Respiratory diagnostic tools and methods

Abstract

In one embodiment, a device for performing a plurality of breath diagnostic tests is provided, comprising: a housing, a sensor assembly, and a control circuit configured to receive a signal from the sensor assembly; wherein the device has a first configuration and a second configuration, wherein in the first configuration, the device is configured to perform a first breath diagnostic test, and in the second configuration, the device is configured to perform a second breath diagnostic test, wherein in the first configuration, an airflow channel is defined by the housing of the device, the sensor assembly is configured to measure at least a first characteristic of air in the airflow channel during the first breath diagnostic test, and wherein in the second configuration, the airflow channel is modified relative to the first configuration, and the sensor assembly is used to measure at least a second characteristic of air in the airflow channel during the second breath diagnostic test. In another embodiment, a stand-alone device is provided, the stand-alone device being configured to perform a pulse oscillometric test.

Description

Technical Field

[0001] The present disclosure relates to devices for performing tests whose results can be used to diagnose or monitor a respiratory condition, and more particularly to devices capable of performing more than one diagnostic test. The present disclosure also relates to devices capable of performing an oscillometric test. Background Art

[0002] Many people suffer from conditions that affect their respiratory system. These conditions can make it difficult to breathe and can negatively affect the person with them day in and day out. They can have many different forms, or subtypes. Asthma is an example of a term used to describe a condition that has many forms, or subtypes. Evidence for asthma subtypes is shown by the fact that different people have different triggers for their symptoms and respond differently to specific treatments. Another example of a respiratory condition is Chronic Obstructive Pulmonary Disease (COPD), an umbrella term used to describe a disease that has many subtypes.

[0003] Diagnosing which condition a subject has, and which subtype, is crucial in order to most effectively treat the condition. While a cure is not always possible, the symptoms of most respiratory conditions can be alleviated, improving the subject's quality of life.

[0004] Over time, many diagnostic tests have been developed. The results of these tests are used to diagnose a condition. In order to correctly and accurately diagnose a condition, the results of more than one test are often needed. This is especially true when trying to diagnose a specific subtype of a condition. Combining and analyzing the results of more than one test is a technical endeavor that often requires a trained medical specialist to make a final diagnosis. Often a diagnosis cannot be made after just one testing phase, so symptoms must be monitored over a period of time that can be as long as several years. Because different subtypes of a condition may require different treatments, it is important that the correct subtype is diagnosed.

[0005] Historically, each diagnostic test has required the use of a different device. Each device can be expensive, especially because some tests require mechanical sample conditioning to ensure accurate results. For example, a common test is the fractional exhaled nitric oxide concentration (FeNO) test, in which the level of nitric oxide in the exhaled air is measured. This can be used as an indicator of lung inflammation and eosinophil activity. Nitric oxide levels can be measured using electrochemical sensors. However, in order for the measurement to be reliable and repeatable, the effects of environmental variables such as humidity, temperature, and pressure need to be eliminated. This is technically challenging and slows down the testing process, and the repeatability of nitric oxide measurements may still be poor. Repeatability is important when monitoring subjects over a series of testing sessions. One factor that affects the repeatability of current FeNO tests is that the required breathing pattern is slow and can be difficult for some people.

[0006] Because individual devices can be costly and expert knowledge may be required to perform or interpret combined results from more than one device, current devices are generally only available in specialty practices or pulmonary function laboratories. As a result, only a small percentage of people suspected of having asthma or other respiratory conditions are tested using such devices. This also makes it difficult to continuously monitor symptoms over the course of a battery of tests. Without objective testing, subjects may be given treatments that are incorrect for their condition. Incorrectly assigning treatments wastes resources, may not prevent a subject's symptoms or attacks, and may result in unnecessary side effects from treatment.

[0007] There is a need for a system for diagnosing respiratory conditions that is inexpensive, accurate, readily available, easy to use, and provides results that are easy to interpret.

[0008] In addition, in order to diagnose and monitor the condition of the subject, it may be necessary to characterize the subject's airway. Many respiratory diagnostic tests that can be used to characterize the airway require specific breathing maneuvers, which need to be accurately performed for the reliability of the results. Some people struggle to perform such actions, or find it impossible. Spirometry test (spirometry test) is an example of a test for characterizing the subject's airway, but it is necessary to perform specific actions for high-flow breathing with force. It may be very difficult to communicate with young children how to perform this test. They may lack the skills or strength required to reliably perform this test. Adults may also find it difficult to perform specific breathing maneuvers, particularly those with severe breathing problems. There are obvious benefits in having a respiratory diagnostic test that can characterize the subject's airway that requires minimal skills and strength to perform.

[0009] One such respiratory diagnostic test that has been developed is impulse oscillometry. In an impulse oscillometry test, an acoustic pulse is generated that propagates into the airway of a subject. Parameters such as air pressure and flow can be measured following the generation of the pulse to provide an indication of the subject's breathing mechanism. This can be used to characterize the airway. The subject only needs to breathe at a relatively constant inhalation or exhalation rate. It is even possible for the subject to simply perform normal tidal breathing with the device. This is relatively easy for the subject.

[0010] Current pulse oscillometric testing equipment uses a loudspeaker to generate acoustic pulses in the subject's airway. This has several disadvantages. Typically, the loudspeaker is located in a branch channel of the main channel, which extends between the mouthpiece and the air inlet. The branch channel has a closed end, i.e. it is a blind channel. Ideally, the acoustic pulse is directed to the mouthpiece. However, most of the energy from the loudspeaker is lost from the air inlet. Therefore, a large loudspeaker with high power requirements is needed to obtain a sufficiently large acoustic pulse at the mouthpiece. This results in a bulky and non-portable device.

[0011] Because pulse oscillometric devices are large and bulky, they are usually only found in hospitals and specialized lung laboratories. This means that access to such devices is limited for the general population, with only a small percentage of people suspected of having asthma or other respiratory conditions being tested with such devices. It also makes it difficult to continuously monitor symptoms over the course of a battery of tests. Without an objective test, subjects may be given treatments that are incorrect for their condition. Incorrectly dispensing treatments wastes resources, may not prevent a subject’s symptoms or attacks, and may cause unwanted side effects.

[0012] There is a need for a device for performing an oscillometric diagnostic test that is compact and potentially portable and can be used to characterize the airways of a subject. Summary of the invention

[0013] The present invention provides an apparatus and a kit for performing a plurality of breath diagnostic tests, and a method for performing a plurality of breath diagnostic tests using an apparatus according to the appended independent claims, to which reference will now be made. Preferred or advantageous features of the invention are defined in the dependent claims.

[0014] In a first aspect of the invention, an apparatus for performing a plurality of breath diagnostic tests is provided, comprising: a housing, a sensor assembly, and a control circuit configured to receive a signal from the sensor assembly. The apparatus has a first configuration, in which the apparatus is configured to perform a first breath diagnostic test, and a second configuration, in which the apparatus is configured to perform a second breath diagnostic test.

[0015] In a first configuration, an airflow channel is defined by a housing of the device, and the sensor assembly is configured to measure at least a first characteristic of air in the airflow channel during a first respiratory diagnostic test.

[0016] In a second configuration, the air flow channel is modified relative to the first configuration, and the sensor assembly is used to measure at least a second characteristic of air in the air flow channel during a second respiratory diagnostic test.

[0017] The device can be configured to perform more than one respiratory diagnostic test, which advantageously means that a single device can provide results that allow a more comprehensive diagnosis or more comprehensive monitoring of respiratory conditions. Diagnostic devices are usually only able to perform one type of test. However, no single test can identify some respiratory diseases including asthma and COPD. Different people with respiratory diseases involve different triggers, symptoms, treatment responses and biological pathways in their conditions. Several useful diagnostic tests have been found or are being developed. However, for medical practice or subjects, it is impractical and expensive to purchase, maintain and use several different devices. The first configuration and the second configuration of the device correspond to the first operating mode and the second operating mode of the device. By providing a device that can be configured to perform multiple respiratory diagnostic tests, only a single device is required to provide results that allow a comprehensive diagnosis or comprehensive monitoring of respiratory conditions. Being able to use only one device simplifies the diagnosis or monitoring process and reduces the amount of hardware required, thereby reducing costs. The hardware may include batteries, control circuits and displays, as well as other hardware such as device housings.

[0018] The first breathing test may be different from the second breathing test. In particular, the first breathing test may be of a different type than the second breathing test. One of the first breathing diagnostic test and the second breathing diagnostic test may be a pulmonary obstruction or flow test. One of the first breathing diagnostic test and the second breathing diagnostic test may be a biomarker test. For example, one of the first breathing diagnostic test and the second breathing diagnostic test may be a flow test or a pulmonary obstruction test, such as a spirometry test or an oscillometric test, etc. The other of the first breathing diagnostic test and the second breathing diagnostic test may be a test for a biomarker (e.g., nitric oxide) indicative of inflammation or disease.

[0019] The airflow channel advantageously has a distal end and a proximal end. The airflow channel may have an opening at the distal end. When the flow direction of the air in the airflow channel is toward the proximal end, the opening may be an air inlet. When the flow direction of the air in the airflow channel is away from the proximal end, the opening may be an air outlet. However, in this article, the opening at the distal end of the airflow channel is generally referred to as an inlet. A mouthpiece may be provided at the proximal end so that a subject using the device can breathe through the airflow channel. The sensor assembly is then configured to measure the characteristics of the inhaled or exhaled air from the subject in the airflow channel. The airflow channel may advantageously be suitable for different tests so that the airflow passes through different sensors and / or through different components of the device, and / or changes the characteristics of the airflow. This may include increasing or decreasing the airflow resistance experienced by the air in the airflow channel, changing the profile of the airflow channel, changing the temperature in the airflow channel, or providing additional inlets or outlets in the airflow channel. The airflow channel may include a plurality of subchannels. A plurality of subchannels may be combined with each other at the proximal end. Different sensors may be provided in different subchannels. Some subchannels may simply be used as bypasses. Preferably, at least a portion of the air flow channel is the same in the first configuration as in the second configuration.

[0020] The device may include a primary component and a first secondary component, the primary component defining at least a portion of an airflow channel, wherein the first secondary component has a first position relative to the primary component in a first configuration and a second position relative to the primary component in a second configuration. The device may include a plurality of secondary components, each of the plurality of secondary components being designed for a specific breath test.

[0021] The first secondary component may include a sensor. The sensor advantageously measures a parameter of the air in the airflow channel. This is in addition to any parameters measured by the sensor assembly and may advantageously be specific to a particular respiratory diagnostic test. The sensor assembly may be located at least partially in the primary component.

[0022] In a first configuration, the primary component and the first secondary component may be engaged with each other to define an airflow channel. In a second configuration, the primary component and the first secondary component may be disengaged from each other or engaged with each other in a different manner. Advantageously, the airflow channel defined by the engagement of the primary component and the first secondary component is optimized for performing the first breathing test. In the second configuration, the primary component may be engaged with the second secondary component. At least a portion of the airflow channel may be defined by the secondary component.

[0023] When the primary and secondary components are not engaged, they may be separate or independent components. It may be up to the subject to engage them to one another. One component may have a male component and the other component may have a corresponding female component into which the male component may be inserted to facilitate engagement. Pushing the male portion into the female portion will connect the two components and hold the two components together. It may be advantageous to have a standard connection system between the primary component and all secondary components. The standard connection system advantageously means that additional secondary components may be added to the system after purchase or initial release. Advantageously, this means that a subject may purchase or obtain new secondary components and use them with their existing system. These new secondary components may configure the device to have additional functionality. These additional functionality may include performing additional respiratory diagnostic tests.

[0024] Alternatively, the primary component and the secondary component can advantageously form a single device so that the primary component and the secondary component are physically inseparable from each other. The primary component and the secondary component can include a selection device configured to define an airflow channel by selecting a portion of the primary component and the secondary component. The airflow channel through the device must be suitable for the test to be performed by the device. The selection device may include one or more valves, which may be used to select the secondary components included in the airflow channel. Changing the path of the airflow channel through the device will change the configuration of the device. The valve arrangement for changing the configuration of the device can be advantageous because it is not necessary to physically connect or remove components in order to configure the device. The valve can be controlled by a control circuit that automatically configures the device. This means that the device can be transported as a unit that can be configured to perform any one of a series of respiratory diagnostic tests. The use of one or more valves can advantageously reduce contamination from the atmosphere before performing the test. The valve can also be configured to partially open at least one of the secondary components. The airflow channel can be configured by intermittently opening and closing one or more valves.

[0025] It may be advantageous for the device to include both configuration options described.In addition to the valve connection, there may be several separate components that can be physically connected or disconnected.

[0026] In at least one of the first and second configurations, the primary component may have a power or data connection with the secondary component. Advantageously, this allows measurements taken using sensors located in the primary or secondary component to be transmitted to the other component and communicated with the control circuitry. It also allows any element in any of these components that requires power to be powered from any other component.

[0027] The control circuit may include a microcontroller. The microcontroller may be configured to process data received from the sensor. The result of the data processing may be a test score that can be used to help monitor or diagnose respiratory diseases. Alternatively, the control circuit may communicate with a portable computer (e.g., a laptop computer or a smart phone, etc.) that includes a microcontroller. In these cases, the microcontroller of the portable device performs the data processing. The communication between the control circuit and the portable device may be a wireless connection. The wireless connection may be a Bluetooth connection.

[0028] The sensor assembly may include a flow sensor. The flow sensor may be located in the main component. The device may be configured to perform a spirometry test in a first configuration and to measure a concentration of a biomarker indicative of lung inflammation in a second configuration. The flow sensor may be used to perform a spirometry test. The device may be configured to measure a peak expiratory flow or a forced expiratory flow using the flow sensor. Spirometry tests measure lung function, in particular the amount and / or rate of air that can be inhaled or exhaled. These tests may be advantageously used to diagnose conditions such as asthma, etc. Advantageously, the flow sensor may be used to perform a spirometry test.

[0029] Spirometry tests can be performed using airflows up to about 850 liters per minute, with measurements having an accuracy of ±5 liters per minute. When the device is configured to perform different respiratory diagnostic tests, the required flow may be much lower. Some tests may require airflows of no more than 5 liters per minute, with measurements having an accuracy of ±<0.5 liters per minute. Some tests may require airflows of no more than 3 liters per minute ±<0.3 liters per minute. The accuracy of the measurements may be + / -<0.15 liters per minute. It would be advantageous to be able to use the same flow sensor in both configurations. In that case, the flow sensor would need to have an appropriate range for measuring airflow and an appropriate accuracy over each range.

[0030] It is technically challenging to produce a flow sensor with an appropriate range and sensitivity. At a lower flow rate of about 5 liters per minute, a flow sensor with a range of 850 liters per minute will generally not have suitable sensitivity. It may be advantageous to use a flow sensor with a smaller range but a higher sensitivity at low flows. It may be advantageous to modify or adjust the effective range of a flow sensor by modifying or adjusting the input to the flow sensor (i.e., the flow rate), or by modifying or adjusting the output of the flow sensor, or by combining the output of the flow sensor with the output of one or more other sensors.

[0031] One way to solve this problem is to allow only a portion of the inhaled or exhaled air to flow through the mass air flow sensor.

[0032] The airflow channel may include at least one subchannel so that in at least one of the first configuration and the second configuration, the airflow through the device bypasses the sensor assembly. For example, the airflow channel may be divided into a plurality of subchannels by one of a plurality of secondary components so that at least one of the subchannels bypasses the sensor assembly. At least one of the subchannels may take the form of an inlet in the housing of the device between the flow sensor and the mouthpiece, which provides fluid communication between the outside air and the remaining airflow channels. Advantageously, this means that the flow sensor only needs to have a range that can measure the proportion of air passing through it. The flow rate of the total airflow can be inferred from the measurement of a certain proportion of the airflow. At least 60% of the volume of the airflow through the airflow channel, and more preferably at least 70% of the volume, can bypass the sensor assembly. Advantageously, this means that less than 40%, more preferably less than 30% of the air flowing through the airflow channel passes through the flow sensor, and the required range of the flow sensor is reduced to a corresponding portion of the total flow provided by the subject. The maximum flow through the subchannel passing the flow sensor is advantageously matched to the range of the flow sensor.

[0033] Another way to solve this problem is to use the measurement from another sensor to electronically adjust the reading from the flow sensor. For example, the sensor assembly may include a pressure sensor. The control circuit may be configured to estimate the flow rate using the signals received from both the flow sensor and the pressure sensor. The flow sensor may have a range of ±200 liters per minute. The flow estimated using the flow sensor and the pressure sensor has a range of ±1000 liters per minute. This value is high enough to measure the flow when the device is in the spirometry configuration, in which the flow estimate for lower flows is primarily determined by the flow sensor, which has a higher sensitivity at lower flows, while the measurement for higher flows is primarily determined by the pressure sensor, which has a larger range than the flow sensor.

[0034] Secondary components may include biomarker sensing components, where the biomarkers are indicative of lung inflammation or disease. In one configuration, the airflow channel may have a resistance of at least 5 cm H2O. Advantageously, this ensures that the nasal soft palate remains closed while the subject exhales through the device. The concentration of biomarkers in nasal air may be high. If the nasal soft palate does not remain closed while the subject exhales, the exhaled air is contaminated with nasal air and will give a falsely high measurement of biomarkers for lung inflammation.

[0035] The device may include an electrochemical sensor configured to detect the presence of a biomarker indicative of lung inflammation. The electrochemical sensor may be part of the secondary component. The control circuit may be configured to receive a signal including an output value from the electrochemical sensor.

[0036] The sensor assembly may include a combination of two or more of a pressure sensor, a flow sensor, a temperature sensor, and a humidity sensor. The electrochemical sensor, the pressure sensor, the flow sensor, the temperature sensor, and the humidity sensor may be located adjacent to each other in the airflow channel. They are advantageously located at substantially the same position in the airflow, as this reduces the pressure and temperature differences between the sensors.

[0037] The control circuit can be configured to use a signal from at least one of a pressure sensor, a flow sensor, a temperature sensor, and a humidity sensor to adjust the output value received from the electrochemical sensor. This adjustment is advantageous because the electrochemical sensor is typically very sensitive to environmental conditions, changes in environmental conditions, and particularly changes in moisture in the air. It is usually exhaled breath that is measured by the device. The exhaled air has a higher moisture content and temperature relative to the atmosphere, and the exhaled airflow may have a variable pressure or flow rate. The lack of controlled and constant sample conditions means that the readings read only from the electrochemical sensor may not be accurate enough. The factors of environmental conditions must be taken into account. The control circuit can use the signals received from the pressure sensor, the flow sensor, the temperature sensor, and / or the humidity sensor to provide an adjustment factor and / or an offset for the measured value from the electrochemical sensor to account for the rate of change of environmental conditions or environmental variables.

[0038] Secondary components may include a purification filter configured to reduce the amount of biomarkers in the air. The biomarkers may indicate lung inflammation. Inhaled air may pass through the purification filter. This means that the amount of biomarkers measured in the exhaled breath may be considered to be generated by the subject, rather than simply being present in the environment, inhaled, and then exhaled.

[0039] The secondary component may include a valve configured to change the airflow path through the airflow channel depending on the direction of the airflow through the airflow channel. For example, the valve may ensure that the airflow channel passes through the purification filter only in one direction.

[0040] The secondary component may include a gas dryer. The gas dryer may be configured to reduce the humidity of the air passing through the gas dryer. As described above, the electrochemical sensor is very sensitive to changes in moisture content. In addition to or in lieu of adjusting the measurements as described above, it may be advantageous to reduce the humidity of the air sampled by the device. This may improve the accuracy of the readings from the electrochemical sensor.

[0041] Reducing the humidity of the air passing through the device can prevent condensation on the sensor, which is advantageous, particularly for nitric oxide sensors. The gas dryer can be an absorbent material, a water trap, a Nafion tube, or the sensor surface can also be heated. The absorbent material advantageously does not require electricity and does not substantially increase the internal volume of the flow channel. The gas dryer can be located in the mouthpiece.

[0042] A biomarker indicative of lung inflammation may be nitric oxide concentration. Exhaled nitric oxide concentration indicates the activity of eosinophils, which are associated with inflammation for about two-thirds of people with asthma and one-third of people with COPD. Therefore, nitric oxide concentration can be used to determine the subtype of the disease a person may have. High nitric oxide concentrations may indicate that a subject is likely to respond to a specific drug treatment. If the treatment is successful, the subject's exhaled nitric oxide concentration should decrease, so the test can be used to find effective drug dosages and confirm that the subject is taking their treatment correctly.

[0043] One of the first respiratory diagnostic test and the second respiratory diagnostic test can be a pulse oscillometric test. An oscillometric test is a diagnostic test whose results indicate the mechanical properties of the airway of the subject performing the test. These properties can be used to help diagnose respiratory diseases such as COPD. Oscillation tests are advantageous because they do not require the subject to perform specific breathing maneuvers such as labored breathing. The subject only needs to breathe at a relatively constant inhalation or exhalation rate. It is even possible for the subject to simply perform normal tidal breathing through the device. This is advantageous because it means that the test is easy to perform and comfortable to perform. This is especially important for children and subjects with respiratory diseases that can make breathing in another way (such as labored breathing with a high flow rate) difficult and uncomfortable.

