Department of Biostatistics, Nanjing Medical University School of Public Health, Nanjing, Jiangsu, China.
China International Cooperation Center for Environment and Human Health, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China.
JAMA Netw Open. 2021 Jan 4;4(1):e2034569. doi: 10.1001/jamanetworkopen.2020.34569.
Acute respiratory distress syndrome (ARDS) confers high mortality risk among critically ill patients. Identification of biomarkers associated with ARDS risk may guide clinical diagnosis and prognosis.
To systematically evaluate the association of blood metabolites with ARDS risk and survival.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data from the Molecular Epidemiology of ARDS (MEARDS) study, a prospective cohort of 403 patients with ARDS and 1227 non-ARDS controls, were analyzed. Patients were recruited in intensive care units (ICUs) at Massachusetts General Hospital and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts, from January 1, 1998, to December 31, 2014. Data analysis was performed from December 9, 2018, to January 4, 2019.
Participants were followed up daily for ARDS development defined by Berlin criteria, requiring fulfillment of chest radiograph and oxygenation criteria on the same calendar day during invasive ventilatory assistance. A 2-stage study design was used to explore novel metabolites associated with ARDS risk and survival.
Of the 1630 participants from MEARDS who were admitted to the ICU , 403 (24.7%) were diagnosed with ARDS (mean [SD] age, 63.0 [17.0] years; 251 [62.3%] male) and 1227 (75.3%) were at-risk but did not have ARDS (mean [SD] age, 62.3 [16.9] years; 753 [61.4%] male). Mendelian randomization suggested that genetically regulated serum mannose was associated with ARDS risk (odds ratio [OR], 0.64; 95% CI, 0.53-0.78; P = 7.46 × 10-6) in the discovery stage. In the functional validation stage incorporating 83 participants with ARDS and matched at-risk participants in the control group from the ICU, the protective association of mannose with ARDS risk was validated (OR, 0.67; 95% CI, 0.46-0.97; P = .03). Furthermore, serum mannose was associated with 28-day (OR, 0.25; 95% CI, 0.11-0.56; P = 6.95 × 10-4) and 60-day (OR, 0.36; 95% CI, 0.19-0.71; P = 3.12 × 10-3) mortality and 28-day (hazard ratio, 0.49; 95% CI, 0.32-0.74; P = 6.41 × 10-4) and 60-day (hazard ratio, 0.55; 95% CI, 0.37-0.80; P = 2.11 × 10-3) survival.
In this study, genetically regulated serum mannose appeared to be associated with ARDS risk and outcome, and increased serum mannose at admission was associated with reduced ARDS risk and better survival. These findings could inform prevention and clinical intervention in ARDS cases, which have increased with the expansion of the coronavirus disease 2019 pandemic.
背景：急性呼吸窘迫综合征（ARDS）会给重症患者带来高死亡率。确定与 ARDS 风险相关的生物标志物，可能有助于临床诊断和预后。
目的：系统评估血液代谢物与 ARDS 风险和生存率的关系。
设计、地点和参与者：在这项队列研究中，分析了来自分子流行病学急性呼吸窘迫综合征（MEARDS）研究的数据。该前瞻性队列纳入了 403 例 ARDS 患者和 1227 例非 ARDS 对照患者，患者均在马萨诸塞州波士顿市的麻省总医院和贝斯以色列女执事医疗中心的重症监护病房（ICU）中招募。数据采集时间为 1998 年 1 月 1 日至 2014 年 12 月 31 日。数据分析时间为 2018 年 12 月 9 日至 2019 年 1 月 4 日。
主要结局和测量：参与者每天通过柏林标准接受 ARDS 发展情况的随访，标准要求在侵入性通气辅助治疗的同日满足胸片和氧合标准。采用两阶段研究设计，探索与 ARDS 风险和生存相关的新型代谢物。
结果：在 MEARDS 中，有 1630 名入住 ICU 的患者，其中 403 名（24.7%）被诊断为 ARDS（平均[SD]年龄 63.0[17.0]岁，251 名[62.3%]为男性），1227 名（75.3%）为高危但未发生 ARDS（平均[SD]年龄 62.3[16.9]岁，753 名[61.4%]为男性）。孟德尔随机化表明，在发现阶段，血清甘露糖的遗传调节与 ARDS 风险相关（比值比[OR]，0.64；95%CI，0.53-0.78；P = 7.46×10-6）。在纳入 83 例 ARDS 患者和 ICU 对照组中匹配的高危患者的功能验证阶段，甘露糖与 ARDS 风险的保护相关性得到了验证（OR，0.67；95%CI，0.46-0.97；P = 0.03）。此外，血清甘露糖与 28 天（OR，0.25；95%CI，0.11-0.56；P = 6.95×10-4）和 60 天（OR，0.36；95%CI，0.19-0.71；P = 3.12×10-3）死亡率以及 28 天（风险比，0.49；95%CI，0.32-0.74；P = 6.41×10-4）和 60 天（风险比，0.55；95%CI，0.37-0.80；P = 2.11×10-3）生存率相关。
结论：在这项研究中，遗传调节的血清甘露糖似乎与 ARDS 风险和结局相关，入院时血清甘露糖的增加与 ARDS 风险降低和生存改善相关。这些发现可能为 ARDS 病例的预防和临床干预提供信息，而随着 2019 年冠状病毒病大流行的扩大，ARDS 病例有所增加。
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