Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA.
Department of Clinical Data Science Research, Endpoint Health, Inc, Palo Alto, CA, USA.
J Pharm Pract. 2024 Aug;37(4):955-966. doi: 10.1177/08971900231185392. Epub 2023 Jun 19.
Acute respiratory distress syndrome (ARDS) is an acute inflammatory process in the lungs associated with high morbidity and mortality. Previous research has studied both nonpharmacologic and pharmacologic interventions aimed at targeting this inflammatory process and improving ventilation. To date, only nonpharmacologic interventions including lung protective ventilation, prone positioning, and high positive end-expiratory pressure ventilation strategies have resulted in significant improvements in patient outcomes. Given the high mortality associated with ARDS despite these advancements, interest in subphenotyping has grown, aiming to improve diagnosis and develop personalized treatment approaches. Previous trials evaluating pharmacologic therapies in heterogeneous populations have primarily demonstrated no positive effect, but hope to show benefit when targeting specific subphenotypes, thus increasing their efficacy, while simultaneously decreasing adverse effects. Although most studies evaluating pharmacologic therapies for ARDS have not demonstrated a mortality benefit, there is limited data evaluating pharmacologic therapies in ARDS subphenotypes, which have found promising results. Neuromuscular blocking agents, corticosteroids, and simvastatin have resulted in a mortality benefit when used in patients with the hyper-inflammatory ARDS subphenotype. The use of subphenotyping could revolutionize the way ARDS therapies are applied and therefore improve outcomes while also limiting the adverse effects associated with their ineffective use. Future studies should evaluate ARDS subphenotypes and their response to pharmacologic intervention to advance this area of precision medicine.
急性呼吸窘迫综合征（ARDS）是一种肺部的急性炎症过程，其发病率和死亡率均较高。既往研究已经探讨了针对该炎症过程和改善通气的非药物和药物干预措施。迄今为止，只有非药物干预措施，包括肺保护性通气、俯卧位和高呼气末正压通气策略，才能显著改善患者结局。尽管在这些进展的基础上，ARDS 的死亡率仍然很高，但对亚表型的研究兴趣日益增加，旨在改善诊断并制定个性化的治疗方法。既往评估药物治疗在异质人群中的试验主要显示没有积极效果，但希望针对特定亚表型进行靶向治疗时能够获益，从而提高其疗效，同时减少不良反应。尽管大多数评估 ARDS 药物治疗的研究并未显示出死亡率获益，但针对 ARDS 亚表型的药物治疗的评估数据有限，这些研究结果令人鼓舞。在高炎症性 ARDS 亚表型患者中使用神经肌肉阻滞剂、皮质类固醇和辛伐他汀可带来死亡率获益。亚表型的应用可能会彻底改变 ARDS 治疗方法的应用方式，从而改善结局，同时限制因无效使用而产生的不良反应。未来的研究应评估 ARDS 亚表型及其对药物干预的反应，以推动这一精准医学领域的发展。
