Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
La Clínica de Vasculitis Sistémicas Primarias, Instituto Nacional de Enfermedades Respiratorias, Tlalpan, Ciudad de México, Mexico.
Am J Respir Crit Care Med. 2024 May 1;209(9):1141-1151. doi: 10.1164/rccm.202308-1426OC.
Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ⩽ 85% as measured by pulse oximetry, or use of mechanical ventilation). At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH ( = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21-1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22-26 vs. 22-27) and fewer with reduced GC (median, 23; IQR, 20-25) versus standard GC (median, 26; IQR, 25-28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Original clinical trial registered with www.clinicaltrials.gov (NCT00987389).
弥漫性肺泡出血 (DAH) 是抗中性粒细胞胞浆抗体相关性血管炎 (AAV) 的一种危及生命的表现。PEXIVAS（血浆置换和糖皮质激素在严重抗中性粒细胞胞浆抗体相关性血管炎中的应用）（NCT00987389）试验是 AAV 中规模最大的试验，也是第一个招募需要机械通气的 DAH 患者的试验。评估有无 DAH 的 AAV 患者的特征、治疗效果和结局。PEXIVAS 将 704 名参与者随机分为血浆置换（PLEX）或非 PLEX 组和减少或标准剂量糖皮质激素（GC）组。DAH 状态在入组时定义为无 DAH、非严重或严重（脉搏血氧饱和度仪测量的血氧饱和度 ⩽ 85%，或使用机械通气）。入组时，191 名（27.1%）参与者有 DAH（61 名严重，包括 29 名需要通气），他们更年轻，更频繁地复发，PR3（蛋白酶 3）-ANCA 阳性，血清肌酐水平较低，但与无 DAH 的参与者相比，他们更频繁地接受透析（=513；72.9%）。在有 DAH 的患者中，8/95（8.4%）接受 PLEX 治疗的患者在 1 年内死亡，而 9/96（15.6%）接受非 PLEX 治疗的患者死亡（风险比，0.52；95%置信区间 [CI]，0.21-1.24），而 13/96（13.5%）接受减少 GC 治疗的患者死亡，而 10/95（10.5%）接受标准 GC 治疗的患者死亡（风险比，1.33；95%CI，0.57-3.13）。在需要通气的患者中，PLEX 与非 PLEX 相比，无通气天数相似（中位数，25；四分位距 [IQR]，22-26 与 22-27），而减少 GC 治疗的天数更少（中位数，23；IQR，20-25）与标准 GC 治疗（中位数，26；IQR，25-28）。死亡率的治疗效果不因 DAH 的存在或严重程度而有所不同。总体而言，191 名有 DAH 的患者中有 23/191（12.0%）在 1 年内死亡，而 513 名无 DAH 的患者中有 34/513（6.6%）死亡。终末期肾病和严重感染在 DAH 状态或治疗方面没有差异。有 DAH 的 AAV 患者与无 DAH 的患者在多个方面存在差异。需要进一步的数据来证实或反驳 PLEX 或 GC 剂量对死亡率的影响。原始临床试验在 www.clinicaltrials.gov 上注册（NCT00987389）。
