Higher Pack-years Research Articles

Abstract 630: Smoking is associated with risks of molecular subtypes of colorectal cancer

Abstract Background: Smoking has been associated with colorectal cancer (CRC) risk; but limited evidence has shown the association between smoking and molecular subtypes of CRC. Methods: We analyzed 9,422 CRC cases and 9,950 controls from 10 observational studies. Multinomial logistic regression analysis was performed to assess the association between sex-study-specific quartiles of pack years of smoking and risk of CRC molecular subtypes, using non-smokers as reference group, adjusting for age, sex, and study. Known oncogenic mutations in four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutations, KRAS mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. Case-only analysis was also performed to estimate heterogeneity in risk of molecular subtypes of CRC. Results: Compared with controls, higher pack years of smoking were statistically significantly associated with increased CRC risk when stratified, individually, by all four markers, and the associations got stronger with higher quartiles pack years (p-trend<0.001). Associations between smoking and CRC risk also differed significantly among molecular subtypes. Compared to nonsmokers, the risk of BRAFmut CRC was 83% higher for smokers within the highest quartile of pack-years (OR=1.83; 95% CI: 1.50, 2.25), and 29% higher for BRAFwt CRC (OR=1.29; 95% CI: 1.17, 1.43; Ratio of ORs (ROR)=1.45; 95% CI: 1.18, 1.17; p=3.45x10-4). Similarly, heavy pack-years of smoking was associated with almost two times higher risk of CIMP-high CRC (OR=1.93; 95% CI: 1.60, 2.31), but only 33% higher risk of CIMP-low/negative CRC (OR=1.33; 95% CI: 1.19, 1.48; ROR=1.49; 95% CI: 1.24, 1.79; p=1.72x10-5). The association between smoking and CRC was also stronger in MSI-high tumors (ORMSI-H=1.65; 95% CI: 1.36, 2.00; ORMSI-L/MSS=1.37; 95% CI: 1.23, 1.52; ROR=1.22; 95% CI: 1.00, 1.48; p=0.046). In contrast, the association between smoking and CRC risk was stronger for KRASwt (OR=1.43; 95% CI: 1.27, 1.60), than KRASmut tumors (OR=1.18; 95% CI: 1.02, 1.37; ROR=0.83; 95% CI: 0.71, 0.97; p =0.016). When combining tumor markers, smoking was found to be significantly associated with higher risk of colorectal tumors from the serrated pathway. Conclusion: In this largest study with a total of 19,372 subjects, we found that heavier pack years of smoking was associated with increased risk of all CRC molecular subtypes. Smokers with heavier pack-years of smoking had particularly higher risk of CRC subtypes with BRAF mutation and CIMP-high, suggesting smoking may be particularly involved in the development of these subtypes of colorectal tumor. Citation Format: Xiaoliang Wang, Efrat Amitay, Barbara L. Banbury, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Jenny Chang-Claude, Steven J. Gallinger, Graham G. Giles, Tabitha A. Harrison, John L. Hopper, Mark A. Jenkins, Yi Lin, Reiko Nishihara, Polly A. Newcomb, Shuji Ogino, Lori C. Sakoda, Robert E. Schoen, Martha L. Slattery, Steven N. Thibodeau, Bethany Van Guelpen, Michael O. Woods, Li Hsu, Michael Hoffmeister, Ulrike Peters. Smoking is associated with risks of molecular subtypes of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 630.

Abstract 643: Poor oral hygiene is associated with HPV-negative and not HPV-positive oral cancer

