Effects of Lipid Mediator Antagonists on Predominant Mediator-Controlled Asthmatic Reactions in Passively Sensitized Guinea Pigs

ABSTRACT The role of cysteinyl leukotrienes (cys-LTs) and thromboxane A 2 (TXA 2 ) in guinea pig models of aspects of bronchial asthma was investigated. In a novel antigen (BSA)-induced asthmatic model using passively sensitized guinea pigs, pretreatment with varying doses of indomethacin controlled the ratio of followed lipid mediators, LTC 4 /D 4 /E 4 and TXB 2 , in lungs of challenged guinea pigs. The predominant mediator in indomethacin-untreated asthma was TXA 2 , and complete inhibition of cyclooxygenase by i.v. injection of 5-mg/kg indomethacin-induced cys-LTs mainly mediated asthmatic response. Furthermore, a 1-mg/kg indomethacin dose induced an asthmatic state where both cys-LTs and TXA 2 equally participated. Either LTD 4 or TXA 2 receptor antagonists given alone inhibited the asthmatic response in conditions where the corresponding mediator plays a predominant role. The combination of LTD 4 and TXA 2 receptor antagonists exhibited significant effects irrespective of the condition used. Under conditions where both mediators equally participate, a combination of both receptor antagonists showed additive inhibition. YM158, a newly synthesized and orally active dual antagonist for LTD 4 and TXA 2 receptors, showed the same antiasthmatic effect as a combinated LTD 4 receptor antagonist and a TXA 2 receptor antagonist mixture. Therefore, broad-acting compounds such as YM158 are expected to have antiasthmatic efficacies in a broader class of asthmatic patients than single-acting drugs

Examining the association of smoking with work productivity and associated costs in Japan

<p><b>Aims:</b> Smoking is associated with significant health and economic burden globally, including an increased risk of many leading causes of mortality and significant impairments in work productivity. This burden is attenuated by successful tobacco cessation, including reduced risk of disease and improved productivity. The current study aimed to show the benefits of smoking cessation for workplace productivity and decreased costs associated with loss of work impairment.</p> <p><b>Materials and methods:</b> The data source was the 2011 Japan National Health and Wellness Survey (<i>n</i> = 30,000). Respondents aged 20–64 were used in the analyses (<i>n</i> = 23,738) and were categorized into: current smokers, former smokers, and never smokers. Generalized linear models controlling for demographics and health characteristics examined the relationship of smoking status with the Work Productivity and Activity Impairment questionnaire (WPAI-GH) endpoints, as well as estimated indirect costs.</p> <p><b>Results:</b> Current smokers reported the greatest overall work impairment, including absenteeism (i.e. work time missed) and presenteeism (i.e. impairment while at work); however, after controlling for covariates, there were no significant differences between former smokers and never smokers on overall work impairment. Current smokers and former smokers had greater activity impairment (i.e. impairment in daily activities) than never smokers. Current smokers reported the highest indirect costs (i.e. costs associated with work impairment); however, after controlling for covariates, there were no significant differences between former smokers and never smokers on indirect costs.</p> <p><b>Limitations and conclusions:</b> Smoking exerts a large health and economic burden; however, smoking cessation attenuates this burden. The current study provides important further evidence of this association, with former smokers appearing statistically indistinguishable from never smokers in terms of work productivity loss and associated indirect costs among a large representative sample of Japanese workers. This report highlights the workplace benefits of smoking cessation across productivity markers and cost-savings.</p