JP2023129716A - Nebulizer monitoring device, system and method - Google Patents

Abstract

To provide devices, systems and methods for monitoring the use of a nebulized medication, such as can be administered using a nebulizer.SOLUTION: These can be used for monitoring a patient undergoing treatment for COPD (chronic obstructive pulmonary disease) and improve compliance with a recommended therapy. Monitored parameters include flow, humidity and acceleration and provide data as to the quantity and quality of nebulizer use.SELECTED DRAWING: Figure 2A

Description

FIELD OF THE INVENTION The present invention generally relates to devices, systems, and methods for monitoring the use of nebulized drugs, such as those that can be administered using a nebulizer.

A nebulizer is a drug delivery device used to aerosolize medicine in solution or suspension form into the respiratory tract so that it can be inhaled by the patient. In order for drugs to reach the lungs, the size of particles in aerosols is an important parameter to control. Particles larger than about 5 μm in diameter are more likely to be deposited in the upper respiratory tract than smaller particles and to be swallowed rather than deposited in the lungs. Conversely, particles with a diameter of about 1 μm or less are less likely to be deposited in the lungs and may simply be inhaled or exhaled. Therefore, nebulizers are typically designed to deliver particles between approximately 1 μm and 5 μm, which generally constitutes the reparable fraction of the inhaled bronchodilator. Size range.

Most commonly, nebulizers use either a pressurized gas source, as in "jet" nebulizers, or ultrasonic energy, as in "ultrasonic" nebulizers and "electronic" or "mesh" nebulizers. aerosols are created by forming atomization or "atomization" of medical solutions or suspensions, either by: Jet nebulizers utilize the Venturi effect, which uses a preset flow rate of pressurized gas to draw a solution through a capillary tube from a nebulizer reservoir containing a drug solution or suspension to produce a wide range of particle sizes. (for example, 2 to 10 L/min) is generally required. These initial liquid particles can be sprayed onto one or more baffles to remove larger particles from the aerosol and return them to the reservoir, while delivering smaller particles to the user who inhales through the mouthpiece. Ultrasonic nebulizers use an alternating current power source to vibrate a piezoelectric element within the nebulizer reservoir, generating standing waves on the surface of the solution/suspension. Small droplets are detached from the solution by this wave and emitted as an aerosol of large and small particles that are sorted out into smaller particles by a baffle, similar to a jet nebulizer. This aerosol can then be delivered to the lungs as described above. Mesh nebulizers use vibrating piezoelectric elements coupled to a fine mesh to generate an aerosol, and control particle size by sizing the mesh (Non-Patent Document 1, Non-Patent Document 2).

There are many potential indications for nebulizer therapy, including bronchial narrowing, airway inflammation, viscous retained secretions, airspace infections and colonization, dyspnea and chronic cough. To alleviate these symptoms/conditions, bronchodilators (e.g., salbutamol, terbutaline, ipratropium), anti-inflammatory agents (e.g., budesonide, fluticasone), secretion disrupters (e.g., saline and DNase/dornase), antibacterial agents ( These include the administration of nebulized medications such as pentamidine (e.g., pentamidine), long-acting bronchodilators (e.g., formoterol, arformoterol, glycoprilolate, levefenacin), and pain management medications (e.g., morphine, lidocaine). These symptoms/conditions occur due to disease settings such as Chronic Obstructive Pulmonary Disease (COPD), asthma, cystic fibrosis, bronchiectasis, HIV, lung cancer, or combinations thereof. Chronic obstructive pulmonary disease COPD refers to progressive symptoms resulting from a number of disease states, including emphysema, chronic bronchitis, and some asthmatics. Chronic obstructive pulmonary disease (COPD) is a disease that generally occurs in men and women over the age of 40, and is associated with a high disease burden, including decreased quality of life (QOL), functional impairment, and large direct/indirect costs. Currently, there is no way to completely cure chronic obstructive pulmonary disease COPD, and as the oxygenation capacity of the lungs decreases as the disease progresses, the only option is to suppress the symptoms (Non-Patent Documents 3 to 5).

In the management of chronic obstructive pulmonary disease COPD, patient compliance with inhalation drug therapy is critical, and central to this is the use of bronchodilators. Bronchodilators include beta-agonists, anticholinergics, methylxanthines (eg, theophylline), and are administered by nebulizer. To date, compliance is based on self-reporting, assessment of reported symptoms, and spirometry to assess whether administration is effective. There is wide variation in patient compliance with prescribed chronic obstructive pulmonary disease (COPD) medications and reporting of symptoms, and many physicians diagnose chronic obstructive pulmonary disease (COPD) based on symptoms and medical history without performing a spirometry assessment. Diagnosing/managing patients. A compliance rate of 50% with prescribed treatment may be considered high. Chronic obstructive pulmonary disease (COPD) patients may periodically experience acute exacerbations of chronic obstructive pulmonary disease (COPD) symptoms. This is caused by inflammation that narrows the airways and builds up mucus. The cause of these exacerbations is not always clear, but they are often caused by viral or bacterial infections of the lungs. It can also be worsened by breathing in irritating substances in the environment, such as air pollution or allergens such as pollen. Inflammation (irritation and swelling) of the lungs during and after exacerbations of chronic obstructive pulmonary disease COPD often leads to prolonged recovery, worsening of comorbidities, and patient death. Early detection of exacerbations often relies on patient reporting. Patients with chronic obstructive pulmonary disease (COPD) also need to receive adequate education about the disease process, including exacerbations and comorbidities, as well as the use of various medications and devices.

Treatment of chronic obstructive pulmonary disease COPD involves a significant financial burden and changes in behavior and lifestyle, such as starting a smoking cessation program, undertaking an exercise program (pulmonary rehabilitation), and inhaling supplemental oxygen in and out of the home. There are many cases. Furthermore, in the case of such patients, there is a possibility that they are receiving other treatments and therapies, which increases the burden of continuing treatment. Poor adherence to chronic obstructive pulmonary disease (COPD) treatment is therefore not surprising, but also troubling. Regarding adherence to inhalation therapy, patients were categorized as (1) regular users who use it well, (2) regular users who do not use it well, (3) non-regular patients who use it well, and (4) non-regular patients who do not use it well. It can be classified into four categories: Patients with irregular use and poor technique (4th category) have the highest mortality rate, while patients with irregular use and good technique (3rd category) have the second highest mortality rate (but 4th category). The incidence of exacerbation is also known to be high. Patients with regular use but poor technique (second category) had better results, albeit with a slightly increased exacerbation rate. Not surprisingly, patients with regular use and good technique have the lowest mortality and exacerbation rates. Adherence behaviors are therefore associated with specific clinical outcomes, with regular use (e.g., prescription, amount used) being the most important factor, and appropriate use (e.g., quality of use) being a less important factor. It can be said that this is an important element (non-patent documents 6 to 10, etc.).

R. Johns et al., Prescriber 2007, 5, 16-28 D. S. Gardenhire et al., A Guide to Aerosol Delivery Devices for Respiratory Therapists, 3rd ed. , American Association for Respiratory Care, 2013 J. L. Peacock et al. Thorax 2011, 66, 591-596 A. Agusti Ur. Repir Rev 2011, 121m 183-194 E. L. Toy et al., Respiratory Medicine, 2011, 105, 435-441 Cushen et al., AJRCCM Articlesin Press, 19-Jan-2018 Arzu Ari Eurasian J. Pulmonol, 2014, 16, 1-7 S. Lareau et al., Am J. Respir. Crit. Care Med. , 2014, 189, P11-P12 Tamas Agh et al., Chronic Obstructive Pulmonary Disease - Current Concepts and Practice, InTech, 2012, Ch. 12, 275-290 R. D. Restrepo et al., International Journal of COPD, 2008, 3(3), 371-384

Although treatments exist for chronic obstructive pulmonary disease COPD, there is a need to improve patient compliance with prescribed inhalation therapy. Early detection of exacerbations also greatly improves the ability to appropriately treat and stabilize patients. Improved compliance and early detection of exacerbations not only significantly reduce treatment costs, but also have the potential to attenuate the decline in lung function and improve the quality of life for patients with chronic obstructive pulmonary disease COPD. is recognized as an unmet need.

Additionally, in tests such as data collection in clinical trials, it is necessary to monitor the usage of drugs using nebulizers. Currently, it is standard practice in these trials for users to complete daily logs regarding drug use. The drug given to subjects during a drug test may be a placebo, and if no effect is seen, they are no longer participating in the study. Verifying compliance with instructions is more difficult, or perhaps more difficult, than in chronic obstructive pulmonary disease COPD. Additionally, unreliable compliance reporting by users in clinical trials is hindering evaluation by sponsors, approval by regulatory agencies, and ultimately healthcare professionals' characterization of drugs for the treatment of patients with chronic obstructive pulmonary disease (COPD). may confound the true effect of a drug candidate on physiological endpoint data (e.g., forced exhaled volume per second, FEV1) utilized in clinical trials. Therefore, expanding the collection and breadth of data on nebulizer use and dosing is another unmet need.

In general, the present invention relates to a nebulizer monitoring device, a system comprising the nebulizer device, and a method of monitoring a user's nebulizer usage using the monitoring device and system. According to some embodiments, devices, systems, and methods provide flow, humidity, temperature, and movement measurements from sensors located within or with the nebulizer that are used to monitor the user's nebulizer. Real-time usage can be monitored. Additionally, data can be collected and processed into data such as exhaled volume, respiratory rate, and body temperature for visualization by users, caregivers, and medical personnel. For example, the data can be used for data collection related to usage compliance, experimental studies, or for tracking or detecting the onset of reactions or exacerbations to inhaled breathing drugs. The present devices, systems, and methods thus facilitate compliance with nebulizer use according to a preset treatment regime, as well as assist in real-time monitoring of the user and the onset of exacerbations.

In one aspect, the present invention relates to a nebulizer system that includes a subsystem for detecting and tracking use of a nebulizer by a user. The system includes one or more sensors configured to detect and measure the flow of nebulized medication through the nebulizer and a controller configured to record and report usage of the nebulizer by the user. Be prepared. The device also includes a base substrate having a first surface and a second surface, and an integrated circuit attached to the second surface of the base substrate.

According to some embodiments of the invention, a nebulizer monitoring device is provided. The nebulizer monitoring device includes a first connector adapted to engage the nebulizer mount and a second connector adapted to engage the nebulizer mouthpiece. The device also includes a conduit having an interior surface forming a fluid connection between the first connector and the second connector. A flow sensor is disposed within the conduit and between the first connector and the second connector, and the flow sensor is configured to measure a flow vector of fluid within the conduit. The at least one indicator is connected to the flow sensor, and the at least one controller is connected to the flow sensor and the first indicator, such that at least one dimension of the at least one indicator is connected to the measured flow vector. varies as a function of In some options of the device, the flow sensor comprises a differential pressure sensor or a flow meter.

Optionally, the nebulizer device comprises at least one light source, for example. Here, the change in the dimensions of the at least one indicator comprises a change in the intensity of the light emitted from the at least one light source. In some embodiments, the at least one light source comprises a first light emitting diode (LED), and the change in intensity of light emitted by the first LED changes as a function of the measured fluid flow vector. Optionally, the at least one indicator comprises a second LED light having a different color than the first LED light, the first light being illuminated when the measured fluid flow vector is in the first direction, and the first light being illuminated when the measured fluid flow vector is in the first direction; When the fluid flow vector determined is in the second direction, the second light is irradiated. Optionally, the at least one light source comprises at least two light emitting diodes (LEDs) and the change in dimension of the at least one indicator comprises a change in state of at least one of the two LEDs. Optionally, the at least one light source comprises an array of LEDs that are sequentially illuminated, the array of LEDs being perceived as an indicator of increasing length, the perceived length being a function of the measured flow vector. where the length direction indicates the vector direction of the measured flow vector.

Optionally, the first indicator of the nebulizer monitoring device comprises an audible indicator comprising at least one audible signal. In some other embodiments, the dimensions of the audible indicator are one or more of the amplitude, frequency, and pattern of sound emitted by the at least one sound emitting device. For example, sounds can change from loud to soft, soft to loud, low to high, high to low, and sounds can vary in duration and/or frequency. A varying beep tone may be emitted, a sound may emit two or more tones (e.g., a chord) that are recognized to be emitted at the same time, and a sound may emit a musical sound (e.g., a song or song). fragments). Also, optionally, the first indicator comprises a tactile indicator comprising one or more of a vibrating device, a radiant heat device, and a shape changing device. Examples include where the indicator provides a vibrating tactile sensation when holding the device and when a dose is completed, or where the indicator provides a display (eg, Braille) that is readable by a visually impaired person. Optionally, the tactile indicator includes a vibration device, and the dimensions of the audible indicator include one or more of an intensity and a frequency of the vibration.

The nebulizer monitoring device may further optionally include a humidity sensor disposed within or connected to the conduit between the nebulizer mount and the mouthpiece, the humidity sensor measuring humidity within the conduit. It is configured as follows. Thus, at least one dimension of the at least one indicator changes as a function of the measured flow vector and the measured humidity from the humidity sensor.

The nebulizer monitoring device may also optionally include a usage indicator comprising an array of light emitting diodes (LEDs) connected to at least one controller. In some optional embodiments, the at least one controller includes the step of: turning off all LEDs of the usage indicator for a preset amount of time; of the usage indicators in a preset order following receipt of multiple measured flow vectors and subsequent reception of no flow vector measurements by the flow sensor for a preset period of time. and turning on one LED. Optionally, the controller includes the step of turning off all LEDs of the usage indicator at a preset time and the controller determining the measured flow vector indicating flow (e.g., in a first direction and optionally in a second direction). and the controller receives multiple measurements of humidity over a preset period of time, and after the average of the multiple measurements of humidity over the preset period exceeds a preset threshold. , turning on one LED of the usage indicator in a preset order. Optionally, the usage indicator can include a visual indicator comprising an array of LED lights such that each dose taken after the specified start time is The array is reset by turning off all LEDs at preset times of the day. Optionally, the preset threshold is 80% relative humidity.

