GB2576136A

GB2576136A - Multi-test respiratory diagnostic device

Info

Publication number: GB2576136A
Application number: GB1811581.6A
Authority: GB
Inventors: Douglas Graeham
Original assignee: Arete Medical Technologies Ltd
Current assignee: Arete Medical Technologies Ltd
Priority date: 2018-07-14
Filing date: 2018-07-14
Publication date: 2020-02-12
Anticipated expiration: 2038-07-14
Also published as: GB2576136B; GB201811581D0

Abstract

A respiratory testing device 100 performing multiple diagnostic tests comprises a housing and a senor assembly. The device has at least two configurations: in the first configuration a first airflow channel (302, fig. 3) is defined and a first respiratory test is performed, and in the second configuration the airflow channel is modified and a second respiratory test is performed. The sensor assembly measures first and second properties of air in the channel during the first and second tests respectively. The device may be modular having a primary component 102 and secondary components (104, 105, 107, 108, 109, fig. 1) to create different configurations. The secondary components may adapt the device to make it suitable for the primary component 102 to perform different tests. E.g. spirometry is performed when a spirometry airway adapter (202, fig. 5) is attached to optimise airflow, biomarkers measured with a nitric oxide sensor module (602, fig. 6) attached, impulse oscillometry testing occurs when oscillometry module (1302, fig 13) with occluder is attached, and capanography performed when a carbon dioxide sensing component is attached. Different mouthpieces may be used in the different arrangements.

Description

MULTI-TEST RESPIRATORY DIAGNOSTIC DEVICE

Field of the Invention

The invention relates to devices for performing tests whose results can be used in the diagnosis of, or monitoring of, respiratory conditions and more particularly to a device capable of performing more than one diagnostic test.

Background to the Invention

There are many people who suffer from conditions that affect their respiratory systems. These conditions can make it difficult to breathe and can have a negative impact day to day for those who suffer from them. They can have many different forms or sub-types. Asthma is an example of a term used to describe such a condition that has several forms or subtypes. Evidence for sub-types of asthma is indicated by different people having different triggers to their symptoms and different responses to particular treatments. Another example of a respiratory condition is Chronic Obstructive Pulmonary Disease (COPD) which is another umbrella term used to describe a condition with numerous sub-types.

Diagnosing which condition a subject is suffering from, and also which sub-type, is essential for effective treatment of that condition. While a cure is not always possible, the symptoms of most respiratory conditions can be alleviated, improving the quality of life for the subject.

There are many diagnostic tests that have been developed over time. The results of these tests are used to diagnose a condition. Often the results of more than one test are necessary in order to properly and accurately diagnose a condition. This is particularly true when trying to diagnose a particular sub-type of a condition. Combining and analysing the results from more than one test is a skilled job and usually requires a trained medical professional to reach a final diagnosis. Often the diagnosis is not reached after only one testing session and it is necessary to monitor the symptoms over a period of time which may be several years. As the different sub-types of a condition may require different treatment it is important that the correct sub-type is diagnosed.

Historically, each diagnostic test has required a different device. Each device can be expensive, particularly 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 levels of nitric oxide in the exhaled air are 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 removed. This is technically challenging, makes the test procedure slow, and the repeatability of the measurement of nitric oxide may still be poor. Repeatability is important when monitoring subjects over a series of testing sessions. A factor affecting repeatability with current FeNO tests is that the breathing pattern required is slow and can be difficult for some people.

As the cost of individual devices can be high and expert knowledge may be required to perform or interpret the combined results from more than one device, current devices are often only available in specialist practices or lung function laboratories. Therefore, only a small portion of people suspected of having asthma or other respiratory diseases are tested with such devices. It also makes it difficult to continually monitor symptoms over a series of testing sessions. Without objective testing, subjects may be given an incorrect treatment for their condition. Incorrect allocation of treatment wastes resources, may not prevent subjects’ symptoms or attacks, and may cause unnecessary side-effects from a treatment.

There is a need for systems for diagnosing respiratory conditions that is inexpensive, accurate, readily available, easy to use and provides easy to interpret results.

Summary of the Invention

The invention provides a device and kit for performing a plurality of respiratory diagnostic tests and a method for performing a plurality of respiratory diagnostic tests using the device according to the appended independent claims, to which reference should now be made. Preferred or advantageous features of the invention are defined in the dependent claims.

In a first aspect of the invention there is a provided a device for performing a plurality of respiratory diagnostic tests comprising: a housing, a sensor assembly, and control circuitry configured to receive signals from the sensor assembly. The device has a first configuration in which the device is configured to perform a first respiratory diagnostic test and a second configuration in which the device is configured to perform a second respiratory diagnostic test.

In the first configuration an airflow channel is defined through the device housing, the sensor assembly being configured to measure at least a first property of air in the airflow channel during the first respiratory diagnostic test.

In the second configuration the airflow channel is modified relative to the first configuration, the sensor assembly being used to measure at least a second property of air in the airflow channel during the second respiratory diagnostic test.

The device being configurable to perform more than one respiratory diagnostic test advantageously means that a single device can provide results allowing for a fuller diagnosis or fuller monitoring of a respiratory condition. Diagnostic devices are typically able to perform only one type of test. However, there is no single test that can identify some respiratory diseases, including asthma and COPD. Different people with a respiratory disease have different triggers, symptoms, treatment responses, and biological pathways involved in their condition. A number of useful diagnostic tests have been discovered or are in development. However, it is impractical and expensive for a medical practice or subject to purchase, maintain, and use a number of different devices. The first and second configurations of the device correspond to first and second modes of operation of the device. By providing a device that is configurable to perform more than one respiratory diagnostic test, only a single device is needed to provide results that allow for a full diagnosis or full monitoring of a respiratory condition. Being able to use just one device simplifies the diagnostic or monitoring process and reduces the amount of hardware required, and so the cost. Said hardware may include batteries, control circuitry and displays, as well as other hardware such as a device housing.

The first respiratory test may be of a different type to the second respiratory test. For example, one of the first and second respiratory diagnostic tests may be a flow rate test or pulmonary obstruction test, such as a spirometry test or an oscillometry test. The other of the first and second respiratory diagnostic tests may be a test for a biomarker indicative of inflammation or disease, such as nitric oxide.

The airflow channel advantageously has a distal end and a proximal end. 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 properties of an inhaled or exhaled breath from the subject in the airflow channel. The airflow channel can advantageously be adapted for the different tests so that the airflow passes over different sensors and/or through different components of the device and/or so that properties of the airflow are changed. This may include increasing or reducing the airflow resistance experienced by air in the airflow channel, changing the cross-section 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 comprise multiple subchannels. The multiple sub-channels may join each other at a proximal end. Different sensors may be provided in different sub-channels. Some sub-channels may act simply as a bypass. Preferably, at least a portion of the airflow channel is the same in the first configuration and in the second configuration.

The device may comprise a primary component defining at least a portion of the airflow channel and a first secondary component, wherein the first secondary component has a first position relative to the primary component in the first configuration and a second position relative to the primary component in the second configuration. The device may comprise a plurality of secondary components, with each of the secondary components being designed for a specific respiratory test.

The first secondary component may comprise a sensor. This sensor advantageously measures a parameter of air in the air flow 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 positioned, at least partially, in the primary component.

In the first configuration, the primary component and the first secondary component may be engaged to one another to define the airflow channel. In the second configuration, the primary component and the first secondary component may be disengaged from one another or engaged to one another in a different manner. The airflow channel defined by engagement of the primary component and the first secondary component advantageously is optimized for performing a first respiratory test. In the second configuration, the primary component may be engaged with a second secondary component. At least a portion of the airflow channel may be defined through the secondary component.

The primary and secondary components may be separate or stand-alone components when they are not engaged. They may be engaged with each other by the subject. One component may have a male part and another component may have a corresponding female part into which the male part can be inserted to facilitate engagement. Pushing the male part into the female part connects the two components and holds the two components together. It may be advantageous to have a standard connection system between the primary component and all of the secondary components. A standard connection system advantageously means that additional secondary components can be added to the system after purchase or first release. This advantageously means that the subject can purchase or obtain new secondary components and use them with their existing system. These new secondary components may configure the device to have additional capabilities. These additional capabilities may include performing additional respiratory diagnostic tests.

Alternatively, the primary and secondary components may advantageously form a single device such that the primary and secondary components are not physically separable from one another. The primary and secondary components may comprise selection means configured to define an airflow channel through a selection of portions of the primary and secondary components. The airflow channel through the device must be appropriate for the test the device is to perform. The selection means may comprise one or more valves which may be used to select the secondary components that are included in the airflow channel. Changing the route of the airflow channel through the device changes the configuration of the device. A valve arrangement for changing the device configuration may be advantageous in there is no need to physically connect or remove components in order to configure the device. The valve(s) can be controlled by the control circuitry which automates configuring the device. This means the device can be shipped as one unit capable of being configured to perform any of a range of respiratory diagnostic tests. The use of a valve or valves may advantageously reduce contamination from the atmosphere before the tests is performed. A valve may also be configured to partially open for at least one of the secondary components. The airflow channel may be configured by intermittently opening and closing one or more valves.

It may be advantageous for the device to comprise both the described configuration options. As well as a valve connection, there may a number of stand-alone components that can physically connected or disconnected.

The primary component may have a power or data connection with the secondary component in at least one of the first and second configurations. This advantageously allows measurements taken using a sensor positioned in either the primary component or the secondary component to be transferred to the other component, and for communication with the control circuitry. It also allows any element that may require power in any of the components to be powered from any of the other components.

The control circuitry may comprise a microcontroller. The microcontroller may be configured to process data received from the sensors. The result of the processing of data may be a test score which can be used to help monitor or diagnose a respiratory disease. The control circuitry may instead be in communication with a portable computer comprising a microcontroller such as a laptop or smartphone. In these cases, the microcontroller of the portable device performs the data processing. The communication between the control circuitry and the portable device may be wireless a connection. The wireless connection may be a Bluetooth connection.

The sensor assembly may comprise a flow sensor. The flow sensor may be positioned in the primary component. The device may be configured to perform a spirometry test in a first configuration and measure the concentration of a biomarker indicating lung inflammation in a second configuration. The flow sensor may be used to perform the spirometry test. The device may be configured to measure peak expiratory flow or forced expiratory flow using the flow sensor. Spirometry tests measure lung function, specifically the amount and/or the speed of air that can be inhaled or exhaled. These tests can advantageously be used to diagnose conditions such as asthma. Advantageously, the flow sensor can be used to perform the spirometry tests.

Spirometry tests may be conducted using an airflow of up to about 850 litres per minute with measurements having an accuracy of ±5 litres per minute. When the device is configured to perform a different respiratory diagnostic test, the required flow rate may be much lower. The required airflow for some tests may be not more than 5 litres per minute, with accuracy of measurements being ±<0.5 litres 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 the appropriate range for measuring airflow and appropriate accuracy across each range.

Producing a flow sensor with the appropriate range and sensitivity is technically challenging. A flow sensor that has a range of 850 litres per minute will generally not have a suitable sensitivity at lower flow rates of around 5 litres per minute. It may be advantageous to use a flow sensor with a lower range but with higher sensitivity at low flow rates. It may be advantageous to modify or adjust the effective range of the flow sensors, 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 from one or more other sensors.

One way of addressing this problem is by allowing only a proportion of the inhaled or exhaled air to flow past the air flow sensor.

The airflow channel may be separated into a plurality of sub-channels through one of the secondary components so that at least one of the sub-channels bypasses the sensor assembly. At least one of the sub-channels can take the form of inlets in the housing of the device between the flow sensor and the mouthpiece, the inlets providing fluid communication between the outside air and the rest of the airflow channel.

Advantageously, this means that the flow sensor is only required to have a range capable of measuring the proportion of air passing it. The flow rate of the total air flow can be inferred from the measurement of a proportion of the airflow. At least 60% and more preferably, at least 70%, of the airflow through the airflow channel may bypass the sensor assembly. This advantageously means that less than 40% and more preferably, less than 30%, of air flowing through the air flow channel passes the flow sensor and the required range of the flow sensor is reduced to a corresponding fraction of the total flow rate that is supplied by a subject. The maximum flow through the sub-channel passing the flow sensor advantageously matches the range of the flow sensor.

