Asthma diagnosis and management system

Abstract

of the Disclosure An asthma diagnosis and management system including a valved holding chamber defining an interior cavity, a backpiece having an opening configured to receive a pressurized metered dose inhaler and a user interface. A microphone is coupled to the valved holding chamber and is in communication with an interior of the valved holding chamber and is configured to capture a sound of a user's lungs.

Description

ASTHMA DIAGNOSIS AND MANAGEMENT SYSTEM

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 727,765, filed December 4, 2024, and entitled “Asthma Diagnosis and Management System,” the entire disclosure of which is hereby incorporated herein by reference.BACKGROUND

[0002] Asthma is a common condition from birth that affects the airways of the lungs, causing them to narrow and produce extra mucous. This condition often results in difficulty breathing, coughing, wheezing, and / or shortness of breath during periods with increased physical activity or even during everyday activities. It is important to initiate the treatment of asthma early to reduce the physical, social and emotion burden of disease on both the individual, family members, and / or friends, yet early treatment requires the disease to be accurately diagnosed by a trained physician.

[0003] The current standard in diagnosing asthma is taking a spirometry test. This is a common lung function test used to diagnose and monitor asthma. This test involves forcefully exhaling into a device that measures the volume of air and the speed of exhalation and is used to determine if there is any obstruction or limitation in the airways. These results are compared against averages for age, sex, ethnicity, height, and other factors, and results below a set threshold quantitively indicate the individual may have asthma. Physicians often use spirometry as an objective measure of airflow limitation, in conjunction with subjective clinical assessment, like asking about symptoms and medical history and conducting a physical examination, to make a diagnosis of asthma.

[0004] Children under the age of 6 ( / .e., preschool children) generally do not have the coordination, understanding, or capacity to undergo such maneuvers nor is there sufficient reference data for this population to inform whether obtained values are clinically significant. As such, spirometry may not be effectively performed in children under the age of 6. Currently there is no widely accepted objective test to identify asthma in preschool aged children.

[0005] Other technologies have been developed to diagnose asthma without the specific limitations of spirometry but have not been widely adopted due to their respective limitations. For example, oscillometry (also known as impulse oscillometry or forced oscillation technique) functions by analyzing the flow and pressure generated while patients breathe tidally into a measurement device. The device records the mechanical impedance of the respiratory system and can provide insight into the function of a patient’s lung. While this test is easy to perform, and can usually be performed with tidal breathing, the downsides of this technology are the difficulty of interpreting results, the lack of standardized cut-offs to determine the severity of the results, the lack of longitudinal data, the lack of education and training among healthcare professionals, and the need for an expensive device to perform the measurement.

[0006] Another technology that has been proposed to monitor and diagnose lung conditions is fractional exhaled nitric oxide (FeNO). FeNO works by measuring the amount of nitric oxide in a person’s breath. This tool, however, also has some shortcomings, including a potentially large number of false positives and negatives, a lack of sensitivity and specificity, and a relatively large expense with a lack of reimbursement in different parts of the world to fund the tests.

[0007] Compounding the problems with asthma diagnosis is that the symptoms of wheezing and breathlessness may occur in up to two thirds of preschool aged children and are a leading cause of ER visits among the age group. These symptoms are not always a direct result of asthma, as asthma and other conditions share significant overlap in symptoms that make it difficult to diagnose. Additionally, these overlapping symptoms manifest differently from child to child, and even manifest differently from season to season within the same child making it difficult to make a sound diagnosis. Although wheezing and breathlessness are typically associated with viral respiratory infections, the lack of accurate spirometry results makes it difficult to ascertain when the symptoms are caused by asthma. As recurrent wheezing in preschool aged children can be associated with substantial morbidity and impact long term health, there is amotivation to expeditiously make a correct diagnosis and treat the condition. Furthermore, asthma medications have known side effects and have associated cost, so it is also beneficial to avoid overdiagnosis.

[0008] This difficulty in identifying asthma in preschool aged children generally results in high costs to the healthcare system as concerned parents and their children are constantly shuffled between doctors and bounced around the healthcare system while looking for a sound diagnosis. These frequent visits and endless tests may also be traumatic for the young child who does not understand what is going on.

[0009] The guideline supported diagnostic approach for preschool aged children’s asthma rules is diagnosis via risk factors and history taking and evaluating the patient’s response to a therapeutic trial of asthma medication. However, currently evaluating a child’s response to medication requires relying on subjective parental accounts.

[0010] For a therapeutic trial, the physician prescribes asthma medication to a child for a period of time (e.g. 3 months) and compares the condition of the child before medication, to when the child is on medication. These primary observations from the doctor are limited as there is no guarantee that the child will present any asthma symptoms with either the initial visit or during the follow-up visit. Additionally, there is no way for the physician to know firsthand the extent in which the child complied to the prescribed medication regime or took their medications properly.

[0011] It is up to the physician to interpret the outcomes of the therapeutic trial through the subjective account of the parent or guardian. Through these subjective accounts the physician must decipher several indicators, including medication adherence, long term trends in symptoms, change in symptoms pre / post reliever, triggers, frequency of reliever use, frequency of illness, trends in activity level, and trends in nocturnal cough, among other indicators. It is important to emphasize the subjective nature of a parental account as some parents may down-play or overemphasize the outcomes of a therapeutic trial to sway the physician into making a biased diagnosis. This adds another layer of complexity and uncertainty onto an already difficult to diagnose disease.

[0012] As a result of this difficulty, some physicians may wait to officially diagnose a child with suspected asthma until they are of the age where spirometry can be performed. Although this is beneficial in preventing misdiagnosis, if the child has a respiratory disease that goes undiagnosed the child could miss out on essential treatment for what can become a span of years. This can also be difficult for the parent as they often experience significant anxiety related to their child’s asthma diagnosis, especially during periods of frequent exacerbations. In other extremes, physicians may liberally prescribe medication to children who do not have asthma. Such practices expose children to side-effect-causing medication that in no way helps manage the disease.

[0013] Previous attempts have been made to resolve the issue of diagnosing pediatric asthma cases. For example, wheeze monitors, electronic stethoscopes, and / or wearable respiration monitors typically require integrating an additional device into an asthma patient’s management routine. Adding a device requires the patient or caregiver to understand how to use the device, understand when to use the device, carry the device on their person, and / or have the motivation or time to use the device during an exacerbation. There are often additional costs associated with this as well, either to the patient / caregiver or the healthcare system in the case where the technology is reimbursed. When the user is having an exacerbation, often their thoughts and actions will be centered on activities that relieve the exacerbation, rather than capturing information to be used for managing their disease in the future. There is also an inherent trend of poor adherence to medication when one’s asthma has temporarily improved. In these situations, an additional device may be forgotten or omitted from use because the user does not feel it is necessary.

[0014] Similarly, other solutions typically require conscious effort to take measurements from the patient. This may include for example performing auscultation using a stethoscope and / or manual logging method via an application. Auscultation is used to understand and assess the condition of a patient’s lungs. Auscultation is defined herein as the act of listening to the sounds of a bodies’ organs through tissue,and it is usually performed with a stethoscope or similar device by a trained clinician. Auscultation enables clinicians to hear the sounds a lung makes, but there are routine difficulties in the interpretation of the sounds, and no definitive diagnoses can be made from simply listening. When sounds are heard, there is a high degree of variability in the origin and requires a high level of skill to interpret the results. This results in a high level of intra-reader interpretability for the same sounds that have been produced. Indeed, there is so much intra-reader interpretability that governing bodies have decided to simply agree on the presence of lung sounds, for example wheeze, rather than attempting to analyze the sound at a more granular level.

[0015] Instead of simply listening, recording lung sounds to assess the conditions of a patient’s lung is a promising tool that can help patients and physicians better assess or manage many lung diseases. These tools work by recording auscultation-like sounds that can then be interpreted by multiple clinicians or a trained artificial intelligence algorithm to make recommendations on the next steps for the patient. This type of tool comes with its own unique challenges of collecting high quality lung sound recordings.

[0016] All auscultation tools require an additional device capable of recording the lung audio and such recording devices often are not passive recording devices, but rather require dedicated time to collect recordings. In addition to these challenges, collecting lung sound recordings brings about new challenges related to the overall quality of audio, which is a critical factor in processing and understanding how a patient is managing their condition. The audio quality may be heavily influenced by ambient noise picked up by the recording. Also, standardizing the method of recording may also prove to be challenging, as current solutions often require the device to be positioned on relatively defined locations of the chest, back, or neck that is difficult to perfectly replicate across repeated placements. The interface, often between the device and the patient’s body, may vary depending on the variables. Even if the device were to be placed in the same location, each patient has different quantities of muscle, bone and fat deposits which filters and influences the noise as it emanates from the lungs. Alongwith patient-to-patient variability, these ratios of biomaterials can also change rapidly over time, which may influence the long-term trends in a patient’s recorded lung sounds.

[0017] In addition to these complications, different lung sounds often emanate from different regions of the lungs. Placing the audio recorder adjacent one location of the lungs would primarily record audio from that area of the lungs and potentially miss other audio sounds that may be used to make important diagnosis or management decisions.

[0018] Further complicating these problems, there is the possibility that these significant breath noises are not present during the session in which the audio is recorded (whether that is through a home-based solution, or through a doctor’s visit). If the lung noise is not present it is unable to be classified and used in the diagnosis or management of the condition. Finally, if the recording solution is home-based then the user needs to be trained on how to use the device / tool, and motivated to be adherent to its use. Long term adherence to any device that does not pose an immediate and gratifying reward, or perceivable benefit to the user is known to be difficult to achieve.

[0019] In an attempt to overcome these issues, wearable respiratory monitors have been developed to continuously monitor the respiratory rate and lung sounds of a patient over a period of time. While these monitors do provide a solution to some of the challenges presented such as the timing of capturing respiratory events or other solutions described herein, it does not solve the issue of lung sounds emanating from different regions of the lungs. In addition, these monitors or patches require the compliance of wearing and managing the continuous recording device, which may cause irritations to the user. Initializing the respiratory monitor requires conscious adherence, and with no immediate benefit the user is unlikely to use the device longterm.

[0020] If a user sees no direct correlation to an improvement in symptoms through using any of the above-mentioned devices, the user may not deem the effort of using them or logging the information worthwhile and may stop using the device altogether. In other examples, the devices focus on a narrow range of measures that are used to indicate asthma in a patient. While there is inherently nothing wrong with this approach,these solutions may miss a range of other asthma indicators which could assist in a quicker diagnosis. If additional measures are to be recorded, additional devices would be needed, which feeds back into the outlined problem of implementing new or too many devices to diagnose or manage asthma.

[0021] Additionally, systems may track when medication was administered, but those systems in the pediatric asthma space typically do not provide any other information about the quality of the medication administration. As a result, vital information may be missing when physicians interpret the data as they have no way to tell the quantity of drug that was administered to their patients’ lungs. For example, a patient may repeatedly administer the medication but have no medication reach the lungs, which may result in an inaccurate diagnosis from the physician.

[0022] Finally, some solutions are limited to the management of asthma symptoms, which does not assist in the diagnosis of pediatric asthma.

