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WO2009147576A2 - Dispositif et procede de prelevement d’air expire - Google Patents

Dispositif et procede de prelevement d’air expire Download PDF

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Publication number
WO2009147576A2
WO2009147576A2 PCT/IB2009/052219 IB2009052219W WO2009147576A2 WO 2009147576 A2 WO2009147576 A2 WO 2009147576A2 IB 2009052219 W IB2009052219 W IB 2009052219W WO 2009147576 A2 WO2009147576 A2 WO 2009147576A2
Authority
WO
WIPO (PCT)
Prior art keywords
gas mixture
gas
patient
container
voc
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2009/052219
Other languages
English (en)
Other versions
WO2009147576A3 (fr
Inventor
Teunis J. Vink
Willem M. J. M. Coene
Nicolaas P. Willard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Koninklijke Philips NV
Original Assignee
Koninklijke Philips Electronics NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Koninklijke Philips Electronics NV filed Critical Koninklijke Philips Electronics NV
Publication of WO2009147576A2 publication Critical patent/WO2009147576A2/fr
Publication of WO2009147576A3 publication Critical patent/WO2009147576A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Measuring devices for evaluating the respiratory organs
    • A61B5/097—Devices for facilitating collection of breath or for directing breath into or through measuring devices

Definitions

  • the present invention relates to a breath collection device and a corresponding method for collecting the breath of a patient for analysis.
  • US 2003/065274 A discloses a method of determining a respiratory parameter for a subject using an indirect calorimeter.
  • the indirect calorimeter includes a respiratory connector for passing inhaled and exhaled gases, a flow pathway operable to receive and pass inhaled and exhaled gases having a flow tube within the flow pathway through which the inhaled and exhaled gases pass, a flow meter for determining an instantaneous flow volume of the inhaled and exhaled gases, a component gas concentration sensor