DE102006039140A1 - Device for fractionating expiration volume for localization of diseases in respiratory tract, comprises inlet for inspired air that flows into cavity and outlet for inspired air leading from cavity to the lungs, means for closing the inlet - Google Patents

Abstract

The device for fractionating expiration volume for the localization of diseases in respiratory tract, comprises an inlet (1) for inspired air that flows into a cavity (2) and an outlet (3) for inspired air leading from a cavity to the lungs, means (4) for closing the inlet and the outlet, and a flow meter (8) for measuring the volume of flow of the inspired air. The means is arranged in the inlet for inspired air. The flow meter is arranged in the inlet for the inspired air or in the cavity and the flow meter is connected to a control unit. The device for fractionating expiration volume for the localization of diseases in respiratory tract, comprises an inlet (1) for inspired air that flows into a cavity (2) and an outlet (3) for inspired air leading from a cavity to the lungs, means (4) for closing the inlet and the outlet, and a flow meter (8) for measuring the volume of flow of the inspired air. The means is arranged in the inlet for inspired air. The flow meter is arranged in the inlet for the inspired air or in the cavity and the flow meter is connected to a control unit. A correlated theoretical value of a volume flow of the expired air can be calculated from the measured value of the volume flow of the inspired air by the control unit and/or a correlated value is stored and can be consulted in the control unit. The theoretical value of the volume flow of the expired air can be broken down into theoretical values of partial volume flow by the control unit, and the partial volume flow can be allocated to different zones of the respiratory tract. The means for closing the inlet for the inspired air and/or the means for closing the outlet for the expired air can be actuated or controlled by the control unit. The operational state such as close or open of the means can be adjusted corresponding to a defined partial volume flow of the expired air. Means for storing the partial volume stream are attached at the outlet. The inlet is closed in the operational state and the outlet is opened in operational state. The means are closing temporally one after another in the closed and opened state. The time span is adjustable between closed and opened operational state after standard of the length of the theoretical part volume streams is controllable by the control unit. A device for analyzing the volume material of the partial volume stream is arranged directly at the outlet. The device consists of ion mobility spectrometer, gas chromatography, high performance liquid chromatography, matrix-assisted laser desorption-time-of-flight, mass spectrometer, biosensor and electrochemical sensor. The means for storing the partial volume stream is lockable and is removable from the device. The means for closing the inlet and the outlet is selected from pneumatic valve, electromagnetic valve, and check valve. An independent claim is included for a method for fractionating expiration volume.

Description

The The invention relates to a device for fractionating the expiratory volume of the respiratory tract, which provides an inlet for inspiratory air into one Cavity into and from the cavity an outlet for inspiratory air to Lung and in the inlet for inspiratory air furnished a means of closing the inlet is. The cavity is equipped with an inlet for expiratory air and at least one outlet for equipped with expiratory air. In the outlet for the expiratory Air is a means of closing the outlet. For measuring the volume flow is in the inlet for inspiratory air or in the cavity a flow meter is set up, which is equipped with a control unit is connected and from the measured value of the volume flow of the inspiratory air by means of the control unit a correlating theoretical value of a volumetric flow of the expiratory air calculated and / or a correlating value in the control unit stored and retrievable from there. By means of the control unit is the theoretical value of the volume flow of the expiratory air can be dismantled into theoretical values of partial volume flows of the volume flow. The partial volume flows are attributable to different zones of the respiratory tract.

The Means for closing the inlet for the inspiratory air and / or the means for closing the Outlet or outlets for the expiratory Air can be controlled and regulated by the control unit, wherein the operating state "to" or "on" the means for close Inlet for inspiratory air and / or the means for closing the Outlet or outlets for expiratory Air according to a certain partial volume flow of the volume flow the expiratory air is adjustable. Moreover, the invention relates a method of fractionation and use of such Contraption.

Such Devices are used, for example, to study the function the lung as well as for the diagnosis of morbid or age-related changes used. In particular, the expiratory volume is determined by markers, which did not originate from the actual respiratory gas, which is an indication or evidence of pathological changes. Such pathological changes can various forms of lung cancer, bronchitis, infectious chronic obstructive pulmonary diseases, Bronchiectasis, pulmonary emphysema and pneumonia. Also can be bacterial or fungal or yeast infections. The list is not finally. Such markers can fleeting or also non-volatile be inorganic or organic compounds.

By the WO 91/05255 A1 A method is known for diagnosing the state of health and for monitoring and monitoring the progress of diseases, especially the lung and the respiratory tract, in which non-volatile substances, possibly together with endogenous and exogenously volatile substances, are analyzed in human respiratory air. For this purpose, a subject breathes on a cooled to -196 ° C, 1cm ² large sample carrier plate crawled. The sample is then lyophilized on the cryotic by ultrahigh vacuum equipment and subsequently analyzed in different ways.