[0023] For these various reasons, it is apparent that no singular system is available for supporting physicians in making a diagnosis for preschool aged patients while taking into consideration the many symptoms related to the disease and also being easy to use.BRIEF SUMMARY

[0024] Due to the various issues regarding pediatric asthma, there is a need to provide quantitative and objective information of value to agents that make decisions through the pediatric patient journey. Doing so will allow for a quicker and a more accurate diagnosis of pediatric asthma, with less costs incurred to the medical system. In one embodiment, a system incorporates a solution into the user’s current regime, thus minimizing the addition of any additional steps and devices and removing potential barriers to continued use.

[0025] In one aspect, one embodiment of an asthma diagnosis and management system includes a valved holding chamber defining an interior cavity, a backpiece having an opening configured to receive a pressurized metered dose inhaler and a userinterface. A microphone is coupled to the VHC and is in communication with an interior of the valved holding chamber and is configured to capture a sound of a user’s lungs.BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 is a schematic representation of one embodiment of an asthma diagnosis and management system.

[0027] Figure 2 is a perspective view of one embodiment of a smart valved holding chamber in communication with parent / patient facing application.

[0028] Figure 3 is a perspective view of one embodiment of a smart valved holding chamber.

[0029] Figure 4 is an end view of a portion of a smart valved holding chamber with a microphone positioned in an in an MDI adapter backpiece.

[0030] Figure 5 shows a schematic for a microphone and supporting hardware architecture.

[0031] Figure 6 discloses other embodiments of a lung sound breath recording element for the smart valved holding chamber.

[0032] Figure 7 shows another smart valved holding chamber embodiment.

[0033] Figure 8 shows another smart valve holding chamber embodiment and ambient sound monitoring device.

[0034] Figure 9 discloses one embodiment of a bedside placement of the smart valved holding chamber and ambient sound monitoring device.

[0035] Figure 10 discloses one embodiment of a system including an ambient sound monitoring device embodiment, wireless connection, lighting, and display.

[0036] Figure 11 discloses one embodiment of a system including an ambient sound monitoring device embodiment, cable connections and locking mechanisms.

[0037] Figure 12 discloses an ambient sound monitoring device embodiment, integrated into the smart VHC.

[0038] Figure 13 illustrates one embodiment of a physician-facing dashboard / application.

[0039] Figure 14 is a perspective view of one embodiment of a smart valved holding chamber.

[0040] Figure 15 is a side view of the smart valved holding chamber shown in Figure 14.

[0041] Figure 16 is a side view of the smart valved holding chamber shown in Figure 14 with an inhalation flow therethrough.

[0042] Figure 17 is a side view of the smart valved holding chamber shown in Figure 14 with an exhalation flow.

[0043] Figure 18 is a side view of the smart valved holding chamber shown in Figure 14 with wheeze sounds being propagated.

[0044] Figure 19 is a side view of an alternative embodiment of a smart valved holding chamber with an exhalation flow.

[0045] Figure 20 is a side view of an alternative embodiment of a smart valved holding chamber configured with a secondary microphone.

[0046] Figure 21 is a side view of a smart valved holding chamber with various sources of external ambient noises directed thereat.

[0047] Figure 22 is a side view of the smart valved holding chamber shown in Figure 14 illustrating the positioning of the microphone relative to the user’s mouth and nose.

[0048] Figure 23 illustrates the positioning of the smart valved holding chamber relative to the trachea.

[0049] Figures 24A and B are end views of an inhalation valve and baffle.

[0050] Figure 25 is a side view of another embodiment of a smart valved holding chamber.

[0051] Figure 26 is a side view of another embodiment of a smart valved holding chamber having an acoustic channel.

[0052] Figure 27 is a side view of another embodiment of a smart valved holding chamber with a secondary air channel.

[0053] Figure 28 is a side view of the smart valved holding chamber shown in Figure 27 during an inhalation event.

[0054] Figure 29 is a side view of the smart valved holding chamber shown in Figure 27 during an exhalation event.

[0055] Figure 30 is a flowchart illustrating a method according to the present disclosure.DETAILED DESCRIPTION OF THE DRAWINGS AND THE PRESENTLY PREFERRED EMBODIMENTS

[0056] It should be understood that the term "plurality," as used herein, means two or more. The term "longitudinal," as used herein, means of or relating to a length or lengthwise direction, for example a direction running from a back to a front of a valved holding chamber (VHC). The term "lateral," as used herein, means situated on, directed toward or running in a side-to-side direction VHC. The term “coupled” means connected to or engaged with whether directly or indirectly, for example with an intervening member, and does not require the engagement to be fixed or permanent, although it may be fixed or permanent. The terms “first,” “second,” and so on, as used herein, are not meant to be assigned to a particular component or feature so designated, but rather are simply referring to such components and features in the numerical order as addressed, meaning that a component or feature designated as “first” may later be a “second” such component or feature, depending on the order in which it is referred. It should also be understood that designation of “first” and “second” does not necessarily mean that the two components, features or values so designated are different, meaning for example a first direction may be the same as a second direction, with each simply being applicable to different components or features.

[0057] The present disclosure relates to a system to aid a physician in diagnosing asthma, including preschool asthma, or other asthma cases with or without spirometry, according to the physician’s judgement. This system aims to gather quantitative and objective information passively that cannot be observed during short visits to the physician’s office, for example due to the episodic nature of asthma.

[0058] In one embodiment, the system includes a smart valved holding chamber 3 (VHC) (e.g., as disclosed for example and without limitation in US Patent No.10,850,050B2, and US Patent No. 11 ,395,890 B2, the entirety of which are hereby incorporated herein by reference). The various elements of the current embodiments are features, attributes, and / or additional devices that are designed to integrate into the use of such a VHC. Referring to FIGS. 14 to 25, various exemplary embodiments of a smart VHC includes a chamber housing 100 having a wall defining an interior space 102 extending along a longitudinal axis 104 and defining an inhalation flow path 118, a backpiece 106 coupled to an input end 108 of the chamber housing 100 and a mouthpiece, mask 15 and / or valve assembly 112 coupled to an output end 110 of the chamber housing. The valve assembly 112 defines a chamber 190 upstream of the interior cavity 102, and is separated therefrom by an inhalation valve 114. The mouthpiece / valve assembly 112 may be releasably and removably coupled to the chamber housing 3, for example with tabs received in grooves. The mouthpiece assembly 112 and / or mask 15 is configured with an inhalation valve 114 and / or an exhalation valve 116, which provides and defines an exhalation flow path 120. The inhalation and exhalation valves 114, 116 may alternatively be disposed on other components of the VHC. In various embodiments, a valve is configured as part of an annular donut valve 122, having an inner periphery that defines the inhalation valve 114 and an outer periphery defining the exhalation valve 116. In other embodiments, the inhalation valve is configured as a duckbill valve, which may also have an outer annular flange defining the exhalation valve. In other embodiments, the inhalation and exhalation valves may not be integral, but rather are separately formed and disposed within the VHC. The backpiece 106 is configured with an opening 124, which is shaped to receive a mouthpiece portion 126 of a pressurized metered dose inhaler pMDI 125, which includes an actuation boot 128 and a container 132. The boot further includes a chimney portion 130 defining a cavity shaped to receive a medicament container 132. The boot further includes a support block defining a well shaped to receive a valve stem of the MDI. The well communicates with an orifice, which releases aerosolized medication into the interior space of the chamber housing. Various embodiments of the VHC and MDI, including the mouthpiece assembly, chamber housing and backpiece, are disclosed for example and withoutlimitation in U.S. Pat. Nos. 6,557,549, 7,201 ,165, 7,360,537 and 8,550,067, all assigned to Trudell Medical International Inc., the Assignee of the present application, with the entire disclosures of the noted patents being hereby incorporated herein by reference.Medication Adherence and Technique Monitoring

[0059] In the present disclosure, medication adherence instances may be collected to determine the overall adherence to a prescribed therapeutic trial. In combination with medication adherence, the device will have a function to calculate the technique of the user while taking the medication. The technique is calculated through an analysis and combination of the available metrics that were recorded around the time of the medication delivery. The data and metrics may be used to gain an understanding of the respirable dose received by the user.

[0060] These combined features convey useful information to physicians that assists in a pediatric asthma diagnosis, as it outlines the overall adherence and quantity of medication that reached the lung during the therapeutic trial. This objective account will remove the need for the physician to decipher the information conveyed by a parent during a visit. This element will also enable physicians to identify individuals who struggle while taking their medication and provide an opportunity for correcting patient behaviors.

[0061] To collect this information, sensors 133 may be placed within the same device that collects medication adherence to understand essential metrics in inhaler technique. These metrics may include at least one of: body position, inhalation speed, volume of inhalation, inhaler identification, inhaler actuation timing, flow rate through the device, orientation of the device, or other metrics not mentioned.Ambient Sound Monitoring

[0062] Another element of the present disclosure may include the ability for the system to monitor and track breathing sounds, for example coughing sounds, in patients over long periods of time when the patient is in the same vicinity as the device. One example of this application would be to track the ambient sounds 300 such as coughs ofa preschool asthma patient throughout the duration of the night, as shown for example in FIG. 2.

[0063] This information will be captured through a device equipped with a microphone 18. The device may be the smart valved holding chamber 3, or an accessory device to the smart valved holding chamber. This device may either be manually or automatically triggered to listen to the environment for identifiable respiratory noises, or other ambient sounds 300. Through artificial intelligence, or other preprogrammed software, the recorded sounds may be analyzed by a controller or computer for important data that may be conveyed to caregivers, patients, or physicians. This analysis may take place on the smart valved holding chamber, a smart valved holding chamber accessory, a companion mobile app or a server. This data includes at least one of the following measures: frequency of coughs, total number of coughs, severity of cough, identifying characteristics and trends of each cough, classification of each cough, etc. The controller, software, and / or algorithms may also calculate breathing rate, sleep patterns, and / or other information that could be correlated to symptoms of asthma. The processed information will be transmitted to the patient or physician’s information portal where it may be displayed for interpretation by the user.

[0064] The device, in particular the smart valved holding chamber 3, is designed so that it does not introduce any new adherence steps beyond initialization. Once initialization is complete, the device, e.g, valved holding chamber 3, may be positioned close to the child when sleeping (e.g., the bedside). Proximity to the child may also enable the smart valved holding chamber 3 to be easily accessed in times of an exacerbation.Lung Sound Breathing Recording

[0065] Similarly, another element of the present disclosure may be the ability for the smart valved holding system 3 to listen to breathing sounds generated when the patient takes medication through the smart valved holding chamber 3. This sound recording isof much higher fidelity than the ambient sound monitoring feature as the microphone 18 will be positioned at roughly the same distance from the lungs (minus any anatomical variation), in the same position at the user’s mouth, within a closed system, and without any major barriers that muffles or distorts clinically important sound artifacts. This higher fidelity sound will be analyzed and compared to gather insights regarding the patient’s respiratory health.

