Early detection and identification of ventilator associated pneumonia

摘要： 呼吸机相关性肺炎（VAP）是机械通气患者的常见并发症， 每年发生超过25万次。VAP发生在机械通气的高百分比 急性呼吸窘迫综合征（ARDS，29%）和COVID-19（>50%）患者。及时发现和 病原体的鉴定是有效治疗的关键，区分定植和急性感染也是关键。 最常见的微生物诊断方法是气管内吸出物或支气管肺泡培养 灌洗。采样抽吸是非侵入性的，但样本容易受到近端污染 航空公司.支气管肺泡灌洗（BAL）允许在没有近端气道的情况下从远端肺收集样本 污染，但这种技术是侵入性的，不能经常重复监测。这里我们 建议开发和测试一种非侵入性、高效的系统，用于收集呼出的呼吸气溶胶 从机械通气的病人身上。该系统将收集大的气溶胶，通常产生在近端 与通常在非常远端的气道中产生的较小的气溶胶分开， 这两个不同的肺区室的独立样本。收集的样本从 远端肺有助于正确诊断VAP。该系统将允许较短的样本收集时间， 便于重复测量和及时监测，并将在体外人体中开发和测试 使用基于培养和非培养的方法的肺模型。我们还将评估收集的气溶胶的效用 用于调查肺中的微生物、真菌和病毒群落成员（肺微生物组）的样本。 细菌群落的失衡（呼吸道生态失调）与存活率下降有关 在机械通气患者中，并且可能在局部和全身炎症中起作用。最后我们将 评价呼出气溶胶样本的使用，以指示宿主对感染和肺损伤的反应， 分析与内皮和上皮通透性、炎症和感染相关的生物标志物。标志物 宿主反应和肺损伤可能有助于区分简单的细菌定植和急性感染， VAP。肺炎是急性呼吸窘迫综合征（ARDS）的主要原因， 一种涉及复杂的炎症反应失调的并发症，导致内皮细胞和 上皮屏障完整性，导致肺水肿和呼吸衰竭。连续生物标志物测量 从远端肺样本也可以阐明肺感染后ARDS的病因。

ABSTRACT: Ventilator associated pneumonias (VAP) are a common complication in mechanically ventilated patients, occurring more than 250,000 times annually. VAPs occur in a high percentage of mechanically ventilated patients with acute respiratory distress syndrome (ARDS, 29%) and COVID-19 (>50%). Timely detection and identification of the pathogen is key to effective treatment, as is differentiating colonization from acute infection. The most common options for microbiological diagnosis are cultures of endotracheal aspirate or bronchoalveolar lavage. Sampling aspirate is non-invasive, but the samples are prone to contamination from the proximal airways. Bronchoalveolar lavage (BAL) allows for sample collection from the distal lung without proximal airway contamination, but this technique is invasive and cannot be repeated frequently for surveillance. Here we propose to develop and test a non-invasive, high-efficiency system for collecting exhaled respiratory aerosols from mechanically ventilated patients. This system will collect large aerosols, typically generated in the proximal airways, separately from smaller aerosols, which are typically generated in the very distal airways, thus providing independent samples from these two distinct compartments of the lung. The collection of a sample from the distal lung will facilitate the correct diagnosis VAP. The system will allow for short sample collection times, facilitating repeated measures and timely surveillance, and will be developed and tested in an ex vivo human lung model using culture and non-culture-based methods. We will also evaluate the utility of collected aerosol samples for surveying the microbial, fungal, and viral community members in the lung (the lung microbiome). Misbalances in the bacterial communities (respiratory dysbiosis) have been associated with decreased survival in mechanically ventilated patients and may play a role in both local and systemic inflammation. Finally, we will evaluate the use of exhaled aerosol samples to indicate host response to infection and lung injury through the analysis of biomarkers related to endothelial and epithelial permeability, inflammation, and infection. Markers of host response and lung injury may help to differentiate simple bacterial colonization from acute infection and VAP. Pneumonia is the leading cause of Acute Respiratory Distress Syndrome (ARDS), an often-lethal complication involving a complex dysregulated inflammatory response that causes loss of endothelial and epithelial barrier integrity, resulting in pulmonary edema and respiratory failure. Serial biomarker measurements from distal lung samples may also elucidate the etiology of ARDS after lung infection.