Search

Background: The rise in electronic cigarette use by smokers may be responsible for the decreased use of licensed nicotine products and/or increased overall use of non-tobacco nicotine-containing products. This paper reports findings from the Smoking Toolkit Study (STS) tracking use of electronic cigarettes and licensed nicotine products to address this issue.Methods: Data were obtained from monthly surveys involving 14 502 cigarette smokers in England between March 2011 and November 2014. Smokers were asked about their use of electronic cigarettes and licensed nicotine products.Results: Prevalence of electronic cigarette use increased rapidly from 2.2% (95% CI 1.4% to 3.2%) in quarter 2 of 2011 to 20.8% (95% CI 18.3% to 23.4%) in quarter 3 of 2013, after which there was no change. Prevalence of licensed nicotine product use in smokers remained stable from quarter 2 of 2011 (17.4%, 95% CI 15.3% to 19.8%) to quarter 3 of 2013 (17.9%, 95% CI 15.62% to 20.5%), and thereafter declined steadily to 7.9% (95% CI 6.0% to 10.4%). Prevalence of use of any product was stable to quarter 1 of 2012, after which it increased from 18.5% (95% CI 16.3% to 21.0%) to 33.3% (95% CI 30.4% to 36.3%) in quarter 3 of 2013, and then decreased to 22.7% (95% CI 19.3% to 26.3%).Conclusions: The shapes of trajectories since 2011 suggest that electronic cigarettes are probably not responsible for the decline in use of licensed nicotine products. Electronic cigarettes appear to have increased the total market for use of non-tobacco nicotine-containing products. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Self-reported smoking underestimates disease risk. Smoking affects DNA methylation, in particular the cg05575921 site in the aryl hydrocarbon receptor repressor (AHRR) gene. We tested the hypothesis that AHRR cg05575921 hypomethylation is associated with risk of smoking-related morbidity and mortality.Methods: From the Copenhagen City Heart Study representing the Danish general population, we studied 9234 individuals. Using bisulphite treated leucocyte DNA, AHRR (cg05575921) methylation was measured. Rs1051730 (CHRN3A) genotype was used to evaluate smoking heaviness. Participants were followed for up to 22 years for exacerbations of COPD, event of lung cancer and all-cause mortality. Six-year lung cancer risk was calculated according to the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCOM2012).Measurements and Main Results: AHRR (cg05575921) hypomethylation was associated with former and current smoking status, high daily and cumulative smoking, short time since smoking cessation (all p values <7×10-31), and the smoking-related CHRN3A genotype (-0.48% per T-allele, p=0.002). The multifactorially adjusted HRs for the lowest versus highest methylation quintiles were 4.58 (95% CI 2.83 to 7.42) for COPD exacerbations, 4.87 (2.31 to 10.3) for lung cancer and 1.67 (1.48 to 1.88) for all-cause mortality. Finally, among 2576 high-risk smokers eligible for lung cancer screening by CT, observed cumulative incidences of lung cancer after 6 years for individuals in the lowest and highest methylation quintiles were 3.7% and 0.0% (p=2×10-7), whereas predicted PLCOM2012 6-year risks were similar (4.3% and 4.4%, p=0.77).Conclusion: AHRR (cg05575921) hypomethylation, a marker of smoking behaviour, provides potentially clinical relevant predictions of future smoking-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Rationale: The role bacteria play in the progression of COPD has increasingly been highlighted in recent years. However, the microbial community complexity in the lower airways of patients with COPD is poorly characterised.Objectives: To compare the lower airway microbiota in patients with COPD, smokers and non-smokers.Methods: Bronchial wash samples from adults with COPD (n=18), smokers with no airways disease (n=8) and healthy individuals (n=11) were analysed by extended-culture and culture-independent Illumina MiSeq sequencing. We determined aerobic and anaerobic microbiota load and evaluated differences in bacteria associated with the three cohorts. Culture-independent analysis was used to determine differences in microbiota between comparison groups including taxonomic richness, diversity, relative abundance, 'core' microbiota and co-occurrence.Measurement and Main Results: Extended-culture showed no difference in total load of aerobic and anaerobic bacteria between the three cohorts. Culture-independent analysis revealed that the prevalence of members of Pseudomonas spp. was greater in the lower airways of patients with COPD; however, the majority of the sequence reads for this taxa were attributed to three patients. Furthermore, members of Bacteroidetes, such as Prevotella spp., were observed to be greater in the 'healthy' comparison groups. Community diversity (α and β) was significantly less in COPD compared with healthy groups. Co-occurrence of bacterial taxa and the observation of a putative 'core' community within the lower airways were also observed.Conclusions: Microbial community composition in the lower airways of patients with COPD is significantly different to that found in smokers and non-smokers, indicating that a component of the disease is associated with changes in microbiological status. [ABSTRACT FROM AUTHOR]

