Lifetime Nonsmokers Research Articles

O59 INFLUENCE OF CIRCADIAN BLOOD PRESSURE PATTERN ON RIGHT VENTRICULAR STRUCTURE AND FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSIION

Background and Objective: It is well proven, that arterial hypertension affects left side of the heart and causes its remodeling and functional changes. Since heart works as a unit and has ventricular interdependence, aim of the study was to assess influence of hypertension and circadian blood pressure (BP) profile on a right ventricular structure and function. Methods: 75 hypertensive patients (57.13±7.27 y/o) and 25 normotensive control subjects (57.56±7.55 y/o) were involved in a study. All of them were males without history of coronary artery disease, cerebrovascular or peripheral artery disease, obstructive lung disease, significant valvular heart disease or heart failure. All of them were either lifetime nonsmokers, or stopped smoking more than 5 years. All the patients underwent to 24-hour ambulatory BP monitoring and heart ultrasound with tissue doppler imaging. Results: Hypertensive patients with dipper circadian BP profile had higher TAPSE (19±1.586 vs 17.708±2.857; P<0.05), higher right ventricular ejection fraction (55.103±4.597 vs 47.829±14.605; P<0,005) and lower right ventricular outflow tract diameter (29.985±3.932 vs 32.639±3.510; P<0/05). None of the echo parameters were different between normotensive subjects with different circadian BP pattern. Trans tricuspid valve early diastolic (E) and late diastolic (A) peak velocities were significantly lower in hypertensive patients (1.416±0.130 vs 0.897±1.49; P<0.005). Hence, non-dipper hypertensives had significantly lower tricuspid E/A ratio in comparison with dippers (0.812±0.094 vs 1.048±0.101; P<0.00001). Interventricular septum and posterior wall diameters were higher in non-dipper hypertensives (1.134±0.131 vs. 1.322±0.138; P<0.00001 and 1.072±0.175 vs. 1.254±0.135; P<0.001; respectively). Conclusion: Study data show increased interdependence between two ventricles. Patients with arterial hypertension have systole-diastolic dysfunction, which especially well is present in patients with non-dipper circadian BP profile.

Histologic Distribution of Lung and Bronchus Tumors: A Population-Based Study in the Upper Peninsula of Michigan.

Lung cancer remains the leadingcause of cancer-related mortality in the United States, with cigarette smoking recognized as the most important modifiable risk factor. The distinct smoking rates and occupational landscape in the Upper Peninsula of Michigan underscore the necessity of investigating the multifactorial influences on the prevalence and distribution of lung and bronchus cancer within this population. This study, conducted from January 2012 to December 2022, included 1035 patients diagnosed with lung or bronchus tumors who were first seen and/or received the first course of treatment at Upper Peninsula Health Systems(UPHS) - Marquette, the largest hospital system in the Upper Peninsula of Michigan and one of only two radiation oncology treatment centers in the Upper Peninsula. This study demonstrated that the histologic trend of lung and bronchus cancers in asample of 1035 patients in the Upper Peninsula of Michigan closely resembles that of national averages. Participants with a lifetime history of smoking made up 943 (91.1%) cases of patients diagnosed with lung or bronchus cancers in this study. Lifetime non-smokers only made up 53 (5.1%) cases of patients diagnosed with lung or bronchus cancers. The median age at diagnosis of participants in this study was 70 years. Our study provides significant insights into the histologic distribution of lung and bronchus cancers within the Upper Peninsula of Michigan, addressing a notable gap in the current literature for this rural and medically underserved population. The histologic distribution of lung and bronchus cancers in this region aligns with national trends. Furthermore, the distinct rates of cigarette smoking in the Upper Peninsula emphasizethe critical role of smoking cessation efforts in reducing the burden of lung and bronchus cancers in this region.

