Exhaled nitric oxide measurement device and method

Abstract

The application discloses a breath nitric oxide measuring device and method, and relates to the field of breath measurement. The three-way valve in the device extracts air into a gas analysis device to realize zero point testing. After zero point testing, the breath channel device is connected with sample gas. The control unit controls the opening of the exhaust valve, and the sample gas is discharged according to the exhaust time. The three-way valve connects the sample gas discharged by the exhaust valve with the gas analysis device to analyze the gas concentration of the sample gas. The control unit determines the concentration of nitric oxide in the sample gas according to the results of zero point testing and sample analysis. The exhaust time is determined according to the gender, age, weight of the subject, the volume of inhaled test gas, the concentration of nitric oxide in the inhaled test gas, the concentration of nitric oxide in the exhaled test gas and the flow of the exhaled test gas. The application can reduce the measurement cost and improve the measurement efficiency.

Description

Technical Field

[0001] This invention relates to the field of exhaled breath measurement, and in particular to an exhaled nitric oxide (NO) measuring device and method. Background Technology

[0002] Nitric oxide, produced by respiratory cells and measured in exhaled breath, is an internationally recognized biomarker of airway inflammation. It can be used to diagnose respiratory inflammation and guide the evaluation of anti-inflammatory treatment. While exhaled nitric oxide testing is currently used for inflammation detection and anti-inflammatory treatment evaluation in respiratory diseases such as asthma and COPD, two major practical problems exist in its widespread adoption:

[0003] Firstly, to ensure that the breath test measures NO produced in the respiratory tract, rather than inhaled and retained in the dead space of the respiratory tract, all currently available technologies use the internationally recommended method: first, clean gas containing no NO or less than 5 ppb is inhaled through a NO filter to replace the dead space gas that may contain environmental NO that was previously retained in the respiratory tract; then, the NO produced in the respiratory tract is measured by exhalation. Compared to the Helicobacter pylori breath test, which only requires exhalation and does not require inhalation, this NO breath test involves a somewhat cumbersome inhalation-exhalation process. More seriously, this inhalation method may cause subjects to refuse the test due to concerns about cross-infection. Furthermore, the additional use of NO filters and the additional gas valves and pumps required for separate sampling and analysis increase the cost of the test, further hindering the widespread adoption of breath test technology.

[0004] Secondly, to ensure that the breath test detects gas produced in the respiratory tract with a stable or plateau concentration, all commercially available sensor technologies currently employ internationally recommended methods: sampling and analysis must be performed after children and adults exhale at a constant 50 ml / s expiratory flow rate (allowing for 10% fluctuation) for more than 6 and 10 seconds, respectively. Since the response time of NO sensors typically exceeds 10 seconds, a method is usually employed where sampling is performed for 6 or 10 seconds followed by 20-30 seconds of sensor detection. Including the zero-point testing required for each test, the total testing time usually exceeds 50 seconds. Such NO breath testing is not only unsuitable for patients who cannot maintain a constant expiratory flow rate for 6 or 10 seconds, but also appears somewhat sluggish.

[0005] In summary, existing methods for measuring exhaled nitric oxide are costly and inefficient. Summary of the Invention

[0006] Based on this, embodiments of the present invention provide a device and method for measuring exhaled nitric oxide, so as to reduce measurement costs and improve measurement efficiency.

[0007] To achieve the above objectives, embodiments of the present invention provide the following solutions:

[0008] A breath nitric oxide measuring device includes: an exhalation channel device, a three-way valve, an exhaust valve, a gas analysis device, and a control unit;

[0009] The output end of the exhalation channel device is connected to the first end of the exhaust valve and the three-way valve, respectively; the second end of the three-way valve is connected to the gas analysis device; the gas analysis device is connected to the control unit.

[0010] The three-way valve is used to draw air from the gas analysis device;

[0011] The gas analysis device is used to analyze the gas concentration in the air to achieve zero-point testing;

[0012] The exhalation channel device is used to introduce sample gas after the zero-point test; the sample gas is the test gas exhaled by the subject.

[0013] The control unit is also used to control the three-way valve to close and the venting valve to open after sample gas is introduced into the exhalation channel device, so that the venting valve starts to discharge the introduced sample gas until the venting time is reached, and then controls the venting valve to close and the three-way valve to open.

[0014] The emptying time is the time it takes for all the gas in the subject's physiological dead space to be expelled; the emptying time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject.

[0015] The three-way valve is also used to introduce the sample gas discharged from the vent valve into the gas analysis device.

[0016] The gas analysis device is also used to analyze the gas concentration of the introduced sample gas to obtain the sample analysis results;

[0017] The control unit is also used to determine the concentration of nitric oxide in the sample gas based on the results of the zero-point test and the sample analysis results.

[0018] Optionally, the formula for calculating the evacuation time is:

[0019]

[0020] Where T0 represents the drainage time; V D Q represents the volume of the physiological dead space; Q represents the flow rate of the test gas exhaled by the subject.