Further, optionally, the device can further include a temperature sensor configured to contact at least one lip of the user when the device is being used to administer medication to the user, and the at least one One controller is connected to a temperature sensor. Optionally, the temperature sensor is inserted into the user's mouth such that when the user inserts the mouthpiece into his or her mouth, the temperature sensor is positioned to measure the temperature of at least a portion of the user's lips. The mouthpiece is disposed at a first end of a mouthpiece configured as follows. Optionally, the second connector extends along the first axis, the second connector further comprising an arm extending along the first axis outwardly of the conduit, and the mouthpiece is attached to the second connector. When connected, the arm extends along the mouthpiece. A first portion of the arm includes a temperature sensor and a second portion of the arm is connected to a conduit for connecting the temperature sensor to at least one controller. Also, optionally, the first portion of the arm is configured to align with the mouthpiece such that the first portion of the arm contacts at least a portion of the user's lips when the user inserts the mouthpiece into the mouth. Ru. The arm can optionally include a hinge connecting the arm to the conduit. The arm can also optionally include a flexible tether to extend the length of the arm to the conduit. In some embodiments, the temperature sensor comprises a thermistor.

Optionally, the nebulizer device further comprises an accelerometer connected to the at least one controller. Optionally, the nebulizer device further comprises a battery connected to at least one controller and a charging circuit for charging the battery. Optionally, the battery charging circuit includes an induction coil configured for inductive charging.

According to some other embodiments of the invention, a system for nebulizer use is provided, the system for nebulizer use comprising a nebulizer monitoring device and a base station in wireless communication with the nebulizer monitoring device. Optionally, the nebulizer monitoring device comprises a battery connected to at least one controller and a charging circuit for charging said battery. Optionally, the base station also includes a port configured to receive and charge a nebulizer monitoring device. Optionally, the base station includes a first induction coil and the nebulizer monitoring device includes a second induction coil such that the base station inductively charges the nebulizer monitoring device when the nebulizer monitoring device is accepted by the base station. We are prepared. In some optional embodiments, the base station includes a plurality of pogo pins, the nebulizer monitoring device includes a plurality of electrical contact pads, and when the nebulizer monitoring device is accepted by the base station, the nebulizer monitoring device includes a plurality of electrical contact pads. At least two pogo pins contact two contact pads of the nebulizer monitor and are adapted to transfer electrical energy to the nebulizer monitor to charge the battery.

Optionally, the base station of the nebulizer-using system is configured to include at least one environmental monitoring sensor and to be connected to the at least one environmental monitoring sensor and configured to receive and store environmental sensor data from the at least one environmental monitoring sensor. Equipped with a controller. Optionally, the at least one environmental monitoring sensor is at least one of a VOC (volatile organic compound) sensor, a _CO2 sensor, a humidity sensor, a temperature sensor, a mold sensor, a pollen sensor, a spore sensor, a bacteria sensor, and a particulate sensor. It is equipped with Optionally, the base station is equipped with a network interface, allowing the base station to transfer data to a remote computer system. Optionally, the remote computer system also includes at least one processor and related components and is configured to receive and store data from the base station.

According to another embodiment of the invention, a method of administering nebulized medication to a user is provided. A method of administering a nebulized drug to a user comprises administering a nebulizer therapy regimen of a preset dose of said drug using a nebulizer equipped with a nebulizer monitoring device or a system for nebulizer use. ing. Optionally, the user is a patient in need of nebulized medication and is at high risk of non-adherence to the nebulizer therapy regimen. Also, optionally, the user is a subject in a drug study or trial. In some options, one or more usage indicators are stored in electronic form. In some embodiments, the one or more usage indicators are displayed on the data visualization system, and the care provider or user views the one or more indicators on the visualization system, and the one or more usage indicators are displayed on the data visualization system. Corrective action is taken by the user or health care provider if the indicators indicate misuse or deterioration of the device. Also, optionally, the usage indicator is selected from the group comprising: temperature, respiratory rate, exhaled volume, dose, device orientation, and combinations thereof. Optionally, each usage indicator constitutes a plurality of timestamped usage indicators.

These and other features of the invention will be more fully understood after considering the following figures, detailed description, and claims, along with the invention itself.
The accompanying drawings, which are incorporated herein, illustrate one or more illustrative embodiments of the invention and, together with the detailed description, serve to explain and explain the principles and applications of these inventions. play a role. The drawings and detailed description are illustrative and not restrictive, and may be adapted and changed without departing from the scope and spirit of the invention.

3D perspective view of a nebulizer monitoring device. FIG. 3 is a 3D perspective view of a nebulizer monitoring device with some additional details. FIG. 2 is a cross-sectional plan view of a nebulizer monitoring device. 1 is a cross-sectional plan view of a nebulizer monitoring device board including control components, sensors, and indicators; FIG. Figures 2C and 2D are two graphs showing respiration data plotted for two different respiration rates. Figure 2C shows 15 breaths per minute. 2C and 2D are two graphs showing respiration data plotted for two different respiration rates. Figure 2D shows 20 breaths per minute. FIG. 4 illustrates a tab and hinge configuration for positioning a thermistor near a mouthpiece for a nebulizer monitoring device. The first panel of FIG. 3A shows the thermistor not in contact with the mouthpiece, and the second panel of FIG. 3A shows the thermistor in contact with the mouthpiece. Figure 2 shows a clip-on retainer configuration for placing a thermocouple near the mouthpiece of a nebulizer monitoring device. The first panel of FIG. 3B shows the thermistor not in contact with the mouthpiece, and the second panel of FIG. 3B shows the thermistor in contact with the mouthpiece. Figure 3 shows a stretchable retainer configuration for placing a thermocouple near a mouthpiece for a nebulizer monitoring device. The first panel of FIG. 3C shows the thermistor not in contact with the mouthpiece, and the second panel of FIG. 3C shows the thermistor in contact with the mouthpiece. FIG. 2 is a top down view of an embodiment showing the mouthpiece and housing of the nebulizer monitoring device. FIG. 14 illustrates pictorially how light intensity can be used as an indicator of inhalation and exhalation intensity in some embodiments. The first panel of Figure 4B shows the LED becoming brighter during inhalation. The second panel of Figure 4B shows that the LED light becomes weaker during exhalation. FIG. 2 is a top view of an embodiment showing the mouthpiece and housing of the nebulizer monitoring device. The first panel of Figure 5B and the second panel of 5B show that an extension within the indicator indicates that the user is inhaling (first panel of Figure 5B), and a contraction within the indicator indicates that the user is inhaling. , an embodiment showing the user spitting (second panel of FIG. 5B). 2 is a top view of the housing of the nebulizer monitoring device with different colored lights as indicators; FIG. The first panel of FIG. 5C shows a green emission indicating an inhale, and the second panel of FIG. 5C shows a purple emission indicating an exhale. 2 is a plot of percent relative humidity versus time showing the response of a humidity sensor used in one embodiment of a device for monitoring nebulizer usage. FIG. 2 is a 3D perspective view of a base station configured to receive a nebulizer monitoring device. FIG. 3 is a 3D perspective view of a base station in a possible environment in which it may be used. 1 is a pictorial diagram of one embodiment of a system using a nebulizer monitoring device. Dashboard for viewing information provided by the system for monitoring the user's use of the nebulizer. 1 schematically depicts an embodiment of components for a system for monitoring a user's use of a nebulizer; 1 schematically depicts an embodiment of steps taken in using a system for monitoring a user's nebulizer usage; FIG. 1 illustrates an embodiment for steps taken when using a base station and a cloud server;

The present application is directed to methods and systems for the management of inhalation therapy. For example, inhalation therapy management involves detecting and recording adherence to an inhalation therapy regimen, as well as determining the dose taken, the user's condition (e.g., body temperature, respiratory rate, exhaled volume), and the environmental conditions to which the user is exposed (e.g., , air quality). Treatment can include nebulizer therapy and monitoring for the treatment of chronic obstructive pulmonary disease COPD or other respiratory diseases treated with nebulizer therapy (eg, asthma, cystic fibrosis). In general, the present invention relates to devices, systems, and methods for assisting users, caregivers, and health care providers in managing therapies requiring nebulizer therapy. The same system can also be used to monitor subjects in clinical research.

As used herein, the term "user" generally refers to a clinical research subject, a patient, or a care provider assisting a subject or patient, as the context permits. . For example, without limitation, a user may use a device as described herein, a system as described herein, or a user as described herein. Patients receiving nebulizer therapy may be monitored for use of the device. Alternatively, without limitation, a user may use a device described herein as part of a clinical trial, use a system described herein as part of a clinical trial, or use a system described herein as part of a clinical trial. Can be a subject in a clinical trial, as will monitor the use of the device. Also, without limitation, the User may assist a patient or subject in using the devices described herein, assist a patient or subject in using the system described herein, or assist a patient or subject in using the system described herein. The patient may be a care provider (eg, a spouse, relative, friend, nurse, and/or hired assistant) who helps monitor the use of the device. In some embodiments, the term user can refer to two or more patients, subjects, and/or care providers. For example, a user being alerted by a display of a monitoring system should be understood to mean that both a care provider and a patient may be alerted by the monitoring system. In some embodiments, the user is both a patient and a subject, eg, a patient undergoing an experimental treatment.

Chronic obstructive pulmonary disease COPD is a disease that typically occurs in male and female patients over the age of 40 and is associated with a high burden of disease, including decreased quality of life, functional disability, and significant direct and indirect costs. associated with disease burden. Furthermore, in patients with chronic obstructive pulmonary disease COPD, the symptoms of chronic obstructive pulmonary disease COPD may become acutely aggravated due to airway narrowing or mucus accumulation due to inflammation. The exact cause of these exacerbations is not always known, but in some cases they may be caused by a viral or bacterial infection of the lungs or inhalation of irritants from the environment, such as severe air pollution or allergens such as pollen. be. Early detection of exacerbations is important because untreated exacerbations often result in delayed recovery, worsening of comorbidities, and death. Therefore, patients with chronic obstructive pulmonary disease (COPD) require sufficient education about the disease process, including exacerbations and comorbidities, and how to use various drugs and devices. Many people with chronic obstructive pulmonary disease (COPD) have other medical issues that require other medications, and in some cases, they have a reduced ability to self-regulate, so inhalation Complying with the law is extremely difficult. Correct use of the device and initiation of exacerbation is often determined by self-report or observation by a health care professional or another person (e.g., the caregiver's spouse).

A nebulizer is a drug delivery device used to deliver drugs in the form of a solution or suspension directly to the respiratory tract, aerosolizing the solution so that the drug is delivered to inflamed and/or irritated airway tissues. The user can inhale for direct delivery. There are three common types of nebulizers: jet nebulizers, ultrasonic nebulizers, and mesh nebulizers. These are aerosolized from medical solutions (e.g., suspensions) with particles of approximately 1-5 μm in diameter that are inhaled and placed into the user's airways through a mouthpiece, nosepiece, or facemask. Designed to produce drugs. Alternatively, use a nebulizer connected to a mechanical ventilator system. Other particle size distributions can be used/targeted, but this is done with the understanding below. Thus, the understanding is that particles with a size of about 10-15 μm tend to deposit mainly in the upper respiratory tract, particles with a size of about 5-10 μm tend to reach the large bronchi, and particles with a size of about 1-5 μm tend to deposit mainly in the upper respiratory tract. Understanding that particles tend to penetrate into the lower respiratory tract and around the lungs, and that smaller particles or vapors are mostly inhaled and exhaled without deposition, although some deposition/condensation may occur. It is.

In a jet nebulizer, a drug solution is added to a reservoir connected to a first open end of a capillary tube. The compressed gas source generates a gas flow, e.g., a jet stream, through a small opening across the second open end of the capillary tube to draw liquid from the reservoir through the tube by a Venturi effect. be projected. The flow of gas (eg, air) thus reduces the pressure at the second end of the tube, causing liquid to be drawn from the reservoir through the first end of the tube and out the second end. The liquid is aerosolized by contact with the jet stream. The jet stream and aerosolized particles are directed into a chamber that may include baffles. Relatively large liquid particles contact the baffle and are captured, allowing liquid from these large particles to flow/drop into a reservoir or another collection chamber. Baffles are typically designed to remove particles larger than about 5 μm in diameter. Small particles, e.g. particles less than 5 μm, remain aerosolized within the chamber and may be connected to a mouthpiece, nosepiece, face mask, via a port attached to a mechanical ventilator system, or to any of these. The chamber can be exited through a port attached to the tube. The mouthpiece is designed to be inserted into the user's mouth to ingest the aerosolized medication when the user inhales. For example, the mouthpiece can be designed to be inserted between the user's teeth and contact/seal against the user's lips. The nosepiece can have two tubes configured to be inserted into the nostrils, and the face mask can be placed over the mouth and/or nose to ingest medication. The chamber also has another opening, called an inhalation port, that allows ambient air to enter the chamber, such as when a user inhales. Other ports may also be included, such as an exhale port on a mouthpiece or face mask. A system of one-way valves also allows the user to access the aerosolized medication via the mouthpiece/facemask and is activated, for example, when the user inhales, and is provided to direct/maintain the exhalation out of the chamber. It is possible to be For example, one-way valves on the mouthpiece, air inlet, and outlet. In some systems, the air intake can be connected to an expandable chamber, such as a collection bag or an expandable elastomeric ball, which, for example, deflates when the user inhales and generates new aerosol when the user exhales. The gas/air source is controlled by a one-way valve, where the gas/air source is controlled by a one-way valve.

Ultrasonic nebulizers use high frequency vibrations from a transducer (eg, a piezoelectric material) to energize a drug solution in a reservoir to generate a standing wave and generate an aerosol within a chamber. The chamber can be connected to a mouthpiece so that when the user breathes in, the aerosol is drawn into the lungs. The ultrasonic nebulizer includes one or more baffles that control particle size (e.g., trap larger aerosol particles) such that the ultrasonic nebulizer provides the user with an aerosol having a particle size of less than about 5 μm. It can be done. Ultrasonic nebulizers are generally more efficient than jet nebulizers, and drug doses are adjusted appropriately to take this into account. For example, a 1 mL dose of a drug used with an ultrasound nebulizer may require a 2 mL dose of the same drug when using a jet nebulizer.