[0044] While using the device to perform an oscillometric test, the subject may inhale and / or exhale through the device, causing air to pass through the air channel of the device and flow into / out of the subject's lungs. The device may include a mouthpiece. The air flow channel may be defined as passing through the device from the mouthpiece to the air inlet. The air inlet may be open to the atmosphere. When the device is configured to perform an oscillometric test, it may include an acoustic pulse generator. The acoustic pulse generator may be configured to generate an acoustic pulse in the air in the air flow channel by pushing the air in the air flow channel in the direction of the mouthpiece, thereby generating an acoustic pulse in the air in the air flow channel. The pushing of the air may generate pressure fluctuations. The acoustic pulse generator may be controlled by a control circuit.

[0045] As used herein, an acoustic pulse is a pressure wave comprising multiple sinusoidal frequencies. The pressure wave may take the form of a square wave or a form approximating a square wave.

[0046] The acoustic pulse travels at the speed of sound. Before returning to the airflow channel of the device, the acoustic pulse may pass through the airflow channel and the mouthpiece and then enter the airway of the subject. After the acoustic pulse is generated, the parameters of the air in the airflow channel can be sensed by the sensor assembly. One measured parameter can be air pressure. Another measured parameter can be air flow. The acoustic pulse can interact with the airway of the subject. This interaction causes changes in the pressure and flow of the air passing through the sensor. Therefore, these parameters can be used to determine the response of the subject's airway to the acoustic pulse. The response can be used to characterize the airway of the subject.

[0047] When one of the first respiratory diagnostic test and the second respiratory diagnostic test is a pulse oscillometric test, the device may include an occluder and a device for moving the occluder between a first position and a second position. The occluder in the second position may occlude the airflow channel to a greater extent than in the first position, and the control circuit may be configured to control the device to move the occluder or receive a signal from the sensor assembly, or both control the device to move the occluder and receive a signal from the sensor assembly.

[0048] Advantageously, the occluder in the second position blocks the airflow channel to a greater extent than in the first position, because this reduces the energy loss of the acoustic pulse in the direction away from the mouthpiece. Energy can escape through any gap between the occluder and the airflow channel, and therefore, any reduction in these gaps (achieved by increasing the blocking) ensures that less energy escapes. Therefore, if the occluder is in the second position during the generation of the acoustic pulse, the energy loss of the acoustic pulse generated in the direction away from the mouthpiece is advantageously reduced. This configuration advantageously allows the acoustic pulse of the air in the airflow channel of the device to be generated in a compact and effective manner.

[0049] The acoustic pulse generator may be a loudspeaker. The loudspeaker may include a cone or diaphragm that pushes air in the air flow channel to generate the acoustic pulses. The loudspeaker may be configured to push air in the air flow channel toward the mouthpiece in a direction parallel to the air flow channel. The loudspeaker may be connected to a signal generator. The signal generator may provide an electrical signal that the loudspeaker converts into an acoustic wave. The signal generator may form part of the control circuit.

[0050] The acoustic pulse generator can be configured to release compressed gas in the air flow channel that pushes the air in the air flow channel in the direction along the mouthpiece. The compressed gas can be stored in a gas tank. The gas tank may include a release valve. The release valve can be configured so that when it is opened, the compressed gas is released from the gas tank into the air flow channel. The compressed gas can be released in a direction parallel to the air flow channel and in the direction of the mouthpiece. The release valve can be connected to a control circuit and can be controlled so that the release of the compressed gas is coordinated with the movement of the occluder from the first position to the second position.

[0051] The control circuit can be configured to control the device that moves the occluder so that the movement of the occluder from the first position to the second position is coordinated with the generation of the acoustic pulse by the acoustic pulse generator. The control circuit can be configured to coordinate the movement of the occluder from the first position to the second position so that it is performed simultaneously with the generation of the acoustic pulse. The occluder can be configured to move from the first position to the second position so that the occluder has a deviation of 5ms or less in the second position relative to the generation of the acoustic pulse. The deviation can cause the occluder to reach the second position after the acoustic pulse is generated, but preferably, the occluder is in the second position before the acoustic pulse is generated. The deviation can advantageously allow the movement of the occluder to be precisely controlled relative to the generation of the acoustic pulse. For a specific configuration of the device, the deviation can be a predetermined value that ensures that the maximum or particularly desired amount of acoustic pulse energy is directed to the mouthpiece rather than away from the mouthpiece.

[0052] Advantageously, the acoustic pulse generator and the occluder may be the same component. In other words, the device may not include a separate acoustic pulse generator. When the occluder is an acoustic pulse generator, an acoustic pulse may be generated by movement of the occluder toward the proximal end of the airflow channel. As the occluder moves from the first position to the second position, the occluder pushes the air in the airflow channel. The occluder may be configured so that movement of the occluder from the first position to the second position pushes the air in the airflow channel from the occluder in the direction of the mouthpiece to generate an acoustic pulse in the air in the airflow channel.

[0053] When the occluder is an acoustic pulse generator, the movement of the occluder from the first position to the second position increases the amount of blocking of the airflow channel and ensures that the amount of energy that can escape the occluder is reduced. Ideally, the acoustic pulse will be generated by the instantaneous movement of the occluder from the first position to the second position. In practice, instantaneous motion is impossible, resulting in asymmetric bell-shaped pulses. The control circuit can advantageously control the device that moves the occluder so that the occluder moves between the first position and the second position at a speed and through a distance, thereby generating an acoustic pulse with desired characteristics. Alternatively, the device that moves the occluder can be driven by the subject's breathing.

[0054] When the occluder is an acoustic pulse generator, a portion of the airflow channel may include a first tapered portion. The occluder in the first position may be located in or near the wider portion of the first tapered portion compared to the second position. In this configuration, the energy of the acoustic pulse generated by moving the occluder from the first position to the second position can be more effectively directed to the mouthpiece through the first tapered portion. The airflow channel may include a second tapered portion adjacent to the first tapered portion, wherein the second tapered portion may be configured to surround the occluder when the occluder is in the first position. The second tapered portion may provide sufficient clearance around the occluder so that the resistance to flow through the airflow channel when the occluder is in the first position is very low without having a long stroke between the first position and the second position.

[0055] The control circuit may be configured to control the acoustic pulse generator so that the acoustic pulse provides a maximum pressure increase of at least 50 Pa at the sensor assembly and a flow increase of at least 0.15 liters per minute through the air flow channel in the direction of the mouthpiece. The increase in pressure is the amount by which the pressure increases above the pressure of the air in the air flow channel when the subject is breathing normally.

[0056] The control circuit can be configured to control the acoustic pulse generator so that the generated acoustic pulse includes pressure fluctuations of multiple frequencies ranging from 5 Hz to 20 Hz. The acoustic pulse can be in the form of a square wave, or a form approximate to a square wave, generated by the movement of the occluder from the first position to the second position.

[0057] Acoustic pulses of different frequencies may be attenuated to varying degrees by the subject's airway. This attenuation may increase with increasing frequency. As a result, higher frequency pressure and flow measurements are primarily determined by the response of the upper airway. Lower frequency pressure and flow measurements may include responses from the periphery of the lungs. Therefore, it is advantageous to probe the subject's airway using pressure fluctuations of multiple frequencies rather than pressure fluctuations of a single frequency, thereby providing a more complete understanding of the mechanical properties of the subject's airway. It allows the identification of characteristic respiratory responses at different frequencies.

[0058] When an acoustic pulse is generated by the movement of the occluder, the highest frequency contained in the pulse may depend on the duration of the pulse. For example, by moving the occluder from the first position to the second position in 50ms or less, a higher frequency of 20Hz contained in the pulse can be obtained. The pulse will contain lower frequencies, such as 5Hz, etc. The highest frequency with a detectable amplitude can be 20Hz. The control circuit can be configured to move the occluder from the first position to the second position in 50ms or less. The control circuit can be configured to move the occluder from the first position to the second position so that the air is continuously pushed in the airflow channel in less than 50ms. This pushes the air in the airflow channel with sufficient force to generate an acoustic pulse with pressure fluctuations, the amplitude of which is large enough to be detected. The duration of 50ms from the first position to the second position is advantageously short enough to make the acoustic pulse generated sufficiently close to a square wave so that the results of the test are accurate and do not complicate calculations such as Fourier transforms. The control circuit may be configured to move the occluder more than once per breath in a cycle from the first position to the second position and back to the first position. For example, the cycling of the occluder may have a frequency or pulse rate of 3 Hz.

[0059] Once an acoustic pulse is generated by a separate acoustic pulse generator or by movement of the occluder from the first position to the second position, the acoustic pulse travels through the airflow channel in the direction of the mouthpiece. Advantageously, this is in the direction of the airway of the subject using the device. In other words, advantageously, the airflow channel does not include any bends or branches between the occluder and the mouthpiece. This means that the maximum amount of energy will reach the subject's airway. The acoustic pulse passes through the airflow channel out of the mouthpiece and into the subject's airway. The acoustic pulse interacts with the subject's airway, causing changes in the pressure and flow of the air passing through the sensor.

[0060] The sensor assembly can be configured to measure the flow rate of the air in the airflow channel or the pressure of the air in the airflow channel or both the flow rate of the air in the airflow channel and the pressure of the air in the airflow channel. The control circuit can be configured to calculate parameters characterizing the respiratory system based on frequency domain analysis of the flow rate of the air in the airflow channel or the pressure of the air in the airflow channel or both the flow rate of the air in the airflow channel and the pressure of the air in the airflow channel. The flow rate and pressure are measured by the sensor assembly as needed.

[0061] The control circuit can receive the measured values ​​of flow and pressure from the sensor assembly, and based on these measured values, several indicators describing the mechanical properties of the airway can be formed. These indicators can be parameters that characterize the respiratory system of the subject. Because the pulse contains multiple frequencies, the indicators can indicate the characteristics of the upper and lower airways and the entire respiratory system. The indicators can give an indication of airway resistance and airway reactance and other mechanical properties of the airway. The mechanical properties of the airway can indicate that the subject suffers from a respiratory disease, so these indicators can help trained medical personnel diagnose respiratory diseases.

[0062] The control circuit may be configured to perform a Fast Fourier Transform on the signals relating to both the measured flow and the measured pressure from the sensor assembly and thereby generate a frequency domain distribution showing the amplitude of each frequency.

[0063] As described, the occluder in the second position can block the airflow channel to a greater extent than when it is in the first position. This change of the occluder causes a change in the resistance to air flowing through the airflow channel. When the occluder is in the second position, the air flowing in the airflow channel is subject to a higher flow resistance than when the occluder is in the first position. The flow resistance when the occluder is in the first position is less than 0.15 kPa s L -1 The higher resistance may result in a change in pressure in the airflow channel when the occluder is in the second position compared to when the occluder is in the first position. The change in pressure in the airflow channel (depending on whether the subject is inhaling or exhaling) may affect the characteristics of the acoustic pulse. Preferably, the increase in resistance may result in a greater portion of the energy of the acoustic pulse being propagated toward the mouthpiece rather than out through the air inlet.

[0064] The length of time that the occluder is in the second position and the configuration of the occluder may affect the characteristics of the acoustic pulse. The configuration of the occluder specifically refers to the amount of flow resistance that the occluder increases when the occluder is in the second position compared to when it is in the first position. Therefore, the length of time that the occluder is in the second position and the configuration of the occluder can be selected to produce an acoustic pulse with desired characteristics.

[0065] In some embodiments, the occluder can be configured so that when the occluder is in the second position, air can flow through the airflow channel. This means that even when the occluder is in the second position, the air in the airflow channel is subject to more resistance and the airflow channel will not be completely blocked. When the occluder is in the second position, the minimum distance between the housing and the occluder can be at least 0.5 mm. At this distance, the flow resistance is low enough that the effect of the change in flow resistance on the characteristics of the acoustic pulse is negligible. A gap of no more than 0.5 mm can be selected because this results in a suitably low flow resistance while also ensuring that the acoustic pulse is effectively guided to the mouthpiece in the airflow channel.

[0066] The test may be more comfortable for the subject and more likely to give accurate results if the pressure changes experienced by the subject while the occluder is in the second position do not result in a significant build-up of pressure in the subject's airway. This can be achieved by ensuring that the occluder is in the second position for only a short period of time and by ensuring that the occluder does not completely close the airflow passage.

[0067] The control circuit can be configured to move the occluder to the first position after the occluder has been in the second position for no more than 20 ms. The time is advantageously short enough so that the pressure change caused by the increase in resistance when the occluder is in the second position is not noticeable to the subject. The mathematical model is advantageously simpler when the calculation does not have to take into account significant pressure changes caused by prolonged occlusion of the airflow channel.

[0068] In some embodiments, it may be advantageous to have a high resistance to the flow of air in the airflow channel when the occluder is in the second position. In such embodiments, the minimum distance between the housing and the occluder may be less than 0.5 mm when the occluder is in the second position. In other embodiments, the occluder is in the second position for a long enough time that the pressure accumulated in the airflow channel has a significant effect on the test. The length of time the occluder is in the second position may be longer than 20 ms.

[0069] Pressure buildup in the airflow channel may increase the amplitude of the acoustic pulse. This may be because the pressure change in the airflow channel contributes additional energy to the acoustic pulse. The occluder maintained in the second position may more effectively direct the energy of the acoustic pulse toward the mouthpiece. This may allow the use of a smaller occluder with lower power requirements. However, the characteristics of the acoustic pulse may also be affected so that it is less close to a square wave.

[0070] The occluder can be configured so that when the occluder is in the second position, air cannot flow through the occluder. This is an extreme case with high flow resistance when the occluder is in the second position, and ensures that the maximum amount of acoustic pulse energy is directed into the airflow channel and toward the mouthpiece. The occluder may include an elastic sealing component configured to contact the housing when the occluder is in the second position. The sealing component may be made of a material that deforms when it contacts the housing. The sealing component advantageously ensures that an airtight seal is achieved in the airflow channel, thereby preventing airflow from flowing through the occluder. It also prevents damage to the housing of the device when the occluder is moved from the first position to the second position with force.

[0071] The device can be configured to generate at least 3 acoustic pulses per second during the test period. The control circuit can also be configured so that the device that moves the occluder during the test period moves the occluder from the first position to the second position and then returns to the first position at least 3 times per second. Generating multiple acoustic pulses throughout the test process advantageously allows a full view of the airway to be obtained. For example, measurements can be taken when the subject's lungs have different inflation volumes. As an alternative to the control circuit being configured to move the occluder back to the first position, a return spring can be used.

[0072] The blocker in the second position may be configured to block the air inlet of the air flow channel.

[0073] The face of the occluder that contacts the airflow channel may be generally concave. This is effective for generating an acoustic pulse when movement of the occluder generates an acoustic pulse. The generally concave shape ensures that as much air as possible is pushed toward the mouthpiece when the occluder is moved from the first position to the second position.

[0074] The device for moving the occluder can be configured to move the occluder in a direction parallel to the airflow through the airflow channel when the subject inhales or exhales through the mouthpiece. This results in the occluder pushing the air caused by the movement of the occluder from the first position to the second position also being parallel to the airflow channel. The pushed air then moves in the direction of the mouthpiece. When the acoustic pulse is generated by a separate acoustic pulse generator, the push on air generated by the acoustic pulse generator can be parallel to the airflow in the direction of the mouthpiece.

[0075] The device for moving the occluder may be a linear actuator. The linear actuator may advantageously be positioned so that the axis of its movement is parallel to the airflow channel. The linear actuator will then move the occluder from a first position to a second position in a direction parallel to the airflow channel. Other devices for moving the occluder are also possible. For example, the occluder may be on a hinged actuator.

[0076] A device configured to perform an oscillometric test may be a stand-alone device that cannot be reconfigured to perform any other respiratory diagnostic test.

[0077] One or more secondary components may include an integral mouthpiece. Alternatively, the mouthpiece may be provided as a separate component. The mouthpiece may advantageously include a microbial filter. The mouthpiece advantageously has low flow resistance, low wasted volume, and a relatively smooth inner surface. Avoiding sharp internal features reduces interference with the pulse / wave traveling into / out of the airway. Otherwise, these features may weaken the signal characteristics of the wave. A different mouthpiece may be used for each test. The mouthpiece may be configured to engage with the primary component or the secondary component or both the primary component and the secondary component.

[0078] The mouthpiece may be configured for a specific respiratory test. The mouthpiece may advantageously increase resistance to air flowing in the air flow channel. The mouthpiece may also advantageously include a gas dryer.

[0079] The device for performing a plurality of breath diagnostic tests may be portable. Advantageously, this means that the device can be taken to a subject rather than the subject having to go to, for example, a hospital. Advantageously, this makes monitoring of the condition easier as the subject will not have to return to, for example, a hospital each time a test is performed. It also allows environmental triggers to be assessed in the real world.

[0080] The device may comprise at least one battery configured to provide power to the control circuitry and the means for moving the occluder. A device comprising a battery advantageously allows the device to be portable and not require proximity to a power source, such as mains electricity, when in use.

[0081] In a second aspect of the invention, a kit for performing a plurality of respiratory diagnostic tests is provided, comprising: a primary component, a secondary component, a control circuit, and a sensor assembly, the sensor assembly being located in the primary component or in the secondary component or in both the primary component and the secondary component. The secondary component is configured to engage with the primary component in a first configuration of the kit so that a first airflow channel is formed through the primary component and the secondary component, thereby enabling the performance of a first respiratory diagnostic test. In a second configuration of the kit, a second airflow channel is formed through the kit through at least the primary component, thereby enabling the performance of a second respiratory diagnostic test. The kit is capable of changing from the first configuration to the second configuration without the use of any tools.

[0082] One of the first respiratory diagnostic test and the second respiratory diagnostic test may be a pulmonary obstruction. One of the first respiratory diagnostic test and the second respiratory diagnostic test may be a flow test, and the other of the first respiratory diagnostic test and the second respiratory diagnostic test may be a biomarker test.

[0083] The main components may include a sensor assembly and a control circuit. The sensor assembly may include a flow sensor. The sensor assembly may include a pressure sensor. The sensor assembly may also include a temperature sensor and a humidity sensor.

[0084] The secondary component may comprise at least one additional air inlet configured such that a portion of the air flowing through the secondary component enters the secondary component through the at least one additional air inlet. Advantageously, the air passing through the additional air inlet does not pass through the sensor assembly.

[0085] The secondary component may include a gas dryer configured to reduce the humidity of air passing through the dryer. The secondary component may include a purification filter. The purification filter may be a nitric oxide purification filter. The secondary component may include a valve configured to allow air flowing along the air flow channel to pass through the purification filter in only one direction.

[0086] The secondary component may include an occluder and a device for moving the occluder from a first position to a second position. The secondary component may include an acoustic pulse generator configured to push the air in the airflow channel in the direction of the mouthpiece to generate an acoustic pulse in the airflow channel. The acoustic pulse generator may be a speaker or a gas tank. Alternatively, it may be an occluder configured to generate an acoustic pulse in the air in the airflow channel. When the occluder moves from the first position to the second position, the acoustic pulse may be generated by pushing the air in the airflow channel by the occluder. In these cases, the secondary component may not include a separate acoustic pulse generator.

[0087] The kit may also include a mouthpiece. The mouthpiece may include a microbial filter. The mouthpiece may be configured to engage with the primary component or the secondary component or both the primary component and the secondary component.

[0088] In a third aspect of the invention there is provided a method of performing a plurality of breath diagnostic tests using an apparatus according to the first aspect of the invention, comprising the steps of:

[0089] placing the device in a first configuration for performing a first breath diagnostic test such that the device defines a first airflow channel through the device, and performing the first breath diagnostic test;

[0090] The device is placed in a second configuration for performing a second breath diagnostic test different from the first breath diagnostic test such that the device defines a second airflow channel through the device different from the first airflow channel, and the second breath diagnostic test is performed.

[0091] Advantageously, the method allows a single device to perform multiple respiratory diagnostic tests simply by reconfiguring the device so that different airflow channels through the device are formed. Each of these airflow channels may advantageously be defined in a manner optimized for a particular test.

[0092] The method may further include the step of outputting a test result from the control circuit after performing either the first breath diagnostic test or the second breath diagnostic test. The test result is a combination of measurements or results from the first breath diagnostic test and the second breath diagnostic test.

[0093] Placing the device in a first configuration may include removing a component from the device. Placing the device in a configuration may include changing the position of a component of the device, or the position of an element within a component of the device, to change the airflow path. Placing the device in a configuration may include connecting additional components. Placing the device in a configuration may include changing the environmental conditions of the air flowing through the device, such as changing the temperature of the air flowing through the device.

[0094] In a fourth aspect of the invention, there is provided an apparatus for performing a plurality of respiratory diagnostic tests comprising a plurality of sensors, each sensor measuring a property of air flowing through the apparatus, and control circuitry.

[0095] In the first configuration, the device is configured to perform a first breath diagnostic test, and in the second configuration, the device is configured to perform a second breath diagnostic test.

[0096] In a first configuration, the control circuit is configured to output results for a first breathing test based on measurements received at the control circuit from a first subset of the plurality of sensors, and in a second configuration, the control circuit is configured to output results for a second breathing test based on measurements received at the control circuit from a second subset of the plurality of sensors.

[0097] At least one sensor of the plurality of sensors is present in both the first subset of the plurality of sensors and the second subset of the plurality of sensors.

[0098] It is advantageous to have at least one sensor present in both the first subset and the second subset of the plurality of sensors. If the sensor is only used in one configuration, this means that a large number of sensors are required. Using at least one sensor in both configurations, i.e. in both the first subset and the second subset, reduces the total number of sensors required in the device. This means that the device can be smaller and cheaper.