[0021] If the subject is male, the formula for calculating the volume of the physiological dead space is:

[0022]

[0023] Among them, V I Indicates the volume of test gas inhaled by the subject; FA NO (t1) represents the concentration of nitric oxide in the test gas inhaled by the subject; FA NO (t2) represents the concentration of nitric oxide in the test gas exhaled by the subject; Age represents the subject's age; Height represents the subject's weight; t1 represents the time when the subject inhaled the test gas; t2 represents the time when the subject exhaled the test gas; t2-t1 represents the exhalation measurement time period;

[0024] If the subject is female, the formula for calculating the volume of the physiological dead space is:

[0025]

[0026] Optionally, the exhaled nitric oxide measuring device further includes: a diverter valve; the diverter valve is connected to the exhaled channel device; the control unit is also used to control the diverter valve to open when the flow rate of the sample gas is greater than a set flow rate value, and the diverter valve and the venting valve together vent the introduced sample gas until the venting time is reached.

[0027] Optionally, the gas analysis device is at least one; different gas analysis devices analyze the concentration of different gas components in the introduced sample gas; at least one gas analysis device analyzes the concentration of nitric oxide in the introduced sample gas.

[0028] Optionally, the exhaled nitric oxide measuring device further includes: a filter; the third end of the three-way valve is connected to the filter; the filter is used to introduce filtered air into the gas analysis device through the three-way valve.

[0029] Optionally, the exhaled nitric oxide measuring device further includes a pump; the second end of the three-way valve is connected to the gas analysis device via the pump.

[0030] Optionally, the exhaled nitric oxide measuring device further includes: a flow sensor; the flow sensor is connected to the exhalation channel device; the flow sensor is used to measure the flow rate of the test gas exhaled by the subject.

[0031] The present invention also provides a method for measuring exhaled nitric oxide, the method being used in the above-mentioned exhaled nitric oxide measuring device; the method includes: a zero-point testing process and a sample gas testing process;

[0032] The zero-point testing process includes:

[0033] Open the three-way valve to draw air into the gas analyzer, and the gas analyzer will analyze the gas concentration of the air to achieve zero-point testing.

[0034] After the zero-point test, the sample gas testing process begins;

[0035] The sample gas testing process includes:

[0036] Sample gas is introduced through an exhalation channel device; the sample gas is the test gas exhaled by the subject.

[0037] After sample gas is introduced into the exhalation channel device, the control unit closes the three-way valve and opens the vent valve, causing the vent valve to begin venting the introduced sample gas until the venting time is reached. Then, the vent valve closes and the three-way valve opens, and the three-way valve introduces the sample gas vented from the vent valve into the gas analysis device.

[0038] The emptying time is the time it takes for all the gas in the subject's physiological dead space to be expelled; the emptying time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject.

[0039] The gas analysis device analyzes the gas concentration of the introduced sample gas to obtain the sample analysis results;

[0040] The control unit determines the concentration of nitric oxide in the sample gas based on the results of the zero-point test and the sample analysis results.

[0041] According to specific embodiments provided by the present invention, the present invention discloses the following technical effects:

[0042] In this embodiment of the invention, the control unit controls the venting valve to release the sample gas according to the venting time, so that all the gas in the subject's physiological dead space is expelled. The venting time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject. It eliminates the need to use an additional NO filter to replace the dead space gas that may contain environmental NO that has been retained in the respiratory tract before the test, reducing the test cost. It also eliminates the need for the subject to exhale continuously at a constant rate for 6 or 10 seconds for sampling, improving the measurement efficiency. Attached Figure Description

[0043] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0044] Figure 1 The structure of the exhaled nitric oxide measuring device provided in the embodiments of the present invention Figure 1 ;

[0045] Figure 2 The structure of the exhaled nitric oxide measuring device provided in the embodiments of the present invention Figure 2 ;

[0046] Figure 3 This is an overall design structural diagram of the exhaled nitric oxide measuring device provided in an embodiment of the present invention;

[0047] Figure 4 An exploded view of the detailed structure of Example 1 provided in the embodiment of the present invention;

[0048] Figure 5 This is a difference graph corresponding to the difference data in Example 1 provided in this embodiment of the invention;

[0049] Figure 6 This is a line graph corresponding to the correlation coefficient data of Example 1 provided in the embodiments of the present invention;

[0050] Figure 7 An exploded view of the detailed structure of Example 2 provided in the embodiment of the present invention;

[0051] Figure 8 This is a difference graph corresponding to the difference data of the first verification experiment provided in Example 2 of the present invention;

[0052] Figure 9 This is a line graph showing the correlation coefficient data from the first verification experiment of Example 2 provided in this embodiment of the invention.

[0053] Figure 10 This is a difference graph corresponding to the difference data of the second verification experiment provided in Example 2 of the present invention.

[0054] Figure 11 This is a line graph showing the correlation coefficient data from the second verification experiment provided in Example 2 of this invention.

[0055] Figure 12 This is a difference graph corresponding to the difference data of the third verification experiment in Example 2 provided in this embodiment of the invention;

[0056] Figure 13Line graph corresponding to the correlation coefficient data of the third verification experiment provided in Example 2 of the present invention.

[0057] Symbol explanation:

[0058] Exhalation channel device—100, flow sensor—200, vent valve—300, three-way valve—400, pump—500, gas analyzer—600, filter—700, control unit—800, diverter valve—300', gas analyzer two—600', instrument top cover—1, instrument bottom cover—2, mounting bracket—3. Detailed Implementation

[0059] The technical solutions of the present invention will now be described with reference to the accompanying drawings in the embodiments of the present invention.

[0060] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0061] See Figure 1 The exhaled nitric oxide measuring device of this embodiment includes: an exhaled channel device 100, a three-way valve 400, an emptying valve 300, a gas analysis device 600, and a control unit 800.