From the EP 0 759 169 B1 is a method for collecting exhaled breath condensate for the diagnosis of health status and metabolic performance of the lung and the respiratory tract and other organs and for the analysis of exhaled exogenous substances, known in which the exhaled air flows through a sample collection tube and in this to a sub-zero temperature below 0 ° C. is cooled, wherein the liquid and soluble components condense and freeze at the, having a low temperature than the respiratory condensate, the inner wall of the sample collection tube.

The DE 199 51 204 C2 describes a method for analyzing the contents of the exhaled air, in which breath condensate obtained from the exhaled air is analyzed and the result is displayed, wherein the amount of breathing condensate obtained from the exhaled air is measured and after reaching a predetermined amount of sample a direct determination of the substances contained by measuring individual and / or sum parameters by means of one or more electrochemical sensors.

A further method for the determination of parameters of a respiratory condensate using one or more sensors for measuring the parameters of the respiratory condensate and an evaluation unit with display for the measurement results is disclosed in US Pat DE 101 37 565 B4 described.

A disadvantage of the methods and devices mentioned in the prior art for analyzing the expiratory volume and for determining markers of pulmonary diseases is that the entire expiratory volume must be examined for markers in order to be able to determine that a disease is present. However, once a marker has been found, the investigating physician remains unclear where in the respiratory tract the disease is located. As a rule, further examinations, such as ultrasound, X-ray, computed tomography, etc., must follow here. In the opposite case, it is a disease of the lungs by X-ray or other investigation methods ent Once again, the entire expiratory volume must be analyzed in order to detect the markers specifying the detected alteration or disease and to make an accurate diagnosis about them.

This requires at least two consecutive examination steps, which mean a high expenditure of time and money.

Out The prior art devices are further known, with which only a partial flow of the expiratory volume has to be analyzed. These are bypass devices, in which a Part expiration volume flow, that of the main expiratory volume flow branched off and parallel to this via a detection sensor or in an analyzer guided becomes. As a result, the expiratory volume to be analyzed is reduced. This structural modification changes nothing about the need, the location of the disease or change to determine by further investigation.

The The problem underlying the invention is therefore, a device with which by means of a single examination of the expiratory volume Type and location of a pulmonary disease or change can be detected.

The present invention solves this technical problem by having a device for fractionating indicates the exhalation volume, which is an inlet for inspiratory Air into a cavity and from the cavity an outlet for inspiratory Air to the lungs and in the inlet for inspiratory air Means for closing of the inlet. The cavity is with an inlet for expiratory Air and at least one outlet for the expiratory air fitted. In the outlet for the expiratory air is a means of closing the Outlet furnished. To measure the volume flow is in the inlet for inspirational Air or in the cavity a flow meter set up with a control unit is connected and from the measured value of Volume flow of the inspiratory air by means of the control unit a correlating theoretical value of a volumetric flow of the expiratory Air calculated and / or a correlating value stored in the control unit and is retrievable from there. By means of the control unit is the theoretical one Value of the volume flow of the expiratory air into theoretical Values of partial volume flows the volume flow can be dismantled. The partial volume flows are different zones attributable to the respiratory tract.

The Device is placed directly on the patient's mouth or is connected to a lead leading to the patient's mouth. The patient breathes in and out through the device, preferably not against a stenosis.

A in- or expiratory controllable stenosis (flow resistance) is insofar Provided that the patient involuntarily responds to this by breathing a certain desired Breathing is animated. Next is an expiratory stenosis (expiratory Resistance) capable of managing the respiratory flow and the width of the respiratory tract to manipulate that the gas exchange and the exhalation standardized for analysis. In order to become repeatable breathing maneuvers possible, to which the subject / patient is instigated involuntarily.

are in the application only means for closing, so are both the means of closure the inlet and the outlet or the outlets meant as well as means to a partial closure or partial release of the respiratory flow around a certain flow resistance to generate. Ideally, the closure and partial closure over one adjustable closing device realized, preferably these are valves with which the cross section the outlet can be narrowed or expanded to any width.

The Means for closing the inlet for the inspiratory air and / or the means for closing the Outlet or outlets for the expiratory Air can be controlled and regulated by the control unit, wherein the operating state "to" or "on" the means for close Inlet for inspiratory air and / or the means for closing the Outlet or outlets for expiratory Air according to a certain partial volume flow of the volume flow the expiratory air is adjustable. In addition, the invention gives a Fractionation method and use thereof Device for solving the technical problem.

