The Basic Science and Molecular Mechanisms of Lung Injury and Acute Respiratory Distress Syndrome

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

“…In ALI/ARDS, AMs and neutrophils are the primary sources of proinflammatory cytokines. Consequently, the balance between proinflammatory (IL-1, IL-6, IL-8, IL-18, TNF- α , and TGF- β ) and anti-inflammatory mediators (IL-10 and IL-13) is broken 13 , 30 , 35 , 38 . This inflammatory dysfunction leads to the disruption of alveolar epithelium constituted of alveolar cells type (ATI), that cover the majority of the alveolar surface area playing a primary role in gas exchange and fluid reabsorption, as well as type II alveolar cells (ATII) playing a critical role in alveolar fluid clearance, the production of pulmonary surfactant, and the repopulation of the damaged ATI 10 , 39 .…”

“…Alveolar epithelial cell (EpiCs) death, either apoptotic or necrotic, is the most extreme form of alveolar barrier injury observed in ALI/ARDS, and one of the most important therapeutic targets for ALI/ARDS. Besides the inflammatory-induced epithelial injury, epithelial cell death can be directly caused by acid aspiration, hyperoxia, and physical forces 13 , 39 . The disruption of the endothelial barrier leads to interstitial and alveolar immune cells infiltration and plasma extravasation, facilitated by the injury of alveolar epithelium increasing the pulmonary edema.…”

“…To date, the best practice against ALI/ARDS remains protective ventilation, including low tidal volumes and high positive end-expiratory pressures (PEEP) levels 11 , 12 . Nevertheless, the mortality remains unchanged at approximately 40%, besides the long-term use of mechanical ventilation can aggravate lung damage [ventilator-associated lung injury (VALI)] or even cause ventilator-induced lung injury (VILI) 8 , 10 , 13 , 14 . Prone position ventilation, neuromuscular blockade, or extracorporeal membrane oxygenation can be used in the short term to manage patients with severe hypoxemia.…”

Proposal for the use of anakinra in acute respiratory distress secondary to COVID-19

“…In 2018, Aranda-Valderrama and Kaynar published a model to determine the flow of cytokines and proinflammatory cells in the pulmonary alveoli of patients affected by ARDS. 5 They observed how inactive IL-1β (pro- IL-1β) progresses to active IL-1β inside the alveolar macrophages ( Fig. 1 ).…”

Propuesta de uso de anakinra en el distrés respiratorio agudo secundario a COVID-19

“…En 2018, Aranda-Valderrama y Kaynar, publican un modelo para conocer el flujo de citocinas y células proinflamatorias existentes en el alveolo pulmonar de aquellos pacientes afectados por SDRA 5 . Se observa como en el interior de los macrófagos alveolares, IL-1␤ inactiva (pro IL-1␤) progresa hacia IL-1␤ activa ( fig.…”