JP2022536584A - Cross-reference to related applications for nebulizer monitoring devices, systems, and methods - Google Patents

Abstract

Described herein are devices, systems, and methods for monitoring the use of nebulized medications, such as those that can be administered using a nebulizer. They can be used to monitor patients undergoing treatment for COPD (chronic obstructive pulmonary disease) and improve compliance with recommended treatments. Parameters monitored include flow, humidity, and acceleration, providing data on the quantity and quality of nebulizer usage.

Description

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

A nebulizer is a drug delivery device used to aerosolize a drug in the form of a solution or suspension into the respiratory tract for inhalation by a patient. The size of the particles in the aerosol is an important parameter to control in order for the drug to reach the lungs. Particles larger than about 5 μm in diameter are more likely to deposit in the upper respiratory tract than smaller particles and be swallowed rather than deposited in the lungs. Conversely, particles less than about 1 μm in diameter are less likely to be deposited in the lungs and may simply be inhaled or exhaled. Accordingly, nebulizers are typically designed to deliver particles between about 1 μm and 5 μm, which is generally the desired particle size that constitutes a restorative fraction of the inhaled bronchodilator. size range.

Most commonly, nebulizers either use a pressurized gas source, like "jet" nebulizers, or ultrasonic energy, like "ultrasonic" nebulizers and "electronic" or "mesh" nebulizers. to form an aerosol by forming an atomization or "atomization" of a medical solution or suspension. A jet nebulizer utilizes the Venturi effect, 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. (eg, 2-10 L/min). These initial liquid particles can be sprayed against one or more baffles to remove the larger particles from the aerosol and return them to the reservoir, while delivering the smaller particles through the mouthpiece to the inhaling user. Ultrasonic nebulizers use an alternating current power source to vibrate piezoelectric elements in the nebulizer reservoir to generate 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 like a jet nebulizer. This aerosol can then be delivered to the lungs as described above. Mesh nebulizers use a vibrating piezoelectric element coupled to a fine mesh to generate an aerosol, with particle size controlled by sizing the mesh [1, 2].

There are many potential indications for nebulizer therapy, including bronchial constriction, airway inflammation, viscous retained secretions, airspace infections and colonization, dyspnea and chronic cough. Relief of these symptoms/conditions includes bronchodilators (such as salbutamol, terbutaline, ipratropium), anti-inflammatory agents (such as budesonide, fluticasone), secretion disintegrants (such as saline and DNase/dornase), antibacterial agents (such as pentamidine), long-acting bronchodilators (formoterol, alformoterol, glycoprilorate, levefenacin, etc.), and pain control drugs (morphine, lidocaine, etc.). These symptoms/conditions are caused by 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 many disease states, including emphysema, chronic bronchitis, and some asthmatics. Chronic obstructive pulmonary disease COPD is a disease that generally affects men and women over the age of 40, and is associated with a high disease burden such as decreased QOL (quality of life), functional impairment, and large direct/indirect costs. At present, there is no cure for chronic obstructive pulmonary disease COPD, and since the oxygenation capacity of the lungs declines 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 adherence to inhaled medication therapy is critical, centered on the use of bronchodilators. Bronchodilators include beta-agonists, anticholinergics, methylxanthines (eg, theophylline), etc., and are administered by nebulizer. To date, compliance is based on self-report, assessment of reported symptoms, and spirometry to assess whether administration is effective. Patient compliance with prescribed COPD medications and symptom reporting is highly variable, and many physicians diagnose COPD based on symptoms and medical history without spirometry evaluation. You are diagnosing/managing a patient. A 50% adherence rate to prescribed treatment may be considered high. Patients with chronic obstructive pulmonary disease COPD may periodically experience acute exacerbations of chronic obstructive pulmonary disease COPD symptoms. This is due to the narrowing of the airways and the accumulation of mucus due to inflammation. The cause of these exacerbations is not always clear, but is often attributed to viral or bacterial infections of the lungs. It can also be exacerbated by inhaling irritants in the environment, such as air pollution or allergens such as pollen. Lung inflammation (irritation and swelling) 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 be well educated about the disease process, including exacerbations and comorbidities, and the use of various drugs and devices.

Treatment of chronic obstructive pulmonary disease (COPD) involves significant financial burden and behavioral and lifestyle changes, such as starting a smoking cessation program, implementing an exercise program (pulmonary rehabilitation), and inhaling supplemental oxygen in and out of the home. There are many things. In addition, such patients may be undergoing other treatments and therapies, increasing the burden of continuing treatment. Therefore, poor adherence to chronic obstructive pulmonary disease COPD treatment is not surprising, but it is also troubling. Regarding adherence to inhalation therapy, patients were rated as (1) good regulars, (2) poor regulars, (3) good regulars, and (4) poor regulars. can be classified into four categories: Patients with irregular use and poor technique (category 4) had the highest mortality rate; ), and the incidence of exacerbations has also been found to be high. Patients with regular use but poor technique (second category) had slightly increased exacerbation rates but better outcomes. Not surprisingly, patients with regular use and good technique have the lowest mortality and exacerbation rates. Adherence behavior is therefore associated with specific clinical outcomes, with regular use (e.g. prescribing, amount used) being the most important factor, and appropriate use (e.g. quality of use) to a lesser extent It can be said that this is an important factor (see 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 Eur. Repir Rev 2011, 121m 183-194 E. L. Toy et al., Respiratory Medicine, 2011, 105, 435-441 Cushen et al., AJRCCM Articles in Press, 19-Jan-2018 Arzu Ari EurasianJ. 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 there are treatments for chronic obstructive pulmonary disease COPD, there is a need to improve patient compliance with prescribed inhalation therapy. Also, early detection of exacerbations 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 attenuate the decline in lung function and have the potential to improve quality of life for patients with chronic obstructive pulmonary disease (COPD). recognized as an unmet need for

There is also a need to monitor the use of nebulized drugs in trials such as data collection in clinical trials. Currently, it is standard practice for these trials for the user to complete a daily log regarding drug use. As with chronic obstructive pulmonary disease COPD, subjects were given a Ensuring compliance with instructions is, if not more difficult than in chronic obstructive pulmonary disease COPD. Moreover, unreliable compliance reports by users in clinical trials have led to evaluation by sponsors, approval by regulatory authorities, and ultimately characterization of drugs for the treatment of patients with chronic obstructive pulmonary disease COPD by healthcare professionals. This can confound the true effects of drug candidates on physiological endpoint data (eg, forceful expiratory volume per second, FEV1) used in clinical studies. Therefore, data collection and broadening of data on nebulizer use and medication is another unmet need.

Generally, the present invention relates to nebulizer monitoring devices, systems comprising nebulizer devices, and methods of monitoring a user's nebulizer usage using the monitoring devices and systems. According to some embodiments, the devices, systems, and methods provide flow, humidity, temperature, and motion measurements by sensors located in or with the nebulizer, which are used to determine the user's nebulizer. Real-time usage can be monitored. In addition, data can be collected and processed into data such as exhalation volume, respiration rate, and body temperature for visualization by the user, caregiver, and medical personnel. For example, the data can be used for data collection related to use compliance, experimental studies, or tracking or detecting the onset of exacerbation or response to inhaled respiratory medications. The present devices, systems, and methods thus facilitate compliance with nebulizer use according to preset treatment regimes, while assisting 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 nebulizer use by a user. The system includes one or more sensors configured to detect and measure flow of nebulized medication through the nebulizer and a controller configured to record and report usage of the nebulizer by a user. can be prepared. It 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.

A nebulizer monitor is provided according to some embodiments of the present invention. The nebulizer monitor comprises 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 inner surface that forms 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, the flow sensor 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, so that at least one dimension of the at least one indicator is the measured flow vector varies as a function of In some options of the device, the flow sensor comprises a differential pressure sensor or flow meter.

Optionally, the nebulizer device comprises, for example, at least one light source. Here, a change in dimension of the at least one indicator comprises a change in intensity of 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 a 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 measuring A second light is emitted when the resulting fluid flow vector is in a second direction. Optionally, the at least one light source comprises at least two light emitting diodes (LEDs) and change in dimension of the at least one indicator comprises change in state of at least one of the two LEDs. Optionally, the at least one light source comprises an array of sequentially illuminated LEDs, the array of LEDs being perceived as a display of increasing length, the perceived length being a function of the measured flow vector and the length direction indicates the vector direction of the measured flow vector.

Optionally, the first indicator of the nebulizer monitor comprises an audible indicator comprising at least one beeper. 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 vary from loud to soft, soft to loud, low to high, high to low, and the sounds can vary in duration and/or frequency. A changing beep sound can be emitted, a sound can emit two or more sounds (e.g., a chord) that are perceived to be emitted at the same time, and a sound can be a musical sound (e.g., a song or song). fragment). Also optionally, the first indicator comprises a tactile indicator comprising one or more of a vibration device, a radiant heat device, and a contour changing device. Examples include a display that provides a vibrating tactile sensation when the device is held to complete a dose, or a display (eg, Braille) that is readable by the visually impaired. Optionally, the tactile indicator comprises a vibration device and the dimensions of the audible indicator comprise one or more of the intensity and frequency of vibration.

The nebulizer monitor can optionally further comprise a humidity sensor positioned in or connected to the conduit between the nebulizer mount and the mouthpiece, the humidity sensor measuring humidity within the conduit. configured as Thus, at least one dimension of the at least one indicator varies as a function of the measured flow vector and the measured humidity from the humidity sensor.

The nebulizer monitor can also optionally further comprise a usage indicator comprising an array of light emitting diodes (LEDs) connected to at least one controller. In some optional embodiments, at least one controller turns off all LEDs of the usage indicator at a preset time; Receiving a plurality of measured flow vectors, and then displaying the usage indicator in a preset sequence following receipt of a no flow vector measurement by the flow sensor for a preset time. and turning on one LED. Optionally, the controller turns off all LEDs of the usage indicator at a preset time and the controller determines the measured flow vector indicating the flow (e.g., the first direction and optionally the second direction). and the controller receives a plurality of humidity measurements over a preset period of time, and after an average of the plurality of humidity measurements over the preset period of time exceeds a preset threshold , turning on one LED of the usage indicator in a preset sequence. Optionally, the usage indicator may comprise a visual indicator comprising an array of LED lights, and each dose taken after the designated start time is indicated by sequential lighting of the LEDs in the array. 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 comprise a temperature sensor configured to contact at least one lip of a user when the device is being used to administer medication to the user, One controller is connected to the temperature sensor. Optionally, the temperature sensor is inserted into the user's mouth such that the temperature sensor is positioned to measure the temperature of at least a portion of the user's lips when the user inserts the mouthpiece into the user's mouth. located at a first end of a mouthpiece configured to: Optionally, the second connector extends along the first axis, the second connector further comprises an arm extending outwardly of the conduit along the first axis, and the mouthpiece engages the second connector. The arm extends along the mouthpiece when connected. A first portion of the arm carries a temperature sensor and a second portion of the arm is connected to the 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. be. The arm can optionally have a hinge connecting the arm to the conduit. The arms can also optionally be provided with soft (flexible) tethers so that the length of the arms can be extended into 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. Also optionally, the nebulizer device further comprises a battery connected to the at least one controller and a charging circuit for charging said battery. Optionally, the battery charging circuit comprises an induction coil configured for inductive charging.