[0099] One of the first respiratory diagnostic test and the second respiratory diagnostic test may be a flow test or a lung obstruction test, such as a spirometry test or an oscillometric test, etc. The other of the first respiratory diagnostic test and the second respiratory diagnostic test may be a test for a biomarker indicative of inflammation or disease, such as nitric oxide.

[0100] The first subset of sensors may include a primary sensor configured to measure a first parameter of the air in the airflow channel. The parameter may be received by the control circuit. It may be used to find an indicator that can be used to monitor or diagnose the behavior of the subject's respiratory system. The indicator may be equal to the parameter or calculated from the parameter.

[0101] The result of the first respiratory diagnostic test output by the control circuit can be an adjusted measurement of a first parameter of air in the airflow channel based on the first sensor measurement from the first subset of sensors. The adjustment can be based on signals from one or more other sensors in the first subset of sensors.

[0102] The result of the second respiratory diagnostic test output by the control circuit can be based on an adjusted measurement of a second parameter of the air in the airflow channel or a first parameter of the air from a first sensor in the second subset of sensors. The adjustment can be based on signals from one or more other sensors in the second subset of sensors.

[0103] The control circuit may include a microcontroller. The microcontroller may be configured to process data received from the sensor. The result of the data processing may be a test score that can be used to help monitor or diagnose respiratory diseases. Alternatively, the control circuit may communicate with a portable computer (e.g., a laptop computer or a smart phone, etc.) that includes a microcontroller. In these cases, the microcontroller of the portable device performs the data processing. The communication between the control circuit and the portable device may be a wireless connection. The wireless connection may be a Bluetooth connection.

[0104] The signals from one or more other sensors may be measurements of additional parameters of the air in the airflow path. The first parameter may depend on these additional parameters. The dependence of the first parameter on the additional parameters may be a linear or non-linear dependence. The additional parameters may be temperature, pressure, humidity or flow. The microprocessor is programmed with models of how the first parameter depends on the additional parameters. It uses these models to calculate adjusted measurements of the first parameter.

[0105] The first sensor may measure a first parameter of the air in the air flow channel within a first range, and the second sensor or the adjusted first sensor may measure the first parameter within a second range. Advantageously, this means that the range of measured values ​​of the first parameter is not limited by the range of a single sensor. Measurements from other sensors or adjusted measurements of the first sensor may be used to extend the range. This allows the use of simple and inexpensive sensors.

[0106] In each configuration of the device, an airflow channel is defined. In a first configuration, a first airflow channel through the device is defined, and in a second configuration, a second airflow channel through the device different from the first airflow channel may be defined.

[0107] The device may include a primary component and at least one secondary component. In a first configuration, the primary component and the secondary component may be removably engaged with each other to define an airflow channel. In a second configuration, a second airflow channel may be formed by disengaging the first secondary component from the primary component, the primary component and the secondary component may be disengaged from each other or engaged with each other in a different manner. Advantageously, the airflow channel defined by the engagement of the primary component and the secondary component is optimized for performing a first breathing test. In the second configuration, the primary component may be engaged with the second secondary component. At least a portion of the airflow channel may be defined by the secondary component.

[0108] In each configuration of the device, the primary components may be the same. It may be that at least one secondary component defines the second airflow path as being different from the first airflow path.

[0109] In a first configuration, the device may be configured to perform a test for a biomarker indicative of lung inflammation, and in a second configuration, the device may be configured to perform a spirometry test. The device may have a number of configurations in which a corresponding number of other respiratory diagnostic tests may be performed. One of the subsets of sensors may include a flow sensor. The flow sensor may be located in the main component. The plurality of sensors may include a pressure sensor, a temperature sensor, or a humidity sensor. A subset of sensors may include an electrochemical sensor. The subset of sensors including the electrochemical sensor may also include at least one of a pressure sensor, a temperature sensor, a humidity sensor, and a flow sensor. The control circuit may be configured to use a measurement from at least one of the pressure sensor, the temperature sensor, the humidity sensor, or the flow sensor to adjust a measurement from a sensor for measuring at least one biomarker. These adjustments advantageously take into account changes in the measurement from the sensor for measuring the biomarker. The control circuit may be configured to use a measurement from at least one of the pressure sensor, the temperature sensor, the humidity sensor, and the flow sensor to calibrate the measurement from the electrochemical sensor.

[0110] The biomarker sensor can be an electrochemical sensor. Since electrochemical sensors are generally very sensitive to environmental conditions, especially to changes in moisture in the air, it may be advantageous to adjust the measured values ​​from the electrochemical sensor. It is usually exhaled breath measured by the device. Exhaled air has a higher moisture content and temperature relative to the atmosphere, and the exhaled airflow may have a variable pressure or flow rate. The lack of controlled and constant sample conditions means that readings from only electrochemical sensors are not always accurate. The factors of environmental conditions must be taken into account. The microcontroller can use the signals received from the pressure sensor, flow sensor, temperature sensor and / or humidity sensor to provide adjustment factors and / or offsets for the measured values ​​from the electrochemical sensor to take into account the rate of change of environmental conditions or environmental variables. Because electrochemical sensors are generally particularly sensitive to changes in moisture in the air, the adjustment factors and / or offsets for the measured values ​​from the electrochemical sensor can be based on the measured values ​​from the humidity sensor. The humidity sensor can be placed closer to the electrochemical sensor than other sensors in a plurality of sensors. In such an arrangement, the humidity sensor can advantageously obtain humidity measurements that more accurately represent the moisture in the air passing through the electrochemical sensor.

[0111] The device may be configured to perform a test for a biomarker indicative of lung inflammation. The device may include a purification filter configured to reduce ambient traces of a biomarker indicative of lung inflammation. Inhaled air may pass through the purification filter. This means that the amount of the biomarker measured in the exhaled breath may be considered to be produced by the subject, rather than simply being present in the environment, inhaled, and then exhaled.

[0112] The device may include a valve configured to change the characteristics of the airflow channel depending on the direction of airflow through the airflow channel. For example, the valve may be configured so that the airflow channel is limited to only one direction through the purification filter. The concentration of the biomarker in the air passing through the purification filter is reduced. The concentration of the biomarker in the inhaled air is reduced. Then when the air is exhaled, the measured biomarker concentration represents the concentration of the biomarker in the lungs, rather than the background or atmospheric level of the biomarker.

[0113] The apparatus may include a gas dryer. The gas dryer may be configured to reduce the humidity of air passing through the gas dryer. As above, electrochemical sensors are very sensitive to changes in moisture content. In addition to or in lieu of adjusting the measurements as in the above method, it may be advantageous to reduce the humidity of the air sampled by the apparatus. This may improve the accuracy of the readings from the electrochemical sensor.

[0114] Reducing the humidity of the air passing through the device can prevent condensation on the sensor, which is advantageous, particularly for nitric oxide sensors. The gas dryer can be an absorbent material, a water trap, a Nafion tube, or the sensor surface can also be heated. The absorbent material advantageously requires no electricity and does not substantially increase the internal volume of the flow channel.

[0115] A biomarker indicative of lung inflammation may be nitric oxide concentration. Exhaled nitric oxide concentration indicates the activity of eosinophils, which are associated with inflammation for about two-thirds of people with asthma and one-third of people with COPD. Therefore, nitric oxide concentration can be used to determine the subtype of the disease a person may have. High nitric oxide concentrations may indicate that a subject is likely to respond to a specific drug treatment. If the treatment is successful, the subject's exhaled nitric oxide concentration should decrease, so the test can be used to find effective drug dosages and confirm that the subject is taking their treatment correctly.

[0116] The device may include a flow sensor. It may be advantageous for the flow sensor to be used in more than one configuration and / or to perform more than one respiratory diagnostic test. Different tests have different typical flow rates and accuracy requirements. One test may have a range of up to about 850 liters per minute, with measurements having an accuracy of ±5 liters per minute. When the device is configured to perform different respiratory diagnostic tests, the required flow rate may be much lower. The airflow required for some tests may not exceed 5 liters per minute, with measurements having an accuracy of ±<0.5 liters per minute. It would be advantageous to be able to use the same flow sensor in both configurations. In that case, the flow sensor needs to have an appropriate range for measuring the airflow and an appropriate accuracy over that range.

[0117] It is technically challenging to produce a flow sensor with an appropriate range and sensitivity. At a lower flow rate of about 5 liters per minute, a flow sensor with a range of 850 liters per minute will generally not have suitable sensitivity. It may be advantageous to use a flow sensor with a smaller range but a higher sensitivity at low flows. It may be advantageous to modify or adjust the effective range of the flow sensor by modifying or adjusting the input to the flow sensor (i.e., the flow rate of air), or by modifying or adjusting the output of the flow sensor, or by combining the output of the flow sensor with the output of one or more other sensors.

[0118] The sensor assembly may include a pressure sensor. The control circuit may be configured to estimate the flow rate using signals received from both the flow sensor and the pressure sensor. The flow sensor may advantageously have a range of ±200 liters per minute. The flow estimated using the flow sensor and the pressure sensor may advantageously have a range of ±1000 liters per minute. This value is high enough to measure the flow rate when the device is in a spirometry configuration, in which the flow estimate at lower flows is primarily determined by the flow sensor, which has a higher sensitivity at lower flows, while the measurement at higher flows is primarily determined by the pressure sensor, which has a larger range than the flow sensor.

[0119] The device may be configured to perform a spirometry test. The device may be configured to perform a spirometry test using a flow sensor. The device may be configured to measure peak expiratory flow or forced expiratory flow. Spirometry tests measure lung function, particularly the amount and / or rate of air that can be inhaled or exhaled. These tests may be advantageously used to diagnose conditions such as asthma.

[0120] The device may include a mouthpiece. The mouthpiece may include a microbial filter.

[0121] In a fifth aspect of the invention, there is provided a method of performing a plurality of respiratory diagnostic tests using an apparatus comprising a plurality of sensors, each sensor measuring a characteristic of air flowing through the apparatus, the apparatus having a first configuration and a second configuration, comprising the steps of:

[0122] placing the device in a first configuration for performing a first respiratory diagnostic test;

[0123] performing a first breath diagnostic test using a first subset of the plurality of sensors;

[0124] placing the device in a second configuration for performing a second respiratory diagnostic test;

[0125] performing a second breath diagnostic test using a second subset of the plurality of sensors; and

[0126] outputting results of a first breath diagnostic test and a second breath diagnostic test based on measurements received from the first subset of sensors and the second subset of sensors,

[0127] There is at least one sensor in both the first subset and the second subset of the plurality of sensors.

[0128] One of the first respiratory diagnostic test and the second respiratory diagnostic test may be a pulmonary obstruction or flow test. One of the first respiratory diagnostic test and the second respiratory diagnostic test may be a biomarker test. The biomarker test may be a test for nitric oxide concentration.

[0129] The result of the first breath diagnostic test can be an adjusted measurement of a first parameter of air in the airflow passage based on the vehicle value from the first sensor in the first subset of sensors, the adjusted measurement being adjusted based on signals from one or more other sensors in the first subset of sensors.

[0130] The result of the second respiratory diagnostic test can be an adjusted measurement of a first parameter of air in the airflow channel based on the measurement from the first sensor in the second subset of sensors, the adjusted measurement being adjusted based on signals from one or more other sensors in the second subset of sensors.

[0131] In a sixth aspect of the invention, there is provided an apparatus for performing a plurality of respiratory diagnostic tests, comprising a plurality of sensors, each sensor measuring a property of air flowing through the apparatus, and control circuitry;

[0132] wherein, in a first configuration, the device is configured to perform a first breath diagnostic test, and in a second configuration, the device is configured to perform a second breath diagnostic test;

[0133] wherein, in a first configuration, the control circuit is configured to output results for a first breath test based on measurements received at the control circuit from a first subset of the plurality of sensors, and in a second configuration, the control circuit is configured to output results for a second breath test based on measurements received at the control circuit from a second subset of the plurality of sensors;

[0134] wherein a result of a first respiratory diagnostic test output by the control circuit is an adjusted measurement of a first parameter of air in an airflow channel based on a measurement from a first sensor in a first subset of sensors, wherein the adjustment is based on signals from one or more other sensors in the first subset of sensors.

[0135] The first breath test may be a test for a biomarker indicative of inflammation or disease. The first sensor in the subset of sensors may be a biomarker sensor. The biomarker sensor may be an electrochemical sensor. The biomarker sensor may be configured to measure a concentration of a biomarker, which may be a first parameter of the air in the airflow channel. The biomarker may be a concentration of nitric oxide measured using an electrochemical sensor. The measured value of the biomarker concentration may be adjusted based on a signal from at least one of a pressure sensor, a temperature sensor, a humidity sensor, and a flow sensor.

[0136] Because electrochemical sensors are often particularly sensitive to changes in moisture in the air, adjustments to the measurements of biomarker concentrations from the electrochemical sensor may preferably be based on measurements from the humidity sensor. The humidity sensor may be placed closer to the electrochemical sensor than other sensors in the plurality of sensors. In such an arrangement, the humidity sensor may advantageously obtain humidity measurements that more accurately represent the moisture in the air passing through the electrochemical sensor.

[0137] In a seventh aspect of the present invention, there is provided an apparatus for performing a pulse oscillometric test, comprising: a housing defining an airflow passage from a mouthpiece to an air inlet, wherein the air inlet is open to the atmosphere; an occluder; means for moving the occluder between a first position and a second position, wherein the occluder in the second position occludes the airflow passage to a greater extent than when in the first position;

[0138] an acoustic pulse generator configured to push air in the airflow channel in the direction of the mouthpiece to generate an acoustic pulse in the air in the airflow channel;

[0139] A control circuit configured to control the device for moving the occluder and the acoustic pulse generator so that the acoustic pulse generator generates an acoustic pulse in coordination with the movement of the occluder from a first position to a second position; and a sensor assembly configured to measure an airflow parameter of air in the airflow channel after the acoustic pulse is generated.

[0140] Oscillometric tests are diagnostic tests whose results indicate the mechanical properties of the airways of the subject performing the test. These properties can be used to help diagnose respiratory diseases such as COPD. Oscillometric tests are advantageous because they do not require the subject to perform specific breathing maneuvers such as labored breathing. The subject only needs to breathe at a relatively constant inhalation or exhalation rate. It is even possible for the subject to simply perform normal tidal breathing through the device. This is advantageous because it means that the test is easy to perform and comfortable to perform. This is especially important for children and subjects suffering from respiratory diseases that would make breathing in another way (such as labored breathing with a high flow rate) difficult and uncomfortable.

[0141] While performing an oscillometric test using the device, the subject may inhale and / or exhale through the device, thereby causing air to flow through the air passages of the device and into / out of the subject's lungs. The configuration of the acoustic pulse generator, the occluder, and the means for moving the occluder advantageously provides a compact and efficient way to generate acoustic pulses of air through the air passages of the device.

[0142] As used herein, an acoustic pulse is a pressure wave comprising multiple sinusoidal frequencies. An acoustic pulse is generated by pushing air into an air flow channel by an acoustic pulse generator. The pushing of the air creates pressure fluctuations. The pressure wave ideally takes the form of a square wave or a form approximating a square wave.

[0143] The acoustic pulse travels at the speed of sound. Before returning to the airflow channel of the device, the acoustic pulse may pass through the airflow channel and the mouthpiece and then enter the airway of the subject. After the acoustic pulse is generated, the parameters of the air in the airflow channel can be sensed by the sensor assembly. One measured parameter can be air pressure. Another measured parameter can be air flow. The acoustic pulse can interact with the airway of the subject, causing changes in the pressure and flow of the air passing through the sensor. Therefore, these parameters can be used to determine the response of the subject's airway to the acoustic pulse. The response can be used to characterize the subject's airway. After the acoustic pulse interacts with the subject's airway, the pressure wave will spread out and may have a bell shape.

[0144] Advantageously, the occluder in the second position blocks the airflow channel to a greater extent than in the first position, because this reduces the energy lost from the acoustic pulse in the direction away from the mouthpiece. Energy can escape through any gap between the occluder and the airflow channel, and therefore any reduction in this gap (achieved by increasing the occlusion) ensures that less energy escapes. Therefore, if the occluder is in the second position during the generation of the acoustic pulse, the energy loss of the generated acoustic pulse in the direction away from the mouthpiece is advantageously reduced.

[0145] The control circuitry may be configured to coordinate movement of the occluder from the first position to the second position such that it occurs simultaneously with generation of the acoustic pulse.

[0146] The control circuit is configured to move the occluder so that the occluder is in the second position while the acoustic pulse is generated. Advantageously, this ensures that occlusion is increased as the acoustic pulse is generated.

[0147] The occluder can be configured to move from a first position to a second position so that the occluder has a deviation of 5ms or less in the second position relative to the generation of the acoustic pulse. The deviation can be such that the occluder reaches the second position after the acoustic pulse is generated, but preferably, the occluder is in the second position before the acoustic pulse is generated. The deviation can advantageously allow the movement of the occluder to be precisely controlled relative to the generation of the acoustic pulse. For a specific configuration of the device, the deviation can be a predetermined value that ensures that the maximum or particularly desired amount of acoustic pulse energy is directed to the mouthpiece rather than away from the mouthpiece.

[0148] Once generated, the acoustic pulse travels through the airflow channel in the direction of the mouthpiece. Advantageously, this is in the direction of the airway of the subject using the device. In other words, advantageously, the airflow channel does not include any bends or branches between the occluder and the mouthpiece. This means that the maximum amount of energy will reach the airway of the subject. The acoustic pulse passes through the airflow channel out of the mouthpiece and into the airway of the subject. The acoustic pulse interacts with the airway of the subject, causing changes in the pressure and flow of the air passing through these sensors.

[0149] The sensor assembly can be configured to measure the flow rate of the air in the airflow channel or the pressure of the air in the airflow channel or both the flow rate of the air in the airflow channel and the pressure of the air in the airflow channel. The control circuit can be configured to calculate parameters characterizing the respiratory system based on frequency domain analysis of the flow rate of the air in the airflow channel or the pressure of the air in the airflow channel or both the flow rate of the air in the airflow channel and the pressure of the air in the airflow channel. The flow rate and pressure are measured by the sensor assembly as needed.

[0150] The control circuit can be configured to receive signals from the sensor assembly. The control circuit can receive measured values ​​of flow and pressure from the sensor assembly, and based on these measured values, several indicators describing the mechanical properties of the airway can be formed. These indicators can be parameters that characterize the respiratory system of the subject. Acoustic pulses of different frequencies can be attenuated to varying degrees by the airway of the subject. The attenuation can increase with increasing frequency. As a result, the measured values ​​of pressure and flow at higher frequencies are mainly determined by the response of the upper airway. Because the acoustic pulse contains multiple frequencies, the indicators can indicate the characteristics of the upper and lower airways and the entire respiratory system. The indicators can give indications of airway resistance and airway reactance and other mechanical properties of the airway. The mechanical properties of the airway can indicate that the subject suffers from a respiratory disease, so these indicators can help trained medical personnel diagnose respiratory diseases.

[0151] The control circuit may include a microcontroller. The microcontroller may be configured to process data received from the sensor. The processing of the data may include performing a fast Fourier transform. The result of the data processing may be a test score that can be used to help monitor or diagnose a respiratory disease. Alternatively, the control circuit may communicate with a portable computer (e.g., a laptop computer or a smart phone, etc.) that includes a microcontroller. In these cases, the microcontroller of the portable device performs the data processing. The communication between the control circuit and the portable device may be a wireless connection. The wireless connection may be a Bluetooth connection.

[0152] The control circuit may be configured to perform a Fast Fourier Transform on the signals relating to both the measured flow and the measured pressure from the sensor assembly and thereby generate a frequency domain distribution showing the amplitude of each frequency.

[0153] The acoustic pulses generated by the acoustic pulse generator may include a plurality of frequencies including a range of 5 Hz to 20 Hz. The acoustic pulses may be in the form of a square wave, or a near square wave, generated by movement of the occluder from the first position to the second position.

[0154] The acoustic pulses generated by the pulse generator may have a maximum pressure increase of at least 50 Pa at the sensor assembly and a flow increase of at least 0.15 liters per minute through the airflow channel in the direction of the mouthpiece. The increase in pressure is an increase in pressure above the air pressure in the airflow channel starting when the subject is breathing normally. The control circuit may be configured to move the occluder from the first position to the second position in 50 ms or less.

[0155] The occluder in the second position blocks the airflow channel to a greater extent than when it is in the first position. This change in the occluder causes a change in the resistance to air flowing through the airflow channel. When the occluder is in the second position, the air flowing in the airflow channel is subject to a higher flow resistance than when the occluder is in the first position. The flow resistance when the occluder is in the first position can be less than 0.15 kPa s L -1 The flow resistance when the occluder is in the first position may be 0.1 kPa s L -1 The higher resistance may result in a change in pressure in the airflow channel when the occluder is in the second position compared to when the occluder is in the first position. The change in pressure in the airflow channel (depending on whether the subject is inhaling or exhaling) may affect the characteristics of the acoustic pulse. Preferably, the pressure change may result in a greater portion of the energy of the acoustic pulse being propagated toward the mouthpiece rather than out through the air inlet.

[0156] The device may also include a terminal resistor in the airflow channel. The terminal resistor may be configured to calibrate the resistance of the airflow channel. The terminal resistor may be configured to increase the resistance of the airflow channel. This has the effect of increasing the resistance of the airflow channel both when the occluder is in the first position and when the occluder is in the second position. The terminal resistor may prevent decoupling between atmospheric pressure and the pressure measured by the sensor in the device.

