Pharmacotherapeutic strategies for critical asthma syndrome: a look at the state of the art

ABSTRACT

Introduction

‘Critical Asthma Syndrome’ (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes.     

Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

分瓶法测定果蝇吸入麻醉药半数麻醉有效浓度

目的　建立测定果蝇吸入麻醉药半数麻醉有效浓度 (ED50 )的方法学。方法　在 11个 32 5ml的三角烧瓶中各放入 30只雄性果蝇 ,分别加入不同容量的异氟醚标准气 ,使 11个烧瓶中异氟醚浓度分布在零效应浓度与百分之百效应浓度之间。以果蝇失去附壁及运动能力为标准计算各瓶中被麻醉果蝇数 ,用正规法计算出ED50 。结果　 11次实验在 2 5及 5 0min时的量 -效关系曲线均呈S形 ,用各自的对数浓度与概率单位作图都呈直线相关 ,相关系数分别为 0 .972± 0 .0 14和 0 .971± 0 .0 2 5 ,ED50 值分别为 (0 .5 1± 0 .0 6 8) %和 (0 .4 7± 0 .0 85 ) % ,变异系数分别为 13.3%和 18.0 %。结论　本法稳定性较好 ,实用可行     

Immunosuppression Minimization in Pediatric Transplantation

The greatest benefit of immunosuppression minimization for children may lie in improving patient morbidity, by the elimination of the inherent side effects of steroid and calcineurin inhibitors (CNI). The newer generation of powerful induction and maintenance immunosuppressants offers an option for selected immunosuppression minimization strategies, some of which have been shown to also reduce graft morbidity. Steroid minimization and avoidance in single-center uncontrolled trials have shown early promise and the availability of data from an ongoing randomized, prospective, controlled trial of steroid avoidance in children will provide necessary data to support a practice change for steroid elimination in children. Calcineurin inhibitor minimization and addition of mycophenolate mofetil (MMF) or sirolimus have shown variable improvements in renal function, though suboptimal efficacy and safety with the currently proposed regimes have limited their application. Randomized, prospective studies of steroid and calcineurin inhibitor minimization and/or avoidance are warranted to clearly confirm the short and long-term safety and efficacy of alternative immunosuppression combinations. Linked pharmacokinetic and mechanistic studies within these trials will allow for optimizing drug dosing and monitoring. This article reviews published experience to date with steroid and calcineurin minimization in pediatric renal transplantation and discusses the risks and benefits of these approaches.     

白炭黑粉尘对肺脏的作用

大鼠气管注入(剂量50mg)或自然吸入白炭黑粉尘,引起肺组织以细胞性结节为主的病理改变。注入组的肺重、肺胶原蛋白及类脂的含量均显著地高于正常对照组,但比石英对照组低得多。说明白炭黑粉尘对肺脏的作用表现为非特异性反应性改变。应重视它的远期作用,做好白炭黑生产和使用部门的劳动保护工作。     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

糖皮质激素在川崎病治疗中作用的循证医学研究

目的 通过循证医学方法研究肾上腺皮质激素在川崎病治疗中的作用.方法 采用循证医学方法,检索国内外5种大型专业数据库,筛选出随机或半随机对照研究的文献,再人工筛查确定适宜文献.通过Meta分析,比较激素与丙种球蛋白治疗川崎病在退热时间和冠状动脉病变发生率方面的差异.结果 初筛得到443篇文献.经过人工检索,8篇文献符合要求而被纳入标准.其中,3篇文献共有49例川崎病患儿接受甲基强的松龙治疗,5篇文献共有406例患儿接受强的松治疗.对照组共有33例接受静脉丙种球蛋白治疗,435例接受阿司匹林治疗.各组间患儿性别、年龄、病程差异无显著意义.①甲基强的松龙组(3篇文献):24例发生冠状动脉病变,对照组18例发生,两组病变发生率差异无显著意义.在退热方面,1篇文献显示甲基强的松龙组发热时间明显较丙种球蛋白组缩短,差异有显著意义;2篇文献显示差异无显著意义.②强的松组(8篇文献):28例发生冠状动脉瘤,阿司匹林对照组11例发生,3篇文献提示强的松组冠状动脉瘤发生率明显高于对照组.强的松组76例发生冠状动脉扩张,对照组75例发生,3篇文献提示强的松组冠状动脉扩张发生率明显高于对照组,2篇文献提示强的松组冠状动脉扩张发生率略低于对照组,但差异无显著意义.结论 目前的研究资料显示,激素治疗与丙种球蛋白治疗川崎病在冠状动脉病变发生率方面尚无差异或增高.在缩短热程上两者差异也不显著.尚可进一步通过更大数量病例的随机对照研究来证实本结果.目前治疗川崎病不主张单独应用激素.     

Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.