According to some other embodiments of the present invention, a system for nebulizer use is provided comprising a nebulizer monitor and a base station in wireless communication with the nebulizer monitor. Optionally, the nebulizer monitor comprises a battery connected to at least one controller and a charging circuit for charging said battery. Also optionally, the base station comprises a port configured to receive a nebulizer monitor and to charge the nebulizer monitor. Optionally, the base station comprises a first induction coil and the nebulizer monitor comprises a second induction coil such that the base station inductively charges the nebulizer monitor when the nebulizer monitor is received by the base station. I have it. In some optional embodiments, the base station comprises multiple pogo pins, the nebulizer monitor comprises multiple electrical contact pads, and when the nebulizer monitor is received by the base station, the base station At least two pogo pins are adapted to contact two contact pads of the nebulizer monitor and transmit electrical energy to the nebulizer monitor to charge the battery.

Optionally, the base station of the nebulizer-based system is configured to be connected to at least one environmental monitoring sensor and to receive and store environmental sensor data from the at least one environmental monitoring sensor. 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 has Optionally, the base station includes a network interface so that the base station can transfer data to remote computer systems. Also optionally, the remote computer system comprises at least one processor and associated 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 having a nebulizer monitor or system for nebulizer use. ing. Optionally, the user is a patient who requires a nebulized medication and is at high risk of non-compliance with the nebulizer therapy regimen. Also optionally, the user is a subject of a drug study or drug trial. In some options, one or more usage indicators are stored in electronic form. In some embodiments, one or more usage indicators are displayed on the data visualization system, and a caregiver or user views the one or more indicators on the visualization system, and one or more indicates device misuse or deterioration, corrective action is taken by the user or health care provider. Also optionally, the usage indicator is selected from the group comprising temperature, respiratory rate, exhaled volume, dose, device orientation, and combinations thereof. Optionally, each of the usage indicators constitutes a plurality of timestamped usage indicators.

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

3D perspective view of a nebulizer monitor; FIG. 3D perspective view of the nebulizer monitor with some additional details. FIG. 2 is a cross-sectional plan view of a nebulizer monitoring device; FIG. 3 is a cross-sectional plan view of a nebulizer monitor board with control components, sensors, and an indicator; Figures 2C and 2D are two graphs plotting respiratory data for two different respiratory rates. FIG. 2C shows 15 breaths per minute. Figures 2C and 2D are two graphs plotting respiratory data for two different respiratory rates. Figure 2D shows 20 breaths per minute. FIG. 10 illustrates a tab and hinge arrangement for positioning the thermistor near a mouthpiece for a nebulizer monitor; The first panel of FIG. 3A shows the thermistor not contacting the mouthpiece, and the second panel of FIG. 3A shows the thermistor contacting the mouthpiece. Fig. 3 shows a clip-on retainer configuration for placing a thermocouple near the mouthpiece of the nebulizer monitor; 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. Fig. 3 shows a stretchable retainer configuration for positioning a thermocouple near a mouthpiece for a nebulizer monitor. 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. 3 is a top down view of an embodiment showing a mouthpiece and housing of a nebulizer monitor; Fig. 10 graphically illustrates how light intensity can be used as an indicator of inhalation and exhalation intensity in some embodiments. The first panel of FIG. 4B shows the LED brightening during inhalation. The second panel of FIG. 4B shows that the LED light fades during exhalation. FIG. 3 is a top view of an embodiment showing a mouthpiece and housing of a nebulizer monitor; The first panel of FIG. 5B and the second panel of 5B show that a stretch within the indicator indicates that the user is inhaling (first panel of FIG. 5B) and a retraction within the indicator indicates , showing the user exhaling (second panel of FIG. 5B). Fig. 3 is a top view of a housing of a nebulizer monitor with different colored lights as indicators; The first panel of FIG. 5C shows green emission indicating inhalation and the second panel of FIG. 5C shows purple emission indicating exhalation. 4 is a plot of percent relative humidity versus time showing the response of a humidity sensor used in one embodiment of an apparatus for monitoring nebulizer usage. 3D is a perspective view of a base station configured to receive a nebulizer monitor; FIG. 3D perspective view of a base station in a possible environment in which it may be used; 1 is a pictorial representation of one embodiment of a system using a nebulizer monitor; A dashboard for viewing information provided by the system for monitoring user nebulizer usage. 1 schematically illustrates an embodiment of components for a system for monitoring a user's nebulizer usage; FIG. 4 schematically illustrates an embodiment of steps taken in using the system for monitoring a user's nebulizer usage; FIG. FIG. 11 pictorially illustrates an embodiment for steps taken in using a base station and a cloud server. FIG.

The present application is directed to methods and systems for the administration of respiratory therapy. For example, inhalation therapy management involves detecting and recording adherence to an inhalation therapy regimen, dose taken, user condition (e.g., body temperature, respiratory rate, exhaled volume), and environmental conditions to which the user is exposed (e.g., , air quality) and monitoring and recording. Treatment can comprise 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, where the context permits, the term "user" generally refers to clinical research subjects, patients, or caregivers who assist subjects or patients. . For example, without limitation, a user may use a device as described herein, use a system as described herein, or monitoring device use and may be a patient undergoing nebulizer therapy. 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 be part of a clinical trial. You can be a subject in a clinical trial, monitoring the use of the device as a patient. Also, without limitation, a user may assist a patient or subject in using a device described herein, assist a patient or subject in using a system described herein, or can be a care provider (eg, spouse, relative, friend, nurse, and/or hired helper) who helps monitor the use of the device. In some embodiments, the term user can refer to two or more patients, subjects, and/or caregivers. For example, a user alerted by a monitor system display should be understood to mean that both caregivers and patients can be alerted by the monitoring system. In some embodiments, the user is both a patient and a subject, eg, a patient undergoing an experimental therapy.

Chronic obstructive pulmonary disease, COPD, is a disease that typically affects men and women over the age of 40 and is associated with reduced quality of life, functional impairment, and significant direct and indirect costs. associated with disease burden. In patients with chronic obstructive pulmonary disease COPD, symptoms of chronic obstructive pulmonary disease COPD may be acutely exacerbated due to airway narrowing and mucus accumulation due to inflammation. The exact cause of these exacerbations is not always known, but in some cases they can be caused by viral or bacterial infections of the lungs, 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 are slow to recover and often lead to worsening comorbidities and death. Patients with chronic obstructive pulmonary disease COPD therefore require adequate 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 problems that require different medications, and in some cases, reduced self-regulation, so inhaling Compliance with the law is extremely difficult. Correct use of the device and initiation of exacerbations is often self-reported or observed by a healthcare professional or someone else (eg, spouse of the caregiver).

A nebulizer is a drug delivery device used to deliver a drug in the form of a solution or suspension directly to the airways by aerosolizing the solution, thereby delivering the drug to inflamed and/or irritated tissues of the airways. 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 a medical solution (eg, suspension) having particles about 1-5 μm in diameter that are inhaled and placed into the user's respiratory tract via a mouthpiece, nosepiece, or face mask. Designed to produce drugs. Alternatively, use a nebulizer connected to a mechanical ventilator system. Other particle size distributions can be used/targeted, with the following understanding. That is, the understanding is that particles with a size of about 10-15 μm tend to deposit primarily 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. Understanding that particles tend to penetrate 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 is.

In a jet nebulizer, a drug solution is added to a reservoir connected to a first open end of a capillary tube. A compressed gas source produces a stream of gas, 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 the venturi effect. projected. Thus, the flow of gas (eg, air) 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 of the second end. Liquids are aerosolized by contact with the jet stream. The jet stream and aerosolized particles are directed into a chamber that may be provided with baffles. Larger liquid particles contact the baffle and become trapped, causing liquid from these larger particles to flow/drip 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 in the chamber and are connected through or to ports attached to mouthpieces, nosepieces, face masks, mechanical ventilator systems. The chamber can be exited through a port attached to the tube. Mouthpieces are designed to be inserted into a user's mouth to ingest an aerosolized medicament as the user inhales. For example, the mouthpiece can be designed to be inserted between the user's teeth and to 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 take medication. The chamber also has another opening, called an intake port, that allows ambient air to enter the chamber, such as when the user inhales. Other ports may also be provided, such as an exhalation port on a mouthpiece or face mask. A system of one-way valves is also provided to allow the user to access the aerosolized medicament via the mouthpiece/facemask, e.g., activated when the user inhales and directs/maintains exhalation out of the chamber. can 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 creates a new aerosolization when the user exhales. It can function as a reservoir for an aerosolized drug that expands with a sprayed drug, 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 medical fluid in a reservoir to create a standing wave and generate an aerosol in a chamber. The chamber can be connected to the mouthpiece, and the aerosol is drawn into the lungs when the user inhales. 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. can be Ultrasonic nebulizers are generally more efficient than jet nebulizers, and drug dosages are adjusted appropriately with this in mind. For example, a 1 mL dose of drug using an ultrasonic nebulizer may require a 2 mL dose of the same drug when using a jet nebulizer.

Another common nebulizer is the mesh nebulizer or electronic nebulizer (eFlownebulizer). A mesh nebulizer electrically vibrates a piezoelectric element connected to a fine mesh to bring the fine mesh into contact with a chemical solution to generate 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. It also differs from jet nebulizers in that it can meter doses more efficiently and can administer small, set amounts of medication in 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, ultrasonic nebulizers, and mesh nebulizers. Additionally, the nebulizer can be equipped with a mouthpiece or face mask.いくつかの実施形態では、ＰＡＲＩＲｅｓｐｉｒａｔｏｒｙ Ｅｑｕｉｐｍｅｎｔ, Ｉｎｃ（例えば、Ｐａｒｉ Ｔｒｅｋ Ｓ、Ｍａｇｎａｉｒ）、ＶＥＬＯＸ、Ｐｈｉｌｉｐｓ Ｒｅｓｐｉｒｏｎｉｃｓ（例えば、Ｒｅｓｐｉｒｏｎｉｃｓ Ｓｉｄｅｓｔｒｅａｍ）、ＲｏｓｃｏｅＭｅｄｉｃａｌ（例えば、Ｒｏｓｃｏｅ Ｍｅｄｉｃａｌ Ｐｏｒｔａｂｌｅ ＴｒａｖｅｌＮｅｂｕｌｉｚｅｒＳｙｓｔｅｍ、Ｒｏｓｃｏｅ Ｐｅｄｉａｔｒｉｃ Ｎｅｂｕｌｉｚｅｒｓなど）、Ｄｙｎａｒｅｘ Ｃｏｒｐｏｒａｔｉｏｎ（ Commercially available nebulizers can be used, such as those available from Meridian and Clinical Guard (such as the Dynarex Portable Compressor Nebulizer), and those available from Meridian and Clinical Guard (such as the ClinicalGuard Ultrasonic Portable Nebulizer).

