CN104407026A - Multi-parameter one-breath exhaled nitric oxide measurement method and device - Google Patents
Multi-parameter one-breath exhaled nitric oxide measurement method and device Download PDFInfo
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- CN104407026A CN104407026A CN201410704361.4A CN201410704361A CN104407026A CN 104407026 A CN104407026 A CN 104407026A CN 201410704361 A CN201410704361 A CN 201410704361A CN 104407026 A CN104407026 A CN 104407026A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/22—Devices for withdrawing samples in the gaseous state
Abstract
The invention discloses a multi-parameter one-breath exhaled NO (Nitric Oxide) measurement method and a multi-parameter one-breath exhaled NO measurement device. According to the device, a slender tube (the flow of gas in the slender tube is ensured to be piston flow during exhaling sampling and analysis measurement) is used for synchronously collecting exhaled gas under different exhaling durations (flow velocities) at a higher speed in an exhaling process, and the gas collected in the slender tube is introduced into a sensor at a lower flow velocity for analysis measurement during analysis; an NO concentration curve recorded by the sensor corresponds to an exhaling flow (time) curve by virtue of a gas path design and control over a gas flow proportion during sampling and measurement, so that the measurement of rapidly-changed exhaled NO concentration through a slow-response electrochemical sensor can be realized, and each parameter of exhaled NO can further be calculated according to an exhaled NO two-compartment model.
Description
Technical field
The present invention relates to expiration nitric oxide measuring method and equipment.
Background technology
Expiration nitric oxide is analyzed as the detection that the mark of airway inflammation is used for the respiratory diseases such as asthma and has been obtained medical profession abundant affirmation.Thoracic cavity association of the U.S. and Europe are breathed association and were combined formulation in 2005 and disclose standardized method (" the ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Low Respiratory Nitric Oxide and Nasal Nitric Oxide carrying out this measurement, 2005 "), within 2011, propose its clinical practice guide (An Official ATS Clinical Practice Guideline:Interpretation of exhaled Nitric Oxide Level (FeNO) for Clinical Applications), these standards and guide are used for instructing diagnosis and therapeutic evaluation how to carry out detecting with testing result being used for the respiratory diseases such as asthma.
Because expiration NO concentration is relevant with exhalation flow rate, and be easily subject to the interference of nasal cavity gas, thus the ATS/ERS standardization expiration nitric oxide measuring method of recommending is for measuring the inflammation of lower respiratory tract, requires at least 5cmH
2under the breath pressure of O, single sustained exhalation is carried out 10 seconds (children are 6 seconds) under the fixing exhalation flow rate of 50ml/s, select the expiratory gas flow of 50ml/s main it is considered that under this flow, the contribution main source of expiration NO and air flue, and expiration control is easier to.
But the nitrogen monoxide in exhaling derives from alveolar and air flue, if the NO concentration of zones of different can be distinguished, can evaluate the NO secretion raised or reduce occurs in which pathological regions, there is clinical reference value widely.
About the meaning of steady state alveolar gas concentration at clinicing aspect, Hogman etc. (J. Breath Res. 6 (2012) 047103) comment more than 100 section of document before 2012, brief summary go out it and some diseases relation:
1) asthma degree of depth diagnosis: bronchitis alveolar air nitric oxide concentration Ca
nOconstant and maximum airway flux Jaw raises, bronchiolitis disease Ca
nOraise;
2) treat therapeutic scheme to select: corticosteroids inhaled is invalid and oral hormone should be taked to treat to bronchiolitis disease;
3) lung and smoking patient: chronic obstructive pulmonary disease patient Ca
nOcompared with normal group is high, and smoking is to the Ca of tester
nOindefinite;
4) property chorionitis: obtain interstitial lung disease (ILD) person Ca in systemic scleroderma patient
nOobvious rising (is done point of contact with 10.8ppb, is functionalityly reached 96%, Ca
nOcan be used as the mark of ILD;
5) pulmonary alveolitis: Ca
nOraise and Jaw is constant;
6) pulmonary fibrosis: Ca
nOraise;
7) hepatic and renal function syndrome: Ca
nOraise (8.3ppb vs 4.7ppb).
About the document of expiration nitric oxide detection method aspect is a lot, to existing various measuring method, Hogman(J. Breath Res. 7 (2013) 017104) do and introduced relatively comprehensively and objectively: Ca
nOdirectly can not measure, must be deduced by certain physiological models and calculate, at present about the model of expiration NO mainly contains three, be respectively: two compartment model (
j Appl Physiol91:2173 – 2181,2001.), three compartment model (
j Appl Physiol96:1832 – 1842,2004.) and loudspeaker model (
j Appl Physiol102:417 – 425,2007), three parameter had nothing to do with flow: steady state alveolar concentration Ca can be analyzed
nO, airway walls diffusing capacity (maximum airway flux) Jaw and airway walls concentration C aw
nO, the loudspeaker model wherein with axial diffusion is believed to the NO output relevant to flow in lung provides good description.
Two Room models (2CM) are the simplest Exhaled nitric oxide physiological models, and it thinks expiration nitric oxide concentration (Ce
nO) be made up of two parts, come from alveolar region and air flue district (as shown in Figure 1) respectively, depend on three parameters according to fluctuations in discharge: NO total flow (the maximum airway flux Jaw deriving from airway walls
nO, pl/s), NO is at diffusivity (DawNO, the pl*s of air flue
-1*ppb
-1) the alveolar air concentration (Ca, and under stable state
nO, ppb).Maximum airway walls flux Jaw
nO(pl/s) and exhalation flow rate F be inversely proportional to; Caw
nOrefer to airway walls NO concentration.
The following relational expression of relation is met between each parameter:
(1)
When VE >5*DawNO ml/s or 50 ml/s(Healthy Peoples) time, this equation can be reduced to "
(2)
In general, Ca
nO<2% Caw
nO, and J ' aw
nO=Daw
nO* Caw
nO, above equation can be reduced to
(3)
Thus, by the Ce under different expiratory gas flow (F)
nOthe mensuration of concentration, can in the hope of alveolar air concentration C a
nO, maximum airway walls flux Jaw.
Usually within the scope of 100 ~ 500ml/s expiratory gas flow, adopt formula (3) linear model to analyze, can Ca be calculated
nOand Jaw
nOtwo parameters, and to wider expiratory gas flow, as 10 ~ 500ml/s, adopt formula (1) nonlinear model to analyze, can calculate and obtain Ca
nO, Jaw
nO,caw
nOand Daw
nOfour parameters.
This model can explain the rule that expiration nitric oxide concentration changes with expiratory gas flow, and experimental data is also substantially identical with theoretical value, thus about Jaw
nOwith Ca
nOmeasurement, major part work all launches based on this model, and general method controls different expiratory gas flows repeatedly to exhale, and measure the expiration NO value under different in flow rate, then basis (1) or (3) formula calculates.
