Method for aerosol dosimetry prediction in whole lung

Abstract

A system including an aerosol-generating device and an inhalation guidance unit is provided. The system comprises: one or more processors configured to perform the steps of: capturing an aerosol inhalation profile of a user of the aerosol-generating device; feeding the captured aerosol inhalation profile to a respiratory system model; generating an inhalation guidance instruction based on the respiratory system model; and providing the inhalation guidance instruction to the user at the inhalation guidance unit. Modular respiratory system models and methods for transient aerosol dosimetry are also provided.

Description

Technical Field

[0001] The present disclosure relates to a model, method, and system for transient aerosol dosimetry. Specifically, the present disclosure relates to generating a modular respiratory system model for determining the deposition of inhaled aerosol in a region of interest of a user's respiratory system over time. Additionally, the present disclosure relates to an aerosol generating device that uses the generated modular respiratory system model to control aerosol deposition in the user's respiratory system. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading cause of death worldwide. COPD is caused by long-term exposure to harmful gases and particles and a combination of individual factors. Pulmonary drug delivery is the first choice for treating respiratory diseases and is very interesting for other diseases, offering several advantages, such as faster onset of action and easier non-invasive administration. A major challenge in evaluating the efficacy of inhalation toxicity or inhaled drugs is to appropriately and accurately determine the delivered dose. The drug dose can be determined experimentally by using idealized geometries (i.e., curved tubes, Alberta ideal larynx, or NGI from Copley Scientific) or by using 3D-printed lung models extracted from micro-CT scans of patients, as described in CN202010101213. The advantage of micro-CT-derived 3D models is the possibility of analyzing the personalized geometry of each patient. However, this technology is limited to analysis of the upper respiratory tract and does not allow for capturing and reproducing aerosol behavior in the deeper alveolar lung. Therefore, analysis of aerosol inhalation is hindered. In addition, experimentally reproducing the correct atmospheric environment inside the lung model is a technically difficult task. In particular, atmospheric conditions related to humidity at the airway surface have proven to be a significant challenge. Finally, experiments are often expensive and time-consuming.

[0003] Alternatively, computational modeling has been used to predict doses, including computational fluid dynamics (CFD) models and whole-lung dosimetry models, such as the Multipath Particle Dosimetry Model (MPPD) and the International Commission on Radiological Protection (ICRP) human breathing model. While CFD allows for very detailed analysis of actual geometries extracted from patient scans, it is subject to similar limitations to experiments in that it is limited to the upper airways. Recent attempts have applied CFD to simplified lung geometries and, by assuming similarities between lung branchings, have allowed for the simulation of representative whole-airway trees. However, CFD remains very labor-intensive, computationally demanding, and, in particular, has long execution times. Whole-lung models, such as the MPPD, have been established as the standard for inhalation dose estimation in the fields of toxicology and pharmaceuticals. However, this whole-lung model is a simplified model that only partially represents the physical properties of the aerosol, which limits its application to simple, non-reactive and non-evolving aerosols. In addition, this model cannot capture the effects of different breathing curves. Summary of the Invention

[0004] Therefore, there is a need to enhance current dosimetry models so that they can estimate inhaled aerosol deposition in the respiratory system under realistic conditions and in a computationally efficient manner. A desired dosimetry model captures all the key processes that determine aerosol transport and aerosol deposition over time. Furthermore, the desired dosimetry model accounts for different aerosol properties, inhalation topologies, and individual lung morphologies while being computationally efficient. Furthermore, the desired dosimetry model provides instructions to the aerosol generating device and guidance to the user to control aerosol deposition in the user's respiratory system.

[0005] According to one aspect of the present invention, a system including an aerosol generating device and an inhalation guidance unit is provided, the system comprising: one or more processors, the one or more processors being configured to perform the following steps: capturing an aerosol inhalation curve of a user of the aerosol generating device; feeding the captured aerosol inhalation curve to a respiratory system model; generating inhalation guidance instructions based on the respiratory system model; and providing the inhalation guidance instructions to the user at the inhalation guidance unit.

[0006] By configuring the system to capture the user's aerosol inhalation curve and feed it back to the respiratory system model, the user of the aerosol generating device can interactively adjust their inhalation behavior based on the inhalation guidance instructions generated according to the model and provided to the inhalation guidance unit, thereby enabling the user to achieve the desired target aerosol deposition. Capturing the user's aerosol inhalation curve can be done in real time. Feeding the captured aerosol inhalation curve to the respiratory system model can be done in real time. Generating the inhalation guidance instructions and providing the inhalation guidance instructions to the user can be done in real time. Therefore, the user may be able to interactively adjust their inhalation behavior in real time based on the generated inhalation guidance instructions, thereby enabling the user to achieve the desired target aerosol deposition, evolution, absorption, and desorption in real time.

[0007] Capturing the user's aerosol inhalation profile may include determining in real time at least one of an inhalation-exhalation flow rate, a puff rate, and a lung volume change rate.

[0008] For example, the inhalation-exhalation flow rate, the suction rate, and the rate of change of lung volume can be determined in real time using sensors that count inhalation-exhalation cycles, sensors that count aerosol puff cycles, and sensors that capture the inhalation-exhalation flow curve.

[0009] By capturing the user's aerosol inhalation profile in real time, the user's inhalation behavior can be realistically and quickly adapted to match the desired target aerosol deposition using inhalation guidance instructions. The inhalation guidance instructions can, for example, indicate to the user a personalized optimal aerosol inhalation profile, inhalation-exhalation flow rate, or puff rate, to interactively guide the user to adjust their inhalation behavior to achieve the desired target aerosol deposition.

[0010] The respiratory system model can be a computer-implemented modular respiratory system model for transient aerosol dose determination, and the model can include: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow includes an aerosol inhalation curve, wherein each airway module is configured to determine the deposition of inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module.

[0011] A modular respiratory system model is advantageously implemented by providing a respiratory system model for transient aerosol dosimetry that includes a plurality of airway modules, each airway module representing at least a portion of an airway generation of a respiratory system, wherein the airway modules can be used as basic building blocks that can be easily and efficiently combined in a modular and computationally efficient manner to rapidly model regions of interest of the respiratory system. The regions of interest can include each airway generation of the respiratory system or any specific portion of a lung lobe of the respiratory system.

[0012] Furthermore, since the inhalation module is configured to set an input stream including an aerosol inhalation profile to the respiratory system model over time, different personalized aerosol inhalation profiles captured by the aerosol generating device can be fed back and applied to the respiratory system model, and the inhaled aerosol deposition for each aerosol inhalation profile can be determined in the region of interest, enabling the model to determine an optimal aerosol inhalation profile that produces a target aerosol deposition over time in the region of interest of the user's respiratory system. Specifically, the modular respiratory system model is capable of determining transient aerosol dose measurements in different regions of interest of the respiratory system, including different airway generation. Furthermore, the disclosed modular respiratory system model reduces modeling effort and execution time compared to existing modeling techniques.

[0013] Each airway module may include one or more component modules, where each component module represents a component of the respiratory system and includes a port for inlet flow and a port for outlet flow.

[0014] Thus, the airway module represents at least a portion of the airway generation and includes components of the respiratory system. Thus, the components of the respiratory system may be components of the airway generation of the respiratory system. This component module may represent, for example, a trachea, a bifurcation, a branch, a bronchiolar or a bronchiolar.

[0015] Several of the plurality of airway modules may include respective alveolar modules, each alveolar module representing a respective airway module or generated several alveoli, wherein each alveolar module may include a port to receive flow.

[0016] For example, several of the multiple airway modules, which may include corresponding alveolar modules, can represent the deeper airway formations of the respiratory system. This provides a detailed and comprehensive modeling of the respiratory system, enabling a more realistic representation of the lungs. This also allows for accurate reproduction of aerosol behavior and deposition in the deeper alveolar lungs of the respiratory system.

[0017] The respiratory system model may be configured to determine, for each of several aerosol inhalation profiles, corresponding deposition of inhaled aerosol in each airway module of the region of interest of the respiratory system over time to determine an optimal aerosol inhalation profile corresponding to a target aerosol deposition.

[0018] The model may also be configured to generate inhalation guidance instructions based on the optimal aerosol inhalation profile.

[0019] By determining an optimal aerosol inhalation profile and generating inhalation guidance instructions based on the optimal aerosol inhalation profile, the user's inhalation behavior can be adapted to match the optimal aerosol inhalation profile corresponding to a desired target aerosol deposition. The inhalation guidance instructions can, for example, indicate to the user a personalized optimal aerosol inhalation profile, inhalation-exhalation flow rate, or puff rate to interactively guide the user to adjust their inhalation behavior to achieve the desired target aerosol deposition.

[0020] According to another aspect of the present invention, a system including an aerosol generating device and a setting determination unit is provided, the system including: one or more processors, the one or more processors being configured to perform the following steps: determining one or more settings of the aerosol generating device based on a respiratory system model at the setting determination unit; and controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit.

[0021] The one or more processors may be configured to perform the following further steps: obtaining, at the setting determination unit, data relating to the aerosol generating device; and adapting the respiratory system model based on the data relating to the aerosol generating device.

[0022] Adapting the respiratory system model may include at least one of the following: adapting aerosol data input to the respiratory system model based on aerosol data associated with the device; adapting the aerosol data of the respiratory system model based on the settings of the device; adapting the aerosol inhalation curve based on an aerosol inhalation curve associated with the device or with one or more users of the device; and adapting the target aerosol deposition based on a target aerosol deposition associated with the device or with one or more users of the device.

[0023] Thus, by obtaining individualized data related to aerosol generation, such as aerosol data associated with the device, settings of the device, aerosol inhalation profiles associated with the device or associated with one or more users of the device, and target aerosol deposition, this data can be used by the respiratory system model to adapt the aerosol generating device.

[0024] Adapting the aerosol data of the respiratory system model based on the settings of the device may include at least one of the following: adjusting the vibration frequency of the grid of the heating system of the device to determine one or more adjusted frequencies of vibration at the setting determination unit; and adjusting the temperature of the grid of the heating system of the aerosol generating device to determine one or more adjusted temperatures of the grid at the setting determination unit.