Idiopathic pulmonary fibrosis is more strongly associated with coronary artery disease than chronic obstructive pulmonary disease

IntroductionPrevious studies have shown that the population attributable risk of low forced expiratory volume in one second (FEV1) for coronary artery disease (CAD) is substantial. FEV1 can be low either because of airflow obstruction or ventilatory restriction. It is not known if low FEV1 arising from spirometric obstruction or restriction are differently associated with CAD. MethodsWe analyzed high resolution computed tomography (CT) scans acquired at full inspiration in lifetime non-smoker adults with no lung disease (controls) and those with chronic obstructive pulmonary disease enrolled in the Genetic Epidemiology of COPD (COPDGene) study. We also analyzed CT scans of adults with idiopathic pulmonary fibrosis (IPF) from a cohort of patients attending a quaternary referral clinic. Participants with IPF were matched 1:1 by FEV1 %predicted to adults with COPD and 1:1 by age to lifetime non-smokers.Coronary artery calcium (CAC), a surrogate for CAD, was measured by visual quantification on CT using the Weston score. Significant CAC was defined as Weston score ≥7. Multivariable regression models were used to test the association of the presence of COPD or IPF with CAC, with adjustment for age, sex, body-mass-index, smoking status, hypertension, diabetes mellitus, and hyperlipidemia. ResultsWe included 732 subjects in the study; 244 with IPF, 244 with COPD, and 244 lifetime non-smokers. The mean (SD) age was 72.6 (8.1), 62.6 (7.4), and 67.3 (6.6) years, and median (IQR) CAC was 6 (6), 2 (6), and 1 (4), in IPF, COPD, and non-smokers, respectively. On multivariable analyses, the presence of COPD was associated with higher CAC compared to non-smokers (adjusted regression coefficient, β = 1.10 ± SE0.51; P = 0.031). The presence of IPF was also associated with higher CAC compared to non-smokers (β = 03.43 ± SE0.41; P < 0.001). The adjusted odds ratio for having significant CAC was 1.3, 95% CI 0.6 to 2.8; P = 0.53 in COPD and 5.6, 95% CI 2.9 to 10.9; P < 0.001 in IPF, compared to non-smokers. In sex stratified analyses, these associations were mainly noted in women. ConclusionAdults with IPF displayed higher coronary artery calcium than those with COPD after accounting for age and lung function impairment.

Negative Association of Smoking History With Clinically Manifest Cardiac Sarcoidosis: A Case-Control Study

BackgroundThe etiology of sarcoidosis is still unknown and is likely related to a genetic susceptibility to unidentified environmental trigger(s). Our group and others have extensively described a specific phenotype of primarily Caucasian patients who have clinically manifest cardiac sarcoidosis (CS). In this study, we sought to explore whether smoking is associated with this specific phenotype of sarcoidosis. MethodsWe performed a case-control study. Cases with clinically manifest CS were prospectively enrolled in the Cardiac Sarcoidosis Multi-Center Prospective Cohort Study (CHASM-CS registry; NCT01477359) and answered a standardized smoking history questionnaire. Cases were matched 10:1 with controls from the Ontario Health Study. Pretreatment positron emission tomography scans with 18F-fluorodeoxyglucose were compared for smokers vs nonsmokers. ResultsEighty-seven cases met the inclusion criteria. A total of 82 of 87 (94.3%) answered the questionnaire and were matched with 820 controls. A clear negative association of sarcoidosis and smoking was found, with 23 of 82 CS cases (28.0%) being current or ex-smokers, vs 392 of 820 controls (47.8%; P = 0.0006). CS patients with a smoking history had significantly less lifetime consumption (8.31 ± 9.20 pack-years) than the controls (15.34 ± 10.84 pack-years; P < 0.003). On 18F-fluorodeoxyglucose-positron emission tomography scan, the mean standardized uptake value of the left ventricle was 4.2 ± 8.98 in lifetime nonsmokers vs 2.89 ± 2.07 in patients with a smoking history (P < 0.0001). ConclusionsWe describe a strong negative association between smoking history and clinically manifest CS. Nonsmokers had more severe myocardial inflammation (greater mean standardized uptake value of the left ventricle) than did patients with a smoking history. Further research is needed to understand these associations and whether they have therapeutic potential.

