouaaline, M; Benbrahim, N Fikri

2010-02-01

Motivations for cessation of smoking should be studied to determine which factors have an impact. Educational messages can then be developed to help smokers become more successful in adopting healthy behavior. The objective of our work was to determine the factors influencing the quality of motivation for smoking cessation among patients attending a lung disease clinic. Between March and June 2008, patients attending the outpatient clinical of the Moulay Youssef Hospital Department of Pneumology in Rabat were studied. Data on the smoking status and motivation to stop smoking (Richmond's test) were collected using a standardized questionnaire. A logistic regression model was developed to analyze the quality of their motivation to quit smoking. The median age for smoking the first cigarette was low (<20 years); pharmacological dependence on nicotine was low (Fagerström score<8 in 71.8%). More than a third of patients (36.6%) had already intended to cease smoking. According to the Richmond test, only 46.0% were well motivated (score>or=8). At multivariate analysis, factors predictive of a good motivation to quit smoking were a previous attempt to stop smoking (OR=5.4 [2.5-11.7]), severe disease (OR=3.7 [1.6-8.2]). Beginning the tobacco addiction before the age of 18 years was predictive of poor motivation (OR=2.7 [1.4-5.3]). Our investigation provides evidence in favor of searching for different factors which might affect motivation to stop smoking among patients seeking care in a lung disease clinic. Lung specialists, who manage the large majority of these patients should be particularly active in this area.

Improved health of hospitality workers after a Swiss cantonal smoking ban.

PubMed

Durham, André-Dante; Bergier, Samuel; Morisod, Xavier; Locatelli, Isabella; Zellweger, Jean-Pierre; Huynh, Cong Khanh; Cornuz, Jacques

2011-12-22

Hospitality workers are a population particularly at risk from the noxious effects of environmental tobacco smoke (ETS). The Canton of Vaud, Switzerland banned smoking in public places in September 2009. This prospective study addresses the impact of the ban on the health of hospitality workers. ETS exposure was evaluated using a passive sampling device that measures airborne nicotine; lung function was assessed by spirometry; health-related quality of life, ETS exposure symptoms and satisfaction were measured by questionnaire. 105 participants (smokers and non-smokers) were recruited initially and 66 were followed up after one year. ETS exposure was significantly lower after the ban. Hospitality workers had lower pre-ban forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values than expected. FEV1 remained stable after the ban, with a near-significant increase in the subgroup of asthmatics only. FVC increased at one year follow-up from 90.42% to 93.05% (p = 0.02) in the entire cohort; women, non-smokers and older participants gained the greatest benefit. The health survey showed an increase in physical wellbeing after the ban, the greatest benefit being observed in non-smokers. ETS exposure symptoms were less frequent after the ban, especially red and irritated eyes and sneezing. The new law was judged useful and satisfactory by the vast majority of employees, including smokers. The recent cantonal ban on smoking in public places brought about an improvement in lung function, physical well-being and ETS symptoms of hospitality workers, including smokers.

Cigarette smoke induces the expression of Notch3, not Notch1, protein in lung adenocarcinoma.

PubMed

Cheng, Zhenshun; Tan, Qiuyue; Tan, Weijun; Zhang, L I

2015-08-01

The aim of the present study was to determine the effect of cigarette smoke on the expression of Notch proteins in lung adenocarcinoma (LAC). Protein expression levels of Notch1 and Notch3 were analyzed using immunohistochemistry in 102 human LAC specimens. Of these, 52 were obtained from smokers and 50 from non-smokers. In addition, cigarette smoke extract (CSE) at varying concentrations (1, 2.5 and 5%) was administered to A549 cells. The expression of Notch1 and Notch3 protein was then detected by western blot analysis at different time points (0, 8, 24 and 48 h). Of the 102 LAC specimens, 42 (41.2%) were positive for Notch1 and 63 (61.8%) were positive for Notch3. There was no significant difference in the level of Notch1 expression between smokers and non-smokers with LAC (P>0.05). The positive rate and staining intensity of Notch3 expression were increased in the smokers compared with the non-smokers (P<0.05). The expression of Notch3 protein in A549 cells increased in a time- and dose-dependent manner following treatment with CSE, whilst the expression of Notch1 protein appeared stable. The results suggested that cigarette smoke was able to induce the expression of Notch3, not Notch1, protein in LAC. The data revealed an upregulation of Notch3 in LAC following cigarette smoke exposure. Such findings may provide a novel therapeutic target for the treatment of LAC.

Consumer's Guide to Radon Reduction: How to Fix Your Home

EPA Pesticide Factsheets

Radon is the leading cause of lung cancer for non-smokers and the second leading cause of lung cancer for the general population. Learn more about testing your home for radon, and how to select a contractor if you have high levels of radon present.

Serum B vitamin levels and risk of lung cancer.

PubMed

Johansson, Mattias; Relton, Caroline; Ueland, Per Magne; Vollset, Stein Emil; Midttun, Øivind; Nygård, Ottar; Slimani, Nadia; Boffetta, Paolo; Jenab, Mazda; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Kaaks, Rudolf; Rohrmann, Sabine; Boeing, Heiner; Weikert, Cornelia; Bueno-de-Mesquita, H Bas; Ros, Martine M; van Gils, Carla H; Peeters, Petra H M; Agudo, Antonio; Barricarte, Aurelio; Navarro, Carmen; Rodríguez, Laudina; Sánchez, Maria-José; Larrañaga, Nerea; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E; Crowe, Francesca; Gallo, Valentina; Norat, Teresa; Krogh, Vittorio; Masala, Giovanna; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Rasmuson, Torgny; Hallmans, Göran; Riboli, Elio; Vineis, Paolo; Brennan, Paul

2010-06-16

B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine. Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65). Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.

Smoking cessation results in a clinical lung cancer screening program

PubMed Central

McKee, Andrea B.; Regis, Shawn M.; Wald, Christoph; Flacke, Sebastian; McKee, Brady J.

2016-01-01

Background Lung cancer screening may provide a “teachable moment” for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Methods Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012® high-risk criteria and had an order for CT lung screening. Results A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715–1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143–0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477–0.877). Conclusions Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates. A positive exam result correlated with reduced relapse rates among smokers recently quit smoking. PMID:27606076

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability

PubMed Central

Zago, Michela; Sheridan, Jared A.; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H.; Hamid, Qutayba

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients. PMID:28749959

Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.

PubMed

2017-07-01

We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P  < .001). Using bronchial gene expression data from the AEGIS-1 patients, we found statistically significant concordant cancer-associated gene expression alterations between the two airway sites ( P  < .001). Differentially expressed genes in the nose were enriched for genes associated with the regulation of apoptosis and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P  = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P  = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

PubMed

Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

Radiation and Smoking Effects on Lung Cancer Incidence by Histological Types Among Atomic Bomb Survivors

PubMed Central

Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

2014-01-01

While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1–4.6) for small-cell carcinoma, 0.75 (0.3–1.3) for adenocarcinoma, and 0.27 (0–1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. PMID:22862780

Former smokers with non-small-cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis.

PubMed

Zheng, Shanbo; Wang, Rui; Zhang, Yang; Pan, Yunjian; Cheng, Chao; Zheng, Difan; Sun, Yihua; Chen, Haiquan

2016-08-01

The aim of this present investigation was to evaluate the clinicopathologic characteristics, oncogenic drivers, and prognosis of former smokers with non-small-cell lung cancer (NSCLC), and to compare them with those of the current and never smokers. This investigation was a single-institution retrospective study of 2289 NSCLC patients, who were classified as former, current, or never smokers. A collection was made of the clinicopathological characteristics, spectra of well-identified driver genes and survival rates. The survival rates were compared using log-rank test, and independent prognostic factors, identified using Cox regression analysis. Of 2289 NSCLC patients, 257 (11.2%) were former smokers; 868 (37.9%), current smokers; and 1164 (50.9%), never smokers. Compared with the current, the former were characterized by older age at diagnosis (64.3y vs. 59.9y; P < 0.001), earlier TNM stage (stage I, 47.9% vs. 39.5%; P = 0.017), fewer solid predominance in adenocarcinomas (16.2% vs. 29.5%; P = 0.005), and more EGFR mutation (33.2% vs. 20.7%; P < 0.001) but less KRAS mutation (6.7% vs. 11.9%, P = 0.041). No statistically significant survival differences were observed between the former and current. However, the light former smokers presented favorable overall survival when compared with the light current and heavy former or current (the light former vs. the heavy former, P = 0.028; the light former vs. the light current, P = 0.048; and the light former vs. the heavy current, P = 0.048). Our findings suggest that the former smokers with NSCLCs can have distinctive clinicopathologic characteristics, oncogenic drivers, and prognosis, and they, especially the light former, can benefit from smoking cessation. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

PubMed Central

Shipp, M A; Tarr, G E; Chen, C Y; Switzer, S N; Hersh, L B; Stein, H; Sunday, M E; Reinherz, E L

1991-01-01

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung. Images PMID:1660144

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

PubMed

Shipp, M A; Tarr, G E; Chen, C Y; Switzer, S N; Hersh, L B; Stein, H; Sunday, M E; Reinherz, E L

1991-12-01

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.

Welding and Lung Cancer in a Pooled Analysis of Case-Control Studies

PubMed Central

Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H.-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; ‘t Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

2013-01-01

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer. PMID:24052544

Welding and lung cancer in a pooled analysis of case-control studies.

PubMed

Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; 't Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

2013-11-15

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer.

Nicotine does not enhance tumorigenesis in mutant K-ras-driven mouse models of lung cancer.

PubMed

Maier, Colleen R; Hollander, M Christine; Hobbs, Evthokia A; Dogan, Irem; Linnoila, R Ilona; Dennis, Phillip A

2011-11-01

Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiologic levels of nicotine on lung tumor formation, tumor growth, or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tumors that develop in this model have mutations in K-ras, which is commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras-driven lung cancer, nicotine did not increase tumor number or size and did not affect overall survival. Likewise, in a syngeneic model using lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable with those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiologic data showing that NRT does not enhance lung cancer risk in former smokers.

Systematic review of the evidence relating FEV1 decline to giving up smoking

PubMed Central

2010-01-01

Background The rate of forced expiratory volume in 1 second (FEV1) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta. Methods Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors. Results Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex. Conclusion The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV1 decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products. PMID:21156048

Misclassification rates for current smokers misclassified as nonsmokers.

PubMed

Wells, A J; English, P B; Posner, S F; Wagenknecht, L E; Perez-Stable, E J

1998-10-01

This paper provides misclassification rates for current cigarette smokers who report themselves as nonsmokers. Such rates are important in determining smoker misclassification bias in the estimation of relative risks in passive smoking studies. True smoking status, either occasional or regular, was determined for individual current smokers in 3 existing studies of nonsmokers by inspecting the cotinine levels of body fluids. The new data, combined with an approximately equal amount in the 1992 Environmental Protection Agency (EPA) report on passive smoking and lung cancer, yielded misclassification rates that not only had lower standard errors but also were stratified by sex and US minority majority status. The misclassification rates for the important category of female smokers misclassified as never smokers were, respectively, 0.8%, 6.0%, 2.8%, and 15.3% for majority regular, majority occasional, US minority regular, and US minority occasional smokers. Misclassification rates for males were mostly somewhat higher. The new information supports EPA's conclusion that smoker misclassification bias is small. Also, investigators are advised to pay attention to minority/majority status of cohorts when correcting for smoker misclassification bias.

Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

PubMed Central

Shrine, Nick R. G.; Loehr, Laura R.; Zhao, Jing Hua; Manichaikul, Ani; Lopez, Lorna M.; Smith, Albert Vernon; Heckbert, Susan R.; Smolonska, Joanna; Tang, Wenbo; Loth, Daan W.; Curjuric, Ivan; Hui, Jennie; Latourelle, Jeanne C.; Henry, Amanda P.; Aldrich, Melinda; Bakke, Per; Beaty, Terri H.; Bentley, Amy R.; Borecki, Ingrid B.; Brusselle, Guy G.; Burkart, Kristin M.; Chen, Ting-hsu; Couper, David; Crapo, James D.; Davies, Gail; Dupuis, Josée; Franceschini, Nora; Gulsvik, Amund; Hancock, Dana B.; Harris, Tamara B.; Hofman, Albert; Imboden, Medea; James, Alan L.; Khaw, Kay-Tee; Lahousse, Lies; Launer, Lenore J.; Litonjua, Augusto; Liu, Yongmei; Lohman, Kurt K.; Lomas, David A.; Lumley, Thomas; Marciante, Kristin D.; McArdle, Wendy L.; Meibohm, Bernd; Morrison, Alanna C.; Musk, Arthur W.; Myers, Richard H.; North, Kari E.; Postma, Dirkje S.; Psaty, Bruce M.; Rich, Stephen S.; Rivadeneira, Fernando; Rochat, Thierry; Rotter, Jerome I.; Artigas, María Soler; Starr, John M.; Uitterlinden, André G.; Wareham, Nicholas J.; Wijmenga, Cisca; Zanen, Pieter; Province, Michael A.; Silverman, Edwin K.; Deary, Ian J.; Palmer, Lyle J.; Cassano, Patricia A.; Gudnason, Vilmundur; Barr, R. Graham; Loos, Ruth J. F.; Strachan, David P.; London, Stephanie J.; Boezen, H. Marike; Probst-Hensch, Nicole; Gharib, Sina A.; Hall, Ian P.; O’Connor, George T.; Tobin, Martin D.; Stricker, Bruno H.

2012-01-01

Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations. Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV1/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis. Conclusions: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction. PMID:22837378

The role of LKB1 in lung cancer.