Background: Emphysema on CT is a risk factor for all-cause mortality in persons with and without airflow obstruction; however, causes of death associated with emphysema remain uncertain, particularly in the general population.Aims: To test associations between quantitatively assessed emphysema on CT and cause of death in persons with and without a substantial smoking history.Methods: The Multi-Ethnic Study of Atherosclerosis recruited 6814 participants, aged 45-84 years and without clinical cardiovascular disease, in 2000-2002. Per cent emphysema was defined on cardiac CT as per cent of lung voxels less than -950 Hounsfield units; emphysema on CT was defined as per cent emphysema above the upper limit of normal. Cause of death was classified by administrative codes. Proportional-hazards models were adjusted for age, race/ethnicity, gender, body mass index, smoking status, pack-years, coronary artery calcium, site and education. Additional adjustment for lung function was made in a subset with spirometry from 2004 to 2006.Results: There were 1091 deaths over 12 years median follow-up. Emphysema on CT was strongly associated with increased mortality due to respiratory diseases (adjusted HR 2.94, 95% CI 1.68 to 5.15), particularly chronic lower respiratory diseases (adjusted HR 9.54, 95% CI 4.70 to 19.35), and lung cancer (adjusted HR 1.84, 95% CI 1.09 to 3.12), but not cardiovascular disease. Associations persisted among participants with fewer than 10 pack-years and those without physician-diagnosed respiratory disease, and were similar after adjustment for airflow measures and in persons without airflow limitation.Conclusions: Quantitatively assessed emphysema on CT is associated with greater respiratory disease and lung cancer mortality, even among persons without traditional risk factors. [ABSTRACT FROM AUTHOR]

Background: Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.Objective: To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.Methods: 3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV1 were tested in cases. We followed-up signals of interest (p<10(-5)) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.Results: Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10(-6)). In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10(-6)). We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5. No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10(-7)).Conclusions: This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study. [ABSTRACT FROM AUTHOR]

Introduction: Long-term air pollution exposure contributes to mortality but there are few studies examining effects of very long-term (>25 years) exposures.Methods: This study investigated modelled air pollution concentrations at residence for 1971, 1981, 1991 (black smoke (BS) and SO2) and 2001 (PM10) in relation to mortality up to 2009 in 367,658 members of the longitudinal survey, a 1% sample of the English Census. Outcomes were all-cause (excluding accidents), cardiovascular (CV) and respiratory mortality.Results: BS and SO2 exposures remained associated with mortality decades after exposure-BS exposure in 1971 was significantly associated with all-cause (OR 1.02 (95% CI 1.01 to 1.04)) and respiratory (OR 1.05 (95% CI 1.01 to 1.09)) mortality in 2002-2009 (ORs expressed per 10 μg/m(3)). Largest effect sizes were seen for more recent exposures and for respiratory disease. PM10 exposure in 2001 was associated with all outcomes in 2002-2009 with stronger associations for respiratory (OR 1.22 (95% CI 1.04 to 1.44)) than CV mortality (OR 1.12 (95% CI 1.01 to 1.25)). Adjusting PM10 for past BS and SO2 exposures in 1971, 1981 and 1991 reduced the all-cause OR to 1.16 (95% CI 1.07 to 1.26) while CV and respiratory associations lost significance, suggesting confounding by past air pollution exposure, but there was no evidence for effect modification. Limitations include limited information on confounding by smoking and exposure misclassification of historic exposures.Conclusions: This large national study suggests that air pollution exposure has long-term effects on mortality that persist decades after exposure, and that historic air pollution exposures influence current estimates of associations between air pollution and mortality. [ABSTRACT FROM AUTHOR]

