Division of Veterinary Pathology, Department of Biomedical Sciences & Pathobiology Virginia Tech, Blacksburg, VA, United States of America.
Dept. of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States of America.
PLoS One. 2021 Jun 10;16(6):e0252455. doi: 10.1371/journal.pone.0252455. eCollection 2021.
Bovine respiratory syncytial virus (RSV) has substantial morbidity in young calves, and closely parallels human RSV in infants. We performed a randomized controlled trial in five to six-week-old Holstein calves (Bos taurus). comparing fusion protein inhibitor (FPI) and non-steroidal anti-inflammatory drug (NSAID) singly and in combination at three and five days after experimental BRSV infection. Thirty-six calves received one of six treatments; Ibuprofen started on day 3, Ibuprofen started on day 5, FPI started on day 5, FPI and Ibuprofen started on day 3, FPI and Ibuprofen started on day 5, or placebo. We have previously reported significant clinical benefits when combined FPI and NSAID treatment was started at three and five days after bovine RSV infection. Necropsy was performed on Day 10 following infection and hematoxylin and eosin staining was performed on sections from each lobe. Histology was described using a four-point scale. We performed canonical discrimination analysis (CDA) to determine the structural level where differences between treatments occurred and mixed effects regression to estimate effect sizes. Separation from placebo was maximal for dual therapy at the levels of the alveolus, septum, and bronchus in CDA. We found that the clinical benefits of combined FPI and NSAID treatment of BRSV extend at least partially from histopathological changes in the lung when treatment was started three days after infection. We found decreased lung injury when ibuprofen was started as monotherapy on day 3, but not day 5 following infection. Combined therapy with both an FPI and ibuprofen was always better than ibuprofen alone. We did not prove that the clinical benefits seen starting FPI and ibuprofen five days after infection can be solely explained by histopathological differences as identified on H&E staining.
牛呼吸道合胞体病毒（RSV）在小牛中发病率很高，与婴儿中的人类 RSV 非常相似。我们在五至六周龄的荷斯坦小牛（Bos taurus）中进行了一项随机对照试验，比较了融合蛋白抑制剂（FPI）和非甾体抗炎药（NSAID）单独使用和联合使用在实验性牛呼吸道合胞病毒（BRSV）感染后三天和五天的效果。36 头小牛接受了以下六种治疗方法之一：布洛芬在第 3 天开始使用，布洛芬在第 5 天开始使用，FPI 在第 5 天开始使用，FPI 和布洛芬在第 3 天开始使用，FPI 和布洛芬在第 5 天开始使用，或安慰剂。我们之前报告过，在牛 RSV 感染后三天和五天开始联合使用 FPI 和 NSAID 治疗时，可显著改善临床症状。感染后第 10 天进行剖检，对每个肺叶的切片进行苏木精和伊红染色。使用四分制描述组织学。我们进行了典型判别分析（CDA），以确定治疗之间差异发生的结构水平，并进行混合效应回归以估计效应大小。在 CDA 中，双重治疗在肺泡、隔和支气管水平上与安慰剂的分离程度最大。我们发现，在感染后三天开始治疗时，联合使用 FPI 和 NSAID 治疗 BRSV 的临床益处至少部分来自肺部的组织病理学变化。我们发现，在感染后第 3 天开始单独使用布洛芬时，肺部损伤减少，但在第 5 天开始使用时则不然。同时使用 FPI 和布洛芬的联合治疗总是优于单独使用布洛芬。我们没有证明在感染后五天开始使用 FPI 和布洛芬时看到的临床益处可以仅通过 H&E 染色识别的组织病理学差异来完全解释。
