Self-reported Smoking History Research Articles

Temporal stability of urinary cadmium in samples collected several years apart in a population of older persons.

There is growing evidence that urine cadmium is a temporally stable biomarker indicative of long-term cadmium exposure; however questions remain with regard to generalizability to older persons, the impact of changes in smoking behavior, and the degree of temporal stability when repeat sample collection spans years instead of weeks or months. Using archived samples from cohorts of older men (Osteoporotic Fractures in Men (MrOS-US)) and women (Study of Osteoporotic Fractures (SOF)) (mean age = 80 at study visit 2), we analyzed two morning urine samples each from 39 men and 18 women with a diverse self-reported smoking history. For MrOS, samples were collected approximately 6 years apart, and 4 years apart for SOF. Intra-class correlations were computed to assess temporal stability, and adjusted for age and body mass index. The median creatinine-adjusted urinary cadmium levels (0.39 μg/g for men, 0.89 μg/g for women) were similar to levels expected for these age/sex groups in the US according to the National Health and Nutrition Examination Survey. The overall intra-class correlation was high (ICC = 0.85; 95% CI: 0.76-0.91) and similar between cohorts (MrOS: ICC = 0.74; 95% CI: 0.58-0.86; SOF: ICC = 0.81; 95% CI: 0.59-0.93), but slightly lower among those who stopped smoking between visits of sample collection (ICC = 0.64; 95% CI: 0.31-0.87) or among former smokers who quit prior to the first sample collection (ICC = 0.68; 95% CI: 0.25-0.93). We report good-to-excellent reproducibility of urine cadmium using morning urine samples collected 4-6 years apart from older men and women, but slightly lower correlations among those with a history of smoking. Single measures of urine cadmium are a reliable biomarker in older men and women.

Measurement of Maximum Tongue Protrusion Force (MTPF) In Healthy Normal Adults

Genioglossus (GG) is the primary lingual muscle responsible for tongue protrusion, which is important for speech, swallow and breathing. Contraction of the GG plays an important role in maintaining upper airway patency, preventing posterior tongue displacement and upper airway closure. GG electromyogram studies report GG tongue muscle activity increases with increased negative pressure in the upper airway. We propose that tongue protrusive strength and tone may be related to upper airway patency, and when protrusive strength is reduced, individuals are at higher risk of developing sleep apnea, or speech/swallow disorders. However, in order to test that hypothesis, it is necessary to determine a normal range for tongue protrusion strength. We designed a device to indirectly measure GG strength by measuring tongue protrusion force. The device is a piston in a cylinder with a force transducer at the base of the piston. The cylinder is held by the front teeth, and the tongue extends 0.5–1 cm beyond the teeth to touch the piston. The goal of the current study was to determine normative values of maximum tongue protrusion force (MTPF) in healthy young adults, using the new device. We hypothesized that MTPF would be greater in males than females. One hundred and one healthy adults (male: 23, female: 78) participated in this study. Inclusion criteria were age 18 or above, no self‐reported history of mouth or tongue disease/surgery, and no self‐reported sleep apnea. Their self‐reported sex, age, and smoking history were recorded; height and weight were measured. The subjects pushed their tongue forward against the device's piston (protrusion) as hard as possible for 2–5 seconds and MTPF was recorded in Newtons (N). Subjects performed 5–10 MTPF efforts. The MTPF for all efforts were averaged for each subject. All subjects were able to perform the MTPF task and no adverse responses were reported. The average MTPF for all subjects was 15.4 N (SD ± 3.8), with a range of 8–29. The male average MTPF was higher than female (17.8 N, SD ± 3.7 versus 14.7 N, SD ± 3.5; p = .001). There was no significant difference for age between males and females; males had significantly greater height and weight. The results demonstrate our novel device can effectively measure tongue protrusive force in health young adults. As well, this study provides normative values for MTPF, and identified significant tongue protrusion strength differences between males and females.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Smoking intensity and bladder cancer aggressiveness at diagnosis.

