Patent Application
20200000372
The present invention relates to a sulfide gas measuring device and sulfide gas measuring method, more particularly, to a sulfide gas measuring device and sulfide gas measuring method suitable for measuring the concentration of sulfide gas contained in exhaled breath.
In recent years, the concentration of sulfide gas (e.g., hydrogen sulfide) contained in exhaled breath has been being proved to be useful information for diagnosis of lung disease such as asthma and chronic obstructive pulmonary disease (COPD). For example, J. Zhang et al. “Correlation between levels of exhaled hydrogen sulfide and airway inflammatory phenotype in patients with chronic persistent asthma”, Respirology. 28 Aug. 2014; 19: 1165-1169 discusses correlation between airway chronic inflammation and hydrogen sulfide in exhaled breath of patients with chronic persistent asthma. J. Zhang et al. “Exhaled Hydrogen Sulfide Predicts Airway Inflammation Phenotype in COPD”, Respiratory Care. 29 Jan. 2015; 60(2): 251-258 discusses a role of hydrogen sulfide in exhaled breath as a marker of airway inflammation and correlation with COPD severity. Furthermore, S. Yun et al. “Exhaled hydrogen sulfide in patients with chronic obstructive pulmonary disease and its correlation with exhaled nitric oxide”, Chinese Medical Journal 2013; 126 (17): 3240-3244 discusses correlation between hydrogen sulfide in exhaled breath and COPD.
Under this background, there have been requirements for technologies for accurately measuring the concentration of sulfide gas contained in exhaled breath. According to an inventors' study, consideration should be given to the following issues in concentration measurement of sulfide gas contained in exhaled breath.
First, it is desired to suppress mixing of sulfide gas generated in tissues other than the lungs into exhaled breath in the concentration measurement of the sulfide gas contained in the exhaled breath. For appropriate diagnosis of lung disease, it is important to obtain information concerning generation of sulfide gas in the lungs. Meanwhile, according to an inventors' knowledge, sulfide gas may be generated in organs other than the lungs, such as the nasal cavities and the stomach. Accordingly, it is useful for lung disease diagnosis to suppress mixing of sulfide gas generated in tissues other than the lungs into exhaled breath.
It is also desired to measure the concentration of the sulfide gas contained in the exhaled breath while variations in the sulfide gas concentration resulting from causes other than the pathology of lung disease are suppressed. According to an inventors' knowledge, the concentration of sulfide gas contained in exhaled breath depends on the flow rate of the exhaled breath as well as the pathology of the lung disease. Accordingly, it is desired to measure the concentration of the sulfide gas contained in the exhaled breath while variations in the flow rate of the exhaled breath of the subject are suppressed.
It is further desired to suppress loss of the sulfide gas contained in the collected exhaled breath in the concentration measurement of the sulfide gas. The concentration of sulfide gas contained in exhaled breath is not so high, whereas the concentration of the sulfide gas contained in the exhaled breath decreases over time due to absorption and decomposition. This means information useful for lung disease diagnosis vanishes.
It is desired to satisfy at least one of these three needs in concentration measurement of sulfide gas in exhaled breath.
It should be noted that devices for concentration detection of hydrogen sulfide in exhaled breath are disclosed in JP 2014-522973 A, JP 2015-526732 A, and JP 2015-526733 A.
Accordingly, an objective of the present invention is to achieve, in concentration measurement of sulfide gas in exhaled breath, at least one of: suppression of mixing of sulfide gas generated in tissues other than the lungs into exhaled breath; suppression of variations in the concentration of sulfide gas resulting from causes other than the pathology of lung disease; and suppression of loss of sulfide gas from collected exhaled breath. Other objectives and new features of the present invention would be understood by a skilled person from the following disclosure.
In one embodiment, a sulfide gas concentration measuring device comprises: an exhaled breath collection tool to be put to a subject to introduce exhaled breath of the subject thereinto; a pressure regulator comprising an inlet port connected to the exhaled breath collection tool; a sulfide gas sensor connected to an outlet port of the pressure regulator to measure a concentration of sulfide gas in the exhaled breath discharged from the outlet port; and a pressure measuring device configured to measure a pressure in the inlet port of the pressure regulator to make the subject aware of the measured pressure.
In another embodiment, a sulfide gas concentration measuring method comprises: putting an exhaled breath collection tool to a subject, the exhaled breath collection tool being connected to an inlet port of a pressure regulator; introducing exhaled breath of the subject into the inlet port of the pressure regulator via the exhaled breath collection tool while a pressure in the inlet port of the pressure regulator is measured to make the subject aware of the measured pressure; introducing the exhaled breath discharged from an outlet port of the pressure regulator into a sulfide gas sensor; and measuring the concentration of sulfide gas contained in the exhaled breath of the subject by the sulfide gas sensor.