Analyze in document about Ca
nO, Jaw
nOand Ce
nOmeasurement result, the Ca that different data processing methods calculates
nO, Jaw
nOthere is not significant difference, various data processing method is equivalence substantially also.It is generally acknowledged adult normal's steady state alveolar gas concentration C a
nOgeneral between 1.0 ~ 5.6ppb, Jaw
nOwithin the scope of 420 ~ 1280pl/s (
j Appl Physiol91:2173 – 2181,2001).
Under the exhalation flow rate of 50ml/s, sustained exhalation 4 ~ 10s easily realizes comparatively speaking, under lower flow velocity (exhalation flow rate as 10ml/s at least needs constant flow rate to exhale 20 seconds) and higher expiration, (lower expiratory resistance is larger) sustained exhalation all can comparatively difficulty, for this reason, calendar year 2001 George team proposes a kind of variable-flow measuring technique without a break, by regulating and controlling expiratory gas flow (from 300ml/s to 50ml/s) continuously, measure and the expiration NO concentration change relation recording expiratory gas flow and follow in time, calculate Jaw according to two Room models
nOand Ca
nO.But until the consistance of Bruno ability first time contrived experiments in 2006 to many implications variable-flow and one breath variable-flow method has carried out evaluating (Respiratory Physiology & Neurobiology 153 (2006) 148 – 156), by carrying out Bland-Altman statistical study to experimental data, think that two kinds of methods are to Jaw
nOand Ca
nOmeasurement result be consistent, think that without a break variable-flow method is more simple and convenient simultaneously.
But may due to following reason, this technology does not obtain the business application of business:
1) this technology is to sensor response time requirement higher (<200ms), only have Chemiluminescence Apparatus to meet this time-resolved requirement at present, but NO value of exhaling under very fast flow velocity is lower, close to Chemiluminescence Apparatus Monitoring lower-cut, the quality of data can not be guaranteed, and measuring error is larger;
2) numerical analysis algorithm must be adopted to carry out analyzing and processing to data, algorithm is comparatively complicated, and reliability reduces;
3) computation process uses airway dead space gas volume Vaw parameter, but article does not provide the method measuring this parameter, just estimates its data and calculates.
Summary of the invention
The present invention, on the basis of expiration nitric oxide two compartment model, method and device is innovated, and overcomes the defect of preceding method.Specific as follows: in the process of one breath sustained exhalation, by accurately controlling expiratory gas flow (as linear change), reduced data Processing Algorithm, reduces flow sensor, NO sensor measurement errors to the impact of last result of calculation, improves the reliability of measurement result.
Measuring directly estimation Vaw(prior art by expiration NO is by dissecting and exhale CO
2analytical estimating Vaw), provide the new method that is measured Vaw.
Designed by gas circuit structure and the design of sampling analysis method, use the slower electrochemical sensor of reaction velocity to achieve measurement to quick exhalation process NO concentration change, this reduces cost on the one hand, also can improve measurement data on the other hand and analyze quality.
Below the introduction to the inventive method and device:
1. Ca
nOand the measuring method of Jaw:
First carry out theoretical analysis according to expiration NO two compartment model, see under the condition to expiratory gas flow linear change, whether can build simple mathematical processing methods, directly measure each expiration NO parameter.
As previously mentioned, measuring alveolar air NO concentration generally needs many implications to exhale under different flow sampling, if regulate expiratory resistance size in exhalation process, control the linear change of expiratory gas flow, obtain flow curve and last result curve as shown in Figure 2 (under normal circumstances along with the reduction of expiratory gas flow F, expiration NO concentration C e rises gradually).
Make brief analysis with regard to this condition below, first define following parameter: expiratory gas flow change slope a: the slope that flow F (t) linearly declines; Air flue residence time τ (F): the time of gas required for alveolar is in air flue exhalation body, relevant to expiratory gas flow and expiration dead volume; Air flue dead volume Vaw: air flue volume.
One breath various flow exhale in, expiration dead volume Vaw be the time from t-τ to t i.e. residence time τ, when flow F (t-τ) changes to F (t), the integration of flow versus time in whole interval:
(4)
By Fig. 2 (expiratory gas flow linear change), the integration carried out formula 4 launches and abbreviation obtains:
(5)
Solution formula 5, about the quadratic equation with one unknown of τ (F), obtains:
(6)
When upon exhalation, t is greater than τ (F), concentration of exhaled NO Ce, for the NO concentration C b sum that alveolar air NO concentration C a and air flue produce, wherein Cb be τ (F) in the time airway walls be diffused into NO cumulative volume in air flue divided by air flue volume, that is:
， (7)
So:
(8)
Formula 5 is substituted into formula 8:
(9)
Order
:
(10)
Wherein:
(11)
Parameter Vaw in formula (11) is relevant with individual difference, and the Vaw of health adult is between 120 ~ 150ml.
Therefore, expiratory gas flow F (t) is controlled from the linear transformation that diminishes greatly in exhaling without a break, measure the expiration NO concentration C e value under different flow, if know air flue dead volume Vaw, correction can be carried out according to formula 11 pairs of flows to obtain revising rear flow F ' (t), then to Ce-1/F ' (t) mapping, the slope obtained is Jaw, and intercept is Ca.And NO concentration of exhaling under 50ml/s flow can calculate according to (3) formula.
Above-mentioned derivation formula hypothesis expiratory gas flow linear change, the benefit that control expiratory gas flow linear change is brought can make whole data processing greatly simplify, the introducing of desirable computing formula and can reduce the requirement to flow and NO sensor accuracy class to the bulk treatment of expiratory gas flow, sensor measurement data, improves data analysis quality.
2. the measuring method of Vaw
Said method needs to know experimenter's air flue dead volume Vaw when measuring Jaw, Ca, there is certain individual difference (Vaw of health adult is at 120 ~ 150ml) in this, the method of current acquisition Vaw value has two, one is directly calculate (Journal of Applied Physiology May 1 by itself and height, body weight or the relation at age, 1963 vol. 18 no. 3 519-522:
), two is by expiration CO
2test obtains (Anesthesiology 2006; 104:696 – 700).
In fact the Vaw on Anatomical significance, CO is passed through
2certain difference may be there is in the exhale Vaw of two Room models definition of the Vaw that disperse is measured and expiration NO, if directly can measure Vaw for the change of expiration NO concentration, except can be applicable to above-mentioned calculating, perhaps be also significant clinically, can be used for the differentiation etc. of airway obstruction degree.
From expiration NO two compartment model, when variable-flow expiratory measurements, expiration NO value is expiratory gas flow (F), alveolar air concentration (Ca
nO), maximum airway walls flux (Jaw
nO) and the function of air flue dead volume Vaw, known air flue dead volume, changes expiratory gas flow and can calculate alveolar air concentration (Ca
nO), maximum airway walls flux (Jaw
nO).
