Departments of Medicine and Anesthesia, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA.
Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA.
Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
Subphenotypes have been identified within heterogeneous diseases such as asthma and breast cancer, with important therapeutic implications. We assessed whether subphenotypes exist within acute respiratory distress syndrome (ARDS), another heterogeneous disorder.
We used data from two ARDS randomised controlled trials (ARMA trial and ALVEOLI trial), sponsored by the National Heart, Lung, and Blood Institute. We applied latent class modelling to identify subphenotypes using clinical and biological data. We modelled data from both studies independently. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the ALVEOLI cohort.
We analysed data for 1022 patients: 473 in the ARMA cohort and 549 in the ALVEOLI cohort. Independent latent class models indicated that a two-class (ie, two subphenotype) model was the best fit for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (phenotype 2) that was characterised by higher plasma concentrations of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate concentrations, and a higher prevalence of sepsis than phenotype 1. Participants in phenotype 2 had higher mortality and fewer ventilator-free days and organ failure-free days in both cohorts than did those in phenotype 1 (p<0·007 for all). In the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on mortality, ventilator-free days and organ failure-free days differed by phenotype (p=0·049 for mortality, p=0·018 for ventilator-free days, p=0·003 for organ-failure-free days).
We have identified two subphenotypes within ARDS, one of which is categorised by more severe inflammation, shock, and metabolic acidosis and by worse clinical outcomes. Response to treatment in a randomised trial of PEEP strategies differed on the basis of subphenotype. Identification of ARDS subphenotypes might be useful in selecting patients for future clinical trials.
National Institutes of Health.
亚表型已在哮喘和乳腺癌等异质性疾病中得到鉴定，具有重要的治疗意义。我们评估了急性呼吸窘迫综合征（ARDS）这一另一种异质性疾病中是否存在亚表型。
我们使用了由美国国立心肺血液研究所（National Heart，Lung，and Blood Institute）赞助的 ARDS 两项随机对照试验（ARMA 试验和 ALVEOLI 试验）的数据。我们应用潜在类别建模，使用临床和生物学数据来识别亚表型。我们分别对两项研究的数据进行建模。然后，我们在两个队列中检验了亚表型与临床结局的相关性，并在 ALVEOLI 队列中检验了亚表型与对呼气末正压（PEEP）反应的相关性。
我们分析了来自 1022 名患者的数据：ARMA 队列中 473 例，ALVEOLI 队列中 549 例。独立的潜在类别模型表明，对于两个队列，两分类（即两个亚表型）模型是最佳拟合。在两个队列中，我们都确定了一个高炎症亚表型（表型 2），其特征是炎症生物标志物的血浆浓度较高，血管加压药使用率较高，血清碳酸氢盐浓度较低，败血症的发生率高于表型 1。在两个队列中，与表型 1 相比，表型 2 患者的死亡率更高，呼吸机自由天数和无器官衰竭天数更少（所有 P 值均<0·007）。在 ALVEOLI 队列中，通气策略（高 PEEP 与低 PEEP）对死亡率、呼吸机自由天数和无器官衰竭天数的影响因表型而异（死亡率的 P 值=0·049，呼吸机自由天数的 P 值=0·018，无器官衰竭天数的 P 值=0·003）。
我们在 ARDS 中发现了两个亚表型，其中一个表型的炎症、休克和代谢性酸中毒更严重，临床结局更差。在 PEEP 策略的随机试验中，对治疗的反应因亚表型而异。鉴定 ARDS 亚表型可能有助于为未来的临床试验选择患者。
美国国立卫生研究院。