Another way of addressing the problem is via electronic adjustment of the readings from the flow sensor using a measurement from another sensor. For example, the sensor assembly may comprise a pressure sensor. The control circuitry may be configured to use signals received from both the flow sensor and the pressure sensor to estimate flow rate. The flow sensor may have a range of ±200 litres per minute. The estimated flow rate using the flow sensor and pressure sensor has a range of ±1000 litres per minute. This is high enough to measure flow when the device is the in a spirometry configuration, where flow rate estimates of lower flow rates are primarily determined by the flow sensor, which has a higher sensitivity at lower flow rates, and measurements of higher flow rates are primarily determined by the pressure sensor, which has a larger range than the flow sensor.

The secondary component may comprise a biomarker sensing component wherein the biomarker indicates lung inflammation or disease. In one of the configurations the airflow channel may have a resistance of at least 5cm H2O. This advantageously ensures that the nasal velum stays closed while the subject is exhaling through the device. Nasal air may have a high concentration of the biomarker. If the nasal velum does not stay closed when the subject exhales, then the exhaled breath is contaminated with the nasal air and would give an artificially high measurement of the biomarker for lung inflammation.

The device may comprise an electrochemical sensor configured to detect the presence of the biomarker indicating lung inflammation. The electrochemical sensor may be part of the secondary component. The control circuitry may be configured to receive signals comprising output values from the electrochemical sensor.

The sensor assembly may comprise a combination of two or more of: a pressure sensor, a flow sensor, a temperature sensor and a humidity sensor. The electrochemical sensor, pressure sensor, flow sensor, temperature sensor and humidity sensor may be positioned adjacent one another within the airflow channel. They are advantageously in substantially the same position in the airflow because that reduces pressure differences and temperature differences between sensors.

The control circuitry may be configured to adjust an output value received from the electrochemical sensor based on signals from at least one of the pressure sensor, flow sensor, temperature sensor and humidity sensor. This adjustment is advantageous because electrochemical sensors are typically very sensitive to environmental conditions, changes to environmental conditions, and especially to changes to moisture in the air. It is typically exhaled breath that is measured by the device. Exhaled air has a high moisture content and temperature relative to atmospheric air, and the exhaled air flow may have variable pressure or flow rate. This lack of controlled and constant sample conditions means that readings from the electrochemical sensor alone may not be sufficiently accurate. Environmental conditions must be factored in. The signals received from the pressure sensor, flow sensor, temperature sensor and/or humidity sensor can be used by the control circuitry to provide an adjustment factor and/or offset to the measurement from the electrochemical sensor to account for the environmental conditions or rates of change of environmental variables.

The secondary component may comprise a scavenger filter configured to reduce the amount of a biomarker in the air. The biomarker may indicate lung inflammation. Inhaled breath may pass through the scavenger filter. This means that the amount of a biomarker measured in the exhaled breath can be assumed to be produced by the subject and not simply present in the environment, inhaled, and then exhaled.

The secondary component may comprise a valve configured to change the airflow path through the airflow channel depending on the direction of the flow of air through the airflow channel. For example, the valve may ensure that in only one direction does the airflow channel pass the scavenger filter.

The secondary component may comprise a gas drier. The gas drier may be configured to reduce the humidity of air passing through the gas drier. As explained above, electrochemical sensors are very sensitive to changes in moisture content. It may be advantageous to reduce the humidity of the air that is being sampled by the device, in addition to or instead of adjusting the measurement as in the method described above. This may improve the accuracy of readings from the electrochemical sensors.

Reducing the humidity of air passing through the device can prevent condensation on the sensors, which is advantageous, especially for the nitric oxide sensor. The gas drier may be an absorbent material, water trap, Nafion tubing, or may warm the sensor surface. An absorbent material advantageously does not require electrical power and does not substantially increase the internal volume of the flow channel. The gas drier may be positioned in the mouthpiece.

The biomarker indicating lung inflammation may be nitric oxide concentration. The exhaled nitric oxide concentration indicates activity of eosinophils, which are involved with inflammation for about two thirds of asthmatics and one third of people with COPD. Therefore, nitric oxide concentration can be used to determine the sub-type of disease a person may have. A high nitric oxide concentration can indicate that a subject is likely to respond to particular pharmaceutical treatments. If the treatment is successful, a subject’s exhaled nitric oxide concentration should decrease, so the test can be used to find an effective drug dose and to confirm the subject is administering their treatment correctly.

One of the first and second respiratory diagnostic tests may be an impulse oscillometry test. Oscillometry tests are diagnostic tests, the results of which indicate mechanical properties of the airways of the subject performing the test. These properties can be used to aid the diagnosis of respiratory diseases such as COPD. Oscillometry tests are advantageous as they do not require the subject to perform a specific breath manoeuvre, such as forced breathing. The subject need only perform normal, tidal, breathing through the device. This is advantageous as it means the test is easy and comfortable to perform. This is particularly important for children and for subjects who are suffering from a respiratory disease that would make breathing in another manner, such as high-flow forced breathing, difficult and uncomfortable.

When one of the first and second respiratory diagnostic tests is an impulse oscillometry test the device may comprise an occluder and a means to move the occluder between a first position and a second position wherein the occluder is configured to create an acoustic impulse in the air in the airflow channel.

While performing an oscillometry test using the device, a subject may breathe into and/or out through the device, such that air passes through the air channel of the device and into/out of the subject’s lungs. The configuration of the occluder, and the means to move the occluder, advantageously provides a compact and efficient way of generating an acoustic impulse that passes through the air in the airflow channel of the device. The airflow channel may be defined through the device from a mouthpiece to an air inlet. The air inlet may be open to the atmosphere.

In the second position, the occluder may occlude 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 create an acoustic impulse in the air in the airflow channel.

The device may comprise a mouthpiece. As used herein, an acoustic impulse is a pressure wave comprising a plurality of sinusoidal frequencies. The acoustic impulse may be created by the push of the of the air into the airflow channel by the occluder as it is moved from the first position to the second position. The push of air creates pressure fluctuations. The pressure fluctuations ideally take the form of, or approximate, a square wave. In an ideal case the impulse would be created by instantaneous movement of the occluder from the first position to the second position. In reality, this instantaneous movement is not possible, resulting in asymmetrical, bell shaped impulse.

The acoustic impulse travels at the speed of sound. Parameters of the acoustic impulse may be sensed by the sensor assembly as the acoustic impulse travels through the airflow channel from the occluder. It is advantageous that the occluder occludes the airflow channel to a greater extent in the second position than in the first position, as this reduces loss of energy from the pressure wave in a direction away from the mouthpiece. Energy can escape through the gap between the occluder and the airflow channel so any reduction in the that gap (achieved by the increased occlusion) ensures less energy escapes.

The characteristics of the acoustic impulse are dependent on the configuration of the occluder, motion of the occluder, and the properties of the air channel including the subject’s lungs. As the configuration of the occluder, motion of the occluder, and properties of the airflow channel within the device can be known or calibrated for, the parameters sensed by the sensor assembly can be used to characterise airway mechanics of the subject’s lungs.

The control circuitry may be configured either to control the means to move the occluder or to receive signals from the sensor assembly, or both to control the means to move the occluder and to receive signals from the sensor assembly.

The control circuitry may advantageously control the means to move the occluder such that the occluder moves between the first position and the second position at a speed and through a distance such that an acoustic impulse with desired properties is created. Alternatively, the means to move the occluder may be driven by the subject’s breathing.

Once created, the acoustic impulse travels through the airflow channel in the direction of the mouthpiece. This is advantageously in the direction of the airways of a 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 a maximal amount of energy will reach the subject’s airways. The acoustic impulse passes through the airflow channel out of the mouthpiece into the airways of the subject. The acoustic impulse interacts with the airways of the subject, resulting in changes in the pressure and flow rate of the air passing the sensor.

The sensor assembly is configured to measure a flow rate of air in the airflow channel or a pressure of air in the airflow channel or both a flow rate of air in the airflow channel and a pressure of air in the airflow channel. The control circuitry may be configured to calculate a parameter that characterises a respiratory system based on a frequency domain analysis of the flow rate of air in the airflow channel or the pressure of air in the airflow channel or both the flow rate of air in the airflow channel and the pressure of air in the airflow channel. The flow rate and pressure are measured by the sensor assembly as required.

The control circuitry may receive measurements of flow and pressure from the sensor assembly, and based on these measurement may form a number of metrics that describe the mechanical properties of the airways. These metrics may be parameters that characterise the respiratory system of the subject. The effect of an acoustic impulse may be different for different frequencies, and different frequencies can penetrate the airways to different depths. Because the impulse comprises multiple frequencies, the metrics can indicate the characteristics of the upper and lower airways as well as the airway system as a whole. The metrics may give an indication of airway resistance and airway reactance and other mechanical properties of the airways. The mechanical properties of the airways may indicate that a subject has a respiratory disease and so these metrics can aid a trained medical person in the diagnosis of respiratory diseases.

The control circuitry may be configured to move the occluder such that the acoustic impulse that is created comprises a plurality of frequencies of pressure fluctuations in a range from 5 Hz to 20 Hz. The acoustic impulse may be in the form of, or approximate, a square wave, created by the movement of the occluder from the first position to the second position. The occluder may move in a cycle from the first position, to the second position, and return to the first position more than once per breath. For example, the cycle of the occluder may have a frequency or pulse rate of 3 Hz. The highest frequency contained in the impulse is dependent on the duration of the impulse. For example, an upper frequency of 20Hz contained in the impulse may be attained by the occluder moving from the first position to the second position in 50 ms or less. The impulse will contain lower frequencies, such as 5 Hz. The highest frequency with a detectable amplitude may be 20 Hz. The lower frequencies within the impulse penetrate deeper into the subject’s airways and may penetrate out to the lung periphery, whereas the higher frequency signals may not penetrate as far, only reaching the proximal airways. It is therefore advantageous to probe the airways of the subject with a plurality of frequencies of pressure fluctuations rather than a single frequency, giving a fuller picture of the mechanical properties of the subject’s airways. It allows for the recognition of characteristic respiratory responses at different frequencies.

The control circuitry may be configured to perform a Fast Fourier Transform on both the signals relating to measured flow and measured pressure from the sensor assembly and so produce a frequency domain distribution showing an amplitude for each frequency.

The control circuitry may be configured to move the occluder from the first position to the second position such that the acoustic impulse provides a maximum pressure increase of at least 50 Pa at the sensor assembly and a flow rate increase of at least 0.15 litres min^-1through the airflow channel in the direction of the mouthpiece. The increase of pressure is the amount the pressure is increased above the pressure of air in the airflow channel from the subject breathing normally. The control circuitry may be configured to move the occluder from the first position to the second position within 50 ms or less.

The control circuitry may be configured to move the occluder from the first position to the second position such that air is pushed in the airflow channel for less than 50 ms. This pushes the air in the airflow channel with enough force to create an acoustic impulse with pressure fluctuations that have an amplitude that is large enough to be detected. The 50 ms duration from the first position to the second position is advantageously short enough that the created acoustic impulse is sufficiently close to a square wave for the results of the test to be accurate and not complicate calculations such as Fourier Transforms.

In the second position the occluder occludes the airflow channel to a greater extent than in the first position. This change in occlusion results in a change in resistance to air flowing the airflow channel. When the occluder is in the second position air flowing in the airflow channel experiences a higher resistance to flow than when the occluder is in the first positon. The resistance to flow when the occluder is in the first position is lower than 0.15 kPa s L’¹. While the occluder is in the second position the higher resistance may cause the pressure in the airflow channel to change compared to when the occluder is in the first position. The pressure change (depending on whether the subject is inhaling or exhaling) in the airflow channel may affect the characteristics of the acoustic impulse.

