Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial.
Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial.
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使用痰液定量聚合酶链反应，在COPD患者中经常检测到高水平的EB病毒（EBV），而气道免疫组化分析显示EBV检测在严重疾病中很常见。伐昔洛韦对COPD患者的EBV抑制是否安全有效？COPD中的爱泼斯坦-巴尔病毒抑制（EViSCO）试验是一项在爱尔兰北方贝尔法斯特Mater医院进行的随机、双盲、安慰剂对照试验。符合条件的患者有稳定的中度至重度COPD和痰EBV（使用定量聚合酶链反应测量），并随机（1：1）分配到伐昔洛韦（1 g tid）或匹配的安慰剂8周。主要疗效结局为第8周痰液EBV抑制（定义为痰液病毒载量降低≥ 90%）。主要安全性结局是严重不良反应的发生率。次要结局指标为FEV 1和药物耐受性。探索性结局包括生活质量、痰细胞计数和细胞因子的变化。从2018年11月2日至2020年3月12日，84例患者被随机分配（n = 43例接受伐昔洛韦治疗）。81例患者完成了试验随访，并被纳入主要结局的意向治疗分析。伐昔洛韦组中更多的参与者实现了EBV抑制（n = 36 [87.8%] vs n = 17 [42.5%]; P < .001）。与安慰剂相比，伐昔洛韦与痰EBV滴度显著降低相关（-90，404拷贝/mL [四分位数范围，-298，000至-15，200拷贝/mL] vs-3，940拷贝/mL [四分位数范围，-114，400至50，150拷贝/mL]; P = .002）。伐昔洛韦组FEV 1数值增加24 mL，差异无统计学意义（差异为-44 mL [95% CI，-150至62 mL]; P = 0.41）。然而，与安慰剂组相比，伐昔洛韦组的痰白色细胞计数减少（差异，2.89 [95% CI，1.5 × 106-7.4 × 106]; P = 0.003）。伐昔洛韦对COPD患者EBV的抑制是安全有效的，并可减轻痰液炎性细胞浸润。目前研究的结果为更大规模的试验提供了支持，以评估长期临床结局。ClinicalTrials.gov;编号：NCT03699904; URL：www.clinicaltrials.gov
Epstein-Barr virus (EBV) frequently is measured at high levels in COPD using sputum quantitative polymerase chain reaction, whereas airway immunohistochemistry analysis has shown EBV detection to be common in severe disease. Is valaciclovir safe and effective for EBV suppression in COPD? The Epstein-Barr Virus Suppression in COPD (EViSCO) trial was a randomized double-blind placebo-controlled trial conducted at the Mater Hospital Belfast, Northern Ireland. Eligible patients had stable moderate-to-severe COPD and sputum EBV (measured using quantitative polymerase chain reaction) and were assigned randomly (1:1) to valaciclovir (1 g tid) or matching placebo for 8 weeks. The primary efficacy outcome was sputum EBV suppression (defined as ≥ 90% sputum viral load reduction) at week 8. The primary safety outcome was the incidence of serious adverse reactions. Secondary outcome measures were FEV1 and drug tolerability. Exploratory outcomes included changes in quality of life, sputum cell counts, and cytokines. From November 2, 2018, through March 12, 2020, 84 patients were assigned randomly (n = 43 to valaciclovir). Eighty-one patients completed trial follow-up and were included in the intention-to-treat analysis of the primary outcome. A greater number of participants in the valaciclovir group achieved EBV suppression (n = 36 [87.8%] vs n = 17 [42.5%]; P < .001). Valaciclovir was associated with a significant reduction in sputum EBV titer compared with placebo (–90,404 copies/mL [interquartile range, –298,000 to –15,200 copies/mL] vs –3,940 copies/mL [interquartile range, –114,400 to 50,150 copies/mL]; P = .002). A statistically nonsignificant 24-mL numerical FEV1 increase was shown in the valaciclovir group (difference, –44 mL [95% CI, –150 to 62 mL]; P = .41). However, a reduction in sputum white cell count was noted in the valaciclovir group compared with the placebo group (difference, 2.89 [95% CI, 1.5 × 106-7.4 × 106]; P = .003). Valaciclovir is safe and effective for EBV suppression in COPD and may attenuate the sputum inflammatory cell infiltrate. The findings from the current study provide support for a larger trial to evaluate long-term clinical outcomes. ClinicalTrials.gov; No.: NCT03699904; URL: www.clinicaltrials.gov
影响因子：
4.3
作者：
Kasuga, Ikuma;Hogg, James C.;Pare, Peter D.;Hayashi, Shizu;Sedgwick, Edward G.;Ruan, Jian;Wallace, Alison M.;He, Jian-Qing;Zhang, Xiaozhu;Sandford, Andrew J.
通讯作者：
Sandford, Andrew J.