CROSS-REFERENCE TO PRIOR APPLICATIONS

This application is the U.S. National Phase application under 35 U.S.C. § 371 of International Application Serial No. PCT/EP2017/083740, filed on 20 Dec. 2017, which claims the benefit of European Application No. 16205200.5, filed on 20 Dec. 2016. These applications are hereby incorporated by reference herein.

FIELD OF THE INVENTION

This invention relates to patient monitoring, and more particular to monitoring cardio-respiratory function of a patient.

BACKGROUND OF THE INVENTION

Monitoring of a patient, and in particular monitoring of cardio-respiratory function of a patient, is often relevant for an enhanced diagnostics and therapy planning for the patient. Examples of patients for which monitoring of cardio-respiratory function may be beneficial include those suffering from medical conditions such as chronic obstructive pulmonary disease (COPD), sleep-related problems (sleep disordered breathing (SDB) or insomnia, for example), respiratory disorders, asthma, and the like.

In COPD, asthma and SDB, disordered breathing causes an increased intrathoracic pressure and an increased pressure alteration between the inspiration and expiration cycle. This changed intrathoracic pressure changes the transmural pressure on the heart chambers and the central blood vessels which, in turn, has an impact on the distension of the veins, the atrial filling, the ejection fraction, the stroke volume. Ultimately, it has an impact on the pulmonary circulation and therefore influences the circulation in the left side and right side of the heart.

In respiratory disorders in persons without heart failure, the cardiac system is capable to compensate this additional mechanical cardiac stress of the transmural pressure. While the cardiac system may compensate for this effect by rebalancing the cardiac hemodynamics, a persistent cardiac stress may lead to a structural change of the heart and the development of heart failure and disease exacerbation.

Existing monitoring and diagnostic approaches employ catheters and Doppler Ultrasound which are invasive and not applicable for night-time (e.g. sleep) monitoring. Accordingly, most of the patients at risk form such disorders are not monitored.

Sleep analysis is important for correct diagnosis of patients with sleep-related problems like SDB or insomnia. It is also gaining attention from people without sleep disorders who are just interested in their sleep patterns and/or general health and well-being.

During sleep people usually go through different sleep stages, being REM sleep and non-REM sleep, where non-REM sleep can be divided in 4 stages (e.g. non-REM 1-4). A person might also be awake for certain periods once or more during the night. The typically preferred method for measuring these sleep stages is obtrusive as it requires electroencephalogram (EEG), electromyogram (EMG) and electrooculogram (EOG) data to be obtained using electrodes on the face and the head of the subject/patient.

It is known that the combination of heart rate (HR), heart rate variability (HRV), respiration rate and respiration rate variability can distinguish between REM-sleep, non-REM sleep and awake periods. Currently, measuring respiration rate variability accurately typically requires a respiration belt to be fitted around the torso of the patient or a ventilator mask to be fitted on the face of the patient, thus being fairly obtrusive.

Less obtrusive approaches to sleep monitoring are therefore desirable. Once such known and less obtrusive method makes use of pressure sensors positioned strategically in the bed of a sleeping patient. However, measuring HR, HRV, respiration rate, and respiration rate variability with bed sensors has been shown to be inaccurate.

Apart from sleep staging, other things that occur during sleep may be important in sleep analysis. Examples of such events include snoring, teeth grinding (bruxism), yawning, blood oxygenation and the occurrence of apnea events. With specific regard to apnea events, it may be desirable to determining whether apnea events are caused by obstruction (obstructive sleep apnea, OSA) or by the brain's respiratory control centers (central sleep apnea, CSA), and whether OSA or snoring are posture dependent (e.g. only occurring when the patient is lying on their back; for OSA, this is called “positional obstructive sleep apnea” (POSA)). None of the above-mentioned methods for sleep staging are able to take all those things into account and therefore extra sensors are needed when a combined measurement of those factors and sleep staging is desired.

Thus, there exists a need for unobtrusive monitoring concepts for monitoring cardio-respiratory function of a patient. Such an unobtrusive monitoring concept may be beneficial for enhanced diagnostics and therapy planning in relation to many medical conditions, including COPD, sleep-related problems, respiratory disorders, asthma, and the like.