[0157] The length of time that the occluder is in the second position and the configuration of the occluder may both affect the characteristics of the acoustic pulse. The configuration of the occluder specifically refers to the amount of flow resistance that the occluder increases when the occluder is in the second position compared to when it is in the first position. Therefore, the length of time that the occluder is in the second position and the configuration of the occluder may be selected to result in an acoustic pulse with desired characteristics.

[0158] In some embodiments, the occluder can be configured so that when the occluder is in the second position, air can flow through the airflow channel. This means that even when the occluder is in the second position, the air in the airflow channel is subject to more resistance and the airflow channel will not be completely blocked. When the occluder is in the second position, the minimum distance between the housing and the occluder can be at least 0.5 mm. At this distance, the flow resistance is low enough that the effect of the change in flow resistance on the characteristics of the acoustic pulse is negligible. A gap of no more than 0.5 mm can be selected because this results in a suitably low flow resistance while also ensuring that the acoustic pulse is effectively guided to the mouthpiece in the airflow channel.

[0159] The test may be more comfortable for the subject and more likely to give accurate results if the pressure changes experienced by the subject while the occluder is in the second position do not result in a significant build-up of pressure in the subject's airway. This can be achieved by ensuring that the occluder is in the second position for only a short period of time and by ensuring that the occluder does not completely close the airflow passage.

[0160] The control circuit can be configured to move the occluder to the first position after the occluder has been in the second position for no more than 20ms. The time is advantageously short enough so that the pressure change caused by the increase in resistance when the occluder is in the second position is not obvious to the subject. The mathematical model required to calculate the indicator based on the acoustic pulse is advantageously simpler when the calculation does not have to take into account the significant pressure changes caused by the long-term blockage of the airflow channel. In some embodiments, the control circuit can be configured to move the occluder to the first position after the occluder has been in the second position for no more than 30ms or 40ms.

[0161] In some embodiments, it may be advantageous to have a high resistance to the flow of air in the airflow channel when the occluder is in the second position. In such embodiments, the minimum distance between the housing and the occluder may be less than 0.5 mm when the occluder is in the second position. In other embodiments, the occluder is in the second position for a long enough time that the pressure accumulated in the airflow channel has a significant effect on the test. The length of time the occluder is in the second position may be longer than 20 ms.

[0162] Pressure buildup in the airflow channel may increase the amplitude of the acoustic pulse. This may be because the pressure change in the airflow channel contributes additional energy to the acoustic pulse. The occluder maintained in the second position may more effectively direct the energy of the acoustic pulse to the mouthpiece. This may allow the use of a smaller occluder and have lower power requirements. However, the characteristics of the acoustic pulse may also be affected so that it is less close to a square wave.

[0163] The occluder can be configured so that when the occluder is in the second position, air cannot flow from the air inlet through the occluder to the mouthpiece. This is an extreme case with high flow resistance when the occluder is in the second position, and ensures that the maximum amount of acoustic pulse energy is directed into the air flow channel and toward the mouthpiece.

[0164] The occluder may include a resilient sealing member configured to contact the housing when the occluder is in the second position. The sealing member may be made of a material that deforms when it contacts the housing. The sealing member advantageously ensures an airtight seal in the airflow channel, thereby preventing airflow from flowing through the occluder. It also prevents damage to the housing of the device when the occluder is moved from the first position to the second position by force.

[0165] The control circuit can be configured so that the device that moves the occluder during the test period moves the occluder from the first position to the second position and then back to the first position at least 3 times per second. The control circuit can be configured so that the acoustic pulse generator is configured to generate at least 3 acoustic pulses per second during the test period, and one acoustic pulse is generated each time the occluder moves from the first position to the second position. Generating multiple acoustic pulses throughout the test process is conducive to obtaining a full picture of the airway. For example, measurements can be taken when the subject's lungs have different inflation volumes. Alternatively or additionally, the results from multiple acoustic pulses can be averaged. This may take into account noise or other inaccuracies in a single measurement.

[0166] The blocker in the second position may be configured to block the air inlet of the air flow channel.

[0167] The occluder may be a plunger or a shutter. When the occluder is a plunger or a shutter, the means for moving the occluder may be a linear actuator. Other means for moving the occluder are also possible. For example, the occluder may be on a hinged actuator.

[0168] The occluder may be a rotary valve. For example, the rotary valve may include a disk positioned perpendicular to an airflow channel defined in a housing of the device. The disk may include a hole. In a first position, the hole may be in communication with the airflow channel. In a second position, the hole may not be in communication with the airflow channel or may only be in communication with a portion of the airflow channel. Therefore, the disk in the second position may block the airflow channel to a greater extent than in the first position. Different blockages between the first position and the second position may be achieved in other ways. The disk may have an irregular shape. The axis of rotation may be eccentric. The rotary valve may include blades. When the occluder is a rotary valve, the device for moving the occluder may be a motor.

[0169] The acoustic pulse generator may include a plunger and a device for moving the plunger between a first position and a second position, and the device may be configured so that movement of the plunger from the first position to the second position pushes air in the airflow channel from the plunger in the direction of the mouthpiece. The control circuit may advantageously control the device for moving the plunger so that the plunger moves between the first position and the second position at a speed and over a distance to produce an acoustic pulse with desired characteristics. This may mean that the flow and pressure fluctuations have a desired amplitude. The acoustic pulse generator may push the air in the airflow channel for 50 ms or less. This produces an acoustic pulse with an amplitude large enough for oscillation method testing.

[0170] The plunger can move in a cycle from a first position to a second position and back to the first position. For example, the cycle of the plunger can have a frequency or pulse rate of 3 Hz. The highest frequency contained in the pulse depends mainly on the duration of the pulse. For example, by moving the occluder from the first position to the second position in 50 ms or less, a higher frequency of 20 Hz contained in the pulse can be obtained. The pulse will contain lower frequencies, such as 5 Hz, etc. The highest frequency with a detectable amplitude can be 20 Hz. Acoustic pulses of different frequencies can be attenuated to different degrees. The attenuation can increase with increasing frequency. As a result, the measurements of pressure and flow at higher frequencies are mainly determined by the response of the upper airway. The measurements of pressure and flow at lower frequencies may include responses from the periphery of the lungs. Therefore, it is advantageous to use pressure fluctuations of multiple frequencies rather than a single frequency to detect the airway of the subject, so as to obtain a more comprehensive understanding of the mechanical properties of the airway of the subject. It allows the identification of characteristic respiratory responses at different frequencies.

[0171] The means for moving the plunger is configured to move the plunger in a direction parallel to the airflow through the airflow channel when the subject inhales or exhales through the mouthpiece. This results in the plunger pushing the air caused by the movement of the plunger from the first position to the second position also being parallel to the airflow channel. The pushed air then moves in the direction of the mouthpiece.

[0172] The means for moving the plunger may be a linear actuator. The linear actuator may advantageously be positioned so that the axis of its movement is parallel to the airflow channel. The linear actuator will then move the plunger from the first position to the second position in a direction parallel to the airflow channel. Other means for moving the plunger are also possible. For example, the plunger may be on a hinged actuator.

[0173] A portion of the housing defining the airflow channel may include a first tapered portion. The plunger in the first position may be located in or near a wider portion of the first tapered portion than in the second position. In this configuration, the energy of the acoustic pulse generated by moving the plunger from the first position to the second position may be more effectively directed toward the mouthpiece through the first tapered portion. The airflow channel may include a second tapered portion adjacent to the first tapered portion, wherein the second tapered portion may be configured to surround the plunger when the plunger is in the first position. The second tapered portion may provide sufficient clearance around the plunger so that the resistance to flow through the airflow channel when the plunger is in the first position is very low without requiring a long distance movement between the first position and the second position.

[0174] When the acoustic pulse generator is a plunger, the plunger can also be an occluder. In that case, while the plunger is moved from a first position to a second position to generate an acoustic pulse, the occlusion of the airflow channel is also increased.

[0175] The acoustic pulse generator may be a loudspeaker. The loudspeaker may include a cone or diaphragm that pushes air in the air flow channel to generate the acoustic pulses. The loudspeaker may be configured to push air in the air flow channel toward the mouthpiece in a direction parallel to the air flow channel. The loudspeaker may be connected to a signal generator. The signal generator may provide an electrical signal that the loudspeaker converts into an acoustic wave. The signal generator may form part of the control circuit.

[0176] Alternatively, the acoustic pulse generator can be configured to release compressed gas in the air flow channel that pushes the air in the air flow channel in the direction of the mouthpiece. The compressed gas can be stored in a gas tank. The gas tank may include a release valve. The release valve can be configured so that when it is opened, the compressed gas is released from the gas tank into the air flow channel. The compressed gas can be released in a direction parallel to the air flow channel and the direction of the mouthpiece. The release valve can be connected to a control circuit and can be controlled so that the release of the compressed gas is coordinated with the movement of the occluder from the first position to the second position.

[0177] The device may be portable. Advantageously, this means that the device can be taken to the subject rather than the subject having to go to, for example, a hospital. Advantageously, this makes monitoring of the condition easier as the subject will not have to return to, for example, a hospital each time a test is performed. It also allows environmental triggers to be assessed in the real world.

[0178] The device may include at least one battery configured to provide power to the control circuit, the acoustic pulse generator and the means for moving the occluder. Devices including batteries advantageously allow the device to be portable and not require proximity to a power source, such as mains electricity, when in use.

[0179] In an eighth aspect of the present invention, there is provided a method for performing an oscillation method test, comprising the steps of:

[0180] generating a sound pulse using a sound pulse generator, the sound pulse generator being configured to push air in the airflow channel in the direction of the mouthpiece to generate a sound pulse in the air in the airflow channel;

[0181] Moving the occluder from a first position to a second position, wherein the occluder in the second position blocks the airflow channel to a greater extent than when in the first position;

[0182] After the occluder has been moved to the second position, returning the occluder to the first position; and

[0183] measuring an airflow parameter of air in the airflow channel during a time period subsequent to generating the acoustic pulse in the airflow channel;

[0184] The control circuit is configured to control the device to move the occluder and the acoustic pulse generator so that the acoustic pulse generator generates an acoustic pulse in coordination with the movement of the occluder from the first position to the second position.

[0185] The control circuit can be configured to move the occluder back to the first position after the occluder has been quickly in the second position to minimize the pressure accumulated in the airflow channel when the occluder is in the second position. The control circuit can be configured to move the occluder to the first position after the occluder has been in the second position for no more than 20ms, or in some embodiments no more than 30ms or 40ms. The occluder can move from the first position to the second position and then return to the first position in 120ms or less. The occluder can move from the first position to the second position and then return to the first position 3 times per second. Whenever the occluder moves from the first position to the second position, an acoustic pulse can be generated. Generating multiple acoustic pulses throughout the test process is conducive to obtaining a full view of the airway. For example, measurements can be obtained when the subject's lungs have different inflation volumes. As an alternative to the control circuit being configured to move the occluder back to the first position, a return spring can be used.

[0186] The acoustic pulses may include multiple frequencies. The acoustic pulses may include frequencies in the range of 5 Hz to 20 Hz. This frequency range may advantageously detect the upper and lower airways of the subject. Lower frequency signals are less attenuated by the subject's airway than higher frequency signals. Therefore, it is advantageous to use pressure fluctuations of multiple frequencies rather than a single frequency to detect the subject's airway in order to more fully understand the mechanical properties of the subject's airway. This also allows identification of characteristic respiratory responses at different frequencies.

[0187] In a ninth aspect of the present invention, there is provided an apparatus for performing a pulse oscillation method test, comprising: a housing defining an air flow passage from a mouthpiece to an air inlet, wherein the air inlet is open to the atmosphere; an occluder; and a device for moving the occluder between a first position and a second position.

[0188] The occluder in the second position occludes the airflow channel to a greater extent than in the first position. The occluder is configured such that movement of the occluder from the first position to the second position pushes air in the airflow channel from the occluder in the direction of the mouthpiece to generate an acoustic pulse in the air in the airflow channel.

[0189] In the apparatus of the ninth aspect of the invention, it is the movement of the occluder from the first position to the second position that generates the acoustic pulse. Thus, in this aspect, the occluder acts as an acoustic pulse generator (as described in the previous aspects) and has a second position, wherein the occluder in the second position blocks the airflow channel to a greater extent than in the first position. The occluder in this aspect of the invention may have the advantages of the occluder and acoustic pulse generator described above with respect to other aspects of the invention.

[0190] The device also includes a sensor assembly configured to measure an airflow parameter of air in the airflow channel after generating the acoustic pulse.

[0191] The acoustic pulse is generated by the occluder pushing air into the airflow channel as the occluder moves from the first position to the second position. The pushing of air generates a pressure wave. The pressure wave ideally takes the form of a square wave or a form close to a square wave. Ideally, the acoustic pulse would be generated by the instantaneous movement of the occluder from the first position to the second position. In practice, this instantaneous movement is impossible, resulting in an asymmetric bell-shaped pulse.

[0192] The acoustic pulse travels at the speed of sound. Before returning to the airflow channel of the device, the acoustic pulse may pass through the airflow channel and the mouthpiece and then enter the airway of the subject. After the acoustic pulse is generated, the parameters of the air in the airflow channel can be sensed by the sensor assembly. One measured parameter can be air pressure. Another measured parameter can be air flow. The acoustic pulse can interact with the airway of the subject, causing changes in the pressure and flow of the air passing through the sensor. Therefore, these parameters can be used to determine the response of the subject's airway to the acoustic pulse. The response can be used to characterize the subject's airway.

[0193] Advantageously, the occluder in the second position blocks the airflow channel to a greater extent than in the first position, because this reduces the energy loss of the pressure wave in the direction away from the mouthpiece. Energy can escape through any gaps between the occluder and the airflow channel, so any reduction in these gaps (achieved by increasing the blockage) ensures that less energy escapes. Therefore, moving the occluder from the first position to the second position will generate an acoustic pulse by pushing air in the airflow channel towards the mouthpiece, while the increased blockage in the second position relative to the first position will simultaneously reduce the energy loss in the direction away from the mouthpiece.

[0194] The control circuit can advantageously control the means for moving the occluder so that the occluder moves between the first position and the second position at a speed and over a distance to produce an acoustic pulse with desired characteristics. This may mean that the flow and pressure fluctuations have a desired amplitude. Alternatively, the means for moving the occluder can be driven by the subject's breathing action.

[0195] Once generated, the acoustic pulse travels through the airflow channel in the direction of the mouthpiece. Advantageously, this is in the direction of the airway of the subject using the device. In other words, advantageously, the airflow channel does not include any bends or branches between the occluder and the mouthpiece. This means that the maximum amount of energy will reach the airway of the subject. The acoustic pulse passes through the airflow channel out of the mouthpiece and into the airway of the subject. The acoustic pulse interacts with the airway of the subject, causing a change in the pressure and flow of air passing through the sensor.

[0196] The measured response to the acoustic pulse depends on the configuration of the occluder, the movement of the occluder, and the characteristics of the air passageway including the lungs of the subject. Because the configuration of the occluder, the movement of the occluder, and the characteristics of the airflow passageway in the device can be known or calibrated, the parameters sensed by the sensor assembly can be used to characterize the airway mechanics of the lungs of the subject.

[0197] The device may further include a control circuit configured to control the device to move the occluder or receive a signal from the sensor assembly, or both control the device to move the occluder and receive a signal from the sensor assembly.

[0198] The sensor assembly is configured to measure the flow rate of the air in the airflow channel or the pressure of the air in the airflow channel or both the flow rate of the air in the airflow channel and the pressure of the air in the airflow channel. The control circuit can be configured to calculate parameters characterizing the respiratory system based on frequency domain analysis of the flow rate of the air in the airflow channel or the pressure of the air in the airflow channel or both the flow rate of the air in the airflow channel and the pressure of the air in the airflow channel. The flow rate and pressure are measured by the sensor assembly as needed.

[0199] The control circuitry may receive flow and pressure measurements from the sensor assembly and based on these measurements may form a number of indices describing the mechanical properties of the airway.

[0200] These indices can be parameters that characterize the subject's respiratory system. Different frequencies of the acoustic pulse can be attenuated to different degrees, and the attenuation can increase with increasing frequency. As a result, higher frequency pressure and flow measurements are primarily determined by the response of the upper airway. Because the pulse contains multiple frequencies, the indices can indicate characteristics of the upper and lower airways and the respiratory system as a whole.

[0201] The indices can give an indication of airway resistance and airway reactance and other mechanical properties of the airway. The mechanical properties of the airway can indicate that the subject has a respiratory disease, so these indices can help trained medical personnel diagnose respiratory diseases.

[0202] The control circuit may include a microcontroller. The microcontroller may be configured to process data received from the sensor. The processing of the data may include performing a fast Fourier transform. The result of the processing of the data may be a test score that can be used to help monitor or diagnose a respiratory disease. Alternatively, the control circuit may communicate with a portable computer (e.g., a laptop computer or a smart phone, etc.) that includes a microcontroller. In these cases, the microcontroller of the portable device performs the data processing. The communication between the control circuit and the portable device may be a wireless connection. The wireless connection may be a Bluetooth connection.

[0203] The control circuit can be configured to move the occluder so that the acoustic pulse generated includes pressure fluctuations of multiple frequencies ranging from 5 Hz to 20 Hz. The acoustic pulse can be in the form of a square wave generated by the movement of the occluder from the first position to the second position, or in the form of an approximate square wave. The occluder can move in a cycle of moving from the first position to the second position and then returning to the first position. For example, the cycle of the occluder can have a frequency or pulse rate of 3 Hz. The highest frequency contained in the pulse depends mainly on the duration of the pulse. For example, by moving the occluder from the first position to the second position in 50 ms or less, a higher frequency of 20 Hz contained in the pulse can be obtained. The pulse will contain lower frequencies, such as 5 Hz, etc. The highest frequency with a detectable amplitude can be 20 Hz. Acoustic pulses of different frequencies can be attenuated to different degrees. The attenuation can increase with increasing frequency. As a result, the measured values ​​of pressure and flow at higher frequencies are mainly determined by the response of the upper airway. The measured values ​​of pressure and flow at lower frequencies can include responses from the periphery of the lungs. Therefore, it is advantageous to use pressure fluctuations at multiple frequencies rather than a single frequency to probe the subject's airway, thereby providing a more complete understanding of the mechanical properties of the subject's airway. It allows for the identification of characteristic respiratory responses at different frequencies.

[0204] The control circuit may be configured to perform a Fast Fourier Transform on the signals relating to both the measured flow and the measured pressure from the sensor assembly and thereby generate a frequency domain distribution showing the amplitude of each frequency.

[0205] The control circuit can be configured to move the occluder from the first position to the second position so that the acoustic pulse provides a maximum pressure increase of at least 50 Pa at the sensor assembly and a flow increase of at least 0.15 liters per minute through the airflow channel in the direction of the mouthpiece. The increase in pressure is an increase in pressure to an amount higher than the air pressure in the airflow channel starting from when the subject is breathing normally. The control circuit can be configured to move the occluder from the first position to the second position in 50 ms or less.

[0206] The occluder in the second position blocks the airflow channel to a greater extent than when it is in the first position. This change in the occluder causes a change in the resistance to air flowing through the airflow channel. When the occluder is in the second position, the air flowing in the airflow channel is subject to a higher flow resistance than when the occluder is in the first position. The flow resistance when the occluder is in the first position is less than 0.15 kPa s L -1 The higher resistance may result in a change in pressure in the airflow channel when the occluder is in the second position compared to when the occluder is in the first position. The change in pressure in the airflow channel (depending on whether the subject is inhaling or exhaling) may affect the characteristics of the acoustic pulse. Preferably, the pressure change may result in a greater portion of the energy of the acoustic pulse being propagated toward the mouthpiece rather than out through the air inlet.

[0207] The length of time that the occluder is in the second position and the configuration of the occluder may affect the characteristics of the acoustic pulse. The configuration of the occluder specifically refers to the amount of flow resistance that the occluder increases when the occluder is in the second position compared to when it is in the first position. Therefore, the length of time that the occluder is in the second position and the configuration of the occluder can be selected to produce an acoustic pulse with desired characteristics.

[0208] In some embodiments, the occluder can be configured so that when the occluder is in the second position, air can flow through the airflow channel. This means that even when the occluder is in the second position, the air in the airflow channel is subject to more resistance and the airflow channel will not be completely blocked. When the occluder is in the second position, the minimum distance between the housing and the occluder can be at least 0.5 mm. At this distance, the flow resistance is low enough that the effect of the change in flow resistance on the characteristics of the acoustic pulse is negligible. A gap of no more than 0.5 mm can be selected because this results in a suitably low flow resistance while also ensuring that the acoustic pulse is effectively guided to the mouthpiece in the airflow channel.

[0209] The test may be more comfortable for the subject and more likely to give accurate results if the pressure changes experienced by the subject while the occluder is in the second position do not result in a significant build-up of pressure in the subject's airway. This can be achieved by ensuring that the occluder is in the second position for only a short period of time and by ensuring that the occluder does not completely close the airflow passage.

[0210] The control circuit can be configured to move the occluder to the first position after the occluder has been in the second position for no more than 20ms. The time is advantageously short enough so that the pressure change caused by the increase in resistance when the occluder is in the second position is not obvious to the subject. The mathematical model required to calculate the indicator based on the acoustic pulse is advantageously simpler when the calculation does not have to take into account the significant pressure changes caused by the long-term blockage of the airflow channel. In some cases, the control circuit can be configured to move the occluder to the first position after the occluder has been in the second position for no more than 30ms or 40ms.

