Low-Dose Lung Radiation Therapy for COVID-19 Lung Disease: A Preclinical Efficacy Study in a Bleomycin Model of Pneumonitis.
Low-Dose Lung Radiation Therapy for COVID-19 Lung Disease: A Preclinical Efficacy Study in a Bleomycin Model of Pneumonitis.
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DOI：
10.1016/j.ijrobp.2021.08.029
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发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Chalmers AJ
中科院分区：
文献类型：
--
作者：
Jackson MR;Stevenson K;Chahal SK;Curley E;Finney GE;Gutierrez-Quintana R;Onwubiko E;Rupp A;Strathdee K;Williams K;MacLeod MKL;McSharry C;Chalmers AJ
低剂量全肺放射治疗（LDLR）已被提议作为与SARS-CoV-2感染相关的急性呼吸窘迫综合征患者的治疗方法，临床试验正在进行中。迫切需要临床前证据来证明这种方法的合理性，并告知剂量，时间表和作用机制。用鼻内硫酸博来霉素（7.5或11.25单位/kg，第0天）处理雌性C57 BL/6小鼠，然后暴露于全肺放射疗法（0.5、1.0或1.5戈伊，或假手术;第3天）。每天测量体重，并在第10天收获肺组织用于组织学和流式细胞术。在放射前（第3天）和终点前（第10天）进行计算机断层扫描肺部成像。博莱霉素引起不同严重程度的肺炎，这与体重减轻有关。在1.0戈伊的LDLR与恢复至初始体重的98%的小鼠比例显著增加相关，并且这些小鼠中的一部分表现出不太严重的组织病理学肺变化。经历中度初始体重减轻的小鼠比经历重度初始体重减轻的小鼠更可能对LDLR作出反应。此外，LDLR（1.0戈伊）显著降低了博来霉素诱导的间质巨噬细胞、CD 103+树突状细胞（DC）和嗜中性粒细胞-DC杂交细胞的增加。总的来说，博来霉素治疗的小鼠左肺中未充气肺的百分比显著高于右肺，LDLR（1.0戈伊）限制了右肺中充气肺体积的进一步减少，但对左肺没有限制。LDLR在0.5和1.5戈伊没有改善体重，流式细胞术，或博莱霉素诱导的肺炎的放射学读数。我们的数据支持LDLR可以改善急性炎症性肺损伤的概念，确定1.0戈伊为最有效剂量，并提供证据表明，它在中度肺炎的背景下比重度肺炎更有效。从机制上讲，1.0戈伊的LDLR显著抑制了博莱霉素诱导的肺间质巨噬细胞、CD 103 + DC和嗜中性粒细胞-DC杂合体的积聚。
Low-dose whole lung radiation therapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection, and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling, and mechanisms of action. Female C57BL/6 mice were treated with intranasal bleomycin sulfate (7.5 or 11.25 units/kg, day 0) and then exposed to whole lung radiation therapy (0.5, 1.0, or 1.5 Gy, or sham; day 3). Bodyweight was measured daily, and lung tissue was harvested for histology and flow cytometry on day 10. Computed tomography lung imaging was performed before radiation (day 3) and pre-endpoint (day 10). Bleomycin caused pneumonitis of variable severity, which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight, and a proportion of these mice exhibited less severe histopathologic lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. In addition, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells (DCs), and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of nonaerated lung in left than right lungs, and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric, or radiologic readouts of bleomycin-induced pneumonitis. Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose, and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ DCs, and neutrophil-DC hybrids.
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DOI：
10.1016/j.ijrobp.2020.12.003
发表时间：
2021-03-15
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
Hanna CR;Robb KA;Blyth KG;Jones RJ;Chalmers AJ
通讯作者：
Chalmers AJ
影响因子：
2.5
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6.2
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Hess CB;Buchwald ZS;Stokes W;Nasti TH;Switchenko JM;Weinberg BD;Steinberg JP;Godette KD;Murphy D;Ahmed R;Curran WJ Jr;Khan MK
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DOI：
10.1016/j.radonc.2020.09.051
发表时间：
2020-12
期刊：
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
影响因子：
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影响因子：
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作者：
Liao, Mingfeng;Liu, Yang;Zhang, Zheng
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