By (8) formula
(12)
Under alveolar concentration and the certain condition of maximum airway walls flux, the size of expiration NO concentration is directly proportional to the residence time τ of gas in air flue, and the residence time is the function of Vaw and expiratory gas flow, same experimenter, Vaw is certain, as long as thus residence time τ is consistent, the concentration of expiration NO is also consistent.In other words, because variable-flow measurement result is relevant with Vaw, independently measure as long as thus carry out at least twice measurement, wherein at least one times for variable-flow is measured, just can set up simultaneous equations and calculate Vaw.
We can draw the method for following survey Vaw thus:
1. constant expired flow combines with change expiratory gas flow
First expiration expiration NO concentration is measured for 2 times in constant expired flow rate F, the relation of expiration NO concentration and flow meets (3) formula under this condition, then carry out variable-flow measurement, record expiration NO concentration with expiratory gas flow change curve, in variable-flow test condition expiration NO concentration and constant expired flow rate F
2when lower measurement exhalation concentrations is equal, the residence time corresponding to the two is consistent, and the expiratory gas flow as now corresponding is F
1, have:
(13)
When expiratory gas flow linear change, by formula (6) and (13), can obtain:
(14)
Realize above-mentioned measurement and can have multiple method, the mode the most easily expected is realized by constant flow and variable-flow twice expiratory measurements, a kind of implementation measured without a break is: control described exhalation flow rate and open that after exhalation dead space gas, begin to maintain expiratory gas flow constant, keep after 1 to 2 seconds, change in a predetermined manner, in 6 ~ 10 seconds, expiratory gas flow drops to 20ml/s from 300ml/s again.
The another kind of mode realizing above-mentioned measurement is: first control described exhalation flow rate and change in a predetermined manner, expiratory gas flow, for drop to 20ml/s from 300ml/s in 6 seconds, to control within the scope of 50ml/s ~ 100ml/s and to maintain 2 ~ 4 seconds by fluctuations in discharge scope subsequently.
2. twice variable-flow is measured but expiratory gas flow Changing Pattern is different
As previously mentioned, residence time of exhaling expiration NO concentration is determined to same experimenter, and the residence time is determined by the size of air flue dead volume, expiratory gas flow variation pattern and expiratory gas flow, thus change expiratory gas flow variation pattern in theory, just solve air flue dead volume by simultaneous equations by the measurement of expiratory gas flow and expiration NO concentration.
A kind of method realizing above-mentioned measurement is that twice variable-flow is measured, as controlled twice expiratory measurements flow linear change but change slope difference, but they all meet formula (11), set up simultaneous equations can solve Vaw by choosing the identical point of twice measurement expiration NO concentration.
The another kind of mode realizing foregoing invention method is: control described expiratory gas flow and change in a predetermined manner, fluctuations in discharge scope for linearly to drop to 20ml/s from 300ml/s in 6 seconds, to exhale to set fluctuations in discharge subsequently, linear change is changed to 200ml/s by 20ml/s, continue 4 seconds, the slope of these two stage expiratory gas flow changes is different.Set up simultaneous equations can solve Vaw by choosing the identical point of twice measurement expiration NO concentration.
Realize foregoing invention method another kind of mode also have: within the scope of certain hour (as 4 ~ 6 seconds) control as described in expiratory gas flow from big to small (as from 300ml/s to 20ml/s) change, controlling subsequently exhales arrives change (4 ~ 6 seconds) from small to large, expiratory gas flow change curve when relatively expiration NO concentration is equal, carries out numerical integration process and also can try to achieve Vaw.
3. utilize electrochemical gas sensor to realize variable-flow to measure
Will realize above-mentioned measuring method at present requires higher to the response speed of sensor, only have Chemiluminescence Apparatus can meet this time-resolved requirement, but chemiluminescent analyzer cost is higher, difficult in maintenance, and NO value of exhaling under very fast flow velocity is lower, close to Chemiluminescence Apparatus Monitoring lower-cut, thus the quality of data can not be guaranteed, and measuring error is larger.
Thinking of the present invention be by gas circuit design will sample and measuring process separate, utilize elongated tubular (ensureing that gas flowing is wherein piston flow when exhaling sampling and analysis to measure) with the expiration gas under the different expiratory duration (flow velocity) of fast speed synchronous collection part in exhalation process, when analyzing to be passed through to carry out analysis to measure into sensor by the gas collected in elongated tubular compared with low flow velocity; Designed by gas circuit and make the NO concentration curve of sensor record corresponding with expiratory gas flow (time) curve to the control of gas flow ratio when sampling and measurement, thus realizing utilizing the measurement of the electrochemical sensor of slow-response realization to fast-changing expiration NO concentration.
Realize said method, measurement mechanism design and metering system need to consider and solves several key issue, being specially:
3.1 expiratory gas flows control
How to ensure experimenter's sustained exhalation ensure the rule change that its expiratory gas flow is wished by us within the scope of certain hour?
About this point, solution of the present invention is that flow sensor and flow controller are combined into a flow automatic feedback control system, during experimenter's sustained exhalation, expiratory gas flow measured by flow sensor, and transfer data to flow controller, these data and the target flow preset compare by described flow controller, and latus rectum (is turned down when flow is excessive by the latus rectum of the pipeline of adjustment expiration in time, when flow is too small, latus rectum is tuned up), its feedback regulation speed is less than 100ms, substantially can ensure that expiratory gas flow is by the fluctuations in discharge rule change preset by the Quick Measurement to expiratory gas flow and the timely adjustment to pipeline latus rectum like this, as in 6 ~ 10 seconds, expiratory gas flow linearly drops to 20ml/s from 300ml/s.
Be make its linear attenuation to the control of expiratory gas flow variation pattern, as made it linearly drop to 20ml/s from 300ml/s within 6 ~ 10 second time, the bound of certain expiratory gas flow can adjust according to actual needs.The large advantage controlling expiratory gas flow linear change is that algorithm model is comparatively simple, and aforementioned theoretical formula draws under this condition.
Expiratory gas flow can certainly be controlled change with index or other any mode, different in algorithm process from expiratory gas flow linear change difference, algorithmically can solve by formulism with the flow of the mode rule changes such as linear or index, and when expiratory gas flow change does not have rule, solve comparatively complicated, numerical integration algorithm may be inevitable selection.
3.2 sample mode designs:
Breath is all collected and gets off to carry out analysis to measure, still an only collection analysis part wherein?
In order to reduce sample chamber volume, simplify synchronized algorithm simultaneously, the method that the present invention adopts be with the pump of a high flow capacity while exhaling by a part for expiratory air with in the elongated air chamber of constant flow rate suction.So just can ensure that the distribution of gas in elongated air chamber of different expiratory duration section is uniform.
3.3 sample storage
Atmosphere storage to be analyzed is in air chamber, and the structure of described air chamber is an elongate conduit, and object is to ensure that the flowing of gas in air chamber meets the condition of piston flow in sampling and analytic process.