[0025] Controlling the aerosol generating device to provide the aerosol based on the one or more settings determined by the setting determination unit may comprise using at least one of one or more adjusted vibration frequencies of the mesh and one or more adjusted temperatures of the mesh.

[0026] Controlling the aerosol generating device to provide an aerosol based on one or more settings determined by the setting determination unit may include adjusting at least one of a voltage and a current applied to a heating system of the aerosol generating device; adjusting at least one of a duration of power supplied to the heating system of the aerosol generating device; adjusting at least one of a pulse width and a pulse density of power supplied to the heating system of the aerosol generating device; adjusting an aerosol generation rate of the aerosol generating device; and adjusting a volume of aerosol generated per puff from the aerosol generating device.

[0027] For example, the setting determination unit may automatically adjust the vibration frequency of the grid of the heating system of the device so as to determine a new vibration frequency corresponding to the new aerosol concentration or dose. The setting determination unit may then adapt the aerosol data of the respiratory system model based on the new aerosol concentration or dose, thereby ensuring that the model is fed with updated aerosol data corresponding to the new aerosol concentration or dose, so as to be able to determine a more accurate aerosol deposition in a specific region of interest, a target lung depth level, or airway formation corresponding to the respiratory system model of the user of the device.

[0028] For example, the setting determination unit may automatically adjust the temperature of the grid of the heating system of the device so as to determine a new temperature of the grid corresponding to the new aerosol concentration or dose. The setting determination unit may then adapt the aerosol data of the respiratory system model based on the new aerosol concentration or dose, thereby ensuring that the model is fed with updated aerosol data corresponding to the new aerosol concentration or dose, so as to be able to determine a more accurate aerosol deposition in a specific region of interest, a target lung depth level, or airway formation corresponding to the respiratory system model of the user of the device.

[0029] The respiratory system model can be a modular respiratory system model for transient aerosol dose determination, the model comprising: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow comprises a captured aerosol inhalation curve, wherein each airway module is configured to determine the deposition of the inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module.

[0030] According to another aspect of the present invention, a computer-implemented modular respiratory system model for transient aerosol dose determination is provided, the model comprising: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow comprises an aerosol inhalation curve, wherein each airway module is configured to determine the deposition of the inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module, so that the model is able to determine the deposition of the inhaled aerosol in the region of interest of the respiratory system over time.

[0031] According to another aspect of the present invention, a computer-implemented method for generating a modular respiratory system model for transient aerosol dose measurement is provided, the method comprising: obtaining physiological data related to the respiratory system; obtaining aerosol data related to aerosol characteristics; generating a plurality of airway modules based on the physiological data and the aerosol data, each airway module representing at least a portion of the airway generation of the respiratory system; generating an inhalation topology module, the inhalation topology module being used to set an input flow to the respiratory system model over time, wherein the input flow includes an aerosol inhalation curve; and generating the modular respiratory system model based on combining the plurality of airway modules and the inhalation topology module.

[0032] As used herein, the term "aerosol-generating device" refers to a device that interacts with an aerosol-forming substrate to generate an aerosol. The aerosol-generating device may interact with one or both of an aerosol-generating article comprising an aerosol-forming substrate or a cartridge comprising an aerosol-forming substrate. In some examples, the aerosol-generating device may heat the aerosol-forming substrate to facilitate release of volatile compounds from the substrate. Electrically operated aerosol-generating devices may include an atomizer, such as an electric heater, to heat the aerosol-forming substrate to form the aerosol.

[0033] As used herein, the term "aerosol-forming substrate" refers to a substrate capable of releasing volatile compounds that can form an aerosol. The volatile compounds can be released by heating or burning the aerosol-forming substrate. As an alternative to heating or burning, in some cases, the volatile compounds can be released by a chemical reaction or by mechanical stimulation (such as ultrasound). The aerosol-forming substrate can be solid or liquid, or can include both solid and liquid components. The aerosol-forming substrate can be part of an aerosol-generating article.

[0034] The power supply may include control electronics. The control electronics may include a microcontroller. The microcontroller is preferably a programmable microcontroller. The circuit may include additional electronic components. The circuit may be configured to regulate the power supply to the heater assembly. Power may be supplied to the heater assembly continuously after system activation, or may be supplied intermittently, such as on a puff-by-puff basis. Power may be supplied to the heater assembly in the form of current pulses.

[0035] The present invention is defined in the claims. However, a non-exhaustive list of non-limiting examples is provided below. Any one or more features of these examples may be combined with any one or more features of another example, embodiment or aspect described herein.

[0036] Example Ex1: A computer-implemented modular respiratory system model for transient aerosol dose determination, the model comprising: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow comprises an aerosol inhalation curve, wherein each airway module is configured to determine the deposition of the inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module, so that the model is able to determine the deposition of the inhaled aerosol in the region of interest of the respiratory system over time.

[0037] Example Ex2: The model of example Ex1, wherein each airway module comprises one or more component modules, wherein each component module represents a component of the respiratory system and comprises a port for input flow and a port for output flow.

[0038] Example Ex3: The model according to example Ex2, wherein the component of the respiratory system comprises a trachea, a bifurcation, a branch, a bronchiole or a bronchiole.

[0039] Example Ex4: The model according to any of Examples Ex2 and Ex3, wherein the component module further comprises a volume port configured to accommodate volume expansion of the component module.

[0040] Example Ex5: The model of any of Examples Ex2 and Ex4, wherein the component module further comprises a thermal port configured to regulate heat transfer in the component module.

[0041] Example Ex6: The model according to any one of Examples Ex2 to Ex5, wherein the airway module further comprises an input pressure drop element configured to apply a pressure drop to the flow input by the port of the component module.

[0042] Example Ex7: The model of any of Examples Ex2 to Ex6, wherein each airway module further comprises an output pressure drop element configured to apply a pressure drop to the flow output by the port of the component module to determine the intermediate flow.

[0043] Example Ex8: The model of any of Examples Ex1 to Ex7, further comprising one or more extrathoracic airway modules representing extrathoracic airway components of the respiratory system.

[0044] Example Ex9: The model of example Ex8, wherein the extrathoracic airway component of the respiratory system includes a mouth, nose, bifurcation, or larynx.

[0045] Example Ex10: The model of example Ex9, wherein a first one of the one or more external thoracic airway modules represents a mouth, and a second one of the one or more external thoracic airway modules represents a nose.

[0046] Example Ex11: A model according to Example Ex10, wherein setting an input flow to the respiratory system model over time includes setting an input flow to the first extrathoracic airway module representing the mouth or to the second extrathoracic airway module representing the nose over time, or setting a first input flow to the first extrathoracic airway module and a second input flow to the second extrathoracic airway module over time, wherein the first input flow and the second input flow constitute the input flow.

[0047] Example Ex12: The model of any of Examples Ex1 to Ex11, wherein the model comprises a single-pathway configuration, wherein each airway module of the single-pathway configuration is configured to represent the entire airway generation.

[0048] Example Ex13: The model of any of Examples Ex1 to Ex12, wherein the model is based on a hybrid respiratory system model, wherein one or more airway modules are configured to represent only a portion of airway generation.

[0049] Example Ex14: The model of Example Ex13, wherein the respective portion of the airway generated by the airway module corresponds to a lobe of a lung of the respiratory system.

[0050] Example Ex15: The model according to any one of Examples Ex8 to Ex14 is further configured to combine the multiple airway modules and the one or more extrathoracic airway modules, and determine a branch of the input flow set to the respiratory system model from the extrathoracic airway module to each airway module in the respiratory system model.

[0051] Example Ex16: The model of Example Ex15, wherein determining the branching of the input flow in each airway module comprises dividing the flow input to the airway module by a branching number parameter of the airway module to determine the flow in the airway module.

[0052] Example Ex17: The model of any of Examples Ex1 to Ex16, wherein several of the plurality of airway modules include respective alveolar modules, each alveolar module representing several alveoli of the respective airway module, wherein each alveolar module includes a port for receiving flow.

[0053] Example Ex18: The model according to Example Ex17, further configured to combine the alveolar module with a component module in each of the airway modules, wherein combining the alveolar module with the component module includes determining a branch of the flow into the alveolar module.

[0054] Example Ex19: A model according to Example Ex18, wherein determining the branching of the flow into the alveolar module includes multiplying the intermediate flow by a branching number parameter in the airway module to determine the total intermediate flow in the airway module, and dividing the total intermediate flow in the airway module by the alveolar number parameter of the airway module to determine the flow received by the port of the alveolar module.

[0055] Example Ex20: The model of any of Examples Ex17 to Ex19, wherein the alveolar module further comprises a thermal port configured to regulate heat transfer in the alveolar module.

[0056] Example Ex21: The model of any of Examples Ex17 to Ex20, wherein the alveolar module further comprises a volume port configured to regulate volume expansion of the alveolar module.

[0057] Example Ex22: A model according to Example Ex21, wherein setting an input flow to the respiratory system model over time includes setting a predetermined volume expansion over time at a volume port of the alveolar module or at a volume port of any component of the airway module, wherein the predetermined volume expansion over time corresponds to the rate of change of the volume over time.

[0058] Example Ex23: The model according to any one of Examples Ex1 to Ex22, further comprising an input module configured to receive input data.

[0059] Example Ex24: A model according to Example Ex23, wherein the input data includes at least one of the following: associated with the respiratory system of the subject, selection of a region of interest of the respiratory system, target aerosol deposition to be delivered to one or more airway generation or regions of interest, corresponding branch number parameters for the airway module, corresponding alveolar number parameters for the alveolar module, aerosol data related to aerosol characteristics, and data related to several aerosol inhalation curves.

[0060] Example Ex25: A model according to Example Ex24, wherein input physiological data related to the respiratory system is used to adapt one or more airway modules, wherein the physiological data includes geometric characteristics of one or more components of the respiratory system, wherein the geometric characteristics include at least one of branch length, branch diameter, bifurcation angle, and gravity angle.