Secondhand Smoke Exposure During Childhood and Cancer Mortality in Adulthood Among Never Smokers: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

We examined whether secondhand smoke exposure during childhood was associated with cancer mortality in adulthood among never smokers. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we analyzed data from 45,722 Japanese lifetime nonsmokers aged 40-79 years with no history of cancer at baseline (1988-1990) who had completed a lifestyle questionnaire, including information on the number of family members who had smoked at home during their childhood (0, 1, 2, or ≥3 family members). A Cox proportional hazards model and competing-risks regression were used to calculate multivariable hazard ratios and subdistribution hazard ratios with 95% confidence intervals for overall and site-specific cancer mortality according to the number of family members who smoked during the participant's childhood, after adjusting for potentially confounding factors. During a median follow-up period of 19.2 years, a total of 2,356 cancer deaths were documented. Secondhand smoke exposure was positively associated with the risk of mortality from pancreatic cancer in adulthood; the multivariable hazard ratio for having 3 or more family members who smoked (as compared with none) was 2.32 (95% confidence interval: 1.14, 4.72). Associations were not evident for total cancer risk or risk of other types of smoking-related cancer. In this study, secondhand smoke exposure during childhood was associated with an increased risk of pancreatic cancer mortality in adulthood.

Men and Those With a History of Smoking Are Associated With the Development of Postoperative Ileus Following Elective Colorectal Cancer Resection at a Private Academic Hospital in Johannesburg, South Africa: A Retrospective Cohort Study.

Introduction: A scarcity of local published data on colorectal cancer (CRC) postoperative complications, including postoperative ileus (POI), exists. POI is a temporary gastrointestinal (GI) state of absent or reduced gastric motility shown to increase patient morbidity, prolong length-of-stay (LOS), and intensify the healthcare resource burden. The pathogenesis of POI involves a neurogenic and inflammatory phase plus a pharmacological component.Aim and Objectives: This study aimed to determine centre-specific preoperative risk factors associated with the development of ileus post elective therapeutic CRC resection. The objectives were to determine whether patient demographics; functional status; comorbidities; GI history; pharmacotherapy (including neoadjuvant chemotherapy); and lastly neoadjuvant radiation and chemoradiation were associated with the development of POI.Method: Patients who underwent CRC resection between January 2016 and May 2019 were retrospectively identified from an existing database. Urgent—or non-therapeutic surgeries; surgeries with the complication anastomotic leak or GI obstruction; patients under 18 at the time of surgery or surgeries preceded by preoperative parenteral nutrition were excluded. A comparison was done of the incidence of exposure in the study cohort to investigated variables as potential risk factors for the complication POI.Results: A total of 155 patient cases were included, and 56 (36%) of them developed POI. Univariate comparison of patients who developed POI with demographic characteristics of patients who did not suggested that women were at lower risk to develop POI compared to men (p = 0,013; RR 0,56; 95% CI 0,36–0,89). Functional status suggested that all previous smokers were at a higher risk to develop POI compared to lifetime non-smokers (p = 0,0069; RR 1,78; 95% CI 1,17–2,70). Multivariable comparison of ≤ 5 qualifying parameters showed no significance.Conclusion: The high local incidence of POI in this patient population shows that intervention is required to reduce the POI rate and improve postoperative outcomes. This study suggests that for men and all patients with a history of smoking both, CRC resection preoperative recommendations with the intention to prevent POI should include instructions initiating the activation of preventive strategies like the Enhanced Recovery After Surgery (ERAS) programme. More studies are needed to adequately determine local perioperative risk factors for POI.

Is chronic low back pain and radicular neuropathic pain associated with smoking and a higher nicotine dependence? A cross-sectional study using the DN4 and the Fagerström Test for Nicotine Dependence.

