WO2024033095A1

WO2024033095A1 - Spirometer

Info

Publication number: WO2024033095A1
Application number: PCT/EP2023/070781
Authority: WO
Inventors: Riccardo Riva Reggiori
Original assignee: Philip Morris Products S.A.
Priority date: 2022-08-12
Filing date: 2023-07-26
Publication date: 2024-02-15

Abstract

A spirometer comprising an air inlet configured to receive exhaled breath; an air outlet; a conduit connecting the air inlet and the air outlet; a flow meter configured to measure at least one of a flow rate, a speed and a volume of exhaled breath passing through the conduit from the air inlet to the air outlet; a light emitter configured to illuminate the exhaled breath passing through the conduit with ultraviolet light of a predetermined wavelength or range of wavelengths; a light receiver configured to receive modified light signals from the illuminated exhaled breath passing through the conduit; and at least one controller configured to process data obtained by the flow meter and the light receiver; wherein the light emitter is configured both to emit light during passage of exhaled breath through the conduit such that the emitted light is modified by exhaled components in the exhaled breath and the modified light is received by the light receiver, and to emit light before or after passage of exhaled breath through the conduit so as to sterilize the conduit.

Description

SPIROMETER

The present disclosure relates to a spirometer, and in particular to a spirometer that is configured to enable measurement of predetermined biomarkers in the form of volatile organic compounds (VOCs) in a user’s breath.

There is a desire to promote healthier behaviour in smokers and users of electronic aerosolgenerating devices that can generate an aerosol and deliver the aerosol to a user’s mouth or lungs. Some aerosol-generating devices use the application of heat to a liquid or solid substrate to generate the aerosol. Other aerosol-generating devices can generate an aerosol from a powder. Even among non-smokers, there may be a desire to test for or monitor levels of certain biomarkers in the form of VOCs, for example to give an indication of exposure to atmospheric pollution.

With particular reference to smokers or users of nicotine-based aerosol-generating devices, it may be desirable to test for or monitor nicotine levels in a person’s body. Indeed, it could be desirable for an aerosol-generating device to incorporate some means of limiting the amount of nicotine delivered by the device when the level of nicotine in the user’s body rises above a predetermined threshold.

However, it is not possible to infer an amount of nicotine in a user’s body from an amount of nicotine generated by an aerosol-generating device. This is because there are many different types of aerosol-generating device using different delivery mechanisms. Furthermore, users of such devices often use them in different ways, with some users preferring to hold the generated aerosol in the mouth, and others preferring to inhale the generated aerosol, and many users employing a combination of methods.

It is known to determine nicotine levels in a person’s bloodstream by way of qualitative and quantitative blood tests. This may be done either by testing nicotine levels directly, or by testing for levels of nicotine metabolites such as cotinine. Testing for cotinine is sometimes preferred, since cotinine has a half-life in the body of between 7 and 40 hours, compared to a half-life of around 1 to 4 hours for nicotine. Another metabolite of interest is anabasine, which is found in tobacco products but not in nicotine-replacement products.

As an example, the cotinine level in the bloodstream of a non-smoker with no second-hand smoke exposure is typically less than 1 ng/ml. Cotinine levels between 10 and 100ng/ml are associated with light smoking or moderate second-hand smoke exposure, and cotinine levels above 300ng/ml are associated with heavy smoking habits.

While blood sample testing is accurate, it is expensive and time consuming. Moreover, taking blood samples is an invasive procedure, and is not suited for frequent use. An alternative is to test for nicotine or metabolites of nicotine in saliva or urine. This is less invasive, but is still expensive and time-consuming. The results of a saliva or urine test, for example using a lateral flow device, typically require about 20 to 30 minutes.

Personal carbon monoxide breath sample analysers are known. Breath sampling is advantageous because it is less invasive than other sampling techniques, and can provide a result in seconds rather than minutes. Such analysers do not provide a direct indication of nicotine levels in a person’s body, but rather an indication of carbon monoxide levels. Carbon monoxide levels have a reasonable correlation with nicotine levels in smokers of traditional “burn” type tobacco products, such as cigarettes and cigars, where smoke from burning organic material is inhaled by a smoker. However, there is much less correlation between carbon monoxide levels and nicotine levels in users of “heat-not-burn” type tobacco products or other nicotine- replacement products, due to the lack of burned materials in the ingested aerosol.

It is also known to test directly for nicotine and other VOCs in exhaled breath, but these tests typically involve complex equipment and procedures, such as gas chromatography or proton transfer reaction mass spectrometry.

Accordingly, it would be desirable to provide a device to help smokers and users of aerosolgenerating devices, as well as any other people, to obtain information about personal nicotine levels or levels of other VOCs, for example with a view to controlling these levels.

According to an aspect of the present invention, there is provided a spirometer comprising: an air inlet configured to receive exhaled breath; an air outlet; a conduit connecting the air inlet and the air outlet; a flow meter configured to measure at least one of a flow rate, a speed and a volume of exhaled breath passing through the conduit from the air inlet to the air outlet; a light emitter configured to illuminate exhaled breath passing through the conduit with ultraviolet light of a predetermined wavelength or range of wavelengths; a light receiver configured to receive modified light signals from the illuminated exhaled breath passing through the conduit; and at least one controller configured to process data obtained by the flow meter and the light receiver; wherein the light emitter is configured both to emit light during passage of exhaled breath through the conduit such that the emitted light is modified by exhaled components in the exhaled breath and the modified light is received by the light receiver, and to emit light before or after passage of exhaled breath through the conduit so as to sterilize the conduit.

The conduit is preferably configured so that the exhaled breath flows directly from the air inlet to the air outlet without circulating or residing in an intervening collection receptacle. The light emitter is configured to illuminate exhaled breath passing through the conduit with ultraviolet light so as to elicit a modified light signal response from chemical components that are present in the exhaled breath and that interact directly with the ultraviolet light so as to generate the modified light signals. The light emitter, the light receiver and the controller may together be configured to perform ultraviolet absorption spectroscopic analysis of the exhaled breath passing through the conduit. In particular, the chemical components in the exhaled breath are not tagged with fluorescent probes in the spirometer. Rather, the presence of relevant chemical components in the exhaled breath is determined solely on the basis of illuminating the as-exhaled breath with ultraviolet light and analysing the ultraviolet light after it has been modified by interaction with the as-exhaled, untagged, chemical components. The modified light signal may differ from the emitted light signal due to absorption of characteristic frequencies of emitted light by the chemical components of interest due to characteristic electronic transitions in the as-exhaled chemical components when they are illuminated by ultraviolet light. The modified light signal may alternatively or additionally differ from the emitted light signal due to absorption of characteristic frequencies of emitted light by the chemical components of interest due to other characteristic transitions between particular vibrational chemical bond states or electron rotational states. Accordingly, it is not necessary to mix the exhaled breath with a supply of fluorescent probes so as to tag the chemical components.