[0061] Example Ex26: A model according to any one of Examples Ex1 to Ex25, further configured to determine, for each of several aerosol inhalation curves, the corresponding deposition of the inhaled aerosol in each airway module of the region of interest of the respiratory system over time to determine the optimal aerosol inhalation curve corresponding to the target aerosol deposition.

[0062] Example Ex27: The model according to Example Ex26 is further configured to generate inhalation guidance instructions based on the optimal aerosol inhalation curve.

[0063] Example Ex28: A model according to Example Ex27, wherein the inhalation guidance instructions include at least one of the optimal aerosol inhalation curve, the inhalation-exhalation flow rate, the suction rate, and the lung volume change rate, wherein the inhalation-exhalation flow rate, the suction rate, and the lung volume change rate are based on the optimal aerosol inhalation curve.

[0064] Example Ex29: A computer-implemented method for generating a modular respiratory system model for transient aerosol dose measurement, the method comprising: obtaining physiological data related to the respiratory system; obtaining aerosol data related to aerosol characteristics; generating multiple airway modules based on the physiological data and the aerosol data, each airway module representing at least a portion of the airway generation of the respiratory system; generating an inhalation topology module, the inhalation topology module being used to set an input flow to the respiratory system model over time, wherein the input flow includes an aerosol inhalation curve; and generating the modular respiratory system model based on combining the multiple airway modules and the inhalation topology module.

[0065] Example Ex30: The method of Example Ex29, further comprising setting, by the inhalation topology module, an input flow to the respiratory system model over time.

[0066] Example Ex31: The method of Example Ex30, further comprising determining deposition of the inhaled aerosol over time in at least a portion of the respiratory system's airway generation represented by a corresponding airway module based on the set input flow.

[0067] Example Ex32: The method of any of Examples Ex29 to Ex31, wherein each airway module comprises one or more component modules, wherein each component module represents a component of the respiratory system and comprises a port for input flow and a port for output flow.

[0068] Example Ex33: The method of Example Ex32, wherein the component of the respiratory system comprises a trachea, a bifurcation, a branch, a bronchiole, or a bronchiole.

[0069] Example Ex34: The method of any of Examples Ex32 and Ex33, wherein the component module further comprises a volume port configured to regulate volume expansion of the component module.

[0070] Example Ex35: The method of any of Examples Ex32 to Ex34, wherein the component module further comprises a thermal port configured to regulate heat transfer in the component module.

[0071] Example Ex36: The method of any one of Examples Ex32 to Ex35, wherein the airway module further comprises an input pressure drop element configured to apply a pressure drop to the flow input by the port of the component module.

[0072] Example Ex37: The method of any of Examples Ex32 to Ex36, wherein each airway module further comprises an output pressure drop element configured to apply a pressure drop to the flow output by the port of the component module to determine the intermediate flow.

[0073] Example Ex38: The method of any one of Examples Ex29 to Ex37, further comprising one or more extra-thoracic airway modules representing one or more extra-thoracic airway components of the respiratory system.

[0074] Example Ex39: The method of example Ex38, wherein the extrathoracic airway component of the respiratory system comprises the mouth, nose, bifurcation, or larynx.

[0075] Example Ex40: The method of Example Ex39, wherein a first one of the one or more external thoracic airway modules represents the mouth, and a second one of the one or more external thoracic airway modules represents the nose.

[0076] Example Ex41: A method according to Example Ex40, wherein setting an input flow to the respiratory system model over time includes setting an input flow to the first extrathoracic airway module representing the mouth or to the second extrathoracic airway module representing the nose over time, or setting a first input flow to the first extrathoracic airway module and a second input flow to the second extrathoracic airway module over time, wherein the first input flow and the second input flow constitute the input flow.

[0077] Example Ex42: The method of any of Examples Ex29 to Ex41, wherein the model comprises a single-pathway configuration, wherein each airway module in the single-pathway configuration is configured to represent the entire airway generation.

[0078] Example Ex43: The method of any of Examples Ex29 to Ex42, wherein the model is based on a hybrid respiratory system model, wherein one or more airway modules are configured to represent only a portion of airway generation.

[0079] Example Ex44: The method of Example Ex43, wherein the respective portion of the airway generation represented by the airway module corresponds to a lobe of a lung of the respiratory system.

[0080] Example Ex45: The method according to any one of Examples Ex38 to Ex44 is further configured to combine the multiple airway modules and the one or more extrathoracic airway modules, and determine a branch of the input flow set to the respiratory system model from the extrathoracic airway module to each airway module in the respiratory system model.

[0081] Example Ex46: The method of Example Ex45, wherein determining the branching of the input flow in each airway module comprises dividing the flow input to the airway module by a number of branches parameter of the airway module.

[0082] Example Ex47: The method of any of Examples Ex29 to Ex46, wherein several of the plurality of airway modules include respective alveolar modules, each alveolar module representing several alveoli of the respective airway module, wherein each alveolar module includes a port for receiving flow.

[0083] Example Ex48: The method of Example Ex47, further configured to combine the alveolar module with a component module in each of the airway modules, wherein combining the alveolar module with the component module includes determining a branch of the flow into the alveolar module.

[0084] Example Ex49: A method according to Example Ex48, wherein determining the branching of the flow into the alveolar module includes multiplying the intermediate flow by a branch number parameter in the airway module to determine the total intermediate flow in the airway module, and dividing the total intermediate flow in the airway module by the alveolar number parameter of the airway module to determine the flow received by the port of the alveolar module.

[0085] Example Ex50: The method of any one of Examples Ex47 to Ex49, wherein the alveolar module further comprises a volume port configured to regulate volume expansion of the alveolar module.

[0086] Example Ex51: The method of any one of Examples Ex47 to Ex50, wherein the alveolar module further comprises a thermal port configured to regulate heat transfer in the alveolar module.

[0087] Example Ex52: A method according to Example Ex51, wherein setting an input flow to the respiratory system model over time includes setting a predetermined volume expansion over time at a volume port of the alveolar module or at a volume port of any component of the airway module, wherein the predetermined volume expansion over time corresponds to the rate of change of the volume over time.

[0088] Example Ex53: A method according to Example Ex34, wherein setting an input flow to the respiratory system model over time includes setting a predetermined volume expansion over time at a volume port of any component of the airway module, wherein the predetermined volume expansion over time corresponds to the rate of change of volume over time.

[0089] Example Ex54: The method according to any one of Examples Ex29 to Ex53 further includes obtaining at least one of the following: selection of a region of interest of the respiratory system, target aerosol deposition to be delivered to one or more airway generation or regions of interest, and data associated with a plurality of aerosol inhalation curves.

[0090] Example Ex55: The method according to any one of Examples Ex29 to Ex54 is also configured to determine, for each of several aerosol inhalation curves, the corresponding deposition of the inhaled aerosol in each airway module of the region of interest of the respiratory system over time to determine the optimal aerosol inhalation curve corresponding to the target aerosol deposition.

[0091] Example Ex56: The method according to Example Ex55, further comprising generating inhalation guidance instructions based on the optimal aerosol inhalation curve.

[0092] Example Ex57: A method according to Example Ex56, wherein the inhalation guidance instructions include at least one of the optimal aerosol inhalation curve, the inhalation-expiration flow rate, the suction rate and the lung volume change rate, wherein the inhalation-expiration flow rate, the suction rate and the lung volume change rate are based on the optimal aerosol inhalation curve.

[0093] Example Ex58: A system comprising an aerosol generating device and an inhalation guidance unit, the system being configured for use as a model of one of Examples Ex1 to Ex28.

[0094] Example Ex59: A system comprising an aerosol generating device and an inhalation guidance unit, the system comprising a memory storing a model of one of Examples Ex1 to Ex28.

[0095] Example Ex60: A system according to any one of Examples Ex58 and Ex59, comprising one or more processors configured to perform the following steps: capturing an aerosol inhalation curve of a user of the aerosol generating device; feeding the captured aerosol inhalation curve to the respiratory system model; generating inhalation guidance instructions based on the respiratory system model; and providing the inhalation guidance instructions to the user at the inhalation guidance unit.

[0096] Example Ex61: The system of example Ex60, wherein capturing the user's aerosol inhalation profile comprises determining at least one of an inhalation-exhalation flow rate, a puff rate, and a lung volume change rate in real time.

[0097] Example Ex62: The system of Example Ex61, wherein determining the inhalation-exhalation flow rate is based on at least one of a sensor that counts inhalation-exhalation cycles or a sensor that captures a flow inhalation-exhalation flow curve.

[0098] Example Ex63: The system of example Ex61, wherein the aerosol generating device comprises a sensor for counting aerosol puff cycles, wherein determining the puff rate is based on the counted aerosol puff cycles.

[0099] Example Ex64: A system comprising an aerosol generating device and a setting determination unit, the system being configured for use with the model of one of Examples Ex1 to Ex28.

[0100] Example Ex65: A system comprising an aerosol generating device and a setting determination unit, the system comprising a memory storing a model of one of Examples Ex1 to Ex28.

[0101] Example Ex66: A system according to any one of Examples Ex64 and Ex65, comprising one or more processors configured to perform the following steps: determining one or more settings of the aerosol generating device based on the respiratory system model at the setting determination unit; and controlling the aerosol generating device to provide an aerosol based on the one or more settings.

[0102] Example Ex67: A system according to Example Ex66, wherein controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit includes at least one of: adjusting at least one of the voltage and current applied to the heating system of the aerosol generating device; adjusting at least one of the duration of the power supplied to the heating system of the aerosol generating device; adjusting at least one of the pulse width and pulse density of the power supplied to the heating system of the aerosol generating device; adjusting the aerosol generation rate of the aerosol generating device; and adjusting the volume of aerosol generated from each puff of the aerosol generating device.

[0103] Example Ex68: The system according to any of Examples Ex66 and Ex67, wherein the one or more processors are configured to perform the following further steps: obtaining data related to the aerosol generating device; and adapting the respiratory system model based on the data related to the aerosol generating device.

