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Open Access 29-04-2024 | Acute Respiratory Distress-Syndrome | ACUTE RESPIRATORY DISTRESS SYNDROME

The Synthetic Surfactant CHF5633 Restores Lung Function and Lung Architecture in Severe Acute Respiratory Distress Syndrome in Adult Rabbits

Authors: Pavol Mikolka, Petra Kosutova, Maros Kolomaznik, Nikolett Nemcova, Juliana Hanusrichterova, Tore Curstedt, Jan Johansson, Andrea Calkovska

Published in: Lung

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Abstract

Purpose

Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decreased lung compliance and alveolar collapse. Lung function in ARDS could potentially be restored with surfactant replacement therapy, and synthetic surfactants with modified peptide analogues may better withstand inactivation in ARDS alveoli than natural surfactants.

Methods

This study aimed to investigate the activity in vitro and the bolus effect (200 mg phospholipids/kg) of synthetic surfactant CHF5633 with analogues of SP‐B and SP‐C, or natural surfactant Poractant alfa (Curosurf®, both preparations Chiesi Farmaceutici S.p.A.) in a severe ARDS model (the ratio of partial pressure arterial oxygen and fraction of inspired oxygen, P/F ratio ≤ 13.3 kPa) induced by hydrochloric acid instillation followed by injurious ventilation in adult New Zealand rabbits. The animals were ventilated for 4 h after surfactant treatment and the respiratory parameters, histological appearance of lung parenchyma and levels of inflammation, oxidative stress, surfactant dysfunction, and endothelial damage were evaluated.

Results

Both surfactant preparations yielded comparable improvements in lung function parameters, reductions in lung injury score, pro-inflammatory cytokines levels, and lung edema formation compared to untreated controls.

Conclusions

This study indicates that surfactant replacement therapy with CHF5633 improves lung function and lung architecture, and attenuates inflammation in severe ARDS in adult rabbits similarly to Poractant alfa. Clinical trials have so far not yielded conclusive results, but exogenous surfactant may be a valid supportive treatment for patients with ARDS given its anti-inflammatory and lung-protective effects.
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Metadata
Title
The Synthetic Surfactant CHF5633 Restores Lung Function and Lung Architecture in Severe Acute Respiratory Distress Syndrome in Adult Rabbits
Authors
Pavol Mikolka
Petra Kosutova
Maros Kolomaznik
Nikolett Nemcova
Juliana Hanusrichterova
Tore Curstedt
Jan Johansson
Andrea Calkovska
Publication date
29-04-2024
Publisher
Springer US
Published in
Lung
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-024-00689-z
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