Method for Predicting Aerosol Dose Measurement in the Whole Lung

Abstract

A system comprising 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 a user's aerosol inhalation profile of the aerosol generating device, supplying the captured aerosol inhalation profile to a respiratory system model, creating an inhalation guidance instruction based on the respiratory system model, and providing the inhalation guidance instruction to the user with the inhalation guidance unit. A modular respiratory system model and a method for transient aerosol dosing are also provided.

Description

Technical Field

[0001] The present disclosure relates to models, methods, and systems for transient aerosol dose measurement. Specifically, the present disclosure relates to creating a modular respiratory system model for determining the deposition of inhaled aerosol over time in regions of interest in a user's respiratory system. Further, the present disclosure relates to an aerosol generating device that uses the created modular respiratory system model to control aerosol deposition in a user's respiratory system.

Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading cause of death worldwide. COPD results from long-term exposure to harmful gases and particles combined with individual factors. Lung delivery is the first choice for treating respiratory diseases and offers several advantages such as faster onset of action and easier non-invasive administration, and is of great concern for other diseases. A major challenge in inhaled toxicity or inhaled drug efficacy assessment is the proper and accurate determination of the delivered dose. The drug dosage can be determined experimentally by using an ideal shape (i.e., a bent pipe from Copley Scientific, an Alberta Idealized Throat, or an NGI) as described in CN202010101213, or by using a 3D printed lung cast extracted from a patient's micro-CT scan. The advantage of a micro-CT extracted 3D cast is the possibility of analyzing the shape of each individual patient. However, this technique is limited to the analysis of only the upper airway and it is impossible to capture and reproduce the aerosol behavior in the deeper alveolar lung. Thus, the analysis of aerosol inhalation is impaired. Further, experimentally reproducing the correct atmospheric environment within the lung cast is a technically difficult task. In particular, the atmospheric conditions related to humidity at the airway surface have proven to be a serious challenge. Finally, experiments tend to be expensive and time-consuming.

[0003] Alternatively, computational modeling is used to predict dosage, which includes computational fluid dynamics (CFD) models, and whole-lung dosimetry models such as the multiple-path particle dosimetry (MPPD) model and the International Commission on Radiological Protection (ICRP) human respiratory model. CFD enables very detailed analysis of realistic shapes extracted from patient scans, but is troubled by similar limitations to experiments in that it is limited to the upper airway only. Recently, attempts have been made to enable simulation of a representative whole airway tree by applying CFD to a simplified lung shape and assuming similarity between lung branch generations. However, CFD is still very labor-intensive, computationally demanding, and especially has a very long execution time. Whole-lung models such as MPPD have been established as the standard for inhaled dose estimation in the fields of toxicology and pharmaceuticals. However, such whole-lung models are simplified models that only have a partial representation of aerosol physics, which limits their application to simple non-reactive and non-generative aerosols. Furthermore, such models cannot capture the effects of different breathing profiles.

[0004] Therefore, there is a need to enhance current dosimetry models so that the deposition of inhaled aerosols in the respiratory system can be estimated under realistic conditions and in a computationally efficient manner. The dosimetry model is desirably capable of capturing all the major processes that determine aerosol transport and deposition over time. Furthermore, the dosimetry model is desirably computationally efficient while considering different aerosol properties, inhalation topologies, and individual lung morphologies. Furthermore, the dosimetry model should desirably provide instructions to the aerosol generator and provide guidance to the user for controlling aerosol deposition in the user's respiratory system. SUMMARY OF THE INVENTION

[0005] According to one aspect of the present invention, a system comprising an aerosol generating device and an inhalation guidance unit is provided, the system comprising one or more processors configured to perform the steps of capturing a user's aerosol inhalation profile of the aerosol generating device, supplying the captured aerosol inhalation profile to a respiratory system model, creating an inhalation guidance instruction based on the respiratory system model, and providing the inhalation guidance instruction to the user by the inhalation guidance unit.

[0006] By configuring the system to capture the user's aerosol inhalation profile and feedback it to the respiratory system model, the user of the aerosol generating device can interactively adapt their inhalation behavior based on the inhalation guidance instruction created based on the model and provided to the inhalation guidance unit, thereby enabling the user to reach the desired target aerosol deposition. Capturing the user's aerosol inhalation profile may be performed in real time. Supplying the captured aerosol inhalation profile to the respiratory system model may be performed in real time. Creating the inhalation guidance instruction and providing the inhalation guidance instruction to the user may be performed in real time. Thus, the user can interactively adapt their inhalation behavior in real time based on the created inhalation guidance instruction, thereby potentially enabling the user to reach the desired target aerosol deposition, generation, adsorption, and desorption in real time.

[0007] Capturing the user's aerosol inhalation profile may include determining at least one of the inspiratory-expiratory flow rate, smoking speed, and rate of change of lung volume in real time.

[0008] Determining the variability of inspiratory-expiratory flow rate, smoking rate, and lung volume in real time may be performed, for example, using a sensor that counts the inspiratory-expiratory cycles, a sensor that counts the aerosol smoking cycles, and a sensor that captures the flowing inspiratory-expiratory flow profile.

[0009] By capturing the user's aerosol inhalation profile in real time, the user's inhalation behavior can be realistically and rapidly adapted to match the desired target aerosol deposition using inhalation guidance instructions. The inhalation guidance instructions may, for example, interactively guide the user to adapt their inhalation behavior to reach the desired target aerosol deposition by indicating to the user an individualized optimal aerosol inhalation profile, inspiratory-expiratory flow rate, or smoking rate.

[0010] The respiratory system model can be a computer-implemented modular respiratory system model for transient aerosol dosimetry, where the model includes a plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system, and an inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow comprising an aerosol inhalation profile, and wherein each airway module is configured to determine the deposition of inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module 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 dose measurement that comprises a plurality of airway modules, each representing at least a portion of an airway generation of the respiratory system. The airway modules can function 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 lobe of the respiratory system.

[0012] Furthermore, by configuring an inhalation module to set an input flow with an aerosol inhalation profile into the respiratory system model over time, different individualized aerosol inhalation profiles captured by an aerosol generating device can be fed back and applied to the respiratory system model, the deposition of inhaled aerosol for each aerosol inhalation profile can be determined in the region of interest, and as a result the model can determine an optimal aerosol inhalation profile that results in the deposition of the target aerosol over time in the region of interest of the user's respiratory system. Specifically, the modular respiratory system model can determine transient aerosol dose measurements in different regions of interest of the respiratory system, including different airway generations. Additionally, the disclosed modular respiratory system model reduces the modeling effort and execution time compared to existing modeling techniques.

[0013] Each airway module may comprise one or more component modules, each component module representing a component of the respiratory system and comprising a port for inputting a flow and a port for outputting a flow.

[0014] Accordingly, an airway module represents at least a portion of an airway generation and includes components of the respiratory system. Accordingly, the components of the respiratory system may be components of an airway generation of the respiratory system. Such component modules can represent, for example, the trachea, a bifurcation, a branch, a bronchus, or a bronchiole.

[0015] Some of the plurality of airway modules may each include an alveolar module, where each alveolar module represents the number of alveoli in each airway module or generation, and each alveolar module may include a port for receiving the flow.

[0016] For example, the number of airway modules of the plurality of airway modules that may each include an alveolar module may represent deeper airway generations of the respiratory system. This provides a detailed comprehensive modeling of the respiratory system and allows for a more realistic representation of the lungs. This also allows for an 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 the corresponding deposition of inhaled aerosol over time in each airway module of the region of interest of the respiratory system for each aerosol inhalation profile of several aerosol inhalation profiles, in order to determine the optimal aerosol inhalation profile corresponding to the target aerosol deposition.

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

[0019] By determining the optimal aerosol inhalation profile and creating inhalation guidance instructions based on the optimal aerosol inhalation profile, the inhalation behavior of the user can be adapted to match the optimal aerosol inhalation profile corresponding to the desired target aerosol deposition. The inhalation guidance instructions may, for example, interactively guide the user to adapt their inhalation behavior to reach the desired target aerosol deposition by indicating to the user an individualized optimal aerosol inhalation profile, inhalation-exhalation flow rate, or smoking rate.

[0020] According to another aspect of the present invention, a system is provided that includes an aerosol generating device and a setting determination unit, the system including one or more processors configured to, in the setting determination unit: determine one or more settings of the aerosol generating device based on a respiratory system model; and control 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 further configured to, in the setting determination unit: obtain data related to the aerosol generating device; and adapt the respiratory system model based on the data related to the aerosol generating device.

[0022] Adapting the respiratory system model may include at least one of: adapting an aerosol data input to the respiratory system model based on aerosol data associated with the device; adapting aerosol data of the respiratory system model based on the settings of the device; 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; and adapting a target aerosol deposition based on a target aerosol deposition associated with the device or associated 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, the settings of the device, the aerosol inhalation profile, and the target aerosol deposition associated with the device or associated with one or more users of the device, this data can be used by the respiratory system model to adapt to 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 adjusting the vibration frequency of the mesh of the heating system of the device and determining, in the setting determination unit, one or more adjusted vibration frequencies, and adjusting the temperature of the mesh of the heating system of the aerosol generator and determining, in the setting determination unit, one or more adjusted temperatures of the mesh.

