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Evaluation of aerosol delivery in ventilated patients via vibrating mesh nebuliser versus other delivery devices using a patient-specific in silico whole-lung model
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DOI：10.1186/s12931-026-03865-2.png)
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Abstract
En 中文
In patients requiring mechanical ventilation, normal aerosol dynamics are disrupted by the artificial airway, circuit configuration and humidification systems. These factors can result in substantial drug losses within the ventilator circuit and markedly lower lung deposition than during spontaneous breathing, thereby potentially limiting therapeutic efficacy. A mechanistic proof-of-concept study using an in silico model has been conducted to evaluate aerosol deposition in the lung under differing delivery flow profiles. Digital Twinhale® technology was used to generate a subject-specific whole-lung model from CT-derived airway and lung geometry data from a healthy adult, using a 16-generation airway tree and calibrated physiological parameters. Aerosol transport was simulated with three-dimensional Lagrangian particle dynamics using in vitro droplet properties. Phase 1 of the study evaluated Aerogen vibrating mesh nebuliser (A-VMN), jet nebuliser (JN) and pressurised metered dose inhaler (pMDI) use under identical delivery flow profiles to assess the impact of the device on delivery efficiency and deposition patterns. In the second phase, deposition via VMN was assessed under two representative simulation scenarios: B1, a sinusoidal (volume controlled ventilation-like) waveform, and B2, a rectangular pressure (pressure controlled ventilation-like) waveform, using matched respiratory settings, including respiratory rate, inhalation-to-exhalation ratio and nominal tidal volume. Digital modelling allowed observation of differences in device performance, with the A-VMN yielding the highest deposited mass fraction across all lobes and lung regions, as well as the greatest level of functional deposition within the alveolar airways. Modelling ventilator mode-like inspiratory flow profiles allowed the observation that the highest deposited mass fraction was obtained with the B1 flow profile, whereas use of B2 resulted in a greater proportion of the emitted dose being lost to exhalation. Overall, differing flow profile had little effect on central-to-peripheral ratios, indicating that deposition patterns were mainly influenced by aerosol characteristics rather than differences in delivered dose or ventilation parameters. These findings support the feasibility of using a patient-specific in silico whole-lung model to compare predicted aerosol deposition under controlled conditions. However, further validation in multi-subject models and clinical studies will be required to determine whether these predicted deposition differences translate into meaningful clinical benefit.
Keywords:
In silico
Vibrating mesh nebuliser
Jet nebuliser
Pressurised metered dose inhaler
Digital twin
Mechanical ventilation
Journal
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5
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803
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1.5W
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