The present invention effectively achieves, in concentration measurement of sulfide gas in exhaled breath, at least one of: suppression of mixing of sulfide gas generated in tissues other than the lungs into exhaled breath; suppression of mixing of sulfide gas generated in tissues other than the lungs into exhaled breath; and suppression of loss of sulfide gas from collected exhaled breath.
and
In the following, a description is given of embodiments of a sulfide gas concentration measuring device and a sulfide gas concentration measuring method according to the present invention, with reference to the attached drawings.
The main unit 1 comprises a housing 1a which accommodates a pressure regulator 4, a sulfide gas sensor 5, a three-way valve 6, and a pump 7.
The pressure regulator 4 comprises an inlet port 4a and an outlet port 4b. The inlet port 4a is connected to the mouth piece 2 via an exhaled breath line 2a. The subject's exhaled breath introduced into the mouth piece 2 is supplied to the inlet port 4a of the pressure regulator 4. The pressure regulator 4 is configured to discharge the subject's exhaled breath received by the inlet port 4a from the outlet port 4b with a predetermined set pressure. The pressure regulator 4 is configured to adjust the pressure in the outlet port 4b (the secondary pressure) to the set pressure, when the pressure in the inlet port 4a (the primary pressure) is sufficiently high. It should be noted that such operation is common as the operation of a pressure regulator. The outlet port 4b of the pressure regulator 4 is connected to the sulfide gas sensor 5.
In this embodiment, the pressure regulator 4 further comprises a pressure measurement port 4c. The pressure measurement port 4c is communicated with the inlet port 4a, and accordingly the pressure in the pressure measurement port 4c is equal to that in the inlet port 4a. In this embodiment, the pressure measurement port 4c is connected to the pressure gauge 3 via a pressure measurement line 3a. In this embodiment, the pressure gauge 3, which is connected to the pressure measurement port 4c, is used as a pressure measuring device which measures the pressure in the inlet port 4a of the pressure regulator 4.
The sulfide gas sensor 5 receives the exhaled breath of the subject from the outlet port 4b of the pressure regulator 4 and measures the concentration of sulfide gas contained in the exhaled breath of the subject. In one embodiment, a controlled potential electrolysis sensor may be used as the sulfide gas sensor 5. In an alternative embodiment, to make it possible to determine the type of sulfide gas (for example, to distinguish hydrogen sulfide from other sulfide gas such as sulfur dioxide), an optical gas sensor configured to perform gas detection based on optical absorption may be used.
The three-way valve 6 is configured as a switch valve comprising one inlet port and two outlet ports. The inlet port of the three-way valve 6 is connected to the outlet port of the sulfide gas sensor 5. One of the outlet ports of the three-way valve 6 is connected to an external outlet port 11, and the other outlet port is connected to the pump 7. The external outlet port 11 is open to the atmosphere. The three-way valve 6 connects the outlet port of the sulfide gas sensor 5 to the pump 7 or the external outlet port 11 depending on the manipulation.
The pump 7 comprises an inlet port connected to the outlet port of the three-way valve 6 and an outlet port connected to an external outlet port 12. The external outlet port 12 is open to the atmosphere. As described later, the pump 7 is used for calibration of the sulfide gas sensor 5.
The connection between the pressure gauge 3 and the inlet port 4a may be variously modified, although the pressure gauge 3 is connected to the pressure measurement port 4c, which is communicated with the inlet port 4a, and the pressure in the inlet port 4a of the pressure regulator 4 is measured by the pressure gauge 3 in this embodiment. For example, the pressure gauge 3 may be connected to the exhaled breath line 2a.
A description is then given of the operation of the sulfide gas concentration measuring device 10, according to this embodiment.
The sulfide gas concentration measuring device 10 in this embodiment is used to measure the concentration of sulfide gas (for example, hydrogen sulfide) contained in exhaled breath. As described above, the concentration of sulfide gas contained in the exhaled breath is useful information for diagnosis of lung disease such as asthma and chronic obstructive pulmonary disease (COPD). The sulfide gas concentration measuring device 10 in this embodiment measures the concentration of the sulfide gas contained in the exhaled breath of the subject through a method suitable for lung disease diagnosis, as described in the following.
As shown in
While the subject 20 blows the exhaled breath into the mouth piece 2, the subject 20 is made aware of the pressure measured by the pressure gauge 3 and asked to blow the exhaled breath so that the pressure indicated by the pressure gauge 3 is adjusted to a specific target pressure (for example, 1.5 kPa) or to a specific target pressure range (for example, a specific pressure range with a center value of 1.5 kPa.) For example, the display unit 3b of the pressure gauge 3 may be shown to the subject 20 and the subject 20 may be asked to blow the exhaled breath into the mouth piece 2 so that the pressure indicated by the pressure gauge 3 is adjusted to the target pressure or the target pressure range. Since the pressure gauge 3 measures the pressure in the inlet port 4a of the pressure regulator 4, this operation resultingly adjusts the pressure in the inlet port 4a to at least the vicinity of the target pressure or the target pressure range. The target pressure or the target pressure range is determined as being sufficient for the pressure regulator 4 to adjust the pressure in the outlet port 4b to a predetermined set pressure.