[0025] Controlling the aerosol generator to provide an aerosol based on one or more settings determined by the setting determination unit may include 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 generator to provide an aerosol based on one or more settings determined by the setting determination unit may include adjusting at least one of the voltage and current applied to the heating system of the aerosol generator, adjusting at least one of the periods of the power supplied to the heating system of the aerosol generator, adjusting at least one of the pulse width and pulse density of the power supplied to the heating system of the aerosol generator, adjusting the aerosol generation rate of the aerosol generator, and adjusting the volume of the aerosol generated per puff from the aerosol generator.

[0027] For example, the setting determination unit may automatically adjust the vibration frequency of the mesh of the heating system of the device so that a new vibration frequency corresponding to a new aerosol concentration or dose is determined. The setting determination unit may then adapt the aerosol data of the respiratory system model based on the new aerosol concentration or dose, and thus supply updated aerosol data corresponding to the new aerosol concentration or dose to the model to ensure that more accurate aerosol deposition in a specific region of interest, target lung depth level, or airway generation of the respiratory system model corresponding to the user of the device can be determined.

[0028] For example, the setting determination unit may automatically adjust the temperature of the mesh of the heating system of the device so that a new temperature of the mesh corresponding to the new aerosol concentration or dosage is determined. The setting determination unit may then adapt the aerosol data of the respiratory system model based on the new aerosol concentration or dosage, and thus supply the model with updated aerosol data corresponding to the new aerosol concentration or dosage to ensure that more accurate aerosol deposition in a specific region of interest, target lung depth level, or airway generation of the respiratory system model corresponding to the user of the device can be determined.

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

[0030] According to another aspect of the present invention, there is provided a computer-implemented modular respiratory system model for transient aerosol dose measurement, the model comprising a plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system, and an inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow comprising an aerosol inhalation profile, wherein each airway module is configured to determine the deposition of inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module, and as a result, the model is enabled to determine the deposition of inhaled aerosol over time in a region of interest of the respiratory system.

[0031] According to another aspect of the present invention, there is provided a computer-implemented method for creating 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, creating a plurality of airway modules based on the physiological data and the aerosol data, each airway module representing at least a part of an airway generation of the respiratory system, creating an inhalation topology module for setting an input flow to the respiratory system model over time, the input flow comprising an aerosol inhalation profile, and creating a 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 that includes an aerosol-forming substrate and a cartridge that includes an aerosol-forming substrate. In some embodiments, the aerosol generating device may heat the aerosol-forming substrate to facilitate the release of volatile compounds from the substrate. An electrically-operated aerosol generating device may comprise an atomizer, such as an electric heater, for heating the aerosol-forming substrate to form an aerosol.

[0033] As used herein, the term "aerosol-forming substrate" refers to a substrate having the ability to release volatile compounds that can form an aerosol. The volatile compounds may be released by heating or combusting the aerosol-forming substrate. As an alternative to heating or combustion, in some cases, the volatile compounds may be released by a chemical reaction or by a mechanical stimulus such as ultrasound. The aerosol-forming substrate may be solid or liquid, or may comprise both solid and liquid components. The aerosol-forming substrate may be part of an aerosol generating article.

[0034] The power source may comprise control electronics. The control electronics may comprise a microcontroller. The microcontroller is preferably a programmable microcontroller. The electrical circuit may include further electronic components. The electrical circuit may be configured to regulate the supply of power to the heater assembly. The power may be supplied continuously to the heater assembly after startup of the system, or may be supplied intermittently (e.g., each time smoking occurs). The 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 of the features of these examples may be combined with any one or more of the features of another example, embodiment, or aspect described herein.

[0036] Example 1: A computer-implemented modular respiratory system model for transient aerosol dose measurement, the model comprising: a plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system; an inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow comprising an aerosol inhalation profile; wherein each airway module is configured to determine the deposition of inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module, and as a result, the model is capable of determining the deposition of inhaled aerosol over time in a region of interest of the respiratory system. A computer-implemented modular respiratory system model for transient aerosol dose measurement. Example 2: The model according to Example 1, wherein each airway module comprises one or more component modules, each component module representing a component of the respiratory system and comprising a port for inputting a flow and a port for outputting a flow. Example 3: The model according to Example 2, wherein the components of the respiratory system include the trachea, tracheal bifurcation, branches, bronchi, or bronchioles. Example 4: The model according to any one of Examples 2 and 3, wherein the component module further comprises a volume port configured to adjust the volume expansion of the component module. Example 5: The model according to any one of Examples 2 and 4, wherein the component module further comprises a heat port configured to adjust the heat transfer of the component module. Example 6: The model according to any one of Examples 2 to 5, further comprising an input pressure drop element configured to apply a pressure drop to the flow input by the port of the component module in the airway module. Example 7: The model according to any one of Examples 2 to 6, further comprising an output pressure drop element configured to apply a pressure drop to the flow output by the port of the component module to determine an intermediate flow in each airway module. Example 8: The model according to any one of Examples 1 to 7, further comprising one or more extrapulmonary airway modules representing extrapulmonary airway components of the respiratory system. Example 9: The model according to Example 8, wherein the extrapulmonary airway components of the respiratory system include the mouth, nose, tracheal bifurcation, or larynx. Example 10: The model according to Example 9, wherein the first extrapulmonary airway module of the one or more extrapulmonary airway modules represents the mouth and the second extrapulmonary airway module of the one or more extrapulmonary airway modules represents the nose. Example 11: Setting the input flow to the respiratory system model over time includes setting the input flow over time to the first extrapulmonary airway module representing the mouth or to the second extrapulmonary airway module representing the nose, or setting the first input flow over time to the first extrapulmonary airway module and the second input flow over time to the second extrapulmonary airway module, where the first input flow and the second input flow constitute the input flow. The model according to Example 10. Example 12: The model according to any one of Examples 1 to 11, wherein the model includes a single-path configuration and each airway module of the single-path configuration is configured to represent an entire airway generation. Example 13: The model according to any one of Examples 1 to 12, wherein the model is based on a hybrid respiratory system model and one or more airway modules are configured to represent only a part of an airway generation. Example 14: The model according to Example 13, wherein each part of the airway generation represented by the airway module corresponds to a lobe of the respiratory system. Example 15: The model according to any one of Examples 8 to 14, further configured to combine a plurality of airway modules and one or more extrapulmonary airway modules, and to determine the branching of the input flow set in the respiratory system model from the extrapulmonary airway module of the respiratory system model to each airway module. Example 16: The model according to Example 15, wherein determining the branching of the input flow in each airway module includes dividing the flow input to the airway module by the number of branches parameter of the airway module to determine the flow in the airway module. Example 17: The model according to any one of Examples 1 to 16, wherein some of the plurality of airway modules each include a respective alveolar module, each alveolar module represents some of the alveoli of the respective airway module, and each alveolar module includes a port for receiving a flow. Example 18: The model according to Example 17, further configured to combine the alveolar module with the component modules in each airway module of some of the plurality of airway modules, and combining the alveolar module with the component modules includes determining the branching of the flow to the alveolar module. Example 19: The model according to Example 18, wherein determining the branching of the flow to the alveolar module includes multiplying the number of branches parameter by the intermediate flow of the airway module to determine the total intermediate flow of the airway module, and dividing the total intermediate flow of the airway module by the number of alveoli parameter of the airway module to determine the flow received by the port of the alveolar module. Example 20: The model according to any one of Examples 17 to 19, wherein the alveolar module further comprises a heat port configured to regulate the heat transfer of the alveolar module. Example 21: The model according to any one of Examples 17 to 20, wherein the alveolar module further comprises a volume port configured to regulate the volume expansion of the alveolar module. Example 22: The model according to Example 21, wherein setting the input flow over time to the respiratory system model includes setting a predetermined volume expansion over time at the volume port of the alveolar module or at the volume port of any component of the airway module, and the predetermined volume expansion over time corresponds to the rate of change of volume over time. Example 23: The model according to any one of Examples 1 to 22, further comprising an input module configured to receive input data. Example 24: The model according to Example 23, wherein the input data includes at least one of a selection of a region of interest of the respiratory system associated with the respiratory system of the subject, a target aerosol deposition delivered to one or more airway generations or regions of interest, each branch number parameter for the airway module, each alveolar number parameter for the alveolar module, aerosol data related to aerosol characteristics, and data related to some aerosol inhalation profiles. Example 25: The model according to Example 24, wherein input physiological data related to the respiratory system is used to adapt one or more airway modules, the physiological data includes geometric characteristics of one or more components of the respiratory system, and the geometric characteristics include at least one of branch length, branch diameter, bifurcation angle, and angle with respect to gravity. Example 26: The model according to any one of Examples 1 to 25, further configured to determine the corresponding deposition of inhaled aerosol over time in each airway module of the region of interest of the respiratory system to determine the optimal aerosol inhalation profile corresponding to the target aerosol deposition for each aerosol inhalation profile of some aerosol inhalation profiles. Example 27: The model described in Example 26, further configured to create inhalation guidance instructions based on an optimal aerosol inhalation profile. Example 28: The inhalation guidance instructions include at least one of an optimal aerosol inhalation profile, an inspiratory-expiratory flow rate, a smoking rate, and a variability rate of lung volume, and the inspiratory-expiratory flow rate, the smoking rate, and the variability rate of lung volume are based on the optimal aerosol inhalation profile. The model described in Example 27. Example 29: A method implemented on a computer for creating 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, and based on the physiological data and the aerosol data, creating a plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system, creating an inhalation topology module for setting an input flow to the respiratory system model over time, the input flow comprising an aerosol inhalation profile, and creating a modular respiratory system model based on combining the plurality of airway modules and the inhalation topology module. Example 30: The method described in Example 29, further comprising setting an input flow to the respiratory system model over time by the inhalation topology module. Example 31: The method described in Example 30, further comprising determining the deposition of inhaled aerosol over time in at least a part of the airway generations of the respiratory system represented by each airway module based on the set input flow. Example 32: The method according to any one of Examples 29 to 31, wherein each airway module comprises one or more component modules, each component module represents a component of the respiratory system, and comprises a port for inputting a flow and a port for outputting a flow. Example 33: The method according to Example 32, wherein the components of the respiratory system include the trachea, bronchial bifurcation, branches, bronchi, or bronchioles. Example 34: The method according to any one of Examples 32 and 33, wherein the component module further comprises a volume port configured to adjust the volume expansion of the component module. Example 35: The method according to any one of Examples 32 to 34, wherein the component module further comprises a heat port configured to adjust the heat transfer of the component module. Example 36: The method according to any one of Examples 32 to 35, wherein the airway module further comprises an input pressure drop element configured to apply a pressure drop to the flow input through the port of the component module. Example 37: The method according to any one of Examples 32 to 36, wherein each airway module further comprises an output pressure drop element configured to apply a pressure drop to the flow output through the port of the component module to determine an intermediate flow. Example 38: The method according to any one of Examples 29 to 37, further comprising one or more extrapulmonary airway modules representing one or more extrapulmonary airway components of the respiratory system. Example 39: The method according to Example 38, wherein the extrapulmonary airway components of the respiratory system include the mouth, nose, bronchial bifurcation, or larynx. Example 40: The method according to Example 39, wherein the first extrapulmonary airway module of the one or more extrapulmonary airway modules represents the mouth and the second extrapulmonary airway module of the one or more extrapulmonary airway modules represents the nose.

