Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.
Groupe de Recherche Clinique CARMAS, Faculté de Santé de Créteil, Université Paris Est Créteil, 94010, Créteil Cedex, France.
Crit Care. 2021 Jan 9;25(1):23. doi: 10.1186/s13054-020-03427-y.
Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes.
Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR monocytes and CD8 PD-1 lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls.
Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8 lymphocytes PD-1 expression and hospital mortality.
IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.
疾病严重程度的生物标志物可能有助于对急性呼吸窘迫综合征（ARDS）患者进行个体化治疗。肺泡内生物标志物的分隔在肺炎相关 ARDS 患者中是否具有临床意义尚不清楚。本研究旨在评估 ARDS/脓毒症生物标志物在肺泡和血液隔室中的相互关系，并探讨其与临床结局的关系。
纳入 2014 年至 2018 年间因肺炎相关性 ARDS 住院的免疫功能正常患者，在入院后 48 小时内采集支气管肺泡灌洗液（BAL）和血液样本。在 BAL 液和血清中定量检测了 22 种生物标志物。使用流式细胞术定量检测 HLA-DR 单核细胞和 CD8 PD-1 淋巴细胞。本研究的主要临床终点为住院死亡率。作为常规治疗一部分接受支气管镜检查的患者被纳入对照组。
共纳入 70 例 ARDS 患者，住院死亡率为 21.4%。ARDS 患者的 BAL 液与血清 IL-8 的比值比对照组高 20 倍（p<0.0001）。休克 ARDS 患者的 BAL 液与血清 IL-1Ra（p=0.026）、IL-6（p=0.002）、IP-10/CXCL10（p=0.024）和 IL-10（p=0.023）比值较低。与死亡患者相比，存活患者的 BAL 液与血清 IL-1Ra 比值更高（p=0.006），即使在调整 SOFA 和驱动压后（p=0.036）。肺泡或肺泡/血液单核细胞 HLA-DR 或 CD8 淋巴细胞 PD-1 表达与住院死亡率之间无显著相关性。
IL-8 是分隔性最强的细胞因子，肺炎相关性 ARDS 患者 BAL 液与血清浓度比值较低的 IL-1Ra 与住院死亡率相关。