3.4 Measurement and analysis
By flow rate that pump drives the gas in sample chamber constant during Measurement and analysis, and record the curve of whole measuring process, if known sampling and the ratio of gas flow and time synchronous point when analyzing, just the experiment curv of sensor can be associated with expiratory gas flow experiment curv, make the graph of a relation between sensor response and expiratory gas flow.
Sampling is larger with the throughput ratio of gas when analyzing, and lower to the requirement of sensor response time, the ratio as the two is 10:1, then the available response time is that the sensor measurement of 10 seconds is exhaled the situation of change of NO concentration in 1 second.Sampling and the size of Measurement and analysis gases used flow select to depend on the response time of sensor and the temporal resolution needed for measuring, analyze expiration NO, sample and analysis throughput ratio can be controlled in 5 ~ 20 times.
3.5 synchronous method
Exhale and with high flow velocities, a part for expiratory air is stored in elongate conduit when sampling, and when analyzing, the gas in described pipeline is passed into sensor with comparatively low flow velocity and carry out analysis to measure, in order to these two relatively independent procedure correlations are got up, must have a synchronizing time point, choosing of described synchronous point realizes by gas circuit design.
One chooses synchronous point method for analysis pump is arranged in elongated air chamber leading portion, and first the gas at the end of sampling of exhaling like this be drawn into sensor analysis when Measurement and analysis, and what this start time point was corresponding is exactly the time point of sampling and terminating of exhaling.
The another kind of method choosing synchronous point is design one cycle analysis gas circuit, now analyze pump in the rear end of elongated air chamber, analyzing pump during analysis to measure drives the gas in air chamber to enter after sensor measures, get back in elongated air chamber after removing NO with NO filtrator, flowing due to gas in air chamber is piston flow, when this part gas is when getting back to sensor, because NO gas is fallen by NO metre filter, the response of NO sensor can rapidly drop to zero, and this time point corresponding be exactly exhale sampling at the end of time point.
Solve the problems referred to above, by designing suitable device, just can realize a bite multiparameter NO and measuring, although measurement mechanism analytic process can be different, the common ground of its Measurement and analysis process can be summarized as follows:
1) exhale: control to exhale with the flow program preset change, record expiratory gas flow change curve in time;
2) sample: the gas of breathe out expiration overall process or one portion collection are in an elongated tubular air chamber;
3) measure: the gas in elongated tubular is passed into sensor and carries out analysis to measure by the gas flow rate adapted with the sensor response time, record sensor responds change curve in time;
4) synchronous: synchronous expiration and analytic process, find the data corresponding relation between expiratory gas flow and expiration NO measured value;
5) revise: according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and expiration NO;
6) calculate: calculate Jaw, Ca and FeNO according to corresponding relation between revised expiratory gas flow and expiration NO
50.
4. implement device
Fig. 3 is a kind of device gas circuit structure schematic diagram realizing above-mentioned analytical approach, described device gas circuit is made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, and is connected between flow regulator (201) and solenoid valve (301) by threeway with the air chamber (401) in analysis module; Described analysis module forms circulation gas circuit by air chamber (401), threeway (501), analysis pump (602), gas humidity regulator (701), NO sensor (801), NO filtrator (901) and T-valve (302) successively; Pump (601) is connected with air chamber (401) by threeway (501), a T-valve (303) in parallel between NO filtrator (901) with NO sensor (801).
Fig. 4 is the another kind of device gas circuit structure schematic diagram realizing above-mentioned analytical approach, described device gas circuit is made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, and is connected between flow regulator (201) and solenoid valve (301) by threeway with the solenoid valve (303) in analysis module; Described analysis module forms circulation gas circuit by solenoid valve (303), air chamber (401), threeway (501), analysis pump (602), gas humidity regulator (701), NO sensor (801), T-valve (302) successively; Pump (601) is connected with air chamber (401) by threeway (501), and NO filtrator (901) is by T-valve (303) connect into analysis gas circuit.
Fig. 5 is the another kind of device gas circuit structure schematic diagram realizing above-mentioned analytical approach, described device gas circuit is made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, by the air chamber (401) in threeway connect into analysis module between flow regulator (201) and solenoid valve (301); Described analysis module is according to this by air chamber (401), threeway (501), NO filtrator (901), NO sensor (801), gas humidity regulator (701), analysis pump (602), circulation gas circuit; Pump (601) is connected with air chamber (401) by threeway (501).
Fig. 6 is the another kind of device gas circuit structure schematic diagram realizing above-mentioned analytical approach, described device gas circuit is made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, by the air chamber (401) in threeway connect into analysis module between flow regulator (201) and solenoid valve (301); Described analysis module is according to this by air chamber (401), threeway (501), NO filtrator (901), NO sensor (801), gas humidity regulator (701), analysis pump (602), circulation gas circuit; Pump (601) is connected with air chamber (401) by threeway (501); Between described NO sensor (801) rear end and NO filtrator (901), add a T-valve (302), another outlet of this valve connects the endpiece of NO filtrator (901).
Fig. 7 is the another kind of device gas circuit structure schematic diagram realizing above-mentioned analytical approach, described device gas circuit is made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, by solenoid valve (302) in threeway connect into analysis module between flow regulator (201) and solenoid valve (301); Described analysis module according to this by T-valve (302), air chamber (401), analyze pump (602), gas humidity regulator (701), NO sensor (801) are composed in series, sampling pump (601) to be connected on air chamber (401) rear end, solenoid valve (302) by threeway another entrance termination NO filtrator (901).
The electrochemical gas sensor utilizing above 5 kinds of gas circuit structures all can realize utilizing reaction velocity slower is followed and is measured fast-changing concentration of exhaled NO, and in fact the professional person of this area can design more implement device according to the principle of the invention.
Accompanying drawing explanation
Fig. 1. alveolar and air flue nitrogen monoxide produce and diffusion fixed double chamber bed.
Fig. 2. variable-flow measures expiratory gas flow change curve and expiration NO measurement of concetration curve without a break.
Fig. 3. variable-flow expiration nitric oxide measuring equipment composition schematic diagram without a break.
Fig. 4 is variable-flow expiration nitric oxide measuring equipment composition schematic diagram without a break.
Fig. 5 is variable-flow expiration nitric oxide measuring equipment composition schematic diagram without a break.
Fig. 6 is variable-flow expiration nitric oxide measuring equipment composition schematic diagram without a break.
Fig. 7 is variable-flow expiration nitric oxide measuring equipment composition schematic diagram without a break.
Fig. 8 expiratory gas flow and expiration NO change curve in time.
Fig. 9 is variable-flow measurement result and curve without a break.
Figure 10 without a break variable-flow CeNO (50ml/s) measures the correlativity with standard expiration equation measurement result.
Figure 11 without a break variable-flow CeNO (50ml/s) measures the consistance with standard expiration equation measurement result.