Measurement of at least one of a flow rate, a speed and a volume of the exhaled breath passing through the conduit helps to ensure that the exhaled breath meets predetermined flow characteristics indicative of an exhalation sufficiently complete so as to ensure that the exhaled breath will include relevant chemical components that have diffused from a user’s bloodstream into the air in the user’s alveoli. Measurement of at least one of a flow rate, a speed and a volume of the exhaled breath passing through the conduit may also allow a measured concentration of chemical components in the exhaled breath to be normalised, thus allowing a meaningful blood concentration of the chemical components in the user’s body to be calculated.

The controller may be a microcontroller or microprocessor. The controller may be configured to control the light emitter so as to switch on and off at predetermined times. The controller may be configured to control the light emitter so as to switch on and off in response to the measurements obtained by the flow meter. The controller may be configured to provide a user indication that the flow meter has determined that the exhaled breath has satisfactory flow characteristics. The controller may be configured to provide a user indication that the flow meter has determined that the exhaled breath does not meet predetermined flow thresholds. The user indication may be a visual indication, such as a light signal; an audible indication, such as a beep; or a haptic indication, such as a vibration.

In some embodiments, the spirometer comprises: a housing having a port; and a removable tubular member having first and second opposed ends and a lumen extending between the first and second ends, wherein the conduit comprises the lumen.

Provision of a removable tubular member with a lumen that defines at least part of the conduit allows different people to use the same spirometer with a reduced risk of crosscontamination. Each user may have their own removable tubular member. The removable tubular member may be a single-use disposable item.

The first end of the removeable tubular member may extend from the housing, and the second end of the removeable tubular member may be adjacent a base of the port when the removeable tubular member is inserted into the port.

The first end of the removeable tubular member extending from the housing may form a convenient mouthpiece allowing a user to form a good seal around the first end of the removable tubular member with their lips. Alternatively, the first end of the removeable tubular member extending from the housing may form a convenient mount for a separate mouthpiece to be attached before using the spirometer. The separate mouthpiece may be a single-use disposable item.

By locating the second end of the removeable tubular member adjacent to the base of the port, for example contacting the base of the port, it is easy for a user to ensure that the removeable tubular member is properly inserted in the housing so as to provide a good flow path for exhaled breath through the spirometer. This arrangement also facilitates electronic or optical or electronic and optical connection between the removeable tubular member and the housing of the spirometer, as will be set out in more detail hereinbelow.

The first end of the removable tubular member may define the air inlet.

The base of the port may comprise an opening in fluid communication with the lumen at the second end of the removeable tubular member, and the opening may define the air outlet.

In this way, a flow path for exhaled breath is established from the air inlet at the first end of the removeable tubular member, through the lumen of the removeable tubular member, and through the opening at the base of the port.

The light emitter may be disposed at the base of the port. The light emitter may be a component of the housing. In other words, the light emitter may not be a component of the removeable tubular member. When the light emitter is a component of the housing, a power source for the light emitter may also be incorporated in the housing. The power source may be a battery. Locating the light emitter and the power source in the housing means that these components do not need to be included in the removeable tubular member, which is advantageous if the removeable tubular member is configured as a single-use disposable item.

The light emitter may comprise a first light emitter and a second light emitter. The first light emitter and the second light emitter may be configured to emit ultraviolet light of different intensities. Additionally or alternatively, the first light emitter and the second light emitter may be configured to emit ultraviolet light of different wavelengths. Additionally or alternatively, the first light emitter and the second light emitter may be configured to emit ultraviolet light with different illumination regimes (for example, steady state illumination, pulsed illumination, differently- directed illumination).

The removable tubular member may comprise an optical guide extending from the second end of the removable tubular member to a wall of the lumen, and the optical guide may be configured to guide light from the first light emitter to the lumen when the removable tubular member is received in the port. Providing an optical guide in the removeable tubular member is cheaper than providing an active light emitter in the removeable tubular member, especially if the removeable tubular member is configured as a single-use disposable component. The optical guide may be made of transparent plastics or glass material configured to promote internal reflection so as to guide light from the first light emitter at the base of the port to a wall of the lumen of the removeable tubular member, where the light can exit an end of the optical guide to illuminate the exhaled breath. The optical guide may be configured so as to illuminate the exhaled breath in the lumen of the removeable tubular member with a more precise directivity than might be possible from a more diffuse direct light source.

The second light emitter may be configured to emit light directly into the lumen at the second end of the removeable tubular member when the removable tubular member is received in the port. This may be advantageous then the second light emitter is configured to emit ultraviolet light with different characteristics to the ultraviolet light emitted by the first light emitter, as will be explained in more detail hereinbelow.

The flow meter may be located on a wall of the lumen of the removable tubular member. The lumen of the removeable tubular member is a region where flow characteristics can be reliably measured, due to the generally uniform flow path in this region.

The light receiver may be located on a wall of the lumen of the removable tubular member. It may be advantageous to separate the light receiver from the light emitter so as to reduce the amount of ultraviolet light impinging on the light receiver directly from the light emitter without interacting with the chemical components in the exhaled breath.

A biosensor may be located on a wall of the lumen of the removable tubular member. The biosensor may comprise one or more sensor sites at which chemical components of interest in the exhaled breath may be adsorbed. The biosensor may comprise at least one silicon photonic device. The biosensor may comprise at least one interferometer. The biosensor may comprise at least one silicon photonic integrated interferometer. The silicon photonic device or interferometer or silicon photonic interferometer may be configured to detect a presence and optionally an amount of a chemical component of interest when adsorbed at the one or more sensor sites.

The controller may be located in the housing. The removable tubular member may have an electrical connection configured electrically to engage with a corresponding electrical connection in the port when the removable tubular member is received in the port. This allows electrical components mounted on or in the removeable tubular member to be powered by the power source in the housing, and to be controlled by the controller in the housing.