PubMed

Sanchez-Cespedes, Montse

2011-09-01

In humans, the LKB1 gene is located on the short arm of chromosome 19, which is frequently deleted in lung tumors. Unlike most cancers of sporadic origin, in non-small cell lung cancer (NSCLC) nearly half of the tumors harbor somatic and homozygous inactivating mutations in LKB1. In NSCLC, LKB1 inactivation strongly predominates in adenocarcinomas from smokers and coexists with mutations at other important cancer genes, including KRAS and TP53. Remarkably, LKB1 alterations frequently occur simultaneously with inactivation at another important tumor suppressor gene, BRG1 (also called SMARCA4), which is also located on chromosome 19p. The present review considers the frequency and pattern of LKB1 mutations in lung cancer and the distinct biological pathways in which the LKB1 protein is involved in the development of this type of cancer. Finally, the possible clinical applications in cancer management, especially in lung cancer treatment, associated with the presence of absence of LKB1 are discussed.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2013-10-01

2012 – 19 Sept 2013 4 biopsies from cancer group. Right cluster is consisting of rest of the high risk and cancer biopsies. Upregulation of Notch3 ...classifiers from bronchial biopsy specimen comparing non-smoker versus smoker with top 5 markers, Notch3 , EGFR.pY1173, LCN2, AXL and Rb.pS807.811 (right

Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers.

PubMed

Roth, Michael D; Whittaker, Katherine; Salehi, Ken; Tashkin, Donald P; Baldwin, Gayle C

2004-02-01

Lung macrophages provide a first line of host defense against inhaled pathogens and their function is impaired in the lungs of inhaled substance abusers. In order to investigate the mechanism for this impairment, alveolar macrophages (AM) were recovered from nonsmokers (NS), regular tobacco smokers (TS), marijuana smokers (MS), or crack cocaine smokers (CS), and evaluated for their production of nitric oxide (NO) and the role of NO as an antimicrobial effector molecule. AM from NS and TS efficiently killed Staphylococcus aureus and their antibacterial activity correlated closely with the production of nitrite and the expression of mRNA encoding for inducible nitric oxide synthase (iNOS). In contrast, AM collected from MS and CS exhibited limited antimicrobial activity that was not affected by an inhibitor of iNOS, or associated with expression of iNOS. Treatment with either granulocyte/macrophage colony-stimulating factor (GM-CSF) or interferon-gamma restored the ability of these cells to produce NO and to kill bacteria. These findings confirm a significant role for NO as an antibacterial effector molecule used by normal human AM and suggest that this host defense mechanism is suppressed by habitual exposure to inhaled marijuana or crack cocaine in vivo.

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.

PubMed

Yang, Mingxing; Kohler, Maxie; Heyder, Tina; Forsslund, Helena; Garberg, Hilde K; Karimi, Reza; Grunewald, Johan; Berven, Frode S; Magnus Sköld, C; Wheelock, Åsa M

2018-03-08

Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV 1 /FVC as well as the percentage of CD8 + T-cells and CD8 + CD69 + T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV 1 /FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. ClinicalTrials.gov identifier NCT02627872 ; Retrospectively registered on December 9, 2015.

De novo activating epidermal growth factor mutations (EGFR) in small-cell lung cancer.

PubMed

Thai, Alesha; Chia, Puey L; Russell, Prudence A; Do, Hongdo; Dobrovic, Alex; Mitchell, Paul; John, Thomas

2017-09-01

In Australia, mutations in epidermal growth factor mutations (EGFR) occur in 15% of patients diagnosed with non-small-cell lung cancer and are found with higher frequency in female, non-smokers of Asian ethnicity. Activating mutations in the EGFR gene are rarely described in SCLC. We present two cases of de novo EGFR mutations in patients with SCLC detected in tissue and in plasma cell free DNA, both of whom were of Asian ethnicity and never-smokers. These two cases add to the growing body of evidence suggesting that screening for EGFR mutations in SCLC should be considered in patients with specific clinical features. © 2017 Royal Australasian College of Physicians.

The effect of habitual waterpipe tobacco smoking on pulmonary function and exercise capacity in young healthy males: A pilot study.

PubMed

Hawari, F I; Obeidat, N A; Ghonimat, I M; Ayub, H S; Dawahreh, S S

2017-01-01

Evidence regarding the health effects of habitual waterpipe smoking is limited, particularly in young smokers. Respiratory health and cardiopulmonary exercise tests were compared in young male habitual waterpipe smokers (WPS) versus non-smokers. 69 WPS (≥3 times/week for three years) and 69 non-smokers were studied. Respiratory health was assessed through the American Thoracic Society and the Division of Lung Diseases (ATS-DLD-78) adult questionnaire. Pulmonary function and cardiopulmonary exercise tests were performed. Self-reported respiratory symptoms, forced expiratory volume in first second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC ratio, forced expiratory flow between 25 and 75% of FVC (FEF 25-75% ), peak expiratory flow (PEF), exercise time, peak end-tidal CO 2 tension (PetCO 2 ), subject-reported leg fatigue and dyspnea; peak O 2 uptake (VO 2 max), and end-expiratory lung volume (EELV) change from baseline (at peak exercise) were measured. WPS were more likely than non-smokers to report respiratory symptoms. WPS also demonstrated: shorter exercise time; lower peak VO 2 ; higher perceived dyspnea at mid-exercise; lower values of the following: FEV 1 , FVC, PEF, and EELV change. Habitual waterpipe tobacco smoking in young seemingly healthy individuals is associated with a greater burden of respiratory symptoms and impaired exercise capacity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regretting Ever Starting to Smoke: Results from a 2014 National Survey.

PubMed

Nayak, Pratibha; Pechacek, Terry F; Slovic, Paul; Eriksen, Michael P

2017-04-06

Background : The majority of smokers regret ever starting to smoke, yet the vast majority continue to smoke despite the fact that smoking kills nearly 50% of lifetime users. This study examined the relationships between regret and smoker characteristics, quit history, risk perceptions, experiential thinking, and beliefs and intentions at time of smoking initiation. Methods : Data from the 2014 Tobacco Products and Risk Perceptions Survey, a nationally representative survey of United States adults, were analyzed to provide the latest prevalence estimates of regret and potential predictors. Relationships among predictor variables and regret were analyzed using correlations, t -tests, and multinomial logistic regression. Results : The majority of smokers (71.5%) regretted starting to smoke. Being older and non-Hispanic white were significant predictors of regret. Smokers having a high intention to quit, having made quit attempts in the past year, worrying about getting lung cancer, believing smoking every day can be risky for your health, perceiving a risk of being diagnosed with lung cancer during one's lifetime, and considering themselves addicted to cigarettes were significant predictors of regret for smoking initiation. Conclusions : This study provides updated prevalence data on regret using a national sample, and confirms that regret is associated with perceived risk. The findings from this study can be used to inform smoking intervention programs and support the inclusion of smoker regret in cost-benefit analyses of the economic impact of tobacco regulations.

Beyond Traditional Newspaper Advertisement: Leveraging Facebook-Targeted Advertisement to Recruit Long-Term Smokers for Research

PubMed Central

Warrick, Adam

2016-01-01

Background Smokers are a stigmatized population, but an important population to reach for the purpose of research. Therefore, innovative recruitment methods are needed that are both cost-effective and efficacious in recruiting this population. Objective The aim of the present article was to evaluate the feasibility of Facebook-targeted advertisement to recruit long-term smokers eligible for lung cancer screening for a descriptive, cross-sectional survey. Methods A social media recruitment campaign was launched using Facebook-targeted advertisement to target age and keywords related to tobacco smoking in the Facebook users profile, interests, and likes. A 3-day newspaper advertisement recruitment campaign was used as a comparison. The study that used both recruitment methods aimed to test the psychometric properties of 4 newly developed lung cancer screening health belief scales. Data were collected via cross-sectional survey methodology using an Web-based survey platform. Results The Facebook-targeted advertisements were viewed 56,621 times over an 18-day campaign in 2015 in the United States. The advertisement campaign yielded 1121 unique clicks to the Web-based survey platform at a cost of $1.51 per completed survey. Of those who clicked through to the study survey platform, 423 (37.7%) consented to participate; 92 (8.2%) dropped out during completion of the survey yielding a final study pool of 331 completed surveys. Recruitment by newspaper advertisement yielded a total of 30 participants in response to a 3-day advertisement campaign; recruitment efficacy resulted in 10 participants/day at $40.80 per completed survey. Participants represented current (n=182; 51%) and former smokers (n=178; 49%) with a mean age of 63.4 years (SD 6.0). Cost of the advertisement campaign was $500 total for the 18-day campaign. Conclusions Recruitment by Facebook was more efficacious and cost-effective compared with newspaper advertisement. Facebook offers a new venue for recruitment into research studies that offer the potential for wider reach at a lower cost while providing privacy and flexibility for potential study participants. The study’s findings extend recent work of other researchers who have demonstrated Facebook’s utility with younger smokers, and Facebook is an effective tool to recruit older smokers. Furthermore, Facebook is a cost-effective alternative to traditional newspaper advertisement offering a new, affordable venue to recruit large numbers of older smokers efficiently. PMID:27306780

Beyond Traditional Newspaper Advertisement: Leveraging Facebook-Targeted Advertisement to Recruit Long-Term Smokers for Research.

PubMed

Carter-Harris, Lisa; Bartlett Ellis, Rebecca; Warrick, Adam; Rawl, Susan

2016-06-15

Smokers are a stigmatized population, but an important population to reach for the purpose of research. Therefore, innovative recruitment methods are needed that are both cost-effective and efficacious in recruiting this population. The aim of the present article was to evaluate the feasibility of Facebook-targeted advertisement to recruit long-term smokers eligible for lung cancer screening for a descriptive, cross-sectional survey. A social media recruitment campaign was launched using Facebook-targeted advertisement to target age and keywords related to tobacco smoking in the Facebook users profile, interests, and likes. A 3-day newspaper advertisement recruitment campaign was used as a comparison. The study that used both recruitment methods aimed to test the psychometric properties of 4 newly developed lung cancer screening health belief scales. Data were collected via cross-sectional survey methodology using an Web-based survey platform. The Facebook-targeted advertisements were viewed 56,621 times over an 18-day campaign in 2015 in the United States. The advertisement campaign yielded 1121 unique clicks to the Web-based survey platform at a cost of $1.51 per completed survey. Of those who clicked through to the study survey platform, 423 (37.7%) consented to participate; 92 (8.2%) dropped out during completion of the survey yielding a final study pool of 331 completed surveys. Recruitment by newspaper advertisement yielded a total of 30 participants in response to a 3-day advertisement campaign; recruitment efficacy resulted in 10 participants/day at $40.80 per completed survey. Participants represented current (n=182; 51%) and former smokers (n=178; 49%) with a mean age of 63.4 years (SD 6.0). Cost of the advertisement campaign was $500 total for the 18-day campaign. Recruitment by Facebook was more efficacious and cost-effective compared with newspaper advertisement. Facebook offers a new venue for recruitment into research studies that offer the potential for wider reach at a lower cost while providing privacy and flexibility for potential study participants. The study's findings extend recent work of other researchers who have demonstrated Facebook's utility with younger smokers, and Facebook is an effective tool to recruit older smokers. Furthermore, Facebook is a cost-effective alternative to traditional newspaper advertisement offering a new, affordable venue to recruit large numbers of older smokers efficiently.

Gene Environment Interactions in Women With Breast and Secondary Lung Cancer

DTIC Science & Technology

2005-07-01

information that may be useful in defining subpopulations sensitive to radiation therapy . 15. SUBJECT TERMS Breast cancer, lung cancer, secondary...risk levels to women choosing a breast cancer therapy . Additionally, this research may provide new data on the susceptibilities of women with...secondary lung cancer risk that increased 2-3 fold for nonsmokers and 30 fold in smokers who receive radiation therapy (4,5). Overall, radiotherapy

The changing epidemiology of smoking and lung cancer histology.

PubMed Central

Wynder, E L; Muscat, J E

1995-01-01

In 1950, the first large-scale epidemiological studies demonstrated that lung cancer is causatively associated with cigarette smoking, a finding subsequently confirmed by the Royal College of Physicians in London, the U.S. Surgeon General, and the World Health Organization. Although cigarette consumption has gradually decreased in the United States from a high of about 3800 cigarettes per adult per year in 1965 to about 2800 cigarettes in 1993, death from lung cancer has reached a high among males at the rate of 74.9/100,000/year and among females at the rate of 28.5. However, in the younger cohorts, the lung cancer death rate is decreasing in both men and women. In this overview we discuss the steeper increase during recent decades of lung adenocarcinoma incidence compared with squamous cell carcinoma of the lung. In 1950, the ratio of these two major types of lung cancer in males was about 1:18; today it is about 1:1.2-1.4. This overview discusses two concepts that are regarded as contributors to this change in the histological types of lung cancer. One factor is the decrease in average nicotine and tar delivery of cigarettes from about 2.7 and 38 mg in 1955 to 1.0 and 13.5 mg in 1993, respectively. Other major factors for the reduced emission of smoke relate to changes in the composition of the cigarette tobacco blend and general acceptance of cigarettes with filter tips; the latter constitute 97% of all cigarettes currently sold. However, smokers of low-yield cigarettes compensate for the low delivery of nicotine by inhaling the smoke more deeply and by smoking more intensely; such smokers may be taking up to 5 puffs/min with puff volumes up to 55 ml. Under these conditions, the peripheral lung is exposed to increased amounts of smoke carcinogens that are suspected to lead to lung adenocarcinoma. Among the important changes in the composition of the tobacco blend of the U.S. cigarette is a significant increase in nitrate content (0.5% to 1.2-1.5%), which raises the yields of nitrogen oxides and N-nitrosamines in the smoke. Furthermore, the more intense smoking by the consumers of low-yield cigarettes increases N-nitrosamines in the smoke 2- to 3-fold. Among the N-nitrosamines is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in animals that is exclusively formed from nicotine. This organ-specific tobacco-specific nitrosamine (TSNA) induces adenocarcinoma of the lung. All of these factors, the more intense smoking, the deeper inhalation of the smoke, and the increased yields of N-nitrosamines in the smoke of low-yield cigarettes, are considered major contributors to the drastic increase in lung adenocarcinoma among cigarette smokers in recent years. This overview also discusses the differences in the major lung cancer types in female compared with male smokers as well as the likely underlying factors for increased lung cancer risk among African Americans compared with that among white Americans. Although the only sure way to prevent smoking-related diseases is giving up the tobacco habit, there must be a measure of protection for those who cannot accomplish this. Therefore, setting upper permissible limits of tar levels for the smoke of U.S. cigarettes, similar to strategies already taken in Western Europe, should be considered. PMID:8741774

Elderly male smokers with right lung tumors are viable candidates for KRAS mutation screening.