[0062] The output end of the exhalation channel device 100 is connected to the first end of the venting valve 300 and the three-way valve 400, respectively; the second end of the three-way valve 400 is connected to the gas analysis device 600; and the gas analysis device 600 is connected to the control unit 800.

[0063] The three-way valve 400 is used to draw air into the gas analysis device 600.

[0064] The gas analysis device 600 is used to analyze the gas concentration of air to achieve zero-point testing and obtain the results of the zero-point test; the results of the zero-point test include: zero-point value; the zero-point value is the concentration of nitrogen monoxide in the air, and the zero-point value is used as a test benchmark.

[0065] The control unit 800 is used to obtain the zero-point value based on the results of the zero-point test.

[0066] The exhalation channel device 100 is used to introduce sample gas after the zero-point test; the sample gas is the test gas exhaled by the subject.

[0067] The control unit 800 is also used to control the three-way valve 400 to close and the venting valve 300 to open after sample gas is introduced into the exhalation channel device 100, so that the venting valve 300 starts to discharge the introduced sample gas until the venting time is reached, and then controls the venting valve 300 to close and the three-way valve 400 to open.

[0068] The emptying time is the time it takes for all the gas in the subject's physiological dead space to be expelled. The emptying time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject.

[0069] The formula for calculating the evacuation time is:

[0070]

[0071] Where T0 represents the drainage time; V D Q represents the volume of the physiological dead space; Q represents the flow rate of the test gas exhaled by the subject.

[0072] If the subject is male, the formula for calculating the volume of the physiological dead space is:

[0073]

[0074] Among them, V I Indicates the volume of test gas inhaled by the subject; FA NO (t1) represents the concentration of nitric oxide in the test gas inhaled by the subject; FA NO (t2) represents the concentration of nitric oxide in the test gas exhaled by the subject; Age represents the subject's age; Height represents the subject's weight; t1 represents the time when the subject inhaled the test gas; t2 represents the time when the subject exhaled the test gas; t2-t1 represents the exhalation measurement time period.

[0075] If the subject is female, the formula for calculating the volume of the physiological dead space is:

[0076]

[0077] The three-way valve 400 is also used to introduce the sample gas discharged by the vent valve 300 into the gas analysis device 600.

[0078] The gas analysis device 600 is also used to analyze the gas concentration of the introduced sample gas to obtain sample analysis results. The sample analysis results include: sample gas value; the sample gas value is the concentration analysis value of nitric oxide in the sample gas.

[0079] The control unit 800 is also used to determine the concentration of nitric oxide in the sample gas based on the results of the zero-point test (i.e., the zero-point value) and the sample analysis results (i.e., the sample gas value). Specifically, the concentration of nitric oxide in the sample gas is calculated according to the formula C = (I1 - I0) / S; C represents the concentration of nitric oxide in the sample gas; I1 represents the sample gas value; I0 represents the zero-point value; and S represents the sensitivity of the gas analysis device 600.

[0080] In one example, please see still Figure 1 The exhaled nitric oxide measuring device further includes: a filter 700, a pump 500, and a flow sensor 200.

[0081] The third end of the three-way valve 400 is connected to the filter 700; the filter 700 is used to introduce filtered air into the gas analyzer 600 through the three-way valve 400. The second end of the three-way valve 400 is connected to the gas analyzer 600 via the pump 500. The flow sensor 200 is connected to the exhalation channel device 100; the flow sensor 200 is used to measure the flow rate of the test gas exhaled by the subject.

[0082] In one example, see Figure 2 The exhaled nitric oxide measuring device further includes: a diverter valve 300'; the diverter valve 300' is connected to the exhalation channel device 100; the control unit 800 is also used to control the diverter valve 300' to open when the flow rate of the sample gas is greater than a set flow rate value, and the diverter valve 300' and the vent valve 300 work together to vent the incoming sample gas until the venting time is reached. For example, when the flow rate of the sample gas is 50 ml / s, the diverter valve is closed, and the vent valve 300 alone is used to vent the incoming sample gas until the venting time is reached; when the flow rate of the sample gas is 200 ml / s, the vent valve 300 and the diverter valve 300' are opened simultaneously to vent the incoming sample gas together until the venting time is reached.

[0083] In one example, please see still Figure 2 The gas analysis device 600 is at least one; different gas analysis devices 600 analyze the concentration of different gas components in the sample gas; at least one gas analysis device 600 analyzes the concentration of nitric oxide in the sample gas.

[0084] In this embodiment, the exhaled nitric oxide measuring device uses an intelligent physiological dead space algorithm to calculate the emptying time, thereby intelligently expelling the dead space gas. It also integrates an analysis device, reducing the internal volume of the instrument. This high level of integration and miniaturization reduces the cost and size of the instrument.

[0085] The above-mentioned exhaled nitric oxide measuring device will be described in further detail below.

[0086] This embodiment establishes a regression equation using NO to determine the physiological dead space and parameters such as height, age, and weight, enabling intelligent setting of exhalation and sampling times. It also incorporates environmental NO detection into the correlation equation to mitigate the impact of environmental NO on the test. Furthermore, it achieves intelligent control of sampling time, allowing for different exhalation sampling times for different populations, thus achieving precise sampling. The integrated analysis device reduces the internal volume of the instrument; this high level of integration also lowers the cost of the instrument.