The removeable tubular member may be disposable.

The spirometer may further comprise a detachable mouthpiece fitted to the first end of the removeable tubular member. The detachable mouthpiece may be a single-use disposable item so as to reduce cross-contamination between users.

The light emitter may be configured to emit light having a wavelength from 10Onm to 400nm. The light emitter may be configured to emit light having a wavelength from 240nm to 280nm. The light emitter may be configured to emit light having a wavelength from 260nm to 265nm. The light emitter may be configured to emit light having a wavelength of substantially 262nm.

Ultraviolet light in the wavelength range from 240nm to 280nm, preferably 260nm to 265nm, for example substantially 262nm, is of particular interest. This is because ultraviolet light of this wavelength or wavelengths is not only centred on a significant ultraviolet absorbance line for nicotine (262nm), but is also at or around the absorbance wavelength for DNA/RNA (about 260nm). Accordingly, not only will ultraviolet light in this range of wavelengths enable detection of nicotine or nicotine-containing VOCs in the exhaled breath, but it will also help to kill viruses or bacteria that might otherwise contaminate the lumen of the removeable tubular member or the inside of the housing or other internal parts of the spirometer.

The light emitter is configured both to emit light during passage of exhaled breath through the conduit such that the emitted light is modified by exhaled components in the exhaled breath and the modified light is received by the light receiver, and to emit light before or after passage of exhaled breath through the conduit so as to sterilize the conduit.

The light emitter may comprise a light emitting diode. The light emitter may comprise a laser. The light emitter may comprise a tuneable diode laser.

The spirometer may comprise a first light emitter and a second light emitter.

The first light emitter may comprise a laser, and the second light emitter may comprise a light emitting diode. Alternatively, the first and second light emitters be both comprise lasers, or may both comprise light emitting diodes, or the first light emitter may comprise a light emitting diode and the second light emitter may comprise a laser.

The first light emitter may be configured to emit light during passage of exhaled breath through the conduit such that the emitted light is modified by exhaled components in the exhaled breath and the modified light is received by the light receiver; and the second light emitter may be configured to emit light before or after passage of exhaled breath through the conduit so as to sterilize the conduit. Using a laser as the first light emitter may be preferred when the first light emitter is being used to elicit a modified light response from the chemical components in the exhaled breath. This is because the light receiver will be looking for characteristic ultraviolet absorptions due to electron transitions in the chemical components of interest, and it is advantageous to utilise ultraviolet light of a well-specified wavelength or narrow band of wavelengths for this purpose. Lasers are well- suited to generating light of a specified wavelength or a narrow band of wavelengths.

Using a light emitting diode as the second light emitter may be preferred when the second light emitter is being used to generate ultraviolet light for the purpose of sterilising the removeable tubular member or other internal parts of the spirometer. This is because a broader range of ultraviolet wavelengths is more appropriate for sterilisation purposes, since the intention is to disrupt a variety of different chemical bonds within DNA or RNA of viruses, bacteria or other microorganisms. A non-laser light emitting diode may be better suited for generating a broader spectrum of ultraviolet light.

The light emitter may be provided with an optical guide to direct light into the conduit. The optical guide may be made of transparent plastics or glass material configured to promote internal reflection so as to guide light from the light emitter to the conduit, where the light can exit an end of the optical guide to illuminate the exhaled breath. The optical guide may be configured so as to illuminate the exhaled breath in the conduit with a more precise directivity than might be possible from a more diffuse direct light source. Separating the light emitter from the conduit by an optical guide may reduce unwanted stray illumination from the light emitter that might otherwise swamp the light receiver.

The conduit may comprise an internal surface, and the internal surface may comprise an optical stopper to reduce reflection of light emitted by the light emitter. The optical stopper may comprise a non-reflective coating on the internal surface.

The predetermined wavelength or range of wavelengths may be selected to detect a presence in the exhaled breath of at least one predetermined volatile organic compound, VOC. The at least one predetermined VOC may be selected from: nicotine, cotinine, anabasine, nicotine metabolites, cannabinoids, cannabinoid metabolites, nitric oxide, nitrous oxide, carbon monoxide, carbon dioxide, and compounds containing one or more of oxygen, sulphur, nitrogen and halogens.

The flow meter may comprise an ultrasonic transducer. The flow meter may comprise a pressure sensor.

The flow meter and the controller may be configured to detect and distinguish between an initial phase of exhalation, in which substantially unmodified air is expelled from a user’s trachea and bronchi and passes through the conduit, and a final phase of exhalation, in which air that has resided in the user’s alveoli and contains levels of VOCs representative of corresponding blood levels of biomarkers of interest passes through the conduit. The controller may be configured to record data from the light receiver only during the final phase of exhalation.

The controller may be configured to normalise detected levels of VOCs with air flow values determined by the flow meter.

As previously noted, in order to detect VOCs representative of particular biomarkers that are present within a user’s bloodstream, it is best to analyse exhaled breath that contains air that has been expelled from a user’s alveoli. This is because of diffusion and gaseous exchange that takes place between air and a user’s bloodstream in the alveoli. The flow meter and the controller can together be used to detect and distinguish between an initial phase of exhalation and a final phase of exhalation, and the light emitter and light receiver can be activated so as to analyse the exhaled breath only in the final phase of exhalation.

The flow meter and the controller may be configured to determine and record an exhalation duration for each exhalation.

The flow meter and the controller may be configured to determine and record an exhalation velocity profile against time for each exhalation.

The flow meter and the controller may be configured to determine and record an exhalation flow rate profile against time for each exhalation.

Determining and recording at least one of the exhalation duration, exhalation velocity profile against time and exhalation flow rate profile against time for each exhalation may enable a personalised data profile to be established for a user. The personalised data profile may facilitate identification of at least one of the initial phase of exhalation and the final phase of exhalation. The personalised data profile may provide other useful data, for example lung function over time or lung capacity over time, which may be useful for health monitoring purposes.