Objective - To evaluate if a current smoking status and a higher nicotine dependence were associated with chronic low back pain and/or radicular neuropathic pain. Materials and methods- A cross-sectional study was conducted on the first eligible consecutive 120 patients. Demographic data, pain intensity, worst pain location, most distal pain radiation, the DN4 questionnaire, STarT back tool, and the Fagerström Test were collected during the initial examination. An age- and gender-matched control group (n=50), free from chronic low back pain was recruited. Results- In the chronic pain group, there was a significant difference between smokers and lifetime non-smokers in the average pain intensity (p=0.037), total DN4 score (p=0.002), STarT Back tool (p=0.006), worst pain location (p=0.023) and the most distal pain radiation (p=0.049). The mean total DN4 score increased with a corresponding increase in the number of cigarettes smoked daily (p=0.002). Current smokers had an OR of 3.071 (p=0.013) (95% CI 1.268-7.438) for developing chronic low back pain and lumbar related leg pain and an OR of 6.484 (p<0.001) (95% CI 2.323-18.099) for developing chronic radicular neuropathic leg pain. For every one-unit increase in the Fagerström test score, the likelihood for chronic low back pain and lumbar related leg pain increased by 40.71% (p=0.008) (95% CI 1.095-1.809) and for chronic radicular neuropathic leg pain increased by 71.3% (p<0.001) (95% CI 1.292-2.272). Conclusion- A current smoking status and a higher nicotine dependence were both independently associated with an increased risk for chronic low back pain and/or chronic radicular neuropathic pain.

Social inequalities in tobacco-attributable mortality in Spain. The intersection between age, sex and educational level.

IntroductionFirst study of social inequalities in tobacco-attributable mortality (TAM) in Spain considering the joint influence of sex, age, and education (intersectional perspective).MethodsData on all deaths due to cancer, cardiometabolic and respiratory diseases among people aged ≥35 years in 2016 were obtained from the Spanish Statistical Office. TAM was calculated based on sex-, age- and education-specific smoking prevalence, and on sex-, age- and disease-specific relative risks of death for former and current smokers vs lifetime non-smokers. As inequality measures, the relative index of inequality (RII) and the slope index of inequality (SII) were calculated using Poisson regression. The RII is interpreted as the relative risk of mortality between the lowest and the highest educational level, and the SII as the absolute difference in mortality.ResultsThe crude TAM rate was 55 and 334 per 100,000 in women and men, respectively. Half of these deaths occurred among people with the lowest educational level (27% of the population). The RII for total mortality was 0.39 (95%CI: 0.35–0.42) in women and 1.61 (95%CI: 1.55–1.67) in men. The SII was -41 and 111 deaths per 100,000, respectively. Less-educated women aged <55 years and men (all ages) showed an increased mortality risk; nonetheless, less educated women aged ≥55 had a reduced risk.ConclusionsTAM is inversely associated with educational level in men and younger women, and directly associated with education in older women. This could be explained by different smoking patterns. Appropriate tobacco control policies should aim to reduce social inequalities in TAM.

High Rates of Nicotine Use Relapse and Ulcer Development Following Roux-en-Y Gastric Bypass.

Given that smoking is known to contribute to gastrojejunal anastomotic (GJA) ulcers, cessation is recommended prior to laparoscopic Roux-en-Y gastric bypass (LRYGB). However, smoking relapse rates and the exact ulcer risk remain unknown. This study aimed to define smoking relapse, risk of GJA ulceration, and complications after LRYGB. We performed a retrospective cohort study of patients who underwent primary LRYGB during 2011-2015. Initially, three patient categories were identified: lifetime non-smokers, patients who were smoking during the initial visit at the bariatric clinic or within the prior year (recent smokers), and patients who had ceased smoking more than a year prior to their initial clinic visit (former smokers). Smoking relapse, GJA ulcer occurrences, reinterventions, and reoperations were recorded and compared. A total of 766 patients were included in the analysis. After surgery, 53 (64.6%) recent smokers had resumed smoking. Out of these relapsed smokers, 51% developed GJA ulcers compared with 14.8% in non-relapsed recent smokers, 16.1% in former smokers, and 6% in lifetime nonsmokers (p < 0.001). Furthermore, relapsed smokers required more frequently endoscopic reinterventions (60.4%) compared with non-relapsed smokers (20.8%, p < 0.001), former smokers (20.7%, p < 0.001), and lifetime non-smokers (15.4%, p < 0.001). Additionally, relapsed smokers required a reoperation (18.9%) more often than non-relapsed recent smokers (5.7%, p < 0.001) and lifetime non-smokers (1.3%, p < 0.001). Smokers relapse frequently after LRYGB, and the majority experience GJA complications. They should be counseled about this risk preoperatively and directed towards less ulcerogenic procedures when possible. Alternatively, longer periods of preoperative smoking abstinence might be needed.