Embodiment
application Example one
Fig. 3 is the gas circuit structure schematic diagram of a kind of device realizing the inventive method, described device is made up of sampling module 100 and analysis module 200, its design feature is that described sampling module is by flow sensor 101, flow regulator 201, solenoid valve 301 is composed in series, and is connected between flow regulator 201 and solenoid valve 301 by threeway (not indicating) with the air chamber 401 in analysis module; Described analysis module successively by air chamber 401, threeway 501, analyze pump 602, gas humidity regulator 701(such as Nafion and manage), NO sensor 801, NO filtrator 901 and T-valve 302 form circulation gas circuit; Pump 601 is connected with air chamber 401 by threeway 501, a T-valve 303 in parallel between NO filtrator 901 with NO sensor 801.
When utilizing this device to carry out one breath variable-flow expiratory measurements, process is as follows:
1) exhale: open valve 301, after experimenter sucks cleaned air, continue expiration maintenance energetically 6 ~ 10 seconds, expiratory gas flow is controlled by the adjustment of programmed control flow regulator in exhalation process, make it with the flow velocity change of program (as linear decline) preset, real-time survey record expiratory gas flow change curve in time measured by flow sensor 101;
2) sample: while expiration, open sampling pump 601, analyze pump 602, adjustment T-valve 302,303 position, a part for the gas of expiration overall process being breathed out is collected in elongated tubular air chamber 401, and now a part for sample gas is emptying through air chamber 401, threeway 501 and sampling pump 601; Another part through air chamber 401, threeway 501, analyze pump 602, gas humidity regulator 701, NO sensor 801, T-valve 303 and T-valve 302 emptying, now gas overall flow rate is about 10ml/s, 6 ~ 10 seconds sampling times;
3) measure: sampled rear valve-off 301 and flow regulator 201, close sampling pump 601, open and analyze pump 602, the position of adjustment T-valve 302,303 makes gas flow direction become: air chamber 401, threeway 501, analysis pump 602, gas humidity regulator 701, NO sensor 801, NO filtrator 901, T-valve 302 and air chamber 401, now gas flow rate is about 1ml/s, the whole analytic process time is about 120 seconds, responds change curve in time at analysis overall process record sensor; The steady-state current that gas is recorded by sensor after NO filtrator 901 is zero current;
4) synchronous: the expiration gas at the end of sampling of exhaling is collected in the least significant end of elongated air chamber 401, when analyzing, pump 602 driving gas flows (flowing of gas in pipeline is piston flow) in circulation gas circuit, after gas is filtered by NO filtrator 901 after sensor 801 is measured, NO concentration reduces to 0, this part gas can be got back in air chamber 401, after the expiration of collecting when air chamber 401 so has all been analyzed, the response current of sensor will be undergone mutation (zero current), and the concentration that this time point is corresponding is exactly the concentration of NO of exhaling at the end of sampling of exhaling;
Owing to demarcating sample gas flow (about 10ml/s) and analytical gas flow (about 1ml/s) in advance, be equivalent to breath per second and can measure 10 seconds on a sensor, Measuring Time has been exaggerated 10 times, there is the consistent of the flex point time of zero current with during analysis in the time that sampling of exhaling from the above mentioned terminates, can find the data corresponding relation between expiratory gas flow and expiration NO measured value thus;
5) revise: according to theoretical analysis and the Gas Diffusion of aforementioned expiration NO two compartment model, need to carry out two corrections to the above results:
A. according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and expiration NO;
B. according to elongated tubular structure and analysis to measure time, the impact of the concentration difference diffusion couple measurement result that the CONCENTRATION DISTRIBUTION inequality on the gas in pipeline causes is revised;
6) calculate: calculate Jaw, Ca and FeNO50 according to corresponding relation between revised expiratory gas flow and expiration NO;
7) self-calibration: the self-calibration to transducer sensitivity be realized, first the homogeneous NO gas of concentration (concrete concentration need not be known) to be collected in air chamber 401, this is by valve-off 301, adjustment T-valve 302, 303, open pump 601, 602 directly bleed sampling realize, now airflow direction is divided into two-way, one tunnel is: NO source of the gas, flow sensor 101, flow regulator 201, air chamber 401, threeway 501, pump 601 is then emptying, another road is: NO source of the gas, flow sensor 101, flow regulator 201, air chamber 401, threeway 501, pump 602, gas humidity adjusting device 701, NO sensor 801, T-valve 303, 302 is then emptying,
T-valve 302,303 position is adjusted during self-calibration, the gas in air chamber 401 is made to get back to air chamber 401 by threeway 501, pump 602, gas humidity regulator 701, NO sensor 801, T-valve 303,302 by pump 602, like this by 2 ~ 3 circulation Measurement and analysis, just NO gas concentration in air chamber 401 is directly calculated by method disclosed in patent ZL201210207872.6, and then calculate its sensitivity that NO is responded according to the response current of cyclic process NO sensor 801, realize self-calibration.
Below for an experimenter time one breath variable-flow sampling analysis process, introduce the data handling procedure of the inventive method:
Expiratory gas flow V (t), concentration of exhaled NO Ce (t) variation diagram in time that obtain after various flow sampling:
Curve (dotted line red in figure) according to expiratory gas flow V (t)-t obtains slope a=-15.6ml/s
2;
The Vaw volume of experimenter can be by
obtaining, is 141ml;
By a and Vaw substitute into
in obtain revised expiratory gas flow F ' (t) curve over time.
(Fig. 9) is mapped in revised expiratory gas flow F ' (t) and expiration NO concentration C e (t), this slope of a curve is maximum airway walls flux Jaw, intercept is steady state alveolar gas NO concentration C a, can calculate mouth expiration NO concentration C e instantly after substituting into standard expiratory gas flow 50ml/s.
Following table is the data processed result of 4 experimenters, and the airway walls flux Jaw of four experimenters is about 950pl/s, 700pl/s, 140pl/s and 480pl/s respectively, and result repeatability is good.Utilize said method to calculate experimenter's alveolar air NO concentration C a, and inverse go out the concentration C e of exhaled NO under the expiratory gas flow of 50ml/s, consistent compared with concentration of exhaled NO when testing with standard expiratory gas flow.
Figure 10 is that 36 volunteers are respectively with variable-flow expiration method and standard expiration method carry out Ce without a break
nO(50ml/s) (often kind of method measures 3 times to the results contrast tested, get average for comparing) consistance of the two result, its linear dependence analysis is good as seen from the figure, its Pearson correlativity is 0.907 (P=0.000), and the two strong correlation, is compared (Figure 11) by Bland-Altman figure, two groups of averages measuring difference are 0.3ppb, standard deviation is 2.8ppb, and in 95% fiducial interval, the distribution of the difference of twice kind of method measurement is between-4.9 to 5.9ppb.Clinical (clinical practice permissible variation +/-5ppb) can think that the result of two kinds of measuring methods is consistent.