Both the length of time that the occluder is in the second position for, and the configuration of the occluder, may affect the characteristics of the acoustic impulse. The configuration of the occluder refers particularly to the amount to which the occluder increases the resistance to flow when the occluder is in the second position compared to when it is in the first position. The length of time that the occluder is in the second position for and the configuration of the occluder can therefore be chosen to result in an acoustic impulse that has desired characteristics.

In some embodiments the occluder may be configured such that when it is in the second position air can flow through the airflow channel. This means that even though the air in the airflow channel experiences more resistance when the occluder is in the second position, the airflow channel is not totally occluded. The minimum distance between the air outlet and the occluder, when the occluder is in the second position, may be at least 0.5 mm. At this distance the resistance to flow is sufficiently low that the effect of the change in flow resistance on the characteristics of the acoustic impulse is negligible. A gap of not much more than 0.5 mm may be chosen as this results in a suitably low resistance to flow while also ensuring that acoustic impulse is efficiently directed in the airflow channel toward the mouthpiece.

The test may be more comfortable for the subject and more likely to give accurate results if the pressure change experienced by the subject when the occluder is in the second position does not result in a significant build-up of pressure in the subject’s airways. This can be achieved by ensuring that the occluder is in the second position for only a short time and by ensuring that the occluder does not fully close the airflow channel.

The control circuitry may 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. This is a time that is advantageously short enough that the pressure change due to the increase in resistance while the occluder is in the second position is not noticeable for the subject. The mathematical model is advantageously simpler when the calculations do not have to take into account a significant pressure change resulting from prolonged occlusion of the airflow channel.

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

A build-up of pressure in the airflow channel may increase the amplitude of the acoustic impulse. This may be because the pressure change in the airflow channel contributes additional energy to the acoustic impulse. The occluder remaining in the second position may more efficiently direct the energy of the acoustic impulse toward the mouthpiece. This may allow a smaller occluder to be used having a lower power requirement. However, the characteristics of the acoustic impulse may also be affected such that is less close to a square wave.

The occluder may be configured so that when it is in the second position air cannot flow past it. This is the extreme case of having high resistance to flow when the occluder is in the second position and ensures that a maximum amount of energy of the acoustic impulse is directed in the airflow channel toward the mouthpiece. The occluder may comprise a resilient 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 comes into contact with the housing. The sealing component advantageously ensures that an air-tight seal is achieved in the airflow channel, preventing the flow of air in the past the occluder. It also prevents damage to the housing of the device when the occluder is moved with force from the first position to the second position.

The control circuitry may be configured such that the means to move the occluder moves said occluder from a first position to a second position and back to a first position at least 3 times each second during a test period. Creating multiple acoustic impulses throughout a test advantageously allows a full picture of the airways.

The occluder, in the second position, may be configured to occlude the air inlet of the airflow channel.

The face of the occluder in contact with the airflow channel may be substantially concave in shape. This is efficient for creating the acoustic impulse, and ensures that as much air as possible is pushed toward the mouthpiece as the occluder is moved from the first position to the second position.

The means to move the occluder may be configured to move the occluder in a direction parallel to the airflow through the airflow channel when a subject is inhaling or exhaling through the mouthpiece. This results in the push of air by the occluder, when caused by the occluder moving 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.

The means to move the occluder may be a linear actuator. The linear actuator may advantageously be positioned such that its axis of movement is parallel to the airflow channel. The linear actuator will then move the occluder from the first position to the second position in a direction parallel to the airflow channel. Other means to move the occluder are possible. For example, the occluder may be on a hinged actuator.

The device, as configured for performing an oscillometry test, may be a stand-alone device that it is not reconfigurable to perform any other respiratory diagnostic tests.

The one or more secondary components may include an integral mouthpiece. Alternatively, a mouthpiece may be provided as a separate component. The mouthpiece may advantageously comprise a microbe filter. The mouthpiece advantageously has a low resistance to flow, low wasted volumes, and relatively smooth internal surfaces. Avoiding sharp internal features reduces disturbance to the impulse/wave travelling into/out of the airways. These features may otherwise damp the signal properties of the wave. A different mouthpiece may be used for each test. The mouthpiece may be configured to engage the primary component or the secondary component, or both the primary component and the secondary component.

A mouthpiece may be configured for a specific respiratory test. The mouthpiece may advantageously increase the resistance to air flowing in the air flow channel. The mouthpiece may also advantageously comprise a gas drier.

The device for performing a plurality of respiratory diagnostic tests may be portable. This advantageously means that the device can be brought to a subject rather than the subject having to visit, for example, a hospital. This advantageously makes monitoring of a condition easier as a subject would not have to return to, for example, a hospital each time the test is performed. It also allows for environmental triggers to be assessed in the real world.

The device may comprise at least one battery configured to provide power to the control circuitry and the means to move the occluder. The device comprising a battery advantageously allows the device to be portable and not required to be near a power source such as mains power when in use.

The device may comprise a capacitor configured to be charged by the at least one battery and to discharge with a power burst greater than the power requirements of the device. This advantageously allows a battery to be fitted to the device that has lower power output than the power output requirement of device. Such a battery will typically be smaller, allowing the device for performing the oscillometry test to be smaller and more portable.

In a second aspect of the invention there is provided a kit for performing a plurality of respiratory diagnostic tests, comprising: a primary component, a secondary component, a control circuitry, and a sensor assembly positioned in the primary component or secondary component or in both the primary and secondary components. The secondary component is configured to engage the primary component in a first configuration of the kit such that a first airflow channel is formed through the primary and secondary components so that a first respiratory diagnostic test can be performed. In a second configuration of the kit a second airflow channel is formed through the kit passing through at least the primary component so that a second respiratory diagnostic test can be performed. The kit can advantageously be changed from a first configuration to a second configuration without using any tools.

One of the first and second respiratory diagnostic tests may be a pulmonary obstruction or flow test and the other of the first and second respiratory diagnostic tests may be a biomarker test.

The primary component may comprise the sensor assembly and the control circuitry. The sensor assembly may comprise a flow sensor. The sensor assembly may comprise a pressure sensor. The sensor assembly may further comprise a temperature sensor and a humidity sensor.

The secondary component may comprise at least one additional air outlet configured so that a proportion of air flowing through the secondary component exits the secondary component through the at least one additional air outlet. Advantageously, air passing through the additional air outlet does not pass the sensor assembly.

The secondary component may comprise a gas drier configured to reduce the humidity of air passing through the drier. The secondary component may comprise a scavenger filter. The scavenger filter may be a nitric oxide scavenger filter. The secondary components may comprise a valve configured so that only air flowing along the airflow channel in one direction can passes the scavenger filter.

The secondary component may comprise an occluder and a means to move the occluder from a first position to a second position wherein the occluder is configured to create an acoustic impulse in the air in the airflow channel.

The kit may further comprise a mouthpiece. The mouthpiece may comprise a microbe filter. The mouthpiece may be configured to engage the primary component or the secondary component, or both the primary component and the secondary component.

In a third aspect of the invention there is provided a method for performing a plurality of respiratory diagnostic tests using a device according to the first aspect of the invention, comprising the steps of:

putting the device in a first configuration for performing a first respiratory diagnostic test such that the device defines a first airflow channel through the device, and performing the first respiratory diagnostic test;

putting the device in a second configuration for performing a second respiratory diagnostic test different to the first such that the device defines a second airflow channel through the device different to the first airflow channel and performing the second respiratory diagnostic test.

Advantageously this method allows a single device to perform multiple respiratory diagnostic tests simply by reconfiguring the device such that the different airflow channels are formed through the device. Each of the airflow channels may be advantageously defined in a way that is optimized for specific test.

The method may further comprise the step of outputting a test result from the control circuitry after performing either of the first or second respiratory diagnostic tests. The test result may be a combination of measurements or results from the first and second respiratory diagnostic tests.

The step of putting the device in a configuration may comprise removing a component from the device. The step of putting the device in a configuration may comprise altering a positon of a component of the device, or a position of an element within a component of the device, to change the airflow channel. The step of putting the device in a configuration may comprise connecting an additional component. The step of putting the device in a configuration may comprise changing environmental conditions of air flowing through the device, such as changing the temperature of air flowing through the device.

It should be clear that features described in relation to one aspect may be applied to other aspects of the invention.

Brief Description of the Drawings

Embodiments in accordance with the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

Figure 1 shows a series of schematics of general configurations of the device in accordance with the invention wherein each configuration may perform one of a plurality of respiratory diagnostic tests;

Figure 2 is a side view of the device in a specific configuration for performing spirometry tests;

Figure 3 is a cross-sectional view of the device of Figure 2 showing the airflow channel that is formed through the device;

Figure 4 is a close-up cross-sectional view of part of Figure 3 showing a sensor in the airflow channel;

Figure 5 is an exploded side view of the device of Figure 2 showing the separate components that are connected to form the device;

Figure 6 is a side view of the device in a specific configuration, different to the configuration shown in Figure 2, for performing nitric oxide concentration tests;

Figure 7 is a cross-sectional view of the device of Figure 6 showing the airflow channel that is formed through the device;

Figure 8 is a series of schematics of general configurations of the device, similarly to Figure 1 but also showing the sensors present and which component comprises the sensors; Figure 9 is a side view of the device in a second spirometry configuration;

Figure 10 is a graph showing flow measurements changing with time as measured a flow a sensor and a pressure sensor in comparison to the true value;

Figure 11 is a graph showing nitric oxide concentration as measured by a nitric oxide sensor in comparison to the true value, it also shows the negative rate of change of relative humidity;

Figure 12 is a flow chart outlining a method for using the device according to the invention; Figure 13 is side view of the device in a different configuration, for performing oscillometry tests, the device in this configuration comprising an occluder wherein the occluder is in a first position;

Figure 14 is the same side view of the device of Figure 13, the occluder of the device is in a second position;

Figure 15 is a cross-sectional view of the oscillometry module of Figures 13 and 14, showing the linear actuator that moves the occluder from the first position to the second position, shown in Figures 13 and 14 respectively;

Figure 16 is a cross-sectional perspective view of the device of Figure 13, showing the airflow channel that is defined through the device;

Figure 17 is a flow chart showing a method of using the device of Figure 1 to perform an oscillometry test;

Figure 18 is a display or user interface of the device, this embodiment is for subjects with limited medical training;

Figure 19 is a display or user interface of the device, this embodiment is for subjects that are medical professionals;

Figure 20 is a display that shows historical data from previous tests; and

Figure 21 is an additional display or user interface where the test results from a current subject are compared to those of other subjects.

Detailed Description

Figure 1 illustrates, in schematic form, five different configurations of a device 100 for performing respiratory diagnostic tests in accordance with the invention. In each configuration, the device 100 is configured to perform a specific respiratory diagnostic test. The device comprises a primary component 102 and control circuitry 106. The control circuitry 106 may be a microcontroller. The device may also comprise any number of secondary components 104, 105 107, 108 or 109. The primary component 102 comprises, or is connected to, the control circuitry 106. The secondary components of the device can be arranged relative to the primary component in numerous ways, as shown in Figure 1, in order to carry out different tests.

All the configurations shown in Figure 1 contain the primary component 102 and the control circuitry 106. Each configuration differs in the number or arrangement of secondary components. Secondary components are added, removed, or rearranged within the assembly to create a new configuration of the device. In each configuration, an airflow channel is defined through the connected primary and secondary components. The characterisation of the airflow channel differs in each configuration in order to be optimised for a specific respiratory diagnostic test.

In some embodiments the control circuitry 106 of the primary component is powered by an external power source. This may be via a USB connection with a computer or portable device such as a laptop. The USB connection is not shown in the figures. In other embodiments the power source may be an internal power source such as a battery. The primary component 102 is in electrical contact with any secondary components in connection with the primary component. This allows power to be transferred from the external power source to the primary component and the secondary components. Some secondary components may require a burst of power greater than can be supplied by the power source. In this case the device (and, typically, the particular secondary component that requires the power burst) may comprise a capacitor that can be charged by the power source. A high power burst can be created when the capacitor is discharged through the capacitor.