Another common nebulizer is a mesh nebulizer or an electronic nebulizer (eFlownebulizer). A mesh nebulizer uses electricity to vibrate a piezoelectric element connected to a fine mesh, brings the fine mesh into contact with a medical solution, and generates an aerosol. A major feature of mesh nebulizers, compared to jet nebulizers and ultrasonic nebulizers, is that the particle size is determined by the diameter of the mesh rather than by the baffle. They also differ from jet nebulizers in that they can meter doses more efficiently and administer small, set amounts of medication within a 2-3 minute time frame.

The devices described by the embodiments herein are universal and can be used with any nebulizer, such as jet nebulizers, ultrasound nebulizers, and mesh nebulizers. Additionally, the nebulizer can be equipped with a mouthpiece or face mask. In some embodiments, PARI Respiratory Equipment, Inc. (e.g., Pari Trek S, Magnair), VELOX, Philips Respironics (e.g., Respironics Sidestream), RoscoeMed ical (e.g., Roscoe Medical Portable Travel Nebulizer System, Roscoe Pediatric Nebulizers, etc.), Dynarex Corporation (Dynarex Portable Co mpressor nebulizer etc. ), Meridian and Clinical Guard (such as the ClinicalGuard Ultrasonic Portable Nebulizer) can be used.

As mentioned above, patient compliance with inhaled drug therapy and early detection of exacerbations are important in the management of chronic obstructive pulmonary disease COPD. It is recognized herein that for treatments using nebulizers, monitoring systems greatly improve treatment compliance and exacerbation detection. Such monitoring systems and apparatus are described herein, for example, where some embodiments of apparatus, methods, and systems are illustrated in the figures.

Additionally, nebulizer monitoring systems that collect physical data such as respiratory rate, exhaled volume, and temperature over time can be used to monitor users (e.g., to monitor disease progression) or during drug testing (e.g., during clinical trials). ) is useful for monitoring subjects.

The methods, systems, and devices described herein can be used with any drug (e.g., bronchodilators, steroids, antibiotics) that can be nebulized by any nebulizer (e.g., the nebulizers described above). can. These agents can include, for example, molecules and polymers (eg, proteins), and often include saline or other carrier media. Examples include long-acting beta agonists (LABA), long-acting muscarinic antagonists (LAMA), inhaled corticosteroids (ICS), short-acting muscarinic antagonists (SAMA), short-acting beta agonists ( SABA), budesonide, azithromycin, tobramycin, pirfenidone, levefenacin, and the like. Therapeutic drugs are used to treat a variety of lung diseases, including COPD (chronic obstructive pulmonary disease), asthma, chronic bronchitis, emphysema, pulmonary fibrosis, cystic fibrosis, and lung cancer. Because inhaled therapeutics also provide entry into the bloodstream, some embodiments of the methods, systems, and devices described herein provide for systemic entry and treatment of non-pulmonary related diseases. Contains drugs used in nebulizers.

Thus, according to some embodiments of the invention, nebulizer sensing device 100 is connected between a source of aerosolized drug (e.g., a nebulizer) and a mouthpiece, nosepiece, or facemask. It can be configured as a conduit. Sensors placed within the conduit can thus detect the flow and flow rate of the user's inhalation and exhalation, as well as the presence or absence of medicated aerosol. FIG. 1A is a 3D perspective view of an embodiment comprising a nebulizer device 10, a nebulizer sensing device 100, and a mouthpiece 12. FIG. Also shown in the figure are the x, y, z translational axes and the R _x , R _y rotational axes assigned to the assembly. Nebulizer device 10 may include a medicated reservoir for containing a liquid drug, a nebulizer element (e.g., jet, ultrasound, or mesh, not shown), and a chamber for containing an aerosolized drug. can. The reservoir and chamber are not shown in this perspective for simplicity, but are components that are well understood in the art. Chambers and reservoirs can include, for example, capillaries, baffles, piezoelectric elements (and electrical connections thereto), gas inlet ports (e.g., connected to a pressurized gas source), and the aforementioned valves. can. In some embodiments, the nebulizer device 10 can also function as a holder, and in these embodiments the nebulizer device 10 is held with suitable handles, grips, grooves, and/or shapes therefor. It can be configured as follows. Nebulizer device 10 also includes a port or nebulizer mount 14 extending from the aerosol-containing chamber. This port or nebulizer mount 14 can be connected to a nebulizer sensing device 100 via a first connector. It will be appreciated that in some alternative embodiments, a conduit, such as a tube, can be inserted between the nebulizer device 10 and the nebulizer sensing device 100, the conduit providing a passage for aerosol/air therein. . The nebulizer sensing device 100 also includes a second connector that can engage/connect to a nebulizer mouthpiece 12, optionally comprising a flap valve 13 that opens upon exhalation and closes upon inhalation by the user of the device. be able to. Nebulizer sensing device 100 includes one or more sensors for detecting use of a nebulizer and an indicator for indicating the dose taken and/or the status of the user, as described herein. can be equipped with.

Nebulizer sensor device 100 is illustrated in more detail by FIG. 1B, which shows a 3D perspective view of the device. Device 100 can include a housing 110 that engages and seals with a first connector 114 (e.g., configured to engage and seal with nebulizer mount 14) and mouthpiece 12. forming a conduit between the outlet port 112 and the outlet port 112 adapted to do so. Housing 110 defines a sealed path from nebulizer mount 14 to mouthpiece 12 so that gas inhaled through mouthpiece 12 or exhaled through mouthpiece does not escape through the conduit. can do. Although the mouthpiece 12 is shown as transparent, the mouthpiece can be, but need not be, transparent. Thus, the housing 110 is configured as a conduit for aerosol/air flow through the first connector 114 and the second connector 112 in either direction, eg, while the user is inhaling or exhaling. In some embodiments, as shown in FIG. 1A but not in FIG. open to the external environment and close when breathing (for example, the device can remain closed when not in use). In these embodiments, the aerosol/air is exhaled through this one-way valve 13 and not returned through the first connector 114. Housing 110 of nebulizer sensor device 100 may also include one or more visual and/or audible indicators. In some embodiments, housing 110 displays a treatment or medication count indicator 140 and a respiration indicator 120. Breathing indicator 120 may be positioned so that it is visible to the user when the user engages mouthpiece 12, as shown. A treatment count indicator 140 may be positioned on the housing 110 as shown for easy viewing before or after completion of a treatment.

FIG. 2A is a cross-sectional view of a nebulizer monitoring device 100 according to some embodiments of the invention. As shown, the nebulizer mount 14 (e.g., the portion of the nebulizer device 10 that engages the first connector 114) is connected to the housing 110 via the first connector 114, and the housing 110 has an outlet port 112. It is connected to the mouthpiece 12 through the mouthpiece. Components 14, 110, and 12 thus define an internal conduit that allows aerosol/air to flow from the nebulizer chamber to mouthpiece 12. In some embodiments, the housing 110 with an interior space or conduit as described and illustrated includes one or more sensors disposed within the conduit, such as a pressure sensor 222 and a humidity sensor 250. ing. Protective elements such as protective membranes (e.g., GoreMembranes available from W.L. Gore & Co.) 223 and 252 also prevent aerosol liquids (e.g., those flowing through the conduit) from accumulating on the sensor and affecting sensor sensitivity. It can be provided to limit the amount given. In some embodiments, the housing can include one or more indicators, such as a breathing indicator. For example, the breathing indicator may include one or more LEDs 224 and one or more light pipes 226 proximate one end to the LEDs 224 such that the light pipes 226 allow light from the LEDs 224 to be viewed by the user. can be transmitted to the exterior surface of the housing. In other embodiments, the housing 110 optionally or additionally includes one or more other LEDs 242 and one or more light pipes 244 to communicate dosage, usage, or other information to the user. It can be done. The housing 110 may also include a controller board, such as a printed circuit board PCB board 210 on which a supervisory controller 230 is mounted, as shown in the detailed view of FIG. 2B. Printed circuit board PCB 210 includes one or more accelerometers or gyroscopes 280 (e.g., for sensing motion and transmitting velocity and/or acceleration signals to monitoring controller 230) and one or more wireless A communications transceiver 290 (eg, for transmitting and receiving data to and from external devices) may be included. Supervisory controller 230 may include a central processing unit (CPU) 231 and memory 233, for example as part of an integrated circuit or system on a chip. Additionally, the CPU 231 can be connected to a timer unit and/or a timer can be included in the CPU (eg, included as a hardware time or programmed as a software time). Supervisory controller 230 may also include other integrated units for communications (eg, transceiver 290) and power management (not shown), for example. Supervisory controller 230 may comprise a microcontroller, e.g., "microcontroller" as used herein describes an integrated circuit designed to implement or control specific operations in an embedded system. It typically includes a processor, memory, and input/output peripherals on a single chip. Supervisory controller 230 and/or microcontroller may comprise, for example, an ARM-based microcontroller, a PIC-based microcontroller, or an Intel-based CPU or microcontroller. The LEDs and sensors can be connected to and communicate with the controller, eg, electrically or wirelessly. In some embodiments, the LED and pressure sensor are mounted/integrated on the printed circuit board PCB board, and the humidity sensor is not mounted on the printed circuit board PCB board, as shown in FIG. 2A. In other embodiments, the various elements may be arranged differently, for example, the humidity sensor may be mounted on the printed circuit board PCB board and the pressure sensor may not be mounted on the printed circuit board PCB board, or multiple It should be understood that some/all of the LEDs may not be directly attached to the printed circuit board PCB board. In some embodiments, internal (e.g., batteries or capacitors) and/or external power sources (e.g., conventional AC power adapters or power supplies) are used to power the supervisory controller 230 and power the various components. It can be distributed as needed to provide power. For example, power may be provided via a connection plug attached to housing 110 that connects to an external power source (not shown) and/or via an internal or external battery 260 as shown. In some embodiments, replaceable batteries may be used. In some embodiments, the battery 260 is rechargeable, e.g., by direct electrical connection using a charging circuit, or by induction using a wireless power transfer technology, e.g., Qi or Near Field Communication (NFC). It can be a battery.

In some embodiments, pressure sensor 222 can include a differential pressure sensor or a flow meter. Differential pressure flow meters introduce a constriction into a pipe, create a pressure drop across the constriction 116 in the direction of the flowing fluid/gas, and use two pressure sensors 222, one on each side of the constriction. and can be measured. The increased flow creates more pressure drop as the fluid/gas flows through the constriction. Thus, a differential pressure sensor can be calibrated for a particular material, such as air/aerosol, to determine the velocity (eg, fluid flow rate) and direction of flow through the pipe/conduit. For example, an upstream pressure sensor is expected to have a higher pressure than a downstream sensor, and the sensor can be calibrated to determine flow rate as a function of upstream pressure and downstream pressure. The monitoring controller 230 determines a volume (e.g., exhalation rate) of gas (e.g., air and/or aerosol) by associating a time stamp with each pressure measurement and a flow rate value determined from the pressure measurement. can do. For example, the volume of air and/or aerosol inhaled or exhaled can be determined as a function of flow rate over a preset period of time. The direction of flow (eg, inhalation or exhalation) may be determined by the position of the pressure sensor relative to mouthpiece 12 or nebulizer device 10 relative to each other. For example, during inhalation, the pressure at the pressure sensor closest to nebulizer device 10 will generally be greater than the pressure at the pressure sensor closest to mouthpiece 12. For example, during exhalation, the pressure at the pressure sensor closest to nebulizer device 10 will generally be less than the pressure at the pressure sensor closest to mouthpiece 12. The monitoring controller 230 records the pressure, flow rate, and time of each measurement in memory so that the monitoring controller 230 or the remote system can determine how long each user is inhaling and exhaling, and how long the user is taking each dose. The amount of exhalation can be determined as a respiratory index such as how many times the person takes a breath. The pressure, flow rate, and time of each measurement can be sent to a remote system for further analysis.

In some embodiments, the nebulizer monitoring device 100 can include a constriction created by a mesh or plate with one or more holes positioned perpendicular to the flow within the conduit. In some embodiments, the stenosis can be minimized to minimize the amount of pressure drop and reduce the difficulty of breathing through the device for the user. A flow meter can be equipped with a time measuring element that allows direct determination of flow rate. The flow meter can, for example, detect the start/stop of a pressure differential and be coupled to the monitoring controller 230 and CPU 231 for data processing to detect the start and stop of flow. It will be appreciated that in some other embodiments, a different flow meter may be used, for example, to replace or supplement pressure sensor 222. For example, a mass flow meter can be used.

The measured flow rate in combination with the amount of time during which flow is detected can be used to determine the total volume during flow. 2C and 2D show representative plotted respiration data as may be measured using pressure sensor 222. Figure 2C shows a respiratory rate of 15 breaths per minute and Figure 2D shows a respiratory rate of 20 breaths per minute. Tidal volume can be calculated, for example, as the area under the suction curve.

In some embodiments, a nebulizer device, such as nebulizer device 10, can include one or more temperature sensors 232 configured to measure the temperature of a user using nebulizer device 10. In some embodiments, the temperature sensor is embedded in the mouthpiece 12 or attached to the mouthpiece such that when the user places their lips on the mouthpiece 12, the temperature sensor measures the temperature of at least one of the user's lips. piece 12. For example, the temperature sensor can include a thermistor or thermocouple connected to the monitoring controller 230, eg, via electrical cables/contacts. In some embodiments, nebulizer device 10 includes a thermistor 232 disposed at the proximal end of mouthpiece 12 and arm 234 can be used to electrically connect thermistor 232 to monitoring controller 230. . 3A, 3B, and 3C show some embodiments for connecting a temperature sensor 232 to the proximal end of the mouthpiece 12 so that it can come into contact with the user's lips during use. shows. FIG. 3A shows an arm and hinge configuration with a rigid arm element 234 and a hinge element 1310, with a thermistor 232 disposed within or on the arm element 234 at the opposite end from the hinge element 1310. Can be done. The first panel of FIG. 3A shows the arm 234 in position when the device is not in use, while the second panel of FIG. 3A shows the arm 234 moved into position for use by a user. The thermistor 232 is located near the proximal end of the mouthpiece 12. FIG. 3B shows another optional embodiment comprising a clip-on retention element 1312 connected to a monitoring controller 230 by a bendable and/or flexible cable 1314. The first panel of FIG. 3B shows the clip 1312 and cable 1314 in the position when the device is not in use, while the second panel of FIG. 3B shows the clip 1312 secured to the mouthpiece 12, thus , the thermistor 232 is positioned against the proximal end of the mouthpiece 12 so as to contact the user's lips or lips during use. FIG. 3C shows an embodiment using a stretch-over elastic retainer 1316 with a flex cable 1314. The first panel of FIG. 3C shows the resilient retainer 1316 and cable 1314 in position when the device is not in use, while the second panel of FIG. Resilient retainer 1316 is shown, thus indicating the location of thermistor 232 at one of the proximal ends of the mouthpiece that contacts the user's lips or lips during use. Note that in FIGS. 3A-3C, the thermistor is not shown, but rather the area where the thermistor is present is indicated by an arrow.