[0104] Example Ex69: A system according to Example Ex68, wherein adapting the respiratory system model includes at least one of the following: adapting aerosol data input to the respiratory system model based on aerosol data associated with the device; adapting the aerosol data of the respiratory system model; adapting the aerosol inhalation curve of the inhalation topology module based on an aerosol inhalation curve associated with the device or with one or more users of the device; and adapting the target aerosol deposition based on the target aerosol deposition associated with the device or with one or more users of the device.

[0105] Example Ex70: A system according to Example Ex69, wherein adapting the aerosol data of the respiratory system model includes at least one of the following: adjusting the vibration frequency of the grid of the heating system of the device to determine one or more adjusted vibration frequencies; and adjusting the temperature of the grid of the heating system of the aerosol generating device to determine one or more adjusted temperatures of the grid, wherein controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit includes using at least one of the determined: one or more adjusted vibration frequencies and one or more adjusted temperatures of the grid.

[0106] Example Ex71: A system comprising an aerosol generating device and an inhalation guidance unit, the system comprising: one or more processors, the one or more processors being configured to perform the following steps: capturing an aerosol inhalation curve of a user of the aerosol generating device; feeding the captured aerosol inhalation curve to a respiratory system model; generating inhalation guidance instructions based on the respiratory system model; and providing the inhalation guidance instructions to the user at the inhalation guidance unit.

[0107] Example Ex72: The system of claim 71, wherein capturing the user's aerosol inhalation profile comprises determining in real time at least one of an inhalation-exhalation flow rate, a puff rate, and a lung volume change rate.

[0108] Example Ex73: A system according to Example Ex71 or Ex72, wherein the respiratory system model is a modular respiratory system model for transient aerosol dose determination, the model comprising: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow comprises a captured aerosol inhalation curve, wherein each airway module is configured to determine the deposition of the inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module.

[0109] Example Ex74: The system of example Ex73, wherein each airway module comprises one or more component modules, wherein each component module represents a component of the respiratory system and comprises a port for input flow and a port for output flow.

[0110] Example Ex75: The system of any of Examples Ex73 and Ex74, wherein several of the plurality of airway modules include respective alveolar modules, each alveolar module representing an alveolus of the respective airway module, wherein each alveolar module includes a port to receive flow.

[0111] Example Ex76: A system according to any one of Examples Ex73 to Ex75, wherein the respiratory system model is configured to determine, for each of several aerosol inhalation curves, the corresponding deposition of the inhaled aerosol in each airway module in the region of interest of the respiratory system over time to determine an optimal aerosol inhalation curve corresponding to the target aerosol deposition.

[0112] Example Ex77: The system of Example Ex76, wherein the respiratory system model is further configured to generate the inhalation guidance instructions based on the optimal aerosol inhalation curve.

[0113] Example Ex78: A system comprising an aerosol generating device and a setting determination unit, the system comprising: one or more processors, the one or more processors being configured to perform the following steps: determining one or more settings of the aerosol generating device based on a respiratory system model at the setting determination unit; and controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit.

[0114] Example Ex79: A system according to Example Ex78, wherein controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit includes at least one of: adjusting at least one of a voltage and a current applied to a heating system of the aerosol generating device; adjusting at least one of a duration of power supplied to the heating system of the aerosol generating device; adjusting at least one of a pulse width and a pulse density of power supplied to the heating system of the aerosol generating device; adjusting an aerosol generation rate of the aerosol generating device; and adjusting a volume of aerosol generated from each puff of the aerosol generating device.

[0115] Example Ex80: A system according to any of Examples Ex78 and Ex79, wherein the one or more processors are configured to perform the following additional steps: obtaining data related to the aerosol generating device at the setting determination unit; and adapting the respiratory system model based on the data related to the aerosol generating device.

[0116] Example Ex81: A system according to Example Ex80, wherein adapting the respiratory system model includes at least one of the following: adapting aerosol data input to the respiratory system model based on aerosol data associated with the device; adapting the aerosol data of the respiratory system model; adapting the aerosol inhalation curve based on an aerosol inhalation curve associated with the device or with one or more users of the device; and adapting the target aerosol deposition based on a target aerosol deposition associated with the device or with one or more users of the device.

[0117] Example Ex82: A system according to Example Ex81, wherein adapting the aerosol data of the respiratory system model includes at least one of the following: adjusting the vibration frequency of the grid of the heating system of the device to determine one or more adjusted vibration frequencies at the setting determination unit; and adjusting the temperature of the grid of the heating system of the aerosol generating device to determine one or more adjusted temperatures of the grid at the setting determination unit, wherein controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit includes using at least one of the determined: one or more adjusted vibration frequencies and one or more adjusted temperatures of the grid.

[0118] Example Ex83: A system according to one of Examples Ex78 to Ex82, wherein the respiratory system model is a modular respiratory system model for transient aerosol dose determination, the model comprising: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow comprises a captured aerosol inhalation curve, wherein each airway module is configured to determine the deposition of the inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module.

[0119] Example Ex84: A computer-implemented modular respiratory system model for transient aerosol dose determination, the model comprising: a plurality of airway modules, each airway module representing at least a portion of the airway generation of the respiratory system; and an inhalation topology module, the inhalation topology module being configured to set an input flow to the respiratory system model over time, wherein the input flow comprises an aerosol inhalation curve, wherein each airway module is configured to determine the deposition of the inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module, so that the model is able to determine the deposition of the inhaled aerosol in the region of interest of the respiratory system over time.

[0120] Example Ex85: A computer-implemented method for generating a modular respiratory system model for transient aerosol dose measurement, the method comprising: obtaining physiological data related to the respiratory system; obtaining aerosol data related to aerosol characteristics; generating multiple airway modules based on the physiological data and the aerosol data, each airway module representing at least a portion of the airway generation of the respiratory system; generating an inhalation topology module, the inhalation topology module being used to set an input flow to the respiratory system model over time, wherein the input flow includes an aerosol inhalation curve; and generating the modular respiratory system model based on combining the multiple airway modules and the inhalation topology module. BRIEF DESCRIPTION OF THE DRAWINGS

[0121] Several examples will now be further described with reference to the accompanying drawings, in which:

[0122] Figure 1 An airway module associated with a modular respiratory system model is shown;

[0123] Figure 2 A first embodiment of a bifurcation module representing a bifurcation in a respiratory system is shown;

[0124] Figure 3 A second embodiment of a bifurcation module representing a bifurcation in a respiratory system is shown;

[0125] Figure 4 An extrathoracic combination module including an extrathoracic airway module is shown, the extrathoracic airway module representing the extrathoracic airway component of the respiratory system;

[0126] Figure 5 A single-path configuration comprising a combination of airway modules associated with a single path of a respiratory system model is shown;

[0127] Figure 6 A hybrid module is shown, comprising a combination of modules associated with a hybrid respiratory system model;

[0128] Figure 7 A modular respiratory system model including a single-path configuration is shown;

[0129] Figure 8 A modular respiratory system model based on a hybrid respiratory system model is shown;

[0130] Figure 9 is a flow chart illustrating a computer-implemented method for generating a modular respiratory system model for transient aerosol dosimetry;

[0131] Figure 10 A system comprising an aerosol generating device and an inhalation guidance unit is shown;

[0132] Figure 11 is a flow chart illustrating a computer-implemented method for providing inhalation coaching instructions to a user;

[0133] Figure 12 A system comprising an aerosol generating device and a setting determination unit is shown;

[0134] Figure 13 is a flow chart illustrating a computer-implemented method for controlling an aerosol generating device;

[0135] Figure 14 shows an input flow including an aerosol inhalation profile; and

[0136] Figure 15 Results are shown for transient aerosol deposition in different airways of the respiratory system. DETAILED DESCRIPTION

[0137] Figure 1 An airway module 100 is shown that is associated with a modular respiratory system model and represents at least a portion of the airway generation of the respiratory system. The airway module 100 includes an input flow port 105a and an output flow port 105b. The airway module 100 also includes a component module 130 that represents a component of the respiratory system and includes a port 130a for input flow and a port 130b for output flow. The components of the respiratory system may include the trachea, bifurcations, branches, small bronchi, or bronchioles.

[0138] Using element 110, the flow input by the input flow port 105a of the airway module 100 is divided by the number of branches parameter of the airway module.

[0139] The number of branches parameter represents the number of branches in the airway module. The number of branches parameter of the airway module 100 can be based on physiological data related to the respiratory system. Therefore, the airway module represents all similar components and all parallel branches in at least a portion of the airway generation of the respiratory system.

[0140] Physiological data related to the respiratory system can be used to adapt the airway module based on the subject's respiratory system physiological data. The subject can be a human or an animal. The physiological data can include geometric characteristics of one or more components of the respiratory system. The geometric characteristics can include at least one of branch length, branch diameter, bifurcation angle, and gravity angle.

[0141] The geometric properties of one or more components can be based on at least one of the expanded volume of the lungs, the size of the trunk, an X-ray of the respiratory system, and detailed airway tree morphology measurements. The geometric properties can be based on at least one of height, age, gender, and weight. The geometric properties can be based on general geometric properties of one or more components. The number of branches parameter of the airway module is greater than or equal to 1.

[0142] The airway module 100 also includes an input pressure drop element 120, which is configured to apply a pressure drop to the flow input by port 130a of the component module 130. The pressure drop in the airway of the respiratory system is directly related to the resistance of the airway of the respiratory system. The resistance of the airway is the opposition to flow caused by friction in the airway. The pressure drop element 120 is configured to model the resistance to the flow input by port 130a of the component module 130.

[0143] Airway module 100 also includes an output pressure drop element 140 configured to apply a pressure drop to the flow output by port 130b of component module 130 to determine the intermediate flow. Pressure drop element 140 is configured to model the resistance to the flow output by port 130b of component module 130.

[0144] The modular respiratory system model is further configured to determine the output flow via port 105b of airway module 100 by multiplying the intermediate flow by the airway module's branch number parameter using element 150 to determine the output flow via port 105b of airway module 100 .