The controller may comprise or be provided with an interface for communication with an external device. The interface may be configured to provide a wired connection to the external device. For example, the interface may comprise a universal serial bus (USB) wired connection. The interface may be configured to provide a wireless connection to the external device. For example, the interface may comprise a Bluetooth® or WiFi® wireless connection. The external device may be a computing device. The external device may be a mobile handset (for example, a smartphone) or a tablet. The external device may be a personal computer. The external device may be an aerosol-generating device. In some embodiments, the interface may be configured for communication with more than one external device. For example, the interface may be configured to communicate with both a mobile handset or tablet and with an aerosol-generating device.

The spirometer of embodiments of the present disclosure may be configured as a standalone device. That is, the spirometer may be configured as a device that is dedicated to measuring flow parameters of exhaled breath and to undertake ultraviolet spectral analysis of chemical components in the exhaled breath. Such a standalone device may optionally be operatively linked with an external device, for example an aerosol-generating device, a computing device (for example a mobile handset or tablet, or a personal computer), or both an aerosolgenerating device and a computing device. The standalone device may be operatively linked by a wired or by a wireless connection, or by a combination of wired and wireless connections.

The spirometer of embodiments of the present disclosure may be incorporated in an electronic aerosol-generating device.

The controller may be configured to adjust operation of the electronic aerosol-generating device in response to detected characteristics of the exhaled breath. The controller may be configured to reduce an amount or concentration of aerosolised compounds generated by the aerosol-generating device in response to the light receiver and controller detecting levels of VOCs associated with the aerosolised compounds above a predetermined threshold level. The controller may be configured to prevent operation of the aerosol-generating device in response to the light receiver and controller detecting levels of VOCs associated with the aerosolised compounds above a predetermined threshold level.

The air inlet may be provided with a detachable mouthpiece. A spirometer of embodiments of the present disclosure could be shared between different users by changing the mouthpiece and sterilising the conduit or the removeable tubular member or other internal parts of the spirometer with ultraviolet light between users.

The conduit may comprise a plurality of conduits. There may be a main conduit for passage of a bulk portion of exhaled breath, and at least one smaller conduit for passage of at least one smaller sample of exhaled breath. In some embodiments, the light emitter and light receiver may be configured to illuminate the exhaled breath in one or more of the smaller conduits rather than in the main conduit. In such embodiments, it may be necessary for the controller to apply a conversion factor to flow data obtained from the flow meter so as to compensate for different flow patterns in the at least one smaller conduit in order to obtain accurate inferred bloodstream levels of the chemical component of interest.

The controller may be configured to provide guidance to a user. The guidance may be provided by way of a display. The guidance may be provided by way of one or more lights, or one or more sounds, or one or more haptic signals, or a combination of such signals.

The controller may be configured to provide a periodic reminder to a user to exhale through the air inlet.

The controller may be configured to provide a confirmation, based on data received from the flow meter, that a user exhalation meets a predetermined flow characteristic.

The controller may be is configured to provide an indication, based on data received from the flow meter and data received from the light receiver, of a detected level of VOCs in the exhaled breath. The controller may be configured to provide an indication, based on data received from the flow meter and data received from the light receiver, of a calculated level of a predetermined chemical in a user’s bloodstream based on a detected level of VOCs in the exhaled breath, the VOCs being associated with the predetermined chemical.

By linking the operating characteristics of the aerosol-generating device to detected characteristics of the exhaled breath, it is possible to assist a user in keeping a level of absorbed aerosolised compounds in the user’s bloodstream below a desired threshold level. For example, where the aerosolised compounds include nicotine, the user may wish to maintain a bloodstream concentration level of nicotine to below a desired threshold level. The spirometer of embodiments of the present disclosure can infer the bloodstream concentration of nicotine by performing an ultraviolet spectral analysis of exhaled breath, and can prevent or limit operation of an operatively- linked aerosol-generating device so as to prevent ingestion of further nicotine from the aerosolgenerating device until the inferred bloodstream concentration of nicotine has fallen below the desired threshold level as determined by the spirometer.

In embodiments where the spirometer is connected to or incorporated in an aerosolgenerating device, the spirometer may be powered by a power source of the aerosol-generating device. Many aerosol-generating devices incorporate a rechargeable battery for driving a heating element.

If a measured or inferred nicotine level is above a predetermined threshold, the controller may issue a signal to the aerosol-generating device to cease operation, at least for a predetermined period of time. The controller may alternatively or additionally generate a warning signal to the user, for example a visual, audible or haptic warning signal. Once the measured or inferred nicotine level has fallen below the predetermined threshold, the controller may issue a signal to the aerosol-generating device to resume operation.

In embodiments where the spirometer is incorporated into an aerosol-generating device, the air inlet may be in fluid communication with a mouthpiece of the aerosol-generating device through which a user ingests aerosol from the aerosol-generating device. Accordingly, a user can provide an exhaled breath sample by using the same mouthpiece as used for ingesting aerosol from the aerosol-generating device. The combined spirometer and aerosol-generating device may sense, for example by way of the flow meter, whether a user is inhaling or exhaling, and may adjust a flow path through the combined device accordingly, for example by way of one or more valves. For example, when the combined device detects that a user is exhaling through the conduit, a valve may be opened to the air outlet so as to allow exhaled breath to leave the device. Conversely, when the combined device detects that a user is inhaling, the valve to the air outlet may be closed.

The spirometer may be configured to measure or infer a rate of increase of nicotine (or other compound of interest) in the user’s bloodstream, for example by requiring or prompting the user to provide repeated exhaled breath samples over a period of time. The rate of increase may be compared with previously-obtained data relating to the user, or with data relating to an aerosolgenerating consumable in the aerosol-generating device, or with data relating both to the user and to the aerosol-generating consumable, so as to determine whether or not the rate of increase of nicotine in the user’s bloodstream is compatible with the type of aerosol-generating consumable, the nicotine level of the aerosol-generating consumable, or personalised data profile of the user relating to nicotine metabolism.

The measured or inferred concentration level of nicotine or rate of increase of nicotine (or other compound of interest) in the user’s bloodstream may be used as a basis for adjusting the operation of the aerosol-generating device. For example, if the nicotine level or rate of increase of nicotine is determined to be higher than a predetermined threshold, the controller may issue a signal to adjust airflow through the aerosol-generating device so that each inhalation comprises a greater proportion of outside air that has bypassed the aerosol-generating consumable in the aerosol-generating device, for instance by operating appropriate valves. Alternatively or in addition, the controller may issue a signal to reduce or limit a temperature of a heater in the aerosol-generating device that causes aerosol to be generated from the aerosol-generating consumable. This could be achieved by reducing or limiting an amount of current available to the heater.

