1 Institute of Cellular Medicine.
2 Institute for Cell and Molecular Biosciences, and.
Am J Respir Crit Care Med. 2018 Aug 1;198(3):340-349. doi: 10.1164/rccm.201709-1819OC.
Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying subglottic colonization in critical illness have not been defined, limiting strategies for targeted prevention of VAP.
To characterize subglottic host defense dysfunction in mechanically ventilated patients in the ICU; to determine whether subglottic mucin contributes to neutrophil phagocytic impairment and bacterial growth.
Prospective subglottic sampling in mechanically ventilated patients (intubated for four or more days), and newly intubated control patients (intubated for less than 30 min); isolation and culture of primary subglottic epithelial cells from control patients; laboratory analysis of host innate immune defenses.
Twenty-four patients in the ICU and 27 newly intubated control patients were studied. Subglottic ICU samples had significantly reduced microbiological diversity and contained potential respiratory pathogens. The subglottic microenvironment in the ICU was characterized by neutrophilic inflammation, significantly increased proinflammatory cytokines and neutrophil proteases, and altered physical properties of subglottic secretions, including accumulation of mucins. Subglottic mucin from ICU patients impaired the capacity of neutrophils to phagocytose and kill bacteria. Phagocytic impairment was reversible on treatment with a mucolytic agent. Subglottic mucus promoted growth and invasion of bacterial pathogens in a novel air-liquid interface model of primary human subglottic epithelium.
Mechanical ventilation in the ICU is characterized by substantial mucin secretion and neutrophilic inflammation. Mucin impairs neutrophil function and promotes bacterial growth. Mucolytic agents reverse mucin-mediated neutrophil dysfunction. Enhanced mucus disruption and removal has potential to augment preventive benefits of subglottic drainage.
在接受机械通气的患者中，感染性下呼吸道分泌物的抽吸会导致呼吸机相关性肺炎（VAP）。重症患者下呼吸道定植的机制尚未明确，限制了针对 VAP 的靶向预防策略。
描述 ICU 中接受机械通气的患者的下呼吸道宿主防御功能障碍；确定下呼吸道黏液是否有助于中性粒细胞吞噬功能障碍和细菌生长。
对机械通气患者（插管 4 天或以上）和新插管的对照患者（插管时间少于 30 分钟）进行前瞻性下呼吸道采样；从对照患者中分离和培养原发性下呼吸道上皮细胞；实验室分析宿主先天免疫防御。
共纳入 24 例 ICU 患者和 27 例新插管的对照患者。下呼吸道 ICU 样本的微生物多样性明显降低，且含有潜在的呼吸道病原体。ICU 下呼吸道微环境以中性粒细胞炎症为特征，促炎细胞因子和中性粒细胞蛋白酶显著增加，下呼吸道分泌物的物理性质发生改变，包括黏蛋白的积累。来自 ICU 患者的下呼吸道黏液会损害中性粒细胞吞噬和杀死细菌的能力。用黏液溶解剂治疗可逆转吞噬功能障碍。在下呼吸道原发性人上皮细胞的新型气液界面模型中，下呼吸道黏液促进了细菌病原体的生长和侵袭。
在 ICU 中接受机械通气会导致大量黏液分泌和中性粒细胞炎症。黏液会损害中性粒细胞的功能并促进细菌生长。黏液溶解剂可逆转黏液介导的中性粒细胞功能障碍。增强黏液破坏和清除可能会增强下呼吸道引流的预防效果。