A New TTZ Feature Extracting Algorithm to Decipher Tobacco Related Mutation Signature Genes for the Personalized Lung Adenocarcinoma Treatment

The big percentage of lung adenocarcinomas (LUAD) arising in lifetime nonsmokers and the low sensitivities of known major tobacco biomarkers urgent the identification of real molecular signatures for corresponding personalized treatment. Moreover, cancer is presumed to have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique important gene. Our aims, therefore, are to identify signature genes by optimizing the tobacco exposure pattern (TEP) classification model and to uncover their interaction relationships at different molecular levels. A new method, TTZ, is proposed to extract features as input variables to TEP classification model. Based on the Z-curve method, TTZ is able to extract features not only from mutation frequencies but also from sequencing information of insertions and deletions. Two independent LUAD datasets, The Cancer Genome Atlas (TCGA) and Broad data, are downloaded to train and test the TEP classification model. Thirty-four genes are identified as tobacco related mutational signature genes with the accuracies of 93.55% and 92.65% for train and validation data, respectively. The inference of genetic and protein-protein interaction (PPI) networks uncover that LAMA1, EGFR, KRAS and TNN are the most connected core genes. Six signature genes are proved significantly involved in the cilium damage pathway, which is considered as one of the root causes of lung cancer. The identified signature genes may serve as potential drug targets for the precision medicine of LUAD. Most importantly, the TTZ feature extracting method can be easily extended to other disease or cancer related mutational signature identification issues.

Normative Data of Pulmonary Function Tests and Radiographic Measures of Chest Development in Children Without Spinal Deformity: Is a T1–T12 Height of 22 cm Adequate?

Study DesignRetrospective case series. ObjectivesTo develop normative data of pulmonary function tests (PFTs) and radiographic measures of chest development in normal children and to determine if the prior proposed T1–T12 height of 22 cm for spinal fusion in a growing child is adequate for pulmonary function based on normative PFT values at skeletal maturity. Summary of Background DataShortening of the spine from T1–T12 is a concern with early thoracic fusion for spinal deformity, as it has a deleterious effect on the development of the pulmonary system. MethodsChildren with mild asthma who had pulmonary function tests (PFTs) >90% and without chest or spinal deformity were identified. PFT data included absolute forced vital capacity (FVC), %-predicted FVC, absolute forced expiratory volume in one second (FEV1), %-predicted FEV1, and FEV1/FVC. Radiographic measurements performed on chest radiographs included T1–T12 height, coronal chest width (CCW), and space available for the lung (SAL) bilaterally. These data were analyzed for all patients and for patients with T1–T12 heights 22–24 cm. To assess the impact of T1–T12 shortening on PFTs at skeletal maturity, spirometric standards for healthy adult lifetime nonsmokers were used. ResultsOf 1,797 PFT studies, 149 children (average age 12.4 ± 3.0 years; girls, 97) were analyzed. For the entire cohort, PFT values were as follows: FVC 3.0 ± 0.9 L, %-predicted FVC 103.9% ± 10.6%, absolute FEV1 2.7 ± 0.9 L, %-predicted FEV1 106.9% ± 11.1%, and FEV1/FVC 90.7% ± 2.6%. The averages for T1–T12 height was 25.6 ± 3.8 cm, CCW 25.5 ± 3.4 cm, and SAL bilaterally 19.0 ± 3.5 cm. For the 21 patients (girls 11; average age 9.7 ± 1.4 years) with T1–T12 heights 22–24 cm, absolute FVC was 2.2 ± 0.3 L, %-predicted FVC was 104.0% ± 13.0%, absolute FEV1 was 2.0 ± 0.3 L, %-predicted FEV1 was 108.2% ± 15.0%, and FEV1/FVC was 91.0% ± 2.7%. If these kids with 22–24 cm T1–T12 heights maintained the same thoracic height, they were calculated to have %-predicted FVC of 44% (girl) and 42% (boy) and %-predicted FEV1 of 42% (girl) and 43% (boy) at skeletal maturity (15 years old). ConclusionsPercent-predicted FEV1 and FVC values for normal children with a T1–T12 height of 22 cm at skeletal maturity were <50%. Though this analysis does not take into consideration radial expansion of the chest or children with scoliosis (idiopathic, congenital, neuromuscular), these values are concerning and may not be adequate to guarantee that children with early-onset scoliosis who are fused with T1–T12 heights of 22 cm will have an asymptomatic pulmonary status in adulthood. Level of EvidenceLevel IV.