ObjectiveTo explore the relation between cigarette smoking intensity and bladder cancer aggressiveness at first diagnosis.MethodsPatients diagnosed with urinary bladder cancer (BC) between 1995–2011 under the age of 75 years were retrospectively identified from the Netherlands Cancer Registry and invited for a study on genetic and lifestyle risk factors for BC. Information on patients’ self-reported smoking history was retrieved by means of a postal questionnaire. Tumors were stratified regarding the risk of progression defined by tumor stage and grade. Multinomial logistic regression was used to analyze the relation between smoking intensity and aggressiveness of the tumor.ResultsThe UBC study population comprised 323 (17.4%) never smokers, 870 (46.8%) former cigarette smokers, and 630 (33.9%) current cigarette smokers. A higher smoking amount was a risk factor of getting high-risk non-muscle invasive bladder cancer (NMIBC) compared with low-risk NMIBC in ever and former cigarette smokers (OR: 1.02 per cigarette smoked, 95% CI: 1.00–1.03 and OR: 1.03, 95% CI: 1.01–1.05, respectively). A statistically significant dose-response increase in the risk of a more aggressive cancer type (high-risk NMIBC and MIBC) was observed with increasing smoking duration among former smokers (p for trend 0.035 and 0.008, respectively). No significant association of the evaluated smoking intensity variables was observed in current smokers. A longer time of smoking cessation correlated with a lower odds of a more aggressive cancer.ConclusionWe observed a weak increase in the risk of a more aggressive tumor type with increasing smoking intensity in former smokers, but this association was absent in current smokers.This conflicting result may suggest that there is no strong relation between smoking intensity and bladder cancer aggressiveness. Analyses of prospective studies with longitudinal smoking assessment may provide a more definitive answer to the research question.

RE: Proportion of Never-Smoker Non-Small Cell Lung Cancer Patients at Three Diverse Institutions.

Background: Approximately 10% to 15% of lung cancer cases in the United States occur in never smokers, but there has been much debate about whether this rate is increasing. To determine whether the proportion of never smokers among lung cancer cases is increasing, we conducted a retrospective study using registries from The University of Texas Southwestern Medical Center, Parkland Hospital, and Vanderbilt University. Methods: Registries were queried for demographic information from 1990 to 2013 including sex, age, stage, and self-reported smoking history. Ten thousand five hundred ninety-three non–small cell lung cancer (NSCLC) case patients and 1510 small cell lung cancer (SCLC) case patients were captured, and logistic regression analysis was performed. All statistical tests were two-sided. Results: The proportion of never-smoker NSCLC patients increased from 8.0% in the years 1990 to 1995 to 14.9% in 2011 to 2013 (P < .001). This increase was also observed using multivariable logistic regression after controlling for sex, stage at diagnosis, and race/ethnicity. The percentage of never smokers among SCLC case patients (1.5% in 1990–1995 to 2.5% in 2011–2013, P = .36) or squamous cell NSCLC case patients did not statistically significantly change during this period. Conclusions: This study demonstrates an increasing proportion of NSCLC patients who have never smoked in a large, diverse patient population between 1990 and 2013. Given that this increase appears independent of sex, stage, and race/ethnicity and also occurred in our county hospital, this trend is unlikely due to changes in referral patterns and suggests that the actual incidence of lung cancer in never smokers is increasing.

Case-control study of cumulative cigarette tar exposure and lung and upper aerodigestive tract cancers.

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population-based case-control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer-free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self-reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack-years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack-years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between "low exposure" to tobacco smoke and risk of these cancer types.

Proportion of Never-Smoker Non-Small Cell Lung Cancer Patients at Three Diverse Institutions.