[0037] Example 41: Setting the input flow to the respiratory system model over time includes setting the input flow over time to a first extrathoracic airway module representing the mouth or a second extrathoracic airway module representing the nose, 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, where the first input flow and the second input flow are the methods described in Example 40 that constitute the input flow. Example 42: The method according to any one of Examples 29 to 41, wherein the model includes a single-path configuration and each airway module of the single-path configuration is configured to represent the entire airway generation. Example 43: The method according to any one of Examples 29 to 42, wherein the model is based on a hybrid respiratory system model and one or more airway modules are configured to represent only a part of the airway generation. Example 44: The method according to Example 43, wherein each part of the airway generation represented by the airway module corresponds to a lobe of the respiratory system. Example 45: The method according to any one of Examples 38 to 44, further configured to combine a plurality of airway modules and one or more extrathoracic airway modules and to determine the branching of the input flow set to the respiratory system model from the extrathoracic airway module of the respiratory system model to each airway module. Example 46: The method according to Example 45, wherein determining the branching of the input flow within each airway module includes dividing the flow input to the airway module by the branch number parameter of the airway module. Example 47: The method according to any one of Examples 29 to 46, wherein some of the plurality of airway modules each include an alveolar module, each alveolar module represents some of the alveoli of the respective airway module, and each alveolar module includes a port for receiving the flow. Example 48: The alveolar module is further configured to combine with component modules within each airway module of several airway modules, and combining the alveolar module with the component modules includes determining the branching of the flow into the alveolar module, the method described in Example 47. Example 49: Determining the branching of the flow into the alveolar module includes multiplying the number of branches parameter by the intermediate flow 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 ports of the alveolar module, the method described in Example 48. Example 50: The method according to any one of Examples 47 to 49, wherein the alveolar module further comprises a volume port configured to regulate the volume expansion of the alveolar module. Example 51: The method according to any one of Examples 47 to 50, wherein the alveolar module further comprises a heat port configured to regulate the heat transfer of the alveolar module. Example 52: Setting the input flow into the respiratory system model over time includes setting a predetermined volume expansion over time at the volume port of the alveolar module or the volume port of any component of the airway module, and the predetermined volume expansion over time corresponds to the rate of change of volume over time, the method described in Example 51. Example 53: Setting the input flow into the respiratory system model over time includes setting a predetermined volume expansion over time at the volume port of any component of the airway module, and the predetermined volume expansion over time corresponds to the rate of change of volume over time, the method described in Example 34. Example 54: The method according to any one of Examples 29 to 53, further comprising obtaining at least one of selection of a region of interest of the respiratory system, targeted aerosol deposition delivered to one or more airway generations or regions of interest, and data related to several aerosol inhalation profiles. Example 55: For each of several aerosol inhalation profiles, further configured to determine the corresponding deposition of inhaled aerosol over time in each airway module of the region of interest of the respiratory system to determine the optimal aerosol inhalation profile corresponding to the target aerosol deposition, the method according to any of Examples 29 to 54. Example 56: The method according to Example 55, further configured to create an inhalation guidance instruction based on the optimal aerosol inhalation profile. Example 57: The method according to Example 56, wherein the inhalation guidance instruction includes at least one of the optimal aerosol inhalation profile, the inspiratory-expiratory flow rate, the smoking rate, and the variability of the lung volume, and the inspiratory-expiratory flow rate, the smoking rate, and the variability of the lung volume are based on the optimal aerosol inhalation profile. Example 58: A system comprising an aerosol generating device and an inhalation guidance unit, configured to use one of the models of Examples 1 to 28. Example 59: A system comprising an aerosol generating device and an inhalation guidance unit, wherein the system comprises a memory for storing one of the models of Examples 1 to 28. Example 60: A system according to any of Examples 58 and 59, comprising one or more processors configured to perform the steps of capturing the user's aerosol inhalation profile of the aerosol generating device, supplying the captured aerosol inhalation profile to a respiratory system model, creating an inhalation guidance instruction based on the respiratory system model, and providing the inhalation guidance instruction to the user by an inhalation guidance unit. Example 61: The system according to Example 60, wherein capturing the user's aerosol inhalation profile includes determining at least one of the inspiratory-expiratory flow rate, the smoking rate, and the variability of the lung volume in real time. Example 62: The system according to Example 61, wherein determining the intake-exhalation flow rate is based on at least one of a sensor that counts the intake-exhalation cycle or a sensor that captures the flow intake-exhalation flow profile. Example 63: The system according to Example 61, wherein the aerosol generating device comprises a sensor for counting the aerosol smoking cycle, and determining the smoking rate is based on the counted aerosol smoking cycles. Example 64: A system comprising an aerosol generating device and a setting determination unit, wherein the system is configured to use one of the models of Examples 1 to 28. Example 65: A system comprising an aerosol generating device and a setting determination unit, wherein the system comprises a memory for storing one of the models of Examples 1 to 28. Example 66: The system according to any of Examples 64 and 65, comprising one or more processors configured to perform a step of determining one or more settings of the aerosol generating device based on a respiratory system model and a step of controlling the aerosol generating device to provide an aerosol based on the one or more settings. Example 67: Controlling the aerosol generating device to provide an aerosol based on 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 periods 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 the aerosol generated per puff from the aerosol generating device. The system according to Example 66. Example 68: One or more processors are configured to perform a further step of obtaining data related to the aerosol generator and a further step of adapting a respiratory system model based on the data related to the aerosol generator, the system according to any of Examples 66 and 67. Example 69: Adapting the respiratory system model includes at least one of: adapting an 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 profile of the inhalation topology module based on an aerosol inhalation profile associated with the device or one or more users of the device; adapting the target aerosol deposition based on a target aerosol deposition associated with the device or one or more users of the device, the system according to Example 68. Example 70: Adapting the aerosol data of the respiratory system model includes at least one of: adjusting the vibration frequency of the mesh of the heating system of the device to determine one or more adjusted vibration frequencies; adjusting the temperature of the mesh of the heating system of the aerosol generator to determine one or more adjusted temperatures of the mesh, wherein controlling the aerosol generator to provide an aerosol based on one or more settings determined by a 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 mesh, the system according to Example 69. Example 71: A system comprising an aerosol generating device and an inhalation guidance unit, the system comprising one or more processors configured to perform the steps of: capturing an aerosol inhalation profile of a user of the aerosol generating device; supplying the captured aerosol inhalation profile to a respiratory system model; creating an inhalation guidance instruction based on the respiratory system model; and providing the inhalation guidance instruction to the user by the inhalation guidance unit. Example 72: The system of claim 71, wherein capturing the aerosol inhalation profile of the user includes determining at least one of an inspiration-expiration flow rate, a smoking rate, and a rate of change of lung volume in real time. Example 73: The respiratory system model is a modular respiratory system model for transient aerosol dose measurement, the model comprising a plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system, and an inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow comprising the captured aerosol inhalation profile, wherein each airway module is configured to determine the deposition of inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module. The system according to Example 71 or 72. Example 74: The system of Example 73, wherein each airway module comprises one or more component modules, each component module representing a component of the respiratory system and comprising a port for inputting a flow and a port for outputting a flow. Example 75: The system according to any one of Examples 73 and 74, wherein some of the plurality of airway modules each include an alveolar module, each alveolar module representing the alveoli of a respective airway module, and each alveolar module including a port for receiving a flow. Example 76: The respiratory system model is configured to determine the corresponding deposition of inhaled aerosol over time in each airway module of the region of interest of the respiratory system for each of several aerosol inhalation profiles to determine the optimal aerosol inhalation profile corresponding to the target aerosol deposition, the system according to any one of Examples 73 to 75. Example 77: The system according to Example 76, wherein the respiratory system model is further configured to create an inhalation guidance instruction based on the optimal aerosol inhalation profile. Example 78: A system comprising an aerosol generator and a setting determination unit, the system comprising one or more processors, wherein the setting determination unit determines one or more settings of the aerosol generator based on a respiratory system model, and controls the aerosol generator to provide an aerosol based on the one or more settings determined by the setting determination unit. Example 79: Controlling the aerosol generator to provide an aerosol based on 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 generator, adjusting at least one of the periods of power supplied to the heating system of the aerosol generator, adjusting at least one of the pulse width and pulse density of the power supplied to the heating system of the aerosol generator, adjusting the aerosol generation rate of the aerosol generator, and adjusting the volume of aerosol generated per puff from the aerosol generator, the system according to Example 78. Example 80: One or more processors are configured in a determination unit to perform a further step of obtaining data related to the aerosol generator and a further step of adapting a respiratory system model based on the data related to the aerosol generator, the system according to any of Examples 78 and 79. Example 81: Adapting the respiratory system model includes at least one of: adapting an 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 an aerosol inhalation profile based on an aerosol inhalation profile associated with the device or one or more users of the device; and adapting a target aerosol deposition based on a target aerosol deposition associated with the device or one or more users of the device, the system according to Example 80. Example 82: Adapting the aerosol data of the respiratory system model includes at least one of: adjusting the vibration frequency of the mesh of the heating system of the device and determining, in a determination unit, one or more adjusted vibration frequencies; and adjusting the temperature of the mesh of the heating system of the aerosol generator and determining, in a determination unit, one or more adjusted temperatures of the mesh. Here, controlling the aerosol generator to provide an aerosol based on one or more settings determined by the determination unit includes using at least one of the determined one or more adjusted vibration frequencies and one or more adjusted temperatures of the mesh, the system according to Example 81. Example 83: The breathing system model is a modular breathing system model for transient aerosol dose measurement. The model includes a plurality of airway modules, each airway module representing at least a part of an airway generation of the breathing system, and an inhalation topology module configured to set an input flow to the breathing system model over time, the input flow comprising a captured aerosol inhalation profile. Each airway module is configured to determine the deposition of inhaled aerosol over time in at least a part of the airway generation of the breathing system represented by the airway module based on the input flow set by the inhalation topology module. The system according to one of Examples 78 - 82. Example 84: A computer - implemented modular breathing system model for transient aerosol dose measurement. The model includes a plurality of airway modules, each airway module representing at least a part of an airway generation of the breathing system, and an inhalation topology module configured to set an input flow to the breathing system model over time, the input flow comprising an aerosol inhalation profile. Each airway module is configured to determine the deposition of inhaled aerosol over time in at least a part of the airway generation of the breathing system represented by the airway module based on the input flow set by the inhalation topology module. As a result, the model is capable of determining the deposition of inhaled aerosol over time in the region of interest of the breathing system. A computer - implemented modular breathing system model for transient aerosol dose measurement. Example 85: A method implemented on a computer for creating a modular respiratory system model for transitional aerosol dose measurement, the method comprising: obtaining physiological data related to the respiratory system; obtaining aerosol data related to aerosol characteristics; creating a plurality of airway modules based on the physiological data and the aerosol data, each airway module representing at least a part of an airway generation of the respiratory system; creating an inhalation topology module for setting an input flow to the respiratory system model over time, the input flow comprising an aerosol inhalation profile; and creating a modular respiratory system model based on combining the plurality of airway modules and the inhalation topology module.

