Challenges in the management of asthma associated with smoking-induced airway diseases

ABSTRACT

Introduction: Smoking-induced airway diseases such as chronic bronchitis, emphysema, and small airway dysfunction contribute to the chronic respiratory symptoms experienced by adults with asthma, including those with spirometric chronic obstructive pulmonary disease (COPD), termed asthma-COPD overlap (ACO). Drug treatment of symptomatic smokers with asthma or ACO is uncertain due to their exclusion from most clinical trials.

Areas covered: This review summarizes evidence for the efficacy of small molecule drugs used in the clinic to treat current and former smokers with a diagnostic label of asthma or ACO. Other therapeutic interventions are reviewed, including smoking cessation and biologics.

Expert opinion: Clinical trials and observational studies suggest that smoking cessation and approved drugs used to treat non-smokers with asthma produce clinical benefits in smokers with asthma or ACO, although the overall quality of evidence is low. The efficacy of some treatments for asthma is altered in current smokers, including reduced responsiveness to short-term inhaled corticosteroids and possibly improved responsiveness to leukotriene receptor antagonists. Preliminary findings suggest that low-dose theophylline, statins, and biologics, such as omalizumab, mepolizumab, and dupilumab, may improve clinical outcomes in smokers with asthma or ACO. Improved phenotyping and endotyping of asthma and smoking-induced airway diseases should lead to better targeted therapies.     

Non-low-density lipoprotein cholesterol-associated actions of ezetimibe: an overview

Ezetimibe, an intestinal cholesterol absorption inhibitor, lowers circulating low-density lipoprotein cholesterol (LDL-C) levels both when administered as monotherapy and in combination with other hypolipidaemic drugs, mostly statins. This review focuses on the effects of ezetimibe on non-LDL-C-associated variables. In most studies, ezetimibe effectively reduced triglyceride and increased high density lipoprotein cholesterol levels. The authors also consider the effect of ezetimibe on other variables such as C-reactive protein levels, insulin sensitivity and endothelial function. Ezetimibe is useful in patients with sitosterolaemia (a rare inherited disorder) as it significantly reduces plasma phytosterol concentrations. Ezetimibe fulfils two of the three essential characteristics of any drug (efficacy and safety). However, clinical studies are required to provide evidence of its ability to reduce vascular events.     

他汀类药物中间体的生物催化合成研究进展

他汀类药物是一类重要的降血脂药物,(3R,5S)-二羟基酯是他汀类药物发挥作用的关键结构,也是合成该类药物过程中的重要中间体,因其结构中具有两个手性碳原子,故含有(3R,5S)-二羟基酯结构中间体的制备在某种程度上已成为他汀类药物制备的限速步骤。该文对他汀类药物的类型、作用机制、化学结构和合成路线进行概述。着重对近几年采用生物催化方式制备具有 (3R,5S)-二羟基酯结构中间体的方法进行简述。     

他汀类药物对中老年人群骨小梁微结构的影响

摘要： 目的 采用骨小梁分数 （TBS） 这种新型的骨微结构评价指标, 探讨他汀类药物对骨小梁微结构的影响。方法 回顾南京医科大学第一附属医院老年医学科 2014 年 1 月—2016 年 3 月收治的中老年患者 253 例, 根据是否服用他汀类药物分为他汀组 （服用他汀类药物 1 年以上） 90 例和对照组 （从未服用过他汀类药物） 163 例。观察 2 组血清三酰甘油、 总胆固醇、 高密度脂蛋白胆固醇、 低密度脂蛋白胆固醇、 碱性磷酸酶、 空腹血糖等生化指标及 25 羟维生素 D 水平。双能 X 线骨密度仪 （DXA） 检测腰椎及股骨颈骨密度, TBS iNsight ®软件分析腰椎 DXA 图像得出 TBS 值。结果 他汀组的总胆固醇及低密度脂蛋白胆固醇水平低于对照组 （P＜0.01）, 而 2 组其他生化指标差异均无统计学意义 （P＞0.05）。他汀组较对照组具有更高的腰椎 BMD （g/cm2 ： 1.04±0.19 vs. 0.96±0.14, P＜0.01） 及 TBS （1.31± 0.09 vs. 1.26±0.09, P＜0.01）, 但 2 组股骨颈 BMD 差异无统计学意义 （P＞0.05）。结论 他汀类药物使用可以提高中老年人群腰椎骨密度, 并改善骨小梁微结构。     

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low‐density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium‐dependent relaxations in cholesterol‐fed rats. For this purpose, rats were fed by 2% cholesterol‐enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium‐dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL‐cholesterol levels were found to be increased in cholesterol‐fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright © 2015 John Wiley & Sons, Ltd.     

1例瑞舒伐他汀联用缬沙坦致梗阻性黄疸的药学监护

目的 探讨临床药师参与的1例冠心病患者联用瑞舒伐他汀和缬沙坦引起肝损害所致的梗阻性黄疸的药学监护。方法 介绍临床药师参与1例冠心病患者的治疗过程,从药理学角度分析他汀类药物引起的肝损害与剂量、代谢及其他药物相互作用的关系,并提供相关建议。结果 医师只考虑由他汀类药物引起,而临床药师利用专业知识,提出瑞舒伐他汀钙与缬沙坦胶囊的相互作用最大,建议同时停用缬沙坦胶囊。结论 通过医师与药师的合作,从而促进合理用药,保证患者用药的安全有效。同时,也为临床药师实施药学监护提供一种新的思维方式。     

Targeting mulitple dyslipidemias with fixed combinations – focus on extended release niacin and simvastatin

Dyslipidemia is a major risk factor in the initiation and progression of cardiovascular diseases such as atherosclerosis. Several pharmacological agents have been developed over the past 50 years which target various lipid components such as low density lipoprotein (LDL) cholesterol, triglyceride, and high density lipoprotein (HDL) cholesterol. Similar to other risk factors such as hypertension and diabetes mellitus, the management of dyslipidemia can be complicated and may require combination therapy for effective treatment. This review discusses the biochemical mechanisms of action and clinical uses for simvastatin (the most widely available and commercially prescribed statin) and niacin, and the combination of these agents in the management and treatment of dyslipidemia.     

CHILD syndrome: A modified pathogenesis‐targeted therapeutic approach

Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X‐linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase‐like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis‐targeted therapy have been developed. We subsequently chose to use the same pathogenesis‐based therapy using a 2% cholesterol and 2% lovastatin cream with or without glycolic acid in two of our patients. Improvement in CHILD skin lesions was seen as early as 4 weeks after initiation. The addition of glycolic acid helped improve the penetrance of the cholesterol and lovastatin cream into the thick waxy scales. Our study confirms the efficacy of the pathogenesis‐targeted therapy and introduces the possibility of modifying its formula by adding glycolic acid in order to improve the treatment.