With of the inventive device can be timed successively following partial volume flows of an expiratory volume be separated, with these subsections certain regions and zones of the respiratory tract. This is founded in that the flow in the lung through the conductive airways predominantly laminar and merely at branch points and constrictions of the bronchi is turbulent. It follows that there are gases that are different lung zones come from, or exhale little or mix.

The lung is coarse in three main zones, the conduction zone, the transition zone and the respira subdivided. Each main zone is subdivided into further subzones.

Of the Percentage of the individual zones on the total size of the lung are considered average values for the people of all age groups and sex literature can be removed.

In addition, the expiratory volume is slightly smaller than the inspiratory volume because less CO _{2 is released} than O ₂ .

The expiratory tidal volume is composed of 2 volumes together, from the exhaled volume of the dead space and the alveolar space. When exhaling, first the gas is released from the anatomical dead space, such as nose and mouth, pharynx, larynx, trachea, bronchi and bronchioles away. The volume of the death space in turn depends on the body size and the Body position of the Patients off. Subsequently the gas volume fractions of the alveolar space are respired.

So far Separate recording of both volumes was done only indirectly Measurement methods.

The Invention over the measurement of the inspiratory air volume flow on the basis of percentage volume fraction of the individual lung zones on the total lung volume and considering, that the expiratory volume is slightly smaller than the inspiratory volume is, a correlation to the size of individual, temporally successive partial volume flows of the expiratory air volume flow ago.

At the Inhalation (inspiration, inhalation) becomes the current volume flow measured. This value becomes a theoretical value of a fictitious one Associated with expiratory volume flow, which is based on knowledge of Quotient of expiratory volume to inspiratory volume in one Control unit such as a calculator can be calculated or from a storage record stored in the control unit be retrieved. At the same time, the fictitious expiratory volume becomes divided by the control unit into theoretical partial volume flows. The size and number the part volume flows to be separated can be controlled via an operating panel in the Control unit entered or stored in the control unit records be retrieved. By size and number the theoretical partial volume flows the fractionation of the real expiratory volume takes place in appropriate real partial volume flows.

Puts now the exhalation (exhalation, exhalation), this event may by an ohmmeter or other measuring devices, such as flowmeter detected and sent a signal to the control unit. Also can the end of inhalation can be used as a signal. This signal can be generated by means of the measured value acquisition on the flow meter become.

The Means for closing are connected to the control unit and can by means of the control unit be controlled. Preferably, only one means for closing is always open while the others are closed are. The time and duration of the operating state "open" or "to" of each agent to close takes place as specified the size of the separating partial volume flow. The individual means of closing will be one after the other opened one after the other and closed.

Everyone separated partial volume flow then corresponds or derives then a defined zone of the respiratory tract.

Advantageous The invention is that each breath of the patient recorded individually and selectively fractionated. This causes measured value differences minimized and the measuring accuracy increased.

The Fractions of several breaths i.e. Multiple expiratory volumes can also be collected and pooled it being understood that the partial volume flows are derived a certain zone of the respiratory tract always in the same Means for storing collected, or through the same outlet guided are, i. it does not cause a mixture of different partial volume flows of different Zones comes.

In a particular embodiment may be at one or more outlets for the expiratory air a means for storing the partial volume flow may be appropriate. The means for storing the partial volume flow is advantageously of the device removable and closable to the separated partial volume flows either for one latter To maintain analysis or another work-up step and / or a separate device respectively to be able to.

It The separated partial flow can also be fed directly into a device for analysis the ingredients of the partial volume flow are introduced, which preferably right at the outlet for the expiratory air is established or from the outlet a line directly into the device leads, making an online determination the ingredients can be made.

Preferably, the device for analyzing the partial flow rate from the group "ion mobility spectrometer (IMS), gas chromatograph, HPLC, Maldi-TOF, mass spectrometer, biosensors, elec trochemical sensors. "selected.

The Means for closing are from the group "Pneumatic Valve, electromagnetic valve, check valve, ..., selected.

• a) Messen des Volumenstroms der inspiratorischen Luft
• b) Zuordnen des Messwertes nach Schritt a) einem theoretischen Wert eines zur Größe des inspiratorischen Volumenstroms korrelierenden exspiratorischen Volumenstroms, wobei der theoretische Wert eines exspiratorische Volumenstroms in theoretische Teilvolumenströme zerlegt ist und diese theoretischen Teilvolumenströme unterschiedlichen Zonen des Respirationstraktes zugeordnet sind
• c) Zerlegen des tatsächlichen exspiratorischen Volumenstroms in Teilvolumenströme, wobei der reale Teilvolumenstrom nach Maßgabe der Größe des theoretischen Teilvolumenstroms isoliert und/oder verworfen wird.