The subject's exhaled breath blown into the mouth piece 2 is introduced into the inlet port 4a of the pressure regulator 4, discharged from the outlet port 4b with its pressure reduced to the set pressure, and introduced to the inlet port of the sulfide gas sensor 5 from the outlet port 4b of the pressure regulator 4 with the set pressure set to the pressure regulator 4. When the pressure in the inlet port 4a is sufficiently high, this allows the pressure regulator 4 to keep the pressure in the outlet port 4b at the predetermined set pressure. The sulfide gas sensor 5 receives the exhaled breath of the subject 20 from the outlet port 4b of the pressure regulator 4 and measures the concentration of the sulfide gas contained in the exhaled breath. The exhaled breath which has been subjected to the concentration measurement of sulfide gas is discharged from the outlet port of the sulfide gas sensor 5 and then discharged to the external atmosphere via the three-way valve 6 and the external outlet port 11.
The operation which involves asking the subject 20 to blow the exhaled breath into the mouth piece 2 while the subject 20 is made aware of the pressure measured by the pressure gauge 3 is effective for suppressing mixing of sulfide gas generated in tissues other than the lungs into the exhaled breath. The route between the lung airways and the mouth is open to the nasal cavities and the stomach in a usual state. In this state, sulfide gas generated in the nasal cavities and the stomach may be mixed into the exhaled breath; however, by asking the subject 20 to keep the pressure measured by the pressure gauge 3 at the target pressure or in the target pressure range, it is possible to introduce the exhaled breath into the mouth piece 2 while the openings to the nasal cavities and the stomach are closed. To keep the pressure measured by the pressure gauge 3 at a certain high pressure, the subject 20 is necessary to exert a force of a certain magnitude to exhale the breath. When the subject 20 exerts a force of a certain magnitude to exhale the breath, the openings to the nasal cavities and the stomach existing along the route between the lung airways and the mouth are closed in the body of the subject 20. This makes it possible to suppress mixing of sulfide gas generated in tissues other than the lungs into the exhaled breath. The configuration of the sulfide gas concentration measuring device 10 according to this embodiment, in which the pressure of the inlet port 4a of the pressure regulator 4 is measured by the pressure gauge 3, preferably suppresses mixing of sulfide gas generated in tissues other than the lungs into the exhaled breath through the above-described operation.
The operation which involves asking the subject 20 to blow the exhaled breath into the mouth piece 2 while the subject 20 is made aware of the pressure measured by the pressure gauge 3 is also effective for suppressing variations in the flow rate of the exhaled breath of the subject 20 and obtaining information useful for lung disease diagnosis. As described above, the concentration of the sulfide gas contained in the exhaled breath depends on the flow rate of the exhaled breath from the subject 20. It is possible to suppress an influence of variations in the flow rate of the exhaled breath by measuring the concentration of the sulfide gas while asking subject 20 to exhale the breath so that the pressure indicated by the pressure gauge 3 is adjusted to the specific pressure. The configuration of the sulfide gas concentration measuring device 10 according to this embodiment, in which the pressure of the inlet port 4a of the pressure regulator 4 is measured by the pressure gauge 3, is suitable for suppressing an influence of variations in the flow rate of the exhaled breath.
Furthermore, the sulfide gas concentration measuring device 10 according to this embodiment achieves in-situ measurement of the concentration of the sulfide gas contained in the exhaled breath of the subject 20 with accuracy sufficient for lung disease diagnosis. To improve the accuracy of the sulfide gas concentration detection with the sulfide gas sensor 5, it is desired that the gas to be subjected to the detection flows into the sulfide gas sensor 5 at a constant flow rate. In this embodiment, the pressure in the outlet port 4b, that is, the pressure in the inlet port of the sulfide gas sensor 5 is kept substantially constant by the operation of the pressure regulator 4, and accordingly the exhaled breath of the subject flows into the sulfide gas sensor 5 at a substantially constant flow rate. This allows the configuration according to this embodiment to achieve in-situ measurement of the sulfide gas contained in the exhaled breath of the subject 20 with accuracy sufficient for lung disease diagnosis.
The in-situ measurement ability of the concentration of the sulfide gas contained in the exhaled breath of the subject 20 is effective for suppressing loss of the sulfide gas from the collected exhaled breath. As described above, the concentration of sulfide gas in exhaled breath decreases over time due to absorption and decomposition. For example, a system configured to blow exhaled breath into a bag and measure the concentration of sulfide gas contained in the exhaled breath accumulated in the bag experiences a decrease in the concentration of the sulfide gas due to absorption of the sulfide gas into the bag. This undesirably implies that information used for lung disease diagnosis is lost. The sulfide gas concentration measuring device 10 according to this embodiment achieves in-situ measurement of the sulfide gas concentration, suppressing loss of the sulfide gas from the collected exhaled breath.