SUMMARY OF THE INVENTION

The invention aims to at least partly fulfil one of the aforementioned needs. To this end, the invention provides devices, methods, computer program products and systems as defined in the independent claims. The dependent claims provide advantageous embodiments.

Thus, the invention provides an apparatus and a corresponding method for monitoring cardio-respiratory function of a patient. Embodiments of the apparatus may comprise a sublingual sensor unit adapted to be positioned at a sublingual vein or sublingual vasculature of the patient's tongue, to detect light or sound from the sublingual vein/vasculature, and to generate a sensor output signal based on the detected light or sound. The apparatus further comprises a processing unit adapted to receive at least one of the sensor unit output signal, wherein the sensor unit and the processing unit are arranged to analyze the venous component in the sensor output signal.

US2010/0152599 describes an oral appliance compliance monitoring system and method. The oral appliance is suitable for wearing in a patient's oral cavity during sleeping periods and has one or more sensors measuring a variety of conditions such as oxygen saturation levels in the oral cavity mucosa. More in particular the sensor is a pulse oximetry sensor. The data generated by the sensor is continuously transmitted to a local scanner which is in communication with a central computer. The computer interprets the data to determine if the patent is wearing the oral appliance in compliance with a prescribed treatment regimen for breathing-related sleep disorders.

DE4130522 describes a sensor inserted under the tongue tip and comprising a light emitting diode emitting light preferably in the 805 nm wavelength region, and a photodetector, preferably a photo cell. Light is reflected from the tongue while the latter is compressed by a pneumatic or hydraulic cushion linked to a pump. The sensor is configured to measure a patient's blood pressure by detecting the volume pulsation in the tongue's arteries. The photodetector is arranged to detect multiple arteries to reduce disturbing influences caused by reactions of individual veins.

Proposed embodiments according to the present invention are based on using the sublingual vein and/or sublingual vein proximity vasculature of a patient's tongue to look at the venous blood volume/flow and that the variations in blood volume/flow in the sublingual vein or vasculature will give information on cardio-respiratory interactions. In this regard, it should be noted that probing only the sublingual vein might not be possible (because the positioning comes very critical) and it might not be desirable either. When an area is probed that is only a very short distance from the sublingual vein, the venules still give the desired signal representative for the respiratory- and blood accumulation-related information. In a preferred embodiment, information is obtained from the arterioles in that area, from which the heart rate, heart rate variability and arterial blood oxygenation can be obtained. For those reasons, in this patent, when reference is made to ‘positioned at a sublingual vein’, ‘aimed at the sublingual vein’, or ‘sublingual vasculature’, it should be understood to include being at an area which is a close distance from (i.e. proximate to) the sublingual vein wherein information from the venules that drain in the sublingual vein can be derived from the signal. This is preferably at a distance less than 1 cm from the sublingual vein, and more preferably at a distance less than 5 mm from the sublingual vein.

Accordingly, in a preferred embodiment a sublingual sensor unit is adapted to be positioned at, aimed at, or proximate the sublingual vein or sublingual venous vasculature of the patient's tongue, preferably at a distance less than 1 cm from the sublingual vein, and more preferably at a distance less than 3 mm from the sublingual vein. When an area is probed that is only a very short distance from the sublingual vein, the venules still give the desired signal representative for the respiratory- and blood accumulation-related information.

The advantage of the sublingual vein is that it lies close to the surface and that the sublingual skin is very thin and optically transparent. Also, the bottom side of the tongue is a highly perfused area. Those properties make the bottom side of the tongue well-suited for photoplethysmography (PPG) monitoring for example. Further, compared to many other veins or vasculature in other places in the body, the sublingual vein or vasculature is of special interest because it drains into the internal jugular vein, which then drains into the vena cava; there is therefore a close connection to the central veins and the right side of the heart. Especially in a lying position information for the right side of the heart and the central veins can be seen derived from the sublingual vein.