[0038] Hereinafter, embodiments will be further described with reference to the drawings.

Brief Description of the Drawings

[0039]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

[0040] FIG. 1 illustrates an airway module 100 associated with a modular respiratory system model and representing at least a part of the airway generations of the respiratory system. The airway module 100 includes an input flow port 105a and an output flow port 105b. The airway module 100 further includes a component module 130 that represents a component of the respiratory system and includes a port 130a for inputting a flow and a port 130b for outputting a flow. The components of the respiratory system may include the trachea, tracheal bifurcation, branches, bronchi, or bronchioles.

[0041] 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 using element 110.

[0042] The branch number parameter represents the number of branches within the airway module. The branch number parameter of the airway module 100 may be based on physiological data related to the respiratory system. Thus, the airway module represents all similar components and all parallel branches in at least a portion of the airway generations of the respiratory system.

[0043] Physiological data related to the respiratory system can be used to adapt the airway module according to the physiological data of the subject's respiratory system. The subject may be a human or an animal. The physiological data may include geometric characteristics of one or more components of the respiratory system. The geometric characteristics may include at least one of branch length, branch diameter, branching angle, and angle with respect to gravity.

[0044] The geometric characteristics of one or more components may be based on at least one of the volume of lung expansion, body size, X-ray of the respiratory system, and detailed airway tree morphometry. The geometric characteristics may be based on at least one of height, age, gender, and weight. The geometric characteristics may be based on the general geometric characteristics of one or more components. The branch number parameter of the airway module is 1 or more.

[0045] The airway module 100 further includes an input pressure drop element 120 configured to apply a pressure drop to the flow input by the 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 opposite to the flow caused by the frictional force within the airway. The pressure drop element 120 is configured to model the resistance to the flow input by the port 130a of the component module 130.

[0046] Each airway module 100 further 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 an intermediate flow. The pressure drop element 140 is configured to model the resistance to the flow output by port 130b of component module 130.

[0047] The modular respiratory system model is further configured to determine the output flow through port 105b of airway module 100 by using element 150 to multiply the intermediate flow by the branch number parameter of the airway module and determine the output flow through port 105b of airway module 100.

[0048] Some airway modules representing deeper airway generations of the respiratory system further include an alveolar module 170 represented by the dashed square in FIG. 1. The alveolar module 170 represents a cluster of alveoli of the airway module and includes a port 170a for receiving the flow. The modular respiratory system model may combine the alveolar module 170 with the component module 130 in each airway module of some airway modules. Combining the alveolar module 170 with the component module 130 includes determining the branching of the flow to the alveolar module 170. The alveolar number parameter of the airway module may be based on physiological data related to the respiratory system.

[0049] Determining the branching of the 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.

[0050] When the airway module includes the alveolar module, the modular respiratory system model is further configured to determine the output flow through port 105b of the airway module 100 by using element 150 to multiply the intermediate flow by a constant equal to the difference between the branch number parameter and the alveolar number parameter to determine the output flow through port 105b of the airway module 100.

[0051] The component module 130 further includes a volume port 130c configured to adjust the volume expansion of the component module 130. The volume port 130c can be configured to set the input flow over time to the respiratory system model by setting a predetermined volume expansion over time at the volume port 130c of the component module 130 of the airway module 100. The predetermined volume expansion over time corresponds to the rate of change of the volume over time. The component module 130 further includes one heat port 130d configured to adjust the heat transfer within the component module.

[0052] The alveolar module 170 further includes a volume port 170c configured to adjust the volume expansion of the alveolar module. The volume port 170c can be configured to set the input flow over time to the respiratory system model 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 the rate of change of the volume over time. The alveolar module 170 further includes one heat port 170d configured to adjust the heat transfer in the alveolar module.