PubMed

Yang, Yang; Shi, Chun; Sun, Hui; Yin, Wei; Zhou, Xiao; Zhang, Lei; Jiang, Gening

2016-01-07

Genetic aberrations in tumor driver genes provide specific molecular targets for therapeutic intervention, which can greatly improve therapeutic outcomes. Here, we analyzed the mutational frequency of EGFR and KRAS gene, as well as EML4-ALK rearrangement, and summarized the clinicopathological characters of Chinese lung cancer patients. We detected the mutation spectrum of 1033 primary lung cancer patients. The analyzed clinicopathological parameters included gender, age at diagnosis, smoking status, pathological TNM stage, tumor morphology and location, visceral pleural invasion, and histological type. A total of 618 patients had mutations in EGFR or KRAS gene as well as rearrangement of EML4-ALK. Exon 19 deletions and L858R in the EGFR gene were the most frequent mutations. Left-side lung cancer was more common in female patients carrying the KRAS mutation. Rearrangement of EML4-ALK was more common in non-tobacco-using male patients, who also exhibited a higher likelihood of visceral pleura invasion. Elderly females who never smoked and possessed 1-20 mm stage I adenocarcinomas in the right side exhibited a higher frequency of EGFR mutations. Elderly male smokers with right lung tumors were viable candidates for KRAS mutation screening.

Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium

PubMed Central

Coté, Michele L.; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G.; Christiani, David C.; Spitz, Margaret R.; Muscat, Joshua E.; Rennert, Gad; Aben, Katja K.; Andrew, Angeline S.; Bencko, Vladimir; Bickeböller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J.; Fabianova, Eleonora; Field, John K.; Foretova, Lenka; Friis, Søren; Harris, Curtis C.; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A.; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Marchand, Loic Le; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I.; McLaughlin, John R.; Morgenstern, Hal; Müeller, Heiko; Orlow, Irene; Park, Bernard J.; Pinchev, Mila; Raji, Olaide Y.; Rennert, Hedy S.; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Teare, M. Dawn; Tjønnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F.M.; Wichmann, Erich; Wiencke, John K.; Woll, Penella J.; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J.; Hung, Rayjean J.

2012-01-01

Background and Methods Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analyzed. Unconditional logistic regression models and generalized estimating equations were used to estimate odds ratios and 95% confidence intervals. Results Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in risk of lung cancer, after adjustment for smoking and other potential confounders(95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (OR=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions The increased risk among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those associated with cigarette smoking. While the role of genetic variation in the etiology of lung cancer remains to be fully characterized, family history assessment is immediately available and those with a positive history represent a higher risk group. PMID:22436981

Diagnostic accuracy of a pocket screening spirometer in diagnosing chronic obstructive pulmonary disease in general practice: a cross sectional validation study using tertiary care as a reference.

PubMed

Labor, Marina; Vrbica, Žarko; Gudelj, Ivan; Labor, Slavica; Plavec, Davor

2016-08-19

COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard. Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD. COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP's office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP's office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all). Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral. ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered.

Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer.

PubMed

Swartz, Michael D; Peterson, Christine B; Lupo, Philip J; Wu, Xifeng; Forman, Michele R; Spitz, Margaret R; Hernandez, Ladia M; Vannucci, Marina; Shete, Sanjay

2013-01-01

Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions. We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status. Rs6893114 in MTRR (odds ratio [OR] = 2.10; 95% credible interval [CI]: 1.20-3.48) and alcohol (drinkers vs. non-drinkers, OR = 0.48; 95% CI: 0.26-0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR = 1.70; 95% CI: 1.10-2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR = 0.42; 95% CI: 0.19-0.88) and betaine*rs16948305 (OR = 0.54; 95% CI: 0.30-0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR = 0.25; 95% CI: 0.11-0.58; rs10512948; OR = 0.61; 95% CI: 0.41-0.90; rs2924471; OR = 3.31; 95% CI: 1.66-6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43-0.95) and three SNP*nutrient interactions (choline*rs10475407; OR = 1.62; 95% CI: 1.11-2.42; choline*rs11134290; OR = 0.51; 95% CI: 0.27-0.92; and riboflavin*rs8767412; OR = 0.40; 95% CI: 0.15-0.95) were associated with lung cancer risk in never smokers. This study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

Primary Care Provider-Delivered Smoking Cessation Interventions and Smoking Cessation Among Participants in the National Lung Screening Trial.

PubMed

Park, Elyse R; Gareen, Ilana F; Japuntich, Sandra; Lennes, Inga; Hyland, Kelly; DeMello, Sarah; Sicks, JoRean D; Rigotti, Nancy A

2015-09-01

The National Lung Screening Trial (NLST) found a reduction in lung cancer mortality among participants screened with low-dose computed tomography vs chest radiography. In February 2015, Medicare announced its decision to cover annual lung screening for patients with a significant smoking history. These guidelines promote smoking cessation treatment as an adjunct to screening, but the frequency and effectiveness of clinician-delivered smoking cessation interventions delivered after lung screening are unknown. To determine the association between the reported clinician-delivered 5As (ask, advise, assess, assist [talk about quitting or recommend stop-smoking medications or recommend counseling], and arrange follow-up) after lung screening and smoking behavior changes. A matched case-control study (cases were quitters and controls were continued smokers) of 3336 NLST participants who were smokers at enrollment examined participants' rates and patterns of 5A delivery after a lung screen and reported smoking cessation behaviors. Prevalence of the clinician-delivered 5As and associated smoking cessation after lung screening. Delivery of the 5As 1 year after screening were as follows: ask, 77.2%; advise, 75.6%; assess, 63.4%; assist, 56.4%; and arrange follow-up, 10.4%. Receipt of ask, advise, and assess was not significantly associated with quitting in multivariate models that adjusted for sociodemographic characteristics, medical history, screening results, nicotine dependence, and motivation to quit. Assist was associated with a 40% increase in the odds of quitting (odds ratio, 1.40; 95% CI, 1.21-1.63), and arrange was associated with a 46% increase in the odds of quitting (odds ratio, 1.46; 95% CI, 1.19-1.79). Assist and arrange follow-up delivered by primary care providers to smokers who were participating in the NLST were associated with increased quitting; less intensive interventions (ask, advise, and assess) were not. However, rates of assist and arrange follow-up were relatively low. Our findings confirm the need for and benefit of clinicians taking more active intervention steps in helping patients who undergo screening to quit smoking.

Occupational exposure to dust and lung disease among sheet metal workers.

PubMed Central

Hunting, K L; Welch, L S

1993-01-01

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was significantly associated with obstructive lung disease but the dose-response relation was inconsistent, especially for those with higher pack-years of smoking exposure. Exposure to fibreglass was not a risk factor for obstructive lung disease. PMID:8507596

Radon testing in rapid access lung clinics: an opportunity for secondary prevention.

PubMed

Smyth, R; Long, S; Wiseman, E; Sharpe, D; Breen, D; O'Regan, A

2017-05-01

Radon is a naturally occurring radioactive gas and a level 1 carcinogen. It acts synergistically with cigarette smoke to cause lung cancer. In Ireland, radon is estimated to be associated with 13 % of all lung cancers. Rapid access lung cancer clinics (RALC's) were established in the UK and Ireland to improve lung cancer management outcomes. There has been no attempt to date to provide advice on household radon exposure assessments in this setting. We performed a prospective feasibility study of radon assessment in our RALC to test the hypothesis that patients would avail of this service and that it would provide an opportunity for secondary prevention in at risk persons. We investigated household radon levels in consecutive patients who were newly referred with symptoms of lung cancer to the RALC in Galway University Hospital, Ireland over a 6-month period. Of 50 patients enrolled, 42 returned valid results. Overall 21 % of patients had radon levels recorded above the national reference level. Only 5 % of patients were aware of the association between radon gas and lung cancer. Smokers were significantly less likely to engage fully in radon testing. The development of RALC's offers a novel opportunity to integrate the concepts of radon exposure, cigarette smoking and the development of lung cancer, and to reinforce this message in the minds of at risk patients.

How risky is it to use e-cigarettes? Smokers' beliefs about their health risks from using novel and traditional tobacco products.

PubMed

Pepper, Jessica K; Emery, Sherry L; Ribisl, Kurt M; Rini, Christine M; Brewer, Noel T

2015-04-01

We sought to understand smokers' perceived likelihood of health problems from using cigarettes and four non-cigarette tobacco products (NCTPs: e-cigarettes, snus, dissolvable tobacco, and smokeless tobacco). A US national sample of 6,607 adult smokers completed an online survey in March 2013. Participants viewed e-cigarette use as less likely to cause lung cancer, oral cancer, or heart disease compared to smoking regular cigarettes (all p < .001). This finding was robust for all demographic groups. Participants viewed using NCTPs other than e-cigarettes as more likely to cause oral cancer than smoking cigarettes but less likely to cause lung cancer. The dramatic increase in e-cigarette use may be due in part to the belief that they are less risky to use than cigarettes, unlike the other NCTPs. Future research should examine trajectories in perceived likelihood of harm from e-cigarette use and whether they affect regular and electronic cigarette use.

The Influence of Smoking on Pulmonary Tuberculosis in Diabetic and Non-Diabetic Patients

PubMed Central

Bai, Kuan-Jen; Lee, Jen-Jyh; Chien, Shun-Tien; Suk, Chi-Won; Chiang, Chen-Yuan

2016-01-01

Background Both smoking and diabetes can increase the risk and influence the manifestations and outcomes of tuberculosis (TB). It is not clear whether the influence of smoking on pulmonary TB differs between non-diabetic and diabetic patients. Herein, we assessed the manifestations and outcomes of TB in relation to smoking in both diabetic and non-diabetic TB patients. Methodology/Principal Findings All diabetic culture-positive pulmonary TB patients notified from 2005–2010 at three teaching hospitals in Taiwan were enrolled. A culture-positive pulmonary TB patient without DM who was notified to the health authority immediately prior to each diabetic TB patient was selected for comparison. The 972 patients in this study cohort included 365 (37.6%) non-diabetic non-smokers, 149 (15.3%) non-diabetic smokers, 284 (29.2%) diabetic non-smokers, and 174 (17.9%) diabetic smokers. The adjusted relative risk of a pretreatment positive smear for a smoker compared with a non-smoker was 2.19 (95% CI 1.38–3.47) in non-diabetic patients and 2.23 (95% CI 1.29–3.87) in diabetic culture-positive pulmonary TB patients. The adjusted relative risk for a positive smear among diabetic smokers was 5.61 (95% CI 3.35–9.41) compared with non-diabetic non-smokers. Smoking was significantly associated with an increased frequency of bilateral lung parenchyma involvement (AdjOR 1.84, 95% CI 1.16–2.93), far-advanced pulmonary TB (AdjOR 1.91, 95% CI 1.04–3.50), cavitary lesions (AdjOR 2.03, 95% CI 1.29–3.20), and unfavorable outcomes of TB (AdjOR 2.35, 95% CI 1.02–5.41) in non-diabetic patients. However, smoking was not associated with cavitary lung parenchyma lesions regarding the location, number or size of the cavity in diabetic TB patients. Conclusions/Significance Smoking and diabetes have joint effects on a pretreatment positive smear. Diabetic smokers had more than a 5-fold increased risk of a pretreatment positive smear than did non-diabetic non-smokers, indicating remarkable joint effects of diabetes and smoking on the risk of TB transmission. PMID:27270725

Correlation Analysis of PM10 and the Incidence of Lung Cancer in Nanchang, China.

PubMed

Zhou, Yi; Li, Lianshui; Hu, Lei

2017-10-19

Air pollution and lung cancer are closely related. In 2013, the World Health Organization listed outdoor air pollution as carcinogenic and regarded it as the most widespread carcinogen that humans are currently exposed to. Here, grey correlation and data envelopment analysis methods are used to determine the pollution factors causing lung cancer among residents in Nanchang, China, and identify population segments which are more susceptible to air pollution. This study shows that particulate matter with particle sizes below 10 micron (PM 10 ) is most closely related to the incidence of lung cancer among air pollution factors including annual mean concentrations of SO₂, NO₂, PM 10 , annual haze days, and annual mean Air Pollution Index/Air Quality Index (API/AQI). Air pollution has a greater impact on urban inhabitants as compared to rural inhabitants. When gender differences are considered, women are more likely to develop lung cancer due to air pollution. Smokers are more likely to suffer from lung cancer. These results provide a reference for the government to formulate policies to reduce air pollutant emissions and strengthen anti-smoking measures.

Correlation Analysis of PM10 and the Incidence of Lung Cancer in Nanchang, China

PubMed Central

Zhou, Yi; Li, Lianshui; Hu, Lei

2017-01-01

Air pollution and lung cancer are closely related. In 2013, the World Health Organization listed outdoor air pollution as carcinogenic and regarded it as the most widespread carcinogen that humans are currently exposed to. Here, grey correlation and data envelopment analysis methods are used to determine the pollution factors causing lung cancer among residents in Nanchang, China, and identify population segments which are more susceptible to air pollution. This study shows that particulate matter with particle sizes below 10 micron (PM10) is most closely related to the incidence of lung cancer among air pollution factors including annual mean concentrations of SO2, NO2, PM10, annual haze days, and annual mean Air Pollution Index/Air Quality Index (API/AQI). Air pollution has a greater impact on urban inhabitants as compared to rural inhabitants. When gender differences are considered, women are more likely to develop lung cancer due to air pollution. Smokers are more likely to suffer from lung cancer. These results provide a reference for the government to formulate policies to reduce air pollutant emissions and strengthen anti-smoking measures. PMID:29048397

Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function.

PubMed

Woodruff, Prescott G; Barr, R Graham; Bleecker, Eugene; Christenson, Stephanie A; Couper, David; Curtis, Jeffrey L; Gouskova, Natalia A; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Kleerup, Eric; Lazarus, Stephen C; Martinez, Fernando J; Paine, Robert; Rennard, Stephen; Tashkin, Donald P; Han, MeiLan K

2016-05-12

Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms. We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest. Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27±0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used bronchodilators and 23% used inhaled glucocorticoids. Although they do not meet the current criteria for COPD, symptomatic current or former smokers with preserved pulmonary function have exacerbations, activity limitation, and evidence of airway disease. They currently use a range of respiratory medications without any evidence base. (Funded by the National Heart, Lung, and Blood Institute and the Foundation for the National Institutes of Health; SPIROMICS ClinicalTrials.gov number, NCT01969344.).