[0066] A closed system is defined as a device or system that, when coupled with the airway, facilitates the isolation and recording of lung sounds from the ambient environment passively during a therapeutic process or diagnostic procedure. Both the design and intended use of a valved holding chamber is advantageous to be a closed system and capture high quality lung audio. The design of the valved holding chamber 3 effectively isolates sounds generated from the patient’s lungs from ambient noise. When this device is coupled with an intentionally positioned microphone 18 which is used to record the lung sounds, a closed system emerges that can capture lung audio passively while the user is administering medication and not during a secondary or additional procedure.

[0067] Given the description of a closed system, it is not necessary that the system is completely sealed or closed off from the outside environment as some fluid communication with ambient is necessary for the proper functioning of the valved holding chamber 3. This fluid communication with ambient may be realized by openings for inhaled air to rush into the input end 108 of the valved holding chamber 3 through the pMDI boot 128 and through the output end via the inhalation valve 114 during inhalation. Exhaled air flows through the exhalation valve 116 during exhalation, with the one-way inhalation valve preventing the exhaled air from reentering the chamber 102. These paths to ambient although present are not direct paths to the open environment, but still provide noise isolation properties and are considered part of the closed system.

[0068] The microphone 18 to record the lung sound information is, in one embodiment, situated in the backpiece 106, nested underneath the opening 124 wherethe pMDI insertion point is, and open to the inside, or interior chamber 102, of the valved holding chamber 103. This location is optimal for audio recording as herein will be described. First, this location is optimal to prevent microphone overload and distortion. Any current of air directed towards the microphone has the capacity to exceed the microphone’s maximum recording capacity, measured through sound pressure levels. If a current of air is forceful enough, it will overload the microphone and create distortion, which is interpreted as a harsh gritty noise that is meaningless in the context of lung audio recordings and results in a loss of useful data. The position of the microphone 18 is situated so that during inhalation, when currents of air are passed through the pMDI and into the second cavity, there is no forceful, or high velocity, air current causing any distortion to the microphone 18. In other words, the microphone 18 is outside the inhalation flow path as shown in FIG. 16. In one embodiment, the microphone 18 is positioned in a pocket 140 below the mouthpiece 126 and between the mouthpiece and the wall of the holding chamber. The mouthpiece 126 protrudes past the microphone 18 into the cavity in the longitudinal direction. The microphone 18 is effectively shielded and any air current in the pocket 140 is much slower, or at a lower flow rate, than the inhalation flow of the main current that is travelling towards and through the one-way valve 114.

[0069] During exhalation, any air pushed into the first cavity, e.g, defined by the valve assembly 112, does not make it into the second cavity, or interior of the holding chamber 102, where the microphone 18 resides. While this initially may seem to be a detriment to the quality of the recorded lung audio, the one-way valve 116 prevents exhalation currents of air from being directed towards and reaching the microphone 18 and thereby causing distortion of the recorded sounds. While air currents are prevented, soundwaves permeate the thin one-way valve 114 and are transferred through relatively slow moving, or motionless, air to reach the microphone 18. In this way the microphone 18 can record audio without distortion. If the microphone would instead be located in front of the valve 114, near, in or on the mouthpiece or mask 15, the microphone may be subjected to higher velocity direct air currents. When coming into contact with themicrophone, these air currents may exceed the rated pressure the microphone is capable of handling and cause distortion. During the high pressure caused by air currents, any recorded sound that was present during the distortion may be lost.

[0070] The design of the valve 114 is so that it is open during inhalation and biased shut exhalation. As mentioned, this difference in valve state during breathing states uniquely protects the recording from distortion when air currents would be directed at the microphone during exhalation and eliminating any needless filtering during inhalation when the microphone 18 is at no risk of distortion due to the intended design of air currents.

[0071] The design of the valve 114 itself is uniquely positioned to allow a high degree of acoustic transparency while providing a physical barrier to prevent any exhaled air from being transmitted into the body or interior space 102 of the valved holding chamber 3 and a low inhalation resistance due to its low opening force. This valve 114 possesses a large surface area, which enables a greater quantity of sound energy through it. This surface area is also important for low-frequency sounds with longer wavelengths that require more area to effectively propagate.

[0072] The ring-shaped structure of the valve 114 allows simple tuning of the valve to allow greater passthrough of specific frequencies. This can be performed by increasing or decreasing the radial width of the ring shape to allow greater passthrough of higher or lower frequencies, respectively. This ringed structure also allows for localized resonant tuning on different sections of the valve, with one area of the valve having the smallest radial width, and the other having the largest, allowing a full range of frequencies to be passed through the valve with minimal dampening. Similarly, the thickness of the valve could also be modified either in localized regions on the valve, or a universal thickness to assist in the resonant frequency tuning. The goal is to enable the valve to be thick enough to prevent unintended deformation during normal airflow while still being thin enough to maximize acoustic transparency. In an alternate embodiment, the valve could have two different areas, one that is the valve portion, intended to open and close in response to inhalation, and a second area that remainsclosed but extends outwards to cover more surface area. This would essentially allow the thin membrane of the valve to cover a larger portion of the end of the chamber and thus allow for greater transmission of acoustic energy yet still function as a seal between the mouthpiece or mask and the body of the chamber. There may be different designs which may include larger, smaller, or discreate areas of membrane to be positioned so to maximize sound transparency yet still support the effective operation of a VHC. As shown in FIG. 17, during exhalation flow there is acoustic transmission through the exhalation valve and into the chamber, while in FIG. 18, there may be acoustic transmission, for example a wheeze sound emanating from the oral cavity of the patient, which may propagate through the membrane in the baffle and through the inhalation valve in to the chamber.

[0073] The valve is also made from a smooth, elastomeric, non-porous material that blocks air passage while the smooth surface minimizes air turbulence and helps maintain consistent sound propagation. Example materials include thermoplastic elastomers (TPE) and silicones. In addition, the opening and closing of the valve is quiet enough to not interfere with the recorded audio as it is made from a non-crystalline material (e.g. silicone rubber), and the valve itself has been designed to be opened and closed at low pressures. Other materials may have more desirable acoustic properties or resonance characteristics which may allow for optimized sound transmission yet still operate as an effective valve or membrane.

[0074] The baffle 150, located in the center of the valve 114 is designed to improve aerosol particle distribution within the chamber. The baffle 150 may also support the transfer of sound through the valve 114. In one embodiment the baffle 150 acts as an acoustic membrane in addition to the valve 114 to help transmit the greatest quantity of noise to the microphone for recording. This would be accomplished through reducing the thickness and surface area of the baffle to tune its acoustic properties to allow the optimal transmission of a desired frequency.

[0075] In an alternate embodiment shown in FIGS. 27-29, the microphone 18 may be situated in a secondary air channel 162, defining a second interior cavity separatefrom the interior cavity 102 of the chamber, that allows a portion of the air drawn in to the chamber to take an alternate path and bypass the inhalation valve 114 on the way to the mouthpiece or mask. The secondary air channel 162 may deliver inhaled air to different patient or caregiver feedback mechanisms in or adjacent to the channel 162 including both visual and audible feedback mechanisms that may provide information about aspects of the use of the valved holding chamber. The feedback may include whether or not the patient is inhaling or exhaling and whether or not they are inhaling at the correct flow rate for optimal drug delivery. There may be other functions that this secondary air channel can support. This secondary channel may also have an inhalation valve 164 that prevents air from flowing back into the channel 162 when the patient exhales. Placing the microphone 18 in the channel 162 provides similar advantages to placing it inside the main body of the valved holding chamber interior 102 as disclosed earlier in that the microphone 18 is positioned outside the path of the high velocity air closer to the mouthpiece or mask and on the other side of the main inhalation valve 114. The channel 162 may also function as an acoustic element, carrying breath sounds from the source back through the channel 162 to the microphone 18 which could also be similarly housed in the backpiece 106. The secondary channel 162 may provide other advantages in that it may prevent the need for a membrane or other protective cover 170 around the microphone, as shown in Figure 25, which may prevent buildup of drug residues on the microphone 18. This is because the secondary channel is unlikely to draw in very much drug due to the fact that the ideal channel inlet location would be in such a location as to not draw aerosol drug particles into the channel. Another advantage of the location of the microphone in the secondary air channel 162 is that the microphone may be positioned near the feedback mechanisms which may also generate noise as part of their operation. For example, a whistle 172 that generates a specific frequency in response to flow or a visual feedback indicator 174, such as a moveable flap, that makes an audible noise when it moves back and forth during each breath. One skilled in the art could apricate that other noise artifacts generated as air flows through these feedback features, orother features of the valved holding chamber, may be recorded by the microphone 18 and through an algorithm, assessed along with recorded breath sounds. The information gathered by analyzing these device generated noises may augment or complement the recording of breath sounds by providing more data about how the patient is inhaling. For instance, a noise generated by one of these features may be quieter or louder depending on how forcefully the patient is inhaling. The algorithm may correlate the volume or characteristic of those noises with other data including data captured from other sensors like flow or pressure sensors and the audio recording if breath sounds. This data may provide a more complete picture of the patients inhalation and drug intake that would not be possible without having the microphone 18 located close to these features 172, 174. Lastly, because the secondary air channel 162, or inlet 180 thereto, would be connected to the air volume in front, e.g., upstream, of the main inhalation valve 114, the acoustic signals emanating from the patient, which may include any wheezing sounds, may be transferred down the length of the secondary air channel 162 to the microphone 18.

[0076] In another embodiment, shown in FIG. 26, an additional noise channel 160, defining a second interior cavity sperate from the interior cavity 102, may fluidly connect the microphone 18 to an outlet 182 near the user’s mouth but does not allow inhalation air flow through the channel 160, or interior cavity defined thereby, as is the case with the secondary air channel 162 described earlier. This is accomplished by adding a tube like feature to create a sound conduit that physically separates the microphone 18 from the interior cavity 102 of the valved holding chamber. On the microphone end, the noise channel 162 encapsulates the microphone 18 and terminates to allow no passage of air to or from the interior cavity 102. The other end 182 of the tube, or channel 160, terminates near the mouthpiece or mask in fluid connection with the proximal cavity of the valved holding chamber, defined for example by the valve assembly 112 upstream of the inhalation valve 114. This sound conduit allows the propagation of sound from the user’s mouth to the microphone 18, while separating the microphone from noises generated during the actuation of the pMDI or noises generally from within the bodyinterior 102 of the valved holding chamber 3. In addition, the conduit 160 protects the microphone 18 from any airflow currents developed in the interior chamber 102 that may distort the audio due to the closed end on the side of the conduit 160 where the microphone 18 is located. The conduit 160 passes around, or through the valve 114, with no impact to its function. The conduit 160 is sized to allow the passage of sounds while minimizing harmonics, peaks, or nulls that may be created through the length of the conduit. It is also made with a nonporous material that accommodates the transfer of sound. This embodiment also has advantages in that it isolates the mic from outlet of the pMDI and would minimize the sound pickup of the pMDI actuation. This is further enhanced by the fact that the acoustic opening 182 is located on the other side (e.g., upstream) of the inhalation valve 114, where the inhalation valve may act as an acoustic barrier to the sounds emanating from the release of aerosol from within the body or interior chamber 102 of the valved holding chamber 3.