Methylation profiling of EGFR mutant primary and metastatic lung cancer with brain metastasis.

e20574 Background: EGFR-mutant lung cancer is a key molecular subtype of lung cancer. In recent years there is clear recognition in the value of using methylation signature of cancer for improving diagnosis and predicting outcome as well as understanding the biology of cancer progression. Methods: In this study we chose to characterize the methylome signature of early stage surgically resected EGFR-mutant lung adenocarcinomas in the primary lung tumor. 90 NSCLC cases and 7 matched metastatic brain samples were profiled using Illumina Infinium MethylationEPIC Beadchip. We compared methylation profiles of 1) smokers versus lifetime non-smokers and 2) matched primary lung versus brain metastasis to identify methylation biomarkers. We performed supervised analysis and unsupervised clustering of the methylation data. Results: Unsupervised clustering of all lung and brain samples based on 10K most variable probes showed a similar methylation signature between metastatic brain samples and lung samples. The 7-matched brain and lung samples formed close cluster groups based on matching pairs for the most variable probes from 2.5K to 10K, reflecting the same cell of origin. Supervised analysis of smokers versus lifetime non-smokers did not show any significant methylation differences between the two groups, while unsupervised analysis did not create clusters of smokers and non-smokers based on various number of probe sets we analyzed. Conclusions: Lung tumors that metastasized to the brain share similar methylation features with primary lung tumors. Comprehensive methylation profiling demonstrated no difference between EGFR mutant tumors in smokers versus non-smokers, suggesting that the EGFR mutation is a stronger determinant of outcome independent of smoking.

Secondhand smoke, obesity, and risk of type II diabetes among California teachers

PurposeTo examine if secondhand smoke (SHS) is associated with elevated risk of type II diabetes among California teachers. We also aim to determine if overall and central obesity are mediators or effect modifiers of this association. MethodsUsing data from the California Teachers Study, conducted in 1995–2013 in California public schools, we obtained information on SHS exposure among 39,887 lifetime nonsmokers. The association between SHS and incident diabetes after 17 years of follow-up was assessed using Cox regression models. The mediation and modification effects of BMI and waist circumference on this association were tested. ResultsAt baseline, 70.2% of the nonsmokers reported exposure to SHS. Higher intensity, duration, and intensity-years of exposure to SHS were associated with higher multivariate adjusted risk of incident diabetes in a dose-response manner (hazard ratio = 1.28; 95% confidence interval, 1.11–1.48 for highest quartile vs. lowest quartile of exposure; P = .001 for trend). Participant's waist circumference (measured 2 years after baseline) could explain greater than 50% of the association between SHS and diabetes. ConclusionsSHS exposure is associated with increased risk of type II diabetes among nonsmokers of California teachers with obesity being a potentially important mediator but not an effect modifier for this association.

Centrilobular emphysema and coronary artery calcification: mediation analysis in the SPIROMICS cohort

BackgroundChronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.MethodsWe included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC.ResultsFEV1/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p = 0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p = 0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV1/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC.ConclusionsThe association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis.Trial RegistrationClinicalTrials.gov: Identifier: NCT01969344.

Association of exposure level to passive smoking with hypertension among lifetime nonsmokers in Japan: a cross-sectional study.

Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders.Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: “sometimes or almost never,” “almost every day, 2 hours/day or less,” “almost every day, 2 to 4 hours/day,” “almost every day, 4 to 6 hours/day,” and “almost every day, 6 hours/day or longer.” Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models.The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03–1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01–1.06, Pfor trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01–1.15, Pfor trend = .036) and 1.03 (95% CI: 1.00–1.05, Pfor trend = .055), respectively.Our findings suggest importance of tobacco smoke control for preventing hypertension.

