致死的な急性呼吸窮迫症候群(ARDS)に関する新たな知見を提供する研究(Study provides new insights into deadly acute respiratory distress syndrome (ARDS))

ad

2023-03-12 ミネソタ大学

Lungs 3D illustration

ミネソタ大学ツインシティー校の研究者は、急性呼吸窮迫症候群(ARDS)の原因となる肺の不安定性に関する機械的な説明を発見した可能性があります。COVID-19や肺炎などの呼吸器疾患後に特にみられます。ARDSの治療法はなく、COVID-19で亡くなった患者の2/3がARDSを発症していました。彼らの研究では、特定のリゾ脂質の濃度が成人のARDSの重症化に寄与することが示されました。この研究は、特定の分子を操作してリゾ脂質の濃度を減少させることでARDSの症状を逆転させる可能性を探ることを目指しています。

<関連情報>

肺サーファクタントの界面力学の進化は急性呼吸窮迫症候群の進行を模倣する Evolution of interfacial mechanics of lung surfactant mimics progression of acute respiratory distress syndrome

Clara O. Ciutara, Steven V. Iasella, Boxun Huang, +1, and Joseph A. Zasadzinski
Proceedings of the National Academy of Sciences  Published:December 12, 2023
DOI:https://doi.org/10.1073/pnas.2309900120

Significance

There is no known mechanism for the initiation and progression of acute respiratory distress syndrome, which has a 40% mortality rate and is one of the major complications of advanced COVID-19 infections. Here, we show that an increased concentration of lysolipids produced by the innate immune system during inflammation can inhibit the surface tension and dilatational properties of lung surfactant, leading to mechanical instabilities during lung inflation or deflation.

Abstract

How acute respiratory distress syndrome progresses from underlying disease or trauma is poorly understood, and there are no generally accepted treatments resulting in a 40% mortality rate. However, during the inflammation that accompanies this disease, the phospholipase A2 concentration increases in the alveolar fluids leading to the hydrolysis of bacterial, viral, and lung surfactant phospholipids into soluble lysolipids. We show that if the lysolipid concentration in the subphase reaches or exceeds its critical micelle concentration, the surface tension, γ, of dipalmitoyl phosphatidylcholine (DPPC) or Curosurf monolayers increases and the dilatational modulus, E(ω), decreases to that of a pure lysolipid interface. This is consistent with DPPC being solubilized in lysolipid micelles and being replaced by lysolipid at the interface. These changes lead to 2E-γ<0, which is the criterion for the Laplace instability that can lead to mechanical instabilities during lung inflation, potentially causing alveolar collapse. These findings provide a mechanism behind the alveolar collapse and uneven lung inflation during ARDS.

ad

医療・健康
ad
ad
Follow
ad
タイトルとURLをコピーしました