[0053] The physical and chemical behavior of an aerosol can be represented by the publicly available AeroSolved model and its system implementation, AeroSolvedSystem (www.aerosolved.com, pmpsa-cfd GitHub). Well-known major processes and conservation laws are described in the basic elements of AeroSolvedSystem adapted to be used as either a component module, an alveolar module, or an extra-thoracic airway module. Each of these modules can be specialized to represent individualized or personalized components of the respiratory system by selecting corresponding physiological data that includes individualized geometric characteristics and by selecting corresponding aerosol data related to aerosol properties.

[0054] Component module 130 may be a model of a component of the respiratory system. Alveolar module 170 may be a model of a cluster of alveoli of the respiratory system. Component module 130, as well as alveolar module 170, may each be configured to impose mass conservation of the aerosol mixture at an appropriate time. The aerosol within the model can be in the gas phase or the liquid / solid phase. Mass conservation of the aerosol mixture at an appropriate time defines the instantaneous rate of change of the total aerosol mixture mass in the volumes of the gas phase and the liquid / solid phase based on the aerosol mixture mass flux at the volume ports of the model and based on the source terms for the liquid / solid and vapor passing through the volume walls of the model, where the consideration of the source terms and processes for the liquid / solid and vapor passing through the volume walls of each model includes deposition, condensation / evaporation, and adsorption / desorption. This is shown by the following equation (1):

Number

[0055] Component module 130, as well as alveolar module 170, may each be configured to impose mass conservation of the aerosol mixture on each aerosol species in the gas phase at an appropriate time. The mass conservation of the aerosol mixture for each aerosol species in the gas phase is defined as the instantaneous rate of change of the total aerosol mixture mass of the aerosol species in the gas phase volume based on the aerosol mixture mass flux at the volume port of the model and on the source terms for vapor through the volume section walls of the model. The source terms for vapor through the volume section walls of each model consider processes including deposition, condensation / evaporation, adsorption / desorption, and nucleation. This is shown by Equation (2) below:

Equation

[0056] Component module 130, as well as alveolar module 170, may each be configured to impose mass conservation of the aerosol mixture on each aerosol species in the liquid / solid phase at an appropriate time, and the mass conservation of the aerosol mixture for an appropriate time for each aerosol species in the liquid / solid phase is defined as the instantaneous rate of change of the total aerosol mixture mass in the liquid / solid phase volume based on at least one of the aerosol mixture mass fluxes at the volume port of each model and on the source terms for vapor through the volume section walls of the model, and the source terms for vapor through the volume section walls of the model consider processes including deposition, condensation / evaporation, and nucleation. This is captured by Equation (3) below:

Equation

[0057] The component module 130 and the alveolar module 170 can each be configured to impose particle number density conservation at an appropriate time for each particle size distribution associated with a diameter representing an evolving distribution of fixed shape. The particle number density conservation at an appropriate time is defined based on at least one of the aerosol mixture mass fluxes at the volume ports of the model, and based on the source terms for the liquid / solid and vapor through the volume part walls of each model, where the source terms for the liquid / solid and vapor through the volume part walls of the model consider processes including deposition, condensation / evaporation, nucleation, and coagulation. This is shown by the following equation (4).

Number

[0058] Processes including deposition, condensation / evaporation, and adsorption / desorption are based on aerosol data related to aerosol characteristics. The aerosol data related to aerosol characteristics may include data related to one or more of the aerosol species, the distribution of aerosol droplets, and the material characteristics for the aerosol model.

[0059] The aerosol model may include a multi-path particle dosimetry model, MPPD, a dosimetry model related to aerosol physics, and a dosimetry model not directly related to aerosol physics. The dosimetry model not directly related to aerosol physics may include a model explaining mucociliary clearance.

[0060] In some embodiments, the overall transient modeling of aerosol transport achieved by the model may further include modeling of chemical reactions. Thus, equations (1)-(4) can be adapted to further include terms explaining chemical reactions.

[0061] Therefore, based on the above description including equations (1)-(4), complete aerosol physics can be modeled. Furthermore, dynamic and fully transient modeling of aerosol transport, generation, and deposition in an individualized whole-lung geometry can be achieved at an optimized computational cost. In embodiments, deposition of aerosol droplets / particles is determined by modeling the aerosol rigorously in the droplet / particle phase. In other embodiments, deposition of gas / vapor is determined by modeling the aerosol in both the droplet / particle phase and the gas / vapor phase, including modeling of the processes of adsorption / desorption and condensation / evaporation, but is still referred to by the term deposition. FIG. 2 illustrates a tracheal bifurcation module 200 comprising a component module 230 representing a tracheal bifurcation. The component module comprises an input port 230a, an output port 230b, a volume port 230c, and a heat port 230d. The tracheal bifurcation module further comprises two input ports 205a and 205b used to input flow and one output port 205c used to output flow. The tracheal bifurcation module 200 further comprises pressure drop elements 210 and 220 used to apply a pressure drop to the flow input by the input port 230a of the component module 200 via respective ports 205a and 205b of the tracheal bifurcation module. The tracheal bifurcation module 200 further comprises a pressure drop element 240 used to apply a pressure drop to the flow output by the output port 230b of the component module. The characteristics of the tracheal 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.

[0062] FIG. 3 illustrates a tracheal bifurcation module 300 including a component module 330 representing a tracheal bifurcation. The component module includes an input port 330a, an output port 330b, a volume port 330c, and a heat port 330d. The tracheal bifurcation module further includes one input port 305a used to input a flow and two output ports 305b and 305c used to output a flow. The tracheal bifurcation module 300 further includes a pressure drop element 340 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 tracheal bifurcation module. The tracheal bifurcation module 300 further includes pressure drop elements 310 and 320 used to apply a pressure drop to each of the flows output by the output port 330b of the component module 300 exiting the tracheal bifurcation module via the respective ports 305b and 305c. The characteristics of the tracheal 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.

[0063] FIG. 4 illustrates an extra-thoracic combination module 400 including a combination of extra-thoracic airway modules 410, 420, 200a, and 430 that can be configured to represent extra-thoracic airway components of the respiratory system. The extra-thoracic airway components of the respiratory system may be the mouth, nose, tracheal bifurcation, or larynx. For example, the extra-thoracic airway module 410 may be configured to represent the nose, the extra-thoracic airway module 420 may be configured to represent the mouth, and the extra-thoracic airway module 430 may be configured to represent the larynx. The extra-thoracic airway module 200a is based on a combination 200 of airway modules and can be configured to represent a tracheal bifurcation used to combine the flows from the extra-thoracic airway module 410 representing the nose and the extra-thoracic airway module 420 representing the mouth.

[0064] FIG. 5 illustrates a single-path configuration module 500 that includes a combination of airway modules 100a - 100d associated with a single-path respiratory system model. Each of the airway modules 100a - 100d is based on the airway module 100 of FIG. 1. Each airway module represents the entire airway generations corresponding to both the left and right lungs of the respiratory system. For example, airway module 100a may be configured to represent the trachea or airway generation 1 of the respiratory system, airway module 100b may be configured to represent the bronchial airway generation, airway generation 2, airway module 100c may represent the bronchiolar airway generation, and airway module 100d may be configured to represent the alveolar airway generation of the respiratory system. Since airway module 100d includes alveolar module 170, it may represent the alveolar generation.

[0065] Since all of the airway modules 100a - 100d are based on airway module 100, the single-path configuration module 500 presents a computationally efficient implementation of the respiratory system model. Thus, the model includes only a single flow path to be computed and shows a computationally efficient way to determine aerosol deposition, generation, adsorption, and desorption for any desired depth level of the airway generations of the respiratory system.

[0066] According to another embodiment of the present invention, different sections of the respiratory system may be modeled with detailed branches in a branching pattern. This detailed modeling may be extended to deeper airway generations based on the availability of individualized data, the need for more detail, and the availability of computational power.

[0067] FIG. 6 illustrates a hybrid module comprising a combination 600 of airway modules 610-640, single path configuration modules 500a-500e, and tracheal bifurcation modules 300a-300d associated with a hybrid respiratory system model. Each of the airway modules 610-640 may be based on the airway module 100 of FIG. 1. Each airway module represents a part of an airway generation, and each airway module may be configured to represent a part of the airway generation corresponding to a lobe of the respiratory system. In particular, each airway module may be configured to represent a part of the airway generation corresponding to one of the one or more left lobes of the left lung of the respiratory system, or a part of the airway generation corresponding to one of the one or more right lobes of the right lung of the respiratory system.

[0068] For example, the airway module 610 may be configured to represent the trachea or airway generation 1. The tracheal bifurcation module 300a may be configured to represent a bifurcation point based on the tracheal bifurcation module 300 of FIG. 3. The airway module 620 may be configured to represent a branch of the airway generation corresponding to the upper right lobe of the right lung. The airway module 640 may be configured to represent a branch of the airway generation corresponding to the upper left lobe of the left lung of the respiratory system. The tracheal bifurcation modules 300b, 300c, and 300d may each be configured to represent a bifurcation point based on the tracheal bifurcation module 300 of FIG. 3. The single path configuration module 500a connected to one port of the tracheal bifurcation module 300b is based on the single path configuration module 500 of FIG. 5. The module 500a may comprise a combination of airway modules that may be configured to represent the remaining portion of the upper right lobe of the right lung of the respiratory system. The remaining portion of the upper right lobe may include bronchial airway generations, bronchiolar airway generations, and alveolar airway generations.