[0077] In another embodiment, the proximal termination point 182 is covered by a membrane 184, and the entire length of the conduit 160 is fluidly isolated from any space within the body of the valved holding chamber. The membrane 184 found at the proximal end of the conduit is made from a nonporous thin material that is acoustically transparent membrane that allows the maximum passage of noise. The surface area of the membrane is optimized to enable passage of the desired frequency range through the membrane to reach the microphone. In another embodiment, the conduit can run external to the body of the VHC, to not interfere with any of the existing internal geometries.

[0078] In a similar embodiment, the baffle 150 incorporates a nonporous thin-walled membrane that allows the passage of noise between the different internal chambers 190, 102 of the valved holding chamber. This noise transmission may occur in addition to the membrane quality of the valve that also enables the transmission of sound.

[0079] In another embodiment the baffle 250 is shaped as dome with the circular face flush with the center of the valve 114 and the tip of the cone being slightly rounded pointing towards, or directed at the user’s mouth, as shown in FIG. 19, rather thantoward the backpiece. This orientation of the baffle 250 ensures that incoming exhaled air is dispersed radially overtop of the valve 114 and that the incoming exhaled air does not approach the valve 114 at nearly a ninety-degree angle, which could result in air becoming trapped and acting as a buffer to reduce the level of noise getting through the membrane.

[0080] In one embodiment, shown in FIGS. 24A and B, the baffle may be centered or off-centered relative to a longitudinal axis of the interior chamber 102, e.g., with the surrounding opening having a variable radius r, r*a and r*b. In this embodiment, the divergences in widths could enable different frequencies to better pass through the valve 114. That is, by tweaking r*a and r*b, some portions of the valves may be optimized to become more acoustically transparent to certain frequencies, and by putting the baffle off-centered, a spectrum of more transparent frequencies than just one set point may be possible.

[0081] In another embodiment, a microphone 218 may be positioned behind a similarly situated membrane 240 on the edge of the baffle 150, with the microphone facing towards the mouthpiece or mask of the valved holding chamber. The membrane is positioned between the microphone and the mouthpiece or mask such that the microphone 218 is not in fluid communication with the inside of the chamber interior 102. In this embodiment, the side of the baffle closest to the pMDI insertion point would have an acoustically opaque material, or layer 270, to prevent additional noise, e.g., from pMDI actuations, from interfering with the recorded audio. In this embodiment a unidirectional microphone is also used, with the microphone oriented to listen through the membrane 240 to detect breathing sounds from the patient’s mouth. This microphone 218 may be used in combination with the microphone 18 previously described in the backpiece, or as a standalone microphone.

[0082] One embodiment of the proposed devices involves the use of a protective barrier or cover 170 used to protect and isolate the microphone 18 from water, particulate matter, or other potentially destructive materials that could impact the accuracy and quality of the recorded audio. These protective barriers, which for thepurpose of this description shall be called membranes, have been developed to retain a high degree of acoustic transparency, while protecting the microphone. The barrier 170 may close off and isolate the pocket 140 from the interior space 102, or simply surround the microphone 18. The design of these protective barriers involves determining the optimal thickness, material, and manner of attachment to the microphone to enable the passthrough of the highest range of frequencies without significant drop-off. The optimal thickness of the acoustic membrane 170 has been revealed to be as thin as possible, while still maintaining an element of durability depending on the material chosen. The material plays a large role in the transmission of audio as the material ultimately dictates the relative ability for sound to pass through. Porous materials result in the capture of sound energy and its conversion from acoustic to thermal energy and results in a greater loss of sound energy than non-porous materials. A uniform material enables reproducibility in captured sound. Durability of the material is also an important consideration as the described embodiment is part of a reuseable device, and will need to withstand several cleaning options. Given these criteria, a uniform-thickness silicone membrane was chosen to create a membrane with overall thickness in the range of 0.15 to 0.6 mm. This membrane may be used as either part of a larger silicone component with a thinner section, or fastened between a clamp like style connector that spans the entirety of the perimeter of the membrane. Fastening the membrane in this method creates a reproducible tension across the membrane, which results in reproducible behaviors of the membranes.

[0083] The membrane 170 is also positioned so that the entirety of the sound port (channel 160 that is in fluid communication with the microphone 18) that the membrane creates is more than 4mm in length away from a PCB the microphone 18 is mounted upon. This ensures the recorded sound is minimally impacted by the narrow diameter port hole.

[0084] As mentioned herein, the closed system representing the valved holding chamber 3 coupled with a microphone 18 to detect breath sounds is effective at isolating against ambient noise, but the positioning of the microphone nested within thebackpiece 106 further isolates the microphone from noise generated as the user handles the device. The rubberlike backpiece 106 that houses the microphone 18 has a less crystalline atomic structure than the rigid materials used for the structural components of the valved holding chamber. This dampens the propagation of sound waves through the material in comparison to the rigid components, and results in lesser intensity of handling noise that overlays the recorded lung audio.

[0085] It is helpful to minimize the noise that is generated and recorded when the device is being used through handling. In the context of the valved holding chamber, as noted, the backpiece 106 may reduce the propagation of soundwaves to reach the microphone 18 due to the reduction in rigidity of the backpiece. Other optimizations that may be made include reducing the amount of material that holds the microphone in its defined position, to limit the ability of the material to propagate acoustic vibrations. Another optimization would be to implement an actively sound dampening material as a barrier between the microphone and the material that holds it in place. This acoustic dampening material would have the same properties as described previously, i.e. , a less crystalline structure.

[0086] In another embodiment, handling noises may be further reduced through a redesign of the backpiece that enables further dampening. This backpiece is created using two different durometer materials, with the lower durometer encapsulating the PCB that the microphone is located on. The lower durometer material reduces vibrations and audio propagation more than the higher durometer material. The lower durometer material may also have a design such that there are open air gaps, or minimal contact with the higher durometer material to encourage the minimum transfer of handling noise. The encapsulated PCB would also be separate from the rest of the electronics, only connected by wires to minimize the transfer of any noise from the original electronics. The connection may also be wireless. In another embodiment the entire electronics are encapsulated in the lower durometer material and cannot be contacted during use.

[0087] Further handling noises may be reduced through a padded or low durometer material encapsulating the exterior of the valved holding chamber or where the main touchpoints are for the user to minimize handling noise. If a mouthpiece is used instead of a mask, the mouthpiece may be made of a material with a lower durometer material to minimize the amount of noise generated when users’ teeth contact the mouthpiece material. In another embodiment the mouthpiece could be made of two separate materials in a two-shot molding process where the part makes contact with the user’s mouth is a softer, lower durometer, material and the remainder of the component is made of the clear rigid material currently used, or similar. This combination of materials allows for rigidity and transparency into the mouthpiece while still minimizing handling noises.

[0088] This material may also be applied to the body 100 of the closed system, to further reduce the capture of ambient noise and increase the isolation of the captured lung sound. An acoustic dampening material could be placed on the exterior if the closed system to facilitate such a change. Or the materials of construction used to form the outside portions of the device are selected from those that have advantageous acoustic dampening properties.

[0089] The proposed embodiments describing a closed environment of a valved holding chamber attempt to minimize the creation of peaks or nulls and create a flat frequency response curve spanning from 0Hz to 20,000Hz. These embodiments may involve reversing the draft of the chamber so the larger end is the side closest to the users mouth, increasing the overall dimensions of the body or other components of the smart valved holding chamber, or creating a separate channel 160 that enables the breath sounds to travel directly to the microphone without interruption from the one-way valve or other obstruction.

[0090] Given that the smart valved holding chamber 100 is in one embodiment a cylindrical tube with a one-way valve 114 at the end closest to the user, there are limited options to optimize the device to achieve a flat audio response over the desired frequencies without impacting medication delivery. As such, corrections can be made toeither nullify peaks or amplify the nulls of the frequencies to better approximate a flat response curve. Implementations of these devices include the inclusions of ribs, bumps, slits, or other diffusion inducing obstruction to encourage a diffusion pattern resulting at the inlet of the microphone or utilizing a porous antistatic sound absorbing material (both in conjunction with the existing body, or used by itself along the perimeter of the inside of the chamber to reduce the reflection of soundwaves that bounce along the edge of the chamber.

[0091] For each of the listed embodiments, or through a combination of the listed embodiments, a typical frequency response curve will be characterized, and all incoming recordings will be digitally transformed to yield an approximation of a flat frequency response curve which will then be used as part of the algorithm. The algorithm may also take in non-normalized frequency responses, depending on the embodiment.

[0092] Another method to further isolate the captured lung sounds from both ambient and handling noise includes the addition of active noise cancellation that may be applied to the recorded audio clips after they are recorded. This active noise cancellation would be implemented through the addition of additional exterior microphones 302 on the exterior of the device which would listen to all noise generated outside the closed system. These microphones, due to the nature of being situated on the device itself would also be subject to similar handling noises the internal microphone would be subject to. After the recording, an algorithm would take the recorded noise from the exterior microphones and the microphone positioned within the closed system and negate any unwanted noises. Further isolating and preserving the quality of the recorded lung audio data.

[0093] An interesting advantage to this procedure is the ability for the processing to happen after the recording has been saved. Existing noise cancelling technologies often focus on live noise cancellation, but post recording noise cancellation allows for decreased processing power and the ability for the algorithm to implement the noisecancelling to a greater extent because it can take in the entire recording and compare them before the system makes its adjustments.

[0094] Other environmental noise could be reduced by the inclusion of a doublewalled valved holding chambers, with an inner layer of material that contacts the inner chamber of the device, an outer layer that contacts the external environment, and an internal region between the two layers that is comprised of a layer of air or another insulating material. This double-walled embodiment enables decreased vibration and noise propagation from the outside environment and results in decreased noise interference in the recordings.

[0095] In another aspect, the proximity of the microphone 18 to the pMDI may pose challenges when medication is administered through the pMDI. While the placement of the microphone in the embodiment described earlier in the backpiece is out of the flow path resulting from pMDI actuation, the actuation of the pMDI creates a loud noise that may impact the recorded audio.

[0096] The noise generated from the pMDI is brief but has the capacity to overload the microphone 18, resulting in lost data. As inhalations are long and often drawn-out during inhalation and as multiple breaths are often taken while using the valved holding chamber, the noise from the pMDI should represent a small fraction of the total collected data. Noise from breath to breath is unlikely to change, and sufficient recorded information will be caught either during preceding or subsequent breaths.

[0097] The actuation of the pMDI can be used as a marker to indicate the beginning of medication treatment, and then the subsequent noises could be used to indicate the number of breaths taken and produce an estimation of the quality of inhalation.

[0098] Given the noise generated from the pMDI, optimizations can still be made to minimize the impact of actuation noise on the recorded audio. One additional embodiment includes the incorporation of additional microphones for noise cancelling purposes. As explained within a separate embodiment disclosed herein, noise cancelling also has opportunities for optimization to reduce the impact of pMDI actuation noise, or other noise generating events that occur during the intended use of the device.For these intended use noises, the noise cancelling algorithm can be able to pick up the actuation noise and filter it out as it has been described herein.