To use the device 100, a subject inhales and/or exhales through the device so that the inhaled or exhaled air flows through the airflow channel defined through the device 100. The primary component 102 comprises at least one sensor. Some, but not all, of the secondary components 104 comprise sensors. The primary 102 and secondary components 104 have a standard connection mechanism which exists across all the components making it easy to switch components around. The primary component may also comprise an additional connection mechanism via which some secondary components can connect. Generally, a mouthpiece is also connected to the primary component 102 or one of the secondary components.

Figures 1a to 1d show four different configurations of the device with various arrangements of primary components in connection with different secondary components. Figure 1a is a configuration with a primary component 102 connected to a secondary component 104. Figure 1b is a configuration with a primary component 102 not connected to any other component. Figure 1c is a configuration with secondary component 105, different to secondary component 104, connected to the primary component 102. Figure 1d is a configuration with secondary component 104 connected to the primary component 102 and to secondary component 107, different to secondary components 104 and 105.

Figure 1e is an alternative embodiment. It shows a number of secondary components 104, 108 and 109 that are fixed to one another. Only secondary component 104 is in connection with the primary component 102. When the device is configured as shown in Figure 1 e, an airflow channel is defined through the primary component 102 and secondary component 104 only. Secondary components 108 and 109 can be connected to the primary component 102 as required to reconfigure the device to perform one of the other respiratory diagnostic tests and so defining an airflow channel through primary component 102 and secondary components 108 or 109 respectively. Connection may be achieved by opening a valve. Closing the valve disconnects the secondary component. In some configurations the valves may allow air to flow through one, more than one or none of the secondary components 104, 108 and 109. An alternative connection may be rotation or other movement of the secondary components into different positions relative to the primary component, to change the airflow path through the device.

Figure 2 is a perspective view of a device 100 for performing a first respiratory diagnostic test. In this configuration the device is configured to perform a spirometry test. Spirometry tests are used to indicate mechanical properties of the airways of the subject. The flow rate is measured and can be integrated over time to calculate lung volumes. The maximum exhaled flow rate is an indicator of airway resistance and obstruction; resistance to flow increases as airway diameter decreases. The reduction in airway diameter reduces the maximum flow rate. Obstructed or narrowed airways suggest the subject may have a respiratory condition such as asthma or COPD.

The device comprises a primary component 102, a first secondary component, which is a spirometry component 202, and a mouthpiece 204. The secondary component is positioned between the mouthpiece and the primary component. The spirometry component 202 comprises eight bypass holes 210.

The primary component comprises a flow sensor held within housing portion 207, a sensor assembly held within a housing portion 209 and a control circuitry held within a housing portion 211. The flow sensor, sensor assembly and control circuitry are not shown in Figure 2. The primary component further comprises mounting plate 212.

Figure 3 is a cross section of the device of Figure 2 and shows the airflow channel 302 defined through the device 200 when it is in a spirometry configuration. In Figure 3 the control circuitry and control circuitry housing portion 211 are not shown. The mounting plate 212 is also not shown.

The sensor assembly 304 and flow sensor 306 are visible in Figure 3. The sensor assembly 304 comprises environmental sensors, which are a pressure sensor, a temperature sensor, and a humidity sensor. The pressure sensor is an All Sensors Co DLHR-L02D. The temperature and humidity sensors are integrated into one component, a Sensirion SHT75. All of the above sensor components are available for purchase from the Digi-Key electronics website: https://www.digikey.com/. The flow sensor is a Sensirion SFM3000. In Figures 2 and 3 the flow sensor 306 and the flow sensor housing 207 are shown as being part of the primary component 102. However, these may form part of the secondary component 202.

The airflow channel 302 is designed to have a low resistance to flow and low internal volume or dead space. The various components forming the airflow channel 302 have similar internal diameters. Where there are changes to the airflow channel 302 diameter, the changes are graduated to reduce airflow resistance and encourage consistent airflow with repeatable characteristics. Some sensors respond better to laminar flow and some sensors respond better to turbulent flow. As the sensors respond differently to different flow characteristics, it is important that the characteristics are repeatable so that every time a diagnostic test is performed a similar air flow occurs in the airflow channel 302 of the device. Spirometry is used to measure airway resistance of the subject, so inconsistent or high resistance in the device could cause inaccurate test results or make it difficult for the subject to perform the test. Local disruptions or turbulence to the airflow in the airflow channel 302 could cause errors or inaccuracies measurements by the sensors.

The flow sensor 306 is connected electrically to the control circuitry, and is able to send data to the control circuitry and receive instructions and power from the control circuitry. For example, the control circuitry can activate, deactivate, and adjust the sampling frequency of the flow sensor 306. A higher sampling frequency can provide better data for respiratory measurements. Electrical power can be used more efficiently if the flow sensor is deactivated when are not being used in a test.

The mouthpiece 204 comprises a microbe filter, not shown, to protect the subject from infection. The microbe filter also acts to avoid contamination of the device 100, absorb some moisture from the exhaled breath to reduce condensation on sensors in the device and protect sensors in the device from exhaled particles, fluids, or debris. A new mouthpiece 204 is used for each person using the device.

Figure 4 is a close up view of the portion 209 of the primary component 102 holding the sensor assembly 304. The sensor assembly comprises environmental sensors. The environmental sensors measure pressure, temperature and humidity. The sensor assembly 304 is fitted in the primary component 102 to expose inlets of the sensors to the air in the airflow channel 302.

The sensor assembly 304 is mounted to reduce thermal conduction from the housing 209 of the primary component 102. Thermal conduction between the housing of the primary component 102 and the sensor assembly 304 could cause the measurement of the air to be influenced by the temperature of the primary component 102. Access holes into the housing of the primary component 102 for the sensor assembly 304 are sealed to avoid interaction between the environment and the airflow channel 302. Flow through these access holes could cause disturbance to the flow profile and cause errors in the measurements made by sensors of the sensor assembly 304.

The sensors of the sensor assembly 304 are connected electrically to the control circuitry, and are able to send data to the control circuitry and receive instructions and power from the control circuitry. For example, the control circuitry can activate, deactivate, and adjust the sampling frequency of the sensors of the sensor assembly 304. A higher sampling frequency can provide better data for respiratory measurements, but can generate heat that can produce errors in temperature measurements. Electrical power can be used more efficiently if the sensors are deactivated when they are not being used in a test.

Figure 5 is an exploded view of Figure 2 and illustrates how the components fit together. In the configuration shown in Figure 2 the primary component 102 is configured to perform spirometry tests when connected to the secondary component 104 and the mouthpiece 204. The spirometry component 202 is detachable from the primary component 102. The mouthpiece is detachable from the secondary component 104 which is spirometry component 202. By connecting the spirometry component 202 to the primary component the device is configured for performing spirometry tests.

The spirometry component 202 has an inner surface that is designed to interface and seal with the outer surface of the flow sensor portion 207 of the primary component 102. The interfacing surface of each component has a conical taper to provide a seal when the spirometry component 202 is installed over the flow sensor portion 207 of the primary component 102. The inner diameter and conical taper of the flow sensor portion end of the spirometry component 202 is the same as the outer diameter and taper of the connecting end of the mouthpiece 204. Thus, the components can be used in a modular way, where components can be added to, removed from, or rearranged within the device for different configurations of the device.

The opposite end of the spirometry component 202 has an inner surface that interfaces with the outer surface of the mouthpiece 204. The dimensions and taper of interfacing surfaces in the device are standardised. This means that these interfacing surfaces will be the same as above. Each secondary component has a standardised interface to interact with the shape and dimensions of at least one end of the primary component or another secondary component.. The interfacing surface of both components has a conical taper to provide a seal when the spirometry component 202 is installed over the mouthpiece 204. Some interfaces have additional features to aid with connection. The inner surface of the spirometry component 202 has an internal step that locates the depth the mouthpiece 204 can be inserted into the spirometry component 202. The internal step also reduces disruptions to airflow within the airflow channel 302 because the internal diameter beyond the step is the same as the internal diameter of the mouthpiece 204.

The mounting plate 212 of the primary component forms part of an additional connection mechanism. Only some of the secondary components utilise the additional connection mechanism. The additional connection mechanism provides an additional point of contact between the primary component 102 and a secondary component to be connected to the primary component by utilising the mounting plate 212. In order to connect a secondary component to the primary component through the mounting plate, the secondary component comprises a threaded knob which passes through the mounting plate 212 of the primary component and screws into the secondary component. This robustly and repeatably aligns the secondary component with the primary component. It also aids with the connection of various shaped and sized components and resists impacts caused by dropping or bumping the device and forces that might cause the secondary component to move relative to the primary component. Other mechanisms may be used to provide this mechanical stability. For example, the rotational position could be located by a spline feature and the axial position could be located by a stepped feature or snapping lock mechanism. Ideally, a mechanism is provided to fix relative rotational position, locate relative axial position, and resist bumps, vibrations, and forces that might seek to displace the secondary component relative to the primary component.

In the spirometry configuration of Figure 2 and 3 the flow sensor 306 used to measure flow rate has a range of ±200 litres per minute. This is lower than typical flow rates for spirometry tests which may reach up to ±850 litres per minute. Such a flow sensor 306 is chosen because other tests performed by the device, when the device is in other configurations, require a low flow rate. A flow sensor with a smaller range, i.e. a range of considerably lower than ±850 litres per minute, has sufficient resolution for these low flow rate applications. For higher flow rate applications, such as spirometry test, the effective range of the flow sensor 306 has to be extended. This is achieved by the spirometry component 202, and in particular the presence of the bypass holes 210.

The design of the spirometry component means that the airflow channel 302 effectively splits. One channel is formed through the bypass holes and another channel is formed past the flow sensor so only a portion of airflow in or out from the subject passes the flow sensor. The airflow channels have different resistances, and it is the resistance of each of the channels that determines the proportion of air that flows through each of the channels. The ratio of the resistances of the airflow channels can be chosen to ensure that the expected flow rate past the sensor always falls within the range of the sensor. The following relationship can be used.

(R_bypass) /(R_sensor) = (Max_Flow_Sensor_Range) I (Expected_Max_Subject_Flow Max_Flow_Sensor_Range)

At the maximum expected flow rate from the subject, the portion of flow in the airflow channel passing 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 passing the flow sensor compared to out of the air bypass holes is dependent on the overall air flow and is a non-linear relationship. The control circuitry is programmed to scale up any measurement at the flow sensor to a value that represents the total flow using the non-linear relationship.

With this configuration, the effective range of the flow sensor 306 increases from ±200 litres per minute to ±1000 litres per minute, as required for a spirometry test (that reaches ±850 litres per minute).

As part of the spirometry test, the control circuitry receives measurements from the flow sensor 306 in order to calculate or measure a number of different metrics. Each metric gives an indication of the mechanical properties of the subject’s lungs. These metrics include Peak Expiratory Flow (PEF), Forced Expiratory Volume in 1 second (FEV1), Forced Expiratory Flow (FEF) and Force Expiratory Volume (FEV) and finally Force Inspiratory Flow (FIF). Lung volumes are calculated by integrating flow rate over time.

To measure PEF the subject inflates their lungs to a maximum volume, then exhales with as high a flow rate as they are able to produce. The PEF value is the maximum flow rate produced, measured in litres per minute by the flow sensor or pressure sensor.

To measure FEV1 the subject inflates their lungs to a maximum volume, then exhales with as high a flow rate as they are able to produce. The FEV1 value is the maximum expired volume within the first second of expiration, typically measured in litres.

FEF and FEV are similar to PEF and FEV1 respectively but are more general metrics representing any expiration flow rate rather than peak flow rate as well volumes over any time interval rather than a fixed first second of expiration. They can be measured at any point of the exhalation. FIF, similar to FEF but for inhalation rather than exhalation, is also calculated.

The tidal volume (VT) is calculated as the volume of gas exchanged in one breath of normal tidal breathing. Tidal breathing is defined as inhalation and exhalation during restful breathing. At rest, also known as “quiet breathing”, tidal breathing tends to have a narrow range between the depth of the breath and amount that is exhaled and tends to be fairly consistent. Respiratory diseases can change the normal character of this breathing and cause inconsistencies over a number of breaths.