[0211] In some embodiments, it may be advantageous to have a high resistance to the flow of air in the airflow channel when the occluder is in the second position. In such embodiments, the minimum distance between the housing and the occluder may be less than 0.5 mm when the occluder is in the second position. In other embodiments, the occluder is in the second position for a long enough time that the pressure accumulated in the airflow channel has a significant effect on the test. The length of time the occluder is in the second position may be longer than 20 ms.

[0212] Pressure buildup in the airflow channel may increase the amplitude of the acoustic pulse. This may be because the pressure change in the airflow channel contributes additional energy to the acoustic pulse. The occluder maintained in the second position may more effectively direct the energy of the acoustic pulse toward the mouthpiece. This may allow the use of a smaller occluder with lower power requirements. However, the characteristics of the acoustic pulse may also be affected so that it is less close to a square wave.

[0213] A portion of the airflow channel may include a first tapered portion. The occluder in the first position may be located in or near the wider portion of the first tapered portion compared to the second position. In this configuration, the energy of the acoustic pulse generated by moving the occluder from the first position to the second position may be more effectively directed toward the mouthpiece through the first tapered portion. The airflow channel may include a second tapered portion adjacent to the first tapered portion, wherein the second tapered portion may be configured to surround the occluder when the occluder is in the first position. The second tapered portion may provide sufficient clearance around the occluder so that the resistance to flow through the airflow channel when the occluder is in the first position is very low without having a long stroke between the first position and the second position.

[0214] The occluder can be configured so that when the occluder is in the second position, air cannot flow through the occluder. This is an extreme case with high flow resistance when the occluder is in the second position, and ensures that the maximum amount of acoustic pulse energy is directed into the airflow channel and toward the mouthpiece. The occluder may include an elastic sealing component configured to contact the housing when the occluder is in the second position. The sealing component may be made of a material that is deformable when it contacts the housing. The sealing component advantageously ensures that an airtight seal is achieved in the airflow channel, thereby preventing airflow from flowing through the occluder. It also prevents damage to the housing of the device when the occluder is moved from the first position to the second position with force.

[0215] The control circuit can be configured so that the device that moves the occluder during the test period moves the occluder from the first position to the second position and then returns to the first position at least 3 times per second. This generates at least 3 sound pulses per second during the test period. Producing multiple sound pulses throughout the test process advantageously allows a full view of the airway. As an alternative to the control circuit being configured to move the occluder back to the first position, a return spring can be used.

[0216] The blocker in the second position may be configured to block the air inlet of the air flow channel.

[0217] The face of the occluder in contact with the airflow channel may be substantially concave, which is effective for generating the acoustic pulse and ensures that as much air as possible is pushed toward the mouthpiece when the occluder is moved from the first position to the second position.

[0218] The means for moving the occluder can be configured to move the occluder in a direction parallel to the airflow through the airflow channel when the subject inhales or exhales through the mouthpiece. This results in the occluder pushing the air caused by the movement of the occluder from the first position to the second position also being parallel to the airflow channel. The pushed air then moves in the direction of the mouthpiece.

[0219] The device for moving the occluder may be a linear actuator. The linear actuator may advantageously be positioned so that the axis of its movement is parallel to the airflow channel. The linear actuator will then move the occluder from a first position to a second position in a direction parallel to the airflow channel. Other devices for moving the occluder are also possible. For example, the occluder may be on a hinged actuator.

[0220] The mouthpiece advantageously has low flow resistance, low wasted volume, and a relatively smooth inner surface. Avoiding sharp internal features reduces interference with the pulse / wave traveling into / out of the airway. Otherwise, these features may weaken the signal characteristics of the wave.

[0221] The device may be portable. Advantageously, this means that the device can be taken to the subject rather than the subject having to go to, for example, a hospital. Advantageously, this makes monitoring of the condition easier as the subject will not have to return to, for example, a hospital each time a test is performed. It also allows environmental triggers to be assessed in the real world.

[0222] The device may comprise at least one battery configured to provide power to the control circuitry and the means for moving the occluder. A device comprising a battery advantageously allows the device to be portable and not require proximity to a power source, such as mains electricity, when in use.

[0223] In a tenth aspect of the present invention, there is provided a method for generating acoustic pulses during a pulse oscillometric test, comprising the steps of:

[0224] providing an air flow passage defined through a housing of an apparatus for performing an oscillometric test, the air flow passage extending from a mouthpiece to an air inlet, wherein the air inlet is open to atmosphere,

[0225] moving the occluder from a first position to a second position, wherein the occluder in the second position occludes the airflow channel to a greater extent than in the first position, and wherein movement of the occluder pushes air in the airflow channel from the occluder in the direction of the mouthpiece to generate sound waves, and

[0226] After the occluder has been moved to the second position, the occluder is returned to the first position.

[0227] The occluder can be moved from the first position to the second position in 50 ms or less. This generates an acoustic pulse with an amplitude large enough for oscillometric testing.

[0228] The control circuit can be configured to move the occluder back to the first position after the occluder has been quickly in the second position to minimize the pressure accumulated in the airflow channel when the occluder is in the second position. The control circuit can be configured to move the occluder to the first position when the occluder has been in the second position for no more than 20ms, or in some embodiments no more than 30ms or 40ms. The occluder can move from the first position to the second position and then return to the first position in 120ms or less. The occluder can move from the first position to the second position and then return to the first position 3 times per second. Generating multiple sound pulses throughout the test process is conducive to obtaining a full view of the airway. As a control circuit configured to move the occluder back to the first position as an alternative, a return spring can be used.

[0229] The acoustic pulses may include multiple frequencies. The acoustic pulses may include frequencies in the range of 5 Hz to 20 Hz. This frequency range may advantageously detect the upper and lower airways of a subject.

[0230] Lower frequency signals are less attenuated by the subject's airway than higher frequency signals. Therefore, it is advantageous to probe the subject's airway using pressure fluctuations at multiple frequencies rather than pressure fluctuations at a single frequency in order to gain a more complete understanding of the mechanical properties of the subject's airway. This also allows for the identification of characteristic respiratory responses at different frequencies.

[0231] In an eleventh aspect of the present invention, there is provided a method for performing an oscillation method test, comprising the steps of:

[0232] providing an air flow passage defined through a housing of an apparatus for performing an oscillometric test, the air flow passage extending from a mouthpiece to an air inlet, wherein the air inlet is open to atmosphere,

[0233] moving the occluder from a first position to a second position, wherein the occluder in the second position occludes the airflow channel to a greater extent than in the first position, and wherein the movement of the occluder pushes air in the airflow channel from the occluder in the direction of the mouthpiece to generate the acoustic pulse,

[0234] after the occluder has been moved to the second position, returning the occluder to the first position, and

[0235] During a time period subsequent to generating the acoustic pulse in the air flow channel, an air flow parameter of the air in the air flow channel is measured.

[0236] It will be appreciated that features described in relation to one aspect of the invention may be applicable to other aspects of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0237] Embodiments according to the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0238] Figure 1 a series of schematic diagrams showing general configurations of an apparatus according to the present invention, each of which can perform one of a plurality of breath diagnostic tests;

[0239] Figure 2 is a side view of the apparatus in a particular configuration for performing a spirometry test;

[0240] Figure 3 yes Figure 2 A cross-sectional view of a device showing an airflow channel formed through the device;

[0241] Figure 4 yes Figure 3 a close-up cross-sectional view of a portion of , showing a sensor in an airflow channel;

[0242] Figure 5 yes Figure 2An exploded side view of a device showing separate components connected to form the device;

[0243] Figure 6 is different from Figure 2 a side view of an apparatus in a particular configuration for performing a nitric oxide concentration test in the configuration shown in FIG.

[0244] Figure 7 yes Figure 6 A cross-sectional view of a device showing an airflow channel formed through the device;

[0245] Figure 8 is a series of schematic diagrams of the general configuration of the device, similar to Figure 1 , but also shows the sensors that exist and the components that include these sensors;

[0246] Fig. 9 is a side view of the device in a second spirometry configuration;

[0247] Fig.10 is a graph showing flow measurement values ​​measured by a flow sensor and a pressure sensor as compared to true values ​​over time;

[0248] Fig.11 is a graph showing nitric oxide concentration measured by a nitric oxide sensor compared to a true value, and also showing a negative rate of change of relative humidity;

[0249] Fig.12 is a flow chart outlining a method for using the apparatus of the present invention;

[0250] Fig.13 is a side view of an apparatus for performing an oscillometric test in a different configuration, the apparatus in the configuration comprising an occluder, wherein the occluder is in a first position;

[0251] Fig.14 yes Fig.13 The same side view of the device of FIG. 1 , wherein the occluder of the device is in a second position;

[0252] Fig.15 yes Fig.13 and Fig.14 A cross-sectional view of an oscillation method module showing the movement of the occluder from a first position to a second position (respectively at Fig.13 and Fig.14 A linear actuator as shown in ;

[0253] Fig.16 yes Fig.13 A cross-sectional perspective view of a device showing an airflow path defined through the device;

[0254] Fig.17 It is shown that the use Figure 1 A flowchart of a method for performing an oscillation method test using a device;

[0255] Fig.18 is a display screen or user interface of the device, and this embodiment is targeted to subjects with limited medical training;

[0256] Fig.19 is a display screen or user interface of a device, and this embodiment is directed to a subject who is a medical professional;

[0257] Fig. 20 is a display showing historical data from previous tests;

[0258] Fig.21 is an additional display screen or user interface in which the test results of the current subject are compared with the test results of other subjects;

[0259] Fig. 22 is a perspective view of an embodiment of the device, wherein both the primary component and the secondary component include a housing;

[0260] Fig.23a and Figure 23b is a cross-sectional schematic diagram of another embodiment of an oscillation method module; and

[0261] Fig.24a and Figure 24b FIG. 4 is a cross-sectional schematic diagram of another embodiment of an oscillation method module. DETAILED DESCRIPTION

[0262] Figure 1 Five different configurations of a device 100 for performing a breath diagnostic test according to the present invention are shown in schematic form. In each configuration, the device 100 is configured to perform a specific breath diagnostic test. The device includes a primary component 102 and a control circuit 106. The control circuit 106 may be a microcontroller. The device may also include any number of secondary components 104, 105, 107, 108, or 109. The primary component 102 includes or is connected to the control circuit 106. Figure 1 As shown in , the secondary components of the device can be arranged in a variety of ways relative to the primary components to perform different tests.

[0263] Figure 1 All configurations shown in the drawings include a primary component 102 and a control circuit 106. The number or arrangement of secondary components differs for each configuration. Secondary components are added, removed, or rearranged within the assembly to create new configurations of the device. In each configuration, an airflow channel is defined by the connected primary and secondary components. The characteristics of the airflow channel differ in each configuration in order to be optimized for a specific respiratory diagnostic test.

[0264] In some embodiments, the control circuit 106 of the main component is powered by an external power source. This can be achieved via a USB connection to a computer or portable device (such as a laptop computer, etc.). The USB connection is not shown in the figure. In other embodiments, the power source can be an internal power source, such as a battery, etc. The main component 102 is electrically connected to any secondary component connected to the main component. This allows power to be transferred from the external power source to the main component and the secondary components.

[0265] To use the device 100, the subject inhales and / or exhales through the device so that the inhaled or exhaled air flows through the airflow channel defined by the device 100. The main component 102 includes at least one sensor. Some, but not all, of the secondary components 104 include sensors. The main component 102 and the secondary components 104 have a standard connection mechanism that runs throughout all components, making it easy to switch between the various components. The main component may also include additional connection mechanisms, through which some of the secondary components can be connected. Typically, the mouthpiece is also connected to the main component 102 or to one of the secondary components.

[0266] Figure 1 a to 1d show four different configurations of the device, in which various arrangements of primary components are connected to different secondary components. Figure 1 a is a configuration in which the primary component 102 is connected to the secondary component 104 . Figure 1 b is a configuration where the main component 102 is not connected to any other components. Figure 1 c is a configuration in which a secondary component 105 different from the secondary component 104 is connected to the primary component 102 . Figure 1 d is a configuration in which the secondary component 104 is connected to the primary component 102 , and is connected to a secondary component 107 different from the secondary components 104 and 105 .

[0267] Figure 11e is an alternative embodiment. It shows several minor components 104, 108 and 109 fixed to each other. Only the minor component 104 is connected to the main component 102. When the device is configured as shown in 1e, the air flow channel is limited only by the main component 102 and the minor component 104. Minor components 108 and 109 can be connected to the main component 102 as needed to reconfigure the device to perform one of other respiratory diagnostic tests, and therefore define the air flow channel by the main component 102 and the minor component 108 or the main component 102 and the minor component 109 respectively. The connection can be achieved by opening the valve. Close the valve to disconnect the minor component. In some configurations, the valve can allow air to flow through one, more than one or none of the minor components 104, 108 and 109. An alternative connection can be that the minor component rotates relative to the main component or otherwise moves to different positions to change the air flow path through the device.

[0268] Figure 2 is a perspective view of an apparatus 100 for performing a first respiratory diagnostic test. In this configuration, the apparatus is configured to perform a spirometry test. The spirometry test is used to indicate the mechanical properties of a subject's airways. Flow is measured and can be integrated over time to calculate lung volume. Maximum expiratory flow is an indicator of airway resistance and obstruction; resistance to flow increases as airway diameter decreases. A decrease in airway diameter decreases maximum flow. An obstructed or narrowed airway indicates that the subject may have a respiratory condition, such as asthma or COPD, among others.

[0269] The device comprises a main part 102, a first secondary part being a spirometry part 202 and a mouthpiece 204. The secondary part is located between the mouthpiece and the main part. The spirometry part 202 comprises eight bypass holes 210.

[0270] The main components include a flow sensor held in housing portion 207, a sensor assembly held in housing portion 209, and a control circuit held in housing portion 211. The flow sensor, sensor assembly, and control circuit are not Figure 2 The main components also include a mounting plate 212.

[0271] Figure 3 yes Figure 2 , which shows the airflow channel 302 defined by the device 200 when the device 200 is in the spirometry configuration. Figure 3 In the embodiment shown, the control circuit and the control circuit housing portion 211 are not shown. The mounting plate 212 is also not shown.

[0272] The sensor assembly 304 and the flow sensor 306 are Figure 3The sensor assembly 304 includes environmental sensors, which are pressure sensors, temperature sensors, and humidity sensors. The pressure sensor is All Sensors CoDLHR-L02D. The temperature sensor and humidity sensor are integrated into one component, namely Sensirion SHT75. All of the above sensor components can be purchased from the Digi-Key electronics website: https: / / www.digikey.com / . The flow sensor is Sensirion SFM3000. Figure 2 and Figure 3 , the flow sensor 306 and the flow sensor housing 207 are shown as part of the primary component 102. However, they may form part of the secondary component 202.

[0273] The airflow channel 302 is designed to have low flow resistance and low internal volume or dead space. The various components that form the airflow channel 302 have similar inner diameters. When the diameter of the airflow channel 302 changes, the changes are graded to reduce airflow resistance and promote consistent airflow with repeatable characteristics. Some sensors respond better to laminar flow, while some sensors respond better to turbulent flow. Because sensors respond differently to different flow characteristics, it is important that these characteristics are repeatable so that similar air flow occurs in the airflow channel 302 of the device each time a diagnostic test is performed. Spirometry is used to measure the airway resistance of a subject, so inconsistencies or high resistance in the device may cause inaccurate test results or make it difficult for the subject to perform the test. Local disturbances or turbulence of the airflow in the airflow channel 302 may cause sensor measurements to be incorrect or inaccurate.

[0274] The flow sensor 306 is electrically connected to the control circuit and is capable of sending data to the control circuit and receiving instructions and power from the control circuit. For example, the control circuit can activate, deactivate, and adjust the sampling frequency of the flow sensor 306. A higher sampling frequency can provide better data for respiratory measurement. If the flow sensor is deactivated when not testing, power can be used more efficiently.

[0275] Mouthpiece 204 includes a microbial filter (not shown) to protect the subject from infection. The microbial filter also serves to avoid contamination of the device 100, absorbs some moisture from the exhaled breath to reduce condensation on the sensors in the device, and protects the sensors in the device from exhaled particles, fluids or debris. A new mouthpiece 204 is used for each person using the device.

[0276] Figure 4304. The sensor assembly includes environmental sensors. These environmental sensors measure pressure, temperature, and humidity. The sensor assembly 304 is mounted in the main component 102 to expose the inlet of the sensor to the air in the air flow channel 302.

[0277] The sensor assembly 304 is mounted to reduce heat conduction from the housing 209 of the main component 102. Heat conduction between the housing of the main component 102 and the sensor assembly 304 may cause the measurement of the air to be affected by the temperature of the main component 102. The inlet holes for the sensor assembly 304 to enter the housing of the main component 102 are sealed to avoid interaction between the environment and the airflow channel 302. Flow through these inlet holes may cause disturbances in the flow distribution and cause errors in the measurements made by the sensors of the sensor assembly 304.

[0278] The sensors of sensor assembly 304 are electrically connected to the control circuit and can send data to the control circuit and receive instructions and power from the control circuit. For example, the control circuit can activate, deactivate, and adjust the sampling frequency of the sensors of sensor assembly 304. A higher sampling frequency can provide better data for respiration measurement, but it can generate heat, which can cause errors in temperature measurement. If these sensors are deactivated when they are not used in the test, power can be used more efficiently.

[0279] Figure 5 yes Figure 2 An exploded view of the , which shows how the parts fit together. Figure 2 In the configuration shown in FIG. 1 , the primary component 102 is configured to perform a spirometry test when connected to the secondary component 104 and the mouthpiece 204. The spirometry component 202 can be detached from the primary component 102. The mouthpiece can be detached from the secondary component 104 as the spirometry component 202. By connecting the spirometry component 202 to the primary component, the device is configured to perform a spirometry test.

[0280] The spirometry component 202 has an inner surface designed to engage and seal with the outer surface of the flow sensor portion 207 of the main component 102. The engaging surface of each component has a conical taper to provide a seal when the spirometry component 202 is mounted over the flow sensor portion 207 of the main component 102. The inner diameter and conical taper of the flow sensor portion end of the spirometry component 202 are the same as the outer diameter and taper of the connecting end of the mouthpiece 204. Thus, these components can be used in a modular manner, where components can be added to, removed from, or rearranged within the device for different configurations of the device.

[0281] The opposite end of the spirometry component 202 has an inner surface that interfaces with the outer surface of the mouthpiece 204. The size and taper of the interface surfaces of the device are standardized. This means that these interface surfaces will be the same as above. Each secondary component has a standardized interface to interact with the shape and size of at least one end of the primary component or another secondary component. The interface surfaces of both components have a conical taper to provide a seal when the spirometry component 202 is installed over the mouthpiece 204.

[0282] Some interfaces have additional features to aid in connection. The inner surface of the spirometry component 202 has an internal step that positions the depth to which the mouthpiece 204 can be inserted into the spirometry component 202. The internal step also reduces disruption to airflow within the airflow channel 302 because the inner diameter beyond the step is the same as the inner diameter of the mouthpiece 204.

[0283] The mounting plate 212 of the main component forms part of the additional connection mechanism. Only some of the secondary components utilize this additional connection mechanism. The additional connection mechanism provides an additional contact point between the main component 102 and the secondary component to be connected to the main component by utilizing the mounting plate 212. In order to connect the secondary component to the main component through the mounting plate, the secondary component includes a threaded knob that passes through the mounting plate 212 of the main component and is screwed into the secondary component. This allows the secondary component to be firmly and repeatably aligned with the main component. It also facilitates the connection of components of various shapes and sizes, and resists shocks caused by equipment drops or collisions and forces that may cause the secondary component to move relative to the main component. Other mechanisms can be used to provide this mechanical stability. For example, the rotational position can be positioned by a spline feature, while the axial position can be positioned by a stepped feature or a snap-on locking mechanism. Ideally, a mechanism is provided to fix the relative rotational position, position the relative axial position, and resist collisions, vibrations, and forces that may attempt to displace the secondary component relative to the main component. Another form of an additional connection mechanism is by using one or more pairs of magnets. In such an embodiment, the primary component includes one magnet of a pair of magnets and the secondary component includes the other magnet. The magnets are configured so that when the primary unit and the secondary unit are connected, there is a holding force between the pair of magnets, thereby holding the two components together. The magnets also provide a means for aligning the primary component and the secondary component in a repeatable manner.

[0284] exist Figure 2 and Figure 3In the spirometry configuration of FIG. 2 , the flow sensor 306 used to measure flow has a range of ± 200 liters per minute. This is lower than the typical flow rates of spirometry testing, which may be as high as ± 850 liters per minute. This flow sensor 306 was chosen because other tests performed by the device when the device is in other configurations require low flow rates. For these low flow applications, a flow sensor with a smaller range (i.e., a range significantly lower than ± 850 liters per minute) has sufficient resolution. For higher flow applications, such as spirometry testing, the effective range of the flow sensor 306 must be extended. This is achieved by the presence of the spirometry component 202, and in particular the bypass hole 210.