[0145] Multiple airway modules representing deeper airway generation in the respiratory system also include Figure 1 The dotted square in the figure represents an alveolar module 170. Alveolar module 170 represents the alveolar cluster of the airway module 100 and includes a port 170a for receiving flow. The modular respiratory system model can combine alveolar module 170 with component module 130 in each of the several airway modules. Combining alveolar module 170 with component module 130 includes determining the branching of flow into alveolar module 170. The alveolar number parameter of the airway module can be based on physiological data related to the respiratory system.

[0146] Determining the branch of flow to the alveolar module 170 includes multiplying the intermediate flow by the alveolar number parameter of the airway module 100 by element 150 to determine the flow received by port 170a of the alveolar module 170 .

[0147] When the airway module includes an alveolar module, the modular respiratory system model is further configured to determine the output flow via port 105b of the airway module 100 by multiplying the intermediate flow by a constant equal to the difference between the number of branches parameter and the number of alveoli parameter using element 150 to determine the output flow via port 105b of the airway module 100.

[0148] Component module 130 also includes a volume port 130c configured to adjust the volume expansion of component module 130. Volume port 130c can be configured to set the input flow to the respiratory system model over time by setting a predetermined volume expansion over time at volume port 130c of component module 130 of airway module 100. The predetermined volume expansion over time corresponds to a rate of volume change over time. Component module 130 also includes a thermal port 130d configured to adjust heat transfer within the component module.

[0149] The alveolar module 170 also includes a volume port 170c configured to regulate the volume expansion of the alveolar module. The volume port 170c can be configured to set the input flow to the respiratory system model over time by setting a predetermined volume expansion over time at the volume port 170c of the component module 130 of the airway module 100. The predetermined volume expansion over time corresponds to a rate of volume change over time. The alveolar module 170 also includes a thermal port 170d configured to regulate heat transfer in the alveolar module.

[0150] The physical and chemical behavior of aerosols can be represented by the publicly available AeroSolved model and its system implementation, AeroSolvedSystem (www.aerosolved.com, pmpsa-cfd, GitHub). The well-known key processes and conservation laws are described in the AeroSolvedSystem base element, which is suitable for use as a component module, an alveolar module, or an extrathoracic airway module. Each of these modules can be designated to represent a component of an individualized or personalized respiratory system by selecting corresponding physiological data including personalized geometric properties and corresponding aerosol data related to aerosol properties.

[0151] The component module 130 can be a model of a component of the respiratory system. The alveolar module 170 can be a model of an alveolar cluster of the respiratory system. The component module 130 and the alveolar module 170 can each be configured to impose aerosol mixture mass conservation over time. The aerosol in the model can be in vapor or liquid / solid phase. The aerosol mixture mass conservation over time is based on the aerosol mixture mass flux at the volume port of the model and based on the source terms of liquid / solid and vapor through the volume wall of the model to define the instantaneous rate of change of the total aerosol mixture mass in the volume of the gas phase and liquid / solid phase, wherein the source terms of liquid / solid and vapor through the volume wall of each model take into account processes including deposition, condensation / evaporation and absorption / desorption. This is described by the following equation (1):

[0152]

[0153] Among them, M tot is the total aerosol mixture mass in the volume of both vapor and liquid / solid phases. The variable w a and w b is the mass flux of the aerosol mixture at the volume port. It includes liquid or solid aerosols passing through the volume wall (W dep ) or steam (W abs ) to account for processes including deposition, condensation / evaporation, and absorption / desorption.

[0154] The component module 130 and the alveolar module 170 can each be configured to apply aerosol mixture mass conservation over time for each aerosol species in the gas phase. The aerosol mixture mass conservation for each aerosol species in the gas phase is based on the aerosol mixture mass flux at the volume port of the model and based on the source term of vapor passing through the volume wall of the model, defining the instantaneous rate of change of the total aerosol mixture mass of the aerosol species in the volume of the gas phase. The source term of vapor passing through the volume wall of each model takes into account processes including deposition, condensation / evaporation, absorption / desorption, and nucleation. This is described by the following equation (2):

[0155]

[0156] Here, a mass balance is applied for each species i in the gas phase Y[i].

[0157] The component module 130 and the alveolar module 170 can each be configured to impose aerosol mixture mass conservation over time for each aerosol species in the liquid / solid phase, wherein for each aerosol species in the liquid / solid phase, the aerosol mixture mass conservation over time is based on at least one of the aerosol mixture mass fluxes at each model volume port and defines the instantaneous rate of change of the total aerosol mixture mass in the volume of the liquid / solid phase based on a source term of vapor passing through the volume walls of the model, wherein the source term of vapor passing through the volume walls of the model takes into account processes including deposition, condensation / evaporation, and nucleation. This is captured by the following equation (3):

[0158]

[0159] where for each particle diameter j, a mass balance is applied to each species i in the liquid / solid phase Z[i,j].

[0160] The component module 130 and the alveolar module 170 can each be configured to apply particle number density conservation over time for each particle size distribution associated with a diameter representing an evolving distribution of a fixed shape. The particle number density conservation over time is based on at least one of the aerosol mixture mass flux at the volume port of the model and the instantaneous rate of change of the volume of the aerosol mixture based on the source terms of liquid / solid and vapor through the volume wall of each model, wherein the source terms of liquid / solid and vapor through the volume wall of the model take into account processes including deposition, condensation / evaporation, nucleation, and condensation. This is described by the following equation (4):

[0161]

[0162] The processes including deposition, condensation / evaporation and absorption / desorption are based on aerosol data related to aerosol properties. The aerosol data related to aerosol properties may include data related to one or more of material properties of aerosol species, distribution of aerosol droplets and aerosol models.

[0163] Aerosol models may include multipath particle dosimetry models, MPPD, dosimetry models related to aerosol physical properties, and dosimetry models not directly related to aerosol physical properties. Dosimetry models not directly related to aerosol physical properties may include models describing mucociliary clearance.

[0164] In some embodiments, the full transient modeling of aerosol transport achieved by the model may also include modeling of chemical reactions. Thus, equations (1)-(4) may be adapted to further include terms describing chemical reactions.

[0165] Thus, based on the above description including equations (1) to (4), full aerosol physics can be modeled. In addition, dynamic, fully transient modeling of aerosol transport, evolution, and deposition in a personalized full lung geometry can be achieved at an optimized computational cost. In embodiments, deposition with respect to aerosol droplets / particles is determined by modeling the aerosol strictly in the droplet / particle phase. In other embodiments, deposition with respect to gas / vapor is determined by modeling the aerosol in both the droplet / particle phase and the gas / vapor phase, including modeling the processes of absorption / desorption and condensation / evaporation, and still referred to by the term deposition. Figure 2A bifurcation module 200 is shown, which includes a component module 230 representing a bifurcation. The component module includes an input port 230a, an output port 230b, a volume port 230c, and a thermal port 230d. The bifurcation module also includes two input ports 205a and 205b for input flow, and one output port 205c for output flow. The bifurcation module 200 also includes pressure drop elements 210 and 220, which are used to apply a pressure drop to the flow input by the input port 230a of the component module 200 via the respective ports 205a and 205b of the bifurcation module. The bifurcation module 200 also includes a pressure drop element 240 for applying a pressure drop to the flow output by the output port 230b of the component module. The characteristics of the bifurcation module 200, including the characteristics of the component module 230 and the pressure drop elements 210, 220, and 240, are based on physiological data.

[0166] Figure 3 A bifurcation module 300 is shown, which includes a component module 330 representing a bifurcation. The component module includes an input port 330a, an output port 330b, a volume port 330c, and a thermal port 330d. The bifurcation module also includes an input port 305a for input flow and two output ports 305b and 305c for output flow. The bifurcation module 300 also includes a pressure drop element 340, which is used to apply a pressure drop to the flow input by the input port 330a of the component module 300 via the input port 305a of the bifurcation module. The bifurcation module 300 also includes pressure drop elements 310 and 320, which are used to apply a pressure drop to the corresponding flow output by the output port 330b of the component module 300, and the corresponding flow leaves the bifurcation module via the corresponding ports 305b and 305c. The characteristics of the bifurcation module 300, including the characteristics of the component module 330 and the pressure drop elements 310, 320, and 340, are based on physiological data.

[0167] Figure 4 An external thoracic combination module 400 is shown, which includes a combination of external thoracic airway modules 410, 420, 200a, and 430 that can be configured to represent the external thoracic airway components of the respiratory system. The external thoracic airway components of the respiratory system can be the mouth, nose, bifurcation, or larynx. For example, external thoracic airway module 410 can be configured to represent the nose, external thoracic airway module 420 can be configured to represent the mouth, and external thoracic airway module 430 can be configured to represent the larynx. External thoracic airway module 200a is based on the combination of airway modules 200 and can be configured to represent a bifurcation for combining the flow from external thoracic airway module 410 representing the nose with the flow from external thoracic airway module 420 representing the mouth.

[0168] Figure 5A single path configuration module 500 is shown, which includes a combination of airway modules 100a to 100d associated with a single path respiratory system model. Each of the airway modules 100a to 100d is based on Figure 1 Airway modules 100 are provided. Each airway module represents the entire airway formation corresponding to both the left and right lungs of the respiratory system. For example, airway module 100a can be configured to represent the trachea or airway formation 1 of the respiratory system, airway module 100b can be configured to represent the bronchial airway formation, i.e., airway formation 2, airway module 100c can represent the bronchiolar airway formation, and airway module 100d can be configured to represent the alveolar airway formation of the respiratory system. Airway module 100d can represent the alveolar formation because it includes alveolar module 170.

[0169] Single-path configuration module 500 presents a computationally efficient implementation of the respiratory system model because airway modules 100a-100d are all based on airway module 100. Thus, the model includes only a single flow path to be calculated, proving to be a computationally efficient way to determine aerosol deposition, evolution, absorption, and desorption for any desired depth level of respiratory system airway generation.

[0170] According to another embodiment of the present invention, different segments of the respiratory system can be modeled in a detailed branching manner. This detailed modeling can be extended to deeper airway generation based on the availability of personalized data, the need for more details, and the availability of computing power.