[0099] In addition to these mitigation strategies, the noise generated from pMDI actuation could also be used as markers to identify when the patient is likely breathing in or out and enable the device to identify sections of recorded audio or other generated data accordingly.

[0100] Another design element of the valved holding chamber that is beneficial in ensuring audio quality is the repeatability of the measurements that it brings. The valved holding chamber is designed such that it fluidly connects to a patients mouth through the use of a mouthpiece or a mask, as shown in FIG. 22. Each of these methods position the device to the same location with respect to the user’s lungs, ensuring that the recordings made over time are repeatable.

[0101] Previously a problem was identified that chest or back measurements with stethoscope like devices may miss important lung sounds as they may happen in differing regions than the placement location of the device. Previous literature has found that auscultation over the trachea 151 compared to the chest is the most effective at detecting wheeze, yet auscultation through the trachea requires sound to travel through a denser medium of dense biomaterials that filters the sound as it travels. This filtering would result in a loss of data. Even so, the quantity of these materials, like fat deposits in more obese patients can cause variations in the recorded audio in a through the body listening device like auscultation.

[0102] Using a closed system such as a valved holding chamber 3 to collect audio sounds capitalizes on the previous literature of tracheal auscultation and improves on it by removing the need to record audio through parts of the human body. As shown in FIG. 23, the lung sounds apparent in the trachea have no major obstacles to the same magnitude as traditional measuring as they do towards the mouth of the patient. It is here that a closed system such as a VHC can collect sounds generated from each region of the lungs also present in the trachea.

[0103] Any valve or membrane like device of a closed system like the one-way valve disclosed of herein of the valved holding chamber also provides a repeatable filtering mechanism with minimal losses that is consistent over time, unlike the ever-changing composition and structure of a patient’s body. Therefore, the mouth 101 is a conduit for sound from all regions of the lungs, so having a recording device affixed a predetermined distance from the mouth 101 will enable lung sounds to be captured in a repeatable fashion, as shown in FIG. 22. In very small children, such as infants, who are generally obligate nose 103 breathers, the mouth may still be open which would allow breathing sounds to propagate or noise propagation can still occur through the nasal passages.

[0104] The lung sound breath recording feature is completely passive and begins recording audio data generated from the lungs when the patient utilizes the Smart Valved Holding Chamber to administer medication from a pressurized metered dose inhaler (pMDI). This action is passive as it ties the act of using a valved holding chamber with sound recording, ensuring that data will be collected every time the user administers medication using the Smart Valved Holding Chamber device.

[0105] For wheeze and other breath sound detection, the microphone-equipped smart valved holding chamber can be used in several distinct methods of use. Each described embodiment can be used in conjunction with other methods of use, or could be standalone, depending on the embodiment. During this process the smart valved holding chamber is activated through any manner of motion or pushing a button, or any manner of environmental detection. After this trigger the device is active and begins to await a confirmation that the patient is breathing through it. This confirmation could come through any manner of external stimulus, through the noise generated from a pMDI actuation, through flow sensors, through detection of other sounds through the microphones, or any other method outlined in the previous sVHC patents, referenced above. In addition, any combination of these external stimulus sensors can be used to determine that the device is to begin recording.

[0106] For example, in one method, illustrated in FIG. 30, the microphone-equipped smart valved holding chamber may transition from a “powered off” state by pushing a power button, thereby entering a “stand-by” mode, where the device monitors for detection of a recording trigger (e.g., motion, button activation, noise, pMDI actuation, flow, etc.). Then, when a breath is also detected, the microphone may begin recording. Following the recording, and depending on connection status of the device to external storage, recording data may be saved locally, pushed to external storage, or saved both locally and via push to external storage.

[0107] In one embodiment, the patient uses the smart valved holding chamber to administer medication, or with the help of a caregiver in the case of a child, through a pressurized metered dose inhaler. The patient uses the smart valved holding chamber 3 and breathes according to the instructions given on the medication instructions: long, slow deep inhales with regular exhales or in the case of a child who cannot follow instructions, to just breathe normally.

[0108] In another embodiment, the patient breathes through the valved holding chamber without administering medication through the pressurized metered dose inhaler. The patient can breathe through the device as if they were about to inhale medication, or through normal breathing.

[0109] Another embodiment involves using the smart valved holding chamber or accessory as an ambient sound monitor to detect respiratory events while the user is in proximity to the device. In this case, the device would recognize an external confirmation such as being placed on a charging receptacle, or a specific orientation which will be detected through a gyroscope, or the lack of motion, or the time of day, or a physical button, switch, or selection in a connected app that the user selects when the device is about to be used without the intent of delivering medication.

[0110] In each of these embodiments, the microphones 18, 218, 302 positioned within or outside of the smart valved holding chamber device or accessory devices record breathing sound or respiratory events from the ambient environment, and theartificial intelligence algorithm will interpret the results according to the description in a separate section.

[0111] One particular advantage is that the use of the VHC is coupled to a relief in symptoms which provides an incentive for a user to use the device to take medication. If a user sees no direct correlation to an improvement in symptoms through using such a device, they may not deem the effort of logging the information worthwhile and may not use the device for a long period of time, if at all. Through coupling the medication delivery with capturing lung audio recordings, the action of seeking relief compels the user into acting and as a result, lung sounds are passively recorded without any additional steps of devices required. Children typically use a Valved Holding Chamber when taking medication from a pMDI as they do not have the coordination necessary to inhale when the drug is actuated. This further enforces the passive nature lung sound breath recording when using a Smart Valved Holding Chamber with children or with anyone who cannot coordinate use of a pMDI effectively.

[0112] Although children would be a primary benefactor of the proposed technology, this device can be used to support and benefit the entire age range of the population. As spirometry is unable to be performed in children under the age of 6 due to the complex maneuvers required, the smart valved holding chamber may be especially useful to this population to help diagnose and monitor these patients and provide needed relief to caretakers through digital queues on how to support the patient’s disease. Although there is a unique proposition to benefit younger children who are unable to perform spirometry, the benefit of the technology is still applicable to other populations as it can aid in the diagnosis and monitoring of all patients with respiratory disease. Pulmonary function testing is not easy to perform for some patients. It also requires specialized equipment and resources that are not always accessible to patients. This companion patient facing application can also adapt the feedback based upon the user’s techniques and provide insight into proper techniques and warn the user and health care practitioner of a pending exacerbation or downward trends in their health. This application can apply to other diseases, including those that may not affectmany children including COPD, Cystic Fibrosis, Bronchiectasis, Emphysema, and others.

[0113] In the case of asthma therapy, a rescue medication is generally only taken when an individual needs rapid relief of symptoms, indicating that they are having some form of breathing abnormalities or exacerbation of their condition. By coupling the lung sound breath recording feature set with the rescue medication delivery, it ensures that the exacerbated breathing will be captured where worsening airway restriction is likely to cause wheezing. This provides a rich dataset that can be later used by physicians and by the patient to help in the diagnosis and / or monitoring of their condition. This is an immense benefit to physicians as they often do not have the opportunity to witness the patient in an exacerbated state unless it coincides with a visit to the doctor’s office or in the case of a methacholine challenge (or similar) is performed to artificially induce symptoms. This is because it is currently difficult to predict the time of an exacerbation due to the episodic nature of asthma, and often patients or caregivers must book a physician appointment well in advance.

[0114] In other uses such as inhaling with an inhaled corticosteroids (ICS) which is taken prophylactically and not in response to symptoms, the device may alert the parent in some way if the child’s breath sounds indicate some form of wheeze, cough, congestion, or other difficulty breathing, and suggest that the parent take action in an appropriate manner. This could include taking a rescue medication to reduce airway restriction. There is also a feature that enables breath sound recordings a period of time after rescue medication was administered. At that time, the user will be prompted to breathe through the device again without dispensing medication. In this second time the user will breathe through the device as normal, but they will not administer any medication. During this time, the smart valved holding chamber will record any breath sounds. The purpose of this post-reliever audio capture is to be able to discern differences between the two audio recordings and evaluate the user’s response to the initially administered rescue medication. Of particular interest is the resolution of wheeze sounds following rescue medication administration. Any change in symptomsbetween before and after reliever medication use may support reversibility and be a strong indication that an individual has asthma.

[0115] Like the last example, the user may use the device without medication to listen for abnormal respiratory sounds, or to record other breathing parameters like flow through the device without being prompted. The device would then analyze the results and provide insights into the user’s respiratory condition with instructions on how to proceed. For example, after breathing through the Smart Valved Holding Chamber the device may validate that the child has a wheeze and instruct the parent and child to administer a rescue medication, or other applicable action. While this added feature introduces a new step the child is not fully familiar with, it is on a device that they are already acquainted with using during drug delivery, so the barriers to adherence are significantly reduced.

[0116] A further explanation of the evaluation may be found in the “Algorithmic Interpretation of Breathing Sounds” section below.

[0117] The Lung Sound Audio Recording element improves upon prior medication management systems as it leverages the widespread knowledge and current practice of using valved holding chambers to gather information that can help inform physicians on proper diagnosis.

[0118] It has historically been a challenge for physicians to convince their patients to adhere to the guidance given to them, whether it is medication that needs to be taken, information that needs to be logged, exercises that need to be performed, etc. Adherence to respiratory related medical conditions is no different, and adherence in this space tends to be below average. Adherence is a multifaceted problem and is affected by numerous factors including, motivation, knowledge of how to use the prescribed medication / device, time to complete the action, etc.Algorithmic Interpretation of Breathing Sounds

[0119] The algorithm could be a smart learning algorithm, or an artificial intelligence (Al) that is used to sort through the data that is collected. This collected data includes breathing sounds (both ambient and direct from lungs), other sounds including thosefrom the inhaler or the VHC, technique, adherence data, airflow information, or other data stored on, or recovered from one or multiple devices that were mentioned in this disclosure. From this information, the artificial intelligence may make recommendations based upon one, or a combination of multiple data points that it will present to parents or physicians. The Al may even make recommendations on next actions to take, or the proper diagnosis of the patient.

[0120] The Al may also create a sound profile based upon inputs for a specific child (as respiratory sounds are different between children). In doing so, the Al would learn the specific respiratory sounds of the child and better identify normal breathing from restricted breathing.

[0121] The device may accomplish most of the data manipulation or learning either on the cloud, on the phone, or on one of the devices.

[0122] In one embodiment, data transfers may be made from the device to the cloud for processing. Physicians and users may access a portal to review and analyze the presented information. The algorithm takes in a recording of variable length and processes the algorithm based on decibel thresholding into regions of silence and regions of activity. The activity may then be converted to a spectrogram using Mel- frequency cepstral coefficients (MFCC), and potentially others to generate features suitable for machine learning and statistical inference. Each region of auditory activity is individually processed to be interpreted. In cases of substantial background noise, heuristics around inhalation and exhalation may be applied to supplement this processing into chunks to allow for processing of the data.

[0123] This algorithm features a multi-stage, adaptable ensemble model which is designed around the forthcoming pre-determined change plans (PDCP) which is expected to be common across the USA, UK, and Canada for the continued improvement of algorithms under a single regulatory body (like FDA) clearance. The ensemble model is expected to consist of six individual algorithms, which are modular, and as part of a linear combinatorial ensemble (see Equation 1 below), which could be expanded upon with future modular and independent components.