According to a second aspect of the present invention, there is provided a removeable tubular member configured for insertion into a spirometer, the tubular member comprising: first and second ends and a lumen extending between the first and second ends; an optical guide extending from the second end of the removable tubular member to a wall of the lumen; a flow meter located on the wall of the lumen; and a light receiver located on the wall of the lumen and configured to receive light emitted by the optical guide.

The spirometer may be the spirometer of the first aspect of the present invention. In other embodiments, the spirometer may not have all of the features of the spirometer of the first aspect of the invention, or may have additional features.

According to a third aspect of the present invention, there is provided a removable tubular member configured for insertion into the spirometer of the first aspect, the tubular member comprising: first and second ends and a lumen extending between the first and second ends, wherein the lumen comprises the conduit; an optical guide extending from the second end of the removable tubular member to a wall of the lumen, the optical guide configured to couple optically with the light emitter of the spirometer; the flow meter, wherein the flow meter is located on the wall of the lumen; and the light receiver, wherein the light receiver is located on the wall of the lumen and configured to receive light emitted by the optical guide.

The removeable tubular member may further comprise a biosensor located on the wall of the lumen.

The removeable tubular member may further comprise an electrical connection configured electrically to engage with a corresponding electrical connection in a port of a spirometer when the removable tubular member is received in the port.

The removeable tubular member may be configured as a consumable product, by which is meant that the removeable tubular member may be disposed of or recycled after use or after a predetermined number of uses. Different users may share the same spirometer device by using different removeable tubular members so as to improve hygiene.

As used herein, the term “aerosol-generating device” refers to a device configured to generate an aerosol from an aerosol-generating substrate. The aerosol-generating substrate may be a solid, a liquid, a gel or a powder. Aerosol may be generated by vaporisation from the aerosol-generating substrate. Vaporisation may be achieved by heating the aerosol-generating substrate.

As used herein, the term “biosensor” refers to an electronic component configured to generate a characteristic electronic or optical signal in response to a presence of a predetermined chemical component. The predetermined chemical component may be adsorbed on a sensor surface and give rise to measurable predetermined effects, for example surface plasmon resonance effects, which can for example be measured by interferometry.

As used herein, the term “conduit” refers to a passageway permitting fluid flow from a first location to a second location.

As used herein, the term “controller” refers to an electronic component or components configured to receive and process electronic signals. The controller may be a microprocessor or a microcontroller. The controller may be configured as one or more integrated circuits.

As used herein, the term “exhaled breath” refers to air that is expelled from a user’s lungs when a user breathes out, for example by blowing into the spirometer.

As used herein, the term “light receiver” refers to an electronic component configured to generate electronic signals representative of characteristics of light impinging on a sensor of the light receiver.

As used herein, the term “lumen” refers to a hollow interior of a tubular member defining a passageway for fluid flow.

As used herein, the term “optical guide” refers to a component configured to guide light from one location to another location, for example a light pipe, an optical waveguide, or a fibre optic guide. As used herein, the term “spirometer” refers to a device for measuring parameters of air exhaled from a user’s lungs.

Examples will now be further described with reference to the figures in which:

Figure 1 shows a schematic visual representation depicting breath phases of a single exhaled breath;

Figure 2 shows a removable tubular member configured for insertion into a spirometer;

Figure 3 shows a schematic cross-section through a port of a spirometer configured to receive the removable tubular member of Figure 2;

Figure 4 shows the removable tubular member of Figure 2 inserted into the port of the spirometer of Figure 3;

Figure 5 shows a user exhaling into the removable tubular member inserted into the port of the spirometer of Figure 4;

Figure 6 is a schematic outline of a system comprising a spirometer, a smartphone and an aerosol-generating device; and

Figure 7 is a flowchart illustrating an operating regime for the spirometer and aerosolgenerating device of Figure 6.

Figure 1 is a schematic visual representation depicting breath phases of a single exhaled breath (from Lawai, O. et al.; “Exhaled breath analysis: a review of ‘breath-taking’ methods for off-line analysis”; Metabolomics; (2017) 13:110; Springer). It is usual to distinguish three main phases in an exhaled breath, namely a dead space phase (Phase I) where the content of the exhaled breath reflects the content of any inhaled components; a transition phase (Phase II); and an alveolar or end tidal phase (Phase III). For the purpose of inferring a blood concentration of chemical components of interest from an exhaled breath concentration of the same or related chemical components of interest, the alveolar phase (Phase III) is of particular interest. This is because the exhaled breath of Phase III comprises air that has resided in a subject’s alveoli, where gaseous exchange and diffusion of chemical components from a subject’s bloodstream with air takes place. Accordingly, a measured concentration of VOCs in Phase III of the exhalation can provide a reasonable indication of a concentration of corresponding biomarkers in the subject’s bloodstream. The exhaled breath in Phase III is less likely to contain significant amounts of VOCs that are not of interest (for example, accidental or random VOCs inhaled from ambient air). Moreover, level of VOCs of interest in the exhaled breath in Phase III is more likely to be representative of the concentration of the corresponding biomarkers in the subject’s bloodstream than the level of VOCs in either Phase I or Phase II. Limiting the analysis of the exhaled breath to Phase III may also allow accurate results to be obtained both for users of aerosol-generating devices who inhale aerosols fully into the lungs, as well as for users of aerosol-generating devices who merely hold the aerosol in the mouth. For these different types of users, the VOC concentrations in Phases I or II may be very different, with neither being truly representative of a corresponding biomarker concentration in the bloodstream. In order to provide the most accurate results, it is desirable to normalise the measured VOC concentration in Phase III of the exhaled breath with air flow measurements for the exhaled breath.

Identification of the alveolar Phase III is usually determined by analysis of an individual’s expiratory pressure curve. This may be done, for example, by measuring an exhaled breath velocity. The measurements obtained may be personalised for an individual by taking measurements over several exhaled breaths and recording the parameters for each of the three phases. This can allow the important final, alveolar Phase III to be easily identified in subsequent exhalations.