[0171] Figure 6 A hybrid module is shown, which includes a combination 600 of airway modules 610 to 640, single path configuration modules 500a to 500e, and bifurcation modules 300a to 300d associated with a hybrid respiratory system model. Each airway module 610 to 640 can be based on Figure 1 The airway modules 100 are configured to represent a portion of the airway generation. Each airway module represents a portion of the airway generation, wherein each airway module can be configured to represent a portion of the airway generation corresponding to a lobe of a lung of the respiratory system. In particular, each airway module can be configured to represent a portion of the airway generation corresponding to one or more left lobes of a left lung of the respiratory system, or a portion of the airway generation corresponding to one or more right lobes of a right lung of the respiratory system.

[0172] For example, the airway module 610 can be configured to represent the trachea or airway generation 1. The bifurcation module 300a can be configured based on Figure 3The bifurcation module 300 of FIG. 6 represents a bifurcation. The airway module 620 may be configured to represent a branch generated by the airway corresponding to the right upper lobe of the right lung. The airway module 640 may be configured to represent a branch generated by the airway corresponding to the left upper lobe of the left lung of the respiratory system. The bifurcation modules 300b, 300c, and 300d may be configured to represent a bifurcation, each of which is based on Figure 3 The single path configuration module 500a connected to one port of the fork module 300b is based on Figure 5 Module 500a may include a combination of airway modules that can be configured to represent the rest of the right upper lobe of the right lung of the respiratory system. The rest of the right upper lobe may include bronchial airway formation, bronchiolar airway formation, and alveolar airway formation.

[0173] The airway module 630 can be configured to represent the branches generated by the airway corresponding to the right middle lobe of the right lung of the respiratory system. The single path configuration module 500b connected to one port of the bifurcation module 300c is based on a single path respiratory system model and is similar to Figure 5 Module 500b may include a combination of airway modules that can be configured to represent the remainder of the right middle lobe of the right lung of the respiratory system. The remainder of the right middle lobe may include bronchial airway formation, bronchiolar airway formation, and alveolar airway formation.

[0174] The single path configuration module 500c connected to one port of the bifurcation module 300c is based on Figure 5 Module 500c may include a combination of airway modules that can be configured to represent the right lower lobe of the right lung of the respiratory system. The right lower lobe may include bronchial airway generation, bronchiolar airway generation, and alveolar airway generation.

[0175] The single path configuration module 500d connected to the airway module 300d is based on Figure 5 Module 500d may include a combination of airway modules that can be configured to represent the remainder of the left upper lobe of the left lung of the respiratory system. The remainder of the left upper lobe may include bronchial airway formation, bronchiolar airway formation, and alveolar airway formation.

[0176] The single path configuration module 500e connected to one port of the bifurcation module 300d is based on Figure 5 Module 500e may include a combination of airway modules that can be configured to represent the left lower lobe of the left lung of the respiratory system. The left lower lobe may include bronchial airway generation, bronchiolar airway generation, and alveolar airway generation.

[0177] Figure 7A modular respiratory system model 700 based on a single path configuration is shown. The model 700 includes an inhalation topology module 710 configured to set an input flow to the respiratory system model 700 over time. The input flow can be set based on an aerosol inhalation curve. The model 700 also includes an extrathoracic combination module 400a, which is based on the extrathoracic combination module 400 and includes a combination of extrathoracic airway modules that can be configured to represent extrathoracic airway components of the respiratory system. The extrathoracic components can include the nose, mouth, bifurcation, or larynx. The model 700 also includes a module 500f, which is based on Figure 5 The single-path configuration module 500 includes a combination of airway modules associated with the single-path respiratory system model. Each airway module in the combination of airway modules can be configured to represent at least a portion of the airway generation of the respiratory system. Each airway module in the combination of airway modules can be configured to determine the deposition, evolution, absorption, and desorption of inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module 710, so that the model 700 can determine the deposition, evolution, absorption, and desorption of inhaled aerosol in the region of interest of the respiratory system over time.

[0178] Setting the input flow to the respiratory system model 700 over time may include setting the input flow to a first extrathoracic airway module representing the mouth or to a second extrathoracic airway module representing the nose over time, or setting a first input flow to the first extrathoracic airway module and a second input flow to the second extrathoracic airway module over time, wherein the first input flow and the second input flow constitute the input flow.

[0179] Setting the input flow to the respiratory system model 700 over time may also include setting conditions for the input flow, including setting at least one of an input flow topology and an input flow thermophysical condition. Setting the input flow thermophysical condition may include setting at least one of an input flow temperature and an input flow aerosol concentration characteristic.

[0180] Model 700 also includes combining multiple airway modules and one or more extrathoracic airway modules.

[0181] Combining the multiple airway modules may include determining a branching of an input flow set to the model by the inhalation topology module 710 from the extrathoracic airway module to each airway module in the respiratory system model. Branching the input flow may include setting an output flow from an output port 105b of the airway module equal to an input flow input by an input port 105a of a subsequent module.

[0182] The flow in the respiratory system model is bidirectional, flowing in a forward direction along the flow path during a first period and in a reverse direction along the flow path during a second period. The flow in the respiratory system model can flow from the extrathoracic airway module to the airway module, or from the airway module to the extrathoracic airway module, thereby capturing the complete inhalation-exhalation cycle.

[0183] Combining multiple airway modules can include combining some or all of the thermal ports of the component modules in the region of interest of the respiratory system model. The combined thermal ports are configured to control heat transfer in the region of interest of the respiratory system model. The modular respiratory system model 700 can also include an interface module to establish closed-loop interaction with external models.

[0184] Figure 8 A modular respiratory system model 800 based on a hybrid respiratory system model is shown. The model includes an inhalation topology module 710 configured to set an input flow to the respiratory system model 800 over time, wherein the input flow includes an aerosol inhalation curve. The model also includes an extrathoracic combination module 400b, which is based on the extrathoracic combination module 400 and includes an extrathoracic airway module that can be configured to represent the extrathoracic airway components of the respiratory system. The extrathoracic components can include the nose, mouth, bifurcation, or larynx.

[0185] The model also includes a module 600a, which represents the Figure 6 The hybrid module 600 is a hybrid module and includes a hybrid combination of airway modules associated with a hybrid respiratory system model. Each airway module is based on Figure 1 Each airway module can be configured to represent a portion of the airway generation corresponding to a lobe of the respiratory system, as described above with reference to Figure 6 Each airway module in the hybrid combination of airway modules can be configured to determine the deposition, or even the deposition, evolution, absorption, and desorption, of inhaled aerosol over time in at least a portion of the airway generation of the respiratory system represented by the airway module based on the input stream set by the inhalation topology module 810, so that the model 800 can determine the deposition, or even the deposition, evolution, absorption, and desorption of inhaled aerosol in the region of interest of the respiratory system over time. Setting the input stream to the respiratory system model over time can include setting the input stream to the extrathoracic airway module representing the mouth or nose over time.

[0186] The model 800 may also include combining multiple airway modules and one or more extrathoracic airway modules. Combining the multiple airway modules may include determining a branching of an input flow set to the model by the inhalation topology module 710 from the extrathoracic airway module to each airway module in the respiratory system model. Branching the input flow may include setting the output flow from the output port 105b of the airway module to be equal to the input flow input by the input port 105a of the subsequent module, or dividing the input flow between the input ports of the subsequent modules based on physiological data related to the respiratory system.

[0187] Flow in the respiratory system model can be bidirectional. Flow in the respiratory system model can flow from the extrathoracic airway module to the airway module, or from the airway module to the extrathoracic airway module.

[0188] Combining the plurality of airway modules may include combining some or all thermal ports of the component modules in the region of interest of the respiratory system model. The combined thermal ports are configured to control heat transfer in the region of interest of the respiratory system model.

[0189] The modular respiratory system models 700, 800 may also include an interface module to establish closed-loop interaction with external models. For example, the respiratory system models 700, 800 that calculate the dynamic evolution, transport, and deposition of aerosols within the region of interest of the lungs may be connected to a physiologically based model (PBPK) to predict the biological effects of inhaled aerosols. The connection between the respiratory system models 700, 800 and the PBPK model may be achieved using an interface element ( Figure 7 and Figure 8 The interface element may also be used to include additional dosimetry models that may not be directly related to the physical properties of the aerosol, such as modeling mucociliary clearance.

[0190] Model 700 or 800 may also be configured to determine corresponding deposition of inhaled aerosol in each airway module of the region of interest of the respiratory system over time for each of several aerosol inhalation profiles to determine an optimal aerosol inhalation profile corresponding to a target aerosol deposition.

[0191] Model 700 or 800 may also be configured to generate inhalation guidance instructions based on the optimal aerosol inhalation curve. The inhalation guidance instructions include at least one of the optimal aerosol inhalation curve, an inhalation-expiration flow rate, a suction rate, and a lung volume change rate, wherein the inhalation-expiration flow rate, the suction rate, and the lung volume change rate are based on the optimal aerosol inhalation curve.

[0192] A system implementing model 700 or 800 may also be configured to obtain data related to an aerosol-generating device and to adapt the respiratory system model based on the data related to the aerosol-generating device.

[0193] The data associated with the aerosol-generating device may include at least one of the following: a type of device, characteristics of the device, settings of the device, aerosol characteristics associated with the device, a target aerosol deposition associated with the device or one or more users of the device, and an aerosol inhalation profile associated with the device or one or more users of the device. The type of device is obtained from a device list that includes at least one of an inhaler and an electronic smoking device.

[0194] Adapting the respiratory system model may include at least one of the following: adapting the aerosol data of the respiratory system model based on aerosol data associated with the device; adapting the aerosol data of the respiratory system model; adapting the aerosol inhalation curve of the inhalation topology module based on the aerosol inhalation curve associated with the device or with one or more users of the device; and adapting the target aerosol deposition based on the target aerosol deposition associated with the device or with one or more users of the device.

[0195] Adapting the aerosol data of the respiratory system model may comprise adjusting a vibration frequency of a mesh of a heating system of the device to determine one or more adjusted vibration frequencies. Alternatively or additionally, adapting the aerosol data of the respiratory system model based on the settings of the device may comprise adjusting a temperature of a mesh of a heating system of the aerosol generating device to determine one or more adjusted temperatures of the mesh.