Background: Although asthma is highly prevalent among certain Hispanic subgroups, genetic determinants of asthma and asthma-related traits have not been conclusively identified in Hispanic populations. A study was undertaken to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator responsiveness (BDR) in Costa Ricans. Methods: Eight extended pedigrees were ascertained through school children with asthma in the Central Valley of Costa Rica. Short tandem repeat (STR) markers were genotyped throughout the genome at an average spacing of 8.2 cM. Multipoint variance component linkage analyses of forced expiratory volume in 1 second (FEV1) and FEV1 / forced vital capacity (FVC; both pre-bronchodilator and post-bronchodilator) and BDR were performed in these eight families (pre-brorichodilator spirometry, n = 640; post-bronchodilator spirometry and BDR, n = 624). Nine additional STR markers were genotyped on chromosome 7. Secondary analyses were repeated after stratification by cigarette smoking. Results: Among all subjects, the highest logarithm of the odds of linkage (LOD) score for FEV1 (post-bronchodilator) was found on chromosome 7q34-35 (LOD = 2.45, including the additional markers). The highest LOD scores for FEV1/FVC (pre-bronchodilator) and BDR were found on chromosomes 2q (LOD= 1.53) and 9p (LOD= 1.53), respectively. Among former and current smokers there was near- significant evidence of linkage to FEV1/FVC (post-bronchodilator) on chromosome Sp (LOD=3.27) and suggestive evidence of linkage to FEV1 on chromosomes 3q (pre-bronchodilator, LOD = 2.74) and 4q (post-bronchodilator, LOD = 2.66). Conclusions: In eight families of children with asthma in Costa Rica, there is suggestive evidence of linkage to FEV1 on chromosome 7q34-35. In these families, FEV1/FVC may be influenced by an interaction between cigarette smoking and a locus (Ioci) on chromosome .5p. [ABSTRACT FROM AUTHOR]

Background: This study sought to determine the rate and patterns of malignancy in patients with extrapulmonary cancers and non-calcified pulmonary nodules, and to develop a statistical model to guide clinicians regarding choice of patients for diagnostic biopsy.Method: The medical records of 151 patients evaluated at the Memorial Sloan-Kettering Cancer Center between January 1999 and December 2001 for non-calcified pulmonary nodules were reviewed. Nodules were considered malignant based on the results of a diagnostic biopsy, and were considered benign if their appearance remained stable 2 years after the initial study, if they resolved, or if a biopsy showed a non-malignant condition.Results: Sixty four of 151 patients (42%) were diagnosed with malignant nodules; 32 had newly diagnosed lung cancers, 28 had metastatic spread of their primary cancers, and four had lesions that were either new cancers or of undetermined aetiology. On univariate analysis the likelihood of malignancy increased with nodule size, tobacco exposure, and the finding of a solitary nodule. On multivariable analysis only nodule size and tobacco exposure were predictive of malignancy. The model had good predictive accuracy (area under the curve 0.751) but had insufficient discrimination for use as a clinical tool to determine which patients should undergo diagnostic biopsy.Conclusion: Nearly half the non-calcified pulmonary nodules identified in this series were malignant. Lung cancer was more common than metastatic disease. These findings support the need for close interval follow up and a low threshold for diagnostic biopsy in patients with extrapulmonary cancers and non-calcified pulmonary nodules. In smokers, such lesions should raise concern for lung cancer. [ABSTRACT FROM AUTHOR]