In a subsidiary claim, the invention further teaches a method for fractionating the expiratory volume, comprising the method steps:

• a) Measuring the volume flow of the inspiratory air
• b) assigning the measured value after step a) to a theoretical value of an expiratory volumetric flow correlating to the size of the inspiratory volumetric flow, wherein the theoretical value of an expiratory volumetric flow is decomposed into theoretical partial volumetric flows and these theoretical partial volumetric flows are assigned to different zones of the respiratory tract
• c) decomposing the actual expiratory volume flow into partial volume flows, wherein the real partial volume flow is isolated and / or discarded in accordance with the size of the theoretical partial volume flow.

Preferably is the first partial flow, the simplest way over the open Inlet for the inspiratory air, discarded. The first partial volume flow contains usually only the exhalation gas from the mouth and throat, possibly also from deeper areas of the anatomical dead space, which for the investigation diseased lung zones are of secondary interest.

In a preferred embodiment the fractionation takes place of the actual expiratory volume flow in partial volume flows after through the length the theoretical partial volume flows predetermined time intervals. The actual expiratory flow rate but also according to specification the size of the partial volume of the fractional theoretical volume flow fractionated into real partial volume flows become.

To the fractionation of the expiratory volume, according to the process steps a), b) and c) in partial volume flows, can by means of a marker-specific test system each partial volume flow be examined for markers of lung diseases. Certain markers stand or are hints for certain lung diseases. Such markers are for example Hydrogen peroxide as a marker of white blood cells (neutrophils) nitric oxide as a marker of activity of the endothelium and / or the eosinophilic blood cell., but also leukotrienes as a marker of inflammation, Cytokines as regulatory proteins, and also tumor markers.

The separated partial volume flows become in a further process step different zones assigned to the respiratory tract. The assignment can be manual or also computer-aided respectively. Through this process step, a correlation of detect markers of lung disease and the site of lung disease produced. After that, the disease or even several diseases in one or in different zones of the respiratory tract localized and based on the information a targeted therapy be developed.

Of Furthermore, the invention teaches the use of a device for Fractionation of expiratory volume for the localization of diseases in the Respiratory tract, with the separated from the expiratory volume Partial volumes are assigned to different zones of the respiratory tract.

The invention will be explained in more detail with reference to an embodiment. 1 shows a device for fractionating the expiratory volume with an inlet for inspiratory air 1 a cavity 2 and an outlet for inspiratory air 3 , which in this embodiment simultaneously the inlet for expiratory air 5 is. These two can also be separated. This opening is placed directly against the patient's mouth or attached to a duct leading to the patient's mouth. The patient breathes in and out through the device. In the inlet for inspiratory air 1 a means is provided for closing the inlet, which is in the operating state. The device is equipped with four outlets for expiratory air 6 equipped. Means for closing the outlet are arranged in the outlets, the means for closing the outlet 7a opened, the other means for closing the outlet 7b are closed. In the cavity 2 is a flow meter 8th installed, which is set up to measure both incoming and outgoing flow. But it can also be set up only to measure the incoming volume flow. The flow meter 8th is with a control unit 9 connected to which the measured values are transmitted. The control unit 9 is also available with the outlets for expiratory air 7a . 7b connected. At two outlets for expiratory air are means for storing the partial volume flow 11 appropriate. Preferably, these are gas-impermeable containers such as gas-tight bags. An outlet for expiratory air ( 7b ) is connected via a line directly to a device for analyzing the constituents of the partial volume flow 11 connected, by means of which the partial volume flow separated by this outlet can be examined for markers for lung diseases.

With I indicated arrows indicate the direction of flow of the inspiratory air, the arrows marked with E those of the expiratory air. The arrows T1 to T4 denote the partial volume flows 1 to 4, which can be assigned to the zones 1 to 4 of the respiratory tract.