Humidity sensor 250 may be any humidity sensor known in the art. As used herein, "humidity" refers to the water vapor content in air or other gases. Humidity measurements can be stated in various terms and units. Three commonly used terms are absolute humidity, dewpoint, and relative humidity (RH). As used herein, "absolute humidity" is the ratio of the mass of water vapor to the volume of air or gas. "Absolute humidity" can be expressed in grams per cubic meter or grains per cubic foot (1 grain = 1/7000 pound). The term "dew point" here refers to the temperature and pressure at which a gas begins to condense into a liquid, and is expressed in degrees Celsius or degrees Fahrenheit. "Relative humidity" or "RH" or "%RH" as used herein means the ratio of the moisture content of the air (expressed as a %) compared to the saturated moisture content at the same temperature and pressure. In some embodiments, humidity sensor 250 is a capacitive humidity sensor. For example, a capacitive RH sensor consisting of a substrate (eg, glass, ceramic, or silicon) with a thin film of polymer or metal oxide deposited between two conductive electrodes. These sensors typically have a sensing surface coated with a porous metal electrode to protect it from contamination and condensation. In some other embodiments, humidity sensor 250 is a resistive humidity sensor that measures changes in the electrical impedance of a hygroscopic medium, such as a conductive polymer, salt, or treated substrate. For example, it consists of an electrode (eg, a noble metal electrode) on a suitable substrate coated with a conductive polymer (such as polyimide), a salt, or an activating chemical. Changes in relative humidity are indicated by corresponding changes in the electrical resistance profile of the coating material. Other humidity sensors known in the art may also be used in embodiments of the device to monitor nebulizer usage.

According to some embodiments of the invention, the sensors (eg, pressure sensor 222 and humidity sensor 250) can be equipped with protective elements, such as hydrophobic breathable membranes that cover sensitive elements of the sensors. As used herein, a hydrophobic breathable membrane is a film or sheet material that allows the passage of gases such as oxygen, nitrogen, and water vapor, but not larger substances such as liquid or solid particulates. It is a structure of For example, a hydrophobic breathable membrane will not pass anything larger than about 10 nm (eg, larger than about 100 nm, larger than about 0.5 μm). In some embodiments, the hydrophobic breathable membranes are Gore membranes 252 and 223. The hydrophobic breathable membrane ensures or minimizes any large particulates, such as liquid particulates in an aerosol, from depositing on sensitive parts of the sensor. These types of membranes can prevent or reduce fouling and corrosion, minimizing abnormal or inaccurate readings and sensor damage.

It should be appreciated that other embodiments of the nebulizer monitoring device 100 may include other sensors in the interior space (conduit) of the housing 110, such as a temperature sensor or a CO ₂ sensor. Additionally, the placement of the sensor is a matter of choice for those skilled in the art; for example, the sensor can be placed on or adjacent to the inner surface of the conduit, or floating or spaced from the inner surface of the conduit. I hope you understand that you can. For example, the placement of any sensor can be determined based on the mode of operation of the sensor and the property it is intended to measure.

In some embodiments, the housing can include an accelerometer and/or gyroscope 280 and is configured to measure movement and position of the nebulizer monitoring device 100 during use. For example, the accelerometer and/or gyroscope 280 can be used to detect when the nebulizer monitoring device 100 is picked up, initiate a monitoring function, and determine the orientation of the nebulizer monitoring device 100 during use. .

In some embodiments, accelerometer 280 may be used to determine whether the device is being used in the correct orientation. As used herein, correct orientation refers to all or a majority (e.g., about 99% or more, about 95% or more, about 90% or more, or about 80% or more) of the medical solution in the nebulizer reservoir. ) is nebulized and is oriented so that the nebulizer can function so that it is not lost, such as by spilling from the reservoir when the nebulizer device 10 is turned sideways during use. According to some embodiments of the invention, each nebulizer device can be designed to operate in an optimal orientation or range of orientations (eg, within 10 degrees of horizontal). For example, for a nebulizer as shown by Figure 1A, the correct orientation is with the mouthpiece horizontal to the ground and without any tilt angle, e.g. the plane set by the xy translation axes shown in the figure is It is parallel to the ground. In this orientation, the rotation axes of R _x and R _y can be set to have zero angle. In some embodiments, the correct orientation is such that the angles of R _x and R _y are between about -5 degrees and +5 degrees (e.g., between about -10 degrees and about +10 degrees, between about -15 degrees and about +15 degrees). or between about -20 degrees and about +20 degrees). As an alternative explanation, accelerometer data can detect gravity vector data and can be used to detect the horizontal/vertical angle of the device. Accordingly, accelerometer 280 can measure the orientation of device 100 and, via supervisory controller (microcontroller) 230, can store this information in memory and transmit this information to a remote system.

Accelerometer 280 can also be used to "wake up" the monitoring device 100 from "sleep" when it is picked up. As used herein, a device is one in which at least some of the device's elements, e.g., some sensors, are off and do not receive power or are below a threshold required to operate as a sensing device. When receiving level power, it is in "sleep" or "sleep mode". In sleep mode, the necessary power may be provided to maintain the sensor, but the sleeping sensor does not collect data or send signals of collected data to the monitoring controller 230. In some embodiments, in sleep mode, accelerometer 280 is connected to, receives power from, and communicates with supervisory controller 230, while other sensors receive little or no power. For example, the supervisory controller 230 may operate in an operating mode that continuously monitors signals from the accelerometer/gyroscope 280 and determines whether the device 100 has been picked up via a software algorithm executed by the CPU 232. (e.g., the algorithm determines that the movement (eg, velocity and/or acceleration over time) of the accelerometer or gyroscope 280 is greater than a preset threshold for more than a short period of time). For example, if the accelerometer/gyroscope 280 detects acceleration and/or velocity that exceeds a preset threshold for a period of time, such as at least about 3 seconds, the algorithm may determine that the device has been picked up by the user. can. The preset time can be selected such that the device does not wake up due to accidental movements, such as bumping into a nightstand on which the device is placed, for example. In some implementations, the nebulizer monitoring device 100 uses accelerometer data and software algorithms executed by the CPU 232 to detect unrelated movements that are picked up or accidental movements, such as those caused by an airplane. It is possible to detect rocking movements on a ship. If it is determined that the device has been picked up by a user, the algorithm can be programmed such that the controller executes an instruction to "wake up" the nebulizer monitoring device 100 and place it in a normal mode of operation. As used herein, the device is in a wake-up mode or an operating mode, or one or more of the sensors, such as pressure sensor 222 and humidity sensor 250, so that flow rate and humidity data can be collected. and indicator LEDs 224 and 242 (e.g., to indicate to the user that the device is operating) and can be used to monitor use of the nebulizer, such as turning on power to associated components on the supervisory controller 230. "Wake up" to a state running software instructions or programs. Optionally, the process of waking up nebulizer monitoring device 100 includes a power-up routine performed by monitoring controller 230 to turn on and verify that each element is connected to monitoring controller 230 and functioning properly. can be equipped with. Optionally, the wake-up process first monitors signals from one or more of the pressure or humidity sensors and processes the received signals to determine whether the nebulizer device 10 is being used by a user. etc., can occur in stages. For example, the time between transporting and using the device 100 may vary; for example, in some embodiments, some assembly may be required before using the device in a nebulizer, as described in more detail below. is required and therefore the device does not need to be fully awake immediately. Fully awake means that at least one, and in some embodiments all, of the device's sensors are on and monitoring the delivery of a dose and the end of delivery of a dose. means. Termination of administration may be due to a sensed decrease in humidity and/or cessation of inhalation/exhalation detected by a flow sensor, as described herein. In some embodiments, "sleep" mode comprises data transfer, as described below. According to some embodiments of the invention, after the device 100 wakes up or enters wakefulness mode, the supervisory controller 230 may be configured to A 30 minute timer may be started, and upon expiration of the timer, supervisory controller 230 may return device 100 to sleep mode.

Prior to use of nebulizer monitoring device 100, a medicated solution is added to the reservoir of nebulizer device 10. The medicated solution can be in a dosage form, such as a cartridge or package, with the nebulizer device 10 configured to receive and pierce or open a portion of the cartridge or package. The medicated solution can then be dripped or flowed into the reservoir. In some configurations, the cartridge or package can function as a reservoir, and, for example, puncturing or opening the cartridge or package can connect the contents to a capillary tube used in a jet nebulizer configuration. In some embodiments, a cartridge or package can contain an amount of medicated solution to be used as a single dose for one treatment session. The time and amount of liquid for administration depends on the treatment and the type of nebulizer device. For example, although nebulizing cycle times differ, jet nebulizers take longer to perform nebulizing treatments than ultrasound nebulizers and require more medicinal liquid to deliver a therapeutically effective amount of nebulized drug. It may be necessary. In some embodiments, it takes 2-20 minutes (eg, 2-3 minutes, 3-7 minutes, 5-12 minutes) to take correctly.

Also, before use, the nebulizer is assembled by either user. Nebulizer device 10, nebulizer sensing device 100, and mouthpiece 12 can be inspected, for example, to ensure they are clean, before being assembled. Also, other components of the nebulizer device can be assembled and connected as required, eg any power supplies and tubes can be connected/switched on as required. As mentioned above, in some embodiments, device 100 is automatically awakened by motion that may be sensed by accelerometer 280 and accelerometer signals received by supervisory controller 230. In addition to assembly, in embodiments, temperature sensor 232 can be moved to an operational position, such as in a position near mouthpiece 12. In some embodiments, an indicator element attached to housing 110 indicates, for example by illumination, vibration, or sound emission, that the device is powered and, optionally, ready for use. i.e., properly assembled). For example, such indicators may be activated by electrical or inductive contacts and switches between members 10, 100, 12 all connected to supervisory controller 230. Also, as previously discussed, in some embodiments using an accelerometer 280 in or on the housing 110, handling of the device 100, such as during assembly, may cause the sensor to be activated based on a preconfigured software algorithm or program. The device wakes up so that it turns on. Motion signals detected by accelerometer 280 can be used by a software program executed by supervisory controller 230 to determine whether the device is assembled correctly. This software algorithm can use machine learning to detect and learn movements associated with correct device 100 assembly. For example, a machine learning algorithm receives as input a sequence of motion signals and determines how closely the sequence of motion signals matches one or more learned acceptable assembly sequences to assemble the device. may generate a correctness measure and optionally trigger a visual indicator (e.g., a green color for correctness if the correctness measure is above or below a preset threshold). light or a red light for incorrect answers if the correctness measure is below or above a preset threshold).

Once properly assembled, the user inserts the mouthpiece into his or her mouth, for example between his teeth. In embodiments where a face mask is used, the face mask is appropriately positioned. In those embodiments using a face mask, the face mask includes a temperature sensor positioned to be inserted into or in contact with the user's mouth, or a temperature sensor placed on the face mask to contact the user's face and measure the user's temperature. A temperature sensor may be provided. In embodiments comprising a temperature sensor such as 232, the temperature sensor contacts at least a portion of the lips, for example the lower lip, where 232 may be set in the mouth, but not the user's teeth/ Make sure not to go past the gums. The thermistor signal or data is sent to monitoring controller 230 for storage in memory, processing (eg, converting the signal to temperature), and optionally transmission to a remote system. In some embodiments, the thermistor signal is measured as a resistance that can be converted to lip temperature by a software program executed by the controller, which is further converted to core temperature (e.g., between the user's lips and core temperature). (by known or measured/calculated correlations). Thus, the use of temperature sensor 232 allows temperature data of the user to be measured and tracked during treatment. Such information is useful in determining the user's general health, including early detection of deteriorating conditions that lead to increased body temperature. Additionally, while proper and consistent placement of the sensor in the mouth can result in temperature sensing consistent with the user's body temperature, improper use can result in absent or erratic temperature sensing. Therefore, temperature monitoring also functions as one indicator of compliance. As previously discussed, in some embodiments the temperature sensor is included in the interior space conduit or the housing 110 conduit. A temperature sensor within the conduit may record the exhalation temperature, which, through correlations of those skilled in the art, is related to the core temperature of the breathing user. The conduit temperature sensor can be a redundant temperature sensor to sensor 232 and can provide an alternative temperature sensor in place of sensor 232.

Continuing from above with respect to a user's use of the nebulizer monitoring system 100, after properly inserting the mouthpiece 12 into the mouth, the user takes a breath (e.g., using slow, deep, or tidal breathing). , inhale, exhale). In some embodiments, a flow sensor (eg, pressure sensor 222) is engaged before allowing nebulization/aerosolization of the medicated solution. In these embodiments, the flow sensor sends signals or data to the monitoring controller 230 that the user is inhaling or exhaling ambient air, and from these signals or data the monitoring controller 230 determines whether the user is inhaling or exhaling ambient air. A software program can be executed to determine how much to spit and how much to spit. For example, data can be sent to a remote system (e.g., an external computer or a cloud-based computer system) and a software program running on the remote system can be used to analyze the data and determine the user's output during each treatment session. Measured values can be determined. In some embodiments, once proper breathing is established, the nebulizing element (e.g., jet nebulizer, piezo nebulizer, mesh nebulizer) is activated and the user begins treatment by inhaling a dose of medication. can do. In addition to temperature, exhalation volume and respiration rate can also be used to monitor the user and can be used to alert the user or caregiver of exacerbating conditions if exhalation volume and/or respiration rate are outside of the user's normal range. can indicate the start of. For example, if a smaller spit volume is measured compared to the user's normal or baseline spit volume (e.g., a previously determined mean, average, or threshold volume value), the monitoring controller 230 or the remote The system can communicate a signal indicating that a potential exacerbation condition has been detected. The monitoring controller 230 or the remote The system can communicate a signal indicating that a potential exacerbation condition has been detected. In some embodiments, the user's measured exhaled volume or respiratory rate, in addition to being stored in memory by the monitoring controller 230, is communicated to the user in real time by a display, such as an LED light 224, or by a smartphone, It may also be communicated wirelessly to a remote computer or base station.