[0069] The airway module 630 can be configured to represent the branches of the airway generations 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 tracheal bifurcation module 300c is similar to the module 500 in FIG. 5 based on the single-path respiratory system model. The module 500b can include a combination of airway modules that can be configured to represent the remaining part of the right middle lobe of the right lung of the respiratory system. The remaining part of the right middle lobe can include bronchial airway generations, bronchiolar airway generations, and alveolar airway generations.

[0070] The single-path configuration module 500c connected to one port of the tracheal bifurcation module 300c is based on the single-path configuration module 500 in FIG. 5. The module 500c can 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 can include bronchial airway generations, bronchiolar airway generations, and alveolar airway generations.

[0071] The single-path configuration module 500d connected to the airway module 300d is based on the single-path configuration module 500 in FIG. 5. The module 500d can include a combination of airway modules that can be configured to represent the remaining part of the left upper lobe of the left lung of the respiratory system. The remaining part of the left upper lobe can include bronchial airway generations, bronchiolar airway generations, and alveolar airway generations.

[0072] The single-path configuration module 500e connected to one port of the tracheal bifurcation module 300d is based on the single-path configuration module 500 in FIG. 5. The module 500e can 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 can include bronchial airway generations, bronchiolar airway generations, and alveolar airway generations.

[0073] FIG. 7 illustrates a modular respiratory system model 700 based on a single-path configuration. 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 may be set based on an aerosol inhalation profile. The model 700 further includes an extra-thoracic combination module 400a comprising a combination of extra-thoracic airway modules configured to represent the extra-thoracic airway components of the respiratory system based on the extra-thoracic combination module 400. The extra-thoracic components may include the nose, mouth, tracheal bifurcation, or larynx. The model 700 further includes a module 500f including a combination of airway modules associated with a single-path respiratory system model based on the single-path configuration module 500 of FIG. 5. Each airway module of the combination of airway modules may be configured to represent at least a part of an airway generation of the respiratory system. Each airway module of the combination of airway modules may be configured to determine the deposition, generation, adsorption, and desorption of inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module 710, such that as a result, the model 700 is enabled to determine the deposition, generation, adsorption, and desorption of inhaled aerosol over time in the region of interest of the respiratory system.

[0074] Setting the input flow to the respiratory system model 700 over time may include setting the input flow over time to a first extra-thoracic airway module representing the mouth or to a second extra-thoracic airway module representing the nose, or setting a first input flow over time to the first extra-thoracic airway module and a second input flow over time to the second extra-thoracic airway module, where the first input flow and the second input flow constitute the input flow.

[0075] Setting the input flow over time to the respiratory system model 700 may further include setting the conditions of the input flow, including setting at least one of the input flow topology and the input flow thermophysical conditions. Setting the input flow thermophysical conditions may include setting at least one of the input flow temperature and the input flow aerosol concentration characteristics.

[0076] Model 700 further includes combining a plurality of airway modules and one or more extrapulmonary airway modules.

[0077] Combining a plurality of airway modules may include determining, by the inhalation topology module 710, the branching of the input flow set in the model from the extrapulmonary airway module to each airway module of 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.

[0078] The flow of the respiratory system model is a bidirectional flow that flows forward along the flow path during a first period and backward along the flow path during a second period. The flow of the respiratory system model may flow from the extrapulmonary airway module to the airway module or from the airway module to the extrapulmonary airway module to capture a complete inhalation-exhalation cycle.

[0079] Combining a plurality of airway modules may 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 may further include an interface module for establishing a closed-loop interaction with an external model.

[0080] Figure 8 illustrates a modular respiratory system model 800 based on a hybrid respiratory system model. The model includes an inhalation topology module 710 configured to set an input flow to the respiratory system model over time, the input flow including an aerosol inhalation profile. The model further includes an extra-thoracic airway module that can be configured to represent the extra-thoracic airway components of the respiratory system based on the extra-thoracic combination module 400, the extra-thoracic combination module 400b. The extra-thoracic components can include the nose, mouth, tracheal bifurcation, or larynx.

[0081] The model further includes a hybrid module 600a that represents a hybrid module based on the hybrid module 600 of FIG. 6 and includes a hybrid combination of airway modules associated with the hybrid respiratory system model. Each airway module is based on the airway module 100 of FIG. 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 FIG. 6. Each airway module of the hybrid combination of airway modules can be configured to determine the deposition, or even deposition, generation, adsorption, 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 flow set by the inhalation topology module 810, such that the model 800 is capable of determining the deposition, or even deposition, generation, adsorption, and desorption of inhaled aerosol over time in the region of interest of the respiratory system. Setting the input flow to the respiratory system model over time can include setting the input flow to the extra-thoracic airway module representing the mouth or nose over time.

[0082] Model 800 may further include combining a plurality of airway modules and one or more extrathoracic airway modules. Combining the plurality of airway modules may include determining, by the inhalation topology module 710, the branching of the input flow set in the model from the extrathoracic airway module to each airway module of 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 setting it to be divided among the input ports of the subsequent modules based on physiological data related to the respiratory system.

[0083] The flow of the respiratory system model can be a bidirectional flow. The flow of the respiratory system model may flow from the extrathoracic airway module to the airway module or from the airway module to the extrathoracic airway module.

[0084] Combining the plurality of airway modules may 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.

[0085] The modular respiratory system models 700, 800 may further include an interface module for establishing a closed-loop interaction with an external model. For example, the respiratory system models 700, 800 that calculate the dynamic generation, transport, and deposition of aerosols within the region of interest of the lung can be connected to a physiological model (PBPK) to predict the biological effects of inhaled aerosols. The connection between the respiratory system models 700, 800 and the PBPK model can be implemented using an interface element (not shown in FIGS. 7 and 8) that processes the output of the respiratory system models 700, 800 and calculates the input for the PBPK. The interface element can also be used to include additional dosimetry models that may not be directly related to aerosol physics, such as modeling of mucociliary clearance.

[0086] Model 700 or 800 may be configured to determine the corresponding deposition of inhaled aerosol over time in each airway module of the regions of interest of the respiratory system for each of several aerosol inhalation profiles to determine the optimal aerosol inhalation profile corresponding to the target aerosol deposition.

[0087] Model 700 or 800 may be further configured to create an inhalation guidance instruction based on the optimal aerosol inhalation profile. The inhalation guidance instruction includes at least one of the optimal aerosol inhalation profile, the inspiratory-expiratory flow rate, the smoking rate, and the variability of the lung volume, and the inspiratory-expiratory flow rate, the smoking rate, and the variability of the lung volume are based on the optimal aerosol inhalation profile.

[0088] The system implementing Model 700 or 800 may be further configured to obtain data related to the aerosol generating device and adapt the respiratory system model based on the data related to the aerosol generating device.

[0089] The data related to the aerosol generating device may include at least one of the type of the device, the characteristics of the device, the settings of the device, the aerosol characteristics associated with the device, the target aerosol deposition associated with the device or one or more users of the device, and the aerosol inhalation profile associated with the device or one or more users of the device. The type of the device may be obtained from a list of devices provided on at least inhalers and electronic smoking devices.

[0090] Adapting the respiratory system model can include at least one of: adapting the aerosol data of the respiratory system model based on the aerosol data associated with the device; adapting the aerosol data of the respiratory system model; adapting the aerosol inhalation profile of the inhalation topology module based on the aerosol inhalation profile associated with the device or one or more users of the device; and adapting the target aerosol deposition based on the target aerosol deposition associated with the device or one or more users of the device.

[0091] Adapting the aerosol data of the respiratory system model can include adjusting the vibration frequency of the mesh of the 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 can include adjusting the temperature of the mesh of the heating system of the aerosol generator to determine one or more adjusted temperatures of the mesh.

[0092] Model 700, or 800, may be further configured to output an instruction to the aerosol generator. The instruction may be transmitted to the control unit 1020 via the communication module 1030 of the aerosol generator. The instruction may be checked and processed by the control unit 1020 and then executed by a designated component of the aerosol generator (e.g., the mesh of the heating system). The instruction may include at least one of one or more adjusted vibration frequencies of the mesh and one or more adjusted temperatures.

[0093] FIG. 9 is a flowchart showing a method 800 implemented on a computer for creating modular respiratory system models 700, 800 for transient aerosol dose measurement. The modular respiratory system models 700, 800 enable real-time modeling of the evolution of aerosol dose measurement over time for an individualized overall lung shape of the respiratory system. The method starts at step 910 where physiological data related to the respiratory system is acquired. As described above, the physiological data related to the respiratory system may include geometric characteristics of one or more components of the respiratory system, and the geometric characteristics include at least one of branch length, branch diameter, branching angle, and angle with respect to gravity.