[0124] D(x )=w_1 f(x )+w_1 f(x )+w_2 g(x )+w_3 h(x )+w_4 i(x )+w_5 j(x )+w_6 k(x )

[0125] Equation 1 : This equation shows the 6 modular components based on statistical or machine learning functions f through k which take as input a vector of features ‘x and a corresponding weighting w n which combines into the total output of the decision function D, which makes the final decision on the breath sound. A simple modification of regression rather than classification to the algorithm allows for extensions into seventy of wheeze rather than identification.

[0126] The first of the six equations is a decision tree algorithm, which is a series of decisions made on numerical thresholds in the data, which can be cleanly visualized in a binary tree structure as a series of decisions, making it popular for interpretability and communication. The second of the six equations is a linear kernel support vector machine (SVM), which has high performance in low data environments and is highly explainable by interpreting the weights on the separating hyperplane produced by the SVM. The third of the equations is a logistic regression with L2 normalization. The fourth of the equations is a convolutional neural network. The fifth of the equations is a vision transformer. The sixth of the equations is a deep neural network that uses a multi-stage representation learning process. Specifically, a variationally autoencoder is used to generate a latent space representation of breathing noises; this representation is then used as input to a radial basis function SVM, which classifies the representation as wheeze or not wheeze. Adaptations are made to the output for the continuous case that would be used in predicting severity; alternatively, if severity is separated into multiple classes, all of the listed algorithms and the combination thereof is adaptable to the multi-class setting.

[0127] The final function D(x) is tuned by adaptive boosting (AdaBoost), which is a meta-learner that works on a combination of classifiers specified. Variations exist for the multi-class setting and for real-valued (i.e. , continuous) output. This process refines the weights of the algorithms to produce an optimal prediction while retaining the different contributions of the algorithms at different parts of the whole problem of interpretingbreath sounds. If the algorithm needs to be customized around non accuracy metrics (run time, space on device, compatibility with lower level language support), then the AdaBoost procedure can be repeated on the remaining algorithms without incident to provide one customized to the use case.

[0128] Some of these algorithms historically are better in low data environments, while others thrive in higher data environments and outperform their comparable family of algorithms once those conditions have been met. In combination with the PDCP, the AdaBoost procedure allows for the stable and reliable performance of the algorithm in batches while ensuring that the original models are still available, and being improved upon, from the earliest iterations of the algorithm to the newest version. Optionally, end users could customize which algorithms are included and then boosted depending on their needs, reflecting the fully modular and adaptable nature of the ensemble of algorithms included here. Suggesting that the entire combination, particularly the to-be- developed representation of breathing sounds through the variational autoencoder representation learning process, represent the novelty in the software / Ai side of things.Information Portals

[0129] The information portals are applications that function to portray the collected data to interested parties. There may be multiple portals, including a physician facing portal, and a parent / guardian / caregiver facing portal. In both portals, all the data collected from the aforementioned elements are displayed in a concise and distinct manner to enable parents and physicians to make educated decisions about the outcome of the therapeutic trial, diagnosis, and the overall management of the patient’s condition. The patient / caregiver facing application may also reduce anxiety and improve engagement in the management of the disease.

[0130] The parent facing application may permit a parent, or other caregiver, to enter symptoms, triggers, past medical history, or other questions that the app would prompt that would be useful for the physician to make a diagnosis. This portal also has a feature set that allows the parent / guardian / caregiver to share pertinent information regarding the entered and collected data to the physician using a PDF, or other suitableelectronic medium. This method would include means to share pertinent information regarding the therapeutic trial, or other information about the child’s condition, including at least one of but not limited to: audio recordings, adherence data, technique information, or any algorithmic or Al interpretation of the collected data. When the app is connected to the internet, it will push the information to the cloud where the information can be readily viewed by the physician through a physician facing dashboard.

[0131] The physician facing portal would share similar feature sets to the parent portal, but it may include other pertinent information, like differential diagnoses, family history, and other necessary information. This portal also would have an ability to be fully integrated with major electronic medical records (EMRs), which would enable the physician to store the resulting information in a method that integrates with their workflows.

[0132] The physician interface may be more pointed towards a diagnosis, or provide more direct actionable items as the clinician would know the optimal way in sharing this information with the patient. The intention of this portal is to compile clinical data in a way that makes it easier to: 1 . track and understand medication adherence, 2. understand patient techniques, 3. discern the presence of clinical wheeze, and 4. understand and display the relationship between the previous points. As mentioned in the section describing the patient facing application, the information needs to be presented in such a manner as to prevent unnecessary physician visits.

[0133] One embodiment of the present disclosure includes a section that addresses the patient’s response to a therapeutic trial. It incorporates information from historical medication delivery and recorded trends in the patient’s respiratory disease control to understand the response to the administered medication. The system may also take in other information as well to aid in the determination, and look at ACT questionnaire responses, symptoms at night, limitations to activity, frequency of rescue medication use, frequency of hospital visits, and overall frequency of symptoms.

[0134] The described embodiment may also feature a summary section with the patient’s needs that displays the pertinent information that springboards the physicianinto making a quicker diagnosis, or into an investigation to determine the best course of action for the patient to take. The presented data will be based upon the recommendations of the algorithm, which will output a recommendation, or a projection based upon the information supplied. That summary may also be presented with supporting data to the recommendation to provide a means for the physician to investigate. This summary will be presented in addition to all the collected data as described herein.

[0135] The portal also may include a physician time tracking feature, that calculates the quantity of time a physician spends investigating a patient’s respiratory condition which could then be reported and used for billing purposes. This feature may stop tracking time if the physician is inactive on the screen.

[0136] There may also be a section of the clinician portal that gives an explanation to the behind the scenes functioning of the artificial intelligence algorithm. This is included as a physician may distrust information provided to them that they do not fully understand. By revealing the mystery of the artificial intelligence algorithm, and explaining it in a way, physicians may be more likely to pay attention to the recommendations given by the platform.System

[0137] In one embodiment, the system couples the act of taking medication with a valved holding chamber with recording clinical quality data that can be used in the management and diagnosis of respiratory conditions. Additionally, the system, including the valved holding chamber, has the functionality of recording sounds generated from within the lungs, or from the ambient environment. The system acts as a tool that physicians can use to gather information to review prior to making a diagnosis, and as a post-diagnosis management tool to ensure that patients, especially pediatric patients, are living to their fullest potential. In this system, the information generated and presented to a physician encompasses a wide breadth of insights that may be difficult for physicians to determine without the use of this tool. This information includes thedata such as wheeze detection, cough monitoring, symptom tracking through the included app and medication and technique tracking. All this information is presented on the patient and physician facing app / dashboard with included algorithmic interpretations on some of the data, like respiratory sound identification.

[0138] Moreover, the embodiments of the system includes tools used to gather information about the pediatric patient using widely adopted practices, such as the use of a valved holding chamber, or are completely passive and require no additional thought to record information beyond the initial set up of the device, like the Ambient Sound Monitoring Device. Ultimately, the combination of passive data that covers a wide range of parameters, used in the diagnosis of pediatric asthma saves all parties involved a significant amount of money, time, and uncertainty. This is because the system works to provide passively collected information to physicians which enables them to make educated diagnoses on children with respiratory symptoms without the use of spirometry. Additionally, after diagnosis, the system empowers parents and caregivers to take charge of their child’s condition. These factors work to reduce time spent within, and the attendant strain on, the healthcare system.

[0139] In the present disclosure, the embodiments of the devices and systems may be used to objectively capture concrete information to either enable a faster diagnosis of respiratory conditions, or better track and manage asthma. If used alongside a physician for diagnosis purposes, the use of the system may be used as part of a therapeutic trial. The system is to be referred by a physician, but a parent / caregiver or patient may also begin utilizing this system of their own volition to manage their child’s or their own respiratory illness. Regardless of the use case, the preferred embodiment as described below will be incorporated into a user's daily respiratory management routine.

[0140] Figure 1 illustrates one embodiment of a system illustrating how the devices may communicate, and how the different users (ex. child, parent, and physician) may interact with the system. The workings of this system will be detailed through theembodiment description. Figure 2 shows one embodiment of a wireless communication between the Smart Valved Holding Chamber and the patient / caregiver application.

[0141] In one embodiment, the parent / patient facing app 1 conveniently stores the information regarding the management of the patient’s respiratory condition. This application is connected to multiple data collecting devices that collect relevant information from the child 2 through the Smart Valved Holding Chamber 3 with breath sound recording and / or a separate Ambient Lung Sound Breath Recording device 4, as shown in FIG. 8. This increased information can be used to assist in the management or diagnosis of the patient. The app may also connect to the internet 5 and upload the collected information to the cloud 6 where it may be accessed by a physician through a patient portal 7 to assist in the diagnosis of the disease or general management. Both the patient portal and parent / patient facing app include information that details the management of their child’s symptom management 8 and medication regime 9.

[0142] To initialize the smart holding chamber 3, the battery 10 on the smart valved holding chamber 3 must be charged to a sufficient degree. If the battery is not charged the device will work in administering medication, but no information will be recorded for assistance in management. The smart valved holding chamber is configured with a port providing for the battery to be charged via a charging cable (USB-C, etc.) or a wireless charging solution. With a charged device, the accompanying application must be downloaded and opened on a smart device 11 and connected to the smart valved holding chamber through a means of wireless communication 12. Upon connection, relevant information regarding the patient’s disease, including prescription information, is to be entered either by the patient or the physician 13. Once the smart valved holding chamber is initialized, the device is ready for use.

[0143] The smart valved holding chamber of the described embodiment may include pressurized metered dose inhaler recognition 14, medication adherence tracking 14, inhalation technique scoring 14 which is calculated through available metrics like flow rate, device orientation, and other metrics, and wireless communication 12 with an accompanying application, among other features.

[0144] One embodiment can be seen in Figure 3, which includes a user interface, configured for example and without limitation as a mouthpiece or mask. In one embodiment, the smart valved holding chamber may incorporate a mask 15 instead of a mouthpiece to fluidly connect to the airway of the patient. When in use, the mask is to be gently pushed onto the patients face to create a seal around the mouth and nose of a patient. This mask is the preferred interface for the smart valved holding chamber 3 when used with young children incapable of using a mouthpiece or forming a proper lip seal.

[0145] The smart valved holding chamber 3 of the current embodiment is to be used whenever a user needs to take medication through a pressurized metered dose inhaler (pMDI). To take medication, a user inserts the desired inhaler (e.g., PMDi) 16 into the rear of the smart valved holding chamber 3 and positions the mouthpiece in the mouth, or the mask 15 onto the face. The patient or caregiver then depresses the top of the inhaler, container 17, 132 to release aerosolized medication into the device while the patient simultaneously inhales through the mask 15 or mouthpiece of the device. In one embodiment, the valved holding chamber 3 includes a feature that enables the recording of breath sounds while a patient is using the device. These breathing sounds will be automatically recorded through a microphone 18 placed in a manner that will record sounds generated within the patient's lungs. Capturing this information requires that the microphone is positioned within the smart valved holding chamber such that it is either adjacent to, on, or within the body of the device to enable the capture of high- fidelity audio 19.