Abstract Background Oral health and hygiene have been implicated as risk factors for oral squamous cell carcinoma (i.e. oral cavity and oropharyngeal cancers, OSCC), and we recently reported that these risk factors also dramatically alter the oral microbiome. Here we performed a more detailed analysis of associations between oral health behaviors and OSCC in a matched case-control study. We stratified our analysis to compare and contrast associations with Human Papillomavirus (HPV)-positive versus HPV-negative OSCC. Methods Cases were patients with newly diagnosed OSCC at The Ohio State University Comprehensive Cancer Center between 2011 and 2014. Controls were patients without cancer from the same outpatient clinic who were matched (2:1) to each case on age, sex, and race. Cases were stratified by tumor high-risk HPV status (HPV-positive, n=117; HPV-negative, n=114) based on E6 or E7 mRNA expression. Data on demographics; tobacco, alcohol, and sexual history; and oral health behaviors were collected using an audio computer-assisted self-interview. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), and oral health behaviors significant in univariable analysis were evaluated in separate multivariable models. Results In univariable analysis, oral health behaviors such as low frequency of dental clinic visit, tooth brushing, and dental flossing; gum bleeding; tooth loss; and denture use significantly increased risk of HPV-negative OSCC, whereas none of these behaviors increased risk of HPV-positive OSCC. In univariable analysis, covariates associated with increased risk of HPV-negative OSCC were low education and income level, high lifetime tobacco pack-years (0, >0-<20, ≥20-<40, >40) and high lifetime heavy (≥14 drinks/week) drinking years (0, >0-<10, ≥10-<20, ≥20). In contrast, covariates associated with increased risk of HPV-positive OSCC were low education level, high lifetime marijuana use years (0, >0-<10, ≥10-<20, ≥20) and high no. of oral sex partners (0-2, 3-6, ≥7). After adjusting for covariates in multivariable analysis, a frequency of less than once per year dental clinic visits significantly increased risk of HPV-negative OSCC (OR = 2.28 [95% CI = 1.14-4.57]). Dental flossing less than once per day also increased risk of HPV-negative OSCC, overall (OR = 3.56 [95% CI = 1.04-12.14]) and in those without denture (OR = 4.34 [95% CI = 1.07-17.63]). In multivariable analysis, frequency of tooth brushing and gum bleeding, denture use, and tooth loss were not associated with HPV-negative OSCC. Conclusion Poor oral health behaviors such as infrequent dental visits and dental flossing were independently associated with HPV-negative OSCC, but not with HPV-positive OSCC. These findings are consistent with a hypothesis that poor oral health behaviors alter oral microbial composition to promote chronic inflammation and the development of HPV-negative OSCC. Citation Format: Jitesh B. Shewale, Robert Pickard, Maura L. Gillison. Poor oral hygiene is associated with HPV-negative and not HPV-positive oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 643.

THE CORRELATION OF ABSOLUTE EOSINOPHIL COUNT IN STABLE COPD FILIPINO PATIENTS

SESSION TITLE: Obstructive Lung Diseases 3 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: The study intended to identify the correlation of absolute eosinophil count with the severity of COPD and degree of exacerbation in stable COPD patients. METHODS: This was a prospective cross sectional study conducted at Philippine Heart Center. All patients >40 years old clinically diagnosed with COPD through spirometry done within six months were included. Demographic characteristics and absolute eosinophil count was recorded. Quantitative variables were summarized as mean and standard deviation, while qualitative variables were tabulated as frequency and percentage. Correlation between eosinophil level and degree of COPD was graphically presented in a scatterplot and analyzed using Pearson’s product – Correlation. RESULTS: We analysed 102 stable COPD patients. There were 59(57.84%) eosinophilic COPD and 43(42.16%) non-eosinophilic COPD patients. The mean age was 69 years old, mostly males, 81.37% (83/102). The mean ages of both groups were 65.74±8.9 and 62.11±9.20 on COPD eosinophilic and non-eosinophilic patients respectively, p=0.05. Both study groups have more male subjects, 52(88.14%) and 31(72%); however, there were more females in the non-eosinophilic compared to the eosinophilic group 12(27.9%) vs 7(11.6%), p=0.04. A high pack years smoked was reported in the eosinophilic group compared to the non-eosinophilic group (54.9±22.0 vs 43.47±17.90 correspondingly, p=0.007). Correlation between absolute eosinophil value and the degree of COPD was weak (r= 0.3467), but statistically significant with p=0.0004. CONCLUSIONS: Absolute eosinophil levels above ≥0.40×109/L showed the possibility of increased risk for exacerbation in stable COPD patients. This study was able to ascertain that as the degree of COPD elevates, the levels of the eosinophil count is also increased. However, there was no established relationship between severity of airflow limitation and the level of eosinophil count. CLINICAL IMPLICATIONS: The study identified that there is a correlation of absolute eosinophil count with the severity of COPD and degree of exacerbation in stable COPD patients and through this study we can determine if absolute eosinophil count can help guide the management of COPD patients. DISCLOSURES: no disclosure on file for Aileen Banzon; no disclosure on file for Ma. Encarnita Blanco-Limpin; No relevant relationships by May Joy Canillas, source=Web Response