Background: Early exposure to parental smoking appears to influence the development of the airways and predispose to respiratory symptoms, A study was undertaken to determine whether the consequences of parental smoking could be traced in adulthood. Methods: Information from interviewer-led questionnaires was available for 18 922 subjects aged 20- 44 years from random population samples in 37 areas participating in the European Community Respiratory Health Survey. Lung function data were available for 15 901 subjects. Results: In men, father's smoking in childhood was associated with more respiratory symptoms (ORwheeze 1.13 (95% Cl 1.00 to 1.28); never smokers: ORwheeze 1.21(95% Cl 0.96 to 1.50)) and there was a dose- dependent association between number of parents smoking and wheeze (one: OR 1.08 (95% Cl 0.94 to 1.24); both: OR 1.24(95% CI 1.05 to 1.47); Ptrend = 0.010). A reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) was related to father's smoking (-0.3% (95% Cl -0.6 to 0)) and number of parents smoking (Ptrend <0.001) among men. In women, mother's smoking was associated with more respiratory symptoms and poorer lung function (ORwheeze 1.15 (95% Cl 1.01 to 1.31), never smokers: ORwheeze 1.21(95% Cl 0.98-1.51); FEV1 -24 ml (95% CI -45 to -3); FEV1/FVC ratio -0.6% (95% Cl -0.9 to -0.3)). These effects were possibly accounted for by maternal smoking in pregnancy (ORwheeze 1.39 (95% Cl 1.17 to 1.65); FEV1 -23 ml (95% Cl -52 to 7); FEV1/FYC ratio -0.9% (95% Cl -1.3 to -0.4)) as there was no association with paternal smoking among women (interaction by sex, p<0.05). These results were homogeneous across centres. Conclusion: Both intrauterine and environmental exposure to parental tobacco smoking was related to more respiratory symptoms and poorer lung function in adulthood in this multicultural study. The age window of particular vulnerability appeared to differ by sex, postnatal exposure being important only in men and a role for prenatal exposure being more evident in women. [ABSTRACT FROM AUTHOR]

Background: Emphysema is currently defined as "a condition of the lung characterised by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis." The functional and morphological changes that occur in emphysema have largely been attributed to changes in alveolar elastin rather than in collagen. A study was performed to determine whether the amount of collagen in the alveolar wall changes with age in the lungs of non-smokers and of smokers with different types of macroscopically defined emphysema in relation to a microscopic measurement of lung structure.Methods: Total alveolar wall collagen was measured (as hydroxyproline) in known volumes of distended lung tissue (by reverse phase high pressure liquid chromatography) in the lungs of non-smokers (n = 23) and in regions sampled away from emphysematous lesions in the lungs of 36 smokers (four with no emphysema, 13 with centriacinar emphysema (CAE), nine with panacinar emphysema (PAE), and 10 with a mixture (MIX) of both PAE and CAE). Mean lung airspace wall surface area per unit volume (AWUV) was calculated from at least six random blocks per lung and on histological sections immediately adjacent to those prepared for collagen measurement with a rapid scanning device (fast interval processor).Results: In non-smokers there was no significant correlation between the amount of collagen in the alveolar wall tissue and either mean lung AWUV or increasing patient age when amounts of collagen were expressed either per unit volume of distended lung (40 mm3 sample) or per unit surface area of airspace wall tissue. Smokers without emphysema had similar amounts of collagen to non-smokers. Lungs with PAE and MIX, but not CAE alone, contained significantly more collagen than normal when expressed per unit volume of airspace wall tissue whereas all groups, including CAE, contained significantly raised amounts of collagen when expressed per unit surface area.Conclusions: There is no significant age related change in the collagen content of the lungs of non-smokers which suggests that, as AWUV is lost with age, the main collagenous framework is maintained. However, in smokers with emphysema there is a loss of airspace wall tissue in regions remote from the macroscopic lesions that is accompanied by a net increase in collagen mass. The greater accumulation of collagen in MIX lungs than in CAE lungs suggests a greater degree of structural damage, indicative of an alternative pathogenetic mechanism operating between the different types of emphysema. Our results suggest an active alveolar wall fibrosis in emphysema as a consequence of cigarette smoking. It is suggested that the definition of emphysema may require further revision to include such change. [ABSTRACT FROM AUTHOR]