[0146] In one embodiment, the microphone 18 is positioned at the back of the VHC, and is attached to the MDI adapter as shown in Figure 4. The acoustic-input of the microphone in this embodiment is thereby facing the back of the VHC valve. Alternate placements of the microphone 18 include in a port (i.e. a hole) located in the sidewall of the VHC body or in the large baffle at the valve seat as shown in Figure 6. A protective, non-porous membrane 170 will protect the microphone from contamination while still permitting sound to reach the microphone regardless of the microphone’slocation. This membrane 170 functions to both add further protection to the microphone by ensuring no air currents are causing distortion in the microphone, and to protect the microphone from the accumulation of dispensed medication.

[0147] In one embodiment, the membrane 170 is built into the backpiece 106 of the valved holding chamber and prevents the microphone from being in direct fluid communication with the inside of the valved holding chamber. The design of the membrane can be a part of the backpiece component itself created with either a one- or two-shot molding process, or a separate component that is added onto the backpiece.

[0148] In the preferred embodiment, valved holding chamber 3 is configured with two omnidirectional MEMS microphones 18, 239 placed within the valved holding chamber facing the valve. This placement ensures that there is minimal bouncing of soundwaves or distortion. The preferred embodiment has at least one microphone 18 inside the chamber, but additional microphones can be implemented within the chamber to gauge the device’s performance and better detect respiratory events while the patient is using the device.

[0149] The placement of a microphone 18 within a valved holding chamber helps reduce the possibility of reflecting soundwaves amplifying or cancelling out and creating nulls within the recorded audio. Having two or more separate and distinct microphones positions the source of audio capture in two locations, to pick up on the unique signatures of that specific location, and may help the device capture a full range of sound. Also, if two different models of microphones are used, it offers the advantage for each microphone to pick up on slightly different sounds, which may prove beneficial for detecting respiratory events.

[0150] In addition, having more than one microphone offers redundancy to the captured audio. The noise from one microphone may be analyzed and used to predict the noise an additional microphone would pick up when subjected to similar sounds. Variations between the predicted and collected noise in one of the microphones provides a method of indicating if one microphone is not performing as intended. This inter-microphone sound sensing opens up the ability for the device to prompt the user totake action and ensure that the microphones are functioning properly. The intermicrophone sound sensing could also add an additional layer in data processing by providing a level of certainty of the microphone performance, which could ultimately play a role in the determination of wheeze or other respiratory illnesses in a patient.

[0151] In another aspect, the microphones could be used to ensure the user sufficiently cleans their valved holding chamber after medication administration. By dispensing medication through the device, there is a risk of residual medication accumulation on the interior walls of the valved holding chamber, and overtop of the microphone position whether it be in a form of protective barrier or on the microphone itself. However, as this medication begins to build up, it has the potential to alter the performance of the microphones, or directly change the recorded sound through changing the mechanical properties of the protective barrier, which could degrade the accuracy of the inferences made from the collected data. Through the inter-microphone redundancy, the user could be notified through a signal sent to the application, or some other means of notification on the device itself to clean the device and therefore restore microphone performance.

[0152] Another use for the two microphones includes the ability for the device to selfcalibrate. Like the previous description, self-calibration would also rely on the intermicrophone redundancy. It would use the recorded and predicted audio from an integrated speaker to understand the performance of the microphone based upon a predetermined audio track played through the integrated speaker. This predetermined track is created to test the performance of the microphone, and the captured data would be compared against a predicted response. If an integrated speaker is not used, another embodiment involves comparing the recorded and predicted sounds between the multiple microphones as described above.

[0153] In an alternate embodiment, the microphone may also be a unidirectional electret condenser microphone (ECM) whose orientation is optimized to pick up sound coming from the mouthpiece / mask adapter of the VHC. The ECM microphone will be more robust against potential contamination (from drug, condensation, water) as itsdiaphragm is larger than that of a MEMS microphone and there is also a protective felt cover, particularly in the absence of a protective membrane. The unidirectionality of the microphone may also make it less prone to noise contamination. The microphone 18 is in communication with the interior of the holding chamber, including the interior of the cavity and / or user interface.

[0154] The microphone 18 signal will connect to a pre-amplifier before entering a 16- bit sigma-delta analog-to-digital converter (ADC) on the microcontroller. The 16-bit converter strikes a balance between the minimal computational power necessary to store, transfer and analyze the collected information and the data density and the resulting algorithm’s ability to recognize and understand breathing events. An increase in bit depth to 24 bits is feasible, but may not warrant the increased computational load for a minimal, if any, increase in actionable data. Alternatively, the microphone 18 may connect to an audio codec with sigma-delta ADC and gain control before being sent to the microcontroller as a digital signal through an I2C interface. The sound may be sampled at 16kHz but is preferably sampled at a rate of 44100Hz. This ensures the full frequency range of intended breath sounds can be captured by the presently disclosed device. Depending on the specific application, sampling rates can be as high as 192kHz.

[0155] It may be desirable for the users to store the sound recordings onboard the VHC in the event the user’s phone is not nearby to send the data to via Bluetooth. For this reason, the VHC architecture may include onboard flash storage proportional to the product of sampling rate (kHz), sample size (16-bit), sample duration (seconds), and number of samples to be stored. A serial peripheral interface (SPI) interface may be used for communication between the microcontroller and flash module. Additionally, an SD card module can be included for additional memory and data transfer capabilities. An architecture diagram of the microphone and supporting hardware can be seen in Figure 5 (SD card not shown). The architecture may also include other systems such as power management or wireless communications transmission / receiving blocks. In one embodiment, a System on a Chip (SOC) will be used which will contain themicrocontroller and other features to enable wireless communications, such as Bluetooth Low Energy (BLE).

[0156] To aid in this capture of audio data, one or more microphones are added to the device 39 to enable active noise cancellation of external sounds while the device is listening for breathing sounds through the microphone mentioned earlier 18. These additional microphones 39 may also be used for other purposes, like ambient noise monitoring for the detection of respiratory events occurring near the device. The data recorded will be temporarily stored on the device where it may be processed before it can be wirelessly transferred 20 to the application on the user’s phone 1 . The processing may include any steps that reduce the magnitude of data that needs to be transferred. Sound recognition algorithms may also run on the smart valved holding chamber.

[0157] If the user takes rescue medication (as opposed to controller medication) through the smart valved holding chamber, the patient may be prompted to repeat the same procedure a short period of time after the rescue medication was taken. This time, the device may be used without actuating the metered dose inhaler, therefore the user will not take any medication. Breathing through the valved holding chamber 3 will allow the onboard microphone that records sounds within the patient’s lungs to record respiratory related audio data. This recording will be used as a comparison against the original recording to enable physicians or caregiver to contrast differences in the patient’s breath sounds before and after the rescue medication took effect. This data will be processed and stored in the same manner as described before.

[0158] The smart valved holding chamber may have other features as seen in Figure 6 and Figure 7, including:

[0159] 1 . A microphone 239 placed in the large baffle of the valve seat instead of in the backpiece on which a mesh cover, or protective element 21 either configurable or built into the microphone apparatus that minimizes the static or background noise sounds generated in the sound recording when air passes directly over or into the microphone.

[0160] 2. A removable microphone element 22 to enable easier cleaning of the device, or ease in charging the element. The removable element may also facilitate the simple repair of the element or enable a user an option to not include breath sound recording if they feel it is an invasion of their privacy.

[0161] 3. A cover, membrane, or protective element 23 that intrinsically repels suspended medication and particulates in the air and minimizes the chance of buildup on the recording device.

[0162] 4. Integrated algorithms that reduce any static, ambient, or constant noise generated through the rushing of air overtop of, or into the recording device.

[0163] 5. A sound emitting device 24 placed alongside the microphone or recording element to enable periodic tests to assess the calibration of the microphone recording sounds over time. This would be worthwhile to ensure that the microphone does not become sufficiently clogged or dirty through everyday use. This sound emitting device may be a feature that is built into the VHC or a feature that has another function that makes a consistent noise as part of its function.

[0164] 6. An electronic stethoscope 25 incorporated into the smart valved holding chamber instead of a microphone 18 to capture lung breath sounds. This stethoscope feature would be used by placing the device against the chest, back, or neck of the patient record breath sounds 25.

[0165] 7. A GPS system built into the smart valved holding chamber. One potential application would be to record locations of the use of the device to capture more information and help users and physicians understand trends in usage.

[0166] Another element of this system may be the ambient sound monitoring device 4. The device is to be set up in an area where the patient resides for extended periods of time, e.g., most of the day / night, for example a bedroom 26. The device is configured by plugging it into electricity 27 and wirelessly pairing it with, or physically connecting it to either the smart valved holding chamber 3 or the accompanying app on the patient's smartphone 28. Once initialized, the device autonomously and actively listens through one or more microphones 29 for respiratory sounds like cough, wheeze, reparatory rate,or other lung related sounds that can be discerned from a distance. This information is recorded 30, processed and sent to either the smart valved holding chamber 3, or the patient app 28. In the present embodiment this device is separate from the smart valved holding chamber 3 and acts as a docking station to enable data transfer between the two devices 31. The docking embodiment also includes either direct electrical connections or a wireless charging pad that function to charge the Smart Valved Holding Chamber.

[0167] The described embodiment could take in other biometric data generated by the patient to help in the diagnosis, management, or prediction of respiratory diseases. These data points may include but are not limited to the inclusion of step count and the information related to when these steps were taken, other activity data, data related to heartrate over the span of a period of time, other determinants of motion, sleep quality and the duration of time slept, oxygenation of the blood over a period of time, and other biometric data that can be collected by other devices. The collected data will be used in conjunction with the data collected through the disclosed embodiment to help the patient, caretaker, or physician better understand the patients state of health both currently and over time.

[0168] In one embodiment the biometric data is collected on the device where the patient facing application is stored. With permission, the patient facing application will then communicate directly with the application responsible for housing the other biometric data to be analyzed, and the algorithm will incorporate it into the information gathered in the patient facing application.

[0169] The ambient sound monitoring device may have other features as seen in Figures 10 - 12, including:

[0170] 1 . The external sensing device 4 may also have either wireless 33 connectivity features to enable the transfer of the recorded data directly to the cloud 6, or other locations while bypassing the need to send information through the smart valved holding chamber 3 or the patient app 1 .

[0171] 2. In some embodiments this external device 4 may also have LED lights 34 or an integrated display 35 to indicate the charging status of the smart valved holding chamber 3, a reminder for the user to take medication, to display that the process of data transfer is happening, a count for the number of times the device has picked up on a patient’s respiratory sounds, or other notifications or information that can be presents to the user.

[0172] 3. Other embodiments may include ports for connection 36 to other devices can be included like a USB port or other standardly widely recognized ports for data transfer, charging, or other uses.

