From Bedside to the Bench-A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema.
From Bedside to the Bench-A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema.
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DOI：
10.3389/fphar.2021.806393
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发表时间：
2021
影响因子：
5.6
通讯作者：
Komissarov AA
中科院分区：
文献类型：
--
作者：
Karandashova S;Florova G;Idell S;Komissarov AA
脓胸是肺炎、创伤和手术的严重并发症，其特征是纤维蛋白脓性积液和定位，可导致肺受限和引流阻力。几十年来，人们一直致力于寻找一种适用于所有患者的通用治疗方法，其实践建议在胸膜内纤溶治疗（IPFT）和手术引流之间存在差异。然而，尽管医学取得了进步，但脓胸的发病率却有所增加，这表明我们对这种疾病的病理生理学的理解存在差距，临床实践与临床前研究之间的交流不足，这减慢了创新、个性化治疗的发展。最近对晚期脓胸进行微创治疗的趋势为药物干预开辟了新的机会。其治疗小儿脓胸的显著疗效使IPFT成为一线治疗方法。不幸的是，儿科使用的治疗方法不能推广到成人的脓胸，在治疗晚期疾病时，IPFT的失败率很高。对于手术禁忌症患者，出血并发症的风险和缺乏有效的低剂量IPFT（高达30%）促进了关于纤溶素选择、剂量和方案的争论。这些挑战，加上缺乏护理点诊断来个性化治疗脓胸，导致成人脓胸死亡率高（高达20%），应使用经过验证的动物模型来解决临床前问题。现代临床前研究正在为临床实践中评估和治疗脓胸提供创新的解决方案：低剂量，靶向治疗，预测IPFT成功或失败的新型生物标志物，新的递送方法，如将纤溶素包埋在回声脂质体载体中以增加纤溶酶原激活剂的半衰期。转化研究的重点是了解控制1)从急性到晚期，慢性脓胸转变的病理生理机制，以及2)儿童和成人患者IPFT结局的差异，将确定新的脓胸分子靶点。我们相信，在床边和实验台上工作的人员之间的无缝双向沟通将导致新的个性化方法，以改善药物治疗结果，从而扩大IPFT在成年晚期脓胸患者中的应用窗口。
Empyema, a severe complication of pneumonia, trauma, and surgery is characterized by fibrinopurulent effusions and loculations that can result in lung restriction and resistance to drainage. For decades, efforts have been focused on finding a universal treatment that could be applied to all patients with practice recommendations varying between intrapleural fibrinolytic therapy (IPFT) and surgical drainage. However, despite medical advances, the incidence of empyema has increased, suggesting a gap in our understanding of the pathophysiology of this disease and insufficient crosstalk between clinical practice and preclinical research, which slows the development of innovative, personalized therapies. The recent trend towards less invasive treatments in advanced stage empyema opens new opportunities for pharmacological interventions. Its remarkable efficacy in pediatric empyema makes IPFT the first line treatment. Unfortunately, treatment approaches used in pediatrics cannot be extrapolated to empyema in adults, where there is a high level of failure in IPFT when treating advanced stage disease. The risk of bleeding complications and lack of effective low dose IPFT for patients with contraindications to surgery (up to 30%) promote a debate regarding the choice of fibrinolysin, its dosage and schedule. These challenges, which together with a lack of point of care diagnostics to personalize treatment of empyema, contribute to high (up to 20%) mortality in empyema in adults and should be addressed preclinically using validated animal models. Modern preclinical studies are delivering innovative solutions for evaluation and treatment of empyema in clinical practice: low dose, targeted treatments, novel biomarkers to predict IPFT success or failure, novel delivery methods such as encapsulating fibrinolysin in echogenic liposomal carriers to increase the half-life of plasminogen activator. Translational research focused on understanding the pathophysiological mechanisms that control 1) the transition from acute to advanced-stage, chronic empyema, and 2) differences in outcomes of IPFT between pediatric and adult patients, will identify new molecular targets in empyema. We believe that seamless bidirectional communication between those working at the bedside and the bench would result in novel personalized approaches to improve pharmacological treatment outcomes, thus widening the window for use of IPFT in adult patients with advanced stage empyema.
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