Clinical trial studies safety and efficacy of adding a kinase inhibitor to chemotherapy with topotecan in small cell lung cancer | Center for Cancer Research

Cancer.gov

Dr. Anish Thomas, Staff Clinician in the Thoracic and Gastrointestinal Oncology Branch (TGIB), is leading a trial of combination therapy in small cell lung cancer (SCLC), a fast-growing malignancy that occurs most commonly in smokers. Learn more...

Prognosis of Lung Cancer: Heredity or Environment

DTIC Science & Technology

2015-06-01

former/never smoker), the primary lung cancer risk factor (Table 1). More blacks smoked menthol cigarettes compared with whites. More whites self...Unknown 5 Smoking status at cohort entry Current 253 (72.5) 102 (68.9) Former 75 (21.5) 40 (27.0) Never 21 (6.0) 6 (4.1) Smokes (or smoked) menthol

Eicosanoids in exhaled breath condensate and bronchoalveolar lavage fluid of patients with primary lung cancer.

PubMed

Ciebiada, Maciej; Górski, Paweł; Antczak, Adam

2012-01-01

Although eicosanoids are involved in lung carcinogenesis they were poorly investigated in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALf) in patients with primary lung cancer. In this study 17 patients with diagnosed non-small cell lung cancer, 10 healthy smokers and 12 healthy nonsmokers were included. The levels of cys-LTs, 8-isoprostane, LTB4 and PGE2 were measured before any treatment in the EBC of all patients and in BALf of patients with lung cancer by enzyme linked immunosorbent assay. 8-isoprostane, LTB4, cys-LTs and PGE2 were detectable in the EBC and BALf. There were no significant differences between healthy smokers and nonsmokers in concentrations of all measured mediators. Compared with both healthy controls, patients with diagnosed lung cancer displayed higher concentrations of cys-LTs (p< 0.05) and LTB4 (p < 0.05) in EBC. In patients with lung cancer, the mean concentrations of all measured mediators were significantly higher in BALf compared with EBC and there was a significant, positive correlation between concentration of cys-LTs, LTB(4) and 8-isoprostane in BALf and their concentrations in the EBC (r=0.64, p < 0.05, r=0.59, p< 0.05, r=0.53, p< 0.05 respectively). Since cys-LT, LTB4 and 8-isoprostane concentrations in EBC from patients with lung cancer reflect their concentrations in BALf, they may serve as a possible non-invasive method to monitor the disease and to assess the effectiveness of therapy.

α1-Proteinase inhibitor (human) in the treatment of hereditary emphysema secondary to α1-antitrypsin deficiency: number and costs of years of life gained.

PubMed

Sclar, David Alexander; Evans, Marc A; Robison, Linda M; Skaer, Tracy L

2012-05-01

α(1)-Antitrypsin deficiency (α-ATD) is a disorder inherited in an autosomal recessive pattern, with co-dominant alleles known as the protease inhibitor system (Pi). The main function of α(1)-antitrypsin (α-AT) is to protect the lungs against a powerful elastase released from neutrophil leucocytes. α-ATD typically presents with a serum α-AT level of <50 mg/dL. In severe α-ATD, phenotype PiZZ, protection of the lungs is compromised, leading to an accelerated decline in forced expiratory volume in 1 second (FEV(1)). As a result, a patient may develop pulmonary emphysema of the panacinar type at a young age (third to fourth decades of life), with cigarette smoking being the most significant additional risk factor. It has been shown that weekly or monthly infusion of human α-AT is effective in raising serum α-AT levels to desired levels (>80 mg/dL), with few, if any, adverse effects. The present study was designed to discern the number of years of life gained, and the expense per year of life gained, associated with use of α-AT augmentation therapy (α(1)-proteinase inhibitor [human]), relative to 'no therapeutic intervention' in persons with α-ATD. Monte Carlo simulation (MCS) was used to: (i) estimate the number of years of life gained; and (ii) estimate the health service expenditures per year of life gained for persons receiving, or not receiving, α-AT augmentation therapy. MCS afforded a decision-analytical framework parameterized with both stochastic (random) and deterministic (fixed) components, and yielded a fiscal risk-profile for each simulated cohort of interest (eight total: by sex, smoking status [non-smoker; or past use (smoker)]; and use of α-AT augmentation therapy). The stochastic components employed in the present inquiry were: (i) age-specific body weight, and height; (ii) age-specific mortality; and (iii) the probability distribution for receipt of a lung transplant, as a function of FEV(1). The deterministic components employed in the present inquiry were: (i) age in years for the simulated cohort; (ii) outlays for α-AT augmentation therapy; (iii) health service expenditures associated with receipt of a lung transplant; (iv) annual decline in FEV(1); (v) percent predicted FEV(1); (vi) initiation of α-AT augmentation therapy as a function of percent predicted FEV(1); (vii) need for a lung transplant as a function of percent predicted FEV(1); (viii) annual rate of lung infection; and (ix) mortality as a function of percent predicted FEV(1). Results are reported from a payer perspective ($US, year of costing 2010). Receipt of α-AT augmentation therapy was associated with a significant increase (p < 0.05) in years of life gained, with female smokers gaining an estimated mean 7.14 years (cost per year: $US248 361 [95% CI 104 531, 392 190]); female non-smokers gained an estimated mean 9.19 years (cost per year: $US160 502 [95% CI 37 056, 283 947)]); male smokers gained an estimated mean 5.93 years (cost per year: $US142 250 [95% CI 48 467, 236 032]); and male non-smokers gained an estimated mean 10.60 years (cost per year: $US59 234 [95% CI 20 719, 97 548]). Use of α-AT augmentation therapy was associated with an increase in years of life gained by sex and history of tobacco use, and at a cost per year of life gained comparable to that of other evidenced-based interventions.

Ventilatory function in rubber processing workers: acute changes over the workshift.

PubMed

Governa, M; Comai, M; Valentino, M; Antonicelli, L; Rinaldi, F; Pisani, E

1987-02-01

When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways.

Pulmonary functions of narghile smokers compared to cigarette smokers: a case-control study.

PubMed

Ben Saad, Helmi; Khemiss, Mehdi; Nhari, Saida; Ben Essghaier, Mejda; Rouatbi, Sonia

2013-01-01

Studies of the lung function profiles of exclusive narghile smokers (ENS) are few, have some methodological limits, and present contradictory conclusions. The present study aimed to compare the plethysmographic profiles of ENS with age- and height-matched exclusive cigarette smokers (ECS). Males aged 35-60 living in Sousse, Tunisia, who have been smoking narghile exclusively for more than 10 narghile-years (n = 36) or cigarettes exclusively for more than 10 pack-years (n = 106) were recruited to participate in this case-control study. The anthropometric and plethysmographic data were measured according to international recommendations using a body plethysmograph (ZAN 500 Body II, Meβgreräte GmbH, Germany). Large-airway-obstructive-ventilatory-defect (LAOVD) was defined as: first second forced expiratory volume/forced vital capacity (FEV1/FVC) below the lower-limit-of-normal (LLN). Restrictive-ventilatory-defect (RVD) was defined as total lung capacity < LLN. Lung hyperinflation was defined as residual volume > upper-limit-of-normal. Student t-test and χ(2) test were used to compare plethysmographic data and profiles of the two groups. The subjects in the ENS and ECS groups are well matched in age (45±7 vs. 47±5 years) and height (1.73±0.06 vs. 1.72±0.06 m) and used similar quantities of tobacco (36±22 narghile-years vs. 35±19 pack-years). Compared to the ENS group, the ECS group had significantly lower FEV1 (84±12 vs. 60±21%), FVC (90±12 vs. 76±18%), and FEV1/FVC (99±7 vs. 83±17%). The two groups had similar percentages of RVD (31 vs. 36%), while the ECS group had a significantly higher percentage of LAOVD (8 vs. 58%) and lung hyperinflation (36 vs.57%). Chronic exclusive narghile smoking has less adverse effects on pulmonary function tests than chronic exclusive cigarette smoking.

Pulmonary functions of narghile smokers compared to cigarette smokers: a case-control study.

PubMed

Saad, Helmi Ben; Khemiss, Mehdi; Nhari, Saida; Essghaier, Mejda Ben; Rouatbi, Sonia

2013-01-01

Background Studies of the lung function profiles of exclusive narghile smokers (ENS) are few, have some methodological limits, and present contradictory conclusions. The present study aimed to compare the plethysmographic profiles of ENS with age- and height-matched exclusive cigarette smokers (ECS). Methods Males aged 35-60 living in Sousse, Tunisia, who have been smoking narghile exclusively for more than 10 narghile-years (n = 36) or cigarettes exclusively for more than 10 pack-years (n = 106) were recruited to participate in this case-control study. The anthropometric and plethysmographic data were measured according to international recommendations using a body plethysmograph (ZAN 500 Body II, Meβgreräte GmbH, Germany). Large-airway-obstructive-ventilatory-defect (LAOVD) was defined as: first second forced expiratory volume/forced vital capacity (FEV 1 /FVC) below the lower-limit-of-normal (LLN). Restrictive-ventilatory-defect (RVD) was defined as total lung capacity < LLN. Lung hyperinflation was defined as residual volume > upper-limit-of-normal. Student t-test and χ 2 test were used to compare plethysmographic data and profiles of the two groups. Results The subjects in the ENS and ECS groups are well matched in age (45±7 vs. 47±5 years) and height (1.73±0.06 vs. 1.72±0.06 m) and used similar quantities of tobacco (36±22 narghile-years vs. 35±19 pack-years). Compared to the ENS group, the ECS group had significantly lower FEV 1 (84±12 vs. 60±21%), FVC (90±12 vs. 76±18%), and FEV 1 /FVC (99±7 vs. 83±17%). The two groups had similar percentages of RVD (31 vs. 36%), while the ECS group had a significantly higher percentage of LAOVD (8 vs. 58%) and lung hyperinflation (36 vs.57%). Conclusion Chronic exclusive narghile smoking has less adverse effects on pulmonary function tests than chronic exclusive cigarette smoking.

Lung-cancer reduction from smoking cessation and radon remediation: a preliminary cost-analysis in Northamptonshire, UK.

PubMed

Groves-Kirkby, C J; Timson, K; Shield, G; Denman, A R; Rogers, S; Phillips, P S

2011-02-01

Domestic radon levels in parts of the United Kingdom are sufficiently high as to increase the risk of lung-cancer among residents. Public health campaigns in the county of Northamptonshire, a designated radon Affected Area with 6.3% of homes having average radon levels in excess of the UK Action Level of 200 Bq m(-3), have encouraged householders to test for radon and then, if indicated to be necessary, to carry out remediation in their homes. These campaigns have been only partially successful, since to date only 40% of Northamptonshire houses have been tested, and only 15% of those householders finding raised levels have proceeded to remediate. Those who remediate have been shown to have smaller families, to be older, and to include fewer smokers than the average population, suggesting that current strategies to reduce domestic radon exposure are not reaching those most at risk. During 2004-2005, the NHS Stop-Smoking Services in Northamptonshire assisted 2847 smokers to quit to the 4-week stage, the 15% (435) of these 4-week quitters remaining quitters at 1year forming the subjects of a retrospective study considering whether smoking cessation campaigns contribute significantly to radon risk reduction. Quantitative assessment of the risk of lung-cancer among the study population, from knowledge of the individuals' age, gender, and smoking habits, together with the radon levels in their homes, demonstrates that smoking cessation programmes have significant added value in reducing the incidence of lung-cancer in radon Affected Areas, and contribute a substantially greater health benefit at a lower cost than the alternative strategy of reducing radon levels in the smokers' homes, while they remain smokers. Both radon remediation and smoking cessation programmes are very cost effective in Northamptonshire, with smoking cessation being significantly more cost effective, and these are potentially valuable programmes to drive health improvements through promotion of the uptake or environmental management for radon in the home. Copyright © 2010 Elsevier Ltd. All rights reserved.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized and log-transformed by...C. V Figure 23. Expression of genes located at chromosome 3q26-3q29. RPKM values were obtained for...airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol 2003;29:331-343 14. Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on

Immunological biomarkers in salt miners exposed to salt dust, diesel exhaust and nitrogen oxides.

PubMed

Backé, Eva; Lotz, Gabriele; Tittelbach, Ulrike; Plitzko, Sabine; Gierke, Erhardt; Schneider, Wolfram Dietmar

2004-06-01

Air pollutants can affect lung function and also the immune system. In a study about lung function of salt miners in relation to the complex exposure in a salt mine, we also analysed selected immunological parameters and inflammation markers in the blood of miners. Effect of salt dust, diesel exhaust, nitrogen oxides (NOx) and smoking on the biomarkers was analysed. Blood was drawn from 286 salt miners, and the soluble intercellular adhesion molecule-1 (s-ICAM), monocyte chemotactic protein (MCP-1) and clara cell protein (CC16) were analysed by an immunoassay, blood profile was done and lymphocyte subpopulations (CD3, CD3/CD4, CD3/CD8, CD19, NK-cells, CD3/HLA-DR) were determined by flow cytometry. Salt dust was measured by two-step gravimetry (personal sampling). Diesel exhaust was measured as elemental carbon concentration by coulometry. NOx were determined by an electrochemical cell method. Differences between non-smokers, former smokers and active smokers were analysed by analysis of variance. Linear regression analysis to describe exposure-response relationships was done with regard to confounding factors [smoking, inflammatory diseases, time of blood drawing, respiratory infection and body-mass index (BMI)]. Significant differences between non-smokers and active smokers were found for most of the leukocyte types (e.g. granulocytes P = 0.000, lymphocytes P = 0.002, T-cells P = 0.033) and for some soluble parameters (ICAM P = 0.000, IgM P = 0.007, IgE P = 0.035). Increasing numbers of total lymphocytes, T-cells and HLA-DR positive T-cells in relation to exposure were found by linear regression analysis (e.g. for inhalable dust:total lymphocytes P = 0.011, T-cells P = 0.061, HLA-DR positive T-cells P = 0.007). CONCLUSION. Comparison of immunological markers in non-smokers and active smokers confirms leukocytosis and inflammation following tobacco consumption. The combined exposure of salt dust, diesel exhaust and NOx seems to influence the immune system. Together, the results suggest that the analysis of leukocytes and their subsets can complete other investigations (lung function, questionnaire) to monitor exposure-response relationships in occupational studies investigating the effect of inhaled substances. Longitudinal studies will be necessary to determine the predictive value of the immunological changes. Copyright 2004 Springer-Verlag

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

PubMed Central

2010-01-01

Background Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD. Methods Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA. Results Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes. Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients. In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A. Conclusions Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis. PMID:20307269

Risks from Radon: Reconciling Miner and Residential Epidemiology

NASA Astrophysics Data System (ADS)

Chambers, Douglas B.; Harley, Naomi H.