The Forced Vital Capacity (FVC) can also be calculated, this is the volume exchanged from a maximum inhalation and maximum exhalation. Other volume measurements that are routinely used in clinical assessment and research can also be calculated using the device, most are calculated as the extreme inspiration or expiration volume relative to a minimum or maximum volume from tidal breathing.

As well as using the above metrics individually, the control circuitry 106 is programmed to combine some metrics in order to calculate additional metrics. In this example, the ratio of FEV1 to FVC (as a percentage) is used as an indicator of airway resistance or obstruction and the control circuitry calculates this ratio. A low value for FEV1 to FVC ratio may indicate high airway resistance or that the airways are obstructed. High airway resistance or the presence of obstruction suggests the subject has a respiratory condition such as asthma or COPD.

Multiple values are calculated from a single inhalation and/or exhalation. The tests can be repeated and a highest, lowest, or average of the test values can be used as the reported value.

Spirometry metrics can be measured over time to monitor the progression of a subject’s disease or to indicate if the subject is responding to a medical treatment. Spirometry metrics for a subject can be compared to expected values for the subject, given their age, weight, height, ethnicity, sex, and other demographic variables. Spirometry values can be measured before and after exposure to a trigger to determine if the subject’s respiratory condition has sensitivity to the trigger. Spirometry values can be measured before and after a treatment such as a bronchodilator, to determine if the subject’s respiratory condition has response to the treatment.

The device 100 may use Bluetooth to transfer data from the control circuitry 106 to a computer. This may be a portable computer such as a laptop or smartphone. The portable computer is configured to process the data to provide a test score which can be used to help monitor or diagnose a respiratory disease. This processing of data may include plotting graphs of flow rate versus time, volume versus time, and volume versus flow rate. The shapes of the curves on these graphs at different events in the respiratory cycle can be indicative of a subject’s respiratory condition. Other data transfer means are possible, for example a wired connection between the device and the external computer. In some embodiments the device will process the data internally using the control circuitry. Test scores and other data outputs can then be displayed to the subject on a display integral to the device. This may include displaying graphs.

In the spirometry configuration the air bypass holes 210 of the spirometry component 202 alters the airflow channel so that the flow sensor is suitable for performing spirometry tests. By changing the spirometry component connected to the primary component to a different component (or simply by removing it), a different airflow channel is formed for performing a different respiratory diagnostic test.

Figure 6 is a perspective view showing the device 100 for performing a plurality of respiratory diagnostic tests in a second configuration for performing a second diagnostic test. In this case the spirometry component 202 is no longer engaged to the primary component 102. Instead the secondary component connected to the primary component 102 is a nitric oxide sensor module 602. Figure 7 shows the second airflow channel 702 in this configuration.

In the second configuration the device is configured to perform a diagnostic test which involves measuring nitric oxide concentration in the exhaled breath. The second secondary component in this configuration is a nitric oxide sensor component 602. In this configuration the primary component 102 is the same as in the first configuration. The control circuitry 106 is also the same. The mouthpiece 603 is different to mouthpiece 204 in this embodiment of the device. The mouthpiece 603 comprises a gas drier 704 which the mouthpiece 204 does not comprise. In some other embodiments the same type of mouthpiece 204 may be used in both the first and second configurations. In these embodiments the gas drier 704 may be located in the nitric oxide sensor component 602.

At the bottom of the nitric oxide sensor component 602 is the nitric oxide sensor 604. The nitric oxide sensor 604 is an electrochemical sensor and is an AlphaSense NO-B4 which is available from Sensor Technology House 300 Avenue West, Skyline 120, Great Notley, Braintree CM77 7AA. The sensor contains an electronics board that establishes electrode voltages for electrochemical reactions within the sensor and amplifies the signal produced by the sensor. The concentration of exhaled nitric oxide is measured by the nitric oxide sensor 604. The measurement is received by the control circuitry. The nitric oxide sensor component 602 is in electrical communication with the control circuitry 106. The control circuitry 106 provides power and receives data from the nitric oxide sensor module 602 by an electrical connection. The nitric oxide sensor module has two outlet holes 608. Only one of these is visible in Figure 6. In Figure 7, the airflow channel 702 is shown to split in the nitric oxide sensor module as it passes through the outlet holes 608.

The nitric oxide sensor component 602 utilises the additional connection mechanism. The threaded knob 606 of the nitric oxide module 602 passes through the mounting plate 212 and into a guide in the nitric oxide module (not visible). The threaded knob 606 at the top of the device axially locates and secures the nitric oxide sensor component to the device. The electrochemical sensor is sensitive to its orientation relative to gravity and vibrations. The aligning guide and threaded knob 606 help ensure the central axis of the cylindrical sensor is aligned vertically, with the correct side upwards.

Nitric oxide concentration is used to indicate biological processes such as eosinophil activity. Eosinophil activity can be raised as part of the airway inflammation process. High exhaled nitric oxide concentration is used as an indicator for the subtype of a respiratory disease and probable response to inhaled corticosteroids. Exhaled nitric oxide concentration can be monitored over time to determine response to a treatment, anticipate attacks or exacerbations or periods of severe symptoms, determine if a subject is taking their prescribed treatment regularly and with good technique, and to titrate dosage of a treatment to a level that controls the subject’s condition but without excess that is wasteful and can cause side effects.

The control circuitry 106, or a separate computing device, is configured for the exhaled nitric oxide test. This software configuration acquires data from the sensors used in this configuration, and displays data and calculated values for the subject’s test. The software may also instruct the subject how to perform the test.

In the nitric oxide respiratory test, the subject exhales into the mouthpiece 204 at a slow and constant flow rate of about 50 mL/s ±10% for a duration of 10 seconds for adults or 6 seconds for some children. The intention of this test is to measure nitric oxide that is produced from the distal airways. 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 portion of the total air flow resistance for breathing. Distal airways encourage laminar flow of air.

Exhalation should be against a positive expiratory pressure, caused by an increased resistance to the exhaled flow in the device. The positive expiratory pressure ensures the nasal velum remains shut. The expiratory pressure should be at least 5 cm H2O to keep the velum shut but pressures above 20 cm H2O can be uncomfortable for the subject. Air in the nasal passages can have high concentrations of nitric oxide, which can contaminate the exhaled air from the lungs if the velum opens during the exhalation.

The gas drier 704 in the mouthpiece 603 acts as a flow resistor to increase the exhaled pressure above 5 cm H2O but keep it less than 20 cm H2O. This contrasts with the spirometry configuration in which flow resistance is desirably as low as possible. The mouthpiece 603 may also comprise a microbe filter to avoid infections being passed from multiple subjects using the device. The microbe filter is not shown.

The exhaled flow rates are lower and therefore exhaled volumes of gas are smaller compared to the spirometry tests. Thus, there is an even greater need to minimize the unused volume or dead space volume within the flow channel 702. The gas drier 704 and microbe filter occupies space within the mouthpiece 603, thus reducing the internal volume of the flow channel 702. 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 at a right angles to the incident airflow channel 702, which are not visible in Figure 7. A change in flow direction above the electrochemical sensor’s sensing surface encourages mixing of the air and avoids stagnant zones of air near the surface membrane of the sensor. The outlet of the airflow channel 602 is preferably near to the nitric oxide sensor.

In another embodiment, the subject may exhale through their nose rather than their mouth at a constant rate to measure the concentration and rate of production of nitric oxide in the nasal passages. In this embodiment the mouthpiece is replaced with a nasal mask.

The nitric oxide sensor 604 is an electrochemical sensor. Electrochemical sensors use reactions in electrochemical cells to detect the presence of gases. The temperature, humidity and pressure of the environment can affect the physics of theses reactions. The rate of change of humidity and changes to pressure from the airflow can also affect the reactions. These changes to the reactions can change cause an inaccurate measurement of nitric oxide concentration.

Exhaled air contains a high moisture content, generally much higher than the ambient humidity of the air that was inhaled. As previously described, the mouthpiece 603 comprises a gas drier 704 which is formed of a moisture absorbent material. This absorbs moisture present in exhaled air and so avoids condensation forming on the flow sensor 306, the environmental sensors 208, and the nitric oxide sensor 604, which may cause errors in the measurements made by those sensors. The moisture absorbent 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 ambient environment.

In alternative embodiments of the device the absorbent material, microbe filter, and flow resistor may be positioned in a secondary component rather than in the mouthpiece.

The axial distances between the mouthpiece 106, flow sensor 306, environmental sensors 208, and nitric oxide sensor module 602 are minimised. Low axial distance between these components results in a low internal volume of the device and thus minimised wasted volume in the flow channel 702. An additional advantage of reducing the axial distance between the sensors is that this ensures the properties of the air are similar at each of the sensors at any given time.

When exhalation begins, the air pressure in the airflow channel 702 increases as a function of downstream resistance and flow rate. As the nitric oxide sensor has a cross-sensitivity to pressure and changes in pressure, the rate of change of pressure at the start of the exhalation should be minimized. Locating the nitric oxide sensor near the outlet minimizes the downstream resistance between the nitric oxide sensor and the outlet and thus minimizes the pressure transient and thus minimizes the nitric oxide sensor’s response to the pressure transient.

The respiratory tract is divided into upper airways and lower airways. The upper airways include the nose and nasal cavity, the Pharynx and the Larynx. The lower airways include the Trachea, Primary Bronchi and Lungs. In tests such as the nitric oxide test it is the air from the lower airways that is important. When breathing out, the first 3 seconds of an exhalation may contain air from the upper airways mixed in with air from the lower airways. In some embodiments the control circuitry contains instructions to disregard this three second portion of the exhalation for nitric oxide concentration measurements. In other embodiments, a control valve could route different durations or portions of exhaled air towards or away from particular sensors within the device.

It has already been described how the device 100 may have a plurality of configurations. Figure 8 is a schematic of four different configurations of device, showing the components that form an airflow path in each of the configurations. Figure 8 differs to Figure 1 in that it shows the sensors that are found in each component. The sensors are shown generally as sensor number 1 to sensor number 6. Each of the sensors is different. In each configuration the primary component comprises the same four sensors 1 to 4. Secondary components may or may not comprise the additional sensors.

Figure 8a shows the device 100 in a configuration where the airflow channel is formed through only the primary component 102. This configuration is the most basic configuration of the device. This configuration of the device can be used to perform spirometry tests. That configuration is described below in relation to Figure 9. The primary component comprises sensors 1 to 4 which can be used to measure parameters of air in the airflow channel. The four sensors are a flow sensor, a temperature sensor, a humidity sensor and a pressure sensor. Each of the configurations of the device shown in Figure 8 comprises the same primary component 102, and so comprises the same four sensors.

Figure 8b shows how the device 100 can 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 such that the airflow channel is defined through the primary component 102 and secondary component 802. The device in this configuration can be used to perform spirometry tests and was described above in relation to Figures 2 and 3. The secondary component 802 does not comprise any sensors. The secondary component changes the airflow channel defined through the device, compared to the airflow channel that is defined through the device of Figure 8a. Secondary component 802 may be equivalent to spirometry component 202 of Figures 2 and 3 and so may comprise air bypass holes that alter the airflow channel, for example. This configuration can also be applied for oscillometry tests, as will be described.

Figure 8c shows another configuration of the device with secondary component 804, different to secondary component 802, connected to the primary component 102 such that an airflow channel is defined through the primary component 102 and secondary component 804. The device in this configuration can be used to perform a biomarker test, where the biomarker may be, for example, nitric oxide concentration. Such a test was described above in relation to Figures 6 and 7. Secondary component 804 comprises sensor number 5. In the case of the biomarker being nitric oxide concentration, sensor number 5 is a nitric oxide sensor equivalent to the nitric oxide sensor 604 of Figures 6 and 7 and secondary component 804 is a nitric oxide sensor module.

Figure 8d shows another configuration of the device with secondary component 806, different to secondary component 802 or secondary component 804, connected to the primary component 102 such that an airflow channel is defined through the primary component 102 and secondary component 806. The device in this configuration can used to perform a test for a biomarker that is not nitric oxide, for example, the biomarker may be carbon dioxide. The secondary component 806 therefore differs to secondary component 804 in that it comprises a sensor for detecting carbon dioxide rather nitric oxide. Such a test is referred to as a capnometry test and is described in more detail below.