Cigarette smoking and cerebral blood flow in a cohort of middle-aged adults

Cigarette smoking is often associated with dementia. This association is thought to be mediated by hypoperfusion; however, how smoking behavior relates to cerebral blood flow (CBF) remains unclear. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (mean age = 50; n = 522), we examined the association between smoking behavior (status, cumulative pack-years, age at smoking initiation, and years since cessation) and CBF (arterial spin labeling) in brain lobes and regions linked to dementia. We used adjusted linear regression models and tested whether associations differed between current and former-smokers. Compared to never-smokers, former-smokers had lower CBF in the parietal and occipital lobes, cuneus, precuneus, putamen, and insula; in contrast, current-smokers did not have lower CBF. The relationship between pack-years and CBF was different between current and former-smokers (p for interaction < 0.05): Among current-smokers, higher pack-years were associated with higher occipital, temporal, cuneus, putamen, insula, hippocampus, and caudate CBF; former-smokers had lower caudate CBF with increasing pack-years. Results show links between smoking and CBF at middle-age in regions implicated in cognitive and compulsive/addictive processes. Differences between current and former smoking suggest that distinct pathological and/or compensatory mechanisms may be involved depending on the timing and history of smoking exposure.

Cigarette smoking and hip volumetric bone mineral density and cortical volume loss in older adults: The AGES-Reykjavik study.

This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. In multivariable linear regression models, compared to never-smokers, current smokers had lower cvol/ivol at baseline and former-smokers had poorer measures on all outcomes (lower trabecular vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential confounders. Further, among former smokers, those with higher pack-years had worse bone outcomes and those with longer duration since smoking cessation had better bone health at baseline. Analyses of change in bone measures revealed that compared to never-smokers, current smokers had significantly greater loss of trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included adjustment for sex, age, education, and baseline body mass index, creatinine, % weight change from age 50, 25OHD, physical activity level, high-sensitive C-Reactive protein levels, alcohol and coffee consumption, history of diabetes mellitus, arthritis, and respiratory diseases. In conclusion, both current and former smoking showed adverse associations with bone health assessed with QCT. Results suggest that current smoking in particular may aggravate the rate of bone loss at older age and highlight implications for targeting this risk factor in populations that present higher smoking prevalence and vulnerability to bone fragility.

Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions

BackgroundMagnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. MethodsNon-smokers (n=43) and smokers (n=40), 22–70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. ResultsSmokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. ConclusionsResults provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions.

Pleural abnormalities in the Framingham Heart Study: prevalence and CT image features

BackgroundThe prevalence of pleural abnormalities in the general population is an epidemiologically important index of asbestos exposure, which has not been investigated since a radiography-based study in 1980.MethodsWe examined 2633...

Abstract PR06: Interactions between nonsteroidal anti-inflammatory drugs and other risk factors on colorectal cancer risk