In the following detailed description, reference will be made to nicotine as the compound of interest. That is to say, aerosol-generating devices will be described in the context of devices that generate a nicotine-containing aerosol from an aerosol-generating consumable, which may for example be in the form of a liquid or gel, or a homogenised tobacco substrate, or a nicotine- containing powder. A user of such an aerosol-generating devices can ingest nicotine from the aerosol by taking the aerosol into their mouth or lungs or both, and the nicotine will enter the user’s bloodstream. The presence of nicotine in the user’s bloodstream, or the presence of metabolites of nicotine in the user’s bloodstream, will cause at least one characteristic VOC to be diffused into air in the user’s alveoli as part of the normal respiration process. It is possible to infer a concentration level of nicotine in the user’s bloodstream by measuring a concentration of the at least one characteristic VOC in the exhaled breath of the user.

However, it will be understood that the present disclosure need not be restricted to nicotine, but may be used to measure concentration levels of other chemical components, for example cannabinoids, atmospheric pollutants, pharmaceuticals, disease indicators, and any other chemical component present in a user’s bloodstream that gives rise to the diffusion of at least one characteristic VOC into air in the user’s alveoli. Such VOCs may, for example, include one or more of oxygen, sulphur, nitrogen or halogens. For instance, nitric oxide (NO2) is known to be a biomarker of airway inflammation, chronic obstructive pulmonary disease (COPD) and asthma.

Ultraviolet spectroscopy analysis is based on the analysis of the absorption of ultraviolet light by a chemical component. Absorption of ultraviolet light excites particular electrons, for example in molecular orbitals, to transition to higher energy states, or to change rotational or vibrational states. Precise details of mechanisms of ultraviolet spectroscopy analysis are outside the scope of the present disclosure, but are well-known to those skilled in the art. All that needs to be understood in the context of the present disclosure is that different chemical components, for example in the form of VOCs, can be reliably identified by analysing how a sample containing these chemical components absorbs ultraviolet light. It is possible to determine which specific frequencies of ultraviolet light are absorbed, and by how much, by analysing how ultraviolet light is modified from a known wavelength or spectrum of wavelengths emitted by a light emitter due to passing through a sample of the chemical components of interest. This analysis can give an indication of the identity of a particular chemical component, such as a VOC, as well as an indication of the concentration of the chemical component in exhaled breath.

Breath sensors and exhaled breath analysis are attractive due to ease of sample collection (as compared to blood, urine or saliva samples). Ultraviolet absorption spectroscopic analysis of a breath sample is also advantageous by providing a very rapid result, within seconds, as opposed to chemical tests on blood, urine or saliva that can take up to half an hour.

A specific embodiment of the present disclosure, comprising a removeable tubular member

I and a housing 12, will now be described with reference to Figures 2 to 5.

Figure 2 shows a tubular member 1 having a first end 2 and a second end 22, and a lumen 30 extending between the first end 2 and the second end 22. The tubular member 1 is open at each of the first end 2 and the second end 22, with the lumen 30 defining a passage through which exhaled breath may pass. The tubular member 1 has a generally cylindrical body 11 that may be made of plastic. A printed circuit board (PCB) 9 is provided on or in the cylindrical body

I I of the tubular member 1. The PCB 9 hosts several electronic components, which may be in the form of integrated circuits or microelectromechanical systems (MEMS) devices or the like. In the illustrated embodiment, the PCB 9 hosts a flow meter 4, a light receiver 5, and a biosensor 6. The flow meter 4 may be a MEMS device. The flow meter 4 is configured to measure flow characteristics, namely at least one of flow rate, speed and volume, of air in the form of exhaled breath passing through the lumen 30 from the first end 2 to the second end 22. The light receiver 5 may be a photosensor, for example comprising at least one of silicon diodes, charge-coupled devices (CCDs), photodiodes, phototransistors, complementary metal-oxide semiconductor (CMOS) devices and the like. A bus 10 of electrical connections connects the various components on the PCB 9 to an electrical connector 8 at the second end 22 of the tubular member 1. The bus 10 and electrical connector 8 allow power to be supplied to the components on the PCB 9, and data to be transferred between the components on the PCB 9 and circuitry connected to the connector 8.

An optical guide 7 is also provided in or on the cylindrical body 11 of the tubular member 1 , extending from the second end 22 to a location 31 on the wall of the lumen 30. The optical guide 7 is configured to channel ultraviolet light from the second end 22 of the tubular member 1 to the location 31 , from where the ultraviolet light is emitted into the lumen 30. The lumen 30 may be lined with an optical stopper 3 to reduce unwanted reflection of the ultraviolet light emitted by the optical guide 7 at the location 31 from the wall of the lumen 30, since such reflection might overwhelm the light receiver 5.

Figure 3 shows a housing 12 having a port 23 configured to receive the tubular member 1 of Figure 2, as shown in more detail in Figures 4 and 5. The housing 12 may have an exterior 21 made of plastic. The port 23 may be sized and shaped to receive the tubular member 1 snugly. The port 23 has a base 40. When the tubular member 1 is correctly inserted into the port 23, the second end 22 of the tubular member 1 will be adjacent the base 40 of the port 23. An air outlet 14 is provided at the base 40 of the port 23 so as to allow egress of exhaled breath that has passed through the lumen 30 of the tubular member 1 when the tubular member 1 has been inserted into the port 23. A PCB 19 is provided at the base 40 of the port 23. The PCB 19 hosts several electronic components, which may be in the form of integrated circuits or microelectromechanical systems (MEMS) devices or the like. In the illustrated embodiment, the PCB 19 hosts a controller 15, a first light emitter 16 in the form of a tuneable ultraviolet laser diode, and a second light emitter 17 in the form of an ultraviolet LED. The PCB 19 is also provided with an electrical connector 18 configured for electrical connection with the electrical connector 8 of the tubular member 1 when the tubular member 1 is correctly inserted into the port 23. The first light emitter 16 is configured to cooperate with the optical guide 7 at the second end 22 of the tubular member 1 so that ultraviolet laser light can be guided from the first light emitter 16, through the optical guide 7 and to the location 31 on the wall of the lumen 30, as shown in Figure 4. The second light emitter 17 is configured to be operable to irradiate the lumen 30 of the tubular member 1 with ultraviolet light so as to sterilise the lumen 30 when required. The controller 15 is configured to control the various electronic components in both the tubular member 1 and the housing 12, and may also be configured to perform ultraviolet spectroscopy analysis of exhaled breath in the lumen 30 by way of the first light emitter 16 and the light receiver 5. A bus 20 of electrical connections connects the various components on the PCB 19 to the electrical connector 18, allowing transfer of power and data between the PCBs 19 and 9 and a power source (not shown). An external electrical connector 13, for example a USB connector, is provided on an external part of the housing 12 to allow data communication with an external computing device 50, for example a mobile handset or tablet, as shown in Figures 4 and 5. Power may also be supplied by way of electrical connector 13.