Figure 9 is a device configured as in Figure 8a for performing spirometry tests in an alternative embodiment to that shown in Figure 2 and Figure 8b. The device in this configuration has only the primary component, which comprises the flow sensor 306 and the control circuitry 106 which is connected to the mouthpiece 204. There is no spirometry component 202 and so there are no air bypass holes 210. Therefore, all the air passes the flow sensor 306. The same flow sensor is used as in the embodiment shown in Figure 2 and so is designed with a range that is lower than the typical flow rates used in spirometry tests. In this embodiment the control circuitry 106 receives signals from a pressure sensor, which is one of the environmental sensors 208, and uses measurements from that sensor in combination with measurements from flow sensor 306 to generate a flow measurement which may be outside the normal range of the flow sensor 306, which is lower than the high flow rate of the spirometry tests as was described previously.

The control circuitry 106 uses measurements from the flow sensor 306 primarily for measuring low flow rates. The pressure sensor is used primarily for measuring high flow rates. Figure 10 is graph showing how the signals from the flow sensor and the pressure sensor can be combined. The graph shows the flow rate of a subject performing a series of inhalation and exhalation breath maneuverers over time. The flow rate increases from zero to a peak flow rate and then decreases back to zero for each breath maneuverer. The true value is shown by 1002.

The flow rate as measured by the flow sensor is shown by 1004. For low flow rates the flow sensor is accurate and measurements of flow are close to the true value. However, once the flow rate goes above the maximum range of the flow sensor, the flow sensor is not able to then measure flow rate.

The flow rate as measured by the pressure sensor is shown by 1006. For low flow rates the pressure sensor is far less accurate than the flow sensor and tends to under-estimate the flow rate. However, as flow rates increase the accuracy of the pressure sensor increases. At flow rates above the maximum range of the flow sensor 306 the pressure sensor is able to reasonably accurately measure the flow rate and provide a value close to the true value.

The control circuitry 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 combined measurement has the benefit of accuracy of the flow sensor at the low range with the extended range of the pressure sensor for higher flow rates. In other embodiments of the device humidity and temperature sensors can be used in addition to the pressure sensor to provide further measurements that can be used in the adjustment of the flow measurements to account for humidity and temperature conditions.

The spirometry configuration of Figure 9 is an example of how the control circuitry can be configured to adjust measurements it receives from one of the sensors of the device that can form a metric for one of the respiratory diagnostic tests using other measurements or signals received from another sensor or sensors. The microprocessor is programmed with various models which describe how a system behaves given certain inputs. This may include different models for each of the different configurations. It can use these models to adjust a measurement which might be inaccurate.

The nitric oxide concentration test described previously also uses an adjustment process. One of the limitations when performing the nitric oxide concentration tests is the crosssensitivity of the electrochemical sensor 604 and how much this is affected by changes in ambient environmental conditions. A device configured for performing the nitric oxide concentration test was described in relation to Figures 6 and 7. A gas drier 704, is used to reduce the effects of environmental conditions on measurements taken by the nitric oxide sensor 604. However, the control circuitry 106 may be programmed to be able to further adjust the measurement from the nitric oxide sensor 604 using measurements from sensors measuring environmental conditions, namely pressure, temperature, and humidity.

Exhaled breath has relative humidity near 100%, which is higher than typical ambient environmental relative humidity. The exhaled air replaces ambient air at the surface of the electrochemical sensor and so there is a high rate of change of relative humidity experienced by the surface of the nitric oxide sensor 604. This rapid change in humidity causes the electrochemical sensor to output a response which cannot be easily separated from the response caused by a change in the concentration of nitric oxide. As such, the measurement will be inaccurate.

The humidity sensor measures the moisture content of air passing over it. The control circuitry 106 receives the measurements from both the humidity sensor and the nitric oxide sensor 604. The control circuitry 106 is programmed with models of the behaviour nitric oxide sensor 604 and its response to different environmental conditions. It uses those models to calculate the true nitric oxide concentration by compensating for the portion of the nitric oxide sensor’s signal that can be attributed to the rate of change of relative humidity. The nitric oxide sensor also has a sensitivity to rates of change of pressure, temperature and flow. In some embodiments the measurements from the electrochemical sensor are further compensated by the control circuitry 106 using measurements of pressure, temperature and flow with a more complex model programmed into the control circuitry 106.

Figure 11 is a graph showing the adjustment of the signal from the nitric oxide sensor to achieve a more accurate measurement nitric oxide concentration. Line 1102 shows the true nitric oxide concentration and how it changes over time. Line 1104 shows the measured nitric oxide taken directly from the electrochemical sensors. These measurements are inaccurate and fall far below the true values. 1106 shows a relative humidity adjustment factor that is calculated as the negative rate of change of the humidity as a percentage. Subtracting the value of line 1106 from the value of line 1104 results in an adjusted signal that is much closer to the true value 1102. This subtraction is demonstrated by lines 1108 and 1110 which are of equal height. In some embodiments temperature, pressure and flow adjustment factors can be calculated and subtracted from the measured nitric oxide concentration 1104 too.

The adjustment process will now be described generally. The control circuitry may receive a measurement of parameter A from a first sensor, which is the parameter of interest and which may be used to form a metric which can be used in the monitoring or diagnosis of a respiratory disease. The measurement of parameter A may have limitations, particularly with respect the accuracy of the measurement. Parameter B may be used to account for these limitations in a model stored in the control circuitry. Parameter B may be an environmental parameter such as temperature, pressure or humidity. A sensor is used to measure parameter B which is received at the microprocessor. Parameter B is generally measured by a second sensor. However, in some embodiments parameter B may be calculated from the measurement of parameter A. For example, parameter B may be the rate of change of parameter A and is calculated by the microprocessor. The adjustment improves accuracy and repeatability of measurements of parameter A. In some cases a linear model is used, in others a more complex non-linear model is more accurate.

There could be any number of additional parameters (parameter C, parameter D etc.) that the accuracy of the measurements of parameter A dependent on. Each of these parameters may also be measured. The model that the microprocessor is programmed with includes these additional parameters and so the measurement 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, it is not a requirement that all sensors are used. Sensors can switched on and off by the control circuitry as required.

In each configuration of the device 100 a subset of sensors is used to measure the relevant parameter A and any subsequent parameters that are required in the adjustment of parameter A.

It is beneficial that subsets of sensors in different configurations share sensors as it reduces the total number of sensors that are required. One sensor can be used in more than one test. If the various tests were being performed by separate devices then sensors that exist in both subsets would need to be duplicated. Having one device, being configurable to perform multiple tests, allows for the sharing of sensors and so leads to a reduction in total number of sensors required to perform the same number of tests.

The subsets of sensors used in the configurations of the device so far described will now be summarised.

The first spirometry configuration, as shown in Figures 2 and 3 as well as being represented by Figure 8b, has a subset of sensors comprising only a flow sensor.

The second spirometry configuration, as shown in Figure 9, as well as being represented by Figure 8a, has a subset of sensors generally comprising a flow sensor and a pressure sensor and the control circuitry is configured to use measurements of to adjust measurements of flow in order to make high flow measurements. In some embodiments of the second spirometry configuration, the subset of sensors may also comprise a temperature and a humidity sensor. The control circuitry is configured to use measurements of temperature and humidity to adjust the measurements of flow.

The nitric oxide concentration configuration, as shown in Figures 6 and 7, as well as being represented by Figure 8c, has a subset of sensors generally comprising a nitric oxide sensor, a pressure sensor, a temperature sensor and a humidity sensor wherein the control circuitry is configured to use measurements of pressure, temperature and humidity to adjust the measurements of nitric oxide concentration. The subset of sensors may also comprise a flow sensor and the control circuitry is configured to use measurements from the flow sensor to adjust measurements made by the nitric oxide sensor.

The flow sensor is common to the subsets of sensors of both the first and second spirometry configurations. The flow sensor is also common to the subset of sensors of the nitric oxide concentration configuration in embodiments that use flow measurements to adjust nitric oxide concentration measurements made by the nitric oxide sensor.

The pressure sensor is common to the subsets of sensors of both the second spirometry configuration and the nitric oxide concentration configuration.

The temperature and humidity sensors are common to both the nitric oxide concentration and embodiments of the second spirometry configuration that use temperature and humidity sensors to adjust flow measurements made by the flow sensor.

Each of the configurations of the device so far described shares sensors with each of the other configurations.

An example method for using the device 100 will now be described with reference to relation to Figure 12. Figure 12 is a flow chart of the method of use of the device.

At step 1202 the device is placed in a first configuration. The first configuration may be the spirometry test configuration shown in Figure 2. A mouthpiece 204 is connected to the spirometry component 202, for a subject to breathe into. A new mouthpiece is used for each individual subject of the device. Only the sensors that are required need be switched on. The switching on and off of sensors is managed by the control circuitry. In some embodiments the control circuitry can detect which configuration the device is in and automatically switch on the correct sensors, in other embodiments a subject input indicates the configuration to the control circuitry.

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

At step 1206, after completion of the breath manoeuvres, the control circuitry outputs the results of the spirometry test. This may be done by wireless data transfer to a smart phone or computer, for example. The wireless data transfer may be over Bluetooth. In some embodiments a display may be fitted into the device itself which displays the results of the test. In some embodiments software either stored in the control circuitry or on a computer or portable device that may 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 may be stored to maintain a record of past tests. This record of past tests can be used in a diagnosis process and to monitor changes in a subject’s health over time.

At step 1208 the device is placed in a second configuration. The second configuration may be the nitric oxide test configuration shown in Figure 6. To achieve this configuration the spirometry component 202 is disconnected from the primary component 102. The mouthpiece 603 is then connected to the primary component 102 in the position that the spirometry component 202 was connected. At the other end of the primary component 102, the nitric oxide sensor module 602 is connected. This defines an airflow channel through the mouthpiece 204, the primary component 102 and into the nitric oxide sensor module 602. In this configuration the control circuitry switches on the nitric oxide sensor 604, the flow sensor 306 and the environmental sensors 208 which includes pressure, temperature and humidity sensors.

At step 1210 the subject completes breath manoeuvres through the device 100 in the nitric oxide concentration test configuration. Again, in some embodiments the control circuitry 106 indicates to the subject what these manoeuvres should be. However, a trained medical professional may instruct the subject. Alternatively, an instruction manual may be provided. These breath manoeuvres include slow inhalation and exhalation. Measurements of nitric oxide concentration are received at the control circuitry 106 from the nitric oxide sensor 604. The control circuitry 106 will adjust the measurements of nitric oxide concentration using measurements from the flow sensor, pressure sensor, temperature sensor and/or humidity sensor to account for the cross-sensitives of the nitric oxide sensor 604.

At step 1212, after completion of the breath manoeuvres, the control circuitry may output the results of the nitric oxide test. This may be done by wireless data transfer to a smart phone or computer, for example. The wireless data transfer may be over Bluetooth. In some embodiments a display may be fitted into the device itself which displays the results of the test. In some embodiments software, either stored in the control circuitry/microcontroller or a computer or portable device, may 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 may be stored to maintain a record of past tests. This record of past tests can be used in a diagnosis process and to monitor changes in a subject’s health over time.

The results of the spirometry test and the NO test may be presented together or in some combined form to aid diagnosis and monitoring of a particular respiratory diagnostic disease.

To demonstrate that the device is configurable to perform a plurality of respiratory diagnostic tests, spirometry and nitric oxide tests have been used as examples of respiratory diagnostic tests the device can be configured to perform. An example of another test that the device may be configured to perform is an oscillometry test which is another diagnostic test which can help to diagnosis of respiratory diseases such as COPD. Oscillometry tests are used to indicate mechanical properties of the airways of the subject. The device in the oscillometry configuration is shown in Figure 13.

In the oscillometry configuration the device comprises the primary component 102 with the microcontroller 106. The primary component 102 is connected to a mouthpiece 204 on a first side and to a secondary component on a second side.

