Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19.
Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19.
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DOI：
10.3389/fimmu.2021.714833
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发表时间：
2021
影响因子：
7.3
通讯作者：
Schrum AG
中科院分区：
文献类型：
--
作者：
Holliday ZM;Earhart AP;Alnijoumi MM;Krvavac A;Allen LH;Schrum AG
最严重的冠状病毒病-2019 （COVID-19）病例会发展为急性呼吸窘迫综合征（ARDS）。有人提出，细胞外脱氧核糖核酸（DNA）可能以中性粒细胞胞外陷阱（NETs）的形式抑制氧合。Dornase alfa （Pulmozyme, Genentech）是一种重组人脱氧核糖核酸酶I，通过切割和降解细胞外DNA起到溶黏液作用。我们进行了一项初步研究，以评估dornase alfa对COVID-19继发性ARDS患者的影响。我们对COVID-19继发性ARDS患者进行了一项吸入dornase的非随机病例对照临床试验。与对照组相比，治疗组在第2天动脉氧饱和度与吸入氧比（PaO2/FiO2）的改善（95% CI, 2.96 ~ 95.66， p值= 0.038），以及在第3 ~ 5天的静态肺顺应性（95% CI，分别为4.8 ~ 19.1 mL/cmH2O, 2.7 ~ 16.5 mL/cmH2O和5.3 ~ 19.2 mL/cmH2O）。这些效果在14天后没有持续。使用dornase alfa治疗后，支气管肺泡灌洗液（BALF）髓过氧化物酶-DNA （DNA: MPO）复合物减少（95% CI, -14.7 ~ -1.32， p值= 0.01）。使用dornase alfa治疗与改善BALF的氧合和降低DNA: MPO复合物有关。然而，积极的影响仅限于给药的时间。这些数据表明，通过吸入α - dornase降解与NETs或其他结构相关的细胞外DNA是有益的。我们建议进行更广泛的临床试验。，标识符：NCT04402970。
The most severe cases of Coronavirus-Disease-2019 (COVID-19) develop into Acute Respiratory Distress Syndrome (ARDS). It has been proposed that oxygenation may be inhibited by extracellular deoxyribonucleic acid (DNA) in the form of neutrophil extracellular traps (NETs). Dornase alfa (Pulmozyme, Genentech) is recombinant human deoxyribonuclease I that acts as a mucolytic by cleaving and degrading extracellular DNA. We performed a pilot study to evaluate the effects of dornase alfa in patients with ARDS secondary to COVID-19. We performed a pilot, non-randomized, case-controlled clinical trial of inhaled dornase for patients who developed ARDS secondary to COVID-19 pneumonia. Improvement in arterial oxygen saturation to inhaled fraction of oxygen ratio (PaO2/FiO2) was noted in the treatment group compared to control at day 2 (95% CI, 2.96 to 95.66, P-value = 0.038), as well as in static lung compliance at days 3 through 5 (95% CI, 4.8 to 19.1 mL/cmH2O, 2.7 to 16.5 mL/cmH2O, and 5.3 to 19.2 mL/cmH2O, respectively). These effects were not sustained at 14 days. A reduction in bronchoalveolar lavage fluid (BALF) myeloperoxidase-DNA (DNA : MPO) complexes (95% CI, -14.7 to -1.32, P-value = 0.01) was observed after therapy with dornase alfa. Treatment with dornase alfa was associated with improved oxygenation and decreased DNA : MPO complexes in BALF. The positive effects, however, were limited to the time of drug delivery. These data suggest that degradation of extracellular DNA associated with NETs or other structures by inhaled dornase alfa can be beneficial. We propose a more extensive clinical trial is warranted. , Identifier: NCT04402970.
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影响因子：
8
作者：
Zuo, Yu;Yalavarthi, Srilakshmi;Knight, Jason S.
通讯作者：
Knight, Jason S.
DOI：
10.12703/r/9-25
发表时间：
2020
期刊：
Faculty reviews
影响因子：
--
作者：
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通讯作者：
Allen LH
DOI：
10.1136/bmj.c332
发表时间：
2010-03-23
期刊：
BMJ (Clinical research ed.)
影响因子：
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作者：
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通讯作者：
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影响因子：
24.3
作者：
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通讯作者：
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影响因子：
30.3
作者：
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