Accordingly, in a preferred embodiment the sensor unit is adapted to be aimed at the sublingual vasculature/area on the bottom side of a patient's tongue, preferably in an area close to the base of the tongue, i.e. deep under the tongue, far from the tip of the tongue. This may, for example, enable more of the venous component to be seen in the sensor signals. Proposed embodiments may therefore leverage the raw signal of the sensor.

A signal from the sensor that is representative of detected light or sound from the sublingual vein may then be used to provide information on cardio-respiratory parameters like respiration rate (RR), respiration rate variability (RRV), onset of inspiration, onset of expiration, duty cycle of respiration, Cheyne-Stokes respiration, obstructive sleep apnea (OSA), central sleep apnea (CSA), distinction between OSA and CSA, obstructive flow limitation (Hypopnea), mean transmural pressure, mean blood accumulation, the presence of edema, sighing, yawning, coughing, paced breathing, and pursed breathing.

In this way, there may be provided a tool for determining and/or monitoring a value of a cardio-respiratory parameter that can be used by a medical professional, a general practitioner without the support of a trained cardiologist, for example. It may assist in the diagnosis of dynamic changes of the preload and blood accumulation in heart failure patients. Similarly, it may help to diagnose and stratify persons who are at the onset of developing heart failure and pulmonary edema. Embodiments may also be used to verify the success of a cardiac therapy and/or to monitor disease progression or exacerbation.

Also, embodiments may be used for detecting or monitoring sleep apnea in a sleep study. For example, proposed embodiments may be employed to detect obstructive and central apnea and may distinguish between these.

Further, an embodiment may be used to monitor the cardio-respiratory response of a ventilation therapy and to better control the device settings of a pressure support therapy in COPD and OSA patients.

It is also envisaged that, using a proposed embodiment, a physician can phenotype during wakefulness the cardiac response on natural spontaneous breathing assisted by ventilation support devices (CPAP) and on voluntarily performed breathing manoeuvres like paced breathing, sighing, periodic breathing to prove applicability and risk of a ventilation therapy. Such monitoring of the preload and the venous blood pooling enables a better control of a mechanical ventilator to avoid the accumulation of fluids (edema) in the lung which are caused by a volume overloading in the lung. Accordingly, monitoring of the cardio-respiratory interaction by a proposed embodiment may improve an outcome of a mechanical ventilation and may lower the morbidity risk in critical care patients.

By way of example, embodiments may be used by a general physician or (medically) un-trained person without the support of a trained cardiologist. This may alleviate a need for close monitoring by medical professionals. It may also reduce a need for medical intervention or treatment. Embodiments may therefore relieve healthcare requirements/resources.

Embodiments may further comprise a supplementary sensor module adapted to be positioned in the patient's mouth and comprising a sensor arrangement adapted to sense a value of at least one of: movement; pressure; temperature; and sound and to generate a supplementary sensor output signal based on the sensed value(s). In such embodiments, the supplementary sensor may provide additional information about the patient which may, for example, be useful for improving accuracy of determinations or refining previously obtained values.

In an embodiment, the apparatus may further comprise a processing unit adapted to receive at least one of the sensor output signal and the supplementary sensor output signal and to process at least one of the received signals in accordance with one or more data processing algorithms to determine a cardio-respiratory value of the patient.

By way of example, the cardio-respiratory value may comprise a value of at least one of: respiration rate; respiration rate variability; onset of inspiration; onset of expiration; duty cycle of respiration; Cheyne-Stokes respiration; obstructive sleep apnea; central sleep apnea; obstructive flow limitation; transmural pressure; blood accumulation; coughing; paced breathing; and pursed breathing.