As mentioned above, patient compliance with inhaled drug therapy and early detection of exacerbations are critical in the management of chronic obstructive pulmonary disease COPD. It is recognized herein that in the case of nebulizer-based therapy, monitoring systems significantly improve therapy adherence and detection of exacerbations. Such monitoring systems and devices are described herein, for example, where several embodiments of devices, methods and systems are illustrated by 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). ) to monitor 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 medium. Specific 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 agents are used to treat a variety of lung diseases such as COPD (chronic obstructive pulmonary disease), asthma, chronic bronchitis, emphysema, pulmonary fibrosis, cystic fibrosis, and lung cancer. Because inhaled therapeutic agents also provide access to the bloodstream, some embodiments of the methods, systems, and devices described herein are useful for systemic access and treatment of non-lung related diseases. includes drugs used in nebulizers.

Thus, according to some embodiments of the present invention, nebulizer sensing device 100 is connected between a source of aerosolized medicament (eg, a nebulizer) and a mouthpiece, nosepiece, or facemask. can be configured as a conduit that Sensors placed within the conduit can thus detect the flow or flow rate when the user inhales and exhales, the presence or absence of a medicated aerosol. FIG. 1A is a 3D perspective view of an embodiment comprising nebulizer device 10 , nebulizer detection device 100 and mouthpiece 12 . Also shown in the figure are the x, y, z translational axes assigned to the assembly, and the R _x , R _y rotational axes. The nebulizer device 10 may comprise a medicated reservoir to contain the liquid medicament, a nebulizer element (eg, jet, ultrasound, or mesh, not shown), and a chamber to contain the aerosolized medicament. can. The reservoir and chamber are not shown in this perspective for simplicity, but are components well understood in the art. Chambers and reservoirs can include, for example, capillaries, baffles, piezoelectric elements (and electrical connections thereto), gas inlet ports (eg, connected to a source of pressurized gas), and valves as previously described. can. In some embodiments, the nebulizer device 10 can also function as a holder, in which the nebulizer device 10 is held with suitable handles, grips, grooves and/or shapes therefor. can be configured as 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 the nebulizer sensing device 100 via a first connector. It is understood that in some alternative embodiments a conduit such as a tube may be inserted between the nebulizer device 10 and the nebulizer sensing device 100, the conduit providing an aerosol/air passageway therein. . The nebulizer sensing device 100 also includes a second connector that can engage/connect to a nebulizer mouthpiece 12 that optionally includes a flap valve 13 that opens when exhaled and closes when inhaled by a user using the device. be able to. The nebulizer sensing device 100 includes one or more sensors to detect use of the nebulizer and, as described herein, an indicator to indicate dose taken and/or user status. can have

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 first connector 114 (eg, configured to engage and seal nebulizer mount 14 ) and mouthpiece 12 . forming a conduit between and exit port 112 adapted to . Housing 110 defines a sealed path from nebulizer mount 14 to mouthpiece 12 such that gas inhaled through mouthpiece 12 or exhaled through mouthpiece 12 does not escape through the conduit. can do. Mouthpiece 12 is shown in a transparent view, but the mouthpiece can be transparent, but need not be. Accordingly, housing 110 is configured as a conduit for aerosol/air flow through first connector 114 and second connector 112 in either direction, eg, during user inhalation and exhalation. In some embodiments, the mouthpiece can include a one-way valve 13, shown in FIG. 1A but not shown in FIG. 1B, which allows exhalation. It opens to the outside environment when it is and closes when you breathe in (eg, it can remain closed when the device is 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 exhibits treatment or medication frequency indicator 140 and respiration indicator 120 . Breathing indicator 120 may be positioned so as to be visible to the user when the user engages mouthpiece 12, as shown. Treatment number indicator 140 may be positioned on housing 110 as shown for easy viewing before or after treatment is completed.

FIG. 2A is a cross-sectional view of nebulizer monitor 100 according to some embodiments of the present invention. As shown, nebulizer mount 14 (eg, the portion of nebulizer device 10 that engages first connector 114) is connected to housing 110 via first connector 114, housing 110 having exit port 112. It is connected to the mouthpiece 12 via. 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, housing 110 with an interior space or conduit as described and illustrated includes one or more sensors disposed within the conduit, such as pressure sensor 222 and humidity sensor 250. ing. Protective elements such as protective membranes (e.g., Gore Membranes available from WL Gore & Co.) 223 and 252 also prevent aerosol liquids (e.g., flowing through conduits) from accumulating on the sensor and affecting sensor sensitivity. Can be provided to limit giving. In some embodiments, the housing can include one or more indicators, such as respiratory indicators. For example, a respiratory indicator includes one or more LEDs 224 and one or more light pipes 226 with one end proximate to the LEDs 224 so that the light from the LEDs 224 is visible to the user. can be transmitted to the outer surface of the housing so as to be able to In other embodiments, housing 110 optionally or additionally includes one or more other LEDs 242 and one or more light pipes 244 to convey dosage, usage, or other information to the user. can be The housing 110 can 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 detail in FIG. 2B. Printed circuit board PCB 210 includes one or more accelerometers or gyroscopes 280 (eg, for sensing motion and transmitting velocity and/or acceleration signals to monitoring controller 230) and one or more radios. A communication transceiver 290 (eg, for transmitting and receiving data to and from an external device). Supervisory controller 230 may comprise a central processing unit (CPU) 231 and memory 233, for example, as part of an integrated circuit or system-on-chip. Also, the CPU 231 can be connected to a timer unit and/or a timer can be included in the CPU (eg, included as hardware time or programmed as software time). Supervisory controller 230 may also include other integrated units, eg, for communications (eg, transceiver 290) and power management (not shown). Supervisory controller 230 may comprise a microcontroller, for example, "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 are connected to the controller and can 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 can be arranged differently, for example, the humidity sensor is mounted on the printed circuit board PCB board and the pressure sensor is not 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 can be supplied via a connection plug attached to the 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 can be used. In some embodiments, the battery 260 is charged by direct electrical connection, e.g., using a charging circuit, or by induction, e.g., using wireless power transfer technologies such as Qi or Near Field Communication (NFC). battery.

In some embodiments, pressure sensor 222 can comprise a differential pressure sensor or a flow meter. A differential pressure flow meter introduces a constriction into the pipe and creates a pressure drop across the constriction 116 in the direction of the flowing fluid/gas and uses two pressure sensors 222, one on each side of the constriction. can be measured as The increased flow creates more pressure drop as the fluid/gas flows through the constriction. Therefore, the differential pressure sensor can be calibrated for a particular material such as air/aerosol to determine the velocity (eg, fluid flow rate) and flow direction 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 and downstream pressures. The monitoring controller 230 determines the volume (e.g., exhaled volume) of the gas (e.g., air and/or aerosol) by associating a time stamp with each of the pressure measurements and flow values determined from the pressure measurements. can do. For example, the volume of inhaled or exhaled air and/or aerosol can be determined as a function of flow rate over a preset period of time. The direction of flow (eg, inhalation or exhalation) can be determined by the position of the pressure sensor relative to mouthpiece 12 or nebulizer device 10, relative to each other. For example, when inhaling, 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 is generally less than the pressure at the pressure sensor closest to mouthpiece 12 . Monitoring controller 230 records the pressure, flow rate, and time of each measurement in memory so that monitoring controller 230 or a remote system can determine how long each user is inhaling and exhaling, and how long the user is taking each dose. To be able to determine the amount of exhalation as a respiratory index such as how many times you are breathing for. Pressure, flow, and time of each measurement can be sent to a remote system for further analysis.

In some embodiments, the nebulizer monitor 100 can comprise a constriction made by a mesh or plate with one or more holes arranged perpendicular to the flow in the conduit. In some embodiments, the constriction can be minimized so as to minimize the amount of pressure drop, making it easier for the user to breathe through the device. The flow meter can be equipped with a time measuring element that can directly determine the flow rate. The flow meter, for example, detects the start/stop of pressure differential and can be coupled to the supervisory controller 230 and CPU 231 for data processing to detect the start and stop of flow. It is understood that in some other embodiments, a different flow meter can be used to replace or supplement the pressure sensor 222, for example. 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 respiratory data as may be measured using pressure sensor 222. FIG. FIG. 2C shows a breathing rate of 15 breaths per minute and FIG. 2D shows a breathing rate of 20 breaths per minute. Tidalvolume can be calculated, for example, as the area under the inhalation 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 in the mouthpiece 12 such that the temperature sensor measures the temperature of at least one of the user's lips when the user places the lips on the mouthpiece 12 . It can be placed on piece 12 . For example, the temperature sensors may comprise thermistors or thermocouples connected to the monitoring controller 230, eg, via electrical cables/contacts. In some embodiments, the nebulizer device 10 includes a thermistor 232 located at the proximal end of the mouthpiece 12, and an arm 234 can be used to electrically connect the thermistor 232 to the monitoring controller 230. . Figures 3A, 3B, and 3C illustrate several embodiments for connecting a temperature sensor 232 to the proximal end of mouthpiece 12 so that it can come into contact with the user's lips during use. indicates FIG. 3A shows an arm and hinge configuration with rigid arm element 234 and hinge element 1310, with thermistor 232 positioned in or on arm element 234 at the end opposite hinge element 1310. can be done. The first panel of FIG. 3A shows the arm positioned when the device is not in use, while the second panel of FIG. 3A shows the arm 234 moved into position for use by the user. , and 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 the monitoring controller 230 by a bendable and/or flexible cable 1314. FIG. The first panel of FIG. 3B shows clip 1312 and cable 1314 in position when the device is not in use, while the second panel of FIG. 3B shows clip 1312 secured to mouthpiece 12, thus , thermistor 232 is positioned against the proximal end of mouthpiece 12 so as to contact one or more lips of the user during use. FIG. 3C shows an embodiment using stretch-over elastic retainers 1316 with flex cables 1314 . The first panel of FIG. 3C shows the elastic retainer 1316 and cable 1314 in position when the device is not in use, while the second panel of FIG. 3C is positioned at the proximal end of mouthpiece 12. Resilient retainer 1316 is shown and thus the location of thermistor 232 is one of the proximal ends of the mouthpiece such that it contacts the user's lip or lips during use. Note that in Figures 3A-3C, the thermistors are not shown, but rather the areas where the thermistors are present are indicated by arrows.