Abstract Background: Long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to be protective against colorectal cancer (CRC). While aspirin is recommended to prevent cardiovascular disease and colorectal cancer in certain subgroups, a broad recommendation is not in place due to concerns about side effects. Evidence from clinical trials among patients with colorectal adenomas suggested stronger effect of aspirin among non-smokers, compared to current smokers; but the effect has not been evaluated for CRC risk. Methods: Using 11,894 cases and 15,999 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR), we performed multivariate logistic regression models to test for the interaction between regular use of NSAIDs (aspirin and non-aspirin NSAIDs) and other CRC risk factors on CRC risk, including age, sex, body mass index (BMI), physical activity, smoking, alcohol consumption, screening, family history of CRC, hormone replacement therapy (HRT) use, as well as intake of fruit, vegetables, red meat, processed meat, dietary fiber, total calcium and total folate. Fixed-effects meta-analyses with inverse variance weighting were used to summarize the estimates from interactions and stratified analyses across studies for each risk factor. A p-value &amp;lt;0.05 was considered statistically significant. Results: Regular use of any NSAID, aspirin, or non-aspirin NSAIDs was statistically significantly associated with a lower risk of CRC across almost all subgroups stratified by sex, body mass index (BMI), smoking, alcohol intake, physical activity and dietary factors. The association between aspirin and CRC risk statistically significantly differed by smoking status after adjusting for other risk factors (p-interaction=0.048). Regular aspirin use was associated with a 25% lower risk of CRC among non-smokers (OR=0.75; 95% CI: 0.64, 0.87), while it was associated with 19% and 16% lower risk of CRC among smokers of lower pack-years (OR=0.81; 95% CI: 0.70, 0.94) and higher pack-years (OR=0.84; 95% CI: 0.73, 0.97), respectively. There was a suggestive interaction between regular use of aspirin and BMI (p-interaction=0.081), where the effect of regular use of aspirin on CRC risk was stronger among individuals with normal BMI (OR=0.77; 95% CI: 0.65, 0.92) and overweight (OR=0.77; 95% CI: 0.66, 0.90), and non-significant among the obese (OR=0.93; 95% CI: 0.80, 1.08). Similarly, the association between any NSAID use and CRC risk was suggested to differ by BMI (p-interaction=0.075). No interaction between non-aspirin NSAIDs and other risk factors of CRC was observed. Conclusions: Our results suggest that the association between regular use of aspirin, but not other NSAIDs, and CRC risk may be modified by smoking status and BMI. The beneficial effect of aspirin on CRC risk appears to be diminished among those with greater CRC risk due to obesity and heavy smoking. The observed effect modifications were borderline significant and did not account for multiple comparisons. This abstract is also being presented as Poster A33. Citation Format: Xiaoliang Wang, Andrew T. Chan, Martha L. Slattery, Jenny Chang Claude, John D. Potter, Steven Gallinger, Caan Bette, Johanna W. Lampe, Polly A. Newcomb, Niha Zubair, Li Hsu, Robert E. Schoen, Hermann Brenner, Loic Le Marchand, Ulrike Peters, Emily White. Interactions between nonsteroidal anti-inflammatory drugs and other risk factors on colorectal cancer risk. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr PR06.

Study Shines Light on ‘Invisible Epidemic’ of Alcohol Use

Study Shines Light on ‘Invisible Epidemic’ of Alcohol Use

Relation between Vitamin D Deficiency and Severity of Chronic Obstructive Pulmonary Disease-A Case Control Study.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by irreversible and progressive limitation of expiratory airflow. COPD is now considered as a systemic disease with several extra-pulmonary manifestations which include osteoporosis, muscle weakness, arrhythmia, stroke, cancer etc. The role of vitamin D in skeletal integrity is well established. Role of it in several other diseases like autoimmune, infectious, respiratory and cardiovascular diseases has been increasingly recognised. Data on vitamin D status in COPD in Indian population was limited while those comparing vitamin D with stage, pack year and body mass index were lacking. To assess Vitamin D in subjects with COPD and matched controls and also to study the variability in serum vitamin D levels with COPD disease characteristics. A total of 162 patients aged 18-65 years from south India presenting to kasturba hospital were included in the study. Serum 25- hydroxy-vitamin D were measured in 81 COPD patients (combined COPD stage A-D) and compared with 81 age and gender matched controls. Level < 20 ng/ml defined deficiency. Risk estimate with Odds ratio and association of COPD characteristics with Vitamin D was assessed using logistic regression analysis. COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for age and gender(OR =2.687 (1.40,5.13)). Variables associated with lower 25(OH) D levels in COPD patients were higher pack year (p=0.001), current smoking status (p=0.026), Low BMI (p=0.02), and GOLD stage III- IV (p=0.001). COPD was associated with an increased risk of vitamin D deficiency, and there was a significant association between vitamin D levels and Combined COPD stage severity. Also, a higher pack year and a low BMI are associated with lower levels of vitamin D.