The tubular member 1 shown in Figure 2 may be personal to a particular user, or may be a consumable or disposable part. The housing 12 shown in Figure 3 may be shared between users.

Figure 4 shows the tubular member 1 fully inserted into the port 23 of the housing 12 so that the electrical connectors 8 and 18 engage with each other, and so that the first light emitter

16 cooperates with the optical guide 7 at the second end 22 of the tubular member 1 . The second end 22 of the tubular member 1 is disposed adjacent to the base 40 of the port 23. Figure 4 shows the second light emitter 17 bathing the lumen 30 of the tubular member 1 with ultraviolet light 60 so as to sterilise the lumen 30. The second light emitter 17 may be activated as required by a user, for example before first inhaling or exhaling through the tubular member 1 , or after the spirometer device has not been used for a predetermined period of time. The second light emitter

17 may additionally or alternatively be activated automatically by the controller 15 at predetermined intervals when the spirometer is being used. Figure 4 also shows an external computing device 50 such as a mobile handset or tablet connected to the external electrical connector 13. Alternatively, the external computing device 50 may communicate with the controller 15 of the spirometer by a wireless connection, such as Bluetooth® or WiFi®. Data from the controller 15 is transmitted to the external computing device 50 for optional further processing, storage and display to a user.

Figure 5 shows a user 70 providing an exhaled breath sample 80 by blowing into the first end 2 of the tubular member 1 . The first end 2 of the tubular member 1 protrudes from the port 23 of the housing 12 and forms a mouthpiece. A user can seal their lips around the mouthpiece so as to provide a good exhaled breath sample 80. The exhaled breath 80 flows from the first end 2 of the tubular member 1 , through the lumen 30, to the second end 22 of the tubular member 1 , and out of the air outlet 14 of the housing 12. The flow meter 4 measures at least one of a flow rate, a speed, and a volume of the exhaled breath 80, and the controller 15 uses these measurements to determine when the exhaled breath 80 is breath from the alveolar Phase III of the exhalation. When alveolar Phase III exhalation has been confirmed, the first light emitter 16 is activated, and ultraviolet light is guided through the optical guide 7 to the location 31 on the wall of the lumen 30. The ultraviolet light from the first emitter 16 illuminates the exhaled breath 80, and the light receiver 5 receives the ultraviolet light after the ultraviolet light has interacted with chemical components, such as VOCs, in the exhaled breath 80. Some of the ultraviolet light will be absorbed by the chemical components in the exhaled breath 80, and this allows the light receiver 5 and the controller 15, optionally in combination with the external computing device 50, to perform an ultraviolet absorbance spectroscopy analysis of the exhaled breath 80. Accordingly, the presence and concentration of predetermined chemical components, such as nicotine, can be determined. Together with the flow data obtained by the flow meter 4, a concentration level of nicotine in the exhaled breath 80 can be calculated, and a bloodstream level of nicotine thereby inferred by calculation. This data can be presented to the user 70 by way of the external computing device 50. The external computing device 50 can also store this data in memory so as to provide the user 70 with information over time of bloodstream levels of nicotine.

Preferably, the first light emitter 16 and the second light emitter 17 do not both operate at the same time, since sterilising ultraviolet light from the second light emitter 17 might interfere with the ultraviolet absorbance spectroscopy analysis.

Figure 6 shows, in schematic outline, another embodiment of the present disclosure. A spirometer 100 has an air inlet 101 configured to receive exhaled breath, an air outlet 102, and a conduit 103 connecting the air inlet 101 and the air outlet 102. A flow meter 5 is configured to measure at least one of a flow rate, a speed and a volume of exhaled breath passing through the conduit 103 from the air inlet 101 to the air outlet 102. A light emitter 104 is located in the conduit 103 and configured to illuminate exhaled breath passing through the conduit 103 with ultraviolet light 105 of a predetermined wavelength or range of wavelengths. A light receiver 106 is also located in the conduit 103 and is configured to receive modified light signals from the illuminated exhaled breath passing through the conduit 103. A controller 15 in the spirometer 100 is configured to process data obtained by the flow meter 5 and the light receiver 106. The flow meter 5 can be used to determine when exhaled breath is from alveolar Phase III exhalation. The controller 15 can activate the light emitter 104 and the light receiver 106 so as to perform ultraviolet absorption spectroscopy analysis of the exhaled breath to identify the presence and concentration of, say, nicotine in the exhaled breath as previously described. The light emitter 104 can also be activated at other times by the controller 15 so as to bathe the conduit 103 with ultraviolet light in order to sterilise the conduit 103. The conduit 103 may be sterilised between uses of the spirometer 100, particularly if the spirometer 100 is shared by several users. The air inlet 101 may be provided with a removeable, disposable mouthpiece for additional hygiene. The spirometer 100 is also provided with a connection 13, which may be wired or wireless, so as to allow communication with an external computing device 50, such as a mobile handset or tablet.

Figure 6 also shows an aerosol-generating device 110. The spirometer 100 may be incorporated in the aerosol-generating device 110. Alternatively, the spirometer 100 may communicate with the aerosol-generating device 110, either directly or by way of the external computing device 50. Communication may be wired or wireless, for example by way of Bluetooth® or WiFi®.

The spirometer 100 is used to determine a bloodstream level of nicotine in a user in the manner already described, namely by way of ultraviolet absorption spectroscopy performed on exhaled breath. In some embodiments, the bloodstream level of nicotine is simply displayed to the user by way of the external computing device 50, and the user is able to make an informed decision as to continued use of the aerosol-generating device 110. In embodiments where the spirometer 100 is incorporated in the aerosol-generating device 110, or where the spirometer 100 is in data communication with the aerosol-generating device 110, operation of the aerosolgenerating device 110 may be controlled in accordance with inferred bloodstream levels of nicotine in the user. For example, if the bloodstream level of nicotine is determined to be above a predetermined threshold, the aerosol-generating device 110 may be rendered temporarily inoperable so as to prevent further ingestion of nicotine, at least until such time that the spirometer 100 determines that the bloodstream level of nicotine has fallen below the predetermined threshold. It may also be possible for the spirometer 100 to control the aerosol-generating device 110 so as to generate an aerosol with a lower nicotine content when the spirometer 100 determines that the bloodstream level of nicotine is approaching the predetermined threshold level. This may be done by adjusting an airflow through the aerosol-generating device 110, or by reducing power to a heater in the aerosol-generating device 110.