Humidity sensor 250 can be any humidity sensor known in the art. As used herein, "humidity" means water vapor content in air or other gas. 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 pounds). As used herein, "dew point" refers to the temperature and pressure at which a gas begins to condense into a liquid, expressed in degrees Celsius or degrees Fahrenheit. As used herein, "relative humidity" or "RH" or "%RH" means the ratio (expressed as a percentage) of the moisture content of air 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 the sensing surface from contamination and condensation. In some other embodiments, humidity sensor 250 is a resistive humidity sensor that measures changes in electrical impedance of hygroscopic media such as conductive polymers, salts, or treated substrates. For example, it consists of a conductive polymer (such as polyimide) and electrodes (eg, noble metal electrodes) on a suitable substrate coated with a salt or an activating chemical. A change in relative humidity is indicated by a corresponding change in the electrical resistance profile of the coating material. Other humidity sensors known in the art can also be used in embodiments of the apparatus for monitoring nebulizer usage.

According to some embodiments of the present invention, sensors (eg, pressure sensor 222 and humidity sensor 250) can include protective elements such as hydrophobic breathable membranes covering sensitive elements of the sensors. As used herein, a hydrophobic breathable membrane is a film or sheet material, such as a film or sheet material, that allows gases such as oxygen, nitrogen, and water vapor to pass, but not larger substances such as liquid or solid particulates. is a structure of For example, a hydrophobic breathable membrane will not pass anything greater than about 10 nm (eg, greater than about 100 nm, greater 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 particles, such as liquid particles in an aerosol, from depositing on sensitive parts of the sensor. These types of membranes can prevent or reduce fouling and corrosion and minimize erratic or inaccurate readings and sensor damage.

It should be appreciated that other embodiments of nebulizer monitoring device 100 may include other sensors, such as temperature or _CO2 sensors, in the interior space (conduit) of housing 110 . Additionally, the placement of the sensors is a matter of choice for those skilled in the art, e.g., the sensors may be placed on or adjacent to the inner surface of the conduit, or may be floating or spaced apart from the inner surface of the conduit. It should be understood that For example, the placement of any sensor can be determined based on the sensor's mode of operation and the property the sensor is intended to measure.

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

In some embodiments, the accelerometer 280 can be used to determine if the device is being used in the correct orientation. As used herein, correct orientation refers to all or a majority of the medical solution in the nebulizer reservoir (e.g., about 99% or more, about 95% or more, about 90% or more, or about 80% or more). ) is nebulized and is not lost, such as by spilling out of the reservoir, when the nebulizer device 10 is turned on its side during use. According to some embodiments of the present 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 FIG. 1A, the correct orientation is with the mouthpiece horizontal to the ground and without any tilt angle, e.g. It is in a state of being parallel to the ground. In this orientation, the R _x and R _y rotation axes can be set to have an angle of zero. In some embodiments, the correct orientation is when the R _x and R _y angles are between about −5 degrees and +5 degrees (eg, 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 angle of the device relative to horizontal/vertical. Accordingly, the accelerometer 280 can measure the orientation of the device 100, store this information in memory, and transmit this information to a remote system, via the supervisory controller (microcontroller) 230. FIG.

The 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 elements of the device, e.g., some sensors, are off and do not receive power or are below the threshold required to operate as a sensing device. It is in "sleep" or "sleep mode" when it receives a level of power. In sleep mode, the necessary power may be supplied 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 monitoring controller 230 and receives power from and communicates to the controller, while other sensors receive little or no power. For example, monitor controller 230 may operate in an operational mode that continuously monitors signals from accelerometer/gyroscope 280 and determines, via software algorithms executed by CPU 232, whether device 100 has been picked up. (eg, the algorithm determines that accelerometer or gyroscope 280 movement (eg, velocity and/or acceleration over time) is greater than a preset threshold for a short period of time or longer). For example, if the accelerometer/gyroscope 280 detects acceleration and/or velocity above 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 chosen such that the device does not wake up due to accidental movements, such as bumping into the nightstand on which the device is placed, for example. In some implementations, nebulizer monitor 100 uses accelerometer data and software algorithms executed by CPU 232 to detect motion unrelated to being picked up or incidental motion, such as motion caused by an airplane. It is possible to detect swaying motion on a ship or on a ship. The algorithm can be programmed such that when the device determines that it has been picked up by a user, the controller executes a command to "wake up" the nebulizer monitoring device 100 and put it into a normal operating mode. As used herein, the device is in a wake-up or operational mode, or one or more of the sensors, such as pressure sensor 222 and humidity sensor 250, so that flow and humidity data can be collected; and indicator LEDs 224 and 242 (e.g., to indicate to the user that the device is working) and power to associated components on the monitoring controller 230, etc., to monitor nebulizer usage. "Wake up" to a state executing software instructions or programs. Optionally, the process of waking up nebulizer monitoring device 100 is a power-up routine executed by monitoring controller 230 to turn on and verify that each element is connected to monitoring controller 230 and is functioning properly. can have Optionally, the process of waking up first monitors signals from one or more of the pressure or humidity sensors and processes the received signals to determine if nebulizer device 10 is being used by a user. etc., can occur in stages. For example, the amount of time between moving the device 100 and using it may vary, for example, some embodiments may require some assembly before the device is used with a nebulizer, as described in more detail below. is required, so the device does not need to be fully aroused immediately. Fully awake means that at least one, and in some embodiments all, of the device's sensors are turned on and monitoring dose delivery and the end of dose delivery. means The end of dosing may be due to a decrease in sensed humidity and/or cessation of inhalation/expiration sensed by the flow sensor, as described herein. In some embodiments, the "sleep" mode comprises data transfers, as described below. According to some embodiments of the present invention, after device 100 has been woken up or has entered an awake mode, supervisory controller 230 controls the time period of 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, or A 30-minute timer may be initiated, 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 that nebulizer device 10 is configured to receive and pierce or open a portion of the cartridge or package. The medicated solution can then drip or flow into the reservoir. In some configurations, the cartridge or package can act as a reservoir, 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, the cartridge or package can contain the 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 type of treatment and nebulizer device. For example, although nebulizing cycle times are different, jet nebulizers take longer to deliver nebulizing treatment than ultrasonic nebulizers and require more medicinal fluid to deliver a therapeutically effective amount of nebulized drug. may be required. In some embodiments, it takes 2-20 minutes (eg, 2-3 minutes, 3-7 minutes, 5-12 minutes) to properly dose.

Also, prior to use, the nebulizer is assembled by one of the users. 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 source or tubing can be connected/switched on as needed. As described above, in some embodiments, device 100 is automatically awakened by motion, which can be sensed by accelerometer 280 and accelerometer signals received by monitoring controller 230 . In addition to assembly, in embodiments the temperature sensor 232 can be moved to an operational position such as a position near the mouthpiece 12 . In some embodiments, for example, an indicator element attached to the housing 110 indicates by lighting, vibrating, or emitting a sound that the device is powered, and optionally that it is available ( 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 described, some embodiments that use accelerometers 280 in or on housing 110 may control the sensor based on preset software algorithms or programs by handling device 100, such as during assembly. The device wakes up so that the 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 the movements associated with correct device 100 assembly. For example, a machine learning algorithm receives a sequence of motion signals as input and determines how closely the sequence of motion signals matches one or more learned acceptable assembly sequences to assist in device assembly. and optionally trigger a visual indicator (e.g. green for correctness if the correctness measure is above or below a preset threshold). or a red light for incorrect answers if the correctness measure is below or above a preset threshold).

After being properly assembled, the user inserts the mouthpiece into his mouth, for example between his teeth. In embodiments where a face mask is used, the face mask is appropriately placed. In those embodiments that use a face mask, the face mask may include a temperature sensor inserted into or placed in contact with the user's mouth or attached to the face mask in contact with the user's face to measure the user's temperature. It can have a temperature sensor located. In embodiments comprising a temperature sensor such as 232, this temperature sensor contacts at least a portion of the lips, e.g., the lower lip where 232 may be set in the mouth, but not the user's teeth/ Avoid going past the gums. The thermistor signal or data is sent to the supervisory 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, and further converted to core temperature (e.g., user's lip and core temperature). by a known or measured/calculated correlation of ). Accordingly, the use of the temperature sensor 232 allows the user's temperature data to be measured and tracked as the therapy is delivered. Such information is useful in determining the general health of the user, such as early detection of deteriorating conditions that lead to elevated body temperature. Also, proper and consistent placement of the sensor in the mouth will result in temperature sensing consistent with the user's body temperature, while improper use will result in missing or erratic temperature sensing. Therefore, temperature monitoring also serves as one indicator of compliance. As previously mentioned, in some embodiments the temperature sensor is contained in a conduit in the interior space or in the housing 110 . A temperature sensor in the conduit can record the exhalation temperature, which is related to the breathing user's core temperature through correlations of those skilled in the art. The conduit temperature sensor can be a redundant temperature sensor for sensor 232 or alternative temperature sensors can be provided in place of sensor 232 .

Continuing from above with respect to the use of nebulizer monitoring system 100 by a user, after proper insertion of mouthpiece 12 into the mouth, the user can breathe (e.g., guided or directed to (inhale, exhale). In some embodiments, a flow sensor (eg, pressure sensor 222) is engaged prior to 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 can inhale or exhale for the therapy session. A software program can be run that determines how much to vomit and how much to vomit. For example, data may 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 may be used to analyze the data to determine the user's exhaled volume during each treatment session. Measurements can be determined. In some embodiments, once proper respiration is established, the nebulizing element (e.g., jet nebulizer, piezo nebulizer, mesh nebulizer) is activated and the user initiates treatment by inhaling a dose of medication. can do. In addition to temperature, exhalation volume and respiratory rate can also be used to monitor the user and can be used to alert the user or caregiver to an exacerbating condition if exhalation volume and/or respiratory rate are outside the user's normal range. can indicate the start of For example, if a lower exhalation volume is measured compared to the user's normal or baseline exhalation volume (e.g., a previously determined average, average, or threshold exhalation volume value), monitoring controller 230 or remote The system can communicate a signal indicating that a possible exacerbated condition has been detected. Also, for example, monitoring controller 230 or the remote The system can communicate a signal indicating that a possible exacerbated condition has been detected. In some embodiments, in addition to being stored in memory by the monitoring controller 230, the user's measured exhaled volume or respiratory rate is communicated to the user in real-time via an indicator such as an LED light 224, or via a smart phone, It can also be communicated wirelessly to a remote computer or base station.

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

4A is a top view of some embodiments showing mouthpiece 12 and housing 110. FIG. In this configuration, the indicator 1410 has an elongated shape in a direction perpendicular to the axis of flow of the medicament in the mouthpiece, and the LED light 224 and the light pipe 226 provide the light intensity of the indicator. Provide increments and decrements. FIG. 4B illustrates how light intensity can be used as an indicator of inhalation and exhalation intensity. For example, the supervisory controller 230 connected to the pressure sensor 222 establishes the flow direction and flow rate and uses algorithms as part of a software program executed by the CPU 232 to adjust the flow direction and flow rate to the appropriate current/voltage. 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 nebulizer usage. For example, the user can get a real-time indication as to whether they are breathing tidally or deep enough for effective therapy.