Approximately 10% to 15% of lung cancer cases in the United States occur in never smokers, but there has been much debate about whether this rate is increasing. To determine whether the proportion of never smokers among lung cancer cases is increasing, we conducted a retrospective study using registries from The University of Texas Southwestern Medical Center, Parkland Hospital, and Vanderbilt University. Registries were queried for demographic information from 1990 to 2013 including sex, age, stage, and self-reported smoking history. Ten thousand five hundred ninety-three non-small cell lung cancer (NSCLC) case patients and 1510 small cell lung cancer (SCLC) case patients were captured, and logistic regression analysis was performed. All statistical tests were two-sided. The proportion of never-smoker NSCLC patients increased from 8.0% in the years 1990 to 1995 to 14.9% in 2011 to 2013 (P < .001). This increase was also observed using multivariable logistic regression after controlling for sex, stage at diagnosis, and race/ethnicity. The percentage of never smokers among SCLC case patients (1.5% in 1990-1995 to 2.5% in 2011-2013, P = .36) or squamous cell NSCLC case patients did not statistically significantly change during this period. This study demonstrates an increasing proportion of NSCLC patients who have never smoked in a large, diverse patient population between 1990 and 2013. Given that this increase appears independent of sex, stage, and race/ethnicity and also occurred in our county hospital, this trend is unlikely due to changes in referral patterns and suggests that the actual incidence of lung cancer in never smokers is increasing.

Abstract P063: Cigarette Smoking and Neuroimaging Indices of Cerebrovascular Health in a Population-based Cohort of Middle-aged Adults

Introduction: Several studies report an association between cigarette smoking and dementia. One proposed hypothesis is that smoking leads to adverse cognitive and brain changes through vascular pathways. To date, few data exist on the link between smoking and vascular brain measures. We examined, in a population-based middle-aged cohort, the association of history of cigarette smoking with three indicators of cerebrovascular health: (i) white matter (WM) integrity measured using WM-fractional anisotropy, (ii) abnormal WM volume, and (iii) cerebral blood flow (CBF) in the gray matter. We focused on lobar measures of these indicators to detect whether specific regional cerebrovascular indicators are differently related to smoking. Hypothesis: We assessed the hypothesis that smoking history is associated with more adverse cerebrovascular measures (lower fractional anisotropy, larger abnormal WM volumes, and lower CBF). Methods: Data come from the Coronary Artery Risk Development in Young Adults CARDIA-brain magnetic resonance imaging sub-study (n=538). Brain measures and self-reported smoking history were obtained at the 25th year follow-up (mean age=50). We used linear (for CBF and WM-fractional anisotropy) and multinomial logistic (for abnormal WM volume) regression models, adjusted for potential confounders (including vascular and lifestyle risk factors and medical conditions). Results: Compared to never-smokers, current smokers had lower WM-fractional anisotropy in all brain lobes (-0.005 lower fractional anisotropy in the occipital lobe and -0.006 in the other lobes; p&lt;0.05). Smoking history was also associated with larger abnormal WM volumes: Compared to never-smokers, smokers and/or former-smokers had patterns of larger abnormal WM volumes in all lobes, with pronounced associations observed in the frontal lobe wherein smokers and former-smokers had up to twice the risk of having larger abnormal frontal WM volumes as never-smokers (p&lt;0.05). Smoking history was associated with lower CBF in the occipital (-2.89 ml/100g/min (95%CI=-5.43, -0.36); p=0.03) and parietal lobes (-3.31 (95%CI=-5.91, -0.71); p=0.01). Conclusions: In this cohort of middle-aged adults, associations between smoking and adverse WM measures were observed in all brain lobes, whereas associations of smoking with CBF were localized in the occipital and parietal lobes. This localization may reflect a link between smoking and blood flow processes related to sensory-cognitive networks. In conclusion, results suggest that smoking is associated with three early-indicators of cerebrovascular burden (WM-fractional anisotropy, WM abnormal volume, and CBF) across the brain and that it may be differentially related to different regional cerebrovascular indicators.

The Association between Smoking Abstinence and Mortality in the National Lung Screening Trial.