[0173] 4. Other elements of the embodiment include a locking mechanism 37 so that the smart valve holding chamber 3 is locked into place to prevent young children from tampering with the device while it is actively recording breath, cough, and other respiratory sound data. It would also prevent children from accessing the inhaler pMDI medication, which may be conveniently left inserted into the VHC for quick administration in the vent of an exacerbation. The locking mechanism can be unlocked by the push of a mechanical button 38 or other suitable locking elements. This locking mechanism could also be part of the VHC instead of the dock with ambient sound monitoring.

[0174] 5. Other embodiments involve the described sensing apparatus being directly integrated into the smart valved holding chamber 3 with microphones and wireless communication equipment built within, on, or adjacent to the smart valved holding chamber 3.

[0175] 6. The docking embodiment may also include unrelated functionality to expand to different use cases, or to increase the overall function. These features include the addition of a Bluetooth enabled speaker system 40, an alarm function 41 , wireless charging capabilities 42, and / or integration with smart home technologies / automation.

[0176] 7. A specifically designed nighttime embodiment that includes a feature set for increased child monitoring. This embodiment enables continuous audio and / or videomonitoring through a smartphone. Also, the smart valved holding chamber would have nighttime lighting that would glow to indicate the approximate time to the child to assist in sleep training. The glow would also assist in administering medication in the event of an exacerbation.

[0177] 8. The ambient sound monitor or dock may have a button that would trigger the smart valved holding chamber to make noise and / or flash it lights to notify the user of its location. This is especially useful in situations where a child or user is experiencing an exacerbation and the patient, parent and / or caregiver is unable to locate the device to administer the medication.

[0178] 9. The docking embodiment would facilitate the placement of a non-smart valved holding chamber, where upon placement or removal of the device the dock would alert the patient to update the child’s conditions in the app, provide an approximate timestamp of when medication was taken, provide audiovisual instructions on how to use the device, or it could send out a periodic reminder to parents that the device is not on the dock, ensuring that the device’s location is known at all times in the event of an exacerbation. The dock may work with a manually placed RFID tag or similar locating tag which would allow the dock to activate a sound or light in the event the VHC is misplaced. This tag may also be located wirelessly, possibly through an app that works in coordination with the dock.

[0179] Data synchronization may be triggered manually or automatically when both the application and the smart valved holding chamber or ambient sound monitoring device is active and in close range.

[0180] On the app 1 , there are analysis tools that depict the patient’s medication adherence, inhalation technique, the number of times the ambient sound monitor picked up on coughs, wheeze, etc., and sound recordings from when the patient breathed through the smart valved holding chamber. The app also features a digital diary where a user can log symptoms related to their disease in order to identify patterns in their or their child’s exacerbations. This information is displayed alongside external information brought in through the app including weather, pollen, air quality, and other location-based triggers pulled from the GPS of the smartphone or from the location of the devices that will help the user to better identify ways to avoid exacerbations. Sensors that measure indoor air quality could be integrated into the bedside monitor and / or the VHC. These sensors could monitor conditions such as pollen, atmospheric pressure, particulates, triggering polluting gasses like Nitrogen Dioxide, Ozone, Sulfur Dioxide, Carbon Monoxide or others. In addition, the app features an education section that teaches users various topics that will help them to better manage their condition. The app can also make use of the phone’s camera function, and have a location to store photos, videos, or audio recordings taken by the parent or user.

[0181] The app also has a feature that enables the user to select information relevant to be shared with doctors. Information selected by users will be is formatted into a PDF that can be emailed or shared with physicians during visits. These PDFs can include embedded audio data, photos, or videos, that were recorded by the devices used in the system. Sharing this information with physicians enables them to no longer rely solely on the opinions of parents and make decisions based upon collected objective data. Additionally, the embedded / shared sound audio allows physicians to listen to a patient during an exacerbation (if the rescue medication was taken during an exacerbation), which would also help them in their decision making. Previously, the only way physicians could witness the child in an exacerbated state is if it happened during the physician visit, or if the parent managed to catch a video / sound recording to share it with the doctor. This audio data collected outside the smart valved holding chamber has varying levels of uncertainty as the information would be recorded with microphones that are not validated.

[0182] The Patient or Caretaker facing application compiles the data collected through the use of the disclosed embodiment, the additional biometric data generated by the patient through the use of other devices, and the information collected through the application itself to help users better understand their respiratory condition. The information the application collects on its own includes location based environmental alerts such as pollen, particulates, humidity, temperature, pollution, etc., and informationprovided by the user such as qualitative accounts of their symptoms, or other indications of their current condition.

[0183] Compiling this information through an artificial intelligence, the application will then be well suited to help users better understand, and therefore better manage their respiratory condition. This includes helping them see trends in their overall health, predicting upcoming exacerbations based upon trends from the incoming data, or providing adaptive education to users based upon their current management technique.

[0184] The application will also serve as a digital warning tool, that will educate and encourage patients to seek appropriate care earlier in an exacerbation pathway. This is made possible as the application will be continuously processing any new information provided to it, which would result in alterations to any of the current assessments or predictions made to the user. With a regular cadence of data input, the algorithm would be able to have more touchpoints with the user than a healthcare provider has capacity to do. In addition, the application would have a multitude of personalized data to make decisions that healthcare providers regularly do not review. Through these higher frequency continuous touchpoints, the application will be able to provide warnings and encourage the user to take action based upon the user’s current or predicted future state. The provided warnings will enable and empower patients to take charge of their own health and may result in improved outcomes of the disease. This information processing would be made possible through the artificial intelligence algorithm which is detailed in a separate section of this document.

[0185] The digital warning system is also an intelligent system that incorporates thresholds to limit the information provided to patients to prevent sending them unnecessarily to their healthcare provider. The system will aim to only recommend patients to see their healthcare provider when meaningful interactions can be had. The system’s aim is to help healthcare providers only see those patients who have a pressing reason to be seen and not increase the provider’s workload.

[0186] The application also features an adaptive educational feedback algorithm that trains users and patients in the areas of disease management that they are lacking in.This algorithm takes in a multitude of data related to the technique of the medication delivery, as well as the overall management style of the user. With trends over time, the application can tailor feedback specific to the area of management that needs improvement, and provide just-in-time learning to the user in aiming to prevent them from progressing towards a disease exacerbation. This feedback mechanism may also be modified by the patients healthcare provider to incorporate learnings the provider feels is critical for the patient to learn in an effort to improve the patient’s disease trajectory.

[0187] When connected to the internet, all the information stored on the application will also be uploaded to the cloud 5, 6, where the information is encrypted 43 and securely stored for access by those who have permission, like the physician. This enables the physician to access the information of the patient without needing to wait for the patient or caregiver to create and send a PDF report.

[0188] The majority of data interpretation and processing will occur on the patient / caregiver application, or the cloud. Through an artificial intelligence or other preprogrammed algorithm, the recorded sounds will be analyzed for important markers that can be conveyed to caregivers, patients, or physicians. This data includes at least one of the following measures: presence of wheeze, breathing rate, identifying characteristics and trends of each breath / breathing pattern, classification of breathing patterns, etc. If processing occurs on the cloud, the information can be accessed by the patient or physician’s information portal where it will be displayed for interpretation by the user. Otherwise, the information processed on the patient application will be sent to the cloud, where it can be accessed by the physician for review.

[0189] The physician accesses this information through a physician portal / application 7, which like the patient / guardian application, combines all the collected information from the described devices within the present disclosure. A representative image of the physician portal / application can be seen in Figure 132. This application stores all the relevant information that enables the patient or the caregiver to review the

Claims

1. Claims:1 . An asthma diagnosis and management system comprising: a valved holding chamber defining an interior cavity, a backpiece having an opening configured to receive a pressurized metered dose inhaler and a user interface; and a microphone coupled to the valved holding chamber and in communication with an interior of the valved holding chamber, wherein the microphone is configured to capture a sound of a user’s lungs.

2. The asthma diagnosis and management system of claim 1 wherein the microphone is attached to the backpiece.

3. The asthma diagnosis and management system of claim 2 wherein the valved holding chamber comprises a valve assembly longitudinally spaced from the backpiece, wherein the microphone faces the valve assembly.

4. The asthma diagnosis and management system of claim 3 wherein the microphone comprises an ECM microphone.

5. The asthma diagnosis and management system of claim 1 wherein the valved holding chamber comprises a valve assembly longitudinally spaced from the backpiece, wherein the microphone is coupled to the valve assembly.

6. The asthma diagnosis and management system of claim 5 wherein the valve assembly comprises a baffle, wherein the microphone is coupled to the baffle.

7. The asthma diagnosis and management system of claim 1 wherein the microphone is releasably coupled to the valved holding chamber.

8. The asthma diagnosis and management system of claim 1 further comprising a protective element covering the microphone.

9. The asthma diagnosis and management system of claim 1 further comprising a sound emitting device coupled to the valved holding chamber and disposed adjacent the microphone, wherein the sound emitting device is configured to emit a sound for calibration of the microphone.

10. The asthma diagnosis and management system of claim 1 further comprising at least one secondary microphone coupled to the valved holding chamber.11 . The asthma diagnosis and management system of claim 10 wherein the secondary microphone is in communication with an exterior ambient environment of the valved holding chamber.

12. The asthma diagnosis and management system of claim 1 further comprising an ambient lung sound breath lung recording device comprising a second microphone and configured to autonomously and actively record respiratory sounds, wherein the ambient lung sound breath lung recording device may be paired with the valved holding chamber.

13. The asthma diagnosis and management system of claim 1 wherein the interior cavity comprises a first interior cavity defining an inhalation flow path, and wherein the valved holding chamber comprises a channel defining a second interior cavity separate from the first interior cavity, wherein the microphone is in communication with the second interior cavity.

14. The asthma diagnosis and management system of claim 13 further comprising a membrane disposed across the opening of the channel.

15. The asthma diagnosis and management system of claim 13 further comprising a one-way valve disposed across the opening of the channel.

16. The asthma diagnosis and management system of claim 6 wherein the baffle has a convex shape facing toward the user.

17. The asthma diagnosis and management system of claim 6 wherein the baffle is off-center relative to the longitudinal axis of the interior cavity.

18. An asthma diagnosis and management system comprising: a valved holding chamber defining an interior cavity, a backpiece having an opening configured to receive a pressurized metered dose inhaler and a user interface; and an electronic stethoscope coupled to the smart valved holding chamber and configured to capture a sound of a user’s lungs.

19. A method of diagnosing and managing a user’s asthma comprising: actuating a pressurized metered dose inhaler coupled to a backpiece of a valved holding chamber; inhaling through a user interface component of the valved holding chamber; capturing a sound of the user’s lungs while inhaling with a microphone in communication with an interior of the valved holding chamber; waiting a predetermined period of time; and breathing through the valved holding chamber without actuating the pressurized dose inhaler after the predetermined period of time and capturing a second sound of the user’s lungs while breathing through the valved holding chamber.

20. The method of claim 19 wherein the interior cavity comprises a first interior cavity defining an inhalation flow path, and wherein the valved holding chamber comprises a channel defining a second interior cavity separate from the first interior cavity, wherein the microphone is in communication with the second interior cavity.

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