To adult normal variable-flow measurement Ca without a break
nOscope be-0.3 ~ 5.3ppb, Jaw
nObe 273 ~ 1348pl/s, this and literature values alveolar air concentration 1.0 ~ 5.6ppb, maximum airway pressure amount 420 ~ 1280pl/s compares, and distribution of results is comparatively reasonable.
application Example two
Fig. 4 be realize the inventive method the gas circuit structure schematic diagram of a kind of another kind of device, described device is made up of sampling module 100 and analysis module 200, its design feature is that described sampling module is by flow sensor 101, flow regulator 201, solenoid valve 301 is composed in series, and is connected between flow regulator 201 and solenoid valve 301 by threeway (not showing) with the solenoid valve 303 in analysis module; Described analysis module successively by solenoid valve 303, air chamber 401, threeway 501, analyze pump 602, gas humidity regulator 701(such as Nafion and manage), NO sensor 801, T-valve 302 form circulation gas circuit; Pump 601 is connected with air chamber 401 by threeway 501, and NO filtrator 901 is by T-valve 303 connect into analysis gas circuit.
When utilizing this device to carry out one breath variable-flow expiratory measurements, process is as follows:
1) exhale: open valve 301, after experimenter sucks cleaned air, continue expiration maintenance energetically 6 ~ 10 seconds, expiratory gas flow is controlled by the adjustment of programmed control flow regulator in exhalation process, make it with the flow velocity change of program (as linear decline) preset, real-time survey record expiratory gas flow change curve in time measured by flow sensor 101;
2) sample: while expiration, open sampling pump 601, analyze pump 602, adjustment T-valve 303,302 position, a part for the gas of expiration overall process being breathed out is collected in elongated tubular air chamber 401, and now a part for sample gas is emptying through air chamber 401, threeway 501 and sampling pump 601; Another part through air chamber 401, threeway 501, analyze pump 602, humidistat 701, NO sensor 801 and T-valve 302 emptying, now gas overall flow rate is about 10ml/s, 6 ~ 10 seconds sampling times;
3) measure: sampled rear valve-off 301 and flow regulator 201, close sampling valve 601, open and analyze pump 602, the position of adjustment T-valve 302,303 makes gas flow direction become: air, NO filtrator 901, air chamber 401, threeway 501, analyze pump 602, humidistat 701, NO sensor 801, T-valve 302 are then emptying, now gas flow rate is about 1ml/s, the whole analytic process time is about 120 seconds, responds change curve in time at analysis overall process record sensor; The steady-state current that gas is recorded by sensor after NO filtrator 901 is zero current;
4) synchronous: the expiration gas at the end of sampling of exhaling is collected in the least significant end of elongated air chamber 401, when analyzing, pump 602 driving gas flows (flowing of gas in pipeline is piston flow) in gas circuit, air is after filtering by NO filtrator 901, NO concentration reduces to 0, the gas that this part gas can promote air chamber 401 moves forward, after the expiration of collecting when air chamber 401 so has all been analyzed, the response current of sensor will be undergone mutation (zero current), and the concentration that this time point is corresponding is exactly the concentration of NO of exhaling at the end of sampling of exhaling;
Owing to demarcating sample gas flow (about 10ml/s) and analytical gas flow (about 1ml/s) in advance, be equivalent to breath per second and can measure 10 seconds on a sensor, Measuring Time has been exaggerated 10 times, there is the consistent of the flex point time of zero current with during analysis in the time that sampling of exhaling from the above mentioned terminates, can find the data corresponding relation between expiratory gas flow and expiration NO measured value thus;
5) revise:
According to theoretical analysis and the Gas Diffusion of aforementioned expiration NO two compartment model, need to carry out two corrections to the above results:
A. according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and expiration NO;
B. according to elongated tubular structure and analysis to measure time, the impact of the concentration difference diffusion couple measurement result that the CONCENTRATION DISTRIBUTION inequality on the gas in pipeline causes is revised;
6) calculate: calculate Jaw, Ca and FeNO50 according to corresponding relation between revised expiratory gas flow and expiration NO;
7)self-calibration: the self-calibration to transducer sensitivity be realized, first the homogeneous NO gas of concentration (concrete concentration need not be known) to be collected in air chamber 401, this is by valve-off 301, adjustment T-valve 302, 303, open pump 601, 602 directly bleed sampling realize, now airflow direction is divided into two-way, one tunnel is: NO source of the gas, flow sensor 101, flow regulator 201, threeway 303, air chamber 401, threeway 501, pump 601 is then emptying, another road is: NO source of the gas, flow sensor 101, flow regulator 201, threeway 303, air chamber 401, threeway 501, pump 602, gas humidity adjusting device 701, NO sensor 901, T-valve 302, then emptying,
T-valve 302,303 position is adjusted during self-calibration, the gas in air chamber 401 is made to get back to air chamber 401 by threeway 501, pump 602, gas humidity regulator 701, NO sensor 801, T-valve 302,303 by pump 602, like this by 2 ~ 3 circulation Measurement and analysis, just NO gas concentration in air chamber 401 is directly calculated by method disclosed in patent ZL201210207872.6, and then calculate its sensitivity that NO is responded according to the response current of cyclic process NO sensor 801, realize self-calibration.
application Example three
Fig. 5 is the gas circuit structure schematic diagram of the another kind of device realizing the inventive method, described device is made up of sampling module 100 and analysis module 200, its design feature is that described sampling module is by flow sensor 101, flow regulator 201, solenoid valve 301 is composed in series, by the air chamber 401 in threeway connect into analysis module between flow regulator 201 and solenoid valve 301; Described analysis module is managed by air chamber 401, threeway 501, NO filtrator 901, NO sensor 801, gas humidity regulator 701(such as Nafion according to this), analyze pump 602, circulation gas circuit; Pump 601 is connected with air chamber 401 by threeway 501.
When utilizing this device to carry out one breath variable-flow expiratory measurements, process is as follows:
1) exhale: open valve 301, after experimenter sucks cleaned air, continue expiration maintenance energetically 6 ~ 10 seconds, expiratory gas flow is controlled by the adjustment of programmed control flow regulator in exhalation process, make it with the flow velocity change of program (as linear decline) preset, real-time survey record expiratory gas flow change curve in time measured by flow sensor 101;
2) sample: while expiration, open sampling pump 601, analyze pump 602, a part for the gas of expiration overall process being breathed out is collected in elongated tubular air chamber 401, and now a part for sample gas is emptying through air chamber 401, threeway 501 and sampling pump 601; Another part is emptying through pump 602, gas humidity regulator 701, NO sensor 801, NO filtrator 901, threeway 501 and analysis pump 601, and now gas overall flow rate is about 10ml/s, 6 ~ 10 seconds sampling times;
3) measure: sampled rear valve-off 301 and flow regulator 201, close sampling pump 601, open and analyze pump 602, now gas flow direction is: air chamber 401 got back to by air chamber 401, analysis pump 602, gas humidity regulator 701, NO sensor 801, NO filtrator 901, threeway 501, now gas flow rate is about 1ml/s, the whole analytic process time is about 120 seconds, responds change curve in time at analysis overall process record sensor; The steady-state current that gas is recorded by sensor after NO filtrator 901 is zero current.
