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Background: This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0–24) at week 6. Secondary and additional endpoints included FEV1 AUC12–24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety. Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]). Compared with placebo, FEV1 AUC0–24 and FEV1 AUC12–24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6. Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo. Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05). Adverse-event (AE) incidence (28%) was similar between treatments. Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group. Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks. Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium. Aclidinium was generally well tolerated.

Electronic cigarettes (e-cigarettes) are an alternative to traditional tobacco cigarette smoking. The aim of this study was to assess the prevalence of cigarette smoking and e-cigarette use among university students from Central and Eastern Europe and to investigate personal characteristics associated with cigarette and e-cigarette smoking. A questionnaire-based cross-sectional survey was performed between 2017–2018 among university students in five European countries: Belarus, Lithuania, Poland, Russia, and Slovakia. The questionnaire included 46 questions related to the frequency and habits of traditional cigarettes and e-cigarettes use. Completed questionnaires were obtained from 14,352 students (8800 medical; aged 20.9 ± 2.4 years) with an overall response rate of 72.2%. Two-thirds of the respondents had smoked a traditional tobacco cigarette and 43.7% had used an e-cigarette. Overall current smoking status included 12.3% traditional cigarette smokers, 1.1% e-cigarette users, and 1.8% were dual users with the remainder being non-smokers. Smoking status differed between the research centres (p < 0.001). Females were less likely to try either cigarettes (OR = 0.83) or e-cigarettes (OR = 0.62) and were less likely to be current cigarette (OR = 0.64), e-cigarette (OR = 0.34), or dual users (OR = 0.33) than males. Perception of e-cigarettes significantly differed between smokers and non-smokers (p < 0.001). Among university students, cigarettes are more popular than e-cigarettes.

The epidemiological association between cancer and exposure to ambient air pollution particles (particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10)) has been related to the ability of PM10 and its constituent nanoparticles (NPs) to cause reactive oxidative species (ROS)-driven DNA damage. However, there are no data on the molecular response to these genotoxic effects.In order to assess whether PM10, NP and ROS-driven DNA damage induce carcinogenesis pathways, A549 cells were treated with tert-butyl-hyperperoxide (Tbh), urban dust (UD), carbon black (CB), nanoparticulate CB (NPCB), benzo(a)pyrene (BaP) and NPCB coated with BaP for f24 h. Single-and double-strand breakage of DNA was determined by comet assay; cell cycle status was analysed using flow cytometry. Nuclear extracts or acid-extracted histones were used for Western blot analysis of p-ser15-p53 (p53 phosphorylated at ser15), p53 binding protein (53BP) 1, phospho-histone H2A.X (p-H2A.X) and phospho-BRCA1 (p-BRCA1).UD caused both single-and double-strand DNA breaks, while other tested NPs caused only single-strand DNA breaks. NPs significantly altered cell cycle kinetics. Tbh enhanced p-H2A.X after 1 and 6 h (2.1-and 2.2-fold, respectively). NP increased 53BP1 expression at 1 h (2.4-8.7-fold) and p-BRCA1 at 1-6 h. N-acetylcysteine blocked NP-driven p-ser15-p53 response.In conclusion, nanoparticles and reactive oxidative species induce DNA damage, activating p53 and proteins related to DNA repair, mimicking irradiation-related carcinogenesis pathways.KEYWORDS: DNA damage, H2A.X histone, nanoparticles, particles with a 50% cut-off aerodynamic diameter of 10 mm, reactive oxidative species I ncreased exposures to particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10) is associated with an increased risk of cardiovascular and respiratory deaths and hospital admissions, as well as lung cancer [1,2]. Direct evidence of DNA damage caused by PM10 has also been confirmed [3]. Attention has focused on the PM10 in cities because that is where most deaths occur, where pollution is routinely monitored and hence the associations are best seen. Typical urban PM10 is comprised of f50% by mass of combustion-derived nanoparticles (CDNPs; particles ,100 nm), which are carbon-centred particles, typically from automobile engine exhausts, with associated compounds including transition metals, ammonium salts of nitrogen, sulphur and chlorine plus geological dust and organic matter [4]. Many toxicological studies over the last decade have confirmed that CDNPs readily generate oxidative stress through reactive oxidative species (ROS) and inflammation and nanoparticles (NPs) are seen as the most harmful components of the PM10 mix [5][6][7].Several investigators have shown that oxidative stress may play a major role in particle-induced DNA damage, which can be prevented by antioxidants and scavengers of ROS [8]. However, detailed molecular mechanisms involved in the hallmark cellular responses to genotoxic effects are currently not known, in contras...