No in vivo data are available regarding the effect of meconium on human surfactant in the early stages of severe meconium aspiration syndrome (MAS). In the present study, we sought to characterize the changes in surfactant composition, function, and structure during the early phase of meconium injury. We designed a translational prospective cohort study of nonbronchoscopic BAL of neonates with severe MAS (n = 14) or no lung disease (n = 18). Surfactant lipids were analyzed by liquid chromatography–high-resolution mass spectrometry. Secretory phospholipase A₂ subtypes IB, V, and X and SP-A (surfactant protein A) were assayed by ELISA. SP-B and SP-C were analyzed by Western blotting under both nonreducing and reducing conditions. Surfactant function was assessed by adsorption test and captive bubble surfactometry, and lung aeration was evaluated by semiquantitative lung ultrasound. Surfactant nanostructure was studied using cryo-EM and atomic force microscopy. Several changes in phospholipid subclasses were detected during MAS. Lysophosphatidylcholine species released by phospholipase A₂ hydrolysis were increased. SP-B and SP-C were significantly increased together with some shorter immature forms of SP-B. Surfactant function was impaired and correlated with poor lung aeration. Surfactant nanostructure was significantly damaged in terms of vesicle size, tridimensional complexity, and compactness. Various alterations of surfactant phospholipids and proteins were detected in the early phase of severe meconium aspiration and were due to hydrolysis and inflammation and a defensive response. This impairs both surfactant structure and function, finally resulting in reduced lung aeration. These findings support the development of new surfactant protection and antiinflammatory strategies for severe MAS.

在严重的胎粪吸入综合征（MAS）的早期阶段，没有关于胎粪对人体表面活性剂的影响的体内数据。在本研究中，我们试图表征胎粪损伤早期表面活性剂组成，功能和结构的变化。我们设计了非重支气管镜下BAL对患有严重MAS（n  = 14）或无肺部疾病（n  = 18）的新生儿的转化前瞻性队列研究。通过液相色谱-高分辨率质谱分析表面活性剂脂质。分泌型磷脂酶A ₂ELISA检测了IB，V和X亚型和SP-A（表面活性蛋白A）。在非还原和还原条件下，通过蛋白质印迹分析SP-B和SP-C。表面活性剂功能通过吸附测试和俘获气泡表面测量法进行评估，肺通气性通过半定量肺超声进行评估。表面活性剂的纳米结构研究使用冷冻EM和原子力显微镜。在MAS期间检测到了磷脂亚类的一些变化。磷脂酶A ₂释放的溶血磷脂酰胆碱种类水解增加。SP-B和SP-C以及一些较短的未成熟形式的SP-B显着增加。表面活性剂功能受损并与肺通气不良有关。表面活性剂纳米结构在囊泡尺寸，三维复杂性和致密性方面受到严重破坏。在严重的胎粪吸入早期，检测到表面活性剂磷脂和蛋白质的各种变化，这是由于水解，发炎和防御反应引起的。这会损害表面活性剂的结构和功能，最终导致肺通气减少。这些发现支持针对严重MAS的新的表面活性剂保护和抗炎策略的开发。