Smoking is the largest contributor to lung cancer risk, and those who continue to smoke after diagnosis have a worse survival. Screening for lung cancer with low-dose computed tomography (LDCT) reduces mortality in high-risk individuals. Smoking cessation is an essential component of a high-quality screening program. To quantify the effects of smoking history and abstinence on mortality in high-risk individuals who participated in the NLST (National Lung Screening Trial). This is a secondary analysis of a randomized controlled trial (NLST). Measurements included self-reported demographics, medical and smoking history, and lung cancer-specific and all-cause mortality. Cox regression was used to study the association of mortality with smoking status and pack-years. Kaplan-Meier survival curves were examined for differences in survival based on trial arm and smoking status. Current smokers had an increased lung cancer-specific (hazard ratio [HR], 2.14-2.29) and all-cause mortality (HR, 1.79-1.85) compared with former smokers irrespective of screening arm. Former smokers in the control arm abstinent for 7 years had a 20% mortality reduction comparable with the benefit reported with LDCT screening in the NLST. The maximum benefit was seen with the combination of smoking abstinence at 15 years and LDCT screening, which resulted in a 38% reduction in lung cancer-specific mortality (HR, 0.62; 95% confidence interval, 0.51-0.76). Seven years of smoking abstinence reduced lung cancer-specific mortality at a magnitude comparable with LDCT screening. This reduction was greater when abstinence was combined with screening, highlighting the importance of smoking cessation efforts in screening programs.

Accuracy of Self-reported Smoking Exposure Among Bladder Cancer Patients Undergoing Surveillance at a Tertiary Referral Center

BackgroundSmoking is a risk factor for developing bladder cancer (BCa). Even though continued exposure after diagnosis may adversely affect prognosis, patients may be reluctant to disclose to their physicians that they are currently smoking, leading to inaccurate reporting of exposure and missed opportunities to deliver smoking-cessation advice and treatment in the context of cancer care. ObjectiveWe examined the extent of misclassification of recent smoking exposure among patients undergoing BCa surveillance. Design, setting, and participantsA consecutive sample of 145 patients with a self-reported smoking history and prior initial diagnosis of BCa was recruited from a tertiary referral urology clinic. Outcome measurements and statistical analysisPatients were asked if they had smoked a cigarette or used nicotine replacement therapy (NRT) within the past week and whether they lived with a smoker. At the same visit, we collected urine under a biospecimen protocol. We used urinary cotinine, the primary metabolite of nicotine, as an objective biomarker of recent smoking exposure. Nine patients whose urine could not be interpreted for cotinine were excluded. We calculated the smoking status misreporting rate by comparing biochemically verified smoking status (≥31.5 ng/ml vs <31.5 ng/ml) against self-reported current smoking status (yes vs no) while considering recent NRT use. Results and limitationsOverall, 11% (15 of 136) of patients had cotinine values consistent with current smoking. Of these 15 patients, 7 reported being former smokers, resulting in a 47% misclassification rate. However, three of the seven patients who denied smoking in the past week were currently using NRT. Excluding NRT users, the misclassification rate was 33%. ConclusionsFuture studies investigating the impact of postdiagnosis nicotine exposure on BCa outcomes should use biochemical verification combined with self-reported smoking exposure to classify patients accurately. Patient summaryBladder cancer patients may misreport smoking exposure, thereby missing opportunities for smoking cessation.

Impact of smoking on the age at diagnosis of upper tract urothelial carcinoma: Subanalysis of the Japanese Urological Association multi-institutional national database.

To examine the influence of smoking history on the diagnosis and other tumor characteristics of upper tract urothelial carcinoma in Japan. A total of 1509 patients with upper tract urothelial carcinoma who were diagnosed in 2005 from 348 Japanese institutions were registered using the multi-institutional national database of the Japanese Urological Association and included in this analysis. Clinical data of the patients were collected in 2011. The associations between the patients' self-reported smoking history and their age at the diagnosis of upper tract urothelial carcinoma, sex, pathological T stage and tumor grade were analyzed. The mean age at the diagnosis of upper tract urothelial carcinoma was approximately 5 years earlier for the 238 current smokers than for the 618 current non-smokers (P < 0.0001). Similar associations between smoking and the early diagnosis of upper tract urothelial carcinoma were shown in the sex subgroups and in subgroups stratified by pathological T stages. Among the current smokers, the age at diagnosis for the smoking ≥ 20 cigarettes per day group was 6.5 years lower than that of the < 20 cigarettes per day group, which was significantly different (P < 0.0001). Current smoking is a significant risk factor for the earlier diagnosis of upper tract urothelial carcinoma. The finding is important from the perspective of both healthcare and medical economies.

