α-1肾上腺素能受体拮抗剂预防下呼吸道感染引起的炎症过度和死亡
Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection
摘要：
在严重的病毒性肺炎中，包括2019年冠状病毒病（COVID-19），病毒复制阶段通常伴随着过度炎症，这可能导致急性呼吸窘迫综合征，多器官衰竭和死亡。我们先前证明了α-1肾上腺素能受体（$α_1$ -AR）拮抗剂可以预防小鼠的过度炎症和死亡。在此，我们对两组急性呼吸窘迫（ARD，n= 18，547）患者和三组肺炎患者（n= 400，907）进行了回顾性分析。在两个ARD队列中，我们发现与未暴露患者相比，暴露于$α_1$ -AR拮抗剂的患者机械通气和死亡的相对风险降低34%（OR=0.70，p=0.021）。我们在三个肺炎队列中重复了这些方法，所有这些方法对两种结果的影响都相似。所有结果均对敏感性分析具有稳健性。这些结果强调了迫切需要进行前瞻性试验，以测试预防性使用$α_1$ -AR拮抗剂是否能改善下呼吸道感染相关的炎症过度和死亡，如在COVID-19中观察到的那样。
英文摘要：
In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($α_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907). Federated across two ARD cohorts, we find that patients exposed to $α_1$-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR=0.70, p=0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of $α_1$-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.
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