5A is a top view of some other embodiments showing mouthpiece 12 and housing 110. FIG. In this configuration, the indicator 1412 has an elongated shape in a direction parallel to the axis of flow of the drug solution within the mouthpiece 12 . In this embodiment, LED lights 224 and light pipes 226 can provide an elongation or growth effect or impression within indicator 1412 . The first panel of FIG. 5B shows the extension within indicator 1412 when the user inhales. The second panel of FIG. 5B shows the contraction within indicator 1412 as the user exhales. Elongation and contraction can be produced, for example, by a series of LED lights that illuminate sequentially according to a software program executed by monitoring controller 230 in response to signals received from pressure sensor 222 . Extend/deflate 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 can 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 display. The first panel of FIG. 5C shows the blue light emission 1413 from the indicator indicating inhalation, and the second panel of FIG. 5C shows the purple light emission 1415 emitted by the indicator upon exhalation. The intensity (or brightness) of the light (of each color) is controlled by the monitoring controller 230 and can be used to indicate inspiratory or expiratory airflow in real time.

According to some embodiments of the invention, only the inspiratory portion of the breath is monitored. For example, an embodiment comprising valve 13 (FIG. 1A), in which exhaled breath does not cause flow past pressure sensor 222 (FIG. 2A), as described herein. A simple flow sensor senses only the 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 positioned 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 can use other indicators to convey the intensity of inhalation and exhalation. For example, some embodiments alternatively or additionally emit loud or soft sounds, beeps, chords or musical pieces to indicate air/aerosol flow within the nebulizer monitoring device 100. Can have an audible indicator. Also, the audible indicator can emit sounds that vary in frequency and/or amplitude (eg, loudness) depending on the strength and/or direction of breathing (eg, inhalation vs. exhalation). Some other optional embodiments can include vibrating members that can vary the vibrating strength based on, for example, air/aerosol flow direction or velocity within the nebulizer monitor 100 .

During a treatment session, use of the nebulizer can be monitored by a nebulizer monitor to record information about the treatment session, for example using memory element 234 . In addition to inspiratory and expiratory data as described above, dose data (e.g., inhalation where a humidity sensor indicates that the humidity of the inspired air is greater than a preset threshold) can be recorded. The monitoring controller 230 records the date and time and the start date and time (eg, when the first inspiration was recorded) and the stop date and time (data and time) of each therapy session (eg, when the last inspiration or expiration was recorded). can be provided with a timer and a real-time clock (eg, either hardware or software) that stores the . Each inhale and exhale is recorded as a series of data points indicating air flow (or pressure from a pressure sensor) and optionally air flow direction, date and time of recording, or time offset from a preset date and time can be recorded with

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

According to some embodiments of the present invention, humidity sensor 250 data can be used to determine whether proper dosing or therapy has occurred. In operation, as the aerosolized drug flows through the conduit and contacts the humidity sensor 250, the humidity within the conduit increases. For example, if the user forgets to fill the medication reservoir with a dose of liquid medication before using the nebulizer, the low humidity will be measured by the humidity sensor and transmitted to the monitoring controller 230 during the therapy session. FIG. 6 shows an example plot of humidity data recorded during use. In this example, approximately 45 seconds prior to humidity sensor 250 being exposed to air in the ambient air stream (no aerosolized medication), and between approximately 45 seconds and 210 seconds humidity sensor 250 was exposed to nebulizer After 210 seconds, the humidity sensor 250 is exposed to the ambient air flow (no aerosolized drug) after exposure to the air stream with the aerosolized drug generated by the device 10 . An abrupt onset or transition is seen when the humidity sensor 250 is exposed to aerosolized medication from the nebulizer and the humidity rises above 80%. A similar sharp drop is seen when the aerosolized medication from the nebulizer is stopped and the humidity sensor 250 is exposed to relatively dry ambient air, with humidity well below 80%. In some embodiments, during proper use of the nebulizer (e.g., while using medicated solutions), the average ambient humidity will be high, but the instantaneous humidity can oscillate up and down at least slightly. (eg, when the user inhales and exhales), nebulizer monitor 100 can determine that changes in the measured humidity are indicative of use (eg, by measuring baseline humidity prior to treatment). by). In some embodiments, a relative humidity of about 20%, 30%, 40%, 50%, 60%, 70%, or 80% or more is sufficient when nebulizer device 10 is operating and nebulized drug formulations are required. indicates that the medicine is filled.

In some embodiments, monitoring of user dosing compliance, in addition to being processed and stored by monitoring controller 230, can also be communicated to the user in real-time via a display on the nebulizer monitor. 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/therapy information to the user.

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

In some embodiments, multiple sensors can be used for dosing compliance determination, eg, both quantity and quality of use can be determined. This is because users are (1) regular users with good skills, (2) regular users with poor skills, (3) irregular users with good skills, and (4) irregular users with poor skills. Useful for determining whether a user is For example, if the user is reclining, looking down (e.g., if the angular orientation measured by the accelerometer 280 is not horizontal and R _x ≠0, see FIG. 1A), or if the head is tilted ( For example, if the angular orientation measured by the accelerometer 280 is not horizontal and R _y ≠ 0, see FIG. Signals received from meter 280 can be used for detection. In this situation, if the user is breathing correctly through the device, flow will be detected, but most likely all or part of the medical solution may spill out of the reservoir. Therefore, the humidity does not reach a typical value (eg, above about 80% RH for the preset treatment period) for the time expected for the nebulized material. In another scenario, the nebulizer may be turned on and placed on the surface (eg, in the correct orientation according to accelerometer 280) for some or all of the typical time duration of treatment. Here, the temperature sensor may indicate that the mouthpiece is not in contact with the user over the duration of the treatment, and the pressure sensor may also detect humidity over time, although the humidity sensor may detect humidity. during part of the time the user is not breathing nebulized material. In yet another scenario, the user may have forgotten to add medication to the nebulizer's reservoir, but may otherwise be using the nebulizer correctly (e.g., correct orientation, mouthpiece preset). position and breathing correctly). In this scenario, the humidity sensor would indicate that nebulizer medication is not being delivered. Therefore, the combination of data from two or more sensors is useful to provide 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 comprises one or more pressure sensors 222, humidity sensors 250, temperature sensors 230, accelerometers or gyroscopes 280 connected to monitoring controller 230. can be In operation, monitoring controller 230 receives a signal from each sensor, converts the signal to raw sensor data (eg, using an analog-to-digital converter), and stores the raw sensor data in memory 233 . Nebulizer monitor 100 includes one or more transceivers 290 that allow monitor controller 230 to transmit data to a remote system (e.g., base station 300, personal computer, smart phone, cloud-based system). can be done. According to some embodiments of the invention, monitoring controller 230 sends some or all of the raw sensor data (e.g., pressure data, humidity data, temperature data, accelerometer data, gyroscope data) to remote systems. can be sent. Raw sensor data may be processed by the monitoring controller 230 and/or remote systems to create processed sensor data. For example, pressure sensors transmit signals in the form of voltage or current levels that are processed and converted into pressure measurements. The processed sensor data can be sent to a remote system along with or instead 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 can associate the sensor raw data with a date and/or timestamp so that it can record the date and time the sensor raw data was received. According to some embodiments, the date and timestamp can be a digital representation of local or GMT time and date. According to some embodiments, the date and timestamp are offset from a preset date and/or time (e.g., a few seconds from midnight on January 1, 1980, or midnight on the current day). seconds from time). According to some embodiments, the monitoring controller 230 stores a date associated with each element (e.g., a data value or group of data values corresponding to a single data point) or element group of raw sensor data stored in memory. and/or timestamp values can be stored. According to some embodiments, the monitoring controller 230 determines the dates and /or a timestamp value can be stored. According to some embodiments of the present invention, the monitoring controller 230 includes corresponding dates and/or timestamps with either raw and/or processed sensor data transmitted to remote systems. be able to.

FIG. 7A shows an embodiment of a base station 300 configured to receive a nebulizer monitor 100 according to some embodiments of the invention. FIG. 7B shows a base station in a possible environment in which it may be used, eg a nightstand. As depicted in these figures, the base station 300 may have a port 710 for receiving one end of the nebulizer monitor 100 (eg, the inlet port or nebulizer connector 114 or the 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 a charging circuit for charging the batteries, shown in FIG. 7A. When the nebulizer monitor 100 is placed on the base station 300 in this manner, the nebulizer monitor 100 can be charged. In some embodiments, one or more batteries 260 can be charged wirelessly and/or inductively. Base station 300 and nebulizer monitoring device 100 each detect that the electric field generated by induction coil 724 of base station 300 will affect the induction coil of nebulizer device 10 when nebulizer device 10 is placed at the base station as shown in FIG. 7A. Induction coils 722 , 724 for inductive charging of the battery 260 may be provided to induce current flow through 722 . The induction coil 722 of the nebulizer device 10 can be connected to a charging circuit that controls current flow to charge one or more of the batteries 260 . In some alternative embodiments, charging is through direct electrical contact. For example, if the base station has multiple pogo pins 734 and the nebulizer mount has multiple contact pads 732 . The pogo pins 734 and contact pads 732, when combined as shown in FIG. 7A, provide an electrical connection between the nebulizer mount and the nebulizer monitor and can transfer electrical energy to charge the battery 260, for example. . It is understood that other forms of contact can be made between the nebulizer monitor 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 (eg, a central processing unit and associated memory and/or system on chip) and one or more wireless transceivers (eg, Bluetooth®). (registered trademark), WiFi, ZigBee (registered trademark), and/or capable of cellular data communication), and the nebulizer monitor 100 is connected to a wireless transceiver 290 (e.g., Bluetooth (registered trademark), WiFi, ZigBee®, and/or cellular data communications are also possible). Transceiver 290 of nebulizer monitor 100 can transmit raw and processed data to the radio transceiver of base station 300 . In some embodiments, base station 300 may be equipped with a wireless transceiver for wireless communication with remote systems such as smart phones, tablets, personal computers, local hubs, or clouds.

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

In some embodiments, a user may have multiple nebulizer monitors and multiple base stations, for example, if the monitors are used for different nebulizer treatments or different patients or subjects. In some of these embodiments, the nebulizer monitor is configured to universally connect to any number of base stations for charging, but with a unique identifier (e.g., software and/or hardware MAC address or device serial number) can be assigned. The unique identifier is used by software within the nebulizer monitoring device to identify the source of the data (e.g., data prefix or source identifier for data streams sent to cloud-based systems), and identification of the device located at the base station. (e.g., by software in the base station where to send data or how to charge the device) and to configure the device for its intended use (e.g., configure a nebulizer for a specific treatment). For example, when a nebulizer monitor attempts to connect to a base station, it can send a unique identifier or key (e.g., string) of data to the base station, and the base station processes the data on the base station's CPU. Through an algorithm (e.g., software module or program) that is executed, it can determine how to process and where to send any data received from that particular device associated with the received unique identifier. can. For example, data can be added to a memory element along with a unique identifier for the device and sent 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 monitor devices have indicators (e.g., visual, audible) to alert the user when the correct device is docked or is docking to the matching base station. can be paired to In this embodiment, the docking station software can be configured to connect only to a specific nebulizer monitoring device based on the device's unique identifier (e.g., the docking station software uses the device's unique identifier to Compared to what is stored in memory, the device can be connected, allowed to transfer data, and/or allowed to charge only if the device's unique identifier matches that stored in memory. ).