Influence of Cigarette Smoking on Burden and Characteristics of Coronary Artery Plaques in Chinese Men.

It is generally well-known that smoking has a substantial impact on general health, and cardiovascular health in particular. The purpose of this study was to analyze the effects of different smoking status on the burden and characteristics of coronary artery plaques in Chinese men. Our study enrolled 1920 individuals with suspected coronary artery disease undergoing 256-detector-row computed tomography scan after clinical assessment. These study participants were stratified into three groups: never smoker, current smoker, and former smoker, according to their smoking status. Thereafter, the associations of different smoking status with the coronary artery plaques were assessed using both univariable and multivariable logistic regression. The prevalences of any plaque, significant stenosis and coronary artery calcium score (CACS) ≥ 10 were highest in the current smokers (all p < 0.05). The proportion of calcified plaques was the lowest and the prevalence of non-calcified plaques was the highest in current smokers (p = 0.004). The higher pack-years group had significantly elevated percentages of any plaque, significant stenosis, ≥ 2/LM vessel disease and CACS ≥ 10 than the lower pack-years group (all p < 0.001). The percent of calcified plaques was lower and the percent of non-calcified plaques was higher in the higher (> 20) pack-years group than in the lower pack-years group (≤ 20) (p = 0.024). Current smoking with higher pack-years was the independent risk factor for any plaque, significant stenosis, CACS ≥ 10, non-calcified and mixed plaques (all p < 0.05) after multivariate adjustments. The current smokers had the most serious burden of coronary artery plaques and the highest percentage of non-calcified plaques. Current smoking with higher pack-years was a significant risk factor for coronary artery plaque burden and non-calcified and mixed plaques. Chinese men; Cigarette smoking; Coronary artery calcium score; Coronary artery plaques; Non-calcified plaques.

Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking.

To investigate CT appearance and size of the thymus in association with participant characteristics. 2540 supposedly healthy participants (mean age 58.9 years, 51 % female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants' age, sex, BMI and smoking history. Of 2540 participants, 1869 (74 %) showed complete fatty replacement of the thymus (Score 0), 463 (18 %) predominantly fatty attenuation (Score 1), 172 (7 %) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 %) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04). Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus. 74% of participants (mean age 58.9 years) demonstrated complete fatty thymus. Women show less fatty thymus compared to men at ages 40-69 years. Smoking and high BMI are associated with advanced fatty degeneration in thymus.

Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes.

Aims/hypothesisThe aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes.MethodsData from 831 participants (aged 60–75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment (‘historical’ data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. ‘Accelerated late-life cognitive decline’ was defined as scoring in the lowest tertile of ‘4 year cognitive change’ regression scores. Analyses controlled for age and sex.ResultsA baseline history of moderate/heavy smoking (≥10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised β range −0.07 to −0.14; all p ≤ 0.05).Conclusions/interpretationIncreased smoking and poorer glycaemic control (with relatively weaker findings for BP) during the life-course were independently associated with accelerated late-life cognitive decline. Where possible, evaluation is warranted of these risk factors as targets for intervention to reduce the burden of cognitive impairment in diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3581-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

(578) - Poor Pre-Operative Pulmonary Function Tests (PFTs) Do Not Predict Worse Outcomes in Patients Undergoing LVAD Placement