National, regional, and global prevalence of smoking during pregnancy in the general population: a systematic review and meta-analysis.

Smoking during pregnancy has been linked to numerous adverse health consequences for both the developing fetus and mother. We estimated the prevalence of smoking during pregnancy by country, WHO region, and globally and the proportion of pregnant women who smoked during pregnancy, by frequency and quantity, on a global level. For this systematic review and meta-analysis, we did a comprehensive systematic literature search for studies reporting the prevalence of smoking during pregnancy in the general population, published between Jan 1, 1985 and Feb 1, 2016, using several electronic bibliographic databases (CINAHL, Embase, ERIC, Medline, Medline in process, PsychINFO, Scopus, and Web of Science), without language or geographical restrictions. We included original research studies published in a peer-reviewed journal and assessed study quality using a tool specifically developed for use in systematic reviews addressing questions of prevalence. Studies were excluded if they did not include lifetime non-smokers in their sample or estimate, used a sample not generalisable to the general population of the respective country, or did not provide primary data. To estimate the prevalence by country, we did country-specific random-effects meta-analyses for countries with two or more available empirical studies, and we predicted the prevalence using a multilevel fractional response regression model with country-specific indicators for countries with one or no study. We estimated the proportion of female daily smokers who do not quit once pregnant by calculating the regional and global averages of the prevalence of daily smoking during pregnancy and of the prevalence of daily smoking in women. To estimate the global prevalence, by frequency and quantity, we did random-effects meta-analyses using available data from all countries and applied the respective proportions to the global prevalence estimate. We did a time-trend analysis using a univariate multilevel fractional response model. The review protocol is available on PROSPERO, registration number CRD42017075837. Of 21 329 studies identified, 295 were retained for data extraction. We calculated estimates via meta-analysis for 43 countries and via statistical modelling for 131 countries. The three countries with the highest estimated prevalence of smoking during pregnancy were Ireland (38·4%, 95% CI 25·4-52·4), Uruguay (29·7%, 16·6-44·8), and Bulgaria (29·4%, 26·6-32·2). The global prevalence of smoking during pregnancy was estimated to be 1·7% (95% CI 0·0-4·5). The prevalence of smoking during pregnancy was 8·1% (95% CI 4·0-12·2) in the European Region, 5·9% (3·2-8·6) in the Region of the Americas, 1·2% (0·7-1·7) in the Southeast Asian Region, 1·2% (0·0-3·7) in the Western Pacific Region, 0·9% (0·0-1·9) in the Eastern Mediterranean Region, and 0·8% (0·0-2·2) in the African Region. Globally, 72·5% (95% CI 70·4-75·0) of pregnant women who smoked were daily smokers, and 27·5% (25·4-29·6) of them were occasional smokers; 51·8% (95% CI 50·0-53·5) women who smoked were light smokers, 34·8% (33·1-36·4) were moderate smokers, and 13·5% (12·3-14·7) were heavy smokers. Furthermore, the proportion of women who smoked daily and continued to smoke daily during pregnancy was 52·9% (95% CI 45·6-60·3), ranging from 30·6% (95% CI 25·6-36·4) in the European Region to 79·6% (44·2-100·0) in the Western Pacific Region. Smoking during pregnancy is still a prevalent behaviour in many countries. These findings should inform smoking prevention programmes and health promotion strategies, as well as draw attention to the need for improved access to smoking cessation programmes for pregnant women. Centre for Addiction and Mental Health.

