Mechanism of benefit of non-invasive ventilation in COPD with hypercapnic respiratory failure.
Mechanism of benefit of non-invasive ventilation in COPD with hypercapnic respiratory failure.
复制标题
无创通气治疗 COPD 合并高碳酸血症呼吸衰竭的获益机制。
DOI：
10.1111/resp.13522
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Gates,KhalilahL
中科院分区：
文献类型：
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作者：
Sporn,PeterHS;Casalino-Matsuda,SMarina;Gates,KhalilahL
货车和Duiverman在他们对高碳酸血症慢性阻塞性肺疾病（COPD）无创通气（NIV）的优秀实践综述1中总结了最近的随机对照试验，这些试验表明，旨在降低动脉PCO 2的高强度NIV可改善COPD和高碳酸血症患者的健康相关生活质量，降低加重频率并降低死亡率。他们讨论了NIV的一些生理效应可能有助于这些益处，包括：减少呼吸肌疲劳;招募小气道以减少气流阻塞和固有呼气末正压;降低肾素-血管紧张素系统的激活，从而减少气道和肺水肿;增加呼吸驱动。我们实验室最近的研究表明，另一种以前未被认识到的机制可能是通过应用NIV减少高碳酸血症的益处的基础。我们已经证明，CO2水平升高选择性地降低骨髓2和肺上皮细胞3中先天免疫和抗病毒基因的表达，高碳酸血症增加小鼠细菌性肺炎4和甲型流感感染5的死亡率。这些效应是pH值无关的，并通过高浓度分子CO2引发的特定细胞内信号传导事件介导。值得注意的是，我们表明，在体外2和体内的免疫抑制作用的CO2升高是可逆的。4因此，我们的研究结果表明，通过减少高碳酸血症，NIV可以改善CO2诱导的免疫抑制，并改善抗菌和抗病毒宿主防御。这些作用可以解释在接受NIV治疗的COPD高碳酸血症患者中观察到的急性加重频率降低和死亡率改善。
In their excellent practical review of non-invasive ventilation (NIV) in hypercapnic chronic obstructive pulmonary disease (COPD), 1 van der Leest and Duiverman summarize recent randomized controlled trials showing that high-intensity NIV targeted to reduce arterial PCO2 improves health-related quality of life, reduces exacerbation frequency and decreases mortality in patients with COPD and hypercapnia. They discuss a number of physiological effects of NIV that might contribute to these benefits, including: reduced respiratory muscle fatigue; recruitment of small airways to reduce airflow obstruction and intrinsic positive endexpiratory airway pressure; decreased activation of the renin–angiotensin system resulting in less airway and lung oedema; and increased respiratory drive. Recent studies from our laboratory suggest another previously unappreciated mechanism that may underlie the benefits of reducing hypercapnia by the application of NIV. We have shown that elevated levels of CO2 selectively decrease expression of innate immune and antiviral genes in myeloid2 and lung epithelial cells, 3 and that hypercapnia increases the mortality of bacterial pneumonia4 and influenza A infection5 in mice. These effects are pH-independent and mediated by specific intracellular signalling events triggered by high concentrations of molecular CO2. Notably, we showed that the immunosuppressive effects of elevated CO2 are reversible in vitro2 and in vivo. 4 Our findings thus suggest that by decreasing hypercapnia, NIV may ameliorate CO2-induced immunosuppression and improve antibacterial and antiviral host defence. These effects could account for the reduced frequency of exacerbations and improved mortality observed in hypercapnic patients with COPD treated with NIV.