2008-08-01

Everyone is exposed to radon, an inert radioactive gas that occurs naturally and is present everywhere in the atmosphere. The annual dose from radon and its (short-lived) decay products is typically about one-half of the dose received by members of the public from all natural sources of ionizing radiation. Data on exposures and consequent effects have recently been reviewed by the National Council on Radiation Protection and Measurements (NCRP) and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Studies of underground miners provides a well-established basis for estimating risks from occupational exposures to radon and for studying factors that may affect the dose response relationship such as the reduction of risk (coefficients) with increasing time since exposure. Miners' studies previously formed the basis for estimating risks to people exposed to radon at home, with downward extrapolation from exposures in mines to residential levels of radon. Presently, the risk estimates from residential studies are adequate to estimate radon risks in homes. Although there are major uncertainties in extrapolating the risks of exposure to radon from the miner studies to assessing risks in the home, there is remarkably good agreement between the average of risk factors derived from miner studies and those from pooled residential case-control studies. There are now over 20 analytical studies of residential radon and lung cancer. These studies typically assess the relative risk from exposure to radon based on estimates of residential exposure over a period of 25 to 30 years prior to diagnosis of lung cancer. Recent pooled analyses of residential case-control studies support a small but detectable lung cancer risk from residential exposure, and this risk increases with increasing concentrations. The excess relative risk of lung cancer from long-term residential exposure is about the same for both smokers and non-smokers; however, because the baseline lung cancer rate for smokers is much higher than for non or never smokers, smokers account for nearly 90% of the population risk from residential exposure to radon. As described in the paper, an excess relative risk (ERR) of 0.12(95% CI: 0.08-0.2)per 100 Bq m-3 (radon gas) can be estimated from combined miner studies. This compares well with the ERR from pooled residential case-control studies (for restricted analysis) for Europe of 0.16(95% CI: 0.05-0.31)[1] and for North America of 0.11(95% CI: 0.0-0.28)[2].

Development of a Just-in-Time Adaptive Intervention for Smoking Cessation Among Korean American Emerging Adults

PubMed Central

Cerrada, Christian Jules; Dzubur, Eldin; Blackman, Kacie C. A.; Mays, Vickie; Shoptaw, Steven; Huh, Jimi

2017-01-01

Purpose Cigarette smoking is a preventable risk factor that contributes to unnecessary lung cancer burden among Korean Americans and there is limited research on effective smoking cessation strategies for this population. Smartphone-based smoking cessation apps that leverage just-in-time adaptive interventions (JITAIs) hold promise for smokers attempting to quit. However, little is known about how to develop and tailor a smoking cessation JITAI for Korean American emerging adult (KAEA) smokers. Method This paper documents the development process of MyQuit USC according to design guidelines for JITAI. Our development process builds on findings from a prior ecological momentary assessment study by using qualitative research methods. Semi-structured interviews and a focus group were conducted to inform which intervention options to offer and the decision rules that dictate their delivery. Results Qualitative findings highlighted that (1) smoking episodes are highly context-driven and that (2) KAEA smokers believe they need personalized cessation strategies tailored to different contexts. Thus, MyQuit USC operates via decision rules that guide the delivery of personalized implementation intentions, which are contingent on dynamic factors, to be delivered “just in time” at user-scheduled, high-risk smoking situations. Conclusion Through an iterative design process, informed by quantitative and qualitative formative research, we developed a smoking cessation JITAI tailored specifically for KAEA smokers. Further testing is under way to optimize future versions of the app with the most effective intervention strategies and decision rules. MyQuit USC has the potential to provide cessation support in real-world settings, when KAEAs need them the most. PMID:28070868

Development of a Just-in-Time Adaptive Intervention for Smoking Cessation Among Korean American Emerging Adults.

PubMed

Cerrada, Christian Jules; Dzubur, Eldin; Blackman, Kacie C A; Mays, Vickie; Shoptaw, Steven; Huh, Jimi

2017-10-01

Cigarette smoking is a preventable risk factor that contributes to unnecessary lung cancer burden among Korean Americans and there is limited research on effective smoking cessation strategies for this population. Smartphone-based smoking cessation apps that leverage just-in-time adaptive interventions (JITAIs) hold promise for smokers attempting to quit. However, little is known about how to develop and tailor a smoking cessation JITAI for Korean American emerging adult (KAEA) smokers. This paper documents the development process of MyQuit USC according to design guidelines for JITAI. Our development process builds on findings from a prior ecological momentary assessment study by using qualitative research methods. Semi-structured interviews and a focus group were conducted to inform which intervention options to offer and the decision rules that dictate their delivery. Qualitative findings highlighted that (1) smoking episodes are highly context-driven and that (2) KAEA smokers believe they need personalized cessation strategies tailored to different contexts. Thus, MyQuit USC operates via decision rules that guide the delivery of personalized implementation intentions, which are contingent on dynamic factors, to be delivered "just in time" at user-scheduled, high-risk smoking situations. Through an iterative design process, informed by quantitative and qualitative formative research, we developed a smoking cessation JITAI tailored specifically for KAEA smokers. Further testing is under way to optimize future versions of the app with the most effective intervention strategies and decision rules. MyQuit USC has the potential to provide cessation support in real-world settings, when KAEAs need them the most.

Clinical and Radiologic Disease in Smokers With Normal Spirometry

PubMed Central

Regan, Elizabeth A.; Lynch, David A.; Curran-Everett, Douglas; Curtis, Jeffrey L.; Austin, John H. M.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bailey, William C.; DeMeo, Dawn L.; Casaburi, Richard H.; Friedman, Paul; Van Beek, Edwin J. R.; Hokanson, John E.; Bowler, Russell P.; Beaty, Terri H.; Washko, George R.; Han, MeiLan K.; Kim, Victor; Kim, Song Soo; Yagihashi, Kunihiro; Washington, Lacey; McEvoy, Charlene E.; Tanner, Clint; Mannino, David M.; Make, Barry J.; Silverman, Edwin K.; Crapo, James D.

2015-01-01

IMPORTANCE Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. OBJECTIVE To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. DESIGN, SETTING, AND PARTICIPANTS Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. MAIN OUTCOMES AND MEASURES Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. RESULTS One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George’s Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. CONCLUSIONS AND RELEVANCE Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone. PMID:26098755

Clinical and Radiologic Disease in Smokers With Normal Spirometry.

PubMed

Regan, Elizabeth A; Lynch, David A; Curran-Everett, Douglas; Curtis, Jeffrey L; Austin, John H M; Grenier, Philippe A; Kauczor, Hans-Ulrich; Bailey, William C; DeMeo, Dawn L; Casaburi, Richard H; Friedman, Paul; Van Beek, Edwin J R; Hokanson, John E; Bowler, Russell P; Beaty, Terri H; Washko, George R; Han, MeiLan K; Kim, Victor; Kim, Song Soo; Yagihashi, Kunihiro; Washington, Lacey; McEvoy, Charlene E; Tanner, Clint; Mannino, David M; Make, Barry J; Silverman, Edwin K; Crapo, James D

2015-09-01

Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

PubMed Central

Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

2013-01-01

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

Psychosocial consequences in the Danish randomised controlled lung cancer screening trial (DLCST).

PubMed

Rasmussen, Jakob F; Siersma, V; Pedersen, J H; Brodersen, J

2015-01-01

To measure the psychosocial consequences in the Danish lung cancer screening trial (DLCST) and compare those between the computed tomography (CT) group and the control group. This study was a single centre randomised controlled trial with five annual screening rounds. Healthy current or former heavy smokers aged 50-70 years (men and women) were randomised 1:1 to a CT group and a control group. Heavy smokers were defined by having smoked ≥20 pack years and former smokers by being abstinent ≤10 years. Both groups were invited annually to the screening clinic to complete the validated lung-cancer-specific questionnaire consequences of screening lung cancer (COS-LC). The CT group was also offered a low dose CT scan of the lungs. The COS-LC measures nine scales with psychosocial properties: Anxiety, Behaviour, Dejection, Negative impact on sleep, Self-blame, Focus on Airway Symptoms, Stigmatisation, Introvert, and Harm of Smoking. 4104 participants were randomised to the DLCST and the COS-LC completion rates for the CT group and the control group were 95.5% and 73.6%, respectively. There was a significant increase in negative psychosocial consequences from baseline through rounds 2-5 for both the CT group and the control group (mean increase >0, p<.0001 for 3 of 4 possible scales). During rounds 2-5 the control group experienced significantly more negative psychosocial consequences in seven of nine scales compared with the CT group (mean Δ score >0 and p<.033). Lung cancer CT-screening trials induced more negative psychosocial reactions in both the CT group and the control group compared with the baseline psychosocial profile. The CT group experienced less negative psychosocial consequences compared with the control group, which might be explained by reassurance among those with normal screening results. ClinicalTrials.gov: NCT00496977. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.

PubMed

Wang, Wen-Tao; Li, Yin; Ma, Jie; Chen, Xiao-Bing; Qin, Jian-Jun

2014-01-01

Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

Continuous quantitative measurement of the proximal airway dimensions and lung density on four-dimensional dynamic-ventilation CT in smokers

PubMed Central

Yamashiro, Tsuneo; Moriya, Hiroshi; Tsubakimoto, Maho; Matsuoka, Shin; Murayama, Sadayuki

2016-01-01

Purpose Four-dimensional dynamic-ventilation computed tomography (CT) imaging demonstrates continuous movement of the airways and lungs, which cannot be depicted with conventional CT. We aimed to investigate continuous changes in lung density and airway dimensions and to assess the correlation with spirometric values in smokers. Materials and methods This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Twenty-one smokers including six patients with COPD underwent four-dimensional dynamic-ventilation CT during free breathing (160 mm in length). The mean lung density (MLD) of the scanned lung and luminal areas (Ai) of fixed points in the trachea and the right proximal bronchi (main bronchus, upper bronchus, bronchus intermedius, and lower bronchus) were continuously measured. Concordance between the time curve of the MLD and that of the airway Ai values was expressed by cross-correlation coefficients. The associations between these quantitative measurements and the forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) values were assessed by Spearman’s rank correlation analysis. Results On the time curve for the MLD, the Δ-MLD1.05 values between the peak inspiratory frame to the later third frame (1.05 seconds later) were strongly correlated with the FEV1/FVC (ρ=0.76, P<0.0001). The cross-correlation coefficients between the airway Ai and MLD values were significantly correlated with the FEV1/FVC (ρ=−0.56 to −0.66, P<0.01), except for the right upper bronchus. This suggested that the synchrony between the airway and lung movement was lost in patients with severe airflow limitation. Conclusion Respiratory changes in the MLD and synchrony between the airway Ai and the MLD measured with dynamic-ventilation CT were correlated with patient’s spirometric values. PMID:27110108

Clinico-pathology of lung cancer in a regional cancer center in Northeastern India.

PubMed

Mandal, Sanjeet Kumar; Singh, Thaudem Tomcha; Sharma, Takhenchangbam Dhaneshor; Amrithalingam, Venkatesan

2013-01-01

Globally, there have been important changes in trends amongst gender, histology and smoking patterns of lung cancer cases. This retrospective study was conducted on 466 patients with lung cancer who were registered in Regional Cancer Center, Regional Institute of Medical Sciences, Manipur from January 2008 to December 2012. Most were more than 60 years of age (67.8%) with a male: female ratio of 1.09:1. Some 78.8% of patients were chronic smokers with male smoker to female smoker ratio of 1.43:1. Consumption of alcohol was found in 29.4%, both smoking and alcohol in 27.5%, betel nut chewing in 37.9% and tobacco chewing in 25.3%. A history of tuberculosis was present in 16.3% of patients. The most frequent symptom was coughing (36.6%) and most common radiological presentation was a mass lesion (70%). Most of the patients had primary lung cancer in the right lung (60.3%). The most common histological subtype was squamous cell carcinoma (49.1%), also in the 40-60 year age group (45.9%), more than 60 year age group (51.6%), males (58.1%) and females (41.8%). As many as 91.9% of squamous cell carcinoma patients had a history of smoking. About 32.5% of patients had distant metastasis at presentation with brain (23.8%) and positive malignant cells in pleural effusions (23.1%) as common sites. The majority of patients were in stage III (34.4%), stage IV (32.5%) and stage II (30.2%). Our analysis suggests that the gender gap has been narrowed such that about half of the patients diagnosed with lung cancer are women in this part of India. This alarming rise in female incidence is mainly attributed to an increased smoking pattern. Squamous cell carcinoma still remains the commonest histological subtype. Most of the patients were elderly aged and presented at locally or distantly advanced stages.

Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk Stratification in Smokers: MESA.

