Therapeutic effects of adenosine in high flow 21% oxygen aereosol in patients with Covid19-pneumonia.
Therapeutic effects of adenosine in high flow 21% oxygen aereosol in patients with Covid19-pneumonia.
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DOI：
10.1371/journal.pone.0239692
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Macheda S
中科院分区：
文献类型：
--
作者：
Correale P;Caracciolo M;Bilotta F;Conte M;Cuzzola M;Falcone C;Mangano C;Falzea AC;Iuliano E;Morabito A;Foti G;Armentano A;Caraglia M;De Lorenzo A;Sitkovsky M;Macheda S
SARS-Cov2 感染可能引发肺部炎症和急性呼吸窘迫综合征 (ARDS)，需要主动通气，并可能导致致命后果。考虑到疾病的严重性和缺乏积极治疗，14 名患有 Covid-19 和严重肺部炎症的患者接受了吸入腺苷，试图在治疗上补偿内源性腺苷→A2A 腺苷受体 (A2AR) 介导的氧相关损失，从而减轻肺部破坏性炎症损伤。这种超说明书治疗基于对 LPS 诱导的 ARDS 小鼠的临床前研究，其中吸入腺苷/A2AR 激动剂可保护含氧肺部免受致命的炎症损伤。考虑到腺苷有多种临床应用，该治疗被允许。连续入组的 14 名患有 Covid19 相关间质性肺炎且 PaO2/FiO2 比值<300 的患者在前 24 小时内每 12 小时接受一次 9 mg 吸入腺苷超说明书治疗，随后在接下来的 4 天内每 24 天接受一次 9 mg 吸入腺苷治疗。 2020 年 2 月至 4 月期间住院且未接受腺苷治疗的 52 名具有类似特征的患者被视为历史对照组。患者监测还包括血流动力学/血液化学研究、CT 扫描和 SARS-CoV2 测试。该治疗耐受性良好，未出现血流动力学变化，仅出现一例中度支气管痉挛。据报道，15 天内，14 名接受腺苷治疗的患者中有 13 名的 PaO2/FiO2 比值显着增加（> 30%），而对照组的 52 名患者中有 7 名观察到 PaO2/FiO2 比值显着增加（> 30%）。此外，我们记录了接受腺苷治疗的患者平均 PaO2/FiO2 比值增加（215 ± 45 vs. 464 ± 136，P = 0.0002），而对照组没有变化（120 小时时为 210±75 vs. 250±85，P>0.05）。 7 名接受腺苷治疗的患者出现了放射学反应，而 13 名患者的 SARS-CoV-2 RNA 载量在 7 天内迅速下降，而对照组在 15 天内没有记录到任何变化。实验组有 1 例与 Covid-19 相关的死亡，对照组有 11 例。我们的短期分析表明，吸入腺苷对 Covid-19 炎症性肺病患者的总体安全性和有益治疗效果表明，需要在对照临床试验中进行进一步研究。
SARS-Cov2 infection may trigger lung inflammation and acute-respiratory-distress-syndrome (ARDS) that requires active ventilation and may have fatal outcome. Considering the severity of the disease and the lack of active treatments, 14 patients with Covid-19 and severe lung inflammation received inhaled adenosine in the attempt to therapeutically compensate for the oxygen-related loss of the endogenous adenosine→A2A adenosine receptor (A2AR)-mediated mitigation of the lung-destructing inflammatory damage. This off label-treatment was based on preclinical studies in mice with LPS-induced ARDS, where inhaled adenosine/A2AR agonists protected oxygenated lungs from the deadly inflammatory damage. The treatment was allowed, considering that adenosine has several clinical applications. Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio<300 received off-label-treatment with 9 mg inhaled adenosine every 12 hours in the first 24 hours and subsequently, every 24 days for the next 4 days. Fifty-two patients with analogue features and hospitalized between February and April 2020, who did not receive adenosine, were considered as a historical control group. Patients monitoring also included hemodynamic/hematochemical studies, CTscans, and SARS-CoV2-tests. The treatment was well tolerated with no hemodynamic change and one case of moderate bronchospasm. A significant increase (> 30%) in the PaO2/FiO2-ratio was reported in 13 out of 14 patients treated with adenosine compared with that observed in 7 out of52 patients in the control within 15 days. Additionally, we recorded a mean PaO2/FiO2-ratio increase (215 ± 45 vs. 464 ± 136, P = 0.0002) in patients receiving adenosine and no change in the control group (210±75 vs. 250±85 at 120 hours, P>0.05). A radiological response was demonstrated in 7 patients who received adenosine, while SARS-CoV-2 RNA load rapidly decreased in 13 cases within 7 days while no changes were recorded in the control group within 15 days. There was one Covid-19 related death in the experimental group and 11in the control group. Our short-term analysis suggests the overall safety and beneficial therapeutic effect of inhaled adenosine in patients with Covid-19-inflammatory lung disease suggesting further investigation in controlled clinical trials.
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影响因子：
5.9
作者：
Seo, Sang-Uk;Kweon, Mi-Na
通讯作者：
Kweon, Mi-Na
氧合抑制了生理组织保护机制，从而加剧了急性炎症肺损伤。
影响因子：
9.8
作者：
Thiel, M;Chouker, A;Ohta, A;Jackson, E;Caldwell, C;Smith, P;Lukashev, D;Bittmann, I;Sitkovsky, MV
通讯作者：
Sitkovsky, MV
DOI：
10.1038/nrrheum.2016.178
发表时间：
2017-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1056/nejmra1205750
发表时间：
2012-12-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eltzschig HK;Sitkovsky MV;Robson SC
通讯作者：
Robson SC
影响因子：
5.6
作者：
Gualtieri, Paola;Falcone, Carmela;De Lorenzo, Antonino
通讯作者：
De Lorenzo, Antonino