Rate of never smokers in non small cell lung cancer (NSCLC) patients.

e19007 Background: There has been significant debate about whether the percentage of never smokers is increasing in lung cancer patients (pts). Using our institutions’ registry data, our objective was to determine if the rate of never smokers is increasing among lung cancer pts. Methods: We conducted a retrospective study using lung cancer registry data from our university hospital at the University of Texas Southwestern Medical Center and our county hospital, Parkland. These registries were queried year by year between 1990 and 2013 for gender, age at diagnosis, diagnosis of NSCLC or small cell lung cancer (SCLC), and self-reported smoking history. Logistic regression analysis was performed to assess the rate of never smokers in NSCLC (N=5,392) and SCLC (N=792) pts. Results: The percentage of never smokers increased among NSCLC pts between 1990 and 2013 [Table]. Univariate logistic regression demonstrated an increasing proportion of never smokers among NSCLC cases (p<0.0001 for year) and multivariate log...

Low oxygen saturation and mortality in an adult cohort: the Tromsø study.

BackgroundOxygen saturation has been shown in risk score models to predict mortality in emergency medicine. The aim of this study was to determine whether low oxygen saturation measured by a single-point measurement by pulse oximetry (SpO2) is associated with increased mortality in the general adult population.MethodsPulse oximetry was performed in 5,152 participants in a cross-sectional survey in Tromsø, Norway, in 2001–2002 (“Tromsø 5”). Ten-year follow-up data for all-cause mortality and cause of death were obtained from the National Population and the Cause of Death Registries, respectively. Cause of death was grouped into four categories: cardiovascular disease, cancer except lung cancer, pulmonary disease, and others. SpO2 categories were assessed as predictors for all-cause mortality and death using Cox proportional-hazards regression models after correcting for age, sex, smoking history, body mass index (BMI), C-reactive protein level, self-reported diseases, respiratory symptoms, and spirometry results.ResultsThe mean age was 65.8 years, and 56% were women. During the follow-up, 1,046 (20.3%) participants died. The age- and sex-adjusted hazard ratios (HRs) (95% confidence intervals) for all-cause mortality were 1.99 (1.33–2.96) for SpO2 ≤ 92% and 1.36 (1.15–1.60) for SpO2 93–95%, compared with SpO2 ≥ 96%. In the multivariable Cox proportional-hazards regression models that included self-reported diseases, respiratory symptoms, smoking history, BMI, and CRP levels as the explanatory variables, SpO2 remained a significant predictor of all-cause mortality. However, after including forced expiratory volume in 1 s percent predicted (FEV1% predicted), this association was no longer significant. Mortality caused by pulmonary diseases was significantly associated with SpO2 even when FEV1% predicted was included in the model.ConclusionsLow oxygen saturation was independently associated with increased all-cause mortality and mortality caused by pulmonary diseases. When FEV1% predicted was included in the analysis, the strength of the association weakened but was still statistically significant for mortality caused by pulmonary diseases.

Risk of Perioperative Respiratory Complications and Postoperative Morbidity in a Cohort of Adults Exposed to Passive Smoking

To evaluate the risks of perioperative respiratory complications and postoperative morbidity associated with active and passive cigarette smoking. Environmental tobacco smoke is associated with perioperative respiratory events in children, but its effect in adults is unknown. We conducted a cohort study of 736 adult patients receiving general anesthesia for major elective surgery. Patients were classified according to their self-reported smoking history and urinary cotinine concentration within 48 hours before surgery. The main outcomes were composite measures of perioperative respiratory complications and postoperative morbidity on the third day after surgery. There were 313 (42.5%) never-smokers (reference group), 92 (12.5%) passive nonsmokers, 157 (21.3%) ex-smokers without environmental tobacco smoke exposure, 53 (7.2%) passive ex-smokers, and 121 (16.4%) smokers. The incidence of perioperative respiratory complications and postoperative morbidity was 9.5% [95% confidence interval (CI), 7.5-11.8] and 29.2% (95% CI, 26.0-32.6), respectively. Smoking was significantly associated with an increased risk of perioperative respiratory complications [relative risk (RR), 4.40; 95% CI, 2.20-8.80] and postoperative morbidity (RR, 1.86; 95% CI, 1.22-2.83). Although passive smoking was not associated with the risk of perioperative respiratory complications, the risk of postoperative morbidity was increased in passive nonsmokers (RR, 1.51; 95% CI, 1.04-2.21) and passive ex-smokers (RR, 2.21; 95% CI, 1.39-3.50). One in 5 adults was exposed to environmental tobacco smoke before surgery. Passive cigarette smoking showed very little, if any, increased risk of perioperative respiratory complications. Both active exposure and passive exposure to cigarette smoke increased the risk of postoperative morbidity.