[0285] The design of the spirometry component means that the airflow channel 302 is effectively split. One channel is formed through the bypass hole and the other channel is formed to pass through the flow sensor, so only a portion of the airflow to or from the subject passes through the flow sensor. The airflow channels have different resistances, and it is the resistance of each channel that determines the proportion of air that flows through each channel. The resistance ratio of the airflow channels can be selected to ensure that the expected flow through the sensor always falls within the range of the sensor. The following relationship can be used.

[0286] (R_Bypass) / (R_Sensor) = (Maximum flow sensor range) / (Expected maximum subject flow - Maximum flow sensor range)

[0287] At the maximum expected flow from the subject, the portion of the flow in the air flow channel that passes through the flow sensor 306 is less than the maximum range of the flow sensor 306. The excess flow passes through the bypass holes in the spirometry component 202. The proportion of air that passes through the flow sensor compared to the air that flows out of the air bypass holes depends on the total air flow and is a non-linear relationship. The control circuit is programmed to scale any measured value at the flow sensor to a value that represents the total flow using the non-linear relationship.

[0288] With this configuration, the effective range of flow sensor 306 is increased from ±200 liters per minute to ±1000 liters per minute, as required for spirometry testing (up to ±850 liters per minute).

[0289] As part of the spirometry test, the control circuit receives measurements from the flow sensor 306 in order to calculate or measure several different indices. Each indices gives an indication of the mechanical properties of the subject's lungs. These indices include: Peak Expiratory Flow (PEF), Forced Expiratory Volume in 1 second (FEV1), Forced Expiratory Flow (FEF) and Forced Expiratory Volume (FEV), and finally Forced Inspiratory Flow (FIF). Lung volumes are calculated by integrating the flow over time.

[0290] To measure PEF, the subject inflates their lungs to maximum volume and then exhales at the highest flow rate they are able to produce. The PEF value is the maximum flow rate produced, measured in liters per minute by a flow sensor or pressure sensor.

[0291] To measure FEV1, the subject inflates their lungs to maximum volume and then exhales at the highest volume they are able to produce. The FEV1 value is the maximum amount of air that can be exhaled in the first second of exhalation, usually in liters.

[0292] FEF and FEV1 are similar to PEF and FEV1, respectively, but they are more general indicators that represent any expiratory flow and volume over any time interval rather than the fixed first second of exhalation, rather than the peak flow and volume. They can be measured at any time point during exhalation. FIF is also calculated, which is similar to FEF, but for inspiration rather than exhalation.

[0293] Tidal volume (VT) is calculated as the volume of gas exchanged in one breath of normal tidal breathing. Tidal breathing is defined as inspiration and expiration during steady breathing. When at rest, also known as "quiet breathing," tidal breathing tends to have a narrow range between breathing depth and expiration volume and tends to be fairly consistent. Respiratory disease can alter the normal characteristics of this breathing and cause inconsistencies from breath to breath.

[0294] Forced Vital Capacity (FVC) can also be calculated, which is the exchange volume between maximal inspiration and maximal expiration. Other volume measurements routinely used in clinical assessment and research can also be calculated using the device, most of which are calculated as the extreme inspiration or expiration relative to the minimum or maximum volume of tidal breathing.

[0295] In addition to using the above indicators alone, the control circuit 106 is also programmed to combine some indicators in order to calculate additional indicators. In this example, the ratio of FEV1 to FVC (expressed as a percentage) is used as an indicator of airway resistance or obstruction, and the control circuit calculates the ratio. A lower value of the ratio of FEV1 to FVC may indicate high airway resistance or airway obstruction. The presence of high airway resistance or obstruction indicates that the subject suffers from a respiratory condition, such as asthma or COPD, etc.

[0296] Multiple values ​​are calculated from a single inspiration and / or expiration. The test can be repeated and the highest, lowest or average of the test values ​​can be used as the reported value.

[0297] Spirometry metrics can be measured over time to monitor the progression of a subject's disease or to indicate whether a subject is responding to drug therapy. Spirometry metrics for a subject can be compared to expected values ​​for that subject given the subject's age, weight, height, race, sex, and other demographic variables. Spirometry values ​​can be measured before and after exposure to a trigger to determine whether the subject's respiratory condition is sensitive to the trigger. Spirometry values ​​can be measured before and after treatment, such as a bronchodilator, to determine whether the subject's respiratory condition is responsive to the treatment.

[0298] The device 100 can use Bluetooth to transfer data from the control circuit 106 to a computer. This may be a portable computer, such as a laptop or a smart phone. The portable computer is configured to process the data to provide a test score, which can be used to help monitor or diagnose respiratory diseases. This processing of data can include plotting flow versus time, volume versus time, and volume versus flow. The shape of the curves on these graphs at different events in the respiratory cycle can indicate the respiratory condition of the subject. Other data transmission devices are also feasible, such as a wired connection between the device and an external computer. In some embodiments, the device will use the control circuit to process the data internally. The test score and other data output values ​​can then be displayed to the subject on a display screen integrated into the device. This may include displaying a graph.

[0299] In the spirometry configuration, the air bypass holes 210 of the spirometry component 202 change the airflow path so that the flow sensor is suitable for performing a spirometry test. By changing the spirometry component connected to the main component to another component (or simply by removing it), different airflow paths are created to perform different respiratory diagnostic tests.

[0300] Figure 6is a perspective view showing the apparatus 100 for performing multiple respiratory diagnostic tests in a second configuration for performing a second diagnostic test. In this case, the spirometry component 202 is no longer engaged with the primary component 102. Instead, the secondary component connected to the primary component 102 is the nitric oxide sensor module 602. Figure 7 A second airflow channel 702 is shown in this configuration.

[0301] In the second configuration, the device is configured to perform a diagnostic test that involves measuring the concentration of nitric oxide in exhaled breath. The second secondary component in this configuration is the nitric oxide sensor component 602. In this configuration, the primary component 102 is the same as in the first configuration. The control circuit 106 is also the same. In this embodiment of the device, the mouthpiece 603 is different from the mouthpiece 204. The mouthpiece 603 includes a gas dryer 704 that the mouthpiece 204 does not include. In some other embodiments, the same type of mouthpiece 204 can be used in both the first configuration and the second configuration. In these embodiments, the gas dryer 704 can be located in the nitric oxide sensor component 602.

[0302] The nitric oxide sensor 604 is at the bottom of the nitric oxide sensor assembly 602. The nitric oxide sensor 604 is an electrochemical sensor and is an AlphaSense NO-B4, which can be obtained from Sensor Technology House 300 Avenue West, Skyline 120, Great Notley, Braintree CM77 7AA. The sensor contains an electronic board that establishes an electrode voltage for the electrochemical reaction within the sensor and amplifies the signal generated by the sensor. The concentration of exhaled nitric oxide is measured by the nitric oxide sensor 604. The measurement is received by the control circuit. The nitric oxide sensor assembly 602 is electrically connected to the control circuit 106. The control circuit 106 provides power and receives data from the nitric oxide sensor module 602 through an electrical connection. The nitric oxide sensor module has two outlet holes 608. Figure 6 Only one of them is visible in the Figure 7 , air flow channel 702 is shown as branching within the nitric oxide sensor module as it passes through exit aperture 608 .

[0303] The nitric oxide sensor component 602 utilizes an additional connection mechanism. The threaded knob 606 of the nitric oxide module 602 passes through the mounting plate 212 and enters a guide (not visible) in the nitric oxide module. The threaded knob 606 at the top of the device axially positions and secures the nitric oxide sensor component to the device. The electrochemical sensor is sensitive to its direction relative to gravity and vibration. Aligning the guide and threaded knob 606 helps ensure that the central axis of the cylindrical sensor is vertically aligned and the correct side is facing up.

[0304] Nitric oxide concentrations are used to indicate biological processes such as eosinophil activity, among others. Eosinophil activity can be elevated as part of the airway inflammatory process. High exhaled nitric oxide concentrations can be used as an indicator for the subtype of respiratory disease and the likely response to inhaled corticosteroids. Exhaled nitric oxide concentrations can be monitored over time to determine response to treatment, to anticipate onset or exacerbation or periods of severe symptoms, to determine whether a subject is taking prescribed medications regularly and with good technique, and to titrate the therapeutic dose to a level that controls the subject's condition but is not excessive and potentially wasteful and can cause side effects.

[0305] The control circuit 106 or a separate computing device is configured for the exhaled nitric oxide test. The software is configured to obtain data from the sensors used in this configuration and display the data and calculated values ​​of the subject's test. The software can also instruct the subject on how to perform the test.

[0306] In the nitric oxide breath test, the subject exhales into the mouthpiece 204 at a slow and constant flow rate of about 50 mL / s ± 10% and for 10 seconds for adults or 6 seconds for some children. The intention of this test is to measure the nitric oxide produced from the distal airways. The distal airways are airways with a diameter of less than 2 mm. These airways contribute to gas exchange in the lungs and cause only a small part of the total airflow resistance to breathing. The distal airways promote laminar flow of air. Exhalation should be against the positive expiratory pressure caused by the increased resistance to the expiratory flow in the device. The positive expiratory pressure ensures that the nasal palate remains closed. The expiratory pressure should be at least 5 cm H2O to keep the soft palate closed, but pressures above 20 cm H2O may cause discomfort to the subject. The air in the nasal passages may have high concentrations of nitric oxide, which can contaminate the air exhaled from the lungs if the soft palate opens during exhalation.

[0307] The gas dryer 704 in the mouthpiece 603 acts as a flow resistor to increase the exhalation pressure above 5 cm H2O, but keep it less than 20 cm H2O. This is in contrast to the spirometry configuration, where it is desirable for the flow resistance to be as low as possible. The mouthpiece 603 may also include a microbial filter to avoid spreading infection from multiple subjects using the device. The microbial filter is not shown.

[0308] Compared to spirometry testing, the exhaled air flow is lower and therefore the exhaled air volume is smaller. Therefore, there is a greater need to minimize the unused volume or dead space volume within the airflow channel 702. The gas dryer 704 and microbial filter take up space within the mouthpiece 603, thereby reducing the internal volume of the flow channel 702. The exhaled air entering the nitric oxide sensor module 602 from the sensor assembly 304 flows parallel to the nitric oxide sensor 604. The nitric oxide sensor module 604 has two outlet holes, both of which are at right angles to the incident airflow channel 702, which is in the Figure 7 604. Thus, the nitric oxide sensor module 604 creates a T-junction in the airflow channel. In some embodiments, the nitric oxide sensor module 604 instead creates a Y-junction. This is the case when the two outlet holes are at an acute angle to the incident airflow channel 702. The change in flow direction over the sensing surface of the electrochemical sensor promotes air mixing and avoids air stagnant areas near the surface membrane of the sensor. The outlet of the airflow channel 602 is preferably close to the nitric oxide sensor.

[0309] In another embodiment, the subject can exhale at a constant rate through their nose rather than their mouth to measure the concentration and production rate of nitric oxide in the nasal passages. In this embodiment, a nasal mask is used instead of a mouthpiece.

[0310] Nitric oxide sensor 604 is an electrochemical sensor. Electrochemical sensors use reactions in electrochemical cells to detect the presence of gas. The temperature, humidity and pressure of the environment can affect the physical effects of these reactions. The rate of change of humidity and pressure changes from the airflow can also affect these reactions. These changes in the reaction can change, causing the measurement of nitric oxide concentration to be inaccurate.

[0311] Exhaled air contains a high moisture content, typically much higher than the ambient humidity of inhaled air. As previously described, the mouthpiece 603 includes a gas dryer 704 formed of a hygroscopic material. This absorbs moisture present in the exhaled air, thereby avoiding the formation of condensation on the flow sensor 306, the ambient sensor 208 and the nitric oxide sensor 604, which could cause errors in the measurements made by these sensors. The hygroscopic material reduces the relative humidity of the air in the airflow channel 702 to be as close as possible to the relative humidity of the surrounding environment.

[0312] In alternative embodiments of the device, the absorbent material, microbial filter and flow resistor may be located in a secondary component rather than in the mouthpiece.

[0313] The axial distance between the mouthpiece 106, flow sensor 306, ambient sensor 208, and nitric oxide sensor module 602 is minimized. The low axial distance between these components results in a small internal volume for the device, thereby minimizing wasted volume in the flow passage 702. An additional advantage of reducing the axial distance between the sensors is that this ensures that the air characteristics for each of the sensors are similar at any given time.

[0314] At the beginning of exhalation, the air pressure in the airflow channel 702 increases with the downstream resistance and flow rate. Since the nitric oxide sensor has cross-sensitivity to pressure and pressure changes, the rate of pressure change at the beginning of exhalation should be minimized. Positioning the nitric oxide sensor near the outlet minimizes the downstream resistance between the nitric oxide sensor and the outlet, thereby minimizing pressure transients and thus minimizing the response of the nitric oxide sensor to pressure transients.

[0315] The respiratory tract is divided into the upper airway and the lower airway. The upper airway includes the nose and nasal cavity, pharynx and larynx. The lower airway includes the trachea, main bronchi and lungs. In tests such as nitric oxide testing, air from the lower airway is important. When exhaling, the first 3 seconds of the exhalation may contain air from the upper airway mixed with air from the lower airway. In some embodiments, the control circuit includes instructions to ignore this three-second portion of the exhalation for the nitric oxide concentration measurement. In other embodiments, the control valve can direct different durations or portions of the exhaled air toward or away from specific sensors in the device.

[0316] It has been described how device 100 can have multiple configurations. Figure 8 is a schematic diagram of four different configurations of the device showing the components that form the airflow path in each of those configurations. Figure 8 and Figure 1 The difference is that Figure 8 The sensors found in each component are shown. These sensors are generally shown as sensor numbered 1 through sensor numbered 6. Each of these sensors is different. In each configuration, the primary component includes the same four sensors 1 through 4. Secondary components may or may not include additional sensors.

[0317] Figure 8 a shows the device 100 in a configuration where the airflow channel is formed only by the main component 102. This configuration is the most basic configuration of the device. This configuration of the device can be used to perform a spirometry test. Fig. 9 Describe the configuration. The main components include sensors 1 to 4, which can be used to measure parameters of the air in the air flow channel. The four sensors are a flow sensor, a temperature sensor, a humidity sensor, and a pressure sensor. Figure 8Each of these configurations of the device shown in comprises the same main component 102 and therefore the same four sensors.

[0318] Figure 8 FIG. 1B shows how the device 100 may be configured differently in this case in a different spirometry configuration. In this configuration, the secondary component 802 is connected to the primary component 102, thereby defining an airflow channel through the primary component 102 and the secondary component 802. The device in this configuration can be used to perform a spirometry test and has been described above with respect to Figure 2 and Figure 3 The secondary component 802 does not include any sensor. Figure 8 Compared to the airflow path defined by the device of a, the secondary component changes the airflow path defined by the device. The secondary component 802 can be equivalent to Figure 2 and Figure 3 The spirometry component 202 may include an air bypass hole that changes the airflow path. As will be described, this configuration may also be applied to oscillation method testing.

[0319] Figure 8 c shows another configuration of the device, which has a secondary component 804 that is different from the secondary component 802 and is connected to the main component 102, thereby defining an airflow channel through the main component 102 and the secondary component 804. The device in this configuration can be used to perform a biomarker test, where the biomarker can be, for example, nitric oxide concentration. Figure 6 and Figure 7 Such a test is described in detail in the following. Secondary component 804 includes sensor 5. In the case where the biomarker is nitric oxide concentration, sensor 5 is equivalent to Figure 6 and Figure 7 The nitric oxide sensor 604 is a nitric oxide sensor, and the secondary component 804 is a nitric oxide sensor module.

[0320] Figure 8 d shows another configuration of the device, which has a secondary component 806 different from the secondary component 802 or the secondary component 804, and the secondary component 806 is connected to the main component 102, thereby defining an airflow channel by the main component 102 and the secondary component 806. The device in this configuration can be used to perform a test on a biomarker that is not nitric oxide, for example, the biomarker can be carbon dioxide. Therefore, the difference between the secondary component 806 and the secondary component 804 is that the secondary component 806 includes a sensor for detecting carbon dioxide instead of nitric oxide. Such a test is called a capnometry test, and it will be described in more detail below.

[0321] Fig. 9 is Figure 2 and Figure 8 In an alternative embodiment to the embodiment shown in b, a device for performing a spirometry test such as Figure 8 a. The device in this configuration has only major components, including the flow sensor 306 and the control circuit 106 connected to the mouthpiece 204. There is no spirometry component 202, and therefore no air bypass hole 210. Therefore, all air passes through the flow sensor 306. Figure 2 , and thus the flow sensor is designed to have a range that is less than the typical flow rates used in spirometry testing. In this embodiment, the control circuit 106 receives a signal from a pressure sensor, which is one of the environmental sensors 208, and uses the measurement from that sensor in conjunction with the measurement from the flow sensor 306 to generate a flow measurement that may be outside the normal range of the flow sensor 306, which is less than the high flow rates used in spirometry testing as previously described.

[0322] The control circuit 106 primarily uses the measurements from the flow sensor 306 to measure low flows. The pressure sensor is primarily used to measure high flows. Fig.10 is a graph showing how the signals from the flow sensor and the pressure sensor can be combined. The graph shows the flow over time as the subject performs a series of inhalation and exhalation breathing maneuvers. For each breathing maneuver performer, the flow increases from zero to the peak flow and then decreases back to zero. The true value is represented by 1002.

[0323] The flow rate measured by the flow sensor is represented by 1004. For low flow rates, the flow sensor is accurate and the measured value of the flow rate is close to the true value. However, once the flow rate exceeds the maximum range of the flow sensor, the flow sensor cannot measure the flow rate.

[0324] The flow rate measured by the pressure sensor is represented by 1006. For low flow rates, the pressure sensor is much less accurate than the flow sensor and tends to underestimate the flow rate. However, as the flow rate increases, the accuracy of the pressure sensor improves. At flow rates above the maximum range of the flow sensor 306, the pressure sensor is able to measure the flow rate reasonably accurately and provide a value close to the true value.

[0325] The control circuit is programmed to combine the measurements it receives from the flow sensor and the pressure sensor to give a measurement that accurately reflects the true flow rate. The benefit of the combined measurement is that the flow sensor has accuracy at low ranges, while the pressure sensor has a wide range for higher flow rates. In other embodiments of the device, humidity and temperature sensors may be used in addition to the pressure sensor to provide other measurements that can be used to adjust the flow measurement to account for humidity and temperature conditions.

[0326] Fig. 9 The spirometry configuration of is an example of how the control circuit can be configured to adjust the measurements it receives from one of these sensors of the device, which measurements may form an indicator for one of the respiratory diagnostic tests that use other measurements or signals received from another sensor or sensors. The microprocessor is programmed with various models that describe how the system behaves given certain input values. This may include a different model for each of the different configurations. It can use these models to adjust measurements that may be inaccurate.

[0327] The nitric oxide concentration test described previously also uses an adjustment process. One of the limitations when performing a nitric oxide concentration test is the cross sensitivity of the electrochemical sensor 604 and the degree to which it is affected by changes in ambient environmental conditions. Figure 6 and Figure 7 An apparatus configured to perform a nitric oxide concentration test is described. Gas dryer 704 is used to reduce the effect of environmental conditions on the measurements taken by nitric oxide sensor 604. However, control circuit 106 can be programmed to be able to use measurements from sensors measuring environmental conditions (i.e., pressure, temperature, and humidity) to further adjust the measurements from nitric oxide sensor 604.

[0328] Exhaled breath has a relative humidity of nearly 100%, which is higher than typical ambient relative humidity. Exhaled air replaces the ambient air at the electrochemical sensor surface and therefore experiences a high rate of change in relative humidity at the surface of the nitric oxide sensor 604. This rapid change in humidity results in an electrochemical sensor output response that cannot be easily distinguished from the response caused by changes in nitric oxide concentration. Therefore, the measurement will be inaccurate.

[0329] The humidity sensor measures the moisture content in the air passing through it. The control circuit 106 receives the measured values ​​from both the humidity sensor and the nitric oxide sensor 604. The control circuit 106 is programmed with a model of the behavior nitric oxide sensor 604 and its response to different environmental conditions. It uses those models to calculate the true concentration of nitric oxide by compensating for the portion of the relative humidity rate of change in the signal of the nitric oxide sensor. The nitric oxide sensor is also sensitive to the rate of change of pressure, temperature and flow. In certain embodiments, the measured values ​​from the electrochemical sensor are further compensated by the control circuit system 106 using the measured values ​​of pressure, temperature and flow through a more complex model programmed into the control circuit system 106.

[0330] Fig.11 1104 shows the nitric oxide concentration measured directly from the electrochemical sensor. These measured values ​​are inaccurate and far below the true value. 1106 shows the relative humidity adjustment factor, which is calculated as the negative rate of change of humidity expressed as a percentage. Subtracting the value of line 1106 from the value of line 1104 will cause the adjusted signal to be closer to the true value 1102. This subtraction is demonstrated by highly equal lines 1108 and 1110. In some embodiments, temperature, pressure and flow adjustment factors may also be calculated and may also be subtracted from the measured nitric oxide concentration 1104.

[0331] The adjustment process will now be generally described. The control circuit can receive a measurement of parameter A from a first sensor, which is a parameter of interest and can be used to form an indicator that can be used for monitoring or diagnosing respiratory diseases. The measurement of parameter A may have limitations, particularly in terms of measurement accuracy. Parameter B can be used to address these limitations in the model stored in the control circuit. Parameter B can be an environmental parameter such as temperature, pressure, or humidity. The sensor is used to measure parameter B received at the microprocessor. Parameter B is typically measured by a second sensor. However, in some embodiments, parameter B can be calculated based on the measurement of parameter A. For example, parameter B can be the rate of change of parameter A and is calculated by the microprocessor. The adjustment improves the accuracy and repeatability of the measurement of parameter A. In some cases, a linear model is used, and in other cases, it is more accurate to use a more complex nonlinear model.