[0196] The model 700 or 800 may also be configured to output instructions to the aerosol generating device. The instructions may be sent to the control unit 1020 via the communication module 1030 of the aerosol generating device. The instructions may be inspected and processed by the control unit 1020 and then executed by a designated component of the aerosol generating device (e.g., a grid of a heating system). The instructions may include at least one of the one or more adjusted vibration frequencies and the one or more adjusted temperatures of the grid.

[0197] Figure 9800 is a flow chart illustrating a computer-implemented method 800 for generating a modular respiratory system model 700, 800 for transient aerosol dosimetry. The modular respiratory system model 700, 800 enables real-time modeling of the evolution of aerosol dosimetry over time for the individualized whole lung geometry of the ventilator system. The method begins at step 910, where physiological data related to the respiratory system is obtained. As described above, the physiological data related to the respiratory system may include geometric properties of one or more components of the respiratory system, where the geometric properties include at least one of branch lengths, branch diameters, bifurcation angles, and gravity angles.

[0198] At step 920, aerosol data related to aerosol characteristics is obtained. As described above, the aerosol data related to aerosol characteristics may include data related to one or more of material properties of aerosol species, distribution of aerosol droplets, and aerosol models.

[0199] At step 930, an optional selection of a region of interest for the respiratory system is obtained. The selection may include a target number of airways or a specific portion of a lung lobe. If no selection is obtained, the model automatically selects the region of interest based on physiological data.

[0200] At step 940, a plurality of airway modules are generated based on the physiological data and the aerosol data, each airway module representing at least a portion of the airway generation of the respiratory system. Figure 1 As described, each airway module includes a component module 130, which represents a component of the respiratory system and includes a port 130a for inputting flow and a port 130b for outputting flow. Components of the respiratory system may include the trachea, bifurcations, branches, small bronchi, or bronchioles. The multiple airway modules representing the deeper airways of the respiratory system also include an alveolar module 170. Alveolar module 170 includes a port 170a for receiving flow.

[0201] At step 950, an inhalation topology module is generated for setting an input flow to the respiratory system model over time. The input flow includes an aerosol inhalation curve. The aerosol inhalation curve is based on aerosol data.

[0202] At step 960, a modular respiratory system model is generated based on combining multiple airway modules and an inhalation topology module. The generated model can be based on a single-path respiratory system model, where each airway module is configured to represent the entire airway generation, as described above with respect to Figure 7 The generated model may be based on a hybrid respiratory system model, where each airway module is configured to represent only the portion of the airway generation corresponding to a lobe of the respiratory system, as described above with respect to Figure 8 As stated.

[0203] At step 970, the inhalation topology module sets an input flow to the respiratory system model over time. Setting the input flow to the respiratory system model over time may include setting an input flow to the extrathoracic combination module 400 over time. The extrathoracic combination module may include a first extrathoracic airway module representing a nose and a second extrathoracic airway module representing an mouth. Setting the input flow to the extrathoracic combination module over time may include setting an input flow to the first extrathoracic airway module representing the mouth or to the second extrathoracic airway module representing the nose over time, or setting a first portion of the input flow to the first extrathoracic airway module and a second portion of the input flow to the second extrathoracic airway module over time, wherein the first input flow and the second input flow constitute the input flow.

[0204] Alternatively, a predetermined volume expansion over time can be set at the volume port of the alveolar module or at the volume port of any component of the airway module, where the predetermined volume expansion over time corresponds to the rate of volume change over time. Flow in the respiratory system model is bidirectional. Flow in the respiratory system model can flow from the extrathoracic airway module to the airway module, or vice versa.

[0205] At step 980, deposition of the inhaled aerosol over time in at least a portion of the airway generation of the respiratory system represented by the airway module is determined based on the set input flow. Full transient modeling of aerosol transport, evolution, and deposition in the personalized full lung geometry can be achieved by modeling the physical and chemical behavior of the inhaled aerosol from the set input flow and by applying relevant process conservation laws based on equations (1) to (4).

[0206] Thus, the model is enabled to determine the deposition of inhaled aerosol in any region of interest of the respiratory system over time. Determining the deposition of inhaled aerosol in any region of interest over time may comprise determining the deposition of inhaled aerosol in each airway generation of the respiratory system model or in a specific airway generation or in a specific portion of a lung lobe over time.

[0207] The above about Figure 9 Some or all of the described method steps may be computer-implemented in that they are performed by (or using) a processor, microprocessor, electronic circuit, or processing circuitry. For example, the implementation may be performed using non-transitory storage media, such as computer-readable storage media. Such computer-readable media may be any available media that can be accessed by a general-purpose or special-purpose computer system.

[0208] Generally, the method can be implemented as a computer program product having program code or computer executable instructions, which, when the computer program product runs on a computer, is operable to perform one of the methods. The program code or computer executable instructions can, for example, be stored on a computer readable storage medium.

[0209] The storage medium (or data carrier or computer-readable medium) may include a computer program or computer-executable instructions stored thereon, for performing one of the methods described herein when executed by a processor. A device may include one or more processors and the above-mentioned storage medium.

[0210] An apparatus may comprise means, such as a processing circuit, such as a processor, for example, in communication with a memory, the means being configured or adapted to perform one of the methods described herein. A computer having installed thereon a computer program or instructions for performing one of the methods described herein.

[0211] Figure 10 A system 1000 is shown that includes an aerosol generating device 1010 and an inhalation guidance unit 1020. The aerosol generating device can be configured to use the modular respiratory system models 700, 800. The system can also include a memory 1030 that stores the modular respiratory system models 700, 800. The system 1000 can also include one or more processors 1040. The system can also include a communication module 1050 that is configured to send and receive instructions to / from other electronic modules or devices, or to send and receive instructions between the aerosol generating device 1010 and the inhalation guidance unit 1020. The system can also include a sensor 1060 that counts inhalation-exhalation cycles or a sensor 1070 that captures an inhalation-exhalation flow curve.

[0212] In an embodiment, the inhalation guidance unit 1020 may be internal to the aerosol generating device 1010 , or may be external to the aerosol generating device 1010 .

[0213] The inhalation guidance unit 1020 can provide the user with inhalation guidance instructions. The inhalation guidance instructions are generated based on the respiratory system model and can be provided to the user using various actuators including a display, a speaker, and a vibration actuator. One or more processors 1040 can be configured to execute the following steps: Figure 11 The following steps of the method 1100 shown in FIG. 1 are used to adjust the user's inhalation behavior based on the provided inhalation coaching instructions:

[0214] Step 1110: Capturing an aerosol inhalation curve of a user of the aerosol generating device;

[0215] Step 1120: feeding the captured aerosol inhalation curve to the respiratory system model;

[0216] Step 1130: Generate inhalation guidance instructions based on the respiratory system model; and

[0217] Step 1140: Providing the inhalation guidance instruction to the user at the inhalation guidance unit.

[0218] Capturing the user's aerosol inhalation profile may include determining in real time at least one of an inhalation-exhalation flow rate, a puff rate, and a rate of change of lung volume. Determining the inhalation-exhalation flow rate may be based on capturing the inhalation-exhalation flow profile by sensor 1060. Determining the puff rate may be based on aerosol puff cycles that may be counted by sensor 1050. Determining the rate of change of lung volume may be based on an external sensor ( Figure 10 ), the external sensor may capture the expansion of the lung volume using a chest strap and may send the determined rate to the aerosol generating device 1000 via the communication module 1030.

[0219] Figure 12 A system 1200 is shown that includes an aerosol-generating device 1210 and a setting determination unit 1220. The aerosol-generating device can be configured to use the modular respiratory system models 700, 800. The system can also include a memory 1230 that stores the modular respiratory system models 700, 800. The system 1200 can also include one or more processors 1240. The system can also include a communication module 1250 that is configured to send and receive instructions to / from other electronic modules or devices, or to send and receive instructions between the aerosol-generating device 1210 and the setting determination unit 1220. The system can also include a sensor 1260 that counts inhalation-exhalation cycles or a sensor 1270 that captures an inhalation-exhalation flow curve, and can also include various actuators (not shown) for providing feedback or guidance to the user. In embodiments, the setting determination unit 1220 can be internal to the aerosol-generating device 1210 or external to the aerosol-generating device 1210.

[0220] The one or more processors 1240 may be configured to perform the following operations: Figure 13 The following steps of the method 1300 are shown in order to control the aerosol generating device 1210:

[0221] Step 1310: At the setting determination unit 1220, one or more settings of the aerosol generating device 1210 are determined based on the respiratory system models 700, 800; and

[0222] Step 1320 : Control the aerosol generating device 1210 to provide an aerosol based on the one or more settings determined by the setting determination unit 1220 .

[0223] Controlling the aerosol generating device 1210 to provide an aerosol based on one or more settings determined by the setting determination unit 1220 may include at least one of: adjusting at least one of a voltage and a current applied to a heating system of the aerosol generating device; adjusting at least one of a duration of power supplied to the heating system of the aerosol generating device; adjusting at least one of a pulse width and a pulse density of power supplied to the heating system of the aerosol generating device; adjusting an aerosol generation rate of the aerosol generating device; and adjusting a volume of aerosol generated per puff from the aerosol generating device.

[0224] At the setting determination unit 1220 , determining one or more settings of the aerosol generating device 1210 based on the respiratory system models 700 , 800 may include the following steps: obtaining data related to the aerosol generating device 1210 at the setting determination unit; and adapting the respiratory system models 700 , 800 based on the data related to the aerosol generating device 1210 .

[0225] Adapting the respiratory system models 700, 800 may include at least one of the following: adapting aerosol data input to the respiratory system models 700, 800 based on aerosol data associated with the device 1210; adapting the aerosol data of the respiratory system models 700, 800; adapting the aerosol inhalation curve of the inhalation topology module based on an aerosol inhalation curve associated with the device or with one or more users of the device; and adapting the target aerosol deposition based on the target aerosol deposition associated with the device or with one or more users of the device.

