anzctr.org.au Identifier: ACTRN12611000567921.
Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non-small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in vitro to study the variation of nAChR subunit gene expression with nicotine exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR A6 (P < 0.001) and B3 (P = 0.007) subunit genes than those from smokers, adjusted for gender. In addition, nAChR A4 (P < 0.001) and B4 (P = 0.029) subunit gene expression showed significant difference between NSCLCs and normal lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes associated with NSCLC nonsmoking nAChR A6B3 phenotype were identified, which gave high sensitivity and specificity of prediction. nAChR A1, A5, and A7 showed significant reversible changes in expression levels in HBECs upon nicotine exposure. We conclude that between NSCLCs from smokers and nonsmokers, different nAChR subunit gene expression patterns were found, and a 65-gene expression signature was associated with nonsmoking nAChR A6B3 expression. Finally, nicotine exposure in HBECs resulted in reversible differences in nAChR subunit gene expression. These results further implicate nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention and therapy in lung cancer. [Cancer Res 2007;67(10):4638-47]
The health and safety claims regarding electronic nicotine delivery devices should be subject to evidentiary review. The potential benefits of electronic cigarettes to an individual smoker should be weighed against potential harm to the population of increased social acceptability of smoking and use of nicotine, the latter of which has addictive power and untoward effects. As a precaution, electronic nicotine delivery devices should be restricted or banned until more information about their safety is available. If they are allowed, they should be closely regulated as medicines or tobacco products.
BackgroundChronic obstructive pulmonary disease (COPD) is a clinical syndrome encompassing a group of chronic, progressive, and debilitating respiratory conditions, that are characterized by incompletely reversible airflow limitation. Within the Asia-Pacific region, prevalence estimates have been derived using various protocols and study methods, and there is little data on the impact of COPD exacerbations. This study aimed to provide a comprehensive picture of the current prevalence and burden of COPD in this region.MethodsA population-based survey was conducted in nine Asia-Pacific territories between 01 February 2012 and 16 May 2012. Overall, 112,330 households were screened to identify eligible subjects (aged ≥40 years, with a physician diagnosis of COPD, chronic bronchitis or emphysema, or with identifiable symptoms of chronic bronchitis). Out of a sample of 69,279 individuals aged ≥40 years, 4,289 subjects with COPD were identified. Data were collected via face-to-face interviews or by fixed-line telephone, using a structured questionnaire. A total of 1,841 completed questionnaires were analyzed.ResultsThe overall estimated COPD prevalence was 6.2%, with 19.1% of subjects having severe COPD. In the 12 months prior to the survey, nearly half of all subjects (46%) had experienced exacerbations, and 19% had been hospitalized as a result of their condition. When subjects were asked about the impact of their condition on employment, 23% said their condition kept them from working, and 42% felt that their condition limited their ability to work or their activities. Of those who reported taking prescription drugs, 20% did not know the name of the drugs they were taking. Prescription of oral corticosteroids was common, with 44% of subjects having used these during the previous year to manage their respiratory symptoms; in contrast, inhaler use was low (25%). Only 37% of subjects had taken a lung function test, and the majority (89%) of those tested did not know their test results.ConclusionsAcross the Asia-Pacific territories surveyed, the prevalence of COPD is high, indicating a substantial socioeconomic burden. Our findings suggest that there is considerable room for improvement in the management of COPD, and highlight a need to enhance patient and physician education in the region.Electronic supplementary materialThe online version of this article (doi:10.1186/s12930-015-0020-9) contains supplementary material, which is available to authorized users.
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