4A-4B and 5A-5B illustrate how the LED lights 224 are placed and operated under the control of the supervisory controller 230 to provide communication and feedback to the user in real time both during and after use. showed how use and dosage can be tracked.

FIG. 4A is a top view of some embodiments showing mouthpiece 12 and housing 110. In this configuration, the indicator 1410 has an elongated shape in a direction perpendicular to the axis of flow of the drug solution in the mouthpiece, and the LED light 224 and light pipe 226 control the light intensity of the indicator. Provide increases and decreases. FIG. 4B shows how light intensity can be used as an indicator of inhale and exhale intensity. For example, the supervisory controller 230 connected to the pressure sensor 222 establishes the flow direction and flow rate and uses an algorithm as part of a software program executed by the CPU 232 to adjust the flow direction and flow rate to the appropriate current/voltage. can be converted to adjust (modulate) the intensity of the light emitted by the LED 224. The first panel of FIG. 4B shows an embodiment in which the intensity of light from indicator 1410 increases when the user inhales. The second panel of FIG. 4B shows an embodiment in which the intensity of light from the display decreases when the user exhales. The intensity of the light can indicate not only the amount of flow, but also the direction of flow, thus providing the user with real-time information regarding the use of the nebulizer. For example, a user can get a real-time indication as to whether they are breathing tidally or deep enough for effective treatment.

FIG. 5A is a top view of some other embodiments showing mouthpiece 12 and housing 110. In this configuration, the indicator 1412 has an elongated shape in a direction parallel to the axis of flow of the medical solution within the mouthpiece 12. In this embodiment, LED lights 224 and light pipes 226 can provide a stretching or growing effect or impression within the display 1412. The first panel of FIG. 5B shows the expansion within indicator 1412 when the user inhales. The second panel of FIG. 5B shows contractions within indicator 1412 as the user exhales. Extensions and contractions can be generated, for example, by a series of LED lights that are illuminated continuously according to a software program executed by supervisory controller 230 in response to signals received from pressure sensor 222. The extension/deflation can provide a real-time indication to the user that they are breathing through the nebulizer to receive their dose of medication.

In some embodiments, different frequencies (colors) of light may be used to indicate inhalation and exhalation, for example. For example, FIG. 5C shows a top view of housing 110 with different colored lights 1413 and 1415 emitted from the indicators. The first panel of FIG. 5C shows the emission of blue light 1413 from the indicator indicating an inhale, and the second panel of FIG. 5C shows the emission of violet light 1415 from the indicator during an exhale. The intensity (or brightness) of the light (of each color) is controlled by the monitoring controller 230 and can be used to indicate in real time the inhalation or exhalation air flow rate.

According to some embodiments of the invention, only the inhalation portion of the breath is monitored. For example, an embodiment with valve 13 (FIG. 1A), in which exhaled breath does not cause flow past pressure sensor 222 (FIG. 2A), as described herein. A flow sensor detects only inhaled breath. In some embodiments, a valve, such as valve 13, may be included in configuration with the device so that exhaled breath is detected. For example, valve 13 may be placed between pressure sensor 222 and nebulizer device 10, as part of nebulizer monitoring device 100 or as part of nebulizer device 10.

It is understood that some other embodiments may use other indicators to convey inhalation and exhalation intensity. For example, some embodiments alternatively or additionally emit a loud or soft tone, beep, chord, or piece of music to indicate air/aerosol flow within the nebulizer monitoring device 100. May be equipped with an audible indicator. Also, the audible indicator can emit a sound that varies in frequency and/or amplitude (eg, loudness) depending on the strength and/or direction of breathing (eg, inhale vs. exhale). Some other optional embodiments may include a vibrating member that can vary the vibration intensity based on the flow direction or velocity of the air/aerosol within the nebulizer monitoring device 100, for example.

During a treatment session, use of the nebulizer can be monitored by a nebulizer monitoring device to record information regarding the treatment session, for example using memory element 234. In addition to inhale and exhale data as described above, dose data (eg, inhales where a humidity sensor indicates that the humidity of the inhaled air is greater than a preset threshold) can be recorded. The monitoring controller 230 records the date and time and includes the start date and time (e.g., when the first inhalation was recorded) and the stop date and time (data and time) (e.g., when the last inhalation or exhalation was recorded) of each treatment session. A timer and a real-time clock (e.g., either hardware or software) can be included to store the timer and real-time clock. Each inhale and exhale is recorded as a series of data points indicating air flow rate (or pressure from a pressure sensor) and optionally direction of air flow, or a time offset from a preset date and time. It can be recorded along with the

In some embodiments, nebulizer monitoring device 100 can use flow data to determine whether a dose has been taken and completed, and then nebulizer monitoring device 100 can be shut down. For example, the CPU 231 may specify a preset time for taking the medication, such as 5 to 20 minutes (eg, 2 to 3 minutes, 3 to 7 minutes, or 5 to 12 minutes); and/or shut down the device after a preset period of device inactivity (e.g., no change in accelerometer signal) (e.g., 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes). , or the device can be programmed to enter sleep mode. The nebulizer monitoring device 100 may alternatively or additionally be used for a preset period of time (e.g., 5 minutes, 10 minutes, 15 minutes, 20 minutes, or 30 minutes) after the nebulizer monitoring device 100 wakes up. ), after no movement (e.g., no change in the accelerometer signal), the monitoring controller 230 (via the pressure sensor 222) is activated for 10 seconds or more (20 seconds or more, 30 seconds or more, 60 seconds or more, or 5 It can be programmed to enter a shutdown or sleep mode if no flow is detected (eg, no pressure or flow signal, or no change in pressure or flow signal) for a period of time (e.g., no pressure or flow signal, or no change in pressure or flow signal) for a period of time (more than 1 minute). In some embodiments, the nebulizer monitoring device 100 allows the monitoring controller 230 (via the pressure sensor 222) to perform a program to enter a shutdown or sleep mode if it does not detect a change in flow rate across zero (see, e.g., FIG. 2C or FIG. 2D), indicating that suction and exhalation through the device has ceased. Can be done. In some embodiments, the monitoring controller 230 processes the amount of time during which inhalation/exhalation flow is detected and compares the amount of time to a preset threshold for administering the dose. can determine whether a dose has been administered. For example, administration can be considered complete if the inhalation and exhalation times measured by the nebulizer monitoring device 100 are at least 80% of the preset time. For example, if the preset time is 2-3 minutes, a dose will be considered taken if the nebulizer monitoring device 100 records at least 1.6 minutes of inhalation and/or exhalation; If the duration is between 5 and 12 minutes, a dose is considered taken if the nebulizer monitoring device 100 records at least 4 minutes of inhalation/exhalation.

According to some embodiments of the invention, humidity sensor 250 data can be used to determine whether proper administration or treatment has occurred. In operation, aerosolized medication flows through the conduit and contacts humidity sensor 250, which increases the humidity within the conduit. For example, if the user forgets to fill the medication reservoir with a dose of liquid medication before using the nebulizer, low humidity will be measured by the humidity sensor and sent to the monitoring controller 230 during that therapy session. FIG. 6 shows an example plot of humidity data recorded during use. In this example, before about 45 seconds, humidity sensor 250 is exposed to ambient airflow (no aerosolized drug), and between about 45 seconds and 210 seconds, humidity sensor 250 is exposed to the nebulizer. After 210 seconds of being exposed to an air flow comprising the aerosolized drug produced by the device 10, the humidity sensor 250 is exposed to an ambient air flow (without aerosolized drug). An abrupt onset or transition is seen when the humidity sensor 250 is exposed to aerosolized drug from a nebulizer and the humidity rises above 80%. A similar rapid drop is seen when the aerosolized drug from the nebulizer is turned off and the humidity sensor 250 is exposed to relatively dry ambient air, with humidity significantly below 80%. In some embodiments, while the nebulizer is in proper use (e.g., while using a medicated solution), the average ambient humidity will be high, but the instantaneous humidity may oscillate at least slightly up and down. (e.g., when the user inhales or exhales), the nebulizer monitoring device 100 can determine that a change in measured humidity is indicative of use (e.g., when measuring baseline humidity before treatment). ). In some embodiments, a relative humidity of about 20%, 30%, 40%, 50%, 60%, 70%, or 80% or more is present when the nebulizer device 10 is operating and the drug formulation being nebulized. , indicating that the medicine is filled.

In some embodiments, monitoring of the user's dosing compliance, in addition to being processed and stored by the monitoring controller 230, can also be communicated to the user in real time by a display on the nebulizer monitoring device. For example, an LED light or display can be used to identify the number of doses taken during a preset time period. These LEDs or displays can provide real-time dosing/treatment information to the user.

FIG. 4A shows an array of dose indicators 1414. Dose indicator 1414 may include a window in the housing connected to one end of light pipe 244 that is illuminated when one or more indicator LEDs 242 mounted on printed circuit board PCB 210 are activated. can. The monitoring controller 230 can determine when the treatment is complete (as described herein) as a function of signals and/or data received from the humidity sensor 250 and/or the pressure sensor 222; One or more indicator elements 1414 can be suitably illuminated, eg, one element for each detected treatment or dose. In some embodiments, indicator element 1414, once illuminated, indicates a preset period of time (e.g., 8 hours or 12 hours - if the treatment is every 6 hours, dose indicator 1414 indicates that the last dose has been received). may remain on for up to 6 hours to indicate ingestion within 6 hours) or until a preset time is reached (e.g., 12:00 a.m., 2:00 a.m., or the last Until any time (e.g., 6 a.m.) between the expected time of administration/therapy and the expected time of the first administration/therapy of the day, indicator 1414 indicates how many doses have been completed during the day. and be reset (e.g., turned off) before the first dose/treatment of the day. Then, after 24 hours, it is reset (eg, turned off) and can begin counting doses again for another day. Thus, indicator element 1414 can provide a user or health care provider with a way to confirm dose counts and can help support and track compliance with nebulizer therapy. In some embodiments, other indicators may be used, such as an audible indicator that emits a sound when a dosing session is complete, or a vibrating element that vibrates when a dosing session is complete. Can be done.

In some embodiments, multiple sensors can be used to determine dosing compliance, eg, to determine both quantity and quality of usage. This means that users are (1) regular users with good skills, (2) regular users with bad skills, (3) irregular users with good skills, and (4) irregular users with poor skills. Useful for determining whether the user is For example, if the user is reclining, facing down (e.g., when the angular direction measured by accelerometer 280 is not horizontal and R _x ≠ 0, see FIG. 1A), or tilting the head ( A nebulizer that is being used in an incorrect or non-optimal orientation, such as when the angular direction measured by accelerometer 280 is not horizontal and R _y ≠ 0 (see FIG. 1A), may cause monitoring controller 230 to Detection can be performed using signals received from a total of 280 sources. In this situation, if the user is breathing correctly through the device, a flow rate will be detected, but most likely all or some of the medical solution may spill from the reservoir. Therefore, the humidity does not reach typical values (eg, above about 80% RH for a predetermined treatment period) over a period of time that is expected for the nebulized material. In another scenario, the nebulizer may be turned on and placed on a surface (eg, in the correct orientation according to accelerometer 280) for some or all of the typical time duration of the treatment. Here, a temperature sensor may indicate that the mouthpiece is not in contact with the user for the duration of the treatment, a pressure sensor may also indicate that the mouthpiece is not in contact with the user, and a humidity sensor may detect humidity, but the will indicate that the user is not breathing the nebulized material for some time. In yet another scenario, the user may have forgotten to add medication to the nebulizer reservoir, but may have otherwise used the nebulizer correctly (e.g. correct orientation, mouthpiece preset). position and breathing correctly). In this scenario, the humidity sensor will indicate that the nebulizer drug is not being delivered. Combining data from two or more sensors is therefore useful in providing more robust data for use by software-based programs or algorithms used to determine dose quantity and quality.

According to some embodiments of the invention, nebulizer monitoring device 100 includes one or more pressure sensors 222, humidity sensors 250, temperature sensors 230, accelerometers or gyroscopes 280 connected to a monitoring controller 230. It can be done. In operation, supervisory controller 230 receives signals from each sensor, converts the signals to raw sensor data (eg, using an analog-to-digital converter), and stores the raw sensor data in memory 233. Nebulizer monitoring device 100 includes one or more transceivers 290 that allow monitoring controller 230 to transmit data to a remote system (e.g., base station 300, personal computer, smartphone, cloud-based system). Can be done. According to some embodiments of the invention, the supervisory controller 230 transmits some or all of the raw sensor data (e.g., pressure data, humidity data, temperature data, accelerometer data, gyroscope data) to a remote system. Can be sent. Raw sensor data may be processed by monitoring controller 230 and/or a remote system to create processed sensor data. For example, a pressure sensor sends a signal in the form of a voltage or current level that is processed and converted into a pressure measurement. The processed sensor data can be sent to a remote system along with or in place of the raw sensor data. The nebulizer monitoring system can include a real-time clock that tracks the date and time of the day, or wirelessly (e.g., WiFi, (using Bluetooth® or ZigBee®). The monitoring controller 230 may associate the sensor raw data with a date and/or time stamp so that the date and time the sensor raw data was received can be recorded. According to some embodiments, the date and timestamp may be a digital representation of local or GMT time and date. In accordance with some embodiments, the date and time stamp are offset from a preset date and/or time (e.g., seconds after midnight on January 1, 1980, or midnight on the current day). seconds). In accordance with some embodiments, the monitoring controller 230 determines the date associated with each element (e.g., a data value or group of data values corresponding to a single data point) or group of elements of raw sensor data stored in memory. and/or timestamp values may be stored. In accordance with some embodiments, the monitoring controller 230 determines the date and time associated with each element (e.g., a data value or group of data values corresponding to a data point) or group of elements of processed sensor data stored in memory. /or a timestamp value may be stored. In accordance with some embodiments of the invention, the monitoring controller 230 includes a corresponding date and/or time stamp with either the raw sensor data and/or the processed sensor data transmitted to the remote system. be able to.