The secondary component is an oscillometry module 1302. In order to connect the oscillometry module 1302 to the primary component 102 through the mounting plate, the secondary component comprises a threaded knob 1303 which passes through the mounting plate 212 of the primary component 102 and screws into the secondary component. This robustly and repeatably aligns the secondary component with the primary component.

The oscillometry module 1302 comprises an occluder 1304 and a means to move the occluder 1305. The means to move the occluder is a linear actuator. The occluder comprises an O-ring 1306. The oscillometry module 1302 is in electrical contact with the primary component 102. This means that signals can be sent and received from the microcontroller 106 in the primary component to the oscillometry module 1302.

Figure 14 is the same side view of the device 100 as Figure 13, but showing the occluder 1304 in the second position rather than in the first position. In Figure 2 the O-ring 1306 of the occluder 1304 is shown to be in contact with housing 209 of the primary component 102.

The microcontroller 106 can send signals to the linear actuator causing it to move the occluder 1304 from the position shown in Figure 13, which is the first position, to the position shown in Figure 2, which is the second position. Power can also be transferred to the oscillometry module 1302 through the electrical contact. This provides power to the linear actuator that can be used to move the occluder between the first and second position. The force of the linear actuator may cause vibrations through the device that cause the oscillometry module 1302 to move relative to the primary component 102. The use of a threaded knob 1303 to connect the oscillometry module to the primary component 102 reduces this movement.

In some embodiments of the device the oscillometry module 1302 comprises a battery in addition to the power source powering the control circuitry of the primary component 102. The power requirements of a linear actuator, such as a solenoid, are higher than what many small batteries are able to produce. By having an additional battery located in the oscillometry module 1302, the power supplied to the linear actuator can be increased to the required level.

In other embodiments of the device, the primary component 102 or the oscillometry module 1302 comprises a capacitor instead of, or as well as, having the additional battery. The capacitor is configured to be charged by the at least one battery and to discharge through the linear actuator. A high power burst can be created when the capacitor is discharged. This high power burst meets the power requirements of the linear actuator.

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

Figure 15 is a cross-sectional view of the oscillometry module 1302 in isolation from the rest of the device 100. The linear actuator 1305 comprises a main body 1502 and a solenoid. The linear actuator is a Johnson Electric Model 51 STA Push DC Tubular Solenoid available from RS components at: 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 such that the occluder moves from the first position to the second position. When the power supply is switched off the occluder 1304 will move back to the first position. This may be due to a biasing spring or magnetic return system, not shown. In some embodiments the linear actuator is a push-pull linear actuator. In these embodiments the occluder is returned to the first position by forces applied by the linear actuator when a voltage of different polarity to the first voltage is applied to the linear actuator.

The control circuitry 106 is configured to cause the linear actuator 1305 to move the occluder 1304 from a first position to a second position and back to a first position again at least 3 times each second during a testing period. Creating multiple acoustic impulses throughout a test allows a full picture of the airways and shows how the airways changes throughout the duration of a breath.

Figure 16 is a cross-sectional perspective view of the device 100. Figure 16 shows the airflow channel represented by dotted line 1602 through the device 100. The airflow channel is defined through the mouthpiece 202 and housing 207 and 209 of the primary component 102. The airflow channel 1602 terminates at an air outlet. The air outlet is at the end of housing 209 nearest the occluder 1304. If the direction of flow of air in the airflow channel is toward the mouthpiece then the air outlet is instead an air inlet. In either case, the air outlet or air inlet are the same thing and positioned at the end of housing 209 nearest the occluder 1304. The direction of movement of the occluder from the first position to the second position is parallel to the airflow channel.

If, when the occluder is in the second position the O-ring 1306 is in contact with the housing 209, then the airflow channel 1602 is sealed at the outlet. In this case, air cannot escape the outlet from the airflow channel when the occluder is in the second position.

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 Oring 1306 and the housing. The airflow channel is then not sealed at the outlet. In this case, air can escape the outlet from the airflow channel when the occluder is in the second position.

A method for using the device in the oscillometry configuration, in order to perform an oscillometry test, will now be described in relation to Figure 17. At step 1702 the subject breaths through the device. The breathing required is normal, tidal breathing. The subject continues to breathe through the device for the duration of the test. The subject breathes in and out through the mouthpiece 204 of the device. The subject’s breath will pass in and out of their airways, through the airflow channel 1602. As the subject inhales, air will enter the airflow channel 1602 through the air inlet, positioned at the end of housing 209 nearest the occluder 1304. As the subject exhales, air will exit the airflow channel out through the air inlet, which is now considered an air outlet.

In some embodiments, the subject may only breathe in through the device 100. In these embodiments air enters the device through the air inlet, passes through the airflow channel 1602 toward the mouthpiece 204 and into the subject’s airways. The subject would then breathe out directly into the atmosphere and so exhaled breath would not pass through the airflow channel 1602 of the device.

In some embodiments, the subject may only breathe out through the device 100. In these embodiments the subject would breathe in air directly from the atmosphere. The subject would then exhale through the mouthpiece 204 of the device 100. The exhaled breath would pass through the airflow channel 1602 of the device 100 and out of the air inlet.

At step 1704 an acoustic impulse is created in the air in the airflow channel. The acoustic impulse is created when the occluder 1304 is moved from the first position to the second position by the linear actuator 1305. 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 the push of air is an impulse of increased flow that passes through the airflow channel 1302 in the direction of the mouthpiece. The occluder is moved by the linear actuator 1305 with enough force that the push on the air in the airflow channel 1602 results in increased flow of at least 0.15 litres per second in the direction of the mouthpiece.

The flow impulse that passes through the airflow channel results in a pressure transient which has an amplitude of at least 50 Pa. The acoustic impulse travels through the airflow channel 1602 and into the airway of the subject resulting in changes in the pressure and flow rate of the air passing the sensor. As the acoustic impulse progresses it experiences damping. This causes a reduction in the amplitudes of pressure and flow. A flow rate increase of 0.15 litres per second and a pressure increase of 50 Pa in the direction of the mouthpiece is enough to provide a significant and measurable response.

The acoustic impulse is made up of sinusoidal pressure fluctuations having frequencies between 5 Hz and 20 Hz.

At the end of step 1704, after the acoustic impulse has been created, the occluder is returned to the first position.

The resistance to flow will be higher when the occluder 1304 is in the second position than when the occluder is in the first position. While 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 impulse. Both the length of time that the occluder is in the second position for and the configuration of the occluder may affect the amount the pressure changes in the airflow channel and so the characteristics of the acoustic impulse. The configuration of the occluder refers particularly to the amount to which the occluder increases the resistance to flow when the occluder is in the second position compared to when it is in the first position.

If the resistance to flow in the airflow channel is sufficiently low when the occluder is in the second position, the pressure build-up in the airflow channel will be negligible. Therefore, the change to the characteristics of the acoustic impulse will also be negligible. In this case the occluder in the second position is not in contact with the housing 209 of the primary 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 with the occluder in the second position is not as high as if the occluder was closer to, or in contact with, the housing. Changes in pressure 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 for. The occluder remains in the second position for no more than 20 ms before being returned to the first position.

A negligible pressure change in the airflow channel, as a result of the occluder being in the second position, means that a relatively simple mathematical model is required. This simplifies the mathematics, particularly calculations using Fast Fourier Transforms. A minimal pressure build-up is also more comfortable for the subject using the device. If the change in pressure in the airflow channel is too substantial the subject will notice the change while breathing through the device which may cause discomfort and interrupt tidal breathing.

If the resistance to flow 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 significant period of time, then there will be a non-negligible pressure change in the airflow channel. Therefore, the changes to the characteristics of the acoustic impulse will also be non-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 primary component 102. There may be no gap between the occluder and the housing 209. The length of time the occluder is in the second position for may be longer than 20 ms.

The change in characteristics of the acoustic impulse may be an increase in the amplitude of the acoustic impulse. This is because a pressure build-up in the airflow channel contributes additional energy to the acoustic impulse. It is also because the occluder in the second position more efficiently directs the energy of the acoustic impulse into the airflow channel and toward the mouthpiece.

At step 1706 the flow and pressure of air in the airflow channel are sensed by the flow sensor 306 and the pressure sensor in the sensor assembly 304. This sensing determines the flow and pressure due to the subject’s breathing which is normal, tidal, breathing. The control circuitry receives the measurements from the flow and pressure sensors. The control circuitry will analyse the signals by performing a Fourier Transform. The amplitude of the pressure fluctuations at frequencies from 5 Hz to 20 Hz can then be continuously measured. The control circuitry stores the results of the measurements and the Fourier Transform.

At step 1708 an acoustic impulse is created by the device by moving the occluder from the first position to the second position. The flow and pressure of air in the airflow channel are sensed continuously by the flow sensor 306 and the pressure sensor in the sensor assembly 304 for a period of 150 ms. The 150 ms sensing period begins momentarily before the occluder begins its movement from the first position to the second position. 150 ms is long enough to include measurements after the acoustic impulse has entered the subject’s airways as well as immediately after creation of the acoustic impulse. The flow and pressure measurements are a superposition of the flow and pressure resulting from the subject’s breathing with the flow and pressure resulting from the acoustic impulse. The control circuitry performs a Fourier Transform on the pressure and flow signals and stores the measurements and the results of the Fourier Transform. The measurements of the superimposed flow and pressure can be compared to the measurements of flow and pressure in step 506. This allows the separation of the pressure and flow signal resulting from the subject’s breathing from the portion of the signal that is caused by and in response to the acoustic impulse. The control circuitry can use the response of the acoustic impulse to calculate metrics indicating characteristics of a subject’s airway.

Steps 1704 to 1708 may be repeated any number of times during a test, while a subject breathes through the device. These steps may be repeated at least three times every second. The measurements taken each time that step 1706 and 1708 is performed are stored in the control circuitry 106. Repeating steps 1704 to 1708 means that measurements can be taken throughout the duration of a breath and so any change in the characteristics of the airways of the subject can be detected.

At step 1710 the control circuitry 106 outputs the results of the oscillometry test. This may be done by wireless data transfer to a smart phone or computer, for example. The wireless data transfer may be over Bluetooth. In some embodiments a display may be fitted into the device itself. In some embodiments software either stored in the control circuitry 106 or on a computer or portable device that may 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 may be stored to maintain a record of past tests. This record of past tests can be used in a diagnosis process and to monitor changes in a subject’s health over time.

Note that the oscillometry configuration has a subset of sensors comprising a flow sensor and a pressure sensor. In some embodiments, the oscillometry configuration also comprises a temperature sensor and a humidity sensor. In these embodiments, the control circuitry is configured to use measurements from the temperature, humidity and pressure sensor to adjust measurements made by the flow sensor.

The flow sensor is the same flow sensor as referred to previously and so is common to the subsets of sensors of both the first and second spirometry configurations. The flow sensor is also common to embodiments of the nitric oxide concentration configuration that use the flow sensor.

The pressure sensor is the same pressure sensor as referred to previously and so is common to the subsets of sensors of the second spirometry configuration and the nitric oxide configuration.

The device 100 may be configured to perform a capnometry test. Capnometry is the measurement of exhaled carbon dioxide. The capnometry configuration of the device is very similar to the configuration for performing nitric oxide concentration tests as shown in Figures 6 and 7. In the case of capnometry, the secondary component, comprising a nitric oxide sensor 604, is replaced with a near identical secondary component that instead comprises a carbon dioxide sensor. The carbon dioxide sensor is a SprintlR-20 from Gas Sensing Solutions.

The carbon dioxide sensor uses a non-dispersive infrared absorption operating principle. It is sensitive to condensation, so a gas drier is used to ensure the humidity at the sensor is non-condensing. The same gas drying component may be used for the capnometry and nitric oxide tests. However, the capnometry test does not require additional flow resistance, as the nitric oxide test does, and it is preferable to have a low flow resistance in the airflow channel.