Poor preoperative pulmonary function has been identified as a risk factor for poor outcomes following cardiac surgery, but this has not been well described in patients undergoing LVAD placement. The objective is to examine the relationship between preoperative pulmonary function and outcomes after LVAD implantation. We evaluated patients who underwent HeartMate II as intent for BTT at a single center from 10/2005 to 7/2014. Moderate to severe obstructive pulmonary disease was defined as a forced expiratory volume in 1s (FEV1) to forced vital capacity ratio (FEV1/FVC) <0.7 and FEV1 <80%. 183 patients were evaluated; of these, 122 had preoperative PFTs; 61 patients had PFTs deferred due to heart failure exacerbation. Of these 122 patients, 47 had moderate to severe obstructive PFTs (group 1) and 75 patients had normal to mild obstructive PFTs. The mean % predicted FEV1 was 56 ± 12L in group 1 and 72± 17L (p = 0.001) in group 2. The FEV1/FVC ratio was 0.63 ± 0.1 in group 1 and 0.80 ± 0.05 in group 2 (p = 0.0001). There were no significant differences in age, etiology, gender, INTERMACS profiles, or baseline hemodynamics (p = NS). Patients in group 1 were significantly more likely to have a smoking history (64% vs 35%, p =0.03) higher pack years of smoking (39 vs 23, p = 0.02), and prior history of COPD (23% vs 5%, 0.004). There was no significant differences in days of ventilation, reintubation, right heart failure, ICU length of stay, length of stay, or LVAD duration of support between group 1 or 2 (p = NS). Actuarial survival at 1 year was 81% in group 1 and 89.5% in group 2 (log rank p = NS). Patients with moderate to severe obstruction on PFTs prior to LVAD placement do not have worse outcomes than those patients with normal PFTs. In patients with end-stage heart failure, poor pulmonary function may be a reflection of decompensated heart failure. Therefore, poor PFTS should not be considered an absolute contraindication to LVAD placement.

Ulnar Neuropathy Among Active Workers Based Upon Hand Diagram Ratings

BackgroundLimited studies have estimated the prevalence of ulnar neuropathy (UN) in the workplace. Hand diagrams have been demonstrated to have a good sensitivity and specificity when attempting to identify patients with UN. ObjectiveTo determine the prevalence and associated risk factors for UN among active workers based on results of a hand diagram, and to determine the reliability of hand diagram scoring. DesignCross-sectional study. SettingSeven different industrial and clerical work sites. MethodsA total of 501 active workers were screened. Subjects completed a hand diagram and the Job Content Questionnaire, and had ergonomic assessment of their job. Each hand diagram was scored independently by 2 raters. Main Outcome MeasuresRating of the hand diagram for UN. ResultsInterrater reliability of scoring the hand diagram for UN was very high. The estimated prevalence of UN was 3.6%. Suspected UN was associated with positioning of the elbow but not by contact stress at the elbow or force at the hand. Smokers had a lower prevalence, but smokers with suspected UN had higher-pack year histories. Workers with suspected UN had a greater sense of job insecurity and lower job satisfaction rating. ConclusionsHand diagram rating has a high interrater reliability. Suspected UN has a relatively high prevalence among active workers in comparison to prior estimates of the prevalence of UN among the general population and is not strongly associated with ergonomic factors.

NNK reduction pathway gene polymorphisms and risk of lung cancer.

The tobacco-specific nitrosamine NNK is a potent carcinogen found in tobacco smoke and implicated in the development of lung cancer. The major route of NNK metabolism is carbonyl reduction by AKR1C1, AKR1C2, CBR1, and 11β-HSD1 to form NNAL. This study investigated the potential role of variants in this pathway on lung cancer risk by examining 53 tag-SNPs representing the common variations in AKR1C1, AKR1C2, CBR1, and HSD11B1 in 456 lung cancer cases and 807 controls. One SNP in CBR1 (rs2835267) was significantly associated with overall risk of lung cancer, but did not pass multiple testing adjustment (OR: 0.76 95% CI: 0.58-0.99, P = 0.048, FDR P = 0.20). After stratification and multiple testing correction, three SNPs showed significance. One SNP (rs2835267) in CBR1 showed a significant decreased risk for smokers with a high pack-years (OR: 0.3595% CI: 0.17-0.69, P = 0.018) and in SCC (OR: 0.4895% CI: 0.29-0.76, P = 0.018). Another SNP located in CBR1 (rs3787728) also showed a significant decreased risk in SCC (OR: 0.4695% CI: 0.26-0.80, P = 0.024) and small cell carcinoma (only in current smokers) (OR: 0.06895% CI: 0.01-0.42, P = 0.028). The HSD11B1 SNP (rs4844880) showed a significant increased risk for adenocarcinoma within former smokers (OR: 3.9495% CI: 1.68-9.22, P = 0.011). Haplotype analysis found significance with six haplotypes and lung cancer risk. These findings indicate that select variants in genes in the carbonyl reduction pathway of NNK may alter the risk of lung cancer.

