Abstract
BackgroundThe most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse. PS instillation therapy is dramatically effective for infant respiratory distress syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that this ineffectiveness of PS instillation for ARDS is caused by insufficient delivery. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions.MethodsTwo types of 3D human airway models were prepared: one was from the trachea to the lobular bronchi and the other was from a subsegmental bronchus to respiratory bronchioles. The thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. The liquid layer was assumed to be replaced by an instilled PS. The flow rate of the instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving the advective-diffusion equation.ResultsThe driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure was given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS does not reach the alveolar regions but moves to and fro within the airway according to the change in ventilator pressure. The driving pressure from subsegmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation.ConclusionsThe simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia before the onset of ARDS. It will be also useful for preventing secondary lung fibrosis.
Highlights
The most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse
Acute respiratory distress syndrome (ARDS) was first reported in 1967 by Ashbaugh et al, who inferred that its essential pathology was alveolar collapse caused by PS dysfunction and likely infant respiratory distress syndrome [4]
Based on the computational fluid dynamics (CFD) simulation results, we propose selective wedge instillations of PS from subsegmental bronchi under bronchoscopic observation for COVID-19 pneumonia with complete infection protection
Summary
The most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse. It is known that SARS-CoV-2 binds angiotensin converting enzyme 2 (ACE2) on the pulmonary epithelial cells and causes acute interstitial pneumonia. Type II pneumocytes are the only cells that produce and secrete pulmonary surfactant (PS), which prevents alveoli from collapsing by reducing the surface tension of the alveolar liquid layer [2]. ARDS is defined as non-cardiogenic pulmonary edema with vascular hyper-permeability; the role of PS dysfunction is regarded as subtle [5]. This conceptual change may be partly because of the clinical ineffectiveness of PS instillation therapy for adults. Steffen et al recently demonstrated the experimental therapeutic effects of surfactant replacement for acute lung injury in a rat bleomycin model [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