[0087] First, we will introduce the specific process by which the control unit uses the built-in intelligent physiological dead space algorithm to calculate the emptying time.

[0088] Determining physiological dead space using NO requires consideration of the following factors: the lung diffusion capacity of NO gas, the subject's height, weight, age, and the environmental nitric oxide (NO) concentration.

[0089] Pulmonary diffusion capacity refers to the ability of a certain alveolar gas to diffuse from the alveoli into the capillaries and into the bloodstream through the alveolar-capillary membrane (composed of the alveolar epithelium and its basement membrane, the alveolar capillary endothelium and its basement membrane, and the connective tissue between the two basement membranes), and to bind to hemoglobin (Hb) in red blood cells. The gases exchanged in the alveolar-capillary membrane are mainly oxygen (O2) and carbon dioxide (CO2). Directly calculating the diffusion capacity of oxygen requires measuring the mean partial pressure of oxygen in the pulmonary capillaries, which is complex. Carbon monoxide (CO) binds to hemoglobin 210 times more strongly than oxygen (O2), and the oxygen partial pressure within the physiological range is not a major interfering factor. Except for heavy smokers, the CO content in the blood plasma of normal individuals is almost zero, making it convenient to calculate CO intake during the test. Furthermore, CO dissolves very little in the blood plasma during transport, making CO an ideal gas for measuring pulmonary diffusion capacity. The pulmonary diffusion capacity of NO gas is four times that of CO.

[0090] To overcome the shortcomings of existing methods for calculating airway dead space, such as significant interference from user breathing and inaccurate measurement, this embodiment includes a method for calculating airway dead space during expiratory nitric oxide measurement, comprising:

[0091] Lung nitric oxide diffusion capacity refers to the volume of nitric oxide passing through the entire respiratory membrane per unit time at a unit partial pressure, reflecting to some extent the degree of obstruction of nitric oxide gas exchange by the respiratory membrane. NOThere are three methods for measuring nitric oxide (NO) in this study: the single-breath method, the repeated-breath method, and the steady-state method. This invention uses only the single-breath method: The subject is connected to a Shangwo nitric oxide analyzer. The subject inhales deeply to the residual volume, rapidly inhales a NO mixture of concentration α to the total lung capacity, holds their breath for 1-2 seconds, and exhales to the residual volume. The flow meter and nitric oxide analyzer record the flow rate and gas concentration changes throughout the entire breathing process. The DL (decompression ratio) is calculated based on the changes in alveolar air volume and alveolar NO concentration over a specific time period. NO This includes physiological dead space air and alveolar air. The measurement should be repeated every 5-10 minutes, with an error within 5%. The calculation formula is as follows:

[0092]

[0093]

[0094] In the formula, DL NO V is the pulmonary nitric oxide diffusion capacity; A V represents alveolar volume; I V is the volume of the test gas (gas mixture) inhaled by the subject. D The volume of physiological dead space; t2-t1 represents the expiratory measurement time period; FA NO (t1) represents the concentration (ppd) of nitric oxide in the test gas inhaled by the subject; FA NO (t2) represents the concentration (ppd) of nitric oxide in the test gas exhaled by the subject; This represents the change in NO index concentration in the exhaled measurement segment; K is a constant, which can take the value of 1000×60 / (PB-47); PB is the atmospheric pressure (mmHg) of the test environment.

[0095] Physiological dead space equals the sum of alveolar dead space and anatomical dead space. Since anatomical dead space is fixed, the ratio of physiological dead space to tidal volume basically reflects the size of alveolar dead space.

[0096] V A =V C +V D (3)

[0097] In the formula, V C Vital capacity (V) C The calculation formula is:

[0098] If the subject is male, the calculation formula is:

[0099] V C =[27.63-0.112*Age]*Height (4)

[0100] If the subject is male, the calculation formula is:

[0101] VC =[27.78-0.101*Age]*Height (5)

[0102] In summary, the formula is derived as follows:

[0103] By combining formulas (1) and (3), we can obtain the following calculation formula:

[0104]

[0105] Substituting formula (6) into (2), we obtain the following calculation formula:

[0106]

[0107] Substituting formula (4) into (7), we obtain the following male V D Calculation formula:

[0108]

[0109] Substituting formula (5) into (7), we obtain the following female V. D Calculation formula:

[0110]

[0111] Substituting formula (7) into (1) yields DL. NO The formula is as follows:

[0112]

[0113] Male lung capacity V C Substituting formula (4) into formula (10) above, we obtain the male DL. NO The formula is as follows:

[0114]

[0115] V of female lung capacity C Substituting formula (5) into formula (10) above, we obtain the female DL. NO The formula is as follows:

[0116]

[0117] The volume of the test gas inhaled by the subject was V. I The flow sensor is responsible for monitoring the volume of the breathed gas during the test process in real time, including the volume of the test gas inhaled by the tester.

[0118] Volume of physiological dead space V DIn the breath-holding test procedure, during the exhalation phase after breath-holding, a sideflow acquisition method is used. An electrochemical nitric oxide sensor provides a real-time signal curve of the concentration of exhaled gas components as a function of exhaled volume. Taking advantage of the characteristic that nitric oxide is not diluted by residual lung gas in the dead space of the device and the human body, the dead space flushing point is obtained. That is, the nitric oxide concentration of the gas is relatively high in the initial stage of exhalation. In order to accurately determine the inflection point of the nitric oxide concentration signal change, the dead space flushing point and the dead space volume are obtained.