[0094] In 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 aerosol species, distribution of aerosol droplets, and material characteristics for the aerosol model.

[0095] In step 930, an optional selection of a region of interest of the respiratory system is obtained. The selection may include a target number of airway generations or a specific portion of a lung lobe. If no selection is obtained, the model automatically selects a region of interest based on the physiological data.

[0096] In step 940, a plurality of airway modules, each representing at least a portion of an airway generation of the respiratory system, are created based on the physiological data and the aerosol data. As described above with respect to FIG. 1, each airway module includes a component module 130 that represents a component of the respiratory system and has a port 130a for inputting flow and a port 130b for outputting flow. The components of the respiratory system may include the trachea, tracheal bifurcation, branches, bronchi, or bronchioles. Some airway modules representing deeper airway generations of the respiratory system further include an alveolar module 170. The alveolar module 170 includes a port 170a for receiving flow.

[0097] In step 950, an inhalation topology module is created to set the input flow to the respiratory system model over time. The input flow includes an aerosol inhalation profile. The aerosol inhalation profile is based on aerosol data.

[0098] In step 960, a modular respiratory system model is created based on combining a plurality of airway modules and an inhalation topology module. The created model may be based on a single-path respiratory system model, and each airway module is configured to represent an entire airway generation as described above with respect to FIG. 7. The created model may be based on a hybrid respiratory system model, and each airway module is configured to represent only a part of the airway generation corresponding to a lung lobe of the respiratory system as described above with respect to FIG. 8.

[0099] In step 970, the input flow to the respiratory system model over time is set by the inhalation topology module. Setting the input flow to the respiratory system model over time may include setting the input flow to the extracorporeal combination module 400 over time. The extracorporeal combination module may include a first extracorporeal airway module representing the nose and a second extracorporeal airway module representing the mouth. Setting the input flow to the extracorporeal combination module over time may include setting the input flow to the first extracorporeal airway module representing the mouth or the second extracorporeal airway module representing the nose over time, or setting the first part of the input flow to the first extracorporeal airway module and the second part of the input flow to the second extracorporeal airway module over time, where the first input flow and the second input flow constitute the input flow.

[0100] Alternatively, a predetermined volume expansion over time may be set to the volume port of the alveolar module or the volume port of any component of the airway module, and the predetermined volume expansion over time corresponds to the rate of change of the volume over time. The flow of the respiratory system model is a bidirectional flow. The flow of the respiratory system model may flow from the extracorporeal airway module to the airway module or from the airway module to the extracorporeal airway module.

[0101] In Project 980, in at least a portion of the airway generations of the respiratory system represented by the airway module, based on the set input flow, the deposition of inhaled aerosol over time is determined. The overall transient modeling of aerosol transport, generation, and deposition in the individualized total lung shape is achieved by modeling the physical and chemical behavior of the inhaled aerosol from the set input flow and by applying the relevant process conservation laws based on Equations (1)-(4).

[0102] Thus, the model enables the determination of the deposition of inhaled aerosol over time in any region of interest of the respiratory system. Determining the deposition of inhaled aerosol over time in any region of interest may include determining the deposition of inhaled aerosol over time in each airway generation of the respiratory system model, or in a specific airway generation, or in a specific portion of a lung lobe.

[0103] Some or all of the method steps described above with respect to FIG. 9 can be implemented by a computer in that they are executed (or used) by a processor, microprocessor, electronic circuit, or processing circuit. For example, the implementation can be carried out using a non-transitory storage medium such as a computer-readable storage medium. Such a computer-readable medium may be any available medium that can be accessed by a general-purpose computer system or a dedicated computer system.

[0104] Generally, the method can be implemented as a computer program product having program code or computer-executable instructions, and the program code or computer-executable instructions are operable to perform one of the methods when the computer program product is executed on a computer. The program code or computer-executable instructions may be stored, for example, on a computer-readable storage medium.

[0105] A memory medium (or data carrier, or computer-readable medium) can store a computer program or computer-executable instructions for performing one of the methods described herein when executed by a processor. An apparatus can include one or more processors and the above-described memory medium.

[0106] The apparatus may comprise processing circuitry means such as a processor communicating with a memory, the means being configured or adapted to perform one of the methods described herein. A computer may have installed thereon a computer program or instructions for performing one of the methods described herein.

[0107] FIG. 10 illustrates a system 1000 comprising an aerosol generating device 1010 and an inhalation guidance unit 1020. The aerosol generating device may be configured to use modular respiratory system models 700, 800. The system may further comprise a memory 1030 for storing modular respiratory system models 700, 800. The system 1000 may further comprise one or more processors 1040. The system may further comprise a communication module 1050 configured to send and receive instructions to / from other electronic modules or devices or between the aerosol generating device 1010 and the inhalation guidance unit 1020. The system may further comprise a sensor 1060 for counting inhalation-exhalation cycles or a sensor 1070 for capturing inhalation-exhalation flow profiles.

[0108] In an embodiment, the inhalation guidance unit 1020 may be inside or outside the aerosol generating device 1010.

[0109] The inhalation guidance unit 1020 may provide inhalation guidance instructions to the user. The inhalation guidance instructions may be created based on a respiratory system model and provided to the user using various actuators including a display, a loudspeaker, and a vibration actuator. One or more processors 1040 may be configured to perform the following steps of method 1100, as shown in FIG. 11, to adjust the user's inhalation behavior based on the provided inhalation guidance instructions. Step 1110: Capturing the aerosol inhalation profile of the user of the aerosol generating device, Step 1120: Supplying the captured aerosol inhalation profile to a respiratory system model, Step 1130: Creating inhalation guidance instructions based on the respiratory system model, and Step 1140: Providing the inhalation guidance instructions to the user by the inhalation guidance unit.

[0110] Capturing the user's aerosol inhalation profile may include determining at least one of the inspiratory-expiratory flow rate, the smoking rate, and the rate of change of lung volume in real time. Determining the inspiratory-expiratory flow rate may be based on a sensor 1060 that captures the inspiratory-expiratory flow profile. Determining the smoking rate may be based on the aerosol smoking cycles that can be counted by a sensor 1050. Determining the rate of change of lung volume may be based on an external sensor (not shown in FIG. 10) that may capture the expansion of the lung volume using a chest belt and transmit the determined rate to the aerosol generating device 1000 via a communication module 1030.

[0111] FIG. 12 illustrates a system 1200 including an aerosol generator 1210 and a setting determination unit 1220. The aerosol generator can be configured to use modular respiratory system models 700, 800. The system may further include a memory 1230 for storing the modular respiratory system models 700, 800. The system 1200 may further include one or more processors 1240. The system may further include a communication module 1250 configured to send and receive instructions to / from other electronic modules or devices, or between the aerosol generator 1210 and the inhalation determination unit 1220. The system may further include a sensor 1260 for counting inhalation-exhalation cycles, or a sensor 1270 for capturing inhalation-exhalation flow profiles, and may further include various actuators (not shown) for providing feedback or guidance to the user. In an embodiment, the setting determination unit 1220 may be inside or outside the aerosol generator 1210.

[0112] As shown in FIG. 13, one or more processors 1240 may be configured to perform the following steps of a method 1300 to control the aerosol generator 1210. Step 1310: In the setting determination unit 1220, determining one or more settings of the aerosol generator 1210 based on the respiratory system models 700, 800, and Step 1320: Controlling the aerosol generator 1210 to provide an aerosol based on the one or more settings determined by the setting determination unit 1220.

[0113] Controlling the aerosol generator 1210 to provide an aerosol based on one or more settings determined by the setting determination unit 1220 may include adjusting at least one of the voltage and current applied to the heating system of the aerosol generator, adjusting at least one of the periods of the power supplied to the heating system of the aerosol generator, adjusting at least one of the pulse width and pulse density of the power supplied to the heating system of the aerosol generator, adjusting the aerosol generation rate of the aerosol generator, and adjusting the volume of the aerosol generated per puff from the aerosol generator.

[0114] Determining one or more settings of the aerosol generator 1210 based on the respiratory system models 700, 800 in the setting determination unit 1220 may include, in the setting determination unit, obtaining data related to the aerosol generator 1210 and adapting the respiratory system models 700, 800 based on the data related to the aerosol generator 1210.

[0115] Adapting the respiratory system models 700, 800 may include adapting the aerosol data input to the respiratory system models 700, 800 based on the aerosol data associated with the device 1210, adapting the aerosol data of the respiratory system models 700, 800, adapting the aerosol inhalation profile of the inhalation topology module based on the aerosol inhalation profile associated with the device or one or more users of the device, and adapting the target aerosol deposition based on the target aerosol deposition associated with the device or one or more users of the device, and may include at least one of them.