Poster #M59 THE “FIBRE” PATH TO PSYCHOSIS? CAN ADVANCED DIFFUSION IMAGING CAPTURE WHITE MATTER BRAIN ANOMALIES IN ADOLESCENTS EXPERIENCING PSYCHOTIC SYMPTOMS?

Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers.Non-smokers (n = 43) and smokers (n = 40), 22–70 years of age, completed a 4 T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined.Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM.Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions.

Do early onset and pack-years of smoking increase risk of type II diabetes?

BackgroundType II diabetes is not only major public health problem but also heavy fiscal burden to each nation’s health care system around the world. This study aimed to investigate the effect of early onset and pack-years of smoking on type II diabetes risk.MethodsWe used the most recent cross-sectional National Health and Nutrition Examination Survey set of South Korea (2010) and the United States (2009–2010). Participants who were diagnosed with diabetes after age 20 were included (South Korea: n = 7273, 44% male; U.S.: n = 3271, 52% male). Cox proportional models, stratified by sex and country, were used to estimate hazard ratios.Results7.1% of South Korean men, 5.5% of South Korean women, 15.5% of U.S. men, and 12.4% of U.S. women had type II diabetes; 40% of South Korean men, 34% of U.S. men, and 21% of U.S. women began smoking before age 20 (57%, 49%, 36% of those who had type II diabetes, respectively). Type II diabetic participants were older and married; have a higher BMI, low income, and less education; lack moderate physical activity, smoked more and earlier compared to those without type II diabetes. Differences in risk factors including life-style behaviors and SES were found in both diabetic and non-diabetic populations. Men who began smoking before age 16 had a higher type II diabetes risk than who never smoked (South Korea: hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.04–5.79; U.S.: HR 1.64, 95% CI 1.01–2.67), as did U.S. men who began smoking between 16 and 20 years (HR 1.58, 95% CI 1.05–2.37). Smoking pack-years were also associated with type II diabetes in U.S. men (HR 1.07, 95% CI 1.01–1.12). In women population, however, associations were not found.ConclusionsEarly onset of smoking increases type II diabetic risk among men in South Korea and the U.S., and type II diabetic risk increases with higher pack-years in U.S. men, however, no associations were found in women population. Underage tobacco policy and education programs are strongly needed in both countries.

Active and passive cigarette smoking and breast cancer risk: Results from the EPIC cohort

Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

Prognostic Impact of Cigarette Smoking on the Survival of Patients with Established Nasopharyngeal Carcinoma

Cigarette smoking is associated with the etiology of nasopharyngeal carcinoma; however, the influence of smoking on survival in patients with established nasopharyngeal carcinoma remains unknown. We retrospectively analyzed 1,849 patients with nasopharyngeal carcinoma who were categorized as never, former, and current smokers. Cumulative effect of smoking was defined in terms of pack-years. Associations between cigarette exposure and survival were estimated by Cox proportional hazards model. The risks of death, progression, locoregional relapse, and distant metastasis were significantly higher for former and current smokers (all P ≤ 0.002) than never smokers. Heavy smokers with high pack-years had HRs for death of 3.31 [95% confidence interval (CI), 2.58-4.26; P < 0.001], for progression of 2.53 (95% CI, 2.03-3.16; P < 0.001), and for distant metastasis of 2.65 (95% CI, 1.89-3.70; P < 0.001). Specifically, in the cohort of 495 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, we obtained similarly significant results. All of the survival outcomes remained significant in multivariate analyses. Pretreatment cigarette smoking is an independent, poor prognostic factor for patients with nasopharyngeal carcinoma, which is associated with increased risk of death, progression, locoregional relapse, and distant metastasis, with the risk increasing with pack-years. It is clear that cigarette smoking not only promotes carcinogenesis in the normal nasopharyngeal epithelium, but also affects the survival of patients with nasopharyngeal carcinoma.