[0119] Exhaled gas component concentration (FA) NO (t)): In the breath-holding exhalation phase of the one-breath test procedure, a sideflow acquisition method was used. The electrochemical nitric oxide sensor provided a real-time signal curve of the concentration of exhaled gas components as a function of exhaled volume, in order to obtain a reasonable evaluation of exhaled gas component concentration (FA). NO The sample taken for (t) should be taken after the concentration of exhaled gas components has stabilized. That is, 500 mL of exhaled gas should be selected as the sample for the concentration of exhaled gas components after the dead space flushing point. At the same time, the user is given the option to manually shift the sample sampling point backward to ensure that the dead space is completely flushed.

[0120] Based on the above formula, and after testing with 30 healthy individuals, the subjects inhaled 1L of clean air (NO concentration less than 5ppb) and underwent an exhalation test for 10 seconds, obtaining an exhaled NO concentration of 10ppb. The subjects also inhaled 1L of a mixture of air containing 100ppb NO and underwent an exhalation test for 10 seconds, obtaining an exhaled NO concentration of 20ppb. The following parameters can be obtained: V I It is 1L.

[0121] t2-t1 is taken as 10s, FA NO (t1) takes the value of 100 ppb; FA NO (t2) takes the value of 20-10=10ppb.

[0122] Male V D Calculation formula:

[0123]

[0124] Women V D Calculation formula:

[0125]

[0126] The emptying time can be calculated:

[0127]

[0128] Male T0:

[0129]

[0130] Women's T0:

[0131]

[0132] T0 represents the emptying time; Q represents the flow rate of the test gas exhaled by the subject.

[0133] With the above design, the user interface can input the subject's height, age, and gender to intelligently empty the physiological dead space, achieving intelligent control and user-friendly quality control while ensuring the subject's comfort.

[0134] Having obtained the emptying time as described above, the following section introduces the exhaled nitric oxide measuring device based on the aforementioned emptying time.

[0135] See Figure 3 The overall design of the exhaled nitric oxide measuring device is as follows: it consists of an exhalation channel device 100, a flow sensor 200, a three-way valve 400, a pump 500, a gas analyzer 600, and a control unit 800. The flow sensor 200 is installed on the exhalation channel device 100 to monitor flow and provide flow data to the control unit 800. The three-way valve 400 is installed at the rear end of the exhalation channel device 100, with one end for exhalation emptying and the other end connected to the pump 500. After emptying, the valve is switched to connect one end of the pump 500. The pump 500 is connected to the rear end of the three-way valve 400 for suction, and the rear end of the pump 500 is connected to the gas analyzer 600 for gas transport and analysis. The control unit 800 controls the three-way valve 400 and the pump 500, and performs data collection and analysis functions for the flow sensor 200 and the gas analyzer 600. The exhalation channel device 100 adopts a streamlined design, and the conical angle of the pipeline design is 10° to 15°, preferably 15°.

[0136] The overall testing approach for the exhaled nitric oxide measuring device is as follows:

[0137] (1) To conduct a zero-point test, the three-way valve 400 is connected to one end of the pump 500 to draw air from the exhalation channel device 100 and enter the gas analysis device 600 for a zero-point test. The control unit 800 collects and calculates the zero-point value I0.

[0138] (2) Conduct sample gas testing. The subject breathes gas into the exhalation channel device 100 at a certain flow rate, such as Q = 50 mL / s or Q = 2 mL / s. The gas is then expelled through the three-way valve 400. After the gas is emptied, the three-way valve 400 is switched to the pump 500 to draw the gas in the exhalation channel device 100 into the gas analysis device 600. The emptying time is calculated by the control unit 800 based on the subject's input data of gender, height, and age to obtain the sample gas value I1. The three-way valve 400 is then intelligently controlled to achieve intelligent emptying.

[0139] (3) Through the above zero-point test and sample gas test, the gas concentration C = I1 - I0 / S can be calculated, where S is the sensitivity of the gas analysis device and S is a fixed value.

[0140] The integrated design described above enables miniaturization.

[0141] The following is combined Figure 1 and Figure 2 Two specific examples are given to further illustrate the testing process, detailed exploded diagram structure, and effectiveness of the exhaled nitric oxide measuring device.

[0142] Example 1:

[0143] Please see again Figure 1 The exhaled nitric oxide measuring device consists of an exhalation channel device 100, a flow sensor 200, an exhaust valve 300, a three-way valve 400, a pump 500, a gas analyzer 600, a filter 700, and a control unit 800. Its testing process is as follows:

[0144] (1) To conduct a zero-point test, the three-way valve 400 is connected to one end of the filter 700 and the pump 500 to draw air into the gas analysis device 600 for a zero-point test. The control unit 800 collects and calculates the data.

[0145] (2) To conduct sample gas testing, the subject inhales gas into the exhalation channel device 100 at a flow rate of Q of 50 mL / s and exhales it through the venting valve 300. After venting, the venting valve 300 is closed. During sample gas testing, the pump 500 draws the gas in the exhalation channel device 100 into the gas analysis device 600 through the three-way valve 400 for gas concentration analysis. The venting time is calculated by the control unit 800 based on the gender, height, and age data input by the subject, and the venting valve 300 is intelligently controlled to achieve intelligent venting.