In some embodiments, the nebulizer monitor includes a memory, such as non-volatile flash data (eg, 233 in FIG. 2B), to store data collected from the sensor for several days (eg, 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, the CPU 231 only processes pressure data to provide flow and dose indications (e.g., illuminates LED lights) and stores other data such as humidity and temperature in memory. 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 humidity, exhalation, and temperature data calculations (with or without date and time stamp information).

In some embodiments, a base station may be equipped with one or more environmental monitoring sensors to receive and store environmental sensor data (sensed data). For example, one or more of VOC sensors, CO sensors, ozone sensors, NOx sensors, _CO2 sensors, smoke sensors, humidity sensors, temperature sensors, and particulate sensors. Other sensors such as mold, spore, bacteria, and other toxin sensors are also contemplated. The base station may also include a controller with a CPU and memory coupled to the sensors and capable of receiving, processing, and storing data received from the base station's sensors.

In some embodiments, the base stations are equipped with indicators, such as LED lights or audible indicators, to communicate to users. For example, to convey collected environmental data such as room temperature, _CO2 levels, particulate levels, etc. In some embodiments, the base station indicator indicates that the nebulizer monitor is properly positioned for charging, that the nebulizer monitor is charging, or that the nebulizer monitor is charged and ready for use. You can tell what the status is. In some embodiments, the indicator can indicate when the base station receives/transmits wireless data.

FIG. 8 is a perspective view of a system 800 comprising a nebulizer monitor 100. FIG. System 800 can include user system 810 and physician system 820 . In some embodiments, user system 810 may comprise a user, nebulizer monitor 100, base station 300, and smart personal device 400, such as a smart phone or tablet. In some embodiments, physician system 820 includes data visualization system 600, such as computer monitors and associated computers for data processing and/or visualization, medical personnel and / Or with a caregiver. User systems and physician systems can be connected 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 may 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 . The cloud-based analysis system 500 can receive raw and processed data from one or more nebulizer monitors 100 and process and analyze the received data. The processed and analyzed data can 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 the user uses the nebulizer, the nebulizer monitoring system can record sensor data such as pressure (eg, flow rate), user temperature, humidity, device orientation, and the like. This data can be transmitted to cloud-based analysis system 500 using network 410 and processed or analyzed by cloud-based analysis system 500 . Optionally, the analyzed data can be sent back to the user, eg sent to the user's smart device 400 to inform the user, eg via an app, that the dose has taken place. Additionally, the analyzed data can be used to generate messages that provide feedback to the user, for example, that the user is not using the nebulizer device 10 correctly (e.g., if the nebulizer device 10 is was not level, the user did not take a deep breath, the user did not breathe enough, or the user did not fill the reservoir with medication prior to 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 smart phone 400 or visualization system 600, for example. The dashboard displays average exhalation volume for treatment duration and/or last treatment, breathing pattern (e.g., breaths per minute), number of treatments per day and/or month, user temperature (e.g., most recent , and/or daily average, weekly average, monthly average, or treatment duration average), nebulizer function, treatment duration (e.g., average duration over the past week or month, or treatment interval), room temperature ( maximum and minimum of the current day, past week or month, or treatment period), room humidity (e.g., maximum and minimum of current day, past week or month, or treatment period) , mouthpiece placement (eg, angular orientation of the device during last use), and VOC can be displayed.

In some embodiments, a health care provider can view the data on system 600 and make assessments regarding the quantity and quality of medications in the short, medium, and long term, as well as the health of the user. Users can view this information to assess their progress and identify indicators of potential exacerbations. The health care provider can view the data in response to the distressed user (e.g., remotely or with the patient) and examine the data to see if an onset of exacerbation has occurred and to identify possible causes. (eg, the nebulizer has not been used correctly in the last two weeks). The medical practitioner then prescribes appropriate treatment, such as administering restorative drugs or antibiotics, and, if necessary, provides the user with additional training in proper nebulizer use and mediation. In the medium to long term, for example, after collecting data over a period of 1 month, 2 months, 3 months, 6 months, or longer, the user meets with a healthcare professional at a scheduled visit independent of exacerbation, Healthcare professionals can pull the data and advise on user compliance and overall health. Long-term monitoring can also help assess the patient's general You can get information about general health conditions. Long-term monitoring also helps establish user thresholds for exhalation volume and respiration rate, which typically change over time, which 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 measurements or calculated values (eg, raw or processed) can be compared to thresholds. If the measured or calculated value is greater or less than the threshold, or if the difference is greater or less than a preset amount, cloud system 500 will issue a message or alert indicating a possible problem with the user's care. , to the user, healthcare provider, or caregiver.

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

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 in contact with contact thermometer 232 , which can be attached to user monitoring tether 130 . User monitoring tether 130 can be mechanically and electrically connected to user monitoring system 100 and monitoring controller 230 to transmit user temperature data from the user to monitoring controller 230, for example. In some alternative embodiments, the user-monitoring tether is mechanically and electrically attached to mouthpiece 12 to transmit, for example, temperature data from the user to monitoring controller 230 of system 100 via the mouthpiece. can be connected. In FIG. 10, the double-headed arrows can indicate not only the flow of nebulized medication, but any flow of air such as that caused by the user's inhalation and exhalation. For example, communication by electrical connection can be through the use of physical connections (e.g. wires, cables, USB, Aux cords) or wireless transmissions (e.g. WiFi, Bluetooth®, ZigBee®, and NFC) may include communication by

Nebulizer mouthpiece 12 can be mechanically (eg, using a press fit or snap fit, or a tapered fitting) and fluidly connected to nebulizer monitoring system 100 . In some embodiments, the mouthpiece is removably mechanically and fluidly connected to nebulizer monitoring system 100 . In some embodiments, mouthpiece 12 is electrically connected (e.g., removably connected) to nebulizer monitoring system 100, e.g., to transmit user temperature data from the user to monitoring controller 230 of nebulizer monitoring system 100. connected). Nebulizer monitoring system 100 can include one or more flow sensors, such as differential pressure sensor 222, in the inhalation and exhalation flow paths from the user. In some embodiments, the flow sensor can comprise a Sensirion SDP31 differential pressure sensor (SKU1649-1080-1-ND, Digi-Key, Minn.). The exhalation can exit out of nebulizer monitoring system 100, for example, via a one-way valve. In some embodiments, the exhalation can flow past/over the flow sensor 222 before being exhausted so that it does not contact the humidity sensor 250 . Other embodiments include an exhaust value located on the nebulizer mouthpiece (e.g., exhalation not detected by flow sensor 222 and humidity sensor 250), or humidity sensor 250 with an exhaust valve in the path of exhalation. can be The differential pressure sensor element 222 can be electrically connected to the monitoring controller 230 and can transmit flow rate and flow direction data (eg, flow vector) to the monitoring controller 230 . Humidity sensor 250 can be electrically connected to monitoring controller 230 and can send humidity data to monitoring controller 230 . The nebulizer monitoring system 100 can also include an accelerometer 280 communicatively connected to the monitoring controller 230 to transmit acceleration data to the 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 (eg, light pipes, windows) and can be coupled to display inspiratory flow, expiratory flow, and dose count. . In some embodiments, the LEDs are Broadcom Avago Surface Mount Tricolor ChipLED0606 (part number 516-1795-6-ND, Digi-Key, MN) and KingbrightLED (part number 754-2121-1-ND, Digi-Key, MN). ). 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. The nebulizer monitoring system 100 can also include a battery 260 electrically connected to the monitoring controller 230 for powering with DC power, for example. In some embodiments, battery 260 may 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, monitoring controller 230 may power one or more of LEDs 120 and 140, accelerometer 280, humidity sensor 250, and pressure sensor 222 from power received from battery 260. can. Some embodiments may include one or more transformers to provide DC or AC power to the components. The transformer may be part of supervisory controller 230 or may be a separate component. The supervisory controller 230 includes one or more memory elements, one or more timers (e.g., hardware-based timers or software-based timers), and one or more microcontrollers, microprocessors, digital signal processors, and/or field programmable gate arrays. In some embodiments, the supervisory controller 230 includes the following components: Microchip's charge management controller (part number MCP73832T-2ACI/OTCT-ND, Digi-Key, MN), Nordic Semiconductor's CPU/Bluetooth® Low Energy Controller (Part No. 1490-156-1-ND, Digi-Key, MN), OnSemiconductor LED Controller (Part No. NCP5623BMUTBGOSDKR-ND, Digi-Key, MN), Texas Instruments Voltage Regulator (Part No. 296-11013--) 1-ND, Digi-Key, MN), Kyocera AVX 32MHz 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 2.4 GHZ (part number 712-1005-1-ND, Digi-Key, MN). The monitoring controller 230, LEDs 120 and 140, accelerometer 280, humidity sensor 250, pressure sensor 222, and battery can be electrically connected and/or mounted on a flexible or rigid printed circuit board, such as a PCB.

Nebulizer monitoring system 100 can be attached to nebulizer device 10 mechanically (eg, using a press fit or snap fit, or a tapered joint), and optionally removably. The nebulized aerosol medication produced by the nebulizer device flows through the nebulizer monitoring system 100 and interacts with and/or one or more of the sensors (eg, pressure sensor 222, humidity sensor 250 and/or temperature sensor not shown). Alternatively, the nebulizer device 10 can be in fluid communication with the nebulizer monitoring system 100 . According to some embodiments, the medication is nebulized into an aerosol by nebulizer device 10 and flows past humidity sensor 250 and pressure sensor 222 and then through mouthpiece 12 to user 1 who inhales the medication. will be made. In some embodiments, the nebulizer device 10 can comprise an ultrasonic nebulizer or a mesh nebulizer, and the nebulizer device 10 can be powered from a conventional household power source (standard 120V at 60Hz or 240V at 50Hz outlet). of AC current) and converted by a conventional power transformer to provide a suitable level of DC power (eg, 3.0 Volts at 1 Ampere). In some embodiments, the nebulizer device 10 can comprise a jet nebulizer and a nebulizer compressor that can be powered from a household outlet to provide airflow to the jet nebulizer elements.

