Abstract
In intensive care units, nebulization is a usual route for drug administration to patients under mechanical ventilation (MV). The effectiveness of inhalation devices as well as depositions sites of aerosols for ventilated patients remain poorly documented. In vivo human inhalation studies are scarce due to ethical restrictions because imaging techniques require radioaerosols to assess regional aerosol deposition. Thus, we developed an ex vivo respiratory model under invasive MV for preclinical aerosol deposition studies. The model was composed of ex vivo porcine respiratory tracts. MV was achieved thanks to a tracheal intubation and a medical ventilator under controlled conditions. Respiratory features were studied using analogical sensors. Then regional homogeneity of gas-ventilation was assessed with 81mKrypton scintigraphies. Finally, a proof of concept study for aerosol deposition was performed. Obtained respiratory features as well as gamma-imaging techniques, which demonstrated a homogenous regional ventilation and about 18% ± 4% of the nebulized dose deposited the respiratory tract, were in good agreement with human data available in the literature. This original ex vivo respiratory model provides a feasible, reproducible and cost-effective preclinical tool to achieve aerosol deposition studies under MV.
Highlights
Development of a preclinical ex vivo respiratory model for aerosol regional deposition Yoann Montigaud[1,4], Quentin Georges[2,4], Jérémie Pourchez 1, Lara Leclerc[1], Clémence Goy 2, Anthony Clotagatide[2], Nathalie Prevot2,3 & Sophie Perinel-Ragey2,3*
intensive care units (ICU) patients frequently suffers of acute respiratory failure (ARF): a prevalence study in 81 ICU claimed that ARF represented 24% of main admission diagnosis and aerosolized drug administration was frequently considered in this situation[4] (49% of these patients received inhaled therapies)
Our results showed a good coherence with human respiratory physiological data of an ICU patient in terms of VT, compliance and resistances
Summary
Development of a preclinical ex vivo respiratory model for aerosol regional deposition Yoann Montigaud[1,4], Quentin Georges[2,4], Jérémie Pourchez 1, Lara Leclerc[1], Clémence Goy 2, Anthony Clotagatide[2], Nathalie Prevot2,3 & Sophie Perinel-Ragey2,3*. Obtained respiratory features as well as gamma-imaging techniques, which demonstrated a homogenous regional ventilation and about 18% ± 4% of the nebulized dose deposited the respiratory tract, were in good agreement with human data available in the literature This original ex vivo respiratory model provides a feasible, reproducible and cost-effective preclinical tool to achieve aerosol deposition studies under MV. The guidelines of the European Respiratory Society[3] underlined that even if metered-dose inhalers (MDI) and nebulizers are usually used in ICU to deliver bronchodilators to mechanically ventilated patients[2], it is not yet known which modality of treatment is more effective. Results generated using in vitro experiments or various animal models remain controversial due to wide differences between these models and human airways in size and bronchial divisions but, in ventilation physiology[15,16]
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