[0146] The exploded view of the detailed structure of Example 1 is as follows: Figure 4As shown, the entire device comprises an instrument cover 1, an exhalation channel device 100, a flow sensor 200, an emptying valve 300, a three-way valve 400, a pump 500, a mounting bracket 3, a gas analyzer 600, a filter 700, a control unit 800, and an instrument cover 2. The exhalation channel device 100 has an interface at its rear end connected to the emptying valve 300 and the three-way valve 400; the normally open end of the three-way valve 400 is connected to the pump 500, and the other end is connected to the filter 700; the rear end of the pump 500 is connected to the gas analyzer 600. The exhalation channel device 100, valve 300, three-way valve 400, and pump 500 are all mounted on the mounting bracket 3. The flow sensor 200 and the gas analyzer 600 are installed inside the instrument cover 2; the control unit 800 is installed on the instrument cover 1.

[0147] The device in Example 1 (HA1101-FeNO) was compared with the existing breath analyzer CA2122-FeNO. A comparative validation was conducted, involving 55 participants. The average difference between the HA1101-FeNO and the Sunvou-CA2122 breath analyzer was -2.1 ppb (ranging from -13.1 to 9.0 ppb), with a correlation coefficient of 0.9412. The difference data are shown in Table 1, and the corresponding difference graph is shown below. Figure 5 As shown in the figure; the correlation coefficient data are shown in Table 2, and the corresponding line graphs are shown in the figure. Figure 6 As shown.

[0148] Table 1. Difference Data Table for Example 1

[0149]

[0150]

[0151] Table 2 shows the correlation coefficient data for Example 1.

[0152] VARIABLE X HA1101-FeNO Sampling size 55 Correlation coefficient r 0.9412 Significance level P<0.0001 95% confidence interval (r) 0.9009-0.9655

[0153] Example 2:

[0154] Example 1 demonstrates FeNO50 testing; this example extends the FeNO200 function by adding a gas analyzer to enable multiple gas testing capabilities. Please refer to [link to previous section]. Figure 2 The exhaled nitric oxide measuring device consists of an exhalation channel device 100, a flow sensor 200, an exhaust valve 300, a diverter valve 300', a three-way valve 400, a pump 500, a gas analyzer 600, a second gas analyzer 600', a filter 700, and a control unit 800. Its testing process is as follows:

[0155] (1) To conduct a zero-point test, the three-way valve 400 is connected to one end of the filter 700 and the pump 500 to draw air into the gas analysis device 600 for a zero-point test. The control unit 800 collects and calculates the data.

[0156] (2) Sample gas testing is conducted. The subject breathes gas into the exhalation channel device 100 at a flow rate of Q of 50 mL / s and then expels it through the emptying valve 300. At this time, the diverter valve 300' is in the closed state. After emptying is completed, the emptying valve 300 is closed. During the sample gas test, the pump 500 draws the gas in the exhalation channel device 100 into the gas analysis device 600 and the gas analysis device 600' through the three-way valve 400 for multiple gas concentration analysis. The emptying time is calculated by the control unit 800 based on the gender, height and age data input by the subject, and the emptying valve 300 is intelligently controlled to achieve intelligent emptying.

[0157] (3) Sample gas testing is carried out. The subject breathes gas into the exhalation channel device 100 at a flow rate of Q of 200 mL / s. At this time, the diversion valve 300' and the emptying valve 300 are in the open state to carry out double emptying. After emptying is completed, the emptying valve 300 and the diversion valve 300' are closed. During sample gas testing, the pump 500 draws the gas in the exhalation channel device 100 into the gas analysis device 600 and the gas analysis device 600' through the three-way valve 400 for multiple gas concentration analysis. The emptying time is calculated by the control unit 800 based on the gender, height and age data input by the subject, and the emptying valve 300 is intelligently controlled to realize intelligent emptying.

[0158] Exploded view of the detailed structure of Example 2 is as follows: Figure 7 As shown, the entire device comprises an instrument cover 1, an exhalation channel device 100, a flow sensor 200, an emptying valve 300, a diverter valve 300', a three-way valve 400, a pump 500, a mounting bracket 3, a gas analyzer 600, a second gas analyzer 600', a filter 700, a control unit 800, and an instrument cover 2. The exhalation channel device 100 has a diverter valve 300' installed at its front end, and the rear end of the exhalation channel device 100 is connected to the valve 300 and the three-way valve 400. The normally open end of the three-way valve 400 is connected to the pump 500, and the other end is connected to the filter 700. The rear end of the pump 500 is connected to the gas analyzer 600, and the rear end of the gas analyzer 600 is connected in series with the second gas analyzer 600'. The exhalation channel device 100, the emptying valve 300, the diverter valve 300', the three-way valve 400, and the pump 500 are all mounted on the mounting bracket 3. The flow sensor 200, gas analyzer 600, and gas analyzer 600' are installed inside the lower cover 2 of the instrument; the control unit 800 is installed on the upper cover 1 of the instrument.

[0159] The device in Example 2 (TM2120-FeNO50) is compared with the existing breath analyzer CA2122-FeNO50.

[0160] (1) FeNO50 comparative verification was conducted, with a total of 29 participants in the first verification experiment. The average difference between TM2120-FeNO50 and CA2122-FeNO50 was -0.6 ppb (-10.9 to 9.8 ppb), with a correlation coefficient of 0.9674. The difference data are shown in Table 3, and the corresponding difference graph is shown in... Figure 8 As shown; the correlation coefficient data are shown in Table 4, and the corresponding line graphs are shown in... Figure 9 As shown.