Typical sampling frequencies of the sensor signal may be 32, 128 or 256 Hz, but the sampling frequency might also have a different value. The data-processing algorithm may be adapted to identify low-frequency variations in the sensor output signal, to get information indicative for the respiration. For example, a RR may be observed as the dominant frequency in the range between. 0.08 Hz and 0.5 Hz. In PPG, this frequency band and lower frequencies are referred to as ‘DC’, as they are lower than the changes caused by heart rate. Changes in the depth of respiration can, for example, be interpreted from amplitude variations of the PPG signal at the respiration frequency. Embodiments may monitor modulation in a low frequency sensor signal component which indicate the signal response to the deviations in respiration (caused by additional stress in the heart for example). Nevertheless, higher frequencies variations in the sensor output signal (for example in the range between 0.6 Hz and 4 Hz) may also be used to provide information on average heart rate. In PPG, fluctuation in the signal caused by the pulsations of the heart are called ‘AC’ fluctuations. Heart rate variability and arrhythmias may be derived from a high-pass-filtered signal with a threshold frequency of e.g. 0.5 or 0.6 Hz. SpO2 (optically measured arterial oxygen saturation) may be derived from both AC and DC components, while RRV may require determination of the duration of each breath.

The processing unit may be adapted to receive at least one of the sensor output signal and the supplementary sensor output signal, to process the received sensor output signal in accordance with a data processing algorithm to determine a cardio-respiratory value of the patient, and to analyse the determined cardio-respiratory value in combination with the received supplementary sensor output signal to determine at least one of: a refined cardio-respiratory value; an indication of accuracy or reliability; a sleep state of the patient; an activity of the patient; and an indication of event occurrence. Embodiments may therefore take account of a context of the patient, such as their current activity or physical attributes for example.

The sensor unit may be used either in reflective or transmissive mode.

In an embodiment, the sensor unit may comprise at least one of: a PPG (photoplethysmography) sensor; a laser speckle sensor; a laser Doppler sensor; an ultrasound sensor; and a camera. It is noted that that PPG sensors exist that, when placed on the finger or ear lobe, may enable the derivation of RR (respiration rate) from the sensor signal. However, for sensors placed at these locations, it is practically impossible to see the RR by eye from the raw PPG signal. Therefore, RR can only be derived with relatively complex algorithms, which generally take into account modulations in frequency, amplitude and DC-level. Even then, the derived RR is not always correct. In contrast, the raw PPG signal of a PPG sensor aimed at the sublingual vein in accordance with proposed embodiment clearly shows RR, onset of inspiration, onset of expiration and depth of inspiration thereby potentially avoiding the need for complex algorithms and/or extensive processing resources.

Typically, the PPG signal or sensor unit signal is viewed as a low frequency component, considered as DC, and the high frequency component, called AC, contains the blood pulsatility. Accordingly, in preferred embodiments the AC component is used to estimate heart rate, heart rate variability, and/or oxygen saturation, while the low frequency component is used to extract the features related to respiration and venous pooling. Typically, the AC component is detected in the range between 0.5 Hz and 4 Hz and the DC component is detected in the range between 0.08 and 0.5 Hz. Respiration rate (RR) preferably can be observed as the dominant frequency in the range between e.g. 0.08 and 0.4 Hz, and respiration rate variability (RRV) is based on the changes in the RR over time. Accordingly, changes in the depth of respiration can be interpreted from amplitude variations of the PPG signal at the respiration frequency.

Embodiments may further comprise a light source adapted to illuminate the patient's tongue. The light source may be adapted to emit first light having a wavelength within a first range of wavelengths and to emit second light having a wavelength within a second, different range of wavelengths, or more than one light sources might be used, which each have their own specific wavelength band. By way of example, the first range of wavelength may comprise visible light and the second range of wavelengths may comprise infra-red light. In order to derive SpO2, commonly red and infra-red light are used. Since blood in the veins and venules contains more deoxygenated blood than blood in the arteries and arterioles and since red light is absorbed substantially more by deoxygenated blood than by oxygenated blood (while the absorption in infra-red is similar), red light is especially suitable to derive venous information. In order to have a further distinction between venous and arterial information, the red signal and the infra-red signal could be compared, e.g. the infra-red signal might (preferably after weighing) be subtracted from the red signal.

In some embodiments, an ultrasound transducer or ultrasound transceiver may be employed to transmit and sense ultrasound signals to/from the patient's tongue.