M138 Do Standard Cardiovascular Risk Scores Identify Risk In Patients With Copd?

Introduction Patients with COPD have increased risk of cardiovascular (CV) disease compared to smokers without COPD, 1 with over 25% of deaths CV related. 2 Several CV risk calculators for the general population exist but it is unclear whether they are applicable for COPD. Hypothesis Standard CV risk calculators do not identify the increased risk in patients with COPD. Methods Subjects with a smoking history >10 pack years, with and without COPD, were assessed at clinical stability, COPD n = 191 and controls n = 106. Post-bronchodilator spirometry and blood pressure were performed, blood taken for lipids and self-reported medical and smoking history recorded. In those without documented established CV disease or diabetes (COPD n = 135 and controls n = 88), 10 year CV risk was calculated using ACC/AHA 3 and NHLBI[4] calculators. Results Both groups were well matched for gender and mean arterial blood pressure (MAP), with the COPD group slightly older, Table 1. Mean CV risk scores were similar between patients with COPD and controls, Table 1, ACC/AHA p = 0.16 and NHLBI p = 0.59. When using an established cut-off point of 20% for high 10 year CV risk, similar proportions were identified as high risk: the ACC/AHA calculator - 37% of the patients with COPD and 33% of controls; and with the NHLBI calculator 15% of the patients with COPD and 10% of controls were identified as high-risk. Discussion Although nearly double the proportion of patients with COPD compared to controls with a smoking history have current CV disease or diabetes in this cross-sectional study, the increased risk of future incident CV disease in patients with COPD was not identified using standard calculators. Supported by a NIHR BRF Fellowship. References Feary, JR, et al . Thorax, 2010;65(11): p. 956-62 McGarvey, LP, et al . Thorax, 2007;62(5): p. 411-5 ACC/AHA Available from: http://my.americanheart.org/professional/StatementsGuidelines/Prevention-Guidelines_UCM_457698_SubHomePage.jsp NHLBI Available from: http://cvdrisk.nhlbi.nih.gov/

Smoking History and Response to Nivolumab in Patients with Advanced Nsclcs

ABSTRACT Aim: Robust responses to nivolumab (Nivo, anti-PD1 antibody) are seen in both melanomas and NSCLCs. Both of these cancers are characterized by high somatic mutation burden, suggesting a potential link between mutational burden and immunogenicity. Since smoking-related NSCLCs have significantly greater mutation burden compared to never smokers, we hypothesized that smoking history may be associated with response to nivolumab in pts with NSCLCs. Methods: Smoking status, histology, and EGFR/KRAS genotype were recorded from 88 of 129 pretreated, advanced NSCLCs treated with Nivo monotherapy at 5 of 11 centers that participated in a previously reported study (NCT00730639, Topalian et al, NEJM 2012). Self-reported smoking history was categorized as never ( 5 pk-yrs, quit > 1 yr prior), or current smokers. In smokers, time-since-quitting was also recorded. Response was assessed every 8 wks by RECIST v1.0. Associations between smoking, histology, genotype, and response were assessed using the Fisher's exact, unpaired T-, log-rank tests. Results: The response rate was significantly higher in former/current smokers (20/75, 27%, 95% CI 17-38%) vs minimal/never smokers (0/13, 0%, 95% CI 0-25%) (p = 0.034). Responders had significantly more tobacco exposure than non-responders (median 50 pk-yrs [range 15-150] vs 36 pk-yrs [range 0-100], p=0.036). Among smokers, there was no association between response and time-since-quitting (Current smokers ORR 27%; Quit 1-15 yrs ago 24%; Quit >15 yrs ago 24%, p=0.18). There was no significant difference in response rate in adeno vs squamous histology (16 vs 21%, p=0.58). In adenos, response rates in EGFR muts vs KRAS muts vs all others were 1/9 vs 3/13 vs 4/27; the one EGFR mut responder was a 40 pk-yr current smoker. Conclusions: In advanced NSCLCs, the response rate to Nivo was significantly higher in former/current smokers compared to never/minimal smokers. There were no objective responses in never or minimal smokers in this subset of pts. Smoking history should be considered as a stratification factor for trials of PD-1 pathway inhibitors in lung cancer. Further work is needed to identify the underlying basis of this differential response rate. Disclosure: S.J. Antonia: Dr. Antonia receives research funding and/or serves as an advisor for Bristol-Myers Squibb. L. Horn: Dr. Horn receives research funding and/or serves as an advisor for Bristol-Myers Squibb; J.R. Brahmer: Dr. Brahmer receives research funding and serves as an advisor for Bristol-Myers Squibb; S. Gettinger: Dr. Gettinger receives research funding and serves as an advisor for Bristol-Myers Squibb; C. Harbison: Dr. Harbison is an employee and stock holder of Bristol-Myers Squibb; N. Rizvi: Dr. Rizvi receives research funding and serves as an advisor for Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