[0161] Table 3. Difference data from the first verification experiment in Example 2.

[0162]

[0163]

[0164] Table 4. Correlation coefficient data for Example 2, First Validation Experiment

[0165] VARIABLE X TM2120-FeNO50 Sampling size 29 Correlation coefficient r 0.9674 Significance level P<0.0001 95% confidence interval (r) 0.9310-0.9848

[0166] (2) A comparative verification of FeNO200 was conducted, involving 92 participants (i.e., the second verification experiment). The average difference between TM2120-FeNO200 and CA2122-FeNO200 was -0.4 ppb (-4.3 to 3.4 ppb), with a correlation coefficient of 0.9674. The difference data are shown in Table 5, and the corresponding difference graph is shown in... Figure 10 As shown; the correlation coefficient data are shown in Table 6, and the corresponding line graphs are shown in... Figure 11 As shown.

[0167] Table 5. Difference data from the second verification experiment in Example 2.

[0168]

[0169]

[0170] Table 6. Correlation coefficient data for Example 2, Second Verification Experiment.

[0171] VARIABLE X TM2120-FeNO200 Sampling size 92 Correlation coefficient r 0.9152 Significance level P<0.0001 95% confidence interval (r) 0.8742-0.9432

[0172] (3) FeCO comparison verification was conducted, with a total of 31 participants (i.e., the third verification experiment). The average difference between TM2120-FeCO and CA2122-FeCO was -1.5 ppm (-5.1 to 2.1 ppm), with a correlation coefficient of 0.9501. The difference data are shown in Table 7, and the corresponding difference graph is shown in... Figure 12 As shown; the correlation coefficient data are shown in Table 8, and the corresponding line graph is shown in... Figure 13 As shown.

[0173] Table 7. Difference data from the third verification experiment in Example 2.

[0174]

[0175]

[0176] Table 8. Correlation coefficient data for the third verification experiment in Example 2.

[0177] VARIABLE X TM2120-FeCO Sampling size 31 Correlation coefficient r 0.9501 Significance level P<0.0001 95% confidence interval (r) 0.8982-0.9759

[0178] The exhaled nitric oxide measuring device described in the above embodiment consists of an exhalation channel, a flow sensor, an empty valve, a three-way valve, a pump, a gas analyzer, and a control unit. The flow sensor monitors the exhaled air flow. The empty valve and three-way valve are connected to the exhalation channel via bypass and are connected in series with the pump and gas analyzer. A regression equation is established using physiological dead space determined by NO and parameters such as height, age, and weight to intelligently set the emptying and sampling times. Environmental NO detection is added to the correlation equation to avoid the influence of environmental NO on the test. Intelligent control of the sampling time is achieved, allowing for different exhaled sampling times for different populations, thus achieving precise sampling. The integrated analysis device reduces the internal volume of the instrument; high integration reduces the cost of the instrument.

[0179] To achieve the device corresponding to Embodiment 1 above and obtain the corresponding functions and technical effects, a method for measuring exhaled nitric oxide is provided below. This measurement method is used in the exhaled nitric oxide measuring device of the above embodiments.

[0180] The method includes: a zero-point testing process and a sample gas testing process.

[0181] The zero-point testing process includes:

[0182] Open the three-way valve to draw air into the gas analyzer, which then analyzes the gas concentration in the air to achieve zero-point testing.

[0183] After the zero-point test, the sample gas testing process begins.

[0184] The sample gas testing process includes:

[0185] Sample gas is introduced through an exhalation channel device; the sample gas is the test gas exhaled by the subject.

[0186] After sample gas is introduced into the exhalation channel device, the control unit closes the three-way valve and opens the vent valve, causing the vent valve to begin venting the introduced sample gas until the venting time is reached. Then, the vent valve closes and the three-way valve opens, allowing the sample gas vented from the vent valve to be introduced into the gas analysis device.

[0187] The emptying time is the time it takes for all the gas in the subject's physiological dead space to be expelled. The emptying time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject.

[0188] The gas analysis device performs gas concentration analysis on the introduced sample gas to obtain the sample analysis results.

[0189] The control unit determines the concentration of nitric oxide in the sample gas based on the results of the zero-point test and the sample analysis results.

[0190] The formula for calculating the evacuation time is as follows:

[0191]

[0192] Where T0 represents the drainage time; V D Q represents the volume of the physiological dead space; Q represents the flow rate of the test gas exhaled by the subject.

[0193] If the subject is male, the formula for calculating the volume of the physiological dead space is:

[0194]

[0195] Among them, V I This indicates the volume of test gas inhaled by the subject; FA NO (t1) represents the concentration of nitric oxide in the test gas inhaled by the subject; FA NO (t2) represents the concentration of nitric oxide in the test gas exhaled by the subject; Age represents the subject's age; Height represents the subject's weight; t1 represents the time when the subject inhaled the test gas; t2 represents the time when the subject exhaled the test gas; t2-t1 represents the exhalation measurement time period.

[0196] If the subject is female, the formula for calculating the volume of the physiological dead space is:

[0197]

[0198] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. Regarding the methods disclosed in the embodiments, since they correspond to the apparatus disclosed in the embodiments, the descriptions are relatively simple; relevant parts can be referred to the apparatus description.