Embodiments may further comprise an output interface adapted to generate an output signal representative of a determined or calculated cardio-respiratory value. For example, a user may be advised of cardio-respiratory value exceeding a predetermined acceptable threshold.

Embodiments may further comprise a user input interface adapted to receive a user input signal representative of at least one of: environmental information; patient information; and a limit value representative of an acceptable upper limit of a cardio-respiratory value. Embodiments may therefore be thought of as providing an interface which enables a user to further specify information or data that may be relevant for the purpose of determining or monitoring a cardio-respiratory value. Such user-specified information may enable unique traits, circumstances and/or conditions specific to the user or the environment to be accounted for when determining or monitoring a cardio-respiratory value.

Thus, there may be provided a tool which enables a user to further specify factors to be included in the determination or monitoring of cardio-respiratory function, e.g. by specifying a value or value range for a user attribute or activity. Embodiments may therefore provide input options, increasing the flexibility and power of risk of cardio-respiratory monitoring.

In some embodiments, the apparatus may further comprise a communication interface adapted to communicate with one or more databases so as to obtain at least one of the information that may be used in determining or monitoring a cardio-respiratory value.

There may be provided a portable computing device comprising apparatus for monitoring a cardio-respiratory function of a patient according to a proposed embodiment.

The system may further comprise a display device for displaying a graphical or non-graphical (e.g. auditory) user interface, wherein the graphical user interface is adapted to communicate information about detected or monitored cardio-respiratory function of a patient to a user.

Embodiments may comprise a client device comprising a data processor device. This may be a standalone device adapted to receive information from one or more remotely positioned information sources (via a communication link for example) and/or even adapted to access information stored in a database for example. In other words, a user (such as a medical professional, technician, researcher, patient etc.) may have an appropriately arranged client device (such as a laptop, tablet computer, mobile phone, PDA, etc.) which provides a system according to an embodiment and thus enables the user to provide data or information for the purpose of monitoring cardio-respiratory function of a patient.

The system may comprise: a server device comprising the at least one processor, where the server device may be configured to transmit generated instructions for determining and/or displaying a cardio-respiratory function of a patient to a client device or communication network. In such a configuration, display instructions are made available by a server. A user may therefore link with the server to work with the system.

The processor may be remotely located from the display device, and a control signal may thus be communicated to the display device via a communication link. Such a communication link can be e.g. the internet and/or a wireless communication link. Other suitable short-range or long-range communication links and/protocols may be employed. In this way, a user (such as a medical researcher, general practitioner, data analyst, engineer, patient etc.) may have an appropriately arranged device that can receive and process information according to an embodiment for monitoring a cardio-respiratory function of a patient. Embodiments may therefore enable a user to remotely monitor cardio-respiratory function of a patient using a portable computing device, such as a laptop, tablet computer, mobile phone, PDA, etc. Embodiments may also enable data retrieval after a monitored time period.

The system may further comprise: a server device comprising the at least one processor; and a client device comprising a display device. Dedicated data processing means may therefore be employed for the purpose of monitoring a cardio-respiratory function or value of a patient, thus reducing processing requirements or capabilities of other components or devices of the system.

Thus, it will be understood that processing capabilities may therefore be distributed throughout the system in different ways according to predetermined constraints and/or availability of processing resources.

According to another aspect of the invention, there may be provided a mouthpiece (or oral appliance) comprising apparatus for monitoring cardio-respiratory function of a patient according to any preceding claim. For example, embodiments may propose the use of a sensor placed in an oral appliance, wherein the oral appliance on the lower teeth houses the sensor. In this way, the sensor may be stably positioned in the mouth, thereby reducing motion artefact. The oral appliance may, for example, be designed such the tongue can rest directly on the sensor. In some embodiments, the sensor may be adapted to be movable with respect to the oral appliance (e.g. under the control of a mechanical or electro-mechanical arrangement), thereby enabling the positioning of the sensor to be optimised or personalised to a specific-patient for example.

According to yet another aspect of the invention, there may be provided a method for monitoring cardio-respiratory function of a patient, the method comprising: positioning a sublingual sensor unit at sublingual vasculature of the patient's tongue; detecting light or sound from the sublingual vasculature; and generating a sensor output signal based on the detected light or sound.

