Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model

Abstract

BackgroundThe knowledge of where particles deposit in the respiratory tract is crucial for understanding the health effects associated with inhaled drug particles.MethodAn ex vivo study was conducted to assess regional deposition patterns (thoracic vs. extrathoracic) of radioactive polydisperse aerosols with different size ranges [0.15 μm–0.5 μm], [0.25 μm–1 μm] and [1 μm–9 μm]. SPECT/CT analyses were performed complementary in order to assess more precisely the regional deposition of aerosols within the pulmonary tract.Experiments were set using an original respiratory tract model composed of a human plastinated head connected to an ex vivo porcine pulmonary tract. The model was ventilated by passive expansion, simulating pleural depressions. Aerosol was administered during nasal breathing.ResultsPlanar scintigraphies allowed to calculate the deposited aerosol fractions for particles in the three size ranges from sub-micron to micron The deposited fractions obtained, for thoracic vs. extra-thoracic regions respectively, were 89 ± 4 % vs. 11 ± 4 % for [0.15 μm–0.5 μm], 78 ± 5 % vs. 22 ± 5 % for [0.25 μm–1 μm] and 35 ± 11 % vs.65 ± 11 % for [1 μm–9 μm].ConclusionResults obtained with this new ex vivo respiratory tract model are in good agreement with the in vivo data obtained in studies with baboons and humans.

Deposition pattern of aerosolized Legionella using an ex vivo human-porcine respiratory model

“…The extra-thoracic dead space was 21 mL, the tracheal internal diameter 1.7 cm and the tracheal length 7.5 cm (Booker, 2009;Criée et al, 2011;Flesch and Dine, 2012). The chimeric model satisfied the major functional and anatomical features necessary to study airborne particle deposition (Perinel et al, 2017(Perinel et al, , 2016. A video showing the lung ventilation is provided as…”

“…It means that no animals were sacrificed specifically for this study since we used, for scientific research, organic wastes that are currently discarded by slaughterhouse. Lungs were ventilated by passive expansion as in human physiological ventilation allowing to reproduce inhalation exposure to aerosols (El Merhie et al, 2016;Le Guellec et al, 2014;Leclerc et al, 2014a;Perinel et al, 2016Perinel et al, , 2017. Previously, characterized Legionella aerosols generated upon nebulization using a fluorescent Legionella strain (Allegra et al, 2016).…”

Experimental human-like model to assess the part of viable Legionella reaching the thoracic region after nebulization

“…Radioactivity was measured over a 2-min period. Images of the setup were acquired by 2D planar scintigraphy with a planar gamma camera (resolution 128 × 128) using a single detector equipped with a low-energy, high-resolution collimator: E-cam camera (Siemens, Germany; 397 mm × 500 mm collimator) [ 43 ]. A region of interest (ROI) was delimited on the images with correction of the background using a mean of 3 external ROIs ( Fig 3B ).…”

Deposition pattern of aerosolized Legionella using an ex vivo human-porcine respiratory model

“…The extra-thoracic dead space was 21 mL, the tracheal internal diameter 1.7 cm and the tracheal length 7.5 cm (Booker, 2009;Criée et al, 2011;Flesch and Dine, 2012). The chimeric model satisfied the major functional and anatomical features necessary to study airborne particle deposition (Perinel et al, 2017(Perinel et al, , 2016. A video showing the lung ventilation is provided as supplementary data.…”