Kassa-Sombo Arthur, Verney Charles, Pasquet Augustin, Vaidie Julien, Brea Deborah, Vasseur Virginie, Cezard Adeline, Lefevre Antoine, David Camille, Piver Eric, Nadal-Desbarats Lydie, Emond Patrick, Blasco Hélène, Si-Tahar Mustapha, Guillon Antoine
Research Center for Respiratory Diseases, INSERM U1100, University of Tours, 37044, Tours, France.
Intensive Care Unit, Tours University Hospital, 2 Bd Tonnellé, 37044, Tours Cedex 9, France.
Ann Intensive Care. 2025 Jun 5;15(1):78. doi: 10.1186/s13613-025-01492-6.
Ventilator-associated pneumonia (VAP) is a significant complication in mechanically ventilated patients. Paradoxically, it lacks precise diagnostic criteria, making the identification of a reliable diagnostic indicator an unmet medical need. Lipids are critical regulators of innate lung defense. The aim of the study was to identify lipid alterations specific to VAP in tracheal aspirates of patients with ARDS.
Tracheal aspirates samples from ventilated patients were collected longitudinally from patients with COVID-19-related ARDS. Tracheal aspirates sampled at the day of VAP diagnosis were used to assess VAP specific lipidome and were compared with matched controls (patients without VAP). Lipid detection was performed using ultra-high-performance liquid chromatography with high resolution mass spectrometry. The statistical analysis included: unsupervised multivariate methods, partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), and the area under the receiver operating characteristic (AUROC) curve to assess classification performance. The Benjamini-Hochberg adjusted p-value was used to control the false discovery rate.
We studied 39 patients (26 VAP and 13 control patients). The characteristics of VAP and control patients were similar, including biological markers such as neutrophils, CRP, and PCT. The lipid signature, composed of 272 lipids, differed between VAP and control patients (p = 0.003). Phosphatidylcholines were the most represented with 17 significantly upregulated and 6 downregulated lipids. OPLSDA identified 8 best candidates as VAP biomarkers with sphingomyelin (34:1) and phosphatidylcholine (O-34:1) presenting the best scores (AUROC = 0.85 [0.71-0.95] and 0.83 [0.66-0.94], respectively). Combinations of several lipid biomarkers did not improve the prediction accuracy. During ARDS, lung lipidome mostly resulted in breakdown product of host-pathogen interactions (surfactant and pulmonary cells).
We investigated VAP-specific lipids in tracheal aspirate and identified significant alterations in lipidomic profiles, likely driven by active infection dynamic and the breakdown of surfactant and pulmonary cells. Among the potential VAP biomarker candidates in COVID-19 ARDS, sphingomyelin (34:1) and phosphatidylcholine (O-34:1) demonstrated predictive performance for VAP that surpassed all previously tested biomarkers.
呼吸机相关性肺炎（VAP）是机械通气患者的一种严重并发症。矛盾的是，它缺乏精确的诊断标准，因此确定可靠的诊断指标成为一项未满足的医疗需求。脂质是肺固有防御的关键调节因子。本研究的目的是确定急性呼吸窘迫综合征（ARDS）患者气管吸出物中VAP特有的脂质变化。
从与新型冠状病毒肺炎相关的ARDS患者中纵向收集机械通气患者的气管吸出物样本。在VAP诊断当天采集的气管吸出物用于评估VAP特有的脂质组，并与匹配的对照组（无VAP的患者）进行比较。使用超高效液相色谱与高分辨率质谱进行脂质检测。统计分析包括：无监督多变量方法、偏最小二乘判别分析（PLS-DA）、正交偏最小二乘判别分析（OPLS-DA）以及受试者操作特征（AUROC）曲线下面积以评估分类性能。采用Benjamini-Hochberg校正p值来控制错误发现率。
我们研究了39例患者（26例VAP患者和13例对照患者）。VAP患者和对照患者的特征相似，包括中性粒细胞、CRP和PCT等生物标志物。由272种脂质组成的脂质特征在VAP患者和对照患者之间存在差异（p = 0.003）。磷脂酰胆碱占比最大，其中17种脂质显著上调，6种脂质下调。OPLSDA确定了8种最佳的VAP生物标志物候选物，鞘磷脂（34:1）和磷脂酰胆碱（O-34:1）得分最高（AUROC分别为0.85 [0.71 - 0.95]和0.83 [0.66 - 0.94]）。几种脂质生物标志物的组合并未提高预测准确性。在ARDS期间，肺脂质组主要是宿主 - 病原体相互作用（表面活性剂和肺细胞）的分解产物。
我们研究了气管吸出物中VAP特有的脂质，发现脂质组谱存在显著变化，这可能是由活跃的感染动态以及表面活性剂和肺细胞的分解所驱动。在新型冠状病毒肺炎ARDS潜在的VAP生物标志物候选物中，鞘磷脂（34:1）和磷脂酰胆碱（O-34:1）对VAP的预测性能超过了所有先前测试的生物标志物。