Embodiments may further comprise the steps of: positioning a supplementary sensor module in the patient's mouth, the sensor module comprising a sensor arrangement adapted to sense a value of at least one of: movement; pressure; temperature; and sound; sensing, with the sensor arrangement, a value of at least one of: movement; pressure; temperature; and sound; and generating a supplementary sensor output signal based on the sensed value(s).

In an embodiment, the method may further comprise: receiving, at a processing unit, at least one of the sensor output signal and the supplementary sensor output signal; and processing at least one of the received signals in accordance with one or more data processing algorithms to determine a cardio-respiratory value of the patient. The cardio-respiratory value may comprise a value of at least one of: respiration rate; respiration rate variability; onset of inspiration; onset of expiration; duty cycle of respiration; Cheyne-Stokes respiration; obstructive sleep apnea; central sleep apnea; obstructive flow limitation; transmural pressure; blood accumulation; coughing; paced breathing; and pursed breathing.

The step of receiving may comprise receiving at least one of the sensor output signal and the supplementary sensor output signal, and the step of processing may comprise processing the received sensor output signal in accordance with a data processing algorithm to determine a cardio-respiratory value of the patient. Further, embodiments may comprise the step of analysing the determined cardio-respiratory value in combination with the received supplementary sensor output signal to determine at least one of: a refined cardio-respiratory value; an indication of accuracy or reliability; a sleep state of the patient; an activity of the patient; and an indication of event occurrence, posture of the patient/head orientation.

By way of example, the step of processing the output signal in accordance with a data processing algorithm may comprise identifying low-frequency variations in the sensor output signal.

Embodiments may further comprise the step of illuminating the patient's tongue with light from a light source. This, may for example comprise: controlling the light source to emit light having a wavelength within a first range of wavelengths and to emit light having a wavelength within a second, different range of wavelengths. Preferably, the first range of wavelength may comprise visible light and the second range of wavelengths may comprise infra-red light. The light source may thus comprise one or more light emitting devices.

Embodiments may provide concepts for monitoring one or more cardio-respiratory functions of a patient. The proposed concepts may comprise positioning a sensor at (e.g. adjacent, proximate, next to, neighbouring, etc.) a sublingual vein of the patient's tongue. Light or sound transmitted through the sublingual vein may be detected by the sensor and the detected light or sound may be used (e.g. processed according to one or more algorithms) to determine a value of a cardio-respiratory functions of the patient. Determining the value of a cardio-respiratory function may comprise taking account of historical information relating to previously determined values of the cardio-respiratory function of the patient. Further, additional sensors may be employed to detect one or more supplementary values of other physical attributes or parameters of the patient. Such supplementary values may be used in combination with the detected light and/or determined value of the cardio-respiratory function to infer or determine other information (such as an indication of accuracy or reliability, a sleep state of the patient, an activity of the patient, or an indication of event occurrence for example) and/or confirm/validate the determined value of the cardio-respiratory function. For this purpose, proposed concepts may employ (or be employed on) at least one processor.

Proposed embodiments may further comprise generating instructions for displaying a GUI on a display device using a processor device, wherein the graphical user interface is adapted to communicate information about detected light or sound from the sublingual vein and/or a determined cardio-respiratory value of the patient to a user. Generating instructions for display of a GUI can mean generating a control signal for use by a display device. Such instructions can be in the form of simple images such as bitmap JPEG or other format. However, such instructions can also be more complex allowing real time build-up of the GUI or parts of the GUI on a regular display device such as for example CRT, LCD, OLED, E-ink or the like.

According to another aspect, there may be provided a computer program product downloadable from a communications network and/or stored on a computer readable medium and/or microprocessor-executable medium wherein the computer program product comprises computer program code instructions, which when executed by at least one processor, implement a method according to a proposed embodiment.

The independent claims define analogous advantages features for method and system claims. The advantages explained for the method herein above and herein below may therefore also apply to the corresponding systems.