4) synchronous: the expiration gas at the end of sampling of exhaling is collected in the least significant end of elongated air chamber 401, analyze pump 602 driving gas when analyzing in gas circuit, flow (flowing of gas in pipeline is piston flow), because pump 602 is connected on the most leading portion of air chamber 401, sensor 801 just started respond gas be exhale sampling end gas, that is can with sensor just start respond time as exhale sampling end synchronous point;
Owing to demarcating sample gas flow (about 10ml/s) and analytical gas flow (about 1ml/s) in advance, be equivalent to breath per second and can measure 10 seconds on a sensor, Measuring Time has been exaggerated 10 times, there is the consistent of the flex point time of zero current with during analysis in the time that sampling of exhaling from the above mentioned terminates, can find the data corresponding relation between expiratory gas flow and expiration NO measured value thus;
5) revise: according to theoretical analysis and the Gas Diffusion of aforementioned expiration NO two compartment model, need to carry out two corrections to the above results:
A. according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and expiration NO;
B. according to elongated tubular structure and analysis to measure time, the impact of the concentration difference diffusion couple measurement result that the CONCENTRATION DISTRIBUTION inequality on the gas in pipeline causes is revised;
6) calculate: calculate Jaw, Ca and FeNO50 according to corresponding relation between revised expiratory gas flow and expiration NO.
application Example four
As shown in Figure 6; this embodiment increases self calibrating function on the basis of Application Example three; gas circuit structure is also basically identical with Application Example three; just between NO sensor 801 rear end and NO filtrator 901, add a T-valve 302; another outlet of this valve connects the endpiece of NO filtrator 901, gets back to air chamber 401 when analysis to measure by NO sensor 801 gas out through T-valve 302, NO filtrator 901, threeway 501; Air chamber 401 is got back to by NO sensor 801 gas out through T-valve 302, threeway 501 when self-calibration.
The expiration sampling of this Application Example and analytic process are with Application Example three, and self-calibration process is as follows:
During self-calibration, first in air chamber 401, collect the homogeneous NO gas of concentration (concrete concentration need not be known), this is by valve-off 301, adjustment T-valve 302, open pump 601, 602 directly bleed sampling, now airflow direction is divided into two-way, one tunnel is: NO source of the gas, flow sensor 101, flow regulator 201, air chamber 401, threeway 501, pump 601 is then emptying, another road is: NO source of the gas, flow sensor 101, flow regulator 201, analyze pump 602, gas humidity regulator 701, NO sensor 801, threeway 501, then emptying by sampling pump 601.
T-valve 302 position is adjusted during self-calibration, make the gas in air chamber 401 by analyzing pump 602, gas humidity regulator 701, NO sensor 801, T-valve 302, threeway 501, getting back to air chamber 401 by pump 602, like this by 2 ~ 3 circulation Measurement and analysis, just NO gas concentration in air chamber 401 is directly calculated by method disclosed in patent ZL201210207872.6, and then calculate its sensitivity that NO is responded according to the response current of cyclic process NO sensor 801, realize self-calibration.
Application Example five
Fig. 7 is the gas circuit structure schematic diagram of the another kind of device realizing the inventive method, described device is made up of sampling module 100 and analysis module 200, its design feature is that described sampling module is by flow sensor 101, flow regulator 201, solenoid valve 301 is composed in series, by the solenoid valve 302 in threeway (not indicating) connect into analysis module between flow regulator 201 and solenoid valve 301; Described analysis module according to this by T-valve 302, air chamber 401, analyze pump 602, gas humidity regulator 701(such as Nafion and manage), NO sensor 801 is composed in series, sampling pump 601 is connected on air chamber 401 rear end, solenoid valve 302 by threeway another entrance termination NO filtrator 901.
When utilizing this device to carry out one breath variable-flow expiratory measurements, process is as follows:
1) exhale: open valve 301, after experimenter sucks cleaned air, continue expiration maintenance energetically 6 ~ 10 seconds, expiratory gas flow is controlled by the adjustment of programmed control flow regulator in exhalation process, make it with the flow velocity change of program (as linear decline) preset, real-time survey record expiratory gas flow change curve in time measured by flow sensor 101;
2) sample: while expiration, open sampling pump 601, analyze pump 602, a part for the gas of expiration overall process being breathed out is collected in elongated tubular air chamber 401, and now a part for sample gas is emptying through T-valve 302, air chamber 401 and sampling pump 601; Another part through T-valve 302, air chamber 401, analyze pump 602, gas humidity regulator 701, NO sensor 801 are emptying, now gas overall flow rate is about 10ml/s, 6 ~ 10 seconds sampling times;
3) measure: sampled rear valve-off 301 and flow regulator 201, close sampling pump 601, open and analyze pump 602, now gas flow direction is: air, NO filtrator 901, T-valve 302, air chamber 401, analyze pump 602, gas humidity regulator 701, NO sensor 801 are emptying, now gas flow rate is about 1ml/s, the whole analytic process time is about 120 seconds, responds change curve in time at analysis overall process record sensor; The steady-state current that gas is recorded by sensor after NO filtrator 901 is zero current;
4) synchronous: the expiration gas at the end of sampling of exhaling is collected in the least significant end of elongated air chamber 401, analyze pump 602 driving gas when analyzing in gas circuit, flow (flowing of gas in pipeline is piston flow), air is after filtering by NO filtrator 901, NO concentration reduces to 0, the gas that this part gas can promote air chamber 401 moves forward, after the expiration of collecting when air chamber 401 so has all been analyzed, the response current of sensor will be undergone mutation (zero current), and the concentration that this time point is corresponding is exactly the concentration of NO of exhaling at the end of sampling of exhaling;
Owing to demarcating sample gas flow (about 10ml/s) and analytical gas flow (about 1ml/s) in advance, be equivalent to breath per second and can measure 10 seconds on a sensor, Measuring Time has been exaggerated 10 times, there is the consistent of the flex point time of zero current with during analysis in the time that sampling of exhaling from the above mentioned terminates, can find the data corresponding relation between expiratory gas flow and expiration NO measured value thus;
5) revise: according to theoretical analysis and the Gas Diffusion of aforementioned expiration NO two compartment model, need to carry out two corrections to the above results:
A. according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and expiration NO;
B. according to elongated tubular structure and analysis to measure time, the impact of the concentration difference diffusion couple measurement result that the CONCENTRATION DISTRIBUTION inequality on the gas in pipeline causes is revised;
6) calculate: calculate Jaw, Ca and FeNO50 according to corresponding relation between revised expiratory gas flow and expiration NO.
Claims (15)
1. one breath multiparameter expiration nitric oxide measuring method, is characterized in that:
Exhale and control: control expiratory gas flow in the internal linear change of 4 ~ 10 second time, record expiratory gas flow change curve in time;
Measurement of concetration: with the change curve of the NO sensor measurement expiration overall process expiration NO concentration responded fast while exhaling;
Flow correction: according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and concentration of exhaled NO;
Parameter calculates: according to corresponding relation between revised expiratory gas flow and concentration of exhaled NO, concentration of exhaled NO FeNO50 under calculating maximum airway flux Jaw, alveolar air NO concentration C a and standard expiratory gas flow 50ml/s.
