Queen's University Belfast, Centre for Infection and Immunity , Belfast , UK
Expert Opin Biol Ther. 2014 Jul;14(7):969-81. doi: 10.1517/14712598.2014.905536. Epub 2014 Apr 5.
The acute respiratory distress syndrome (ARDS) is characterised by life-threatening respiratory failure requiring mechanical ventilation, and multiple organ failure. It has a mortality of up to 30 - 45% and causes a long-term reduction in quality of life for survivors, with only approximately 50% of survivors able to return to work 12 months after hospital discharge.
In this review we discuss the complex pathophysiology of ARDS, describe the mechanistic pathways implicated in the development of ARDS and how these are currently being targeted with novel biological therapies. These include therapies targeted against inflammatory cytokines, mechanisms mediating increased alveolar permeability and disordered coagulation, as well as the potential of growth factors, gene therapy and mesenchymal stem cells.
Although understanding of the pathophysiology of ARDS has improved, to date there are no effective pharmacological interventions that target a specific mechanism, with the only potentially effective therapies to date aiming to limit ventilator-associated lung injury. However, we believe that through this improved mechanistic insight and better clinical trial design, there is cautious optimism for the future of biological therapies in ARDS, and expect current and future biological compounds to provide treatment options to clinicians managing this devastating condition.
急性呼吸窘迫综合征(ARDS)的特征是危及生命的呼吸衰竭,需要机械通气和多器官衰竭。其死亡率高达 30-45%,并导致幸存者长期生活质量下降,只有大约 50%的幸存者在出院后 12 个月能够重返工作岗位。
在这篇综述中,我们讨论了 ARDS 的复杂病理生理学,描述了参与 ARDS 发展的机制途径,以及目前如何用新型生物疗法来靶向这些途径。这些疗法包括针对炎症细胞因子、增加肺泡通透性和凝血紊乱的调节机制的靶向治疗,以及生长因子、基因治疗和间充质干细胞的潜在应用。
尽管对 ARDS 的病理生理学的理解有所提高,但迄今为止,还没有针对特定机制的有效药物干预措施,迄今为止唯一可能有效的治疗方法是限制呼吸机相关性肺损伤。然而,我们相信,通过这种机制的深入了解和更好的临床试验设计,对 ARDS 的生物疗法的未来抱有谨慎的乐观态度,并期望当前和未来的生物化合物为治疗这种破坏性疾病的临床医生提供治疗选择。