1

inlet for inspirational air

2

cavity

3

outlet for inspirational air

4

medium to close of the inlet

5

inlet for expiratory air

6

outlet for expiratory air

7

medium to close the outlet

8th

Flowmeter

9

A control unit

10

medium for storing the partial volume flow

11

Device for analysis the ingredients of the partial volume flow

a

Operating state "open"

b

Operating condition "closed"

Claims (15)

Device for fractionating the expiratory volume, the device having an inlet for inspiratory air ( 1 ) into a cavity ( 2 ) into and from the cavity ( 2 ) an outlet for inspiratory air ( 3 ) to the lung, wherein in the inlet for inspiratory air ( 1 ) means for closing the inlet ( 4 ), wherein the cavity ( 2 ) an inlet for expiratory air ( 5 ), wherein the cavity ( 2 ) at least one outlet for the expiratory air ( 6 ), wherein in the outlet for the expiratory air ( 6 ) means for closing the outlet ( 7a . 7b ), wherein at least one flow meter ( 8th ) in the inlet for inspiratory air ( 1 ) or in the cavity ( 2 ) and the flow meter ( 8th ) with a control unit ( 9 ), whereby by means of the control unit ( 9 ) a correlating theoretical value of a volumetric flow of the expiratory air can be calculated from the measured value of the volumetric flow of the inspiratory air and / or a correlating value in the control unit ( 9 ) is stored and retrievable, wherein by means of the control unit ( 9 ) the theoretical value of the volumetric flow of the expiratory air can be decomposed into theoretical values of partial volumetric flows of the volumetric flow and the partial volumetric flows can be assigned to different zones of the respiratory tract, wherein the means for closing the inlet ( 4 ) for the inspiratory air and / or the means for closing the outlet or outlets ( 7a . 7b ) for the expiratory air by the control unit ( 9 ) are controllable and controllable, wherein the operating state "closed" (a) or "open" (b) of the means for closing inlet for inspiratory air ( 4 ) and / or the means for closing the outlet or outlets for expiratory air ( 7a . 7b ) is adjustable according to a certain partial volume flow of the volumetric flow of the expiratory air. Device for fractionating the expiratory volume according to claim 1, characterized in that at the outlet for the expiratory air, a means for storing the partial volume flow ( 10 ) are mounted. Device for fractionating the expiratory volume according to claim 1 or 2, characterized in that the inlet for inspiratory air ( 4 ) is closed when at least one outlet for expired air ( 7a . 7b ) is open. Device for fractionating the expiratory volume according to one of claims 1 to 3, characterized in that the individual closing means ( 4 . 7 ) are opened and closed individually one after the other, whereby the time span between "opening" (a) and "closing" (b) in accordance with the length of the theoretical partial volume flows by means of the control unit ( 9 ) is adjustable and adjustable. Device for fractionating the expiratory volume according to one of Claims 1 to 4, characterized in that a device for analyzing the contents ( 11 ) of the partial volume flow, preferably directly at the outlet for the expiratory air ( 7a . 7b ) is set up. Device for fractionating the expiratory volume according to one of claims 1 to 5, characterized in that the device for analyzing the partial volume flow ( 11 ) is selected from the group "Ion Mobility Spectrometer, Gas Chromatograph, HPLC, Maldi-TOF, Mass Spectrometer, Biosensors, Electrochemical Sensors." Device for fractionating the expiratory volume according to one of claims 1 to 6, characterized in that the means for storing the partial volume flow ( 10 ) is closable and removable from the device. Device for fractionating the expiratory volume according to one of claims 1 to 7, characterized in that the means for closing ( 4 . 7 ) are selected from the group "Pneumatic valve, electromagnetic valve, check valve. Method for fractionating the expiratory volume, comprising the method steps: a) Measuring the volume flow the inspiratory air b) Assigning the measured value after step a) a theoretical value of the size of the inspiratory volume flow correlated expiratory flow rate, the theoretical Value of an expiratory volume flow decomposed into theoretical partial volume flows and these theoretical partial volume flows are different zones of the Respiratory tract are assigned c) disassemble the actual expiratory volume flow in partial volume flows, the real part volume flow in accordance with the size of the theoretical Partial volume flow isolated and / or discarded. A method for fractionating the expiratory volume according to claim 9, characterized in that the first partial volume flow, preferably via the open inlet for the inspiratory air ( 1 . 4 ), discarded. Method for fractionating the expiratory volume according to claim 9 or 10, characterized in that the decomposing of the actual expiratory Volume flow in partial volume flows after through the length the theoretical partial volume flows predetermined time intervals. Method for fractionating the expiratory volume according to one of the claims 9 or 10, characterized in that the decomposition of the actual expiratory volume flow in partial volume flows according to the size of the theoretical Partial volume flows predetermined partial volume takes place. Method for fractionating the expiratory volume according to one of the claims 9 to 12, characterized in that after steps a), b) and c) the partial volume flow by means of a marker-specific test system is examined for markers of lung diseases. Method for fractionating the expiratory volume according to one of the claims 9 to 13, characterized in that the separated partial volume flows different Zones of the respiratory tract. Use of a device according to one of claims 1 to 8 for the fractionation of the expiratory volume for localization of diseases in the respiratory tract, those from the expiratory volume separated partial volumes of different zones of the respiratory tract assigned.