The system illustrated by FIG. 10 can also include a base station 300 that can be powered by a domestic power supply, eg, a standard AC outlet. Power may be distributed and converted to elements of base station 300 as needed. Base station 300 may comprise 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, 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 are provided. The base station may also have a user interface 302 comprising indicators such as, for example, an LCD display, LED lights, speakers, and vibrating elements. Interface 302 may also include a verbal communication component such as, for example, a telephone or verbal monitoring and transmission device (eg, one-way or two-way radio). A base station may be equipped with a clock such as displaying the time and providing an alarm. The base station may also comprise a base station controller 303 comprising one or more CPUs, memory, timers, microcontrollers and transceivers. Environmental sensor array 301 can be electrically connected to base station controller 303 to transmit environmental data signals to base station controller 303 . The base station 300 may be configured to charge the battery 260 of the nebulizer monitoring system 100 wired and/or wirelessly. According to some embodiments of the present invention, the base station 300 may include an induction coil for inductive charging of the battery 260 and/or to power the nebulizer monitoring system 100 directly. direct electrical connection (eg, pogo pin, wired power connector, USB port, or standard 2/3 prong plug). 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 the base station controller 303 and periodically after therapy is completed, such as hourly, daily, or when the nebulizer is being charged. It can be sent to cloud system 500 . Alternatively or additionally, in some embodiments, therapy data is transmitted from the monitoring controller 230 to the base station controller 303 and to the cloud system 500 in real-time to account for transmission delays. be able to. The base station controller 303 can also connect to a network 410 such as the Internet to connect to the cloud system 500 . According to some embodiments, nebulizer monitoring system 100 can transmit therapy data to base station 300, which transmits the therapy data via network 410 to, for example, cloud-based analysis system 500. Can be sent to a remote system. Additionally, the base station 300 can transmit commands and configuration data to the nebulizer monitoring system 100 and transmit data in response to commands. The configuration can be used to control and modify the operation of the nebulizer monitoring system 100, including new software program modules as well as updates to existing software program modules being executed by the monitoring controller 230 of the nebulizer monitoring system 100. can 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 present invention. A user (1101) preparing to take a medication picks up (picks up) a mouthpiece with a device (1102). The accelerometer 1103 of the sensor system 1105 detects motion (eg, for a period of 200ms or longer consistent with the user's handling of the mouthpiece and device). Thus, the detected motion awakens (wakes up) the device (1108), which is turned on (1110) and begins detecting airflow (1112). The patient then inhales and exhales through mouthpiece 1106 . The airflow caused by inhalation and exhalation is then detected 1114 using differential pressure sensors 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 started (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 modulation (modulation) based on flow rate. At some point, e.g., when the administration is complete, the user stops breathing into the mouthpiece (1124) and the differential pressure sensor is at 1 second or more (e.g., 2 seconds or more, 3 seconds or more, 4 seconds or more, or 5 seconds). above) is detected (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 by any means whether administration is complete. 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, to indicate that administration is complete.

FIG. 12 is a schematic diagram illustrating elements of a base station and cloud server method with a system for monitoring user nebulizer usage parameters 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 the device daily when the device is not in use by the user. While charging, nebulizer monitor 100 may wirelessly connect to a base station (eg, using Bluetooth®) (1204). Thus, the data can be sent 1206 to the base station and the data log of the nebulizer monitor 100 can be reset (eg, by setting a flag indicating that the data has been offloaded to the base station 300). can be done) (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 each day), and the base station can access treatment data. can be sent to the cloud server (1212). The cloud server can process the data according to one or more preset software programs (1214). Software running on the cloud server performs temperature analysis using one or more algorithms (1216) 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), expiratory volume (TV), and breath volume (TV). 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 usage angle relative to horizontal/vertical (1228). This accelerometer-derived information can be used by a caregiver or algorithm to determine whether the user is correctly holding and turning the nebulizer device during use.

Data collected using the apparatus, 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. Treatment data, in combination with other users' health data, may be used to determine the user's condition, including conditions related to respiratory disorders being treated by nebulized mediation, as well as other conditions not related to respiratory disorders. can be evaluated. For example, the machine learning algorithm may use one or more of user temperature data, exhalation volume data, ambient temperature, ambient humidity, ambient air quality (e.g., particulate content), nebulizer accelerometer data, nebulizer humidity data, and user dose data. A plurality can 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, data from the nebulizer monitor is simply collected, processed, and provided to the healthcare provider as previously described (see, for example, the dashboard shown in FIG. 9), who then , the data can be reviewed to identify appropriate treatment or changes in treatment or care. For example, a doctor can contact the user to discuss and implement a course of action (eg, review nebulizer usage, take remedial doses, prescribe antibiotics).

In some embodiments, low-level or rule-based artificial intelligence systems can be used to process therapy data and send messages or alerts to users or healthcare providers. For example, it can have algorithms used by cloud-based analysis systems to alert users 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 a .

In some embodiments, intermediate levels of artificial intelligence can be used. For example, this includes algorithms used by cloud-based analysis systems to detect/recognize exacerbations and send alerts to users and physicians. For example, an algorithm may detect that the user's temperature is elevated for more than 24 hours, their respiratory rate is higher than baseline, and their exhaled volume is decreasing. Thus, in the present embodiment, diagnosis is made by the system using baseline data and two or more user-responsive indicators (eg, temperature, flow, humidity).

In some embodiments, high-level artificial intelligence can be implemented. It detects exacerbations, determines appropriate therapy, prescribes therapy (e.g., alerts pharmacies and sends instructions to users), alters care providers, insurance companies, and users. algorithms used by cloud-based analysis systems to Artificial intelligence can also, for example, determine when a user has finished a required dose and alert the 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 data set regarding various uses of nebulizers, and encourages the development of artificial intelligence to monitor and assist the care of users using nebulizers. be possible. Of course, such data can be very sensitive from a privacy standpoint, so proper implementations include the ability to share data when necessary while ensuring the security of individual data. . For example, cloud network datasets based on blockchain infrastructure can ensure the transparency, security, and access of all relevant parties to the data collected.

Embodiments of various aspects described herein can be described by the following numbered sections (paragraphs).
Section 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 that forms a fluid connection between the first connector and the second connector; and positioned within the conduit between the first connector and the second connector and within the conduit. a flow sensor configured to measure a fluid flow vector;
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 varies as a function of the measured flow vector; A nebulizer monitor, comprising: a controller.

Section 2. 2. A nebulizer monitor according to clause 1, wherein the at least one indicator comprises at least one light source.
Item 3. 3. A nebulizer monitor according to clause 2, wherein a change in dimension of said at least one indicator comprises a change in intensity of light emitted from said at least one light source.

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

Item 5. 5. Nebulizer monitoring device according to clause 4, wherein said at least one indicator comprises a second LED light having a different color than said first LED light, said first LED light A nebulizer monitor that illuminates when a flow vector is in a first direction and wherein said second LED light illuminates when said measured fluid flow vector is in a second direction.

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

Item 7. 7. Nebulizer monitoring device according to clause 6, wherein the at least one light source comprises an array of LEDs, the indicator is perceived as a lengthening indicator, the perceived length of the measured flow vector and wherein the array of LEDs are sequentially illuminated such that the direction of the length indicates the vector direction of the measured flow vector.

Item 8. 8. A nebulizer monitor according to any one of clauses 1-7, wherein the first indicator comprises an audible indicator comprising at least one sound emitting device.

Item 9. 9. Nebulizer monitoring device according to clause 8, wherein the dimensions of the audible indicator are one or more of the amplitude, frequency and pattern of the sound emitted by the at least one sound emitting device. There is a nebulizer monitor. For example, the sound can vary from loud to soft, soft to loud, low to high, high to low. The sound can emit beeps of varying duration and/or frequency. A sound can emit two or more sounds (eg, a chord) that are perceived to have been emitted at the same time. The sound can also be musical (eg, a song or song fragment).

Item 10. 10. The nebulizer monitoring device of any one of clauses 1-9, wherein the first indicator comprises a tactile indicator, the tactile indicator comprising a vibration device, a radiant heat device, and a topography. ) a nebulizer monitor, comprising one or more of: a change device; For example, it provides a vibrating tactile sensation when the nebulizer monitor is held or, for example, a dose is completed. For example, it has a display (eg Braille) that can be read by the visually impaired.

Item 11. 11. The nebulizer monitor of clause 10, wherein the tactile indicator comprises a vibration device and the dimensions of the audible indicator comprise one or more of the intensity and frequency of vibration. surveillance equipment.

Item 12. 12. A nebulizer monitor according to any one of clauses 1-11, wherein the flow sensor comprises a differential pressure sensor or a flow meter.
Item 13. 13. The nebulizer monitoring device according to any one of items 1 to 12, further comprising a humidity sensor disposed in or connected to the conduit between the nebulizer mount and the mouthpiece, the sensor is configured to measure humidity within the conduit;
The nebulizer monitor, wherein at least one dimension of the at least one indicator varies as a function of the measured flow vector and the measured humidity from the humidity sensor.

Item 14. 14. The nebulizer monitor of any one of clauses 1-13, further comprising a usage indicator comprising an array of light emitting diodes (LEDs) connected to said at least one controller, wherein said at least one one controller turns off all LEDs of the usage indicator at a preset time; After receiving, turning on one LED of said usage indicator in a preset sequence following receiving flow vector-free measurements by said flow sensor for a preset period of time. and a nebulizer monitor.

Item 15. 15. The nebulizer monitor of clause 14, wherein the usage indicator is a visual indicator comprising an array of LED lights, and each dose taken after a designated start time is indicated within the array. wherein the array is reset by turning off all the LEDs at a preset time of the day.

Item 16. 16. The nebulizer monitoring device of any one of clauses 1-15, further comprising 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 and 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), wherein the at least one controller turns off all LEDs of the usage indicator at a preset time. said controller receiving a measured flow vector indicative of flow in said conduit; said controller receiving a plurality of humidity measurements over a preset time period; and 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 monitor.

Item 17. 17. Nebulizer monitor according to clause 16, wherein the usage indicator is a visual indicator comprising an array of LED lights, and each dose taken after a designated start time is indicated in the array A nebulizer monitor, indicated by the sequential illumination of the LEDs, where the array is reset by turning off all LEDs at a preset time of the day.

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

Item 20. 20. A nebulizer monitor according to clause 19, wherein a temperature sensor is disposed at a first end of the mouthpiece configured for insertion into a user's mouth, the temperature sensor being detected when the user inserts the mouthpiece into the mouth. , the nebulizer monitor, wherein the temperature sensor is arranged to measure the temperature of at least a portion of a user's lips.

Item 21. 20. Nebulizer monitor according to clause 19, wherein said second connector extends along a first axis and said second connector further extends outwardly of said conduit along said first axis. wherein the arm extends along the mouthpiece when the mouthpiece is connected to the second connector;
a first portion of the arm comprises 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 monitor.

Item 22. 22. A nebulizer monitor according to clause 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 monitor, wherein one portion is configured to align with the mouthpiece.