2. without a break multiparameter expiration nitric oxide measuring method as claimed in claim 1, the flow automatic feedback control system that wherein expiratory gas flow controls to be combined into by flow sensor and flow controller realizes, it is characterized by: when experimenter's sustained exhalation, flow sensor measures expiratory gas flow in real time, and transfer data to flow controller, these data and the target expiratory gas flow preset compare by flow controller, and the latus rectum of the pipeline of adjustment expiration in time, ensure that expiratory gas flow is by the fluctuations in discharge rule change preset.
3. measure the method for airway dead space gas volume for one kind, it is characterized in that: carry out at least twice expiration NO measurement of concetration by control break expiratory gas flow state, wherein the measured value of expiration NO concentration is relevant to airway dead space gas volume at least one times, then airway dead space gas volume according to the correlation calculations of the two.
4. a kind of method measuring airway dead space gas volume as claimed in claim 3, is characterized by: twice expiration state is that a constant rate is measured, and one time variable-flow is measured.
5. a kind of method measuring airway dead space gas volume as claimed in claim 4, it is characterized by: the change of twice expiration state realizes in a sustained exhalation process by flow controller, ensuring the exhalation process of one section of constant flow rate at expiration leading portion or expiration latter end, is variable-flow exhalation process At All Other Times.
6. a kind of method measuring airway dead space gas volume as claimed in claim 3, is characterized by: twice expiration state is measured for being variable-flow, but the Changing Pattern of twice expiratory gas flow is different.
7. utilize electrochemical sensor to realize a method for multiparameter expiration nitric oxide measurement without a break, it is characterized in that:
Exhale: control the flow velocity change of program of exhaling to preset, record expiratory gas flow change curve in time;
Sampling: the gas of breathe out expiration overall process or a part are wherein collected in an elongated tubular;
Measure: with the flow velocity of bleeding adapted with the sensor response time, the gas in elongated tubular is passed into sensor and carry out analysis to measure, record sensor responds change curve in time;
Synchronous: the time of synchronous expiration sampling process and Measurement and analysis process, to find the data corresponding relation between expiratory gas flow and expiration NO concentration measurement;
Revise: according to airway dead space gas volume and the corresponding relation between exhalation flow rate Changing Pattern correction expiratory gas flow and expiration NO;
Calculate: according to corresponding relation between revised expiratory gas flow and expiration NO concentration measurement, concentration of exhaled NO FeNO50 under calculating maximum airway flux Jaw, alveolar air NO concentration C a and standard expiratory gas flow 50ml/s.
8. a kind of method utilizing electrochemical sensor to realize without a break multiparameter expiration nitric oxide to measure as claimed in claim 7, the feature of wherein said sampling process is: exhale sampling time by sampling pump, a part of gas in expiratory air is collected in an elongated tubular air chamber with fixing flow velocity.
9. a kind of method utilizing electrochemical sensor to realize without a break multiparameter expiration nitric oxide to measure as claimed in claim 7, the feature of wherein said measuring process is: by measurement pump, the gas in elongated tubular air chamber is passed into sensor with the gas flow rate that the sensor response time adapts during measurement and carry out analysis to measure, record sensor responds change curve in time, and during sampling, gas flow rate is when analyzing 5 ~ 20 times of gas flow rate.
10. the method for without a break measuring multiple parameters expiration nitric oxide as claimed in claim 7, it is characterized in that: when carrying out flow correction, wherein the long-pending method measurement according to claim 3 of dead space air obtains.
11. 1 kinds of one breath multiparameter expiration nitric oxide measurement mechanisms, be made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, and is connected between flow regulator (201) and solenoid valve (301) by threeway with the air chamber (401) in analysis module; Described analysis module forms circulation gas circuit by air chamber (401), threeway (501), analysis pump (602), gas humidity regulator (701), NO sensor (801), NO filtrator (901) and T-valve (302) successively; Pump (601) is connected with air chamber (401) by threeway (501), a T-valve (303) in parallel between NO filtrator (901) with NO sensor (801).
12. 1 kinds of one breath multiparameter expiration nitric oxide measurement mechanisms, be made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, and is connected between flow regulator (201) and solenoid valve (301) by threeway with the solenoid valve (303) in analysis module; Described analysis module forms circulation gas circuit by solenoid valve (303), air chamber (401), threeway (501), analysis pump (602), gas humidity regulator (701), NO sensor (801), T-valve (302) successively; Pump (601) is connected with air chamber (401) by threeway (501), and NO filtrator (901) is by T-valve (303) connect into analysis gas circuit.
13. 1 kinds of one breath multiparameter expiration nitric oxide measurement mechanisms, be made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, by the air chamber (401) in threeway connect into analysis module between flow regulator (201) and solenoid valve (301); Described analysis module is according to this by air chamber (401), threeway (501), NO filtrator (901), NO sensor (801), gas humidity regulator (701), analysis pump (602), circulation gas circuit; Pump (601) is connected with air chamber (401) by threeway (501).
14. 1 kinds of one breath multiparameter expiration nitric oxide measurement mechanisms, be made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, by the air chamber (401) in threeway connect into analysis module between flow regulator (201) and solenoid valve (301); Described analysis module is according to this by air chamber (401), threeway (501), NO filtrator (901), NO sensor (801), gas humidity regulator (701), analysis pump (602), circulation gas circuit; Pump (601) is connected with air chamber (401) by threeway (501); Between described NO sensor (801) rear end and NO filtrator (901), add a T-valve (302), another outlet of this valve connects the endpiece of NO filtrator (901).
15. 1 kinds of one breath multiparameter expiration nitric oxide measurement mechanisms, be made up of sampling module (100) and analysis module (200), it is characterized in that: described sampling module is by flow sensor (101), flow regulator (201), solenoid valve (301) is composed in series, by solenoid valve (302) in threeway connect into analysis module between flow regulator (201) and solenoid valve (301); Described analysis module according to this by T-valve (302), air chamber (401), analyze pump (602), gas humidity regulator (701), NO sensor (801) are composed in series, sampling pump (601) to be connected on air chamber (401) rear end, solenoid valve (302) by threeway another entrance termination NO filtrator (901).
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| WO2007029164A2 (en) * | 2005-09-06 | 2007-03-15 | Koninklijke Philips Electronics N.V. | Nitric oxide detection |
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| EP2459063A1 (en) * | 2009-07-30 | 2012-06-06 | Koninklijke Philips Electronics N.V. | Method and apparatus of determining exhaled nitric oxide |
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Also Published As
| Publication number | Publication date |
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| CN105445343A (en) | 2016-03-30 |
| CN105445343B (en) | 2019-01-11 |
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Application publication date: 20150311 |