Heme oxygenase activity increases after exercise in healthy volunteers

Heme oxygenase (HO) is an essential, rate-limiting protein which catalyses the breakdown of heme to iron, carbon monoxide (CO), and biliverdin. The alpha methene bridge of the heme is eliminated as CO which can be measured as blood carboxyhaemoglobin (COHb). Using blood concentrations of COHb as a measure reflecting HO activity, we tested the postulate that the activity of HO changes with exercise. Ten healthy, nonsmoking volunteers (5 females and 5 males with a mean age ± standard deviation of 25.7 ± 3.2 years), lifetime nonsmokers with no history of respiratory diseases and not taking any medication, were included in the study. Subjects were exposed to filtered air for 2 hrs while alternating exercise for 15 minutes on a cycle ergometer with rest for 15 minutes. Workload was adjusted so that subjects breathed at a ventilatory rate, normalised for body surface area, of 25 L/m2/minute. Immediately before, immediately after, and the day following exercise, blood was drawn by standard venipuncture technique. COHb was determined using the interleukin (IL) 682 Co-Oximeter (Instrumentation Laboratory, Bedford, MA). COHb increased in each participant during the exercise session with the mean value (± standard deviation) almost doubling (1.1 ± 1.6 to 2.1 ± 1.6%) and returned to baseline by the following day (1.3 ± 1.3%). We conclude that exercise increases HO activity.

High neutrophil-to-lymphocyte ratio predicts poor prognosis in patients with squamous cell carcinoma of the head and neck treated with definitive chemoradiotherapy.

To evaluate the role of neutrophil-to-lymphocyte ratio as a prognostic marker in squamous cell carcinoma of the head and neck treated with definitive chemoradiotherapy. A retrospective chart review was performed on patients presenting to our service between 2001 and 2014. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. The association between neutrophil-to-lymphocyte ratio and survival was analyzed by both univariate and multivariate analysis. Across all patients, OS and PFS at 5 years was 59% and 54%, respectively. Increasing T stage correlated with a statistically significant decrease in OS (P = 0.004) and PFS (P = 0.005). Both overall (P = 0.003) and PFS (P = 0.002) were highest in lifetime nonsmokers and lowest in current smokers. Patients who commenced treatment in 2010 or later had a significantly greater overall (P = 0.014) and PFS (P = 0.009) compared to those treated prior. Patients with p16 negative tumors had a significantly lower overall (P<0.001) and PFS (P<0.001) compared to those with p16 positive tumors. Patients treated with cisplatin had an overall and PFS of 66.8% and 59.9% respectively at 5 years. Patients with a neutrophil-to-lymphocyte ratio of less than 4 at treatment initiation had a significantly greater overall (P = 0.015) and PFS (P = 0.017). The trend for OS remained significant in multivariate analysis (P = 0.05). A high neutrophil-to-lymphocyte ratio at treatment initiation is a negative predictive marker for squamous cell carcinoma of the head and neck treated with definitive chemoradiotherapy.

Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians.

There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (T LCO); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T LCOData from 19 centres in 14 countries were collected to define T LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660 T LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for T LCO, transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative T LCO data, and the first global reference values available for T LCO.

Spirometry reference values for population aged 7-80 years in China.

Lung function tests are widely used in clinical and public health practice; however, no valid spirometry reference values were available for the general population in China. This study aimed to provide valid spirometry predictive equations for the general population in China, and to evaluate the predictive performance of previously used equations. Data from the China National Health Survey 2012-2015 and the 'Generalized Additive Models for Location, Scale and Shape' statistical modelling method were used to establish spirometry predictive equations for forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC) and FEV1 /FVC. Paired t-tests were used to examine differences between spirometry measurements in this sample and predicted values of four previous spirometry predictive equations. This study included 3130 lifetime non-smokers (713 males and 2417 females) aged 7-80 years in China. Spirometry predictive equations with age and height as predictive variables plus age-specific splines were established separately by gender. Most previous spirometry predictive equations were found to significantly overestimate (maximum of 3.69% in FEV1 , 1.87% in FVC and 4.19% in FEV1 /FVC for males; 11.46% in FEV1 , 7.28% in FVC and 3.78% in FEV1 /FVC for females) or underestimate (maximum of 5.75% in FEV1 and 8.12% in FVC for males; 7.89% in FEV1 and 9.32% in FVC for females) lung function measurements when applied to this sample population. This study addressed the urgent need for valid and up-to-date spirometry reference values for the general population in China. Moreover, previous spirometry predictive equations showed unfavourable generalizability to this sample population.