[0199] This document uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of the above embodiments are only for the purpose of helping to understand the method and core ideas of the present invention. Furthermore, those skilled in the art will recognize that, based on the ideas of the present invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A breath nitric oxide measuring device, characterized in that, include: Exhalation channel device, three-way valve, emptying valve, gas analysis device and control unit; The output end of the exhalation channel device is connected to the first end of the exhaust valve and the three-way valve, respectively; the second end of the three-way valve is connected to the gas analysis device; the gas analysis device is connected to the control unit. The three-way valve is used to draw air from the gas analysis device; The gas analysis device is used to analyze the gas concentration in the air to achieve zero-point testing; The exhalation channel device is used to introduce sample gas after the zero-point test; the sample gas is the test gas exhaled by the subject. The control unit is also used to control the three-way valve to close and the venting valve to open after sample gas is introduced into the exhalation channel device, so that the venting valve starts to discharge the introduced sample gas until the venting time is reached, and then controls the venting valve to close and the three-way valve to open. The emptying time is the time it takes for all the gas in the subject's physiological dead space to be expelled; the emptying time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject. The three-way valve is also used to introduce the sample gas discharged from the vent valve into the gas analysis device. The gas analysis device is also used to analyze the gas concentration of the introduced sample gas to obtain the sample analysis results; The control unit is also used to determine the concentration of nitric oxide in the sample gas based on the results of the zero-point test and the sample analysis results; The formula for calculating the evacuation time is: ； in, T 0 indicates the draining time; V D Indicates the volume of physiological dead space; Indicates the flow rate of the test gas exhaled by the subject; If the subject is male, the formula for calculating the volume of the physiological dead space is: ； in, V I This indicates the volume of test gas inhaled by the subject; This indicates the concentration of nitric oxide in the test gas inhaled by the subject; This indicates the concentration of nitric oxide in the test gas exhaled by the subject; Indicates the age of the subject; Indicates the subject's weight; Indicates the time when the subject inhaled the test gas; Indicates the moment when the subject exhales the test gas; Indicates the time period for expiratory breath measurement; If the subject is female, the formula for calculating the volume of the physiological dead space is: 。 2. The exhaled nitric oxide measuring device according to claim 1, characterized in that, Also includes: Flow divider valve; The diversion valve is connected to the exhalation channel device; the control unit is also used to control the diversion valve to open when the flow rate of the sample gas is greater than the set flow rate value, and the diversion valve and the venting valve work together to vent the incoming sample gas until the venting time is reached.

3. The exhaled nitric oxide measuring device according to claim 1, characterized in that, The gas analysis device is at least one; different gas analysis devices analyze the concentration of different gas components in the sample gas; at least one gas analysis device analyzes the concentration of nitric oxide in the sample gas.

4. The exhaled nitric oxide measuring device according to claim 1, characterized in that, Also includes: Filter; The third end of the three-way valve is connected to the filter; The filter is used to introduce filtered air into the gas analysis device through the three-way valve.

5. The exhaled nitric oxide measuring device according to claim 1, characterized in that, Also includes: Pump; the second end of the three-way valve is connected to the gas analysis device via the pump.

6. The exhaled nitric oxide measuring device according to claim 1, characterized in that, Also includes: A flow sensor; the flow sensor is connected to the exhalation channel device; the flow sensor is used to measure the flow rate of the test gas exhaled by the subject.

7. A method for measuring exhaled nitric oxide, characterized in that, The measurement method is used in the exhaled nitric oxide measuring device according to any one of claims 1-6; The method includes: a zero-point testing process and a sample gas testing process; The zero-point testing process includes: Open the three-way valve to draw air into the gas analyzer, and the gas analyzer will analyze the gas concentration of the air to achieve zero-point testing. After the zero-point test, the sample gas testing process begins; The sample gas testing process includes: Sample gas is introduced through an exhalation channel device; the sample gas is the test gas exhaled by the subject. After sample gas is introduced into the exhalation channel device, the control unit closes the three-way valve and opens the vent valve, causing the vent valve to begin venting the introduced sample gas until the venting time is reached. Then, the vent valve closes and the three-way valve opens, and the three-way valve introduces the sample gas vented from the vent valve into the gas analysis device. The emptying time is the time it takes for all the gas in the subject's physiological dead space to be expelled; the emptying time is determined based on the subject's gender, age, weight, the volume of test gas inhaled by the subject, the concentration of nitric oxide in the test gas inhaled by the subject, the concentration of nitric oxide in the test gas exhaled by the subject, and the flow rate of the test gas exhaled by the subject. The gas analysis device analyzes the gas concentration of the introduced sample gas to obtain the sample analysis results; The control unit determines the concentration of nitric oxide in the sample gas based on the results of the zero-point test and the sample analysis results; The formula for calculating the evacuation time is: ； in, T 0 indicates the draining time; V D Indicates the volume of physiological dead space; Indicates the flow rate of the test gas exhaled by the subject; If the subject is male, the formula for calculating the volume of the physiological dead space is: ； in, V I This indicates the volume of test gas inhaled by the subject; This indicates the concentration of nitric oxide in the test gas inhaled by the subject; This indicates the concentration of nitric oxide in the test gas exhaled by the subject; Indicates the age of the subject; Indicates the subject's weight; Indicates the time when the subject inhaled the test gas; Indicates the moment when the subject exhales the test gas; Indicates the time period for expiratory breath measurement; If the subject is female, the formula for calculating the volume of the physiological dead space is: 。

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