The effect of smoking and timing of smoking cessation on clinical outcome in non–muscle-invasive bladder cancer

ObjectivesCigarette smoking is the most important risk factor for urinary bladder cancer. The prognostic effect of cigarette smoking on disease recurrence and progression in patients with non–muscle-invasive bladder cancer (NMIBC), however, is still unclear. We evaluated the effect of smoking status and intensity, and timing of smoking cessation, on NMIBC prognosis. Methods and materialsA population-based series of patients diagnosed with NMIBC from 1995 until 2010 was identified through the Netherlands Cancer Registry. Self-reported smoking history was obtained by a postal lifestyle questionnaire at study inclusion. Detailed clinical data concerning diagnosis, treatment, and disease course were collected retrospectively through a medical file survey. The association of smoking variables with recurrence- and progression-free survival of 963 patients with primary NMIBC was studied using cumulative incidence curves and competing risk regression analyses. ResultsThe study population comprised 181 never smokers (18.8%), 490 former smokers (50.9%), and 292 current smokers (30.3%) at the time of diagnosis. No statistically significant difference or trend in risk of recurrence (Ptrend = 0.47) or progression (Ptrend = 0.23) across the 3 smoking status categories was found. Moreover, no dose-response association was observed across categories of smoking quantity, duration, or cumulative exposure in relation to NMIBC prognosis. The timing of smoking cessation (i.e., ceased smoking≥10y before diagnosis,<10y before diagnosis, vs. current smoker at diagnosis) did not significantly affect the risk of recurrence (Ptrend = 0.31) and progression (Ptrend = 0.19). ConclusionsBased on our study, smoking status, smoking intensity, or cessation at any time before diagnosis does not seem to alter the risks of recurrence and progression among patients with NMIBC. Patients’ smoking history is not useful for the guidance of clinical management decisions. Patients should nevertheless be advised to quit considering the known beneficial effects on other non-NMIBC–related end points such as cardiovascular disease and second primary cancers.

Urinary tobacco smoke-constituent biomarkers for assessing risk of lung cancer.

Tobacco-constituent biomarkers are metabolites of specific compounds present in tobacco or tobacco smoke. Highly reliable analytic methods, based mainly on mass spectrometry, have been developed for quantitation of these biomarkers in both urine and blood specimens. There is substantial interindividual variation in smoking-related lung cancer risk that is determined in part by individual variability in the uptake and metabolism of tobacco smoke carcinogens. Thus, by incorporating these biomarkers in epidemiologic studies, we can potentially obtain a more valid and precise measure of in vivo carcinogen dose than by using self-reported smoking history, ultimately improving the estimation of smoking-related lung cancer risk. Indeed, we have demonstrated this by using a prospective study design comparing biomarker levels in urine samples collected from smokers many years before their development of cancer versus those in their smoking counterparts without a cancer diagnosis. The following urinary metabolites were associated with lung cancer risk, independent of smoking intensity and duration: cotinine plus its glucuronide, a biomarker of nicotine uptake; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), a biomarker of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); and r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbons (PAH). These results provide several possible new directions for using tobacco smoke-constituent biomarkers in lung cancer prevention, including improved lung cancer risk assessment, intermediate outcome determination in prevention trials, and regulation of tobacco products.

