MEASUREMENT ARRANGEMENT FOR PREDICTING RISK OF COPD AND / OR ASTHMA ATTACK AND METHOD FOR MAINTENANCE OF MEASUREMENT ARRANGEMENT - Patent application

Abstract

A sensing device for determining the risk and / or probability of a COPD and / or asthma attack in a patient, said sensing device being provided with: a. a sampling device for non-invasively sampling a biological sample; b. a biosensor for determining the presence and / or amount of a biomarker in said biological sample, preferably without the need for sample preparation; c. a control and evaluation device; and d. an output unit for outputting the risk and / or probability of a COPD and / or asthma attack and / or for a warning about the risk and / or probability of a COPD and / or asthma attack, preferably within less than 48 hours after measurement, said control and evaluation device being provided for determining the risk and / or probability of a COPD and / or asthma attack based on the presence and / or measured amount; a measurement arrangement and a method for maintenance of said sensing device or said measurement arrangement.

Description

[Technical field]

[0001] The present invention relates to a sensing device and a method for predicting the risk of chronic obstructive pulmonary disease (COPD) and / or an asthma attack. The present invention further relates to a measurement arrangement and a method for the maintenance of the sensing device. [Background technology]

[0002] Chronic obstructive pulmonary disease (COPD) is a variety of progressive lung disease defined by long-term respiratory symptoms and airflow limitation. Symptoms that characterize the disease include coughing and shortness of breath, which may be caused by mucus.

[0003] Asthma is a variant of COPD, a long-term chronic inflammatory disease of the lung's airways. In asthma, airways may narrow, expand, and produce excess mucus. This makes breathing difficult, inducing coughing, wheezing, and shortness of breath. Asthma is characterized by fluctuating and recurrent symptoms, reversible airflow obstruction, and easily triggered bronchospasm. It is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens. Other potential triggers include medications such as aspirin and beta-blockers.

[0004] Symptoms include episodes of wheezing, coughing, chest tightness and shortness of breath. These may occur several times a day or several times a week. The asthmatic condition may culminate in an asthma attack, a severe and life-threatening event. During an asthma attack (also called an asthma exacerbation), the airways swell and constrict. The muscles around the airways contract and the airways produce excess mucus, both effects narrowing the breathing (bronchial) tubes and severely restricting breathing in a life-threatening manner.

[0005] Currently, there is no cure for asthma patients. In 2019, asthma affected approximately 262 million people and caused approximately 461,000 deaths. Most of the deaths occurred in developing countries. Asthma often begins in childhood, and its incidence and prevalence worldwide have increased significantly since 1960. It has been reported that one in ten children has asthma, making it one of the top ten most frequent causes of death worldwide.

[0006] Diagnosis is usually based on recognition of a set / pattern of symptoms, spirometry testing, and induced bronchoconstriction pulmonary function testing. Diagnosis is also typically confirmed by the expected response to pharmacological treatment.

[0007] Asthma is treatable as a chronic condition and relieved by medications taken chronically. The severity of symptoms can be reduced by avoiding triggers such as allergens and respiratory irritants, and suppressed by the use of inhaled corticosteroids. If asthma symptoms remain uncontrolled, long-acting beta agonists (LABAs) or anti-leukotrienes can be used in addition to inhaled corticosteroids. Treatment of rapidly worsening symptoms is usually with inhaled short-acting beta 2 agonists such as salbutamol and corticosteroids taken orally. In very severe cases and during or after an asthma attack, intravenous corticosteroids, magnesium sulfate, and hospitalization may be required.

[0008] Asthma management aims to control the occurrence and frequency of asthma attacks and tries to ensure a good quality of life. However, at this time, there are no established mechanisms to predict and prevent asthma attacks. This makes it very difficult for patients to plan their lives around the disease, and there is a need for methods to estimate the risk of a sudden attack that may be life-threatening. Fatal asthma attacks are frequently observed even in patients who are unaware of the possibility of experiencing a fatal attack. The fatality rate may be higher when the person undergoing the attack is alone (unattended).

[0009] In 2019, asthma affected approximately 262 million people worldwide and caused approximately 461,000 deaths. Most of the deaths occurred in developing countries. Asthma often begins in childhood, and its rates have increased significantly since 1960. Sudden attacks can cause loss of life, especially in infants and children whose early symptoms are not recognized. Parents often notice an attack when they hear wheezing, coughing, and shortness of breath. However, if a child, or a young adult or elderly person is unattended, such as during nighttime sleep, the sudden onset of an attack can put a person's life at risk.

[0010] EP 3367101 discloses a method for predicting asthma attacks by measuring the biomarker IL-17 (alone or together with other specific biomarkers) present in blood, serum or plasma. However, there are major drawbacks to applying this approach, making it less suitable for the daily management of asthma.

[0011] Since in this prior art the biomarkers are derived from blood, either serum or plasma, the methods disclosed therein are invasive, and therefore the patient experiences discomfort every time a blood sample is taken.