FIG. 7A illustrates an embodiment of a base station 300 configured to receive a nebulizer monitoring device 100, according to some embodiments of the invention. FIG. 7B shows a possible environment in which it may be used, for example a base station in a nightstand. As depicted in these figures, base station 300 can have a port 710 for receiving one end of nebulizer monitoring device 100 (e.g., inlet port or nebulizer connector 114 or outlet port or mouthpiece connector 112). can. In some embodiments, base station 300 includes an electrical connection, eg, 712, to a power source such as a wall outlet. In some embodiments, nebulizer monitoring device 100 can include one or more batteries 260 connected to monitoring controller 230 and charging circuitry for charging the batteries, as shown in FIG. 7A. When the nebulizer monitoring device 100 is placed on the base station 300 in this way, the nebulizer monitoring device 100 can be charged. In some embodiments, one or more batteries 260 can be wirelessly and/or inductively charged. The base station 300 and the nebulizer monitoring device 100 each have an electric field generated by the induction coil 724 of the base station 300 when the nebulizer device 10 is placed at the base station as shown in FIG. 7A. Induction coils 722 , 724 can be included for inductive charging of battery 260 , such as inducing a current through 722 . The induction coil 722 of the nebulizer device 10 can be connected to a charging circuit that controls the flow of current to charge one or more of the batteries 260. In some alternative embodiments, charging occurs via direct electrical contact. For example, if the base station is equipped with multiple pogo pins 734 and the nebulizer mount is equipped with multiple contact pads 732. Pogo pins 734 and contact pads 732, when combined as shown in FIG. 7A, can provide an electrical connection between the nebulizer mount and the nebulizer monitoring device to transfer electrical energy, for example, to charge battery 260. . It is understood that other forms of contact can be made between the nebulizer monitoring device and the base station for charging, such as, for example, a USB connection, a standard two or three prong plug, or an auxiliary power cord. sea bream.

In some embodiments, base station 300 includes one or more controllers (e.g., a central processing unit and associated memory and/or systems on a chip) and one or more wireless transceivers (e.g., Bluetooth ( nebulizer monitoring device 100 can include a wireless transceiver 290 (e.g., Bluetooth®, WiFi, and/or cellular data communication). ZigBee(R), and/or cellular data communications (also possible). Transceiver 290 of nebulizer monitoring device 100 may transmit raw data and processed data to a wireless transceiver of base station 300. In some embodiments, base station 300 may include a wireless transceiver for wireless communication with remote systems such as a smartphone or tablet, a personal computer, a local hub, or the cloud.

The nebulizer monitoring device 100 collects usage data when the nebulizer device 10 is used by a user, and the data collected from sensors and stored in memory by the monitoring controller 230 is transmitted via, for example, Bluetooth® or WiFi. Communications may be used to transmit wirelessly to base station 300. In some embodiments, data may be transmitted in real time while nebulizer device 10 is in use (eg, including a delay due to monitoring controller 230 processing the data prior to transmission). According to some embodiments, data may be transmitted at a later time, for example, while nebulizer monitoring device 100 is docked or located at a base station and nebulizer monitoring device 100 is being charged. In some embodiments, the base station can, for example, calibrate the nebulizer monitoring device 100 (e.g., one or more sensors), reconfigure the settings or operation of the nebulizer monitoring device 100, or 100 firmware or software can be used to send data to a nebulizer monitoring device.

In some embodiments, a user may have multiple nebulizer monitoring devices and multiple base stations, for example, if the monitoring devices are used for different nebulizer treatments or for different patients or subjects. In some of these embodiments, the nebulizer monitoring device is configured to universally connect to any number of base stations for charging, but with a unique identifier (e.g., in software and/or hardware). (such as a MAC address or device serial number). A unique identifier is used by software within the nebulizer monitoring device to identify the source of the data (e.g., a data prefix or source identifier for a data stream sent to a cloud-based system), and the identification of the device located at the base station. (e.g., by software within the base station to determine where to send data or how to charge the device) and to configure the device for its intended use (e.g., by software in the base station to determine where to send data or how to charge the device) configuring the nebulizer for specific treatments). For example, when a nebulizer monitoring device attempts to connect to a base station, it can send unique identifier or key (e.g., a string) data to the base station, and the base station Through an algorithm (e.g. a software module or program) executed, it is possible to determine how to process and where to send any data received from that particular device associated with the received unique identifier. can. For example, the data can be added to a memory element along with a unique identifier of the device and transmitted to a cloud-based computer system for processing, or the data can be ignored, e.g. not added by a particular base station or You can prevent it from being sent. In some embodiments, the base station and nebulizer monitoring device are configured such that an indicator (e.g., visual, audible) alerts the user when the correct device is docked or is being docked to a matching base station. You can pair it as you like. In this embodiment, the docking station software may be configured to connect only to a particular nebulizer monitoring device based on the device's unique identifier (e.g., the docking station software may may be compared to what is stored in memory and may connect to the device, permit data transfer, and/or permit charging only if the device's unique identifier matches that stored in memory; ).

In some embodiments, the nebulizer monitoring device includes memory (e.g., 233 in FIG. 2B), such as non-volatile flash data, to store data collected from the sensor for several days (e.g., at least 7 days, at least about 3 days). (days) can be stored. For example, the memory may contain approximately 24 megabits of non-volatile data. In some embodiments, CPU 231 only processes pressure data to provide flow rate and dose instructions (e.g., turns on an LED light) and stores other data in memory, such as humidity and temperature. do. The stored data can be sent to a remote system and processed externally (eg, sent to a base station or cloud-based computing system). In other embodiments, CPU 231 may process raw sensor data to determine calculations of humidity, spit volume, and temperature data (with or without date and timestamp information).

In some embodiments, a base station can include one or more environmental monitoring sensors to receive and store environmental sensor data. For example, one or more of a VOC sensor, a CO sensor, an ozone sensor, a NOx sensor, a _CO2 sensor, a smoke sensor, a humidity sensor, a temperature sensor, and a particulate sensor. Other sensors are also possible, such as mold, spore, bacteria, and other toxin sensors. The base station can also include a controller connected to the sensors and including a CPU and memory that can receive, process, and store data received from the base station's sensors.

In some embodiments, the base station includes an indicator, such as an LED light or an audible indicator, for communicating to the user. For example, to convey collected environmental data such as room temperature, CO ₂ levels, particulate levels, etc. In some embodiments, an indicator at the base station indicates that the nebulizer monitoring device is properly positioned for charging, that the nebulizer monitoring device is charging, or that the nebulizer monitoring device is charged and ready for use. You can tell the status. In some embodiments, the indicator may indicate when the base station receives/transmits wireless data.

FIG. 8 is a perspective view of a system 800 that includes a nebulizer monitoring device 100. System 800 may include a user system 810 and a physician system 820. In some embodiments, user system 810 may include a user, nebulizer monitoring device 100, base station 300, and smart personal device 400, such as a smartphone or tablet. In some embodiments, the physician system 820 includes a data visualization system 600, such as computer monitoring and associated computers for data processing and/or visualization, and a medical professional who can view the data on the screen and and/or a caregiver. User systems and physician systems may connect to one or more cloud-based analysis systems 500 via a network 410, such as the Internet or a private data network. In some embodiments, network 410 can communicate wirelessly to smart device 400. In some embodiments, network 410 may communicate wired or wirelessly to cloud system 500 and may communicate to data visualization system 600. Cloud-based analysis system 500 can receive raw and processed data from one or more nebulizer monitoring devices 100 and process and analyze the received data. Processed and analyzed data may be transmitted to physician system 600 via network 410.

The system depicted in FIG. 8 can be used to monitor the use and compliance of nebulizer therapy by one or more users. For example, each time a user uses a nebulizer, the nebulizer monitoring system can record sensor data such as, for example, pressure (eg, flow rate), user temperature, humidity, device orientation, etc. This data can be sent to cloud-based analysis system 500 using network 410 and can be processed or analyzed by cloud-based analysis system 500. Optionally, the analyzed data can be sent back to the user, eg, to the user's smart device 400 to notify the user, eg, via an app, that a dose has taken place. Furthermore, the analyzed data can be used to generate messages that provide feedback to the user, e.g., that the user is not using the nebulizer device 10 correctly (e.g., during treatment, the nebulizer device 10 the user did not take a deep breath, the user did not take enough breaths, or the user did not fill the reservoir with medication before use) .

In some embodiments, the system can include a user dashboard 900, as shown in FIG. Dashboard 900 can be displayed on any computer system, including, for example, smartphone 400 or visualization system 600. The dashboard displays average exhaled volume for the duration of treatment and/or last treatment, breathing pattern (e.g., breaths per minute), number of treatments per day and/or month, user's body temperature (e.g., most recent , and/or daily average, weekly average, monthly average, or treatment period average), nebulizer function, treatment period (e.g., average period over the past week or month, or treatment interval), room temperature ( room humidity (e.g., maximum and minimum of the current day, past week or month, or treatment period); , mouthpiece placement (eg, angular orientation of the device at last use), and VOC.

In some embodiments, a health care provider can view data on the system 600 and make assessments regarding the quantity and quality of medications and the user's health in the short, medium, and long term. The user can view this information to assess the user's progress and identify indicators of potential exacerbation. Healthcare providers view the data in response to users complaining of distress (e.g., remotely or with the patient) and examine the data to determine if the onset of an exacerbation is occurring and to identify possible causes. (eg, the nebulizer has not been used correctly for the past two weeks). The medical professional then prescribes appropriate treatment, such as administration of restorative agents, administration of antibiotics, and, if necessary, provides additional training to the user on the correct use and mediation of the nebulizer. In the medium to long term, for example, after collecting data over a period of 1 month, 2 months, 3 months, 6 months, or more, the user may meet with a healthcare professional at a scheduled visit independent of the exacerbation; Healthcare professionals can pull the data and make recommendations about the user's compliance and overall health. Long-term monitoring can also be used to detect changes in the patient's general health, such as changes in exhalation volume or respiratory rate over time (e.g., increasing and improving, or decreasing and decreasing). You can obtain information about your health condition. Long-term monitoring also helps establish user thresholds for exhalation volume and breathing rate, which typically vary over time, that software running on cloud system 500 can use to trigger alerts. For example, after each treatment session, treatment data can be uploaded to cloud system 500 and certain measured or calculated values (eg, raw data or processed) can be compared to threshold values. If the measured or calculated value is greater than or less than the threshold, or if the difference is greater or less than a preset amount, the cloud system 500 sends a message or alert indicating that there may be a problem with the user's care. , to the user, health care provider, or caregiver.

In some embodiments, the analysis system 500 alerts the user and/or health care provider when one or more parameters, such as temperature, exhaled volume, respiratory rate, or humidity, are above or below a threshold. Can be sent. The threshold may be based on an expected mean or mean value determined from a large sample population (e.g., a value adjusted based on weight, age, and other characteristics of the user) or using the nebulizer monitoring device 100. The settings may be based on the user's historical baseline data collected over a period of one month, two months, three months, six months, or more. For example, an alert can be triggered if the value of a parameter deviates from a threshold by about 5% or more (eg, about 10% or more, about 15% or more, or about 20% or more). Alerts can be sent to different parties depending on the amount of deviation from the set threshold. For example, if a user's body temperature increases by 1°C or more over a period of 2-3 days, an alert will be sent to the primary caregiver, and if a user's body temperature increases by 2°C or more over a 2-3 day period can send alerts to medical institutions. In another example, an alert may be sent to a primary caregiver if a user's vomiting rate decreases by more than about 5% over a 2-3 day period; % or more, an alert can be sent to a healthcare provider who can retrieve the user's data and/or contact the user to initiate corrective action. The alert can be in the form of a phone message, text message, email message, or other visual message sent to the health care provider.

FIG. 10 is a schematic diagram of a nebulizer monitoring system according to some embodiments of the invention. In interacting with the system, user 1 inhales and exhales (double-headed arrows) through nebulizer mouthpiece 12 while contacting a contact thermometer 232 that can be attached to user monitoring tether 130. User monitoring tether 130 may be mechanically and electrically connected to user monitoring system 100 and monitoring controller 230, for example, to transmit user temperature data from the user to monitoring controller 230. In some alternative embodiments, the user monitoring tether is mechanically and electrically connected to the mouthpiece 12, for example, to transmit temperature data from the user through the mouthpiece to the monitoring controller 230 of the system 100. Can be connected. In FIG. 10, double-headed arrows can indicate not only the flow of nebulized medication, but also any flow of air, such as due to the user's inhalation and exhalation. For example, communication via an electrical connection can be accomplished through the use of a physical connection (e.g., wire, cable, USB, Aux cord), or wireless transmission (e.g., WiFi, Bluetooth®, ZigBee®, and NFC). may include communications by.