Figure 7 is a flowchart illustrating one possible operating regime for the spirometer 100 and the aerosol-generating device 110 of Figure 6. When a user 70 first starts using the aerosol- generating device 110 to ingest nicotine, a bloodstream level of nicotine will start to rise. The spirometer 100 can require the user 70 to provide periodic samples of exhaled breath in order to monitor the bloodstream level of nicotine. So long as the bloodstream level of nicotine is below a predetermined threshold, the aerosol-generating device can continue to operate normally. When the spirometer 100 determines that the bloodstream level of nicotine has reached a predetermined threshold, the spirometer 100 issues an off signal to the aerosol-generating device 110 to prevent further generation of nicotine-containing aerosol. When the spirometer 100 determines that the bloodstream level of nicotine has fallen below the threshold, or a predetermined amount below the threshold, the spirometer 100 issues an on signal to the aerosolgenerating device 110, allowing normal operation of the aerosol-generating device 110 to resume. In this way, a user is assisted in controlling a bloodstream level of nicotine below a desired threshold.

For the purpose of the present description and of the appended claims, except where otherwise indicated, all numbers expressing amounts, quantities, percentages, and so forth, are to be understood as being modified in all instances by the term "about". Also, all ranges include the maximum and minimum points disclosed and include any intermediate ranges therein, which may or may not be specifically enumerated herein. In this context, therefore, a number A is understood as A ± 5% of A. Within this context, a number A may be considered to include numerical values that are within general standard error for the measurement of the property that the number A modifies. The number A, in some instances as used in the appended claims, may deviate by the percentages enumerated above provided that the amount by which A deviates does not materially affect the basic and novel characteristic(s) of the claimed invention. Also, all ranges include the maximum and minimum points disclosed and include any intermediate ranges therein, which may or may not be specifically enumerated herein.

Claims

1 . A spirometer comprising: an air inlet configured to receive exhaled breath; an air outlet; a conduit connecting the air inlet and the air outlet; a flow meter configured to measure at least one of a flow rate, a speed and a volume of exhaled breath passing through the conduit from the air inlet to the air outlet; a light emitter configured to illuminate the exhaled breath passing through the conduit with ultraviolet light of a predetermined wavelength or range of wavelengths; a light receiver configured to receive modified light signals from the illuminated exhaled breath passing through the conduit; and at least one controller configured to process data obtained by the flow meter and the light receiver; wherein the light emitter is configured both to emit light during passage of exhaled breath through the conduit such that the emitted light is modified by exhaled components in the exhaled breath and the modified light is received by the light receiver, and to emit light before or after passage of exhaled breath through the conduit so as to sterilize the conduit.

2. The spirometer according to claim 1 , comprising: a housing having a port; and a removable tubular member having first and second opposed ends and a lumen extending between the first and second ends, wherein the conduit comprises the lumen.

3. The spirometer according to claim 2, wherein the first end of the removeable tubular member extends from the housing, the second end of the removeable tubular member is adjacent a base of the port when the removeable tubular member is inserted into the port, and wherein the first end of the removable tubular member defines the air inlet.

4. The spirometer according to claim 3, wherein the base of the port comprises an opening in fluid communication with the lumen at the second end of the removeable tubular member, and wherein the opening defines the air outlet.

5. The spirometer according claim 3 or 4, wherein the light emitter is disposed at the base of the port.

6. The spirometer according to claim 5, wherein the light emitter comprises a first light emitter and a second light emitter.

7. The spirometer according to claim 6, wherein the removable tubular member comprises an optical guide extending from the second end of the removable tubular member to a wall of the lumen, and wherein the optical guide is configured to guide light from the first light emitter to the lumen when the removable tubular member is received in the port; optionally wherein the second light emitter is configured to emit light directly into the lumen at the second end of the removeable tubular member when the removable tubular member is received in the port.

8. The spirometer according to any one of claims 2 to 7, wherein the removeable tubular member is disposable.

9. The spirometer according to any preceding claim, wherein the light emitter is configured to emit light having a wavelength from 100nm to 400nm; optionally wherein the light emitter is configured to emit light having a wavelength from 240nm to 280nm; optionally wherein the light emitter is configured to emit light having a wavelength from 260nm to 265nm.

10. The spirometer according to any preceding claim, wherein the flow meter and the controller are configured to detect and distinguish between an initial phase of exhalation, in which substantially unmodified air is expelled from a user’s trachea and bronchi and passes through the conduit, and a final phase of exhalation, in which air that has resided in the user’s alveoli and contains levels of VOCs representative of corresponding blood levels of biomarkers of interest passes through the conduit.

11 . The spirometer according to claim 10, wherein the controller is configured to record data from the light receiver only during the final phase of exhalation.

12. The spirometer according to any preceding claim, incorporated in an electronic aerosolgenerating device.

13. The spirometer according to claim 12, wherein the controller is configured to adjust operation of the electronic aerosol-generating device in response to detected characteristics of the exhaled breath.

14. A removeable tubular member configured for insertion into a spirometer, the tubular member comprising: first and second ends and a lumen extending between the first and second ends; an optical guide extending from the second end of the removable tubular member to a wall of the lumen; a flow meter located on the wall of the lumen; and a light receiver located on the wall of the lumen and configured to receive light emitted by the optical guide.

15. A removable tubular member configured for insertion into the spirometer of any one of claims 1 to 13, the tubular member comprising: first and second ends and a lumen extending between the first and second ends, wherein the lumen comprises the conduit; an optical guide extending from the second end of the removable tubular member to a wall of the lumen, the optical guide configured to couple optically with the light emitter of the spirometer; the flow meter, wherein the flow meter is located on the wall of the lumen; and the light receiver, wherein the light receiver is located on the wall of the lumen and configured to receive light emitted by the optical guide.