Various methods may be used to make the subject 20 aware of the pressure measured by the pressure gauge 3. The subject 20 may be made visually aware of the pressure measured by the pressure gauge 3. The subject 20 may be made aurally aware of the pressure (for example, by generating sound corresponding to the pressure). In one embodiment, the display unit 3b of the pressure gauge 3 may be shown to the subject 20. In this case, the display unit 3b may comprise a display element 3c (e.g., an indicator) visually indicating the measured pressure, a marking 3d indicating the target pressure and/or a marking 3e indicating the target pressure range, where the display element 3c and the markings 3d and 3e are all configured to be visually perceivable. In this case, the subject 20 may be asked to blow the exhaled breath into the mouth piece 2 so that the position of the display element 3c is adjusted to match the position of the marking 3d indicating the target pressure or the marking 3e indicating the target pressure range.
The pump 7 is used for calibration and cleaning of the sulfide gas sensor 5.
In the calibration, the pump 7 is operated to suck gas therein at a constant flow rate and calibration gas containing sulfide gas with a known concentration is introduced into the inlet port of the sulfide gas sensor 5. Since the pump 7 connected to the outlet port of the sulfide gas sensor 5 is operated to suck gas therein at the constant flow rate, the sulfide gas is resultingly introduced into the sulfide gas sensor 5 at a constant flow rate. The sulfide gas sensor 5 measures the concentration of the sulfide gas contained in the calibration gas in this state. The sulfide gas sensor 5 is calibrated by using the measured sulfide gas concentration of the calibration gas.
In the cleaning, cleaning gas is introduced into the mouth piece 2 in a state in which the pump 7 is operated. This achieves introducing the cleaning gas into the inlet port of the sulfide gas sensor 5 via the exhaled breath line 2a and the pressure regulator 4. Since the pump 7 is operated, the cleaning gas which has cleaned the internal of the sulfide gas sensor 5 is sucked by the pump 7 from the outlet port of the sulfide gas sensor 5 and discharged from the external outlet port 12. This operation achieves cleaning of the route from the mouth piece 2 to the inlet port of the sulfide gas sensor 5 and the internal of the sulfide gas sensor 5.
The sulfide gas concentration measuring device 10 may be configured to automatically perform cleaning of the sulfide gas sensor 5 after the sulfide gas concentration measurement of the exhaled breath.
The pressure regulator 14 comprises a gas introduction port 4d in addition to an inlet port 4a, an outlet port 4b, and a pressure measurement port 4c. The gas introduction port 4d is connected to the external connection port 13. The external connection port 13 is connected to a cleaning gas source (not shown) which supplies cleaning gas.
The sulfide gas concentration measuring device 10 configured as shown in
When completing the concentration measurement of the sulfide gas contained in the exhaled breath, the sequencer 15 operates to clean the sulfide gas sensor 5. The sequencer 15 sets the pressure regulator 14 so that the gas introduction port 4d communicates with the outlet port 4b. This achieves communicating the external connection port 13, which is connected to the cleaning gas source, with the inlet port of the sulfide gas sensor 5. Furthermore, the sequencer 15 sets the three-way valve 6 to connect the outlet port of the sulfide gas sensor 5 to the pump 7 and operates the pump 7. This allows the cleaning gas to be introduced into the sulfide gas sensor 5 from the external connection port 13 via the pressure regulator 14. This achieves cleaning of the internal of the sulfide gas sensor 5 and the line connected to the inlet port of the sulfide gas sensor 5.
A three-way valve (switch valve) controlled by the sequencer 15 may be disposed on the line connecting the pressure regulator 14 to the sulfide gas sensor 5, in place of providing the gas introduction port 4d for the pressure regulator 14. In this case, the three-way valve connects the inlet port of the sulfide gas sensor 5 to one of the outlet port 4b of the pressure regulator 14 and the external connection port 13 under the control of the sequencer 15. When the sulfide gas concentration of the exhaled breath is measured, this three-way connects the inlet port of the sulfide gas sensor 5 to the outlet port 4b of the pressure regulator 14. When the sulfide gas sensor 5 is cleaned, the three-way connects the inlet port of the sulfide gas sensor 5 to the external connection port 13, which is connected to the cleaning gas source.
Although embodiments of the sulfide gas concentration measuring device according to the present invention have been specifically disclosed, the present invention must not be construed as being limited to the above-described embodiments. It would be apparent to a skilled person that the present invention can be implemented with various modifications.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2017/013137 | 3/30/2017 | WO | 00 |