[0332] The accuracy of the measured value of parameter A may depend on any number of additional parameters (parameter C, parameter D, etc.). Each of these parameters may also be measured. The model that the microprocessor is programmed with includes these additional parameters, so the measured value of parameter A can be adjusted based on any or all of the dependent parameters. In many embodiments and configurations of the device, there will be more sensors than parameters measured, and it is not required that all sensors be used. The sensors can be turned on and off by the control circuit as needed.

[0333] In each configuration of the device 100 , a subset of sensors is used to measure the relevant parameter A and any subsequent parameters required to adjust parameter A.

[0334] It is advantageous to share sensors between subsets of sensors in different configurations because it reduces the total number of sensors required. One sensor can be used in more than one test. If the various tests were performed by separate devices, sensors that were present in both subsets would need to be duplicated. Having one device that is configured to perform multiple tests allows for sharing of sensors, thus resulting in a reduction in the total number of sensors required to perform the same number of tests.

[0335] A subset of the sensors used in the configurations of the devices described thus far will now be summarized.

[0336] like Figure 2 and Figure 3 As shown in and by Figure 8 The first spirometry configuration represented by b has a subset of sensors including only flow sensors.

[0337] like Fig. 9 As shown in and by Figure 8 The second spirometry configuration represented by a has a subset of sensors that typically includes a flow sensor and a pressure sensor, and the control circuit is configured to use the measurements to adjust the measurement of flow to achieve a high flow measurement. In some embodiments of the second spirometry configuration, the subset of sensors may also include a temperature sensor and a humidity sensor. The control circuit is configured to use the measurements of temperature and humidity to adjust the measurement of flow.

[0338] like Figure 6 and Figure 7 As shown in and by Figure 8 The nitric oxide concentration configuration represented by c has a subset of sensors that typically includes a nitric oxide sensor, a pressure sensor, a temperature sensor, and a humidity sensor, wherein the control circuit is configured to use the measurements of pressure, temperature, and humidity to adjust the measurement of nitric oxide concentration. The subset of sensors may also include a flow sensor, and the control circuit is configured to use the measurement from the flow sensor to adjust the measurement taken by the nitric oxide sensor.

[0339] The flow sensor is common to a subset of sensors for both the first spirometry configuration and the second spirometry configuration. In embodiments where the flow measurement is used to adjust the nitric oxide concentration measurement taken by the nitric oxide sensor, the flow sensor is also common to a subset of sensors for the nitric oxide concentration configuration.

[0340] The pressure sensor is common to a subset of the sensors of the second spirometry configuration and the nitric oxide concentration configuration.

[0341] The temperature sensor and humidity sensor are common to both the nitric oxide concentration and the embodiment of the second spirometry configuration that uses the temperature sensor and humidity sensor to adjust the flow measurement taken by the flow sensor.

[0342] Each of the configurations of devices described so far shares sensors with each of the other configurations.

[0343] Now refer to Fig.12 An example method of using device 100 is described below. Fig.12 It is a flow chart of how to use the device.

[0344] At step 1202, the device is placed in a first configuration. The first configuration may be Figure 2 204 is connected to the spirometry component 202 for the subject to breathe into. A new mouthpiece is used for each individual subject of the device. Only the required sensors need to be turned on. The turning on and off of the sensors is managed by the control circuit. In some embodiments, the control circuit can detect which configuration the device is in and automatically turn on the correct sensors, in other embodiments, the subject input indicates the configuration to the control circuit.

[0345] At step 1204, the subject completes breathing maneuvers with the device in the spirometry configuration. In some embodiments, the control circuitry instructs the subject what these maneuvers should be. However, a trained medical professional can instruct the subject. Alternatively, an instruction manual can be provided. These breathing maneuvers include forced exhalation. Measurements of flow are received at the control circuitry 106 from the flow sensor 306. As previously described, when the device is in the configuration with the spirometry component 202, the control circuitry 106 will adjust the measurements so that they are scaled up to account for the airflow lost through the air bypass holes 210.

[0346] In step 1206, after the breathing maneuver is completed, the control circuit outputs the results of the spirometry test. For example, this can be accomplished by wireless data transmission to a smartphone or computer. The wireless data transmission can be performed via Bluetooth. In some embodiments, a display can be built into the device itself, which displays the results of the test. In some embodiments, software stored in the control circuit or on a computer or portable device can be used to process the results of the test and provide a simplified test score or result. In some embodiments, the results of the test can be stored to maintain a record of past tests. Records of past tests can be used in diagnostic procedures and to monitor changes in the health of the subject over time.

[0347] At step 1208, the device is placed in a second configuration. The second configuration may be Figure 6 . To achieve this configuration, the spirometry component 202 is disconnected from the main component 102. The mouthpiece 603 is then connected to the main component 102 at the location where the spirometry component 202 was connected. At the other end of the main component 102, the nitric oxide sensor module 602 is connected. This defines an airflow path through the mouthpiece 204, the main component 102, and into the nitric oxide sensor module 602. In this configuration, the control circuit turns on the nitric oxide sensor 604, the flow sensor 306, and the environmental sensors 208 including the pressure sensor, the temperature sensor, and the humidity sensor.

[0348] In step 1210, the subject completes a breathing maneuver through the device 100 in the nitric oxide concentration test configuration. Again, in some embodiments, the control circuit 106 indicates to the subject what these actions should be. However, a trained medical professional can guide the subject. Alternatively, an instruction manual can be provided. These breathing maneuvers include slow inhalation and exhalation. The measured value of the nitric oxide concentration is received from the nitric oxide sensor 604 at the control circuit 106. The control circuit 106 will use the measured values ​​from the flow sensor, pressure sensor, temperature sensor and / or humidity sensor to adjust the measured value of the nitric oxide concentration to take into account the cross sensitivity of the nitric oxide sensor 604.

[0349] In step 1212, after the breathing maneuver is completed, the control circuit can output the results of the nitric oxide test. For example, this can be accomplished by wireless data transmission to a smartphone or computer. The wireless data transmission can be performed via Bluetooth. In some embodiments, a display can be assembled into the device itself, which displays the results of the test. In some embodiments, software stored in the control circuit / microprocessor or on a computer or portable device can be used to process the results of the test and provide a simplified test score or result. In some embodiments, the results of the test can be stored to maintain a record of past tests. Records of past tests can be used in diagnostic procedures and to monitor changes in the health of the subject over time.

[0350] The results of the spirometry test and the nitric oxide test may be presented together or in some combination to help diagnose and monitor specific respiratory diagnostic conditions.

[0351] To demonstrate that the device may be configured to perform a number of respiratory diagnostic tests, a spirometry test and a nitric oxide test have been used as examples of respiratory diagnostic tests that the device may be configured to perform. Another example of a test that the device may be configured to perform is an oscillometric test, which is another diagnostic test that can help diagnose respiratory diseases such as COPD. An oscillometric test is used to indicate the mechanical properties of a subject's airways. A device in an oscillometric configuration such as Fig.13 as shown in .

[0352] In the oscillation method configuration, the device comprises a primary component 102 with a microcontroller 106. The primary component 102 is connected to the mouthpiece 204 on a first side and to a secondary component on a second side.

[0353] The secondary component is an oscillating method module 1302. In order to connect the oscillating method module 1302 to the primary component 102 via the mounting plate, the secondary component includes a threaded knob 1303 that passes through the mounting plate 212 of the primary component 102 and screws into the secondary component. This allows for secure and repeatable alignment of the secondary component with the primary component.

[0354] The oscillation method module 1302 includes an occluder 1304 and a device for moving the occluder 1305. The device for moving the occluder is a linear actuator. The occluder may have a diameter of about 40 mm. The device for moving the occluder has a stroke length of about 9 mm. The occluder includes an O-ring 1306. The oscillation method module 1302 is in electrical contact with the main component 102. This means that signals can be sent and received from the microcontroller 106 in the main component to the oscillation method module 1302.

[0355] Fig.14 is and Fig.13The same side view of the device 100 is shown, but showing the occluder 1304 in the second position instead of the first position. Figure 2 , the O-ring 1306 of the occluder 1304 is shown in contact with the housing 209 of the main component 102.

[0356] The microcontroller 106 may send a signal to the linear actuator to cause the linear actuator to move the occluder 1304 from Fig.13 The position shown in (which is the first position) is moved to Figure 2 1302 (which is the second position). Power can also be delivered to the oscillatory method module 1302 through the electrical contacts. This provides power to the linear actuator, which can be used to move the occluder between the first position and the second position. The force of the linear actuator can cause vibrations through the device, which cause the oscillatory method module 1302 to move relative to the main component 102. Connecting the oscillatory method module to the main component 102 using a threaded knob 1303 reduces this movement.

[0357] In some embodiments of the device, the oscillation method module 1302 includes a battery in addition to a power source for powering the control circuitry of the main component 102. The power requirements of linear actuators (e.g., solenoids, etc.) are higher than what many small batteries can produce. By having an additional battery located in the oscillation method module 1302, the power provided to the linear actuator can be increased to the desired level.

[0358] When the occluder is moved from the first position to the second position, the O-ring 1306 prevents damage to the housing 209 or the occluder 1304. In many embodiments of the device, when the occluder is in the second position, the O-ring 1306 does not contact the housing 209. Instead, there is a gap of at least 0.5 mm between the housing 209 and the O-ring 1306. However, in all embodiments, the occluder 1304 in the second position will be closer to the housing 209 than in the first position.

[0359] Fig.151 is a cross-sectional view of the oscillation method module 1302 independent of the rest of the device 100. The linear actuator 1305 includes a body 1502 and a solenoid. The linear actuator is a Johnson Electric Model 51STA Push DC TubularSolenoid or Mecalectro Solenoid Latching-8.MB0.AA.29, both of which are available from RS Components: https: / / uk.rs-online.com / web / . When a first voltage is applied to the solenoid of the linear actuator, a force is applied to the occluder 1304 so that the occluder moves from a first position to a second position. When the power is turned off, the occluder 1304 will move back to the first position. This may be due to a bias spring or magnetic reset system not shown. In some embodiments, the linear actuator is a push-pull linear actuator. In these embodiments, when a voltage of a different polarity than the first voltage is applied to the linear actuator, the occluder is returned to the first position by the force applied by the linear actuator.

[0360] The control circuit 106 is configured to cause the linear actuator 1305 to move the occluder 1304 from the first position to the second position and back to the first position at least three times per second during the test period. Multiple acoustic pulses are generated throughout the test to provide a comprehensive understanding of the airway and show how the airway changes throughout breathing.

[0361] Fig.16 is a cross-sectional perspective view of the device 100 . Fig.16 An airflow channel represented by a dotted line 1602 through the device 100 is shown. The airflow channel is defined by the mouthpiece 202 and the housings 207 and 209 of the main component 102. The airflow channel 1602 terminates at an air outlet. The air outlet is at the end of the housing 209 closest to the occluder 1304. If the direction of flow of air in the airflow channel is toward the mouthpiece, the air outlet will instead become an air inlet. In either case, the air outlet or air inlet is the same and is located at the end of the housing 209 closest to the occluder 1304. The direction of movement of the occluder from the first position to the second position is parallel to the airflow channel.

[0362] If when the occluder is in the second position, the O-ring 1306 contacts the housing 209, the airflow channel 1602 is sealed at the outlet. In this case, when the occluder is in the second position, air cannot escape from the airflow channel to the outlet.

[0363] However, when the occluder is in the second position, the O-ring 1306 may not be in contact with the housing 209, and there may be a gap of at least 0.5 mm between the O-ring 1306 and the housing. Then, the airflow channel is not sealed at the outlet. In this case, when the occluder is in the second position, air can escape the outlet from the airflow channel.

[0364] Figure 3 , Figure 7 and Fig.16 Shown is a cross-sectional perspective view of the device 100 in different configurations for performing different respiratory diagnostic tests. In these figures, flow sensor 306 and sensor assembly 304 have been shown as two separate components at different positions in the air flow channel. However, the position of flow sensor 306 and sensor assembly 304 is not necessarily in the position as shown in the figure. In addition, sensor assembly 304 can actually include several different sensors located along the air flow channel. For example, in the oscillation method configuration, the time-varying signal from pressure sensor and flow sensor is used to calculate the result. Therefore, it is advantageous to make the pressure sensor be located as close to flow sensor 306 as possible in the flow channel. In the configuration for measuring the concentration of nitric oxide in the exhaled breath, the measured value of nitric oxide depends on humidity. In that case, it is advantageous to position the humidity sensor at the far end of the air flow channel, away from the mouthpiece and as close to the nitric oxide sensor 604 as possible.

[0365] Now about Fig.17 A method for using a device in an oscillometric configuration to perform an oscillometric test is described. In step 1702, the subject breathes through the device. The required breathing is continuous, constant breathing or normal tidal breathing. Preferably, the subject breathing into the device uses a nose clip. Clipping the nose can improve the results of the oscillometric test. During the test, the subject continues to breathe through the device. The subject inhales and exhales through the mouthpiece 204 of the device. The subject's breath will enter and exit their airway through the airflow channel 1602. When the subject inhales, air will enter the airflow channel 1602 through the air inlet, which is located at the end of the housing 209 closest to the occluder 1304. When the subject exhales, air will flow out of the air channel through the air inlet, at which time the air inlet is considered to be the air outlet.

[0366] In some embodiments, the subject can only inhale through the device 100. In these embodiments, air enters the device through the air inlet, passes through the air flow channel 1602 toward the mouthpiece 204, and enters the airway of the subject. The subject will then exhale directly into the atmosphere, so the exhaled air will not pass through the air flow channel 1602 of the device.

[0367] In some embodiments, the subject can only exhale through the device 100. In these embodiments, the subject will inhale air directly from the atmosphere. The subject will then exhale through the mouthpiece 204 of the device 100. The exhaled air will pass through the airflow channel 1602 of the device 100 and out of the air inlet.

[0368] At step 1704, an acoustic pulse is generated in the air in the airflow channel. When the occluder 1304 is moved from a first position to a second position by the linear actuator 1305, an acoustic pulse is generated. The direction of movement of the occluder 1304 from the first position to the second position is in the direction of the mouthpiece 204. This movement has the effect of pushing the air in the airflow channel 1302 in the direction of the mouthpiece 204. The result of pushing the air is a pulse of increased flow through the airflow channel 1302 in the direction of the mouthpiece. The occluder is moved by the linear actuator 1305 with sufficient force so that the push on the air in the airflow channel 1602 results in an increased flow of at least 0.15 liters per second in the direction of the mouthpiece.

[0369] The flow pulse through the airflow channel causes a pressure transient with an amplitude of at least 50Pa. The acoustic pulse travels through the airflow channel 1602 and enters the subject's airway, causing changes in the pressure and flow of the air passing the sensor. As the acoustic pulse travels, it experiences damping. This causes the amplitude of the pressure and flow to decrease. An increase in flow of 0.15 liters per second and an increase in pressure of 50Pa in the direction of the mouthpiece is sufficient to provide a significant and measurable response.

[0370] The acoustic pulses consist of sinusoidal pressure fluctuations with a frequency between 5 Hz and 20 Hz.

[0371] At the end of step 1704, after the acoustic pulse has been generated, the occluder returns to the first position.

[0372] The flow resistance when the occluder 1304 is in the second position will be greater than the flow resistance when the occluder is in the first position. When the occluder is in the second position, the higher resistance may cause the pressure in the airflow channel 1602 to change. The change in pressure may affect the characteristics of the acoustic pulse. The length of time that the occluder is in the second position and the configuration of the occluder may affect the amount of pressure change in the airflow channel, thereby affecting the characteristics of the acoustic pulse. The configuration of the occluder specifically refers to the amount of flow resistance increased by the occluder when the occluder is in the second position compared to when it is in the first position.

[0373] If the flow resistance in the airflow channel is low enough when the occluder is in the second position, the pressure accumulated in the airflow channel will be negligible. Therefore, the change in the acoustic pulse characteristics is also negligible. In this case, the occluder in the second position does not contact the housing 209 of the main component 102, and there is a gap of at least 0.5 mm between the occluder and the housing 209. When the occluder is in the second position, air is still able to flow through the device, and the resistance of the occluder in the second position is not as high as if the occluder is closer to the housing or in contact with the housing. The pressure change when the occluder is in the second position can also be reduced by limiting the amount of time the occluder is in the second position. The occluder stays in the second position for no more than 20ms before returning to the first position.

[0374] Because the occluder is in the second position, the pressure change in the airflow channel is negligible, which means that a relatively simple mathematical model is required. This simplifies the mathematical operations, especially the calculations using fast Fourier transforms. The minimal pressure buildup is also more comfortable for the subject using the device. If the pressure change in the airflow channel is too great, the subject will notice the change when breathing through the device, which may cause discomfort and interrupt Cheyne-Stokes breathing.

[0375] If the flow resistance in the airflow channel is significantly higher when the occluder is in the second position and the occluder is in the second position for a considerable period of time, the pressure change in the airflow channel will not be negligible. Therefore, the change in the acoustic pulse characteristics will not be negligible. When the occluder is in the second position, there may be a gap of less than 0.5 mm between the occluder and the housing 209 of the main component 102. There may be no gap between the occluder and the housing 209. The length of time that the occluder is in the second position may be longer than 20 ms.

[0376] The change in the characteristic of the acoustic pulse may be an increase in the amplitude of the acoustic pulse. This is because the pressure accumulated in the air flow channel contributes additional energy to the acoustic pulse. This is also because the occluder in the second position directs the energy of the acoustic pulse more effectively into the air flow channel and towards the mouthpiece.

[0377] At step 1706, the flow rate and pressure of the air in the airflow channel are sensed by the flow sensor 306 and the pressure sensor in the sensor assembly 304. The sensing determines the flow rate and pressure caused by the subject's breathing (which is normal tidal breathing). The control circuit receives the measured values ​​from the flow sensor and the pressure sensor. The control circuit will analyze the signal by performing a Fourier transform. The pressure fluctuations at a frequency from 5 Hz to 20 Hz can then be continuously measured. The control circuit stores the measured values ​​and the results of the Fourier transform.

[0378] In step 1708, the device generates an acoustic pulse by moving the occluder from a first position to a second position. The flow rate and pressure of the air in the airflow channel are continuously sensed by the flow sensor 306 and the pressure sensor in the sensor assembly 304 for a period of 150ms. The sensing period of 150ms starts immediately before the occluder starts to move from the first position to the second position. 150ms is long enough to measure immediately after the acoustic pulse has entered the airway of the subject and after the acoustic pulse is generated. The flow measurement value and the pressure measurement value are the superposition of the flow rate and pressure caused by the breathing of the subject and the flow rate and pressure caused by the acoustic pulse. The control circuit performs a Fourier transform on the pressure and flow signals and stores the measured values ​​and the results of the Fourier transform. In step 506, the measured values ​​of the superimposed flow and pressure can be compared with the measured values ​​of the flow and pressure. This allows the pressure and flow signals caused by the breathing of the subject to be distinguished from the signal portion caused by the acoustic pulse and in response to the acoustic pulse. The control circuit can use the response of the acoustic pulse to calculate an indicator indicating the characteristics of the airway of the subject.

[0379] During the test, steps 1704 to 1708 may be repeated any number of times as the subject breathes through the device. These steps may be repeated at least 3 times per second. The measurements taken each time steps 1706 and 1708 are performed are stored in control circuitry 106. Repeating steps 1704 to 1708 means that measurements may be taken throughout the breathing period, so any changes in the characteristics of the subject's airway may be detected.

[0380] In step 1710, the control circuit 106 outputs the results of the oscillometric test. For example, this can be accomplished by wireless data transmission to a smartphone or computer. The wireless data transmission can be performed via Bluetooth. In some embodiments, a display can be assembled into the device itself. In some embodiments, software stored in the control circuit 106 or on a computer or portable device can be used to process the results of the test and provide a simplified test score or result. In some embodiments, the results of the test can be stored to maintain a record of past tests. Records of past tests can be used for diagnostic procedures and to monitor changes in the health of the subject over time.

[0381] Note that the oscillation method configuration has a subset of sensors that includes a flow sensor and a pressure sensor. In some embodiments, the oscillation method configuration also includes a temperature sensor and a humidity sensor. In these embodiments, the control circuit is configured to use the measurements from the temperature sensor, the humidity sensor, and the pressure sensor to adjust the measurements taken by the flow sensor.

[0382] The flow sensor is the same as the previously mentioned flow sensor, so it is common to a subset of sensors for both the first spirometry configuration and the second spirometry configuration.The flow sensor is also common to the embodiment of the nitric oxide concentration configuration using the flow sensor.

[0383] The pressure sensor is the same as the previously mentioned pressure sensor, so it is common to a subset of the sensors of the second spirometry configuration and the nitric oxide configuration.

[0384] The device 100 may be configured to perform a capnography test. Capnography is the measurement of exhaled carbon dioxide. The capnography configuration of the device is similar to that of Figure 6 and Figure 7 The configuration for performing the nitric oxide concentration test shown in is very similar. In the case of carbon dioxide determination, the secondary components including the nitric oxide sensor 604 are replaced by a nearly identical secondary component, which instead includes a carbon dioxide sensor. The carbon dioxide sensor is a SprintIR-20 from Gas Sensing Solutions.