[0116] Adapting the aerosol data of the breathing system models 700 and 800 may include at least one of adjusting the vibration frequency of the mesh of the heating system of the device and determining, in a setting determination unit, one or more adjusted vibration frequencies, and adjusting the temperature of the mesh of the heating system of the aerosol generator and determining, in a setting determination unit, one or more adjusted temperatures of the mesh.

[0117] Controlling the aerosol generator 1210 to provide an aerosol based on 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 mesh.

[0118] In an alternative embodiment, the setting determination unit 1220 of the system 1200 may be integrated within the system 1000 described above with respect to FIG. 10.

[0119] FIG. 14 shows the input flow set by the inhalation topology module to the breathing system model over time. The input flow may be applied to the breathing system model via an extracorporeal airway module representing the nose and mouth.

[0120] According to one embodiment of the present invention, the input flow may include a first input flow applied to a first extracorporeal airway module and a second input flow applied to a second extracorporeal airway module. The first extracorporeal airway module may represent the nose, and the second extracorporeal airway module may represent the mouth. Alternatively, the first extracorporeal airway module may represent the mouth, and the second extracorporeal airway module may represent the 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.

[0121] According to another embodiment of the present invention, setting the input flow over time to the respiratory system model may include setting the input flow over time to a first extrathoracic airway module representing the mouth or to a second extrathoracic airway module representing the nose.

[0122] Setting the input flow over time to the respiratory system model may include setting the conditions of the input flow, including setting at least one of the input flow topology and the input thermal-physical conditions of the input flow. Setting the input thermal-physical conditions of the input flow may include setting at least one of the input flow temperature and the input aerosol concentration characteristics.

[0123] As illustrated in the example of FIG. 14, for the first 2 seconds, an aerosol inhalation profile including aerosol smoke 1400 is applied to the extrathoracic module representing the mouth. After a 1-second hold 1410, an air inhalation profile including two complete inhalation-exhalation cycles 1420, 1430 is applied to the extrathoracic module representing the nose. After each inhalation cycle, an additional hold of 1 second 1440, 1450 is applied. In this case, at the start of the inhalation-exhalation cycle 1420, the extrathoracic airway module representing the mouth contracts and the aerosol smoke is moved to the airway module representing the lungs. Next, the aerosol smoke is applied and the process is repeated by setting the input flow. According to one embodiment of the present invention, realistic and measured aerosol inhalation profiles and air inhalation profiles can be used by the inhalation topology module to set the input flow to the respiratory system model.

[0124] FIG. 15 shows the results of transient aerosol deposition in different regions of interest of a modular respiratory system model based on a single-path configuration similar to that shown in FIG. 7. In this case, a 4-region respiratory system model was simulated. The extrathoracic region including extrathoracic airway modules representing the nose, mouth, and larynx. The bronchiolar region with airway modules representing the bronchial airway generations. The bronchiolar region including airway modules representing the bronchiolar airway generations, and the alveolar region including airway modules representing the alveolar airway generations of the user's respiratory system.

[0125] Figure 15 shows the results of the particle number deposition profiles in different regions of interest. The results shown in Figure 15 are obtained by using the above-described four-region respiratory system model and applying an input flow that includes the aerosol inhalation profile and the airflow profile visualized in Figure 14. According to Figure 15, the aerosol begins to deposit at approximately t = 4 seconds at 1500 in the trachea, i.e., airway generation 1, when the aerosol is transferred from the extra-thoracic airway module representing the mouth to the airway module representing the lungs. The respiratory system model captures deposition peaks 1510, 1520, 1530 that move deeper and deeper in time within the lungs during the first inhalation 1420. At the end of the inhalation, the aerosol reaches the alveolar region and deposition within the alveoli begins 1540. Secondary deposition peaks 1550, 1560 are seen during the first exhalation phase 1420. Finally, since aerosol remains in the lung volume, it is also possible to observe further deposition 1570 during the second inhalation-exhalation cycle 1430.

[0126] For the purposes of this specification and the appended claims, unless otherwise indicated, all numbers expressing amounts, quantities, percentages, etc. are to be understood as being modified in all instances by the term "about." Also, all ranges include the disclosed maximum and minimum points and any intermediate ranges therebetween, whether or not specifically enumerated herein. In this context, a number A may be considered to include numerical values within the general standard error of the measurement of the property that the number A modifies. The number A may deviate by the percentages recited above in some instances as used in the appended claims, provided that the amount by which A deviates does not substantially affect the basic and novel characteristics of the claimed invention. Also, all ranges include the disclosed maximum and minimum points and any intermediate ranges therebetween, whether or not specifically enumerated herein.

Claims

1. A system comprising an aerosol generating device and an inhalation guidance unit, wherein the system is one or more processors, and capturing a user's aerosol inhalation profile of the aerosol generating device; supplying the captured aerosol inhalation profile to a respiratory system model; creating an inhalation guidance instruction based on the respiratory system model; and providing, by the inhalation guidance unit, the inhalation guidance instruction to the user. A system comprising one or more processors configured to perform the steps.

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

3. The respiratory system model is a modular respiratory system model for transient aerosol dose measurement, and the model includes a plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system; and an inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow including the captured aerosol inhalation profile. The system according to claim 1 or 2, wherein each airway module is configured to determine deposition of the inhaled aerosol over time in at least a part of the 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 according to claim 3, wherein each airway module comprises one or more component modules, each component module representing a component of the respiratory system and having a port for inputting a flow and a port for outputting a flow.

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

6. The system according to any one of claims 3 to 5, wherein the respiratory system model is configured to determine the corresponding deposition of the inhaled aerosol over time in each airway module of the region of interest of the respiratory system for each aerosol inhalation profile of several aerosol inhalation profiles, in order to determine the optimal aerosol inhalation profile corresponding to the target aerosol deposition.

7. The system according to claim 6, wherein the respiratory system model is further configured to create the inhalation guidance instruction based on the optimal aerosol inhalation profile.

8. A system comprising an aerosol generator and a setting determination unit, the system comprising one or more processors, in the setting determination unit, a step of determining one or more settings of the aerosol generator based on a respiratory system model; controlling the aerosol generator to provide an aerosol based on one or more settings determined by the setting determination unit, one or more processors configured to perform.

9. Controlling the aerosol generator to provide an aerosol based on one or more settings determined by the setting determination unit is adjusting at least one of the voltage and current applied to the heating system of the aerosol generator; adjusting the period of the power supplied to the heating system of the aerosol generator; adjusting at least one of the pulse width and pulse density of the power supplied to the heating system of the aerosol generator; adjusting the aerosol generation rate of the aerosol generator; and adjusting the volume of the aerosol generated per puff from the aerosol generator, the system according to claim 8, comprising at least one of.

10. The one or more processors are in the setting determination unit, a further step of obtaining data related to the aerosol generator; a further step of adapting the respiratory system model based on the data related to the aerosol generator, the system according to claim 8 or 9, configured to perform.

11. Adapting the respiratory system model is Adapting an 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 an aerosol inhalation profile based on an aerosol inhalation profile associated with the device or with one or more users of the device, and Adapting a target aerosol deposition based on a target aerosol deposition associated with the device or with one or more users of the device, the system of claim 10 comprising at least one of the foregoing.

12. Adapting the aerosol data of the respiratory system model comprises Adjusting the vibration frequency of the mesh of the heating system of the device to determine, in the setting determination unit, one or more adjusted vibration frequencies, and Adjusting the temperature of the mesh of the heating system of the aerosol generating device to determine, in the setting determination unit, one or more adjusted temperatures of the mesh, comprising at least one of the foregoing, Controlling the aerosol generating device to provide an aerosol based on the one or more settings determined by the setting determination unit, comprising using at least one determined of the one or more adjusted vibration frequencies and the one or more adjusted temperatures of the mesh, the system of claim 11.

13. The respiratory system model is a modular respiratory system model for transient aerosol dose measurement, the model comprising A plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system, a plurality of airway modules, and An inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow including the captured aerosol inhalation profile, an inhalation topology module, including, Each airway module is configured to determine the deposition of the inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module, the system of any one of claims 8 to 12.

14. A computer-implemented modular respiratory system model for transient aerosol dose measurement, wherein the model comprises: A plurality of airway modules, each airway module representing at least a part of an airway generation of the respiratory system; An inhalation topology module configured to set an input flow to the respiratory system model over time, the input flow including an aerosol inhalation profile; Each airway module is configured to determine the deposition of the inhaled aerosol over time in at least a part of the airway generation of the respiratory system represented by the airway module based on the input flow set by the inhalation topology module, such that the model is capable of determining the deposition of the inhaled aerosol over time in the region of interest of the respiratory system. **Claim 15** A computer-implemented method for creating 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 properties; Creating a plurality of airway modules based on the physiological data and the aerosol data, each airway module representing at least a part of an airway generation of the respiratory system; Creating an inhalation topology module for setting an input flow to the respiratory system model over time, the input flow including an aerosol inhalation profile; Creating the modular respiratory system model based on combining the plurality of airway modules and the inhalation topology module.

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