Nebulizer mouthpiece 12 can be mechanically (eg, using a press-fit or snap-fit, or tapered fitting) and fluidly connected to nebulizer monitoring system 100. In some embodiments, the mouthpiece is removably mechanically and fluidically connected to the nebulizer monitoring system 100. In some embodiments, the mouthpiece 12 is electrically connected (e.g., removably connected) to the nebulizer monitoring system 100 to transmit user temperature data from the user to the monitoring controller 230 of the nebulizer monitoring system 100. connected). Nebulizer monitoring system 100 can include one or more flow sensors, such as differential pressure sensor 222, in the inlet and outlet flow paths from the user. In some embodiments, the flow sensor can include a Sensirion SDP31 differential pressure sensor (SKU1649-1080-1-ND, Digi-Key, MN). The exhale can be vented out of the nebulizer monitoring system 100, for example via a one-way valve. In some embodiments, the exhale can be exhausted after flowing past the flow sensor 222 and not contact the humidity sensor 250. Other embodiments include an exhaust value placed on the mouthpiece of the nebulizer (e.g., exhalation is not detected by flow sensor 222 and humidity sensor 250), or humidity sensor 250 includes an exhaust valve in the exhalation path. I can be there. Differential pressure sensor element 222 can be electrically connected to supervisory controller 230 and can transmit flow rate and flow direction data (eg, flow vectors) to supervisory controller 230 . Humidity sensor 250 can be electrically connected to supervisory controller 230 and can send humidity data to supervisory controller 230 . Nebulizer monitoring system 100 can also include an accelerometer 280 communicatively connected to monitoring controller 230 to transmit acceleration data to monitoring controller 230 . In some embodiments, accelerometer 280 comprises an NXP Freescale ACCELEROMETER_2-8G_12C_16QFN (part number MMA8452QR1CT-ND, Digi-Key, MN). Nebulizer monitoring system 100 can include LEDs 120 and 140 and associated display elements (e.g., light pipes, windows) and can be coupled to display inhalation flow rate, exhalation flow rate, and dose count. . In some embodiments, the LEDs include Broadcom AvagoSurface Mount Tricolor Chip LED0606 (part number 516-1795-6-ND, Digi-Key, MN) and Kingbright LED (part number 754-2121-1-ND, Digi-Key, MN). i-Key, MN) one or more of the following. The LEDs can be electrically connected to the monitoring controller 230 to illuminate signals determined as a function of flow data and/or humidity sensor data. Nebulizer monitoring system 100 can also include a battery 260 that is electrically connected to monitoring controller 230 to power it, for example with DC power. In some embodiments, battery 260 can be directly connected to one or more of LEDs 120 and 140, accelerometer 280, humidity sensor 250, and pressure sensor 222. In some other embodiments, the supervisory controller 230 may power one or more of the LEDs 120 and 140, the accelerometer 280, the humidity sensor 250, and the pressure sensor 222 from the power received from the battery 260. can. In some embodiments, one or more transformers may be included to provide DC or AC power to the components. The transformer may be part of the supervisory controller 230 or may be a separate component. Supervisory controller 230 includes one or more memory elements, one or more timers (e.g., hardware-based or software-based timers), and one or more microcontrollers, microprocessors, digital signal processors, and/or a field programmable gate array. In some embodiments, the supervisory controller 230 includes the following components: Microchip Charge Management Controller (Part Number MCP73832T-2ACI/OTCT-ND, Digi-Key, MN), Nordic Semiconductor CPU/Bluetooth® Low Energy Controller (Part Number 1490-156-1-ND, Digi-Key, MN), On Semiconductor LED Controller (Part Number NCP5623BMUTBGOSDKR-ND, Digi-Key, MN), Texas Instruments Voltage Regulator (Part Number 296-11013- 1-ND, Digi-Key, MN), Kyocera AVX32MHz Crystal (Part No. 1253-1586-1-ND, Digi-Key, MN), Texas Instruments MOSFET_N-CH12V (Part No. 296-41412-1-ND, Digi-Key , MN), Johanson Antenna Chip 2.4GHZ (Part Number 712-1005-1-ND, Digi-Key, MN). Monitoring controller 230, LEDs 120 and 140, accelerometer 280, humidity sensor 250, pressure sensor 222, and battery may be electrically connected and/or mounted on a flexible or rigid printed circuit board, such as a PCB.

Nebulizer monitoring system 100 can be mechanically (eg, using a press fit or snap fit, or a tapered fitting) and optionally removably attached to nebulizer device 10 . Nebulized aerosol medicament produced by the nebulizer device flows through nebulizer monitoring system 100 and interacts with and/or interacts with one or more of the sensors (e.g., pressure sensor 222, humidity sensor 250, and/or temperature sensor not shown). The nebulizer device 10 can be in fluid communication with the nebulizer monitoring system 100, such as or in contact. According to some embodiments, the medication is nebulized into an aerosol by the nebulizer device 10, passes through the humidity sensor 250 and the pressure sensor 222, and then flows through the mouthpiece 12 to the user 1 who inhales the medication. It will be done like this. In some embodiments, the nebulizer device 10 can include an ultrasonic nebulizer or a mesh nebulizer, and the nebulizer device 10 can be powered from a conventional household power source (from a standard 120V at 60Hz or 240V at 50Hz). AC current) and can be converted by a conventional power transformer to provide the appropriate level of DC power (e.g., 3.0 volts at 1 amp). In some embodiments, nebulizer device 10 can include a jet nebulizer and a nebulizer compressor that can be powered from a household electrical outlet to provide air flow to the jet nebulizer element.

The system illustrated by FIG. 10 can also include a base station 300 that can be powered by a household power source, such as a standard AC outlet. Power may be distributed and converted to elements of base station 300 as needed. Base station 300 may include a sensor array 301 having, for example, one or more temperature sensors, one or more humidity sensors, and one or more air quality sensors. In some embodiments, the air quality sensors include VOC sensors, CO sensors, ozone sensors, NOx sensors, _CO2 sensors, humidity sensors, temperature sensors, particulate sensors, mold, spores, bacteria, smoke detectors, and other one or more of the toxin sensors. The base station may also include a user interface 302 that includes indicators such as, for example, an LCD display, LED lights, speakers, and vibrating elements. Interface 302 may also include verbal communication elements, such as, for example, a telephone or verbal monitoring and transmitting device (eg, a one-way or two-way radio). The base station may be equipped with a clock, such as displaying the time and providing alarms. The base station may also include a base station controller 303 that includes one or more CPUs, memory, timers, microcontrollers, and transceivers. Environmental sensor array 301 may be electrically connected to base station controller 303 to transmit environmental data signals to base station controller 303. Base station 300 may be configured to wire and/or wirelessly charge battery 260 of nebulizer monitoring system 100. According to some embodiments of the invention, the base station 300 may be equipped with an inductive coil for inductive charging of the battery 260 and/or for directly powering the nebulizer monitoring system 100. direct electrical connections (e.g., pogo pins, wired power connectors, USB ports, or standard 2/3 prong plugs). The monitoring controller 230 of the nebulizer monitoring system 100 electrically connects the base station controller 303 of the base station 300 to transmit data to and receive data from the base station controller 303 of the base station 300. can be connected.

In some embodiments, user data is collected and stored in a memory element of base station controller 303 and periodically after treatment is completed, e.g., hourly, daily, or when the nebulizer is being charged. It can be sent to cloud system 500. Alternatively or additionally, in some embodiments, the treatment data is transmitted from the monitoring controller 230 to the base station controller 303 and to the cloud system 500 in real time, taking into account transfer delays. be able to. Base station controller 303 can also connect to cloud system 500 by connecting to network 410 such as the Internet. According to some embodiments, nebulizer monitoring system 100 may transmit treatment data to base station 300, which transmits treatment data via network 410 to a cloud-based analysis system 500, etc. Can be sent to remote systems. Additionally, base station 300 can send commands and configuration data to nebulizer monitoring system 100 and send data in response to commands. The configurations can be used to control and modify the operation of nebulizer monitoring system 100, including new software program modules as well as updates to existing software program modules being executed by monitoring controller 230 of nebulizer monitoring system 100. Be prepared.

FIG. 11 is a schematic diagram illustrating elements of a method of using a system for monitoring nebulizers according to some embodiments of the invention. A user (1101) preparing to take medication picks up (picks up) (1102) a mouthpiece with a device. The accelerometer 1103 of the sensor system 1105 detects movement (eg, a period of 200 ms or more corresponding to handling of the mouthpiece and device by the user). Thus, the detected motion wakes up (wakes up) the device (1108) and the device is turned on (1110) and begins detecting airflow (1112). The patient then inhales and exhales through the mouthpiece 1106. The air flow caused by the inhalation and exhalation is then detected using differential pressure sensors (1114) for an array of sensors such as differential pressure sensor 222, humidity sensor 250, air temperature sensor 1118, and contact thermistor 250. , sampling (eg, at a rate of 10 Hz) is initiated (1115). The device board 1110 stores and timestamps (1120) the data received from the array of sensors. Differential pressure data is displayed (1122) using LED intensity adjustment (modulation) based on flow rate. At some point, e.g., once administration is complete, the user stops breathing into the mouthpiece (1124) and the differential pressure sensor is activated for 1 second or more (e.g., 2 seconds or more, 3 seconds or more, 4 seconds or more, or 5 seconds). (1126). The device can then stop collecting data (1128) and return to sleep mode, where it monitors the accelerometer for initiation of another dose by the user picking up the mouthpiece and device again. (1102). The user can determine whether administration is complete by any means. For example, some nebulizers have an indicator, such as an audible indicator with automatic power off. Some other nebulizers, such as jet nebulizers, emit a sputtering sound when the drug reservoir is empty or nearly empty, indicating that administration is complete.

FIG. 12 is a schematic diagram illustrating elements of a method for a base station and a cloud server with a system for monitoring nebulizer usage parameters by a user of pressure, temperature, and accelerometer data, according to some embodiments of the present invention. be. In other embodiments, other data (eg, humidity) can be monitored. Base station 300 is configured to charge the monitoring device (1202). For example, charging daily when the device is not in use by the user. During charging, nebulizer monitoring device 100 may wirelessly connect (eg, using Bluetooth®) to a base station (1204). Accordingly, the data may be transmitted 1206 to the base station and the data log of the nebulizer monitoring device 100 may be reset (e.g., setting a flag indicating that data has been offloaded to the base station 300). (1208). The base station can connect 1210 to a network such as the Internet (e.g., wired Ethernet or WiFi) at a preset time (e.g., midnight every day), and the base station can be sent to the cloud server (1212). The cloud server can process the data according to one or more preconfigured software programs (1214). Software running on the cloud server performs temperature analysis (1216) using one or more algorithms to detect temperature changes and trends over time (1218), which are then provided to the user (1222). ) can be generated (1220). Software running on the cloud server can process the pressure data and convert the pressure data to flow rate (1224), breaths per minute (BPM), exhaled volume (TV), and tidal volume. A therapeutic amount of can be determined (1226). Software running on the cloud server can process the accelerometer data to determine gravity vector data and calculate the user's angle of use relative to horizontal/vertical (1228). This accelerometer-derived information can be used by a care provider or an algorithm to determine whether the user is correctly holding and orienting the nebulizer device during use.

Data collected using the devices, methods, and systems described herein can be input into artificial intelligence, machine learning, or deep learning systems to provide further analysis of the user's condition. can. The treatment data, in combination with other users' health data, determines the user's condition, including not only conditions related to the respiratory disease being treated by nebulized mediation, but also other conditions not related to the respiratory disease. can be evaluated. For example, the machine learning algorithm uses one or more of user temperature data, exhaled volume data, ambient temperature, ambient humidity, ambient air quality (e.g., particulate load), nebulizer accelerometer data, nebulizer humidity data, and user dose data. A plurality may be received as input to determine one or more conditions including the user's health status, likelihood of deterioration, and/or effectiveness of treatment.

In some embodiments, the data from the nebulizer monitoring device is simply collected, processed, and provided to the healthcare provider as described above (see, e.g., the dashboard shown in FIG. 9), and the provider then , the data can be reviewed to identify appropriate treatment or changes in treatment or care. For example, a physician may contact the user to discuss and implement a course of action (e.g., discuss how to use a nebulizer, take a recovery dose, prescribe antibiotics).

In some embodiments, a low-level or rules-based artificial intelligence system may be used to process treatment data and send messages or alerts to users or health care providers. For example, it may include algorithms used by a cloud-based analysis system to alert the user that a dose has been taken improperly or that a high temperature has been detected. The system can record and determine one or more baseline physiological health indicators of the user (e.g., body temperature, respiratory rate, exhaled volume) and send messages or alerts when measurements exceed thresholds. You can set a threshold in the rule to send .

In some embodiments, intermediate levels of artificial intelligence may be used. For example, this includes algorithms used by cloud-based analysis systems to detect/recognize exacerbations and send alerts to users and doctors. For example, the algorithm may detect that the user's body temperature has increased for more than 24 hours, that the respiratory rate is higher than a reference value, and that the exhaled volume is decreased. Accordingly, in this embodiment, the system performs diagnosis using baseline data and two or more indicators to which the user can react (eg, temperature, flow rate, humidity).

In some embodiments, high-level artificial intelligence may be implemented. It detects exacerbations, determines appropriate treatments, prescribes treatments (e.g., alerts pharmacies, sends instructions to users), and alters care providers, insurance companies, and users. can be equipped with algorithms used by cloud-based analysis systems. Artificial intelligence can also, for example, determine when a user has finished a required dose and alert a pharmacy and/or care provider that a new prescription is needed.

Implementation of the methods, devices, and systems described herein provides a rich and diverse set of data regarding various uses of nebulizers and facilitates the development of artificial intelligence to monitor and assist in the care of users using nebulizers. It becomes possible. Of course, such data can be very sensitive from a privacy perspective, so a good implementation will include the ability to share data as needed while ensuring the security of individual data. . For example, cloud network datasets based on blockchain infrastructure can ensure that the data collected is transparent, secure, and accessible to all relevant parties.

Embodiments of the various aspects described herein may be described by the following numbered sections (paragraphs).
Item 1. A nebulizer monitoring device, the nebulizer monitoring device comprising:
a first connector adapted to engage the nebulizer mount;
a second connector adapted to engage the nebulizer mouthpiece;
a conduit having an inner surface forming a fluid connection between the first connector and the second connector; a flow sensor configured to measure a flow vector of the fluid;
at least one indicator connected to the flow sensor;
at least one controller connected to the flow sensor and the first indicator, wherein at least one dimension of the at least one indicator changes as a function of the measured flow vector; A nebulizer monitoring device comprising: a controller;

Item 2. 2. The nebulizer monitoring device according to item 1, wherein the at least one indicator comprises at least one light source.
Item 3. 3. The nebulizer monitoring device of item 2, wherein the change in dimension of the at least one indicator comprises a change in the intensity of light emitted from the at least one light source.