PubMed

Leigh, Adam; McEvoy, John W; Garg, Parveen; Carr, J Jeffrey; Sandfort, Veit; Oelsner, Elizabeth C; Budoff, Matthew; Herrington, David; Yeboah, Joseph

2018-02-09

This study assessed the utility of the pooled cohort equation (PCE) and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk assessment in smokers, especially those who were lung cancer screening eligible (LCSE). The U.S. Preventive Services Task Force recommended and the Centers for Medicare & Medicaid Services currently pays for annual screening for lung cancer with low-dose computed tomography scans in a specified group of cigarette smokers. CAC can be obtained from these low-dose scans. The incremental utility of CAC for ASCVD risk stratification remains unclear in this high-risk group. Of 6,814 MESA (Multi-Ethnic Study of Atherosclerosis) participants, 3,356 (49.2% of total cohort) were smokers (2,476 former and 880 current), and 14.3% were LCSE. Kaplan-Meier, Cox proportional hazards, area under the curve, and net reclassification improvement (NRI) analyses were used to assess the association between PCE and/or CAC and incident ASCVD. Incident ASCVD was defined as coronary death, nonfatal myocardial infarction, or fatal or nonfatal stroke. Smokers had a mean age of 62.1 years, 43.5% were female, and all had a mean of 23.0 pack-years of smoking. The LCSE sample had a mean age of 65.3 years, 39.1% were female, and all had a mean of 56.7 pack-years of smoking. After a mean of 11.1 years of follow-up 13.4% of all smokers and 20.8% of LCSE smokers had ASCVD events; 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during the follow-up. One SD increase in the PCE 10-year risk was associated with a 68% increase risk for ASCVD events in all smokers (hazard ratio: 1.68; 95% confidence interval: 1.57 to 1.80) and a 22% increase in risk for ASCVD events in the LCSE smokers (hazard ratio: 1.22; 95% confidence interval: 1.00 to 1.47). CAC was associated with increased ASCVD risk in all smokers and in LCSE smokers in all the Cox models. The C-statistic of the PCE for ASCVD was higher in all smokers compared with LCSE smokers (0.693 vs. 0.545). CAC significantly improved the C-statistics of the PCE in all smokers but not in LCSE smokers. The event and nonevent net reclassification improvements for all smokers and LCSE smokers were 0.018 and -0.126 versus 0.16 and -0.196, respectively. In this well-characterized, multiethnic U.S. cohort, CAC was predictive of ASCVD in all smokers and in LCSE smokers but modestly improved discrimination over and beyond the PCE. However, 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during follow-up. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of breathing exercises on lung capacity and muscle activities of elderly smokers.

PubMed

Jun, Hyun-Ju; Kim, Ki-Jong; Nam, Ki-Won; Kim, Chang-Heon

2016-06-01

[Purpose] Elderly smokers have a reduced chest diameter due to weakening of the respiratory muscles, and this results in decreased ventilation, leading to a vicious circle. Therefore, the present study investigated the effects of an intervention program to enhance the pulmonary function and muscle activity of elderly smokers. [Subjects and Methods] Participants were randomly assigned to one of two experimental groups or a control (CG) group. The experimental groups performed exercises three times per week for six weeks, whereas the CG performed no exercises. One of the experimental groups performed a Feedback Breathing Exercise (FBE) for 15 minutes, and the other repeated three sets of Balloon-Blowing Exercises (BBE) with sufficient rest of more than one minute between sets. [Results] In the experimental groups, FVC, FEV1/FVC, PEF and muscle activity of the rectus abdominis significantly improved after four weeks, but no significant differences were observed in FEV1 or VC after six weeks. [Conclusion] The results show that FBE and BBE improved the pulmonary functions of elderly smokers, demonstrating the potential benefits of the development of various training methods using balloons, and group programs, including recreational factors, for increasing respiratory muscles strength.

Effects of breathing exercises on lung capacity and muscle activities of elderly smokers

PubMed Central

Jun, Hyun-Ju; Kim, Ki-Jong; Nam, Ki-Won; Kim, Chang-Heon

2016-01-01

[Purpose] Elderly smokers have a reduced chest diameter due to weakening of the respiratory muscles, and this results in decreased ventilation, leading to a vicious circle. Therefore, the present study investigated the effects of an intervention program to enhance the pulmonary function and muscle activity of elderly smokers. [Subjects and Methods] Participants were randomly assigned to one of two experimental groups or a control (CG) group. The experimental groups performed exercises three times per week for six weeks, whereas the CG performed no exercises. One of the experimental groups performed a Feedback Breathing Exercise (FBE) for 15 minutes, and the other repeated three sets of Balloon-Blowing Exercises (BBE) with sufficient rest of more than one minute between sets. [Results] In the experimental groups, FVC, FEV1/FVC, PEF and muscle activity of the rectus abdominis significantly improved after four weeks, but no significant differences were observed in FEV1 or VC after six weeks. [Conclusion] The results show that FBE and BBE improved the pulmonary functions of elderly smokers, demonstrating the potential benefits of the development of various training methods using balloons, and group programs, including recreational factors, for increasing respiratory muscles strength. PMID:27390394

Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

PubMed

Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

2014-01-01

It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

Ion Channel Gene Expression in Lung Adenocarcinoma: Potential Role in Prognosis and Diagnosis

PubMed Central

Ko, Jae-Hong; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Eun A.; Zhou, Tong

2014-01-01

Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts. PMID:24466154

Rotating Night-Shift Work and Lung Cancer Risk Among Female Nurses in the United States

PubMed Central

Schernhammer, Eva S.; Feskanich, Diane; Liang, Geyu; Han, Jiali

2013-01-01

The risk of lung cancer among night-shift workers is unknown. Over 20 years of follow-up (1988–2008), we documented 1,455 incident lung cancers among 78,612 women in the Nurses' Health Study. To examine the relationship between rotating night-shift work and lung cancer risk, we used multivariate Cox proportional hazard models adjusted for detailed smoking characteristics and other risk factors. We observed a 28% increased risk of lung cancer among women with 15 or more years spent working rotating night shifts (multivariate relative risk (RR) = 1.28, 95% confidence interval (CI): 1.07, 1.53; Ptrend = 0.03) compared with women who did not work any night shifts. This association was strongest for small-cell lung carcinomas (multivariate RR = 1.56, 95% CI: 0.99, 2.47; Ptrend = 0.03) and was not observed for adenocarcinomas of the lung (multivariate RR = 0.91, 95% CI: 0.67, 1.24; Ptrend = 0.40). Further, the increased risk associated with 15 or more years of rotating night-shift work was limited to current smokers (RR = 1.61, 95% CI: 1.21, 2.13; Ptrend < 0.001), with no association seen in nonsmokers (Pinteraction = 0.03). These results suggest that there are modestly increased risks of lung cancer associated with extended periods of night-shift work among smokers but not among nonsmokers. Though it is possible that this observation was residually confounded by smoking, our findings could also provide evidence of circadian disruption as a “second hit” in the etiology of smoking-related lung tumors. PMID:24049158

Benefits and harms of lung cancer screening in HIV-infected individuals with CD4+ ≥ 500: a simulation study.

PubMed

Kong, Chung Yin; Sigel, Keith; Criss, Steven D; Sheehan, Deirdre F; Triplette, Matthew; Silverberg, Michael J; Henschke, Claudia I; Justice, Amy; Braithwaite, R Scott; Wisnivesky, Juan; Crothers, Kristina

2018-04-19

Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. Target population: HIV-infected current and former smokers. Lifetime. Population. Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. For HIV-infected patients with CD4 at least 500 and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55-77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. Strategies assumed 100% screening adherence. Lung cancer screening reduces mortality in HIV-infected patients with CD4 at least l500, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

PubMed

West, Howard L; Moon, James; Wozniak, Antoinette J; Mack, Philip; Hirsch, Fred R; Bury, Martin J; Kwong, Myron; Nguyen, Dorothy D; Moore, Dennis F; Miao, Jieling; Redman, Mary; Kelly, Karen; Gandara, David R

2018-01-01

Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

Sustained response to standard dose osimertinib in a patient with plasma T790M-positive leptomeningeal metastases from primary lung adenocarcinoma.

PubMed

Chan, Oscar Siu-Hong; Leung, Warren Kam-Wing; Yeung, Rebecca Mei-Wan

2017-12-01

A 44-year-old male, never smoker, suffers from stage IV adenocarcinoma of the right lung with epidermal growth factor receptor (EGFR) exon-21 L858R point mutation on initial presentation. After 23 months of treatment with gefitinib, intercalated with multiple courses of radiotherapy, leptomeningeal metastases (LMs) developed. Acquired T790M mutation was confirmed by the droplet digital polymerase chain reaction plasma EGFR test. After switching to osimertinib at the standard dose, his neurocognitive function improved clinically, coupled with sustained radiological improvement. As this clinical entity is underrepresented in clinical trials, the practicability of plasma EGFR testing and the optimal dose-response relationship of osimertinib in T790M-positive lung cancer complicated with LM deserves further exploration. © 2017 John Wiley & Sons Australia, Ltd.

Primary Lung Signet Ring Cell Carcinoma Presenting as a Cavitary Pancoast Tumor in a 32-Year-Old Man.

PubMed

Corvini, Michael; Koorji, Alysha; Sgroe, Erica; Nguyen, Uyen

2018-06-01

Signet ring cell carcinoma, a subtype of adenocarcinoma, is a rare cause of primary lung cancer. The authors report a case of primary lung signet ring cell carcinoma presenting as a cavitary Pancoast tumor in a 32-year-old male smoker. Beyond the rarity of primary lung signet ring cell carcinoma itself, the youth of the patient, his smoking status, the presence of cavitation, and the location of the tumor in the superior sulcus make it especially atypical.

Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210.

PubMed

Little, J B; Kennedy, A R; McGandy, R B

1975-05-16

Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer.

Factors affecting Taiwanese smokers' identification of smuggled cigarettes.

PubMed

Hsieh, Chi-Jung; Cheng, Chun-Hao; Lee, Jie-Min

2015-05-01

To analyze whether the perception that smuggled cigarettes are a greater health risk than legal cigarettes affects Taiwanese smokers' intention to distinguish smuggled cigarettes from legal cigarettes. The study used the Recursive Bivariate Probit Model to analyze data from a survey conducted in 2013 of 450 smokers of smuggled cigarettes. The study found that when smokers believe they are more likely to get lung cancer from consuming smuggled cigarettes than they are from consuming legal cigarettes, the probability of the intention to identify smuggled cigarettes increased by 42.46%. The government should strengthen educational policies and programs that teach consumers about the health risks of smoking in general and the even greater health risks of smoking smuggled cigarettes in particular.

LUNG TUMOR KRAS AND TP53 MUTATIONS IN NON-SMOKERS REFLECT EXPOSURE TO PAH-RICH COAL COMBUSTION EMISSIONS

EPA Science Inventory

Abstract

We determined the TP53 and codon 12 KRAS mutations in lung tumors from 24 nonsmokers whose tumors were associated with exposure to smoky coal. Among any tumors studied previously, these showed the highest percentage of mutations that (a) were G -+ T transver...

How rapidly does the excess risk of lung cancer decline following quitting smoking? A quantitative review using the negative exponential model.

PubMed

Fry, John S; Lee, Peter N; Forey, Barbara A; Coombs, Katharine J

2013-10-01

The excess lung cancer risk from smoking declines with time quit, but the shape of the decline has never been precisely modelled, or meta-analyzed. From a database of studies of at least 100 cases, we extracted 106 blocks of RRs (from 85 studies) comparing current smokers, former smokers (by time quit) and never smokers. Corresponding pseudo-numbers of cases and controls (or at-risk) formed the data for fitting the negative exponential model. We estimated the half-life (H, time in years when the excess risk becomes half that for a continuing smoker) for each block, investigated model fit, and studied heterogeneity in H. We also conducted sensitivity analyses allowing for reverse causation, either ignoring short-term quitters (S1) or considering them smokers (S2). Model fit was poor ignoring reverse causation, but much improved for both sensitivity analyses. Estimates of H were similar for all three analyses. For the best-fitting analysis (S1), H was 9.93 (95% CI 9.31-10.60), but varied by sex (females 7.92, males 10.71), and age (<50years 6.98, 70+years 12.99). Given that reverse causation is taken account of, the model adequately describes the decline in excess risk. However, estimates of H may be biased by factors including misclassification of smoking status. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Cellular morphometry of the bronchi of human and dog lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, E.S.

1991-09-01

One hundred and forty-seven bronchial samples (generations 3--6) from 66 patients (62 usable; 36 female, 26 male; median age 61) have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. In addition, one hundred and fifty-six mongol dog bronchi (generations 2--6) dissected from different lobes of 26 dog lungs have also been similarly prepared. One hundred and twenty-seven human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 655 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurement ofmore » the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 328 micrographs of dog epithelium from 33 bronchial samples have been used to measure the distances of basal and mucous cell nuclei to the epithelial free surface and have been entered into COSAS. Using the COSAS planimetry program, we continue to expand our established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the same 5 epithelial cell types of dog bronchi. Our micrographs of human bronchial epithelium have allowed us to analyze the recent suggestion that the DNA of lymphocytes may be subject to significant damage from Rn progeny while within the lung. Since the last progress report three papers have been submitted for publication. 17 refs., 4 tabs.« less

T2* measurements of 3-T MRI with ultrashort TEs: capabilities of pulmonary function assessment and clinical stage classification in smokers.

PubMed

Ohno, Yoshiharu; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Keiko; Takahashi, Masaya; Van Cauteren, Marc; Sugimura, Kazuro

2011-08-01

The purpose of this study was to determine the usefulness of MRI with ultrashort TEs on a 3-T system and of thin-section MDCT for pulmonary function assessment and clinical stage classification of chronic obstructive pulmonary disease (COPD) in smokers. Forty smokers (24 men and 16 women; mean age ± SD, 68.0 ± 9.3 years) underwent MRI with ultrashort TEs and thin-section MDCT. Pulmonary function testing was also performed to determine the following: the ratio of forced expiratory volume in 1 second to forced vital capacity (percentage predicted) (FEV(1/)FVC%), percentage predicted forced expiratory volume in 1 second (%FEV(1)), and percentage predicted diffusing capacity of lung for carbon monoxide corrected for alveolar volume (%DLCO/V(A)). All subjects were classified into one of four groups as follows: smokers without COPD, with mild COPD, with moderate COPD, and with severe or very severe COPD. T2(*) maps were expressed using proprietary software. Regional T2(*) values were determined by region of interest measurements and were averaged to determine a mean T2(*) value for each subject. CT-based functional lung volume and the ratio of the wall area to the total airway area were also determined. All indexes were statistically correlated with pulmonary function parameters. Then, all indexes were compared among all groups by means of Tukey's honest significance test. All indexes had significant correlation with FEV(1)/FVC%, %FEV(1), and % DLCO/V(A) (p < 0.05). All indexes except WA% of smokers without COPD and smokers with mild COPD differed significantly from those of smokers with moderate COPD and smokers with severe or very severe COPD (p < 0.05). Moreover, the mean T2(*) value of the moderate COPD group was significantly different from that of the severe or very severe COPD group (p < 0.05). MRI with ultrashort TEs is potentially as useful as quantitatively assessed MDCT for pulmonary function loss assessment and clinical stage classification of COPD in smokers.