[0385] The CO2 sensor uses the principle of non-dispersive infrared absorption. It is sensitive to condensation, so a gas dryer is used to ensure that moisture does not condense at the sensor. The same gas dryer components can be used for both CO2 and NO testing. However, the CO2 test does not require the additional flow resistance that is required for the NO test, and preferably has a low flow resistance in the gas flow path.

[0386] In order to accurately record transients that show how CO2 concentration changes over time, it is best to use a sampling frequency of at least 20 Hz for the CO2 sensor. Peaks in CO2 concentration may be of interest. Capnography transients are thought to change as symptoms worsen and can provide a warning that a subject may soon have an asthma attack or COPD exacerbation. Higher peaks in exhaled CO2 indicate high CO2 concentrations in the blood. This suggests that the subject's respiratory or cardiovascular system is compromised.

[0387] The shape of the carbon dioxide concentration transient during tidal breathing can also be used as an indicator of breathing characteristics. A more gradual increase in exhaled carbon dioxide concentration may indicate respiratory obstruction or higher airway resistance. However, this method cannot distinguish whether the lower rate of increase in carbon dioxide concentration comes from slower airflow or slower transfer of carbon dioxide from the blood to the airway. In some embodiments, the carbon dioxide concentration measurement is combined with the flow measurement. This provides more information about the relative contribution of the exhaled carbon dioxide signal, i.e., whether it is related to the airflow indicator or to the rate of transfer of carbon dioxide from the blood to the air in the lungs.

[0388] In some embodiments, the capnometry configuration has a subset of sensors including a carbon dioxide sensor and a flow sensor. The flow sensor is common to both the first spirometry configuration and the second spirometry configuration, the subset of sensors of the nitric oxide testing configuration and the oscillometric measurement configuration.

[0389] In some embodiments, the device includes a display. The display can serve as a user interface for the device. The display or user interface can be a touch screen display. The user interface allows the subject to manually input data into the device, the subject to send instructions to the device, the device to provide instructions to the subject, and the device to present the results to the subject. It can be a trained medical professional to interact with the user interface instead of the subject. The display can be a part of the device. However, it can also be a part of a portable computer (such as a laptop or smart phone, etc.), and the control circuit can transfer data to the portable computer.

[0390] Fig.18 A first embodiment of a display screen on the interface of the device is shown. This shows the device in test mode. The interface in this embodiment is designed for subjects with limited medical training, so only simple feedback is provided to the subject instead of complex indicators.

[0391] The display includes an option 1802 for entering the subject for whom the test was conducted, which allows the results to be saved in a database belonging to the user. In this case, the subject is John Smith.

[0392] The display includes an option 1804 for indicating which test the device is about to perform. In this case, the test to be performed is a nitric oxide test. Figure 1 a to Figure 1 In an embodiment of the device of claim d, the device instructs the subject to reconfigure components of the device to modify the airflow path for the selected test. Figure 1 In an embodiment of the device of e, the device itself will reconfigure the components of the device to modify the airflow path required for the test. For example, the control circuit can send signals to valves between components to open or close to configure the airflow path through the device.

[0393] In alternative embodiments, after the subject has manually configured components of the device to modify the airflow pathway for the desired test, the device can detect what configuration it is in. In these embodiments, there is no need for the subject to select the test that the device will perform.

[0394] The subject can enter the data manually into the device. Fig.181806. Other useful data that can be manually entered include recent allergen exposure, weather, air quality, and medications taken. In some embodiments, additional data can be automatically imported from other sources such as wearable devices, smart inhalers, smartphones, electronic health records, or Internet-based APIs. The user interface can include an entry to view this additional data as well as data or results generated by tests on the device itself.

[0395] The display includes a test action input 1808 for instructing the device to begin a test or to cancel a test in progress.

[0396] The display includes a test instruction output 1809, which typically provides instructions to the subject after the test has begun. Fig.15 In the example above, the test being performed is a test for the concentration of nitric oxide in the exhaled air. This test needs to be performed with the subject controlling the exhalation. The rate of the exhaled air needs to be maintained at a controlled rate or flow and for a minimum duration. The display tells the subject if the exhalation rate is appropriate and how long they have been exhaling.

[0397] The display includes an output 1810 for showing the test results. In this example, the test is an exhaled nitric oxide test, so the output is the concentration of nitric oxide in parts per billion. The panel also provides the user with a test verification output 1812 to indicate to the user whether the result was successful or whether the next one needs to be repeated. Determining whether the test was successful may depend on whether the user followed the test guidance instructions described above.

[0398] Fig.19 Another embodiment of a user interface designed for medical professionals is shown. Fig.18 It allows medical professionals to review a subject's test with more detailed test results than traditional methods.

[0399] like Fig.18 As shown in , input buttons 1802 and 1804 allow selection of a subject and a test. In this case, the selected test is a spirometry test.

[0400] Test results panel 1810 shows the output metrics calculated from the test. Fig.181902 , but shows results for a different test (for a spirometry test instead of a FeNO test). The detailed test results 1902 panel shows a graph of the test results in more detail than the calculated metrics. An experienced and trained medical professional may gain additional detail from the graph in addition to the individual output metrics. Preferably, the metrics in the test results panel 1810 and the axes of the detailed test results panel 1902 graph are pre-populated based on the test type selected using the select test input button 1804. However, in some embodiments, the user can select which output metrics and axes are displayed.

[0401] In some embodiments, less detailed results of another test may be displayed in a separate panel of the display.The display of multiple tests allows a user to interpret results from multiple data sources together.

[0402] The display includes an input for adding details for the subject 1904. For example, entering details of the subject (such as height, weight, age, gender, and race, etc.) can be used to establish a predicted value for the test result.

[0403] exist Fig.15 and Fig.16 In both, the display includes an input button test history 1906, which the user selects to instruct the device to display previous results on the user interface. Pressing this button causes the device to display Fig. 20 The screen shown in , which is a display that calls up data from a previous test.

[0404] Fig. 20 The display shown in includes an input button 2002 for selecting the user for whom the display data is to be directed, an input button 2004 for placing the device into a test mode, and an input button 2006 for adding a test type to the display. After selecting a subject and a test, a graph of the test results versus time is plotted in panels 2008, 2010, and 2012 of the user interface. As illustrative examples, spirometry, exhaled nitric oxide, and manually entered data are plotted in the display. These displays can help a subject or medical professional understand the time history of indicators related to their medical condition. The benefit of having multiple tests on the device is that it is easier to display multiple tests in a comparable and interpretable manner.

[0405] Fig.21It is an additional display screen of the user interface, wherein the test result of the current subject is compared with the test result of other subjects. The input button allows the user to select subject 2102, the first index 2104 and the second index 2106. Two indicators are shown here by way of example; this display screen can also be used with one indicator or more than two indicators. A curve graph on the main panel 2108 is generated and displayed, which is compared with the results of these tests for subject 2102 and the results of other subjects from different subject groups in the existing database together with the graphical representation of these different groups shown in the explanation panel 2110. Other subjects can be classified into, for example, a group, b group and c group. This classification and display screen can help the user determine whether the current subject has a feature similar to the classified group of other subjects from the existing database. Subjects can be divided into a group, b group, c group, etc. based on the successful response to a specific treatment, or if it is known that these people have a certain disease subtype.

[0406] Fig. 22 An embodiment of the device is shown, wherein the primary component is enclosed by a housing 2202 and the secondary component is enclosed by a housing 2204. The housing for the secondary component 2204 includes an opening 2206 corresponding to the air inlet and in fluid communication with the airflow channel. Air can pass through the opening 2206. The housings 2202 and 2204 provide protection to the components contained therein. Each of the secondary components already described can include such a housing. When an additional connection mechanism is required between the primary component and the secondary component, this can be achieved by using one or more pairs of magnets in the housing not shown. The primary component includes one magnet in a pair of magnets, and the secondary component includes another magnet. The magnets are configured so that when the primary unit and the secondary unit are connected, there is a holding force between the pair of magnets, thereby holding the two components together. The magnets can also provide a device for aligning the primary component and the secondary component in a repeatable manner.

[0407] The opening 2206 can be optimized depending on the secondary components. Generally, preferably, the opening 2206 does not significantly increase the resistance of the airflow path defined as passing through the device. However, when the device is configured to perform an oscillation method test, the opening 2206 of the housing of the oscillation method module can be configured to increase the airflow resistance in the airflow channel. In particular, when the occluder is in the first position, the airflow resistance can be significantly increased through the opening 2206, but when the occluder is in the second position, the airflow resistance can be less significantly increased. For example, the system can be configured so that when the occluder is in the first position, a portion of the blocking mechanism partially blocks the opening 2206, but when the occluder is in the second position, a portion of the blocking mechanism does not partially block the opening 2206.

[0408] As described, the movement of the occluder from the first position to the second position increases the flow resistance in the airflow channel by reducing the gap between the occluder and the housing. This helps to ensure that as much energy from the acoustic pulse is directed to the mouthpiece as possible, but the movement of the occluder from the first position to the second position can cause a relatively large increase in the total resistance in the airflow channel, which may affect the results of the oscillation method test and may make the subject uncomfortable. By reducing the resistance through the opening 2206 when the occluder moves from the first position to the second position, the increased resistance in the airflow channel caused by the reduction of the gap around the occluder can be partially offset by the reduction of the resistance through the opening 2206, while still maintaining the benefits provided by the occluder.

[0409] There are other methods for at least partially offsetting the increase in resistance caused by the reduction of the gap around the occluder. For example, the housing of the oscillation method module may include additional holes used as air inlets and outlets. In this embodiment, the occluder is configured so that the additional holes are blocked when the occluder is in the first position, and the additional holes are not blocked when the occluder is in the second position. Alternatively, it is possible to include an additional occluder at the opening 2206 for use with the first occluder. The additional occluder is configured so that, relative to when the first occluder is in the second position, the additional occluder blocks the opening 2206 to a greater extent when the first occluder is in the first position.

[0410] Fig.23a and Figure 23b It is about Figures 13 to 18 23 is a cross-sectional schematic diagram of another embodiment of an oscillation method module. In this embodiment, the oscillation method module 2302 includes an occluder 1304 and a device for moving the occluder 1305. Fig.23a In , the occluder 1304 is in the first position. Figure 23b In the embodiment of the present invention, the occluder 1304 is in the second position. As described above, the movement of the occluder 1304 from the first position to the second position generates an acoustic pulse in the air flow channel.

[0411] The oscillation method module 2302 includes a housing 2304 that communicates with the air flow channel defined in the main component 102. The housing 2304 is tapered, and the taper has a first tapered portion 2306 and a second tapered portion 2308. The shapes of the first tapered portion 2306 and the second tapered portion 2308 cause the housing 2304 to have a funnel-like shape.

[0412] At its maximum diameter, the second tapered portion 2308 has an opening that provides sufficient clearance around the occluder 1304 that, when in the first position, air passing through the gap between the housing 2304 and the occluder encounters little resistance. As the occluder moves from the first position to the second position, the gap between the occluder 1304 and the housing 2304 decreases, while the flow resistance increases. In the second position 2304, the occluder is adjacent to the widest portion of the first tapered portion. The diameter of the widest portion of the first tapered portion 2306 is similar to or the same as the diameter of the occluder 1304. If the occluder has a diameter of 40 mm, the widest portion of the first tapered portion may have a diameter slightly larger than 40 mm. In embodiments where complete occlusion is desired, the diameter of the widest portion of the tapered portion is equal to the diameter of the occluder. The narrowest portion of the first tapered portion 2306 is 20 mm. The housing 2304 having this shape causes the energy from the acoustic pulse to be directed toward the mouthpiece into the airflow channel of the device. With Fig.13 Compared to the embodiment of the oscillating method module shown in , less energy is lost to the surrounding environment.

[0413] Fig.24a and Figure 24b FIG. 2 is a cross-sectional view of another embodiment of the oscillation method module 2402. Fig.24a and 24b 2404. The oscillation method module 2402 includes an occluder in the form of a shutter 2404, a device for moving the shutter in the form of a linear actuator 2405, and an acoustic pulse generator in the form of a speaker 2406. In this embodiment, the airflow path is defined as reaching the distal end of the bifurcation through the oscillation method module 2402. The speaker 2406 is located in the first branch 2408 of the bifurcation. The shutter 2404 is located in the second branch of the bifurcation 2410. The air inlet is located at the end of the second branch of the bifurcation.

[0414] The oscillation method module 2404 is in electrical contact with the main unit 102 (not shown). This means that signals can be sent and received from the microcontroller 106 in the main unit to the oscillation method module 2402. The microcontroller 106 can send a signal to the linear actuator 2405 to cause the linear actuator 2405 to move the shutter 2404 from the Fig.24a The position shown in (which is the first position) is moved to Figure 24b 2402. The shutter in the second position blocks the air inlet in the housing of the oscillation method module 2402 to a greater extent than in the first position. When the shutter 2404 is in the first position, the resistance at the air inlet is minimal. Power can also be delivered to the oscillation method module 2402 through the electrical contacts. This provides power to the linear actuator, which can be used to move the occluder between the first position and the second position.

[0415] The microcontroller 106 controls the signal generator. The generated signal is sent to the speaker 2406. The speaker comprises a speaker cone 2407 which generates an acoustic pulse in the direction of the mouthpiece in response to the signal. The signal sent to the speaker results in the generation of an acoustic pulse comprising a frequency from 5 Hz to 20 Hz. The signal generator is not shown.

[0416] The signal sent to the speaker is coordinated with the control signal sent to the linear actuator. This means that the shutter 2404 can be moved from the first position to the second position while the acoustic pulse is being generated by the speaker 2406. When the shutter 2404 is in the second position, the resistance at the air inlet is increased. This ensures that a greater portion of the energy of the acoustic pulse is directed toward the mouthpiece than when the shutter is in the first position.

[0417] If the resistance is at an increased level for too long, it may be uncomfortable for the subject using the device. Therefore, the shutter 2404 is not maintained in the second position for a long time. By coordinating the movement of the shutter 2404 with the generation of the sound pulse by the speaker 2406, the resistance need only be increased for a short period of time, for example while the sound pulse is in the airflow path of the oscillation method module. The duration of the higher resistance should not be too long so as not to interfere with the subject's breathing effort and breathing pattern. The timing of the occluder in the first position and the second position can be similar to the timing described in the previous embodiment with respect to the oscillation method module. However, in the previous embodiment, as Fig.13 and Fig. 22 As shown in , the occluder both increases resistance and generates acoustic pulses. Fig.24a and 24b In the embodiment shown in , the occluder is a separate element from the acoustic pulse generator. This means that there may be some decoupling between the generation of the pulse and the change in flow resistance. For example, the timing of the shutter 2404 moving from the first position to the second position before the acoustic pulse is generated can be as long as 5ms.

[0418] In an alternative embodiment of the oscillation method module 2402, the speaker 2406 is replaced by a compressed gas tank. The compressed gas tank is configured to release gas through a release valve. The release valve is configured so that the released gas pushes the air in the airflow channel in the direction of the mouthpiece. The compressed gas is released in a direction parallel to the airflow channel and in the direction of the mouthpiece. The release valve is connected to a control circuit and can be controlled so that the release of the compressed gas is coordinated with the movement of the occluder from the first position to the second position. Fig.24a and Figure 24b The embodiment shown in describes this coordination.

[0419] Embodiments of the device have generally been described with respect to a configurable device, i.e., a device having a first configuration and a second configuration, wherein different configurations of the device can be used to perform different breath diagnostic tests. In other embodiments, the device may be a stand-alone device that is non-configurable and is designed to perform only one breath diagnostic test. For example, the device may be a stand-alone oscillometric test. In a stand-alone device, the components that make up the device are permanently connected to each other. However, other features and advantages of such a stand-alone device will be the same as described with respect to a device for performing multiple breath diagnostic tests in a configuration for performing an oscillometric test.

Claims

1. Equipment for performing multiple respiratory diagnostic tests, including: case, Sensor components, and a control circuit configured to receive a signal from the sensor assembly; wherein the device has a first configuration and a second configuration, wherein in the first configuration the device is configured to perform a first breath diagnostic test, and in the second configuration the device is configured to perform a second breath diagnostic test, wherein, in the first configuration, an airflow channel is defined by a housing of the device, the sensor assembly being configured to measure at least a first property of air in the airflow channel during the first respiratory diagnostic test, wherein, in the second configuration, the air flow channel is modified relative to the first configuration, the sensor assembly is used to measure at least a second property of air in the air flow channel during the second respiratory diagnostic test, wherein the first breath diagnostic test is different from the second breath diagnostic test, wherein the housing comprises a primary component and a first secondary component, the primary component defining at least a portion of the airflow channel, wherein the first secondary component has a first position relative to the primary component in the first configuration and has a second position relative to the primary component in the second configuration, wherein, in the first configuration, the primary component and the first secondary component are engaged with each other to define the airflow channel, and wherein, in the second configuration, the primary component and the first secondary component are disengaged from each other, and Wherein, when the primary component and the first secondary component are not engaged, the primary component and the first secondary component are separate or independent components.

2. The apparatus for performing a plurality of respiratory diagnostic tests according to claim 1, wherein: At least a portion of the airflow channel is the same in the first configuration and the second configuration.

3. The apparatus for performing a plurality of respiratory diagnostic tests according to claim 1, wherein: One of the first respiratory diagnostic test and the second respiratory diagnostic test is a lung obstruction or flow test.

4. The apparatus for performing a plurality of respiratory diagnostic tests of claim 1, wherein: One of the first breath diagnostic test and the second breath diagnostic test is a biomarker test.

5. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, wherein: In the second configuration, the airflow path is changed relative to the first configuration such that: increasing or decreasing airflow resistance experienced by air in the airflow channel; Changing the cross-section of the airflow channel; changing the temperature in the air flow channel; providing additional inlets or outlets in the airflow channel; or A gas dryer is positioned in the air flow passage, the gas dryer being configured to reduce the humidity of air passing through the gas dryer.

6. The apparatus for performing a plurality of respiratory diagnostic tests of claim 1, wherein: The first secondary component includes a sensor.

7. The apparatus for performing a plurality of respiratory diagnostic tests of claim 1, wherein: The sensor assembly is at least partially located within the main component.

8. The apparatus for performing a plurality of breath diagnostic tests of claim 1 further comprising a second secondary component, and wherein: In the second configuration, the primary component is engaged with the second secondary component.

9. The apparatus for performing a plurality of respiratory diagnostic tests of claim 1, wherein: The sensor assembly includes a flow sensor, and wherein the flow sensor is located in the main component.

10. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, wherein: The first respiratory diagnostic test or the second respiratory diagnostic test is a spirometry test.

11. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, wherein: The airflow channel includes at least one sub-channel such that, in at least one of the first configuration and the second configuration, a portion of the airflow through the device bypasses the sensor assembly.

12. The apparatus for performing a plurality of respiratory diagnostic tests according to claim 11, wherein: In at least one of the first configuration and the second configuration, airflow through the device bypasses the sensor assembly by at least 60% by volume.

13. The apparatus for performing a plurality of breath diagnostic tests according to any one of claims 1 to 4, further comprising an electrochemical sensor, wherein: The sensor assembly includes at least one of a pressure sensor, a flow sensor, a temperature sensor, and a humidity sensor, and wherein the control circuit is configured to use a signal from at least one of the pressure sensor, the flow sensor, the temperature sensor, and the humidity sensor to adjust a signal from the electrochemical sensor.

14. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, further comprising a purge filter in the air flow channel.

15. The apparatus for performing a plurality of respiratory diagnostic tests of claim 14, further comprising a valve configured to change a path of air flow through the air flow channel depending on a direction of air flow through the air flow channel, wherein: The air flow passes through the purification filter in one direction only.

16. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, further comprising a gas dryer in the gas flow channel.

17. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, wherein: One of the first breath diagnostic test and the second breath diagnostic test is a pulse oscillometric test.

18. Apparatus for performing a plurality of respiratory diagnostic tests according to claim 17, comprising an occluder and means for moving the occluder between a first position and a second position.

19. Apparatus for performing a plurality of respiratory diagnostic tests according to any one of claims 1 to 4, wherein: The control circuit is configured to output a test result after performing either the first breath diagnostic test or the second breath diagnostic test.

20. A method of performing a plurality of breath diagnostic tests using an apparatus according to any one of claims 1 to 19, comprising the steps of: placing the device in a first configuration for performing a first breath diagnostic test such that the device defines a first airflow channel through the device, and performing the first breath diagnostic test; The device is placed in a second configuration for performing a second breath diagnostic test different from the first breath diagnostic test such that the device defines a second airflow channel through the device different from the first airflow channel, and the second breath diagnostic test is performed.

21. The method of performing a plurality of breath diagnostic tests of claim 20, further comprising: A test result is output, wherein the test result is a combination of results from the first breath diagnostic test and the second breath diagnostic test.

22. A method of performing a plurality of breath diagnostic tests according to claim 20 or claim 21, wherein: One of the first respiratory diagnostic test and the second respiratory diagnostic test is a lung obstruction or flow test.

23. A method of performing a plurality of respiratory diagnostic tests according to claim 20 or 21, wherein: One of the first breath diagnostic test and the second breath diagnostic test is a biomarker test.

24. The method of performing a plurality of breath diagnostic tests of claim 20 or 21, further comprising the step of outputting test results from the control circuit after performing either of the first breath diagnostic test or the second breath diagnostic test.

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