Item 4. 4. The nebulizer monitoring device of clause 3, wherein the at least one light source comprises a first light emitting diode (LED), and the change in intensity of light emitted by the first LED is a function of a measured fluid flow vector. A nebulizer monitoring device that changes as

Item 5. 5. The nebulizer monitoring device according to item 4, wherein the at least one indicator comprises a second LED light having a color different from the color of the first LED light, and the first LED light A nebulizer monitoring device, wherein the second LED light is on when the flow vector is in a first direction, and the second LED light is on when the measured fluid flow vector is in a second direction.

Item 6. 3. The nebulizer monitoring device of clause 2, wherein the at least one light source comprises at least two light emitting diodes (LEDs), and the change in dimension of the at least one indicator is caused by at least one of the two LEDs. Nebulizer monitoring device with one state change. For example, a "state" can mean on or off, the perceived length or movement of light (e.g., the speed of light traveling on a line or in a circle), or whether a particular set of lights in an array is on or off in a pattern. It can mean becoming, or it can mean flashing lights. Moreover, the state may also refer to a change in intensity.

Section 7. 7. The nebulizer monitoring device of clause 6, wherein the at least one light source comprises an array of LEDs, and the indicator is perceived as a lengthening indicator, and the perceived length is determined by the measured flow vector. and wherein the array of LEDs is sequentially illuminated such that the direction of the length is a function of the vector direction of the measured flow vector.

Section 8. Nebulizer monitoring device according to any one of items 1 to 7, wherein the first indicator comprises an audible indicator comprising at least one sound emitting device.

Item 9. 9. The nebulizer monitoring device of clause 8, wherein the dimensions of the audible indicator are determined by one or more of the amplitude, frequency, and pattern of sound emitted by the at least one sound emitting device. A nebulizer monitoring device. For example, the sound can change from loud to soft, from soft to loud, from low to high, and from high to low. The sound can be a beep that varies in duration and/or frequency. A sound can emit two or more tones (eg, a chord) that are perceived to be emitted at the same time. The sound can also be musical (eg, a song or song fragment).

Item 10. 10. The nebulizer monitoring device according to any one of Items 1 to 9, wherein the first indicator includes a tactile indicator, and the tactile indicator includes a vibration device, a radiant heat device, and a topography. ) a nebulizer monitoring device comprising one or more of the following: For example, the nebulizer monitoring device provides a vibrating tactile sensation when held or, for example, when a dose is completed. For example, it is equipped with a display (eg, Braille) that can be read by visually impaired people.

Item 11. 11. The nebulizer monitoring device of clause 10, wherein the tactile indicator comprises a vibration device, and the audible indicator dimension comprises one or more of vibration intensity and frequency. Monitoring equipment.

Item 12. The nebulizer monitoring device according to any one of Items 1 to 11, wherein the flow rate sensor includes a differential pressure sensor or a flow meter.
Item 13. The nebulizer monitoring device according to any one of Items 1 to 12 further includes a humidity sensor disposed within or connected to the conduit between the nebulizer mount and the mouthpiece, and a sensor configured to measure humidity within the conduit;
The nebulizer monitoring device wherein at least one dimension of the at least one indicator changes as a function of the measured flow vector and measured humidity from the humidity sensor.

Section 14. The nebulizer monitoring device according to any one of clauses 1 to 13 further comprises a usage indicator comprising an array of light emitting diodes (LEDs) connected to the at least one controller; one controller includes the step of turning off all LEDs of the usage indicator at a preset time; and the controller receiving a plurality of measured flow vectors from the flow sensor for a preset minimum time. turning on one LED of the usage indicator in a preset order subsequent to receiving flow vector free measurements by the flow sensor for a preset period of time; and a nebulizer monitoring device.

Item 15. 15. The nebulizer monitoring device of clause 14, wherein the usage indicator is a visual indicator comprising an array of LED lights, and each dose taken after a specified start time is displayed within the array. a nebulizer monitoring device, indicated by continuous illumination of an LED, said array being reset by turning off all said LEDs at a preset time of the day.

Section 16. The nebulizer monitoring device according to any one of items 1 to 15 further includes a humidity sensor disposed within or connected to the conduit between the nebulizer mount and the mouthpiece, The humidity sensor is connected to the at least one controller with a humidity sensor configured to measure humidity within the conduit and transmit a measurement of humidity within the conduit to the at least one controller. a usage indicator comprising an array of light emitting diodes (LEDs), the at least one controller turning off all LEDs of the usage indicator at a preset time; , the controller receives a measured flow vector indicative of the flow rate in the conduit, the controller receives a plurality of humidity measurements over a preset time period, and the controller receives a plurality of humidity measurements over a preset time period; turning on one LED of the usage indicator in a preset order after an average of a plurality of humidity measurements exceeds a preset threshold; Nebulizer monitoring device.

Section 17. 17. The nebulizer monitoring device of clause 16, wherein the usage indicator is a visual indicator comprising an array of LED lights, and each dose taken after a specified start time is Nebulizer monitoring device, indicated by sequential illumination of LEDs, the array being reset by turning off all LEDs at preset times of the day.

Section 18. 17. The nebulizer monitoring device according to item 16, wherein the threshold is 80% relative humidity.
Item 19. The nebulizer monitoring device according to any one of paragraphs 1 to 18 is further configured to contact at least one lip of a user when the nebulizer monitoring device is being used to administer medication to the user. A nebulizer monitoring device comprising a sensor, the at least one controller being connected to the temperature sensor.

Section 20. 20. The nebulizer monitoring device according to item 19, wherein the temperature sensor is disposed at the first end of the mouthpiece configured to be inserted into a user's mouth, and when the user inserts the mouthpiece into the mouth. , wherein the temperature sensor is arranged to measure the temperature of at least a portion of the user's lips.

Section 21. 20. The nebulizer monitoring device of clause 19, wherein the second connector extends along a first axis, and the second connector further includes an arm extending along the first axis outwardly of the conduit. the arm extends along the mouthpiece when the mouthpiece is connected to the second connector;
a first portion of the arm includes the temperature sensor, a second portion of the arm is connected to the conduit, and a second portion of the arm connects the temperature sensor to the at least one controller; Nebulizer monitoring device.

Section 22. 22. The nebulizer monitoring device of item 21, wherein the first portion of the arm contacts at least a portion of the user's lips when the user inserts the mouthpiece into the mouth. A nebulizer monitoring device, one portion configured to align with the mouthpiece.

Section 23. 22. The nebulizer monitoring device according to clause 21, wherein the arm comprises a hinge connecting the arm to the conduit, or the arm is flexible. , wherein the first portion is configured to be attached to the mouthpiece during use of the nebulizer monitoring device.

Section 24. 20. The nebulizer monitoring device according to item 19, wherein the temperature sensor includes a thermistor.
Section 25. 25. The nebulizer monitoring device according to any one of paragraphs 1 to 24, further comprising an accelerometer connected to the at least one controller.

Section 26. The nebulizer monitoring device according to any one of Items 1 to 25 further includes a battery connected to the at least one controller, and a battery charging circuit for charging the battery.

Section 27. 27. The nebulizer monitoring device according to item 26, wherein the battery charging circuit includes an induction coil configured for inductive charging.
Section 28. A system for using a nebulizer, the system comprising:
The nebulizer monitoring device according to any one of items 1 to 27;
A system comprising: a base station that performs wireless communication with the nebulizer monitoring device.

Section 29. 29. The system according to item 28, wherein the nebulizer monitoring device includes a battery connected to the at least one controller, and a charging circuit for charging the battery.
The system wherein the base station comprises a port configured to accept the nebulizer monitoring device for charging the nebulizer monitoring device.

Section 30. 30. The system according to item 28 or 29, wherein the base station includes a first induction coil, and the nebulizer monitoring device is configured to be connected to the base station when the nebulizer monitoring device is accepted by the base station. a second inductive coil for inductively charging the nebulizer monitoring device.

Section 31. 31. The system of any one of clauses 28-30, wherein the base station comprises a plurality of pogo-pins, the nebulizer monitoring device comprises a plurality of electrical contact pads, and the base station comprises a plurality of electrical contact pads, When a nebulizer monitoring device is accepted by the base station, at least two pogo pins of the base station contact two electrical contact pads of the nebulizer monitoring device and transfer electrical energy to the nebulizer monitoring device to transmit the electrical energy to the nebulizer monitoring device. A system designed to charge a battery.

Section 32. 32. The system according to any one of paragraphs 28 to 31, wherein the base station includes at least one environmental monitoring sensor and is connected to the at least one environmental monitoring sensor to receive environmental information from the at least one environmental monitoring sensor. a controller configured to receive and store sensor data.

Section 33. 33. The system of clause 32, wherein the at least one environmental monitoring sensor is at least one of a VOC sensor, a _CO2 sensor, a humidity sensor, a temperature sensor, a mold sensor, a pollen sensor, a spore sensor, a bacteria sensor, and a particulate sensor. The system is equipped with one. 33. The system according to clause 32, wherein the environmental monitoring sensor is a VOC sensor. 33. The system of clause 32, wherein the environmental monitoring sensor is a _CO2 sensor. 33. The system of clause 32, wherein the environmental monitoring sensor is a humidity sensor. 33. The system of clause 32, wherein the environmental monitoring sensor is a temperature sensor. 33. The system of clause 32, wherein the environmental monitoring sensor is a particulate sensor.

Section 34. 34. The system of any one of clauses 28-33, wherein the base station comprises a network interface that allows the base station to transfer data to a remote computer system.

Section 35. 35. The system of clause 34, wherein the remote computer system comprises at least one processor and associated components, and the remote computer system is configured to receive and store data from the base station. There is a system.

Section 36. A method of administering a nebulized drug to a user, the method comprising the nebulizer monitoring device according to any one of items 1 to 27 or the system according to any one of items 28 to 35. administering a nebulizer therapy regimen of a preset dose of said drug using a nebulizer.

Section 37. 37. The method of clause 36, wherein the user is a patient in need of nebulizer medication and the user is at high risk of non-compliance with a nebulizer therapy regimen.

Section 38. 38. The method of paragraph 36 or 37, wherein the user is a subject in a drug study or clinical trial.
Section 39. 39. The method of any one of paragraphs 36-38, wherein the one or more usage indicators are stored in electronic form.

Section 40. 40. The method of clause 39, wherein the one or more usage indicators are displayed on the data visualization system and the care is provided or the user displays the one or more usage indicators on the visualization system. A method of viewing a device and taking corrective action if one or more usage indicators indicate incorrect use of the nebulizer monitoring device.

Section 41. 40. The method of clause 39, wherein the one or more usage indicators are displayed on the data visualization system, the care provider views the one or more usage indicators, and the one or more usage indicators are displayed on the data visualization system. The method wherein the care provider initiates corrective action if the usage indicator indicates an exacerbation.

Section 42. 40. The method of clause 39, wherein the usage indicator is selected from the group comprising temperature, respiratory rate, exhaled volume, nebulizer monitoring device dose and orientation, and combinations thereof. The way it is done.

Section 43. 43. The method of clause 42, wherein each of the usage indicators includes a plurality of time-stamped usage indicators.
Except in the operating examples, or when otherwise indicated, all numbers expressing amounts of components or reaction conditions used herein are as modified in all cases by the term "about." should be understood. The term "about" used in connection with a percentage may mean ±1% of the referenced value. For example, about 100 means from 99 to 101.

The singular terms "a," "an," and "the" (above) include plural references unless the context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise.

Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The term "configuration" means "comprising." The abbreviation "e.g." is derived from the Latin exempligratia and is used herein to indicate a non-limiting example. Thus, the abbreviation "e.g." is synonymous with the term "forexample."

Although preferred embodiments have been illustrated and described in detail herein, those skilled in the relevant art will appreciate that various modifications, additions, substitutions, etc. can be made without departing from the spirit of the invention. and are therefore considered to be within the scope of the invention as set out in the following claims. Additionally, to the extent not already indicated, any one of the various embodiments described and illustrated herein may be further modified to include any of the other embodiments disclosed herein. It will be understood by those skilled in the art that the features described above can be incorporated.

All patents and other publications cited throughout this application, including literature references, issued patents, published patent applications, and co-pending patent applications, are cited herein, including, but not limited to, These publications are expressly incorporated herein by reference for the purpose of describing and disclosing the methodologies described in such publications that may be used in connection with the technology. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing herein shall be construed as an admission that the inventors are not entitled to advance such disclosure by virtue of prior invention or otherwise. All statements regarding the dates or contents of these documents are based on information available to applicant and no admission is made as to the correctness of the dates or contents of these documents.

The descriptions of embodiments of the disclosure are not intended to be exhaustive or to limit the disclosure to the precise forms disclosed. Although specific embodiments of the present disclosure and examples thereof are described herein for purposes of illustration, those skilled in the relevant art will recognize that various equivalents are within the scope of this disclosure. Changes are possible. For example, although method steps or functions are presented in a predetermined order, alternative embodiments may perform the functions in a different order or substantially simultaneously. The disclosed teachings provided herein can be applied to other procedures or methods as appropriate. The various embodiments described herein can be combined to provide further embodiments. Aspects of the present disclosure can be modified as necessary to adopt the composition, features, and concepts of the above-mentioned documents and applications to provide further embodiments of the present disclosure.

Certain elements of any of the embodiments described above may be combined with or substituted for elements of other embodiments. Furthermore, while advantages associated with particular embodiments of the present disclosure have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and all embodiments incorporate the present disclosure. Such benefits need not necessarily be demonstrated to be within scope.

Claims (1)

a conduit having an inner surface forming a fluid connection;
a flow sensor disposed within the conduit and configured to measure a flow vector of fluid within the conduit;
at least one indicator connected to the flow sensor;
at least one controller connected to the flow rate sensor and a first indicator;
A nebulizer monitoring device comprising:
at least one dimension of the at least one indicator changes as a function of the measured flow vector;
Nebulizer monitoring device.