Canine scent detection for the diagnosis of lung cancer in a screening-like situation.

PubMed

Hackner, Klaus; Errhalt, Peter; Mueller, Michael Rolf; Speiser, Manulea; Marzluf, Beatrice A; Schulheim, Andrea; Schenk, Peter; Bilek, Johannes; Doll, Theodor

2016-09-27

The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex-smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respectively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers.

Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

PubMed

Saccone, Nancy L; Culverhouse, Robert C; Schwantes-An, Tae-Hwi; Cannon, Dale S; Chen, Xiangning; Cichon, Sven; Giegling, Ina; Han, Shizhong; Han, Younghun; Keskitalo-Vuokko, Kaisu; Kong, Xiangyang; Landi, Maria Teresa; Ma, Jennie Z; Short, Susan E; Stephens, Sarah H; Stevens, Victoria L; Sun, Lingwei; Wang, Yufei; Wenzlaff, Angela S; Aggen, Steven H; Breslau, Naomi; Broderick, Peter; Chatterjee, Nilanjan; Chen, Jingchun; Heath, Andrew C; Heliövaara, Markku; Hoft, Nicole R; Hunter, David J; Jensen, Majken K; Martin, Nicholas G; Montgomery, Grant W; Niu, Tianhua; Payne, Thomas J; Peltonen, Leena; Pergadia, Michele L; Rice, John P; Sherva, Richard; Spitz, Margaret R; Sun, Juzhong; Wang, Jen C; Weiss, Robert B; Wheeler, William; Witt, Stephanie H; Yang, Bao-Zhu; Caporaso, Neil E; Ehringer, Marissa A; Eisen, Tim; Gapstur, Susan M; Gelernter, Joel; Houlston, Richard; Kaprio, Jaakko; Kendler, Kenneth S; Kraft, Peter; Leppert, Mark F; Li, Ming D; Madden, Pamela A F; Nöthen, Markus M; Pillai, Sreekumar; Rietschel, Marcella; Rujescu, Dan; Schwartz, Ann; Amos, Christopher I; Bierut, Laura J

2010-08-05

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Oral bisphosphonate use and lung cancer incidence among postmenopausal women

PubMed Central

Tao, M H; Chen, S; Freudenheim, J L; Cauley, J A; Johnson, K C; Mai, X; Sarto, G E; Wakelee, H; Boffetta, P; Wactawski-Wende, J

2018-01-01

Abstract Background Bisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women’s Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI. Patients and methods The association between oral bisphosphonate use and lung cancer risk was examined in 151 432 postmenopausal women enrolled into the WHI in 1993–1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates. Results After a mean follow-up of 13.3 years, 2511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio = 0.91; 95% confidence intervals, 0.80–1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (hazard ratio = 0.57, 95% confidence interval, 0.39–0.84; P < 0.01). Conclusion In this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings. PMID:29617712

Sensitivity and specificity of 3-D texture analysis of lung parenchyma is better than 2-D for discrimination of lung pathology in stage 0 COPD

NASA Astrophysics Data System (ADS)

Xu, Ye; Sonka, Milan; McLennan, Geoffrey; Guo, Junfeng; Hoffman, Eric

2005-04-01

Lung parenchyma evaluation via multidetector-row CT (MDCT), has significantly altered clinical practice in the early detection of lung disease. Our goal is to enhance our texture-based tissue classification ability to differentiate early pathologic processes by extending our 2-D Adaptive Multiple Feature Method (AMFM) to 3-D AMFM. We performed MDCT on 34 human volunteers in five categories: emphysema in severe Chronic Obstructive Pulmonary Disease (COPD) as EC, emphysema in mild COPD (MC), normal appearing lung in COPD (NC), non-smokers with normal lung function (NN), smokers with normal function (NS). We volumetrically excluded the airway and vessel regions, calculated 24 volumetric texture features for each Volume of Interest (VOI); and used Bayesian rules for discrimination. Leave-one-out and half-half methods were used for testing. Sensitivity, specificity and accuracy were calculated. The accuracy of the leave-one-out method for the four-class classification in the form of 3-D/2-D is: EC: 84.9%/70.7%, MC: 89.8%/82.7%; NC: 87.5.0%/49.6%; NN: 100.0%/60.0%. The accuracy of the leave-one-out method for the two-class classification in the form of 3-D/2-D is: NN: 99.3%/71.6%; NS: 99.7%/74.5%. We conclude that 3-D AMFM analysis of the lung parenchyma improves discrimination compared to 2-D analysis of the same images.

Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

PubMed Central

Zhou, Si-jing; Li, Min; Zeng, Da-xiong; Zhu, Zhong-ming; Hu, Xian-Wei; Li, Yong-huai; Wang, Ran; Sun, Geng-yun

2015-01-01

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were significantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These findings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD. PMID:25708588

Radon, Secondhand Smoke, and Children in the Home: Creating a Teachable Moment for Lung Cancer Prevention.

PubMed

Huntington-Moskos, Luz; Rayens, Mary Kay; Wiggins, Amanda; Hahn, Ellen J

2016-11-01

This study determined whether having minor children in the home was associated with the teachable moment (TM) constructs of lung cancer worry, perceived risk, health-related self-concept, and the novel construct of synergistic risk. Secondary data analysis of baseline data from a randomized controlled trial of an intervention to reduce home exposure to radon and secondhand smoke (SHS). Quota sample of adults recruited at a Central Kentucky academic medical center (N = 556). Survey items assessed lung cancer worry, perceived risk, synergistic risk perception, and health-related self-concept. The presence of children in the home was not a significant predictor of any construct needed to create a TM for lung cancer prevention. Individuals with children living in the home were more likely to be younger, a racial/ethnic minority, a current smoker, and live with a smoker compared to those without children in the home. There is a critical need to raise parental awareness on child health inequities related to the home exposure to radon and SHS. Public health nurses can create TMs for lung cancer prevention through greater awareness of the risks posed by radon and SHS along with promoting home testing and low-cost resources to reduce risk. © 2016 Wiley Periodicals, Inc.

The effect of smoking on lung cancer: ethnic differences and the smoking paradox

PubMed Central

2016-01-01

The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians. PMID:28092929

Radon, Secondhand Smoke and Children in the Home: Creating a Teachable Moment for Lung Cancer Prevention

PubMed Central

Huntington-Moskos, Luz; Rayens, Mary Kay; Wiggins, Amanda; Hahn, Ellen J.

2016-01-01

Objective This study determined whether having minor children in the home was associated with the Teachable Moment (TM) constructs of lung cancer worry, perceived risk, health-related self-concept, and the novel construct of synergistic risk. Design Secondary data analysis of baseline data from a randomized controlled trial of an intervention to reduce home exposure to radon and secondhand smoke (SHS). Sample Quota sample of adults recruited at a Central Kentucky academic medical center (N = 556). Measurements Survey items assessed lung cancer worry, perceived risk, synergistic risk perception, and health-related self-concept. Results The presence of children in the home was not a significant predictor of any construct needed to create a teachable moment for lung cancer prevention. Individuals with children living in the home were more likely to be younger, a racial/ethnic minority, a current smoker, and live with a smoker compared to those without children in the home. Conclusions There is a critical need to raise parental awareness on child health inequities related to the home exposure to radon and SHS. Public health nurses can create teachable moments for lung cancer prevention through greater awareness of the risks posed by radon and SHS along with promoting home testing and low cost resources to reduce risk. PMID:27443982

Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women.

PubMed

Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E

2016-09-01

The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.

A randomized controlled trial on the efficacy of thoracic CT screening for lung cancer in non-smokers and smokers of <30 pack-years aged 50-64 years (JECS study): research design.

PubMed

Sagawa, Motoyasu; Nakayama, Tomio; Tanaka, Makoto; Sakuma, Tsutomu; Sobue, Tomotaka

2012-12-01

In order to assess the efficacy of lung cancer screening using low-dose thoracic computed tomography, compared with chest roentgenography, in people aged 50-64 years with a smoking history of <30 pack-years, a randomized controlled trial is being conducted in Japan. The screening methods are randomly assigned individually. The duration of this trial is 10 years. In the intervention arm, low-dose thoracic computed tomography is performed for each participant in the first and the sixth years. In the control arm, chest roentgenography is performed for each participant in the first year. The participants in both arms are also encouraged to receive routine lung cancer screening using chest roentgenography annually. The interpretation of radiological findings and the follow-up of undiagnosed nodules are to be carried out according to the guidelines published in Japan. The required sample size is calculated to be 17 500 subjects for each arm.

Baseline Characteristics of Participants in the Randomized National Lung Screening Trial

PubMed Central

Aberle, Denise R.; Adams, Amanda M.; Berg, Christine D.; Clapp, Jonathan D.; Clingan, Kathy L.; Gareen, Ilana F.; Marcus, Pamela M.; Pinsky, Paul F.

2010-01-01

Background The National Lung Screening Trial (NLST), a randomized study conducted at 33 US sites, is comparing lung cancer mortality among persons screened with reduced dose helical computerized tomography and among persons screened with chest radiograph. In this article, we present characteristics of the study population. Methods Eligible participants were aged 55–74 years and were current or former smokers with a cigarette smoking history of at least 30 pack-years. Randomization was stratified by site, sex, and age. To assess representativeness of the study population, demographic characteristics of individuals from the general population who met NLST age and smoking history inclusion criteria were obtained from the Tobacco Use Supplement of the US Census Bureau Current Population Surveys. Results The NLST enrolled 53 456 persons, with 26 733 randomly assigned to chest radiograph screening and 26 723 to computerized tomography screening. Characteristics of the participants were as follows: 31 533 (59%) were men, 39 234 (73%) were younger than 65 years, 25 779 (48%) were current smokers, and 16 839 (32%) had a college or higher degree. Median cigarette exposure was 48 pack-years. Among Tobacco Use Supplement respondents who met NLST age and smoking history criteria, 59% were men, 65% were younger than 65 years, and 57% were current smokers. Median cigarette exposure among this group was 47 pack-years, and 14% had a college degree or higher. Conclusion The NLST cohort has a distribution of sex and pack-year history that is similar to the component of the general US population that meets the major NLST eligibility criteria; however, NLST participants are younger, better educated, and less likely to be current smokers. PMID:21119104

Bronchoarterial ratio in never-smokers adults: Implications for bronchial dilation definition.

PubMed

Diaz, Alejandro A; Young, Thomas P; Maselli, Diego J; Martinez, Carlos H; Maclean, Erick S; Yen, Andrew; Dass, Chandra; Simpson, Scott A; Lynch, David A; Kinney, Gregory L; Hokanson, John E; Washko, George R; San José Estépar, Raul

2017-01-01

Bronchiectasis manifests as recurrent respiratory infections and reduced lung function. Airway dilation, which is measured as the ratio of the diameters of the bronchial lumen (B) and adjacent pulmonary artery (A), is a defining radiological feature of bronchiectasis. A challenge to equating the bronchoarterial (BA) ratio to disease severity is that the diameters of airway and vessel in health are not established. We sought to explore the variability of BA ratio in never-smokers without pulmonary disease and its associations with lung function. Objective measurements of the BA ratio on volumetric computed tomography (CT) scans and pulmonary function data were collected in 106 never-smokers. The BA ratio was measured in the right upper lobe apical bronchus (RB1) and the right lower lobe basal posterior bronchus. The association between the BA ratio and forced expiratory volume in 1 s (FEV 1 ) was assessed using regression analysis. The BA ratio was 0.79 ± 0.16 and was smaller in more peripheral RB1 bronchi (P < 0.0001). The BA ratio was >1, a typical threshold for bronchiectasis, in 10 (8.5%) subjects. Subjects with a BA ratio >1 versus ≤1 had smaller artery diameters (P < 0.0001) but not significantly larger bronchial lumens. After adjusting for age, gender, race and height, the BA ratio was directly related to FEV 1 (P = 0.0007). In never-smokers, the BA ratio varies by airway generation and is associated with lung function. A BA ratio >1 is driven by small arteries. Using artery diameter as reference to define bronchial dilation seems inappropriate. © 2016 Asian Pacific Society of Respirology.

[The importance of lung volumes in the investigation of heavy smokers].

PubMed

Ben Saad, H; Ben Amor, L; Ben Mdalla, S; Ghannouchi, I; Ben Essghair, M; Sfaxi, R; Garrouche, A; Rouatbi, N; Rouatbi, S

2014-01-01

Lung hyperinflation (LH) has become a major concern in the management of chronic obstructive pulmonary disease (COPD). To evaluate the role of lung volumes in the positive diagnosis of COPD and in the assessment of airway obstruction reversibility. Three hundred and sixty-six male smokers over the age of 35 with more than 40 pack-years exposure were included in the study. Plethysmographic data were determined before/after taking a bronchodilator (BBD, ABD). Applied definitions: airflow obstruction: BBD FEV1/FVC<0.70. LH: BBD residual volume (RV)>upper limit of normal. Expressions of reversibility: Δvariable=(ABD-BBD) values; Δinit%=Δvariable/BBD value and Δref%=Δvariable/reference value. A 12%init and a 0.2L increase in either FEV1 or FVC or a 10%ref or - 300 mL decrease in RV were considered as clinically significant. Over the 85 smokers without airflow obstruction, 68% had LH. In the hyperinflated group (n=314), and compared to changes in FEV1 and FVC, these RV changes detected more respondents (54% for FEV1 and FVC vs. 65% for RV, P=0.002). This was not the case for the group free from LH (n=52) (23% for FEV1 and FVC vs. 35% for RV, P=0.09). In the 58 hyperinflated groups free from airflow obstruction, and compared to changes in FEV1 and FVC, changes in RV detected more respondents (24% for FEV1 and FVC vs. 71% for RV, P=0.0001). In heavy smokers, it seems essential to include LH as a criterion for a positive diagnosis of COPD and of reversibility evaluation. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Cigarette smoking and lead levels in occupationally exposed lead workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, C.P.; Spivey, G.H.; Valentine, J.L.