[0226] Adapting the aerosol data of the respiratory system model 700, 800 may include at least one of: adjusting the vibration frequency of the grid of the heating system of the device to determine one or more adjusted vibration frequencies at the setting determination unit; and adjusting the temperature of the grid of the heating system of the aerosol generating device to determine one or more adjusted temperatures of the grid at the setting determination unit.

[0227] Controlling the aerosol generating device 1210 to provide the aerosol based on the one or more settings determined by the setting determination unit 1220 may include using at least one of: one or more adjusted vibration frequencies and one or more adjusted temperatures of the grid.

[0228] In an alternative embodiment, the setting determination unit 1220 of the system 1200 may be integrated into the Figure 10 Within the system 1000 described.

[0229] Figure 14The input flow to the respiratory system model over time is shown as being set by the inhalation topology module. The input flow can be applied to the respiratory system model via the extrathoracic airway module representing the nose and mouth.

[0230] According to one embodiment of the present invention, the input flow may include a first input flow applied to a first external airway module and a second input flow applied to a second external airway module. The first external airway module may represent a nose, and the second external airway module may represent a mouth. Alternatively, the first external airway module may represent a mouth, and the second external airway module may represent a nose. The first input flow may include an air inhalation profile, and the second input flow may include an aerosol inhalation profile. The first input flow and the second input flow constitute the input flow.

[0231] According to another embodiment of the present invention, setting the input flow to the respiratory system model over time may include setting the input flow to a first extrathoracic airway module representing the mouth or to a second extrathoracic airway module representing the nose over time.

[0232] Setting the input flow to the respiratory system model over time may include setting a condition of the input flow, including setting at least one of an input flow topology and an input flow thermophysical condition. Setting the input flow thermophysical condition may include setting at least one of an input flow temperature and an input flow aerosol concentration characteristic.

[0233] like Figure 14 As shown in the example of , during the first 2 seconds, an aerosol inhalation curve including an aerosol puff 1400 is applied to the extrathoracic module representing the mouth. After a hold of 1 second 1410, an air inhalation curve including two complete inhalation-exhalation cycles 1420, 1430 is applied to the extrathoracic module representing the nose. After each inhalation cycle, another hold of one second 1440, 1450 is applied. In this case, at the beginning of the inhalation-exhalation cycle 1420, the extrathoracic airway module representing the mouth contraction and aerosol puff is transferred to the airway module representing the lungs. The process is then repeated by applying aerosol puff and setting the input flow. According to one embodiment of the present invention, the inhalation topology module can use the actual and measured tabular aerosol inhalation curves and air inhalation curves to set the input flow to the respiratory system model.

[0234] Figure 15 Shown based on something similar to Figure 7Results of transient aerosol deposition in different regions of interest for a modular respiratory system model in a single-path configuration are shown in Figure 1. In this case, a four-region respiratory system model was simulated: an extrathoracic region, which includes extrathoracic airway modules representing the nose, mouth, and larynx; a bronchiolar region, which includes airway modules representing the generation of bronchial airways; a bronchiolar region, which includes airway modules representing the generation of bronchiolar airways; and an alveolar region, which includes airway modules representing the generation of alveolar airways in the user's respiratory system.

[0235] Figure 15 Results of particle number deposition curves in different regions of interest are shown. Figure 15 The results shown in Figure 3 were obtained by using the above 4-zone respiratory system model and by applying the Figure 14 The aerosol inhalation curve and airflow curve can be obtained from the input flow. Figure 15 As the aerosol transfers from the extrathoracic airway module, representing the mouth, to the airway module, representing the lungs, aerosol begins to deposit in the trachea at approximately t = 4 seconds 1500, i.e., airway generation 1. The respiratory system model captures deposition peaks 1510, 1520, 1530 that move deeper and deeper into the lungs over time during the first inhalation 1420. At the end of inhalation, the aerosol reaches the alveolar region and begins to deposit in the alveoli 1540. Secondary peaks in deposition 1550, 1560 are visible during the first exhalation phase 1420. Finally, additional deposition 1570 may also be observed during the second inhalation-exhalation cycle 1430 due to residual aerosol in the lung volume.

[0236] For the purposes of this specification and the appended claims, unless otherwise indicated, all numbers representing amounts, quantities, percentages, etc. should be understood to be modified by the term "about" in all cases. Moreover, all ranges include the disclosed maximum and minimum points, and include any intermediate ranges therein that may be specifically listed or may not be listed herein. In this case, the number A may be considered to include a numerical value within the general standard error for the measurement of the attribute modified by the number A. In certain cases used in the appended claims, the number A may deviate from the percentages listed above, provided that the amount of A deviation does not substantially affect the basic characteristics and novel features of the claimed invention. Moreover, all ranges include the disclosed maximum and minimum points, and include any intermediate ranges therein that may be specifically listed or may not be listed herein.

Claims

1. A system comprising an aerosol generating device and an inhalation guidance unit, the system include: One or more processors configured to perform the following steps: capturing an aerosol inhalation profile of a user of the aerosol generating device; feeding the captured aerosol inhalation curve to the respiratory system model; generating inhalation guidance instructions based on the respiratory system model; as well as The inhalation guidance instructions are provided to the user at the inhalation guidance unit.

2. The system of claim 1, wherein capturing the user's aerosol inhalation profile comprises determining in real time at least one of an inhalation-exhalation flow rate, a puff rate, and a lung volume change rate.

3. The system according to claim 1 or 2, wherein the respiratory system model is a modular respiratory system model for transient aerosol dosimetry, the model include: a plurality of airway modules, each airway module representing at least a portion of an airway generation of a respiratory system; as well as an inhalation topology module configured to set an input stream to the respiratory system model over time, wherein the input stream includes the captured aerosol inhalation curve, Each airway module is configured to determine deposition of inhaled aerosol over time in at least a portion of an airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module.

4. The system of claim 3, wherein each airway module comprises one or more component modules, wherein each component module represents a component of the respiratory system and comprises a port for input flow and a port for output flow.

5. The system of any one of claims 3 and 4, wherein several of the plurality of airway modules include respective alveolar modules, each alveolar module representing an alveolus of the respective airway module, wherein each alveolar module includes a port for receiving a flow.

6. A system according to any one of claims 3 to 5, wherein the respiratory system model is configured to determine, for each of a number of aerosol inhalation curves, the corresponding deposition of the inhaled aerosol in each airway module of the region of interest of the respiratory system over time to determine an optimal aerosol inhalation curve corresponding to a target aerosol deposition. 7 . The system of claim 6 , wherein the respiratory system model is further configured to generate the inhalation guidance instructions based on the optimal aerosol inhalation curve.

8. A system comprising an aerosol generating device and a setting determination unit, the system include: One or more processors configured to perform the following steps: at the settings determination unit, determining one or more settings of the aerosol generating device based on a respiratory system model; as well as The aerosol generating device is controlled to provide an aerosol based on the one or more settings determined by the setting determination unit.

9. The system of claim 8, wherein controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit comprises at least one of: adjusting at least one of a voltage and a current applied to a heating system of the aerosol generating device; adjusting the duration of power supplied to a heating system of the aerosol generating device; adjusting at least one of a pulse width and a pulse density of power supplied to a heating system of the aerosol generating device; adjusting an aerosol generation rate of the aerosol generating device; as well as The volume of aerosol produced with each puff from the aerosol generating device is adjusted.

10. The system of claim 8 or 9, wherein the one or more processors are configured to perform the following further steps: obtaining, at the settings determination unit, data relating to the aerosol generating device; and The respiratory system model is adapted based on the data related to the aerosol generating device.

11. The system of claim 10, wherein adapting the respiratory system model comprises at least one of: adapting aerosol data input to the respiratory system model based on aerosol data associated with the device; adapting the respiratory system model to aerosol data; adapting an aerosol inhalation profile based on an aerosol inhalation profile associated with the device or associated with one or more users of the device; as well as The target aerosol deposition is adapted based on a target aerosol deposition associated with the device or with one or more users of the device.

12. The system of claim 11, wherein the aerosol data for adapting the respiratory system model comprises at least one of the following: adjusting a vibration frequency of a grid of a heating system of the apparatus to determine one or more adjusted vibration frequencies at the setting determination unit; and adjusting a temperature of a grid of a heating system of the aerosol generating device to determine one or more adjusted temperatures of the grid at the setting determination unit, Wherein controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit comprises using at least one of the determined: the one or more adjusted vibration frequencies and the one or more adjusted temperatures of the grid.

13. The system according to one of claims 8 to 12, wherein the respiratory system model is a modular respiratory system model for transient aerosol dosimetry, the model include: a plurality of airway modules, each airway module representing at least a portion of an airway generation of a respiratory system; as well as an inhalation topology module configured to set an input stream to the respiratory system model over time, wherein the input stream includes the captured aerosol inhalation curve, Each airway module is configured to determine deposition of inhaled aerosol over time in at least a portion of an airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module.

14. A computer-implemented modular respiratory system model for transient aerosol dosimetry, the model include: a plurality of airway modules, each airway module representing at least a portion of an airway generation of a respiratory system; as well as an inhalation topology module configured to set an input stream to the respiratory system model over time, wherein the input stream comprises an aerosol inhalation curve, Each airway module is configured to determine the deposition of inhaled aerosol in at least a portion of the airway generation of the respiratory system represented by the airway module over time based on the input flow set by the inhalation topology module, so that the model can determine the deposition of inhaled aerosol in the region of interest of the respiratory system over time.

15. A computer-implemented method for generating a modular respiratory system model for transient aerosol dosimetry, the method include: Obtain physiological data related to the respiratory system; Obtain aerosol data related to aerosol characteristics; generating a plurality of airway modules based on the physiological data and the aerosol data, each airway module representing at least a portion of an airway generation of the respiratory system; generating an inhalation topology module for setting an input stream to the respiratory system model over time, wherein the input stream includes an aerosol inhalation curve; and The modular respiratory system model is generated based on combining the plurality of airway modules and the inhalation topology module.

Images