A sampling frequency of at least 20 Hz, from the carbon dioxide sensor, is preferred to accurately record the transient showing how carbon dioxide concentration changes with time. The peak value of carbon dioxide concentration may be of interest. The capnometry transient is thought to change as symptoms worsen and may provide warning that a subject may soon have an asthma attack or COPD exacerbation. Higher peak values of exhaled carbon dioxide indicate a high concentration of carbon dioxide in the blood. This suggests impairment of the respiratory or cardiovascular system of the subject.

The shape of the carbon dioxide concentration transient during tidal breathing can also be used as an indicator of respiratory performance. A more gradual increase in exhaled carbon dioxide concentration may indicate respiratory obstruction or higher airway resistance. However, this method is not able to distinguish if a lower rate of increase in carbon dioxide concentration is from slower airflow or slower transfer of carbon dioxide from the blood to the airways. In some embodiments the carbon dioxide concentration measurements are combined with measurements of flow rate. This provides more information as to the relative contributions to the exhaled carbon dioxide signal i.e. whether it is related to airflow speed or from transfer rate of carbon dioxide from the blood to the air in the lungs.

The capnometry configuration, in some embodiments, has a subset of sensors comprising a carbon dioxide sensor and a flow sensor. The flow sensor is common to the subsets of sensors of both the first and second spirometry configurations, the nitric oxide test configuration and the oscillometry configuration.

In some embodiments the device comprises a display. The display can act as a user interface for the device. The display or user interface may be a touch screen display. The user interface allows the subject to manually input data into the device, the subject to send commands to the device, the device to provide instructions to the subject, and the device to present results to the subject. It may be a trained medical professional that interacts with the user interface rather than the subject. The display may be part of the device. However, it may also be part of a portable computer such as a laptop or smartphone which the control circuitry is able to transfer data to.

Figure 18 shows a first embodiment of a display on an interface of the device. This shows the device in testing mode. The interface in this embodiment is designed for subjects with limited medical training and so provides only simple feedback to the subject rather than complicated metrics.

The display includes an option for entering the subject the test is for 1802, which allows the result to be saved in a database as belonging to that user. In this case the subject is John Smith.

The display includes an option for instructing the device which test is to be performed 1804. In this case the test that is to be performed is a nitric oxide test. In embodiments of the device in accordance with Figures 1a to 1d, the device instructs the subject to reconfigure the components of the device to modify the airflow channel for the selected test. In embodiments of the device in accordance with Figure 1e, the device itself will reconfigure the components of the device to modify the airflow channel required for the test. For example, the control circuitry may send a signal to valves between components to open or close to configure an airflow path through the device.

In an alternative embodiment, the device may detect what configuration it is in after the subject has manually configured the components of the device to modify the airflow channel for the required test. In these embodiments, there is no need for an option for the subject to select what test the device is to perform.

The subject can manually input data into the device. This is shown in Figure 18 as the symptom score input 1806. Other useful data that could be manually entered includes recent allergen exposure, weather, air quality, and medicine taken. In some embodiments additional data could be imported automatically from other sources such as from a wearable device, smart inhaler, smartphone, electronic health record, or internet-based API. The user interface can include provision to view these additional data alongside data or results created by tests on the device itself.

The display includes a test action input 1808 that is used to instruct the device to begin a test or cancel a test in progress.

The display includes a test coaching output 1809 that provides instruction to the subject, generally after the test has begun. In Figure 15, the test that is being performed is a test of nitric oxide concentration in exhaled air. This test needs to be performed with a controlled exhalation of breath by the subject. The speed of the exhaled breath needs to be maintained at a controlled speed or flow rate and for a minimum duration. The display informs the subject as to whether the exhale speed is suitable and for how long they have been exhaling for.

The display includes an output for showing the test result 1810. In this example, the test was an exhaled nitric oxide test and so the output is a concentration of nitric oxide given in parts per billion. This panel also provides the user with a test validation output 1812 to indicate to the user if the result was successful or if the next needs to be repeated.

Determining whether the test was a success may depend on whether the user followed the test coaching instructions as above.

Figure 19 shows another embodiment of the user interface that is designed for medical professionals. It allows the medical professional to review the test of a subject with more detail of the results of the test than Figure 18.

As in Figure 18, input buttons 1802 and 1804 allow the subject and test to be selected. In this case the test that has been selected is a spirometry test.

The test result panel 1810 shows output metrics calculated from the test. The panel is the same as the previous embodiment shown in Figure 18, but shows the results for a different test (for a spirometry test instead of an FeNO test). The detailed test result 1902 panel shows a graph of the test result, in greater detail than the calculated metrics. An experienced and trained medical professional may gain additional detail from the graph than the output metric alone. Preferably, the metrics in the test result panel 1810 and the axes of the detailed test result panel 1902 graphs are pre-populated according to the type of test selected using the select test input button 1804. However, in some embodiments there is provision for the user to select what output metrics and axes are shown.

In some embodiments, a less detailed result for another test could be shown in a separate panel of this display. The display of multiple tests allows the user to interpret the results of multiple data sources jointly.

The display includes an input to add details for the subject 1904. For example, entering details for a subject such as height, weight, age, sex, and ethnicity can be used to establish predicted values for the test result.

In both Figures 15 and 16 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 the screen shown in Figure 20 which is a display that recalls data from previous tests.

The display shown in Figure 20 includes an input button to select the user to display data for 2002, an input button to put the device into test mode 2004, and to add a type of test to the display 2006. After a subject and test are selected, graphs of test results versus time are plotted in the panels of the user interface 2008, 2010 and 2012. As illustrative examples, spirometry, exhaled nitric oxide, and manually entered data are plotted in the display. These displays can assist a subject or medical professional in understanding the time history of metrics related to their medical condition. A benefit of having multiple tests on the device is that it is easier for multiple tests to be displayed in a way that can be compared and interpreted.

Figure 21 is an additional display of the user interface where the test results from a current subject are compared to those of other subjects. Input buttons allow the user to select the subject 2102, a first metric 2104, and a second metric 2106. Two metrics are shown here illustratively; this display can also be used with one metric or more than two metrics. The graph on the main panel 2108 is generated and displayed, which compares the results for these tests for the subject 2102, with those from other subjects from different subject groups from an existing database with the representation of the different groups shown in the legend panel 2110 The other subjects can be classified, for example as group a, group b, and group c. This classification and display can aid the user in determining if the current subject has characteristics similar to a classified group of other subjects from the existing database. The classification of subjects into group a, group b, group c, etc. could be based on successful response to a particular treatment or if these people are known to have a certain disease sub-type.

Claims

1. A device for performing a plurality of respiratory diagnostic tests, comprising:

a housing, a sensor assembly, and control circuitry configured to receive signals from the sensor assembly; wherein the device has a first configuration in which the device is configured to perform a first respiratory diagnostic test and a second configuration in which the device is configured to perform a second respiratory diagnostic test, wherein in the first configuration an airflow channel is defined through the device housing, the sensor assembly being configured to measure at least a first property of air in the airflow channel during the first respiratory diagnostic test, and wherein in the second configuration the airflow channel is modified relative to the first configuration, the sensor assembly being used to measure at least a second property of air in the airflow channel during the second respiratory diagnostic test.

2. A device 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. A device for performing a plurality of respiratory diagnostic tests according to claim

1 or claim 2, wherein one of the first and second respiratory diagnostic tests is a pulmonary obstruction or flow test and the other of the first and second respiratory diagnostic tests is a biomarker test.

4. A device for performing a plurality of respiratory diagnostic tests according to any preceding claim wherein the housing comprises a primary component defining a least a portion of the airflow channel and a first secondary component, wherein the first secondary component has a first position relative to the primary component in the first configuration and a second position relative to the primary component in the second configuration.

5. A device for performing a plurality of respiratory diagnostic tests according to claim

4 wherein the first secondary component comprises a sensor.

6. A device for performing a plurality of respiratory diagnostic tests according to claims 4 or 5 wherein the sensor assembly is positioned at least partially in the primary component.

7. A device for performing a plurality of respiratory diagnostic tests according to claims 4 to 6 wherein in the first configuration the primary component and the first secondary component are engaged to one another to define the airflow channel and wherein in the second configuration the primary component and the first secondary component are disengaged from one another.

8. A device for performing a plurality of respiratory diagnostic tests according to claim 7, further comprising a second secondary component and wherein in the second configuration the primary component is engaged with a second secondary component.

9. A device for performing a plurality of respiratory diagnostic tests according to any one of claims 4 to 8 wherein the sensor assembly comprises a flow sensor and wherein the flow sensor is positioned in the primary component.

10. A device for performing a plurality of respiratory diagnostic tests according to any one of the preceding claims, wherein the first or second respiratory diagnostic test is a spirometry test.

11. A device for performing a plurality of respiratory diagnostic tests according to any one of the preceding claims wherein the airflow channel comprises a least one bypass channel such that in at least one of the first and second configurations a portion of an airflow through the device bypasses the sensor assembly.

12. A device for performing a plurality of respiratory diagnostic tests according to claim

11 wherein in at least one of the first and second configurations at least 60% by volume of the airflow through the device bypasses the sensor assembly.

13. A device for performing a plurality of respiratory diagnostic tests according to any preceding claim further comprising an electrochemical sensor, wherein the sensor assembly comprises at least one of a pressure sensor, flow sensor, temperature sensor and humidity sensor, and wherein the control circuitry is configured to adjust a signal from the electrochemical sensor using a signal from at least one of the pressure sensor, flow sensor, temperature sensor and humidity sensor.

14. A device for performing a plurality of respiratory diagnostic tests according to any one of the preceding claims further comprises a scavenger filter in the airflow channel.

15. A device for performing a plurality of respiratory diagnostic tests according to claim 14 further comprising a valve configured to change an airflow path through the airflow channel depending on the direction of the flow of air through the airflow channel wherein the airflow passes the scavenger filter in only one direction.

16. A device for performing a plurality of respiratory diagnostic tests according to any one of the preceding claims, further comprising a gas drier in the airflow channel.

17. A device for performing a plurality of respiratory diagnostic tests according to any preceding claim wherein in one of the first and second respiratory diagnostic tests is an impulse oscillometry test.

18. A device for performing a plurality of respiratory diagnostic tests according to claim 17 comprising an occluder and a means to move the occluder between a first position and a second position wherein the occluder is configured to create an acoustic impulse in the air in the airflow channel.

19. A kit for performing a plurality of respiratory diagnostic tests, comprising:

a primary component, a secondary component, a control circuitry, and a sensor assembly positioned in the primary component or secondary component or in both the primary and secondary components, wherein the secondary component is configured to engage the primary component in a first configuration of the kit such that a first airflow channel is formed through the primary and secondary components so that a first respiratory diagnostic test can be performed, and wherein in a second configuration of the kit a second airflow channel is formed through the kit passing through at least the primary component so that a second respiratory diagnostic test can be performed and wherein the kit can be changed from a first configuration to a second configuration without using any tools.

20. A kit for performing a plurality of respiratory diagnostic tests according to claim 19 wherein one of the first and second respiratory diagnostic tests is a pulmonary obstruction or flow test and the other of the first and second respiratory diagnostic tests is a biomarker test.

21. A kit for performing a plurality of respiratory diagnostic tests according to claim 19 or 20 wherein the primary component comprises the sensor assembly and the control circuitry.

22. A kit for performing a plurality of respiratory diagnostic tests according to claim 19,

20 or 21, further comprising a mouthpiece configured to engage the primary component or the secondary component, or both the primary component and the secondary component.

23. A method for performing a plurality of respiratory diagnostic tests using a device according to any of claims 1 to 18, comprising the steps of:

putting the device in a first configuration for performing a first respiratory diagnostic test such that the device defines a first airflow channel through the device and performing the first respiratory diagnostic test;

24. A method for performing a plurality of respiratory diagnostic tests using a device according to claim 23 further comprising outputting a test result, wherein the test result is a combination of results from the first and the second test.

25. A method for performing a plurality of respiratory diagnostic tests using a device according to claims 23 or 24 wherein one of the first and second respiratory

5 diagnostic tests is a pulmonary obstruction or flow test and the other of the first and second respiratory diagnostic tests is a biomarker test.