Association Between Stillbirth and Illicit Drug Use and Smoking During Pregnancy

To compare illicit drug and smoking use in pregnancies with and without stillbirth. The Stillbirth Collaborative Research Network conducted a case-control study from March 2006 to September 2008, covering more than 90% of deliveries to residents of five a priori-defined geographically diverse regions. The study attempted to include all stillbirths and representative liveborn controls. Umbilical cord samples from cases and controls were collected and frozen for subsequent batch analysis. Maternal serum was collected at delivery and batch analyzed for cotinine. For 663 stillbirth deliveries, 418 (63%) had cord homogenate and 579 (87%) had maternal cotinine assays performed. For 1,932 live birth deliveries, 1,050 (54%) had cord homogenate toxicology and 1,545 (80%) had maternal cotinine assays performed. A positive cord homogenate test for any illicit drug was associated with stillbirth (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.16-3.27). The most common individual drug was cannabis (OR 2.34 95% CI 1.13-4.81), although the effect was partially confounded by smoking. Both maternal self-reported smoking history and maternal serum cotinine levels were associated in a dose-response relationship with stillbirth. Positive serum cotinine less than 3 ng/mL and no reported history of smoking (proxy for passive smoke exposure) also were associated with stillbirth (OR 2.06, 95% CI 1.24-3.41). Cannabis use, smoking, illicit drug use, and apparent exposure to second-hand smoke, separately or in combination, during pregnancy were associated with an increased risk of stillbirth. Because cannabis use may be increasing with increased legalization, the relevance of these findings may increase as well. II.

Race as a Moderator of the Relationship Between Distress Tolerance and Cigarette Smoking

The present study examined the role of distress tolerance (DT) and race in relation to cigarette smoking. For this study, between 2008 and 2010, 153 women (62.1% White, 37.9% African American) from the Washington, DC metropolitan area completed a computerized behavioral DT task and self-reported smoking history. Results suggest that low DT (OR = .23, p = .03) and the interaction between DT and race (OR = 4.58, p = .05) were significantly related to greater odds of being a smoker, such that African American women, but not White women, with low DT were at increased risk for being a lifetime smoker.

Tobacco-specific N-nitrosamine exposures and cancer risk in the Shanghai Cohort Study: remarkable coherence with rat tumor sites.

The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent carcinogens for the rat esophagus and lung, respectively. Consistent with the animal carcinogenicity data, we previously reported a remarkably strong association between prospectively measured urinary total NNN, a biomarker of human NNN intake, and the risk of developing esophageal cancer among smokers in the Shanghai Cohort Study. We also demonstrated that urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a biomarker of exposure to the lung carcinogen NNK, is strongly associated with the risk of lung, but not esophageal cancer in smokers. In this study, we investigated the potential relationship between NNN intake and lung cancer risk in the same cohort. The prospectively collected urine samples from lung cancer cases and matching controls selected for this study, all current smokers, have been previously analyzed for total NNAL, cotinine (a biomarker of nicotine intake) and phenanthrene tetraol (PheT) (a biomarker of exposure to polycyclic aromatic hydrocarbons). Urinary levels of total NNN were not associated with the risk of lung cancer: odds ratios (95% confidence intervals) associated with the second and third tertiles of total NNN, relative to the lowest tertile, were 0.82 (0.36-1.88) and 1.02 (0.39-2.89), respectively (p for trend = 0.959), after adjustment for self-reported smoking history, urinary cotinine and PheT. The results of this study reaffirm the previously reported specificity of urinary total NNN and total NNAL as predictors of esophageal and lung cancer risks, respectively, in smokers, and demonstrate remarkable coherence between rat target tissues of these carcinogens and susceptibility to cancer in smokers.