One hundred eleven workers at a secondary Pb smelter were surveyed to determine smoking and personal hygiene habits. Fifty-three percent of the smokers had blood Pb levels in excess of 60 ..mu..g/dl, compared to 31% of nonsmokers (p = 0.02). Among smokers, 66% of heavy smokers (greater than or equal to 1 pack a day) had blood Pb levels over 60 ..mu..g/dl, compared to 39% of the light smokers (p = O.05). Those who kept their cigarettes on their person had a higher proportion of blood Pb greater than 60 ..mu..g/dl than workers who kept their cigarettes elsewhere (63 vsmore » 36%, respectively; p = 0.08). The difference in blood Pb levels between smokers and nonsmokers may be due in part to direct environmental contamination of cigarettes or impaired lung clearance mechanisms, and could be important in workers with already elevated blood Pb levels.« less

Lung cancer prevalence associated with radon exposure in Norwegian homes.

PubMed

Hassfjell, Christina Søyland; Grimsrud, Tom Kristian; Standring, William J F; Tretli, Steinar

2017-08-22

Radioactive radon gas is generated from uranium and thorium in underlying rocks and seeps into buildings. The gas and its decay products emit carcinogenic radiation and are regarded as the second most important risk factor for lung cancer after active tobacco smoking. The average radon concentration in Norwegian homes is higher than in most other Western countries. From a health and cost perspective, it is important to be able to quantify the risk of lung cancer posed by radon exposure. We estimated the radon-related risk of lung cancer in Norway based on risk estimates from the largest pooled analysis of European case-control studies, combined with the hitherto largest set of data on radon concentration measurements in Norwegian homes. Based on these estimates, we calculate that radon is a contributory factor in 12 % of all cases of lung cancer annually, assuming an average radon concentration of 88 Bq/m3 in Norwegian homes. For 2015, this accounted for 373 cases of lung cancer, with an approximate 95 % confidence interval of 145 – 682. Radon most likely contributes to a considerable number of cases of lung cancer. Since most cases of radon-associated lung cancer involve smokers or former smokers, a reduction of the radon concentration in homes could be a key measure to reduce the risk, especially for persons who are unable to quit smoking. The uncertainty in the estimated number of radon-associated cases can be reduced through a new national radon mapping study with an improved design.

Not All Smokers Die Young: A Model for Hidden Heterogeneity within the Human Population

PubMed Central

Levine, Morgan; Crimmins, Eileen

2014-01-01

The ability of some individuals to reach extreme old age in the presence of clearly high exposure to damaging factors may signal an innate biological advantage. For this study we used data on 4,655 current and never smokers, ages 50 and above, from NHANES III to examine whether long-lived smokers represent a biologically resilient phenotype that could facilitate our understanding of heterogeneity in the aging process. Using a proportional hazards model, our results showed that while smoking significantly increased mortality in most age groups, it did not increase the mortality risk for those who were age 80 and over at baseline. Additionally when comparing the adjusted means of biomarkers between never and current smokers, we found that long-lived smokers (80+) had similar inflammation, HDL, and lung function levels to never smokers. Given that factors which allow some individuals to withstand smoking may also enable others to cope with everyday biological stressors, the investigation of long-lived smokers may eventually allow us to identify molecular and genetic mechanisms which enable longevity extension. PMID:24520332

Developing an effective lung cancer program in a community hospital setting.

PubMed

Fischel, Richard J; Dillman, Robert O

2009-07-01

Lung cancer remains the number one cause of cancer-based mortality in men and women. The importance of proper lung cancer care outside of major academic centers cannot be overemphasized because the vast majority of lung cancer care occurs in community hospital settings. We have had the opportunity to develop a highly successful community hospital-based lung cancer program. Utilizing a multidisciplinary approach, we have achieved steadily improving survival rates that are much higher than those observed nationally for patients diagnosed with lung cancer. Key components of this successful program include: (1) a weekly multidisciplinary lung cancer case conference with medical doctor representatives from medical oncology, thoracic surgery, pulmonary medicine, radiology, radiation oncology, and nuclear medicine who discuss patient presentation, test results, treatment history, and plans for therapy; (2) thoracic surgeons skilled in minimally invasive video-assisted thoracoscopic surgery; (3) nurse navigator/coordinators to help patients through the process from detection to recovery and provide a personal bond that greatly improves patient satisfaction; (4) utilization of treatment guidelines for patient-specific treatment strategies; (5) formal continuing medical education; (6) an emphasis on early detection that includes consideration of computed tomography screening of former smokers; (6) a cancer center that allows for many services to be offered at a single location for patient convenience and to promote interdisciplinary care; and (7) access to research protocols. These components have helped us provide a quality lung cancer program in a community hospital setting that is associated with excellent clinical outcomes.

Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium.

PubMed

Coté, Michele L; Liu, Mei; Bonassi, Stefano; Neri, Monica; Schwartz, Ann G; Christiani, David C; Spitz, Margaret R; Muscat, Joshua E; Rennert, Gad; Aben, Katja K; Andrew, Angeline S; Bencko, Vladimir; Bickeböller, Heike; Boffetta, Paolo; Brennan, Paul; Brenner, Hermann; Duell, Eric J; Fabianova, Eleonora; Field, John K; Foretova, Lenka; Friis, Søren; Harris, Curtis C; Holcatova, Ivana; Hong, Yun-Chul; Isla, Dolores; Janout, Vladimir; Kiemeney, Lambertus A; Kiyohara, Chikako; Lan, Qing; Lazarus, Philip; Lissowska, Jolanta; Le Marchand, Loic; Mates, Dana; Matsuo, Keitaro; Mayordomo, Jose I; McLaughlin, John R; Morgenstern, Hal; Müeller, Heiko; Orlow, Irene; Park, Bernard J; Pinchev, Mila; Raji, Olaide Y; Rennert, Hedy S; Rudnai, Peter; Seow, Adeline; Stucker, Isabelle; Szeszenia-Dabrowska, Neonila; Dawn Teare, M; Tjønnelan, Anne; Ugolini, Donatella; van der Heijden, Henricus F M; Wichmann, Erich; Wiencke, John K; Woll, Penella J; Yang, Ping; Zaridze, David; Zhang, Zuo-Feng; Etzel, Carol J; Hung, Rayjean J

2012-09-01

Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment. The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer.

PubMed

Tan, Jiunn-Liang; Yong, Zheng-Xin; Liam, Chong-Kin

2016-10-01

Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water. This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex- or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen ® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. Analysis of multivariate variance and post-hoc Tukey test revealed that the peak output and the time to peak values for the lung cancer patients were statistically different from that for both the COPD patients and the controls without lung disease, Pillai's Trace =0.393, F=3.909, df = (4, 64), P=0.007. A 2.20% sensor peak output and a 90-s time to peak gave 83.3% sensitivity and 88% specificity in diagnosing lung cancer. Tobacco smoking did not affect the diagnostic accuracy of the sensor. The alkane sensor could discriminate patients with lung cancer from COPD patients and people without lung disease. Its potential utility as a simple, cheap and non-invasive test for early lung cancer detection needs further studies.

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer

PubMed Central

Tan, Jiunn-Liang; Yong, Zheng-Xin

2016-01-01

Background Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water. This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. Methods In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex- or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. Results Analysis of multivariate variance and post-hoc Tukey test revealed that the peak output and the time to peak values for the lung cancer patients were statistically different from that for both the COPD patients and the controls without lung disease, Pillai’s Trace =0.393, F=3.909, df = (4, 64), P=0.007. A 2.20% sensor peak output and a 90-s time to peak gave 83.3% sensitivity and 88% specificity in diagnosing lung cancer. Tobacco smoking did not affect the diagnostic accuracy of the sensor. Conclusions The alkane sensor could discriminate patients with lung cancer from COPD patients and people without lung disease. Its potential utility as a simple, cheap and non-invasive test for early lung cancer detection needs further studies. PMID:27867553

Lung Cancer in HIV Infection

PubMed Central

Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

2011-01-01

Lung cancer is the most prevalent non-AIDS-defining malignancy in the HAART era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is 2–4 times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the commonest histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Since pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies for this population frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. PMID:21802373

AJRCCM: 100-Year Anniversary.The Shifting Landscape for Lung Cancer: Past, Present, and Future

PubMed Central

Vachani, Anil; Sequist, Lecia V.

2017-01-01

The past century has witnessed a transformative shift in lung cancer from a rare reportable disease to the leading cause of cancer death among men and women worldwide. This historic shift reflects the increase in tobacco consumption worldwide, spurring public health efforts over the past several decades directed at tobacco cessation and control. Although most lung cancers are still diagnosed at a late stage, there have been significant advances in screening high-risk smokers, diagnostic modalities, and chemopreventive approaches. Improvements in surgery and radiation are advancing our ability to manage early-stage disease, particularly among patients considered unfit for traditional open resection. Arguably, the most dramatic progress has occurred on the therapeutic side, with the development of targeted and immune-based therapy over the past decade. This article reviews the major shifts in the lung cancer landscape over the past 100 years. Although many ongoing clinical challenges remain, this review will also highlight emerging molecular and imaging-based approaches that represent opportunities to transform the prevention, early detection, and treatment of lung cancer in the years ahead. PMID:28459327

Protective Role of γδ T Cells in Cigarette Smoke and Influenza Infection

PubMed Central

Hong, M. J.; Gu, B. H.; Madison, M.; Landers, C.; Tung, H. Y.; Kim, M.; Yuan, X.; You, R.; MacHado, A. A.; Gilbert, B. E.; Soroosh, P.; Elloso, M.; Song, L.; Chen, M.; Corry, D. B.; Diehl, G.; Kheradmand, F.

2017-01-01

Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited gamma delta (γδ) T cells to the lungs that predominantly expressed interleukin 17A (IL-17A). Il-17a-/- mice exposed to smoke and infected with Influenza A also recruited γδ T cells to the lungs, but in contrast to wild type mice, expressed increased IFNs, made protective influenza specific antibodies, and recovered from infection. Depletion of IL-17A with blocking antibodies significantly increased T-bet expression in γδ T cells and improved recovery from acute Influenza A infection in air, but not smoke exposed mice. In contrast, when exposed to smoke, γδ T cell deficient mice failed to mount an effective immune response to Influenza A and showed increased mortality. Our findings demonstrate a protective role for γδ T cells in smokers and suggest that smoke-induced increase in IL-17A inhibits the transcriptional programs required for their optimal anti-viral responses. PMID:29091081

Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes.

PubMed

Staudt, Michelle R; Salit, Jacqueline; Kaner, Robert J; Hollmann, Charleen; Crystal, Ronald G

2018-05-14

Little is known about health risks associated with electronic cigarette (EC) use although EC are rising in popularity and have been advocated as a means to quit smoking cigarettes. Ten never-smokers, without exposure history to tobacco products or EC, were assessed at baseline with questionnaire, chest X-ray, lung function, plasma levels of endothelial microparticles (EMP), and bronchoscopy to obtain small airway epithelium (SAE) and alveolar macrophages (AM). One week later, subjects inhaled 10 puffs of "Blu" brand EC, waited 30 min, then another 10 puff; n = 7 were randomized to EC with nicotine and n = 3 to EC without nicotine to assess biological responses in healthy, naive individuals. Two hr. post-EC exposure, subjects were again assessed as at baseline. No significant changes in clinical parameters were observed. Biological changes were observed compared to baseline, including altered transcriptomes of SAE and AM for all subjects and elevated plasma EMP levels following inhalation of EC with nicotine. This study provides in vivo human data demonstrating that acute inhalation of EC aerosols dysregulates normal human lung homeostasis in a limited cohort of healthy naïve individuals. These observations have implications to new EC users, nonsmokers exposed to secondhand EC aerosols and cigarette smokers using EC to quit smoking. ClinicalTrials.gov NCT01776398 (registered 10/12/12), NCT02188511 (registered 7/2/14).

Cigarette packaging and health warnings: the impact of plain packaging and message framing on young smokers.

PubMed

Mays, Darren; Niaura, Raymond S; Evans, W Douglas; Hammond, David; Luta, George; Tercyak, Kenneth P

2015-03-01

This study examined the impact of pictorial cigarette-warning labels, warning-label message framing and plain cigarette packaging, on young adult smokers' motivation to quit. Smokers aged 18-30 years (n=740) from a consumer research panel were randomised to one of four experimental conditions where they viewed online images of four cigarette packs with warnings about lung disease, cancer, stroke/heart disease and death, respectively. Packs differed across conditions by warning-message framing (gain vs loss) and packaging (branded vs plain). Measures captured demographics, smoking behaviour, covariates and motivation to quit in response to cigarette packs. Pictorial warnings about lung disease and cancer generated the strongest motivation to quit across conditions. Adjusting for pretest motivation and covariates, a message framing by packaging interaction revealed gain-framed warnings on plain packs generated greater motivation to quit for lung disease, cancer and mortality warnings (p<0.05), compared with loss-framed warnings on plain packs. Warnings combining pictorial depictions of smoking-related health risks with text-based messages about how quitting reduces risks, may achieve better outcomes among young adults, especially in countries considering or implementing plain packaging regulations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease

PubMed Central

Zhao, Huaqing; Boriek, Aladin M.; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P.; Rennard, Stephen I.; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W.; Kinney, Gregory L.; Han, MeiLan K.; Martinez, Carlos H.; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J.; Hanania, Nicola A.; Sharafkhaneh, Amir; Crapo, James D.; Make, Barry J.; Silverman, Edwin K.; Curtis, Jeffrey L.

2016-01-01

Rationale: Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. Objectives: To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. Methods: We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0–IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis– (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Measurements and Main Results: Compared with the persistent chronic bronchitis– group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis– group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George’s Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved chronic bronchitis group. On multinomial logistic regression, quitting smoking conferred an odds ratio (OR) of 4.289 (95% confidence interval [CI], 2.689–6.842) for resolved chronic bronchitis, whereas resuming smoking had an OR of 4.585 (95% CI, 2.008–10.471) for new chronic bronchitis. Persistent smoking had an OR of 2.621 (95% CI, 1.677–4.096) and 5.767 (95% CI, 3.702–8.983) for subjects with new chronic bronchitis and subjects with persistent chronic bronchitis, respectively. Conclusions: Persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes. PMID:27158740