Item 23. 22. Nebulizer monitor according to clause 21, wherein said arm comprises a hinge connecting said arm to said conduit, or said arm is flexible. , the nebulizer monitor, wherein the first portion is configured to be attached to the mouthpiece when the nebulizer monitor is in use.

Item 24. 20. A nebulizer monitor according to clause 19, wherein the temperature sensor comprises a thermistor.
Item 25. 25. The nebulizer monitor of any one of clauses 1-24, further comprising an accelerometer connected to the at least one controller.

Item 26. 26. The nebulizer monitor of any one of clauses 1-25, further comprising a battery connected to said at least one controller, and a battery charging circuit for charging said battery.

Item 27. 27. A nebulizer monitor according to clause 26, wherein the battery charging circuit comprises an induction coil configured for inductive charging.
Item 28. A system for nebulizer use, said system comprising:
28. The nebulizer monitoring device according to any one of Items 1 to 27;
a base station that performs wireless communication with the nebulizer monitoring device;
A system that has

Item 29. 29. The system of clause 28, wherein the nebulizer monitor comprises 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 receive the nebulizer monitor for charging the nebulizer monitor.

Item 30. 30. A system according to clause 28 or 29, wherein the base station comprises a first induction coil and the nebulizer monitor is adapted to the base station when the nebulizer monitor is received by the base station. comprises a second induction coil for inductively charging said nebulizer monitor.

Item 31. 31. The system of any one of clauses 28-30, wherein the base station comprises a plurality of pogo-pins, the nebulizer monitor comprises a plurality of electrical contact pads, and the When the nebulizer monitor is received by the base station, at least two pogo pins of the base station contact two electrical contact pads of the nebulizer monitor to transmit electrical energy to the nebulizer monitor and the A system adapted to charge a battery.

Item 32. 32. The system of any one of Clauses 28-31, wherein the base station comprises at least one environmental monitoring sensor and connected to the at least one environmental monitoring sensor to monitor the environment from the at least one environmental monitoring sensor. a controller configured to receive and store the sensor data.

Item 33. 33. The system of Claim 32, wherein said 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. A system that has one. 33. The system of 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.

Item 34. 34. The system of any one of Clauses 28-33, wherein the base station comprises a network interface such that the base station can transfer data to a remote computer system.

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

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

Item 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 noncompliance with a nebulizer therapy regimen.

Item 38. 38. The method of paragraph 36 or 37, wherein the user is a subject of drug research or clinical trials.
Item 39. 39. The method of any one of clauses 36-38, wherein the one or more usage indicators are stored in electronic form.

Item 40. 40. The method of Claim 39, wherein the one or more usage indicators are displayed on the data visualization system and care is provided or the user displays the one or more usage indicators on the visualization system. and correctiveaction is taken if one or more usage indicators indicate misuse of the nebulizer monitoring device.

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

Item 42. 40. The method of clause 39, wherein the usage indicator is selected from the group comprising temperature, respiratory rate, exhalation volume, nebulizer monitor dose and orientation, and combinations thereof. done, method.

Item 43. 43. The method of clause 42, wherein each of the usage indicators includes a plurality of time-stamped usage indicators.
Except in working examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein are in all instances modified by the term "about." should be understood. The term "about" used in connection with percentages 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 dictates 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 the present disclosure, suitable methods and materials are described below. The term "configure" means "comprising." The abbreviation "eg" (for example) is derived from the Latin exempligratia and is used herein to denote a non-limiting example. Thus, the abbreviation "eg" is synonymous with the term "forexample" (for example).

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

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

The description of embodiments of the disclosure is not intended to be exhaustive or to be limited to the precise forms disclosed. Although specific embodiments of the disclosure and examples therefor are described herein for purposes of illustration, various equivalents within the scope of the disclosure will be recognized by those skilled in the relevant arts. Change is possible. For example, although method steps or functions are presented in a preset order, alternative embodiments may perform the functions in a different order, or perform the functions substantially concurrently. The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate. Various embodiments described herein can be combined to provide further embodiments. Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions, and concepts of the above documents and applications to provide further embodiments of the disclosure.

Specific elements of any of the embodiments described above may be combined or substituted with elements of other embodiments. Moreover, while advantages associated with specific embodiments of the disclosure have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and all embodiments are subject to the disclosure. It is not necessary to exhibit such advantages to be within the scope.

Claims (35)

a first connector adapted to engage the nebulizer mount;
a second connector adapted to engage the mouthpiece of the nebulizer;
a conduit having an inner surface that forms a fluid connection between the first connector and the second connector;
a flow sensor disposed within the conduit between the first connector and the second connector 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 sensor and the first indicator;
A nebulizer monitoring device comprising:
at least one dimension of the at least one indicator varies as a function of the measured flow vector;
Nebulizer monitor. the at least one indicator comprises at least one light source;
A nebulizer monitor according to claim 1. said change in said dimension of said at least one indicator comprises a change in intensity of light emitted from said at least one light source;
3. A nebulizer monitor according to claim 2. said at least one light source comprising a first light emitting diode (LED);
said change in intensity of light emitted from said first LED varies as a function of a measured fluid flow vector;
4. A nebulizer monitor according to claim 3. the at least one indicator comprises a second LED light having a different color than the first LED light;
the first LED light is illuminated when the measured fluid flow vector is in a first direction;
the second LED light is illuminated when the measured fluid flow vector is in a second direction;
5. A nebulizer monitor according to claim 4. the at least one light source comprises at least two light emitting diodes (LEDs);
said change in dimension of said at least one indicator comprises a change in state of at least one of said two LEDs;
3. A nebulizer monitor according to claim 2. said at least one light source comprising an array of LEDs;
wherein said indicator is perceived as a lengthening indicator, the perceived length being a function of said measured flow vector, and said the array of LEDs is illuminated in sequence,
7. A nebulizer monitor according to claim 6. the first indicator comprises an audible indicator comprising at least one sound emitting device;
A nebulizer monitor according to claim 1. 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;
9. A nebulizer monitor according to claim 8. the first indicator comprises a tactile indicator;
the tactile indicator comprises one or more of a vibration device, a radiant heat device, and a shape changing device;
A nebulizer monitor according to claim 1. the tactile indicator comprises a vibrating device;
the dimensions of the audible indicator comprising one or more of the intensity and frequency of vibration;
11. A nebulizer monitor according to claim 10. the flow sensor comprises a differential pressure sensor or a flow meter;
A nebulizer monitor according to claim 1. The nebulizer monitor further comprises a humidity sensor disposed within or connected to the conduit between the nebulizer mount and the mouthpiece, the humidity sensor adapted to measure humidity within the conduit. is configured to
at least one dimension of the at least one indicator varies as a function of the measured flow vector and the measured humidity from the humidity sensor;
A nebulizer monitor according to claim 1. The nebulizer monitor further comprises a usage indicator comprising an array of light emitting diodes (LEDs) connected to the at least one controller, the at least one controller comprising:
turning off all LEDs of the usage indicator at a preset time;
After the controller has received a plurality of measured flow vectors from the flow sensor for a preset minimum time, receiving no flow vector measurements by the flow sensor for a preset time period. followed by illuminating one LED of the usage indicator in a preset order;
is configured to run
A nebulizer monitor according to claim 1. the usage indicator is a visual indicator comprising an array of LED lights;
each dose taken after the designated start time is indicated by continuous illumination of the LEDs in the array;
the array is reset by turning off all the LEDs at a preset time of day;
15. A nebulizer monitor according to claim 14. The nebulizer monitoring device further comprises:
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 and measuring humidity within the conduit. a humidity sensor configured to transmit to said at least one controller a humidity measurement of and a usage indicator comprising an array of light emitting diodes (LEDs) connected to said at least one controller wherein the at least one controller comprises:
turning off all LEDs of the usage indicator at a preset time;
The controller receives a measured flow vector indicative of flow in the conduit, the controller receives a plurality of humidity measurements over a preset period of time, and the controller receives a plurality of humidity measurements over the preset period of time. 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;
is configured to run
A nebulizer monitor according to claim 1. the usage indicator is a visual indicator comprising an array of LED lights;
each dose taken after the designated start time is indicated by continuous illumination of the LEDs in the array;
the array is reset by turning off all LEDs at a preset time of the day;
17. A nebulizer monitor according to claim 16. the threshold is 80% relative humidity;
17. A nebulizer monitor according to claim 16. the nebulizer monitor further comprising a temperature sensor configured to contact at least one lip of the user when the nebulizer monitor is being used to administer medication to the user;
the at least one controller is connected to the temperature sensor;
A nebulizer monitor according to claim 1. the temperature sensor is positioned at a first end of the mouthpiece configured for insertion into the user's mouth;
the temperature sensor is positioned to measure the temperature of at least a portion of the user's lips when the user inserts the mouthpiece into the mouth;
20. A nebulizer monitor according to claim 19. The second connector extends along a first axis, the second connector further comprises an arm extending along the first axis outwardly of the conduit, and the mouthpiece extends along the first axis. the arm extends along the mouthpiece when connected to the second connector;
a first portion of the arm comprises 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;
20. A nebulizer monitor according to claim 19. The first portion of the arm is aligned 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. configured as
22. A nebulizer monitor according to claim 21. 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;
22. A nebulizer monitor according to claim 21. the temperature sensor comprises a thermistor;
20. A nebulizer monitor according to claim 19. said nebulizer monitor further comprising an accelerometer connected to said at least one controller;
A nebulizer monitor according to claim 1. The nebulizer monitor further comprises a battery connected to the at least one controller and a battery charging circuit for charging the battery.
A nebulizer monitor according to claim 1. wherein the battery charging circuit comprises an induction coil configured for inductive charging;
27. A nebulizer monitor according to claim 26. a nebulizer monitoring device according to claim 1;
a base station that performs wireless communication with the nebulizer monitoring device;
A system for nebulizer use, comprising: said nebulizer monitoring device comprising a battery connected to said at least one controller and a charging circuit for charging said battery;
the base station comprises a port configured to receive the nebulizer monitor for charging the nebulizer monitor;
29. System according to claim 28. The base station comprises a first induction coil,
said nebulizer monitor comprising a second induction coil such that said base station inductively charges said nebulizer monitor when said nebulizer monitor is received by said base station;
29. System according to claim 28. the base station comprises a plurality of pogo pins;
the nebulizer monitor comprises a plurality of electrical contact pads;
When the nebulizer monitor is received by the base station, at least two pogo pins of the base station contact two of the electrical contact pads of the nebulizer monitor, transferring electrical energy to the nebulizer monitor to power the battery. is designed to charge,
29. System according to claim 28. The base station comprises at least one environmental monitoring sensor and a controller coupled 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. ing,
29. System according to claim 28. the at least one environmental monitoring sensor comprises 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;
33. The system of claim 32. the base station has a network interface that allows the base station to transfer data to a remote computer system;
29. System according to claim 28. said remote computer system comprising at least one processor and associated components;
the remote computer system is configured to receive and store data from the base station;
35. The system of claim 34.

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