[0012] In this prior art, the main target biomarker is IL-17, and several supplementary biomarkers are of interest, which are disclosed by the following term: "measuring IL-17 and at least one biomarker selected from the group consisting of IL-10, IL-4, IL-25, IL-9, and IFN-y". However, biomarkers related to asthma and risk of asthma attacks are not targeted. Measurement of IL-17 is only possible by skilled artisans, e.g., laboratory technicians, but remains inaccessible to patients or end users. Detection further requires special laboratory equipment, such as a microplate fluorescence reader, and is therefore not practical for non-skilled personnel to use at the point of care.

[0013] The prediction accuracy is 12 months. Therefore, there is no practical use of the prior art to predict attacks that may occur at high speeds over a short prediction period. Summary of the Invention

[0014] It is an object of the present invention to provide a sensing device and method for predicting the risk and probability of a COPD and / or asthma attack.

[0015] Apparatus and methods are disclosed for predicting the risk and probability of a COPD and / or asthma attack and informing a patient, caregiver, or medical professional of said risk and prediction.

[0016] This is accomplished by continuous and / or frequent monitoring and treatment of levels and changes in biomarkers associated with asthma disease.

[0017] The invention includes a device for taking an oral sample from a patient, a method for measuring the levels of biomarkers in the sample, an algorithm for predicting the risk and likelihood of a stroke, and a system for notifying the user so that the user can take preventive or countermeasures to avoid such strokes.

[0018] It has been observed that people are more likely to experience asthma symptoms and attacks during sleep, referred to as nighttime or nocturnal asthma events / conditions. If occurring suddenly, nighttime attacks can be fatal from infants, children, adults and the elderly. Different users belonging to different age groups can utilize different preferred devices with integrated sensing for monitoring the risk of asthma attacks and preventing exacerbations. Infants preferably use pacifier or baby bottle based devices, children and adults toothbrush devices, and the elderly other types of oral appliances, or even solutions with prosthetic devices with integrated sensing.

[0019] Certain biomarkers have been shown to be associated with asthmatic disease.

[0020] The present invention solves the problem of predicting exacerbations in less than 48 hours, whereby an estimated risk is calculated based on novel non-invasive sampling, novel biomarker sensing methods, and novel devices. The results of the analysis of current and historical data and data patterns are presented daily to the user and medical professionals along with one or more daily updates of the estimated risk of asthma attack and current asthma condition.

[0021] Based on the updates, patients and caregivers will be able to take steps to counter their increased risk and effectively prevent asthma attacks in a controlled and conscious way.

[0022] Benefits range from better chronic disease management of asthma, to prevention of severe asthma attacks and complications, and ultimately, possible prevention of loss of life.

[0023] It is advantageous if the device is adapted to repeat measurements multiple times a day by non-invasive sensing of biomarkers associated with asthma status and asthma exacerbations, as well as the risk and probability of occurrence of asthma exacerbations.

[0024] The present invention focuses on a novel set of biomarkers including immunoglobulins IgE, IgA, interleukins, and other related biomarkers such as CRP, TSLP and lysozyme.

[0025] A further focus is on the integration of biomarker sensors, also referred to herein as biosensors, for determining the presence and / or amount of a biomarker in a biological sample. Said amount can be, for example, the content, also referred to as concentration, of a particular biomarker or biomarkers in a sample.

[0026] In a preferred embodiment, no sample preparation is necessary for the detection of a biomarker by the biosensor. In other words, the biosensor is provided for directly determining the biomarker or the amount of this biomarker in a sample without further sample preparation. Of course, there are other embodiments according to the invention in which sample preparation, such as the addition of a marker, such as a fluorescent marker, is provided prior to the measurement by said biosensor.

[0027] An oral appliance device or apparatus for use in the oral cavity by different users including the elderly and infants.The present invention addresses the problems listed above to provide a practical method useful in the daily management of asthma.

[0028] In a first preferred embodiment of the present invention, biomarkers are collected from oral excretions or secretions (saliva) in a non-invasive manner. The device of the present invention is therefore provided with a sampling section, also called collection device, preferably with a sampling channel for collecting samples of excretions or secretions. The aforementioned collection device is designed for non-invasive collection of biological samples such as saliva.

[0029] The present invention addresses the problems listed above to provide practical methods of the invention useful in the daily management of asthma.

[0030] The samples are processed in the device of the present invention, which is preferably a portable device, such as a handheld, which can be operated by the patient or a caregiver by activating the portable device.

[0031] The aforementioned sensors may be adapted to selectively measure the concentration of biomarkers from the group consisting of IgE, IgA, CRP, TSLP, lysozyme, interleukins IL4, IL5, IL6, IL-10, IL-13, IL-17, IL-19, IL-25, and / or IL32.

[0032] The present invention comprises a non-invasive method and device for obtaining a biological sample from a patient.

[0033] The sample may be an oral discharge such as sputum or an oral secretion such as saliva.

[0034] There are various possibilities for the collection of said oral excretions and / or secretions. For this purpose, the sensing device of the invention comprises a collection device, which can be sampled through an extra-oral container, such as a tube or vial, through which the patient delivers the sample to a channel or chamber of the collection device. The collection device as mentioned above can be part of the device of the invention, and in particular can be integrated into the device of the invention.

[0035] Further possibilities for sampling are via intra-oral appliances such as sampling sticks, pacifier devices, toothbrush devices, baby bottle devices, dental equipment, preferably for application to the teeth and / or tooth replacement, such as brackets, bridges and / or dental bracelets and / or dental implants.

[0036] The device according to the invention, in particular the sensing device, is provided with a control and evaluation device adapted to quantitatively measure the level of the biomarker in the sample. Said control and evaluation device may be provided with a processing unit and a data storage. Said data storage may be provided with the aforementioned algorithms and computer programs for implementing the aforementioned methods of the invention.

[0037] The above sensing has been described with respect to oral appliances or other external devices.

[0038] The aforementioned sensing device, and in particular the aforementioned biosensor, may be provided for determining or using at least one or more biochemical properties of a sample.

[0039] The aforementioned sensing device, and in particular the aforementioned biosensor, may be provided for determining or using at least one or more immunochromatographic properties of a sample.

[0040] The aforementioned sensing devices, and in particular the aforementioned biosensors, may be provided to determine or use at least one or more electrochemical properties of a sample after reaction with a reagent or assay.

[0041] The aforementioned sensing device, and in particular the aforementioned biosensor, may be provided for determining or using at least one or more optoelectronic properties of a sample, in addition to measuring the concentration of a biomarker.

[0042] The sensing device may further include a turbidity sensor.

[0043] The aforementioned control and evaluation devices can in particular be provided for measuring and using electrical or magnetic properties of the sample.

[0044] The sensing device may be provided to use any combination of the aforementioned measurements. In particular, the sensing device may be provided with a docking port for replacing sensors that are defective or have reached the end of their life and are not suitable for the person. Infants in general may require other biosensors to detect other biomarkers, or different sensors than older adults. The sensing device may be used as a platform for prediction of different types of COPD depending on the patient's biological factors such as age.

[0045] The biomarkers for predicting the risk of COPD attacks measured and tested by the sensing device of the present invention are at least one or a combination of compounds from the group of IgE, IgA, CRP, lysozyme and / or interleukins such as IL4, IL5, IL6, IL10, IL-13, IL17, IL-19, IL25, IL32, TSLP.

[0046] The aforementioned algorithms used by the control and evaluation device predict, as early as possible, the clinical manifestations of the disease on the basis of the measured values.

[0047] Such prediction of a COPD attack can detect the risk before a patient experiences audible and / or visible symptoms.

[0048] Predictions can be made based on advanced signal and data processing of biomarker data, preferably further data determined by other sensor devices such as conductivity, etc. Data processing can be designed based on historical data processing and analysis or advanced methods such as model building, machine learning, and / or advanced methods of detection, prediction, classification, and / or pattern recognition.

[0049] A further subject of the invention is a measurement arrangement comprising one or more sensing devices according to the invention.The aforementioned sensing devices are electronic devices.

[0050] The devices may be provided with two-way radio capabilities, mobile computing devices, and / or networking or cloud-based systems and / or software applications that inform the patient, caregiver, or medical personnel of the risk and / or probability of an impending asthma attack. This information may be provided, preferably on a continuous basis.

[0051] The above measurement configuration is used to calculate a total risk score for impending COPD and / or asthma exacerbation, which will allow the patient to take preventative measures such as preparing or taking medication, or notifying an HCP or caregiver.

[0052] The sensing device may be adapted to calculate and communicate a risk score of impending COPD and / or asthma exacerbation using specific software algorithms and / or based on machine learning.

[0053] The sensing device or measurement arrangement of the present invention may be equipped with an analysis program that collects data over a longer period of time, such as a month or more. In this way, chronic management of the COPD and / or asthma condition may be improved.

[0054] The above described measurement arrangement is provided for carrying out a non-invasive method for collecting biological samples from a patient from the oral cavity by using a collection device for oral secretions.

[0055] Said collection device may be an integral or replaceable part of the sensing device of the invention, or may be an extra-oral container such as a tube or vial through which the patient delivers the sample to said container. The same applies to a biosensor or a sensing unit comprising said biosensor.

[0056] Additionally or alternatively, the sampling device may be or may be provided with a sampling stick through which a sample is taken from the oral cavity, or a pacifier, or a toothbrush, or a dental device such as a bracket, bridge, bracelet and / or dental implant.

[0057] Said sensing device for quantitatively measuring the level of a biomarker in a sample. Said sensing device or preferably said measuring arrangement comprising said sensing device comprises: assessing the biochemical characteristic of the sample; assessing the immunochromatographic properties of the sample; evaluating the electrochemical properties of the sample after reaction with an assay; evaluating the optical or electro-optical properties of the sample; Evaluating the electrical or magnetic properties of the sample; and / or assessing any of the above combinations of properties of said sample; A control and / or evaluation device may be provided which is arranged to:

[0058] The sensing method of the present invention may also include one or more of the above assessments. The above assessments may be combined in preferred embodiments of the present invention.

[0059] Said sensing device is arranged such that the device employs the sensing method together with said one or more data processing algorithms. Said sensing device is further arranged to inform a user about an asthma state and the risk and probability of an asthma attack.

[0060] Said device is further provided for predicting clinical symptoms, disease state, risk and / or probability of COPD attack and / or exacerbation and / or asthma attack and / or exacerbation. Provision of said device is based on measuring and processing oral sample characteristics and biomarker levels contained therein.

[0061] The aforementioned data processing algorithms are based on advanced signal and data detection, classification, prediction, pattern recognition, machine learning that is capable of learning, differentiating and / or predicting the pattern of biomarker changes and their relationship with COPD attacks and / or asthma attacks for a particular individual or patient group.

[0062] Alternatively or additionally, such algorithms may be based on statistical or probabilistic or neural network or machine learning modeling or other types of model-based algorithm design.

[0063] The above-described measurement arrangement with sensing device notifies the patient, caregiver or medical professional with sufficient accuracy and foresight of the risk and probability of an escalating COPD and / or asthma attack or an impending COPD and / or asthma attack, with or without audible or visible symptoms.

[0064] The aforementioned measurement configuration is further provided to inform whether the sensing method is viable or if it has to be retuned.

[0065] A further object of the invention is a method for the maintenance of said sensing device and / or said measuring arrangement, said method comprising the steps of: A. Sampling a biological sample from a patient's oral cavity by a non-invasive method; B. determining the content of biomarkers in the sample by measurement with a sensing method; C. comparing the result of step B to one or more previous measurements or to a predetermined threshold; D. initiating cleaning of the collection device and / or the biosensor and / or the sensing unit comprising the biosensor, and / or providing information regarding replacement of the collection device and / or the biosensor and / or the sensing unit comprising the biosensor.

[0066] The sensing method described above is the sensing method described above and is also the present invention insofar as it is permissible in the jurisdiction in which the invention seeks protection.

[0067] A control and evaluation device is provided for carrying out the aforementioned sensing method. This provision can be realized, for example, by one or more computer programs and / or electronic circuits. The aforementioned computer programs can be stored in a storage device, such as a RAM or ROM, of the aforementioned control and evaluation device and can be executed by one or more CPUs.

[0068] The inventive measurement arrangement, the sensing device and / or the inventive method will be further explained with reference to the figures in the context of different embodiments. [Brief description of the drawings]

[0069] [Figure 1] 1 is a cross-sectional view of a toothbrush-like device as an embodiment of a sensing device of the present invention. [Diagram 2] 1 is a cross-sectional view of a baby bottle as an embodiment of a sensing device of the present invention. [Diagram 3] 1 is a cross-sectional view of a pacifier as an embodiment of a sensing device of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0070] FIG. 1 discloses a particular embodiment in which the sensing device 11 is preferably a toothbrush as an intraoral appliance with a replaceable tip saliva as a collecting and sensing part equipped with a sensor, in particular a biosensor for determining the content of a particular biomarker in a biological sample, in particular a collected saliva sample. The determination of the content may be a determination of a value and a comparison of said value with a threshold value. The content may also be a concentration measurement, the concentration being compared with a number of threshold values, each of which comprises a different risk and / or probability of a COPD and / or asthma attack. The determination at least comprises the determination of the content of only one biomarker sample. For reasons of higher accuracy and / or redundancy, the determination may comprise the determination of the content of two or more, i.e. a plurality of biomarkers in the sample. Thus, there may be two or more biosensors for determining the content of a particular biomarker in a biological sample incorporated in the device of the invention, or only one biosensor as mentioned above may determine the content of two or more particular biomarkers in a biological sample.

[0071] In the case where the sensing device is a toothbrush, a sampling or collection device with a saliva inlet 1 can be incorporated into a replaceable toothbrush head 2 used as an oral excreta or secretion collection component. Said sampling or collection device can include one or more fluid channels and / or a set of capillaries used to collect saliva from the apex of the toothbrush bristle region or tip and direct the saliva to a collection chamber where it contacts a biosensor for determining the content of a particular biomarker in the biological sample 3.

[0072] 3. In one particular embodiment not shown in the figures, a variation of the toothbrush of FIG. 1 with capillary tubes can be used. At each use and saliva collection, one capillary tube can be opened by the user while the other capillary tube remains blocked by a special multi-plug system. The capillary tubes can be extracted one by one for successive uses. Alternatively or additionally, the toothbrush head can be removed after use and the saliva tubes can be rinsed with water or another suitable fluid.

[0073] A biosensor for determining the content of a particular biomarker in a biological sample 3 is connected by electrical communication means 4, such as a cable, to the sensor electronics via a connection unit and an electrical connector 7, used for power transmission and communication. The exchangeable head component is connected to the base component by a connector unit 6 via a suitable interface.

[0074] The toothbrush handle may include a control and evaluation unit 8, which may preferably be provided as an embedded electronic system with one or more CPUs processing several input sensing channels conditioned and digitized with analog electronics. Said control and evaluation unit 8 further comprises a data storage device in which is stored a computer program product for carrying out the aforementioned algorithms, preferably the method of the present invention.

[0075] Said control and evaluation device 8 can be located in the toothbrush handle, but alternatively, the control and evaluation device 8 or at least a part of it can be located outside the toothbrush in an external device, such as an electronic mobile device like a handy or laptop. In this context, a mobile device is defined as being part of the measurement setup of the present invention comprising said sensing device 100 and said external device, e.g. a mobile device.

[0076] In the same context, the external device of the sensing device and / or measuring arrangement of the invention may be provided with an output device, also called output unit, such as a screen, a scaling of the risk like 0, 10%, 20%...100%, or a light signal, and / or an acoustic or even a vibration device, capable of providing the user with information and / or a warning regarding the risk of a COPD and / or asthma attack. The said output device preferably gives information of the risk, warning and / or probability of a COPD and / or asthma attack within the next 48 hours, more preferably within the next 24 hours, after the measurement.

[0077] In this regard, an output device may be provided to generate an awakening signal, such as an acoustic, vibration or heat signal, to the user when a high risk of COPD and / or asthma is determined for the user's sleep stage.

[0078] The output device may be integrated within a sensing device that is part of the measurement arrangement of the present invention, or may be part of an external device.

[0079] The processed signals and data samples are then transferred to a communication unit 9. The communication unit 9 preferably comprises bidirectional wireless communication means which may be realized by different wireless communication technologies such as, for example, LoRA, Bluetooth, 4G or 5G, preferably using corresponding low power radios and chipsets.

[0080] The electronics is powered by a power electronics unit 10 with an accumulator and / or battery, preferably a rechargeable battery. Said power electronics unit also allows wireless power transmission to the toothbrush in order to recharge the integrated battery. The biosensor for determining the presence and / or amount of a particular biomarker in a biological sample can also include means for removing excess saliva and allowing the outflow of saliva through an additional channel passing through the sensing unit. One or more additional saliva channels 5 with an inlet and an outlet are necessary for sampling saliva and removing excess saliva.

[0081] Priming of these saliva channels 5, also referred to herein as tubes, can be accomplished by priming with water or air or other fluids. This can be done, for example, by a small syringe that the user fills with air and then pushes the air out after connecting the syringe or a suitable syringe connector to the saliva inlet 1 or saliva channel 5.

[0082] 2 discloses a baby bottle as a second embodiment of the inventive sensing device 1' according to the present invention. The inventive sensing device is a baby bottle device with a replaceable saliva collection and sensing tip equipped with a biosensor for determining the presence and / or amount of a specific biomarker in a biological sample 3'.

[0083] In case the sensing device 1' is a baby bottle, this functional unit comprises an exchangeable nipple component with an integrated saliva duct 2' used as an oral excretion or secretion collection component. The nipple part used for oral suction and saliva collection is attached to a screw cap 3' that incorporates the sensing unit 4' and connects to the baby bottle and can include various biosensors for determining the presence and / or amount of specific biomarkers in a biological sample for different biomarkers, or other sensors such as sensors for measuring electrical conductivity. The sensing unit 4' is further provided with a control and evaluation device 5' for signal and data processing in one or several CPUs. The sensing unit 4' may further be provided with a communication unit 6', preferably wireless communication electronics with a chipset and / or radio. The sensing unit 4' may further be provided with a power source 7', preferably including one or more of the following power electronics components: an antenna / coil, a PU chipset, and / or a battery.

[0084] The electronics and device components can preferably be connected to each other by a communication cord 8' and / or a connector arrangement 9'. The housing 10' of the sensing device 1 can preferably be a real bottle for feeding a baby or a dummy bottle having no feeding function but the form of a feeding bottle.

[0085] In a third embodiment of the present invention, the sensing device 1" is a pacifier. Thus, said sensing device 1" can be provided with a replaceable tip saliva collection portion and a sensing unit 4" having the same parts as the sensing device 1' shown in Figure 2.

Claims

1. 1. A sensing device for determining a patient's risk and / or probability of a COPD attack and / or an asthma attack, the sensing device comprising: a. a collection device for non-invasively collecting a biological sample; b. a biosensor for determining the presence and / or amount of a biomarker in said biological sample, preferably without the need for sample preparation; c) A control and evaluation device; d. an output unit for outputting the risk and / or probability of a COPD and / or asthma attack, preferably within less than 48 hours after the measurement, and / or for warning about the risk and / or probability of a COPD and / or asthma attack; wherein the control and evaluation device is arranged for determining the risk and / or probability of a COPD and / or asthma attack based on the presence and / or measured amount of at least one of the biomarkers. Sensing device.

2. 2. The sensing device of claim 1, wherein the sensing device is provided as a handheld device.

3. 3. A sensing device according to claim 1 or 2, characterised in that the sensing device is provided as a stand-alone device.

4. 4. Sensing device according to any one of claims 1 to 3, characterized in that the biosensor is provided for determining a biomarker selected from the group consisting of IgE, IgA, CRP, TSLP and / or lysozyme.

5. Sensing device according to any one of claims 1 to 4, characterized in that the biosensor is provided for determining an interleukin, in particular an interleukin selected from the group consisting of IL4, IL5, IL6, IL-10, IL-13, IL-17, IL-19, IL-25 and / or IL32.

6. 6. The sensing device of any one of claims 1 to 5, wherein the biosensor or biosensors are provided for determining at least one of the biomarkers of claim 4 and at least one of the biomarkers of claim 5.

7. 7. A sensing device according to any one of claims 1 to 6, characterised in that the collection device is provided for collecting oral discharges or secretions, such as saliva.

8. 8. The sensing device according to claim 1 , wherein the sampling device comprises a sampling stick.

9. 9. The sensing device according to any one of claims 1 to 8, characterized in that the sensing device comprises a housing, and the collection device and / or the housing have the form of a baby pacifier and / or a baby bottle.

10. 10. The sensing device according to any one of claims 1 to 9, characterized in that the sensing device is a toothbrush.

11. 11. The sensing device according to any one of claims 1 to 10, characterized in that the sensing device is a dental device, preferably one or more brackets, bridges, bracelets, replaceable or permanent dental braces, and / or dental implants.

12. 12. The sensing device of claim 1, wherein the collection device comprises a container such as a tube or vial, the collection device further comprising a channel or tube for delivery of oral excretions or secretions from a surface of the sensing device to the container.

13. 13. The sensing device according to claim 1, wherein the container is replaceably arranged inside the sensing device.

14. Sensing device according to any one of claims 1 to 13, characterized in that the sensing device comprises a communication unit for communicating with an external device.

15. 15. The sensing device according to any one of claims 1 to 14, characterized in that the control and evaluation device is arranged to use biochemical, immunochromatographic, electrochemical, optoelectronic, electrical and / or magnetic properties of the sample to determine the risk and / or probability of a COPD and / or asthma attack.

16. Sensing device according to any one of claims 1 to 15, characterized in that the control and evaluation unit is arranged to use data processing algorithms, preferably designed based on historical data processing and analysis or on advanced methods, more preferably on model building, machine learning and / or on advanced methods of detection, prediction, classification and / or pattern recognition.

17. 17. The sensing device according to any one of claims 1 to 16, characterized in that the sensing device is arranged to use and communicate a total risk score of impending COPD and / or asthma exacerbation.

18. 18. Sensing device according to any one of claims 1 to 17, characterised in that the control and evaluation device is arranged to use an analysis program which takes data over a longer period of time, preferably one or more months.

19. 19. The sensing device according to any one of claims 1 to 18, characterized in that the control and evaluation device is provided for carrying out a non-invasive method for collecting a biological sample from a patient from the oral cavity by using a collection device for oral excretions or secretions.

20. The control and evaluation device A. assessing said biochemical characteristic of said sample; B. assessing the immunochromatographic properties of the sample; C. Evaluating the electrochemical properties of the sample after reaction with an assay. D. evaluating the optical or electro-optical properties of said sample; E. evaluating the electrical or magnetic properties of the sample; and / or F. assessing any of the above combinations of properties of said sample; Sensing device according to any one of claims 1 to 19, characterized in that it is provided for:

21. 21. The sensing device according to any one of claims 1 to 20, characterized in that the control and evaluation device is provided for predicting the risk and / or the probability of a clinical symptom, a disease state, a COPD attack and / or an asthma attack, in particular an exacerbation.

22. 22. The sensing device according to any one of claims 1 to 21, characterized in that the data processing algorithms are based on advanced signal and data detection, classification, prediction, pattern recognition, machine learning, which is capable of learning, differentiating and / or predicting the pattern of biomarker changes and their relationship with COPD and / or asthma attacks for a particular individual or patient group.

23. Alternatively or additionally, the algorithm may be based on statistical or probabilistic or neural network or machine learning modelling or other type of model-based algorithm design.

24. 24. A sensing device according to any one of claims 1 to 23, characterized in that the sensing device is arranged to inform the patient, carer or healthcare professional with sufficient accuracy and foresight of the risk and probability of an increasing or impending COPD and / or asthma attack, irrespective of the presence or absence of audible or visible symptoms.

25. Sensing device according to any one of claims 1 to 24, characterised in that the control and evaluation device is provided for detecting and / or indicating whether the detection is feasible or has to be readjusted.

26. 26. Sensing device according to any one of claims 1 to 25, characterised in that the collection device, the biosensor and / or the sensing unit comprising the biosensor are replaceable parts of the sensing device.

27. A measurement arrangement for determining the risk and / or probability of a COPD attack and / or an asthma attack in a patient, said measurement arrangement comprising: a. a collection device for non-invasively collecting a biological sample; b. a biosensor for determining the presence and / or amount of a biomarker in a biological sample, preferably without the need for sample preparation; c) A control and evaluation device; d. an output unit for outputting the risk and / or probability of a COPD and / or asthma attack, preferably within less than 48 hours after the measurement, and / or for warning about the risk and / or probability of a COPD and / or asthma attack; There is a system in place, A measurement arrangement, characterized in that the control and evaluation device is arranged for determining the risk and / or probability of a COPD and / or asthma attack based on the presence and / or measured amount of at least one of the biomarkers.

28. The measurement arrangement comprises a sensing device, the sensing device comprising at least A collection device according to claim 27; The biosensor according to claim 27; 28. A measurement arrangement according to claim 27, characterized in that it comprises:

29. 29. A measuring arrangement according to claim 27 or 28, characterised in that the measuring arrangement comprises a device external to the sensing device comprising at least a control and evaluation device according to claim 27 and / or an output unit according to claim 27.

30. 30. A measurement arrangement according to any one of claims 27 to 29, characterised in that the sensing device is provided as a handheld.

31. 31. Measuring arrangement according to any one of claims 27 to 30, characterized in that the biosensor is provided for determining a biomarker selected from the group consisting of IgE, IgA, CRP and / or lysozyme.

32. 32. Measuring arrangement according to any one of claims 27 to 31, characterized in that the biosensor is provided for determining an interleukin, in particular an interleukin selected from the group consisting of IL4, IL5, IL6, IL-10, IL-17, IL-25 and / or IL32.

33. 33. A measurement configuration according to any one of claims 27 to 32, wherein the biosensor or biosensors are provided for determining at least one biomarker according to claim 4 and at least one biomarker according to claim 5.

34. 34. A measurement arrangement according to any one of claims 27 to 33, characterised in that the collection device is provided for collecting oral emissions or secretions, such as saliva.

35. 35. The measurement arrangement according to any one of claims 27 to 34, characterized in that the sampling device comprises a sampling stick.

36. 36. A measuring arrangement according to any one of claims 27 to 35, characterised in that the sensing device comprises a housing, and the collection device and / or the housing have the form of a baby pacifier and / or a baby bottle.

37. 37. A measuring arrangement according to any one of claims 27 to 36, characterised in that the sensing device is a toothbrush.

38. 38. The measuring arrangement according to any one of claims 27 to 37, characterized in that the sensing device is a dental appliance, preferably one or more brackets, bridges, bracelets, replaceable or permanent dental braces, and / or dental implants.

39. 39. The measurement configuration of any one of claims 27 to 38, characterized in that the collection device comprises a container such as a tube or vial, the collection device further being provided with a channel or tube for delivery of oral excretions or secretions from the surface of the sensing device to the container.

40. 40. The measurement arrangement according to any one of claims 27 to 39, characterized in that the container is replaceably arranged inside the sensing device.

41. 41. A measuring arrangement according to any one of claims 27 to 40, characterised in that the sensing device comprises a communication unit for communicating with a device external to the sensing device.

42. 42. The measurement arrangement according to any one of claims 27 to 41, characterized in that the control and evaluation device is arranged for using biochemical, immunochromatographic, electrochemical, optoelectronic, electrical and / or magnetic properties of the sample to determine the risk and / or probability of a COPD and / or asthma attack.

43. 43. A measuring arrangement according to any one of claims 27 to 42, characterised in that the control and evaluation device is arranged to use data processing algorithms, preferably designed based on historical data processing and analysis or on advanced methods, more preferably on model building, machine learning and / or on advanced methods of detection, prediction, classification and / or pattern recognition.

44. 44. A measuring arrangement according to any one of claims 27 to 43, characterised in that the measuring arrangement is arranged to use and communicate a total risk score of an impending COPD and / or asthma exacerbation.

45. 45. A measuring arrangement according to any one of claims 27 to 44, characterised in that the control and evaluation device is arranged to use an analysis program which takes data over a longer period of time, preferably one or more months.

46. 46. ​​The measurement arrangement according to any one of claims 27 to 45, characterized in that the control and evaluation device is provided for carrying out a non-invasive method for obtaining a biological sample from a patient from the oral cavity by using a collection device for oral effluent or secretions.

47. The control and evaluation device A. assessing said biochemical characteristic of said sample; B. assessing the immunochromatographic properties of the sample; C. Evaluating the electrochemical properties of the sample after reaction with an assay. D. evaluating the optical or electro-optical properties of said sample; E. evaluating the electrical or magnetic properties of the sample; and / or F. assessing any of the above combinations of properties of said sample; 47. A measuring arrangement according to any one of claims 27 to 46, characterized in that it is provided for:

48. 48. The measuring arrangement according to any one of claims 27 to 47, characterized in that the control and evaluation device is arranged for predicting the risk and / or the probability of a clinical condition, a disease state, a COPD and / or asthma attack, in particular a COPD and / or asthma exacerbation.

49. 49. The measuring arrangement according to any one of claims 27 to 48, characterized in that the data processing algorithms are based on advanced signal and data detection, classification, prediction, pattern recognition, machine learning, said machine learning being able to learn, differentiate and / or predict for a specific individual or patient group the pattern of biomarker changes and their relationship with COPD and / or asthma attacks.

50. Alternatively or additionally, the measurement arrangement according to any one of claims 27 to 49, characterized in that the algorithm can be based on statistical or probabilistic or neural network or machine learning modelling or other type of model-based algorithm design.

51. 51. A measuring arrangement according to any one of claims 27 to 50, characterized in that the measuring arrangement is provided to inform the patient, a caregiver or a medical professional with sufficient accuracy and foresight about the risk and probability of an increasing or impending COPD and / or asthma attack, irrespective of the presence or absence of audible or visible symptoms.

52. 52. A measuring arrangement according to any one of claims 27 to 51, characterised in that the control and evaluation device is provided for detecting and / or indicating whether the detection is feasible or has to be readjusted.

53. 53. The measuring arrangement according to any one of claims 27 to 52, characterized in that the collection device, the biosensor and / or the sensing unit comprising the biosensor are replaceable parts of the sensing device.

54. A method for the maintenance of a sensing device according to any one of claims 1 to 26 and / or a measuring arrangement according to any one of claims 27 to 53, comprising: A. Sampling a biological sample from a patient's oral cavity by a non-invasive method; B. Determining the presence and / or amount of a biomarker in a biological sample, preferably without the need for sample preparation by measurement in a sensing method; C. comparing the result of step B to one or more previous measurements or to a predetermined threshold; D. initiating a cleaning of the collection device and / or the biosensor and / or the sensing unit comprising the biosensor and / or providing information regarding the replacement of the collection device and / or the biosensor and / or the sensing unit comprising the biosensor; A method comprising:

55. The sensing method comprises: A. evaluating said biochemical characteristic of said sample; B. evaluating the immunochromatographic properties of the sample; C. Evaluating the electrochemical properties of the sample after reaction with an assay. D. evaluating the optical or electro-optical properties of the sample; E evaluating the electrical or magnetic properties of the sample; and / or F. evaluating any of the above combinations of properties of the sample.

55. The method of claim 54, comprising at least one, and preferably all, of:

56. 56. The method according to claim 54 or 55, characterized in that the sensing method uses biochemical, immunochromatographic, electrochemical, optoelectronic, electrical and / or magnetic properties of the sample to determine the risk and / or probability of a COPD and / or asthma attack.

57. 57. The method according to any one of claims 54 to 56, characterized in that the sensing method uses data processing algorithms, preferably designed based on historical data processing and analysis or advanced methods, more preferably model building, machine learning and / or advanced methods of detection, prediction, classification and / or pattern recognition.

58. 58. The method according to any one of claims 54 to 57, characterized in that the detection method uses specific software algorithms based on machine learning to calculate and communicate a risk score of impending COPD and / or asthma exacerbation.

59. 59. A method according to any one of claims 54 to 58, characterized in that the sensing method uses an analysis program that collects data over a longer period of time, preferably one or more months.

60. 60. The method according to any one of claims 54 to 59, characterized in that the method comprises carrying out a non-invasive method for collecting a biological sample from a patient from the oral cavity by using a collection device for oral excretions or secretions.

61. 61. The method according to any one of claims 54 to 60, characterized in that the sensing method predicts the risk and / or the probability of a clinical symptom, a disease state, a COPD attack and / or an asthma attack, in particular an exacerbation.

62. 62. The method according to any one of claims 54 to 61, characterized in that the sensing method is based on advanced signal and data detection, classification, prediction, pattern recognition, machine learning, which is capable of learning, differentiating and / or predicting the pattern of biomarker changes and their relationship with COPD and / or asthma attacks for a particular individual or patient group.

63. Alternatively or additionally, the method according to any one of claims 54 to 62, characterized in that the sensing method uses an algorithm based on statistical or probabilistic or neural network or machine learning modelling or other type of model-based algorithm design.

64. 64. The method of any one of claims 54 to 63, characterized in that the sensing method informs the patient, caregiver or healthcare professional with sufficient accuracy and foresight of the risk and probability of an increasing or impending COPD and / or asthma attack, regardless of the presence or absence of audible or visible symptoms.

65. 65. A method according to any one of claims 54 to 64, characterized in that the sensing method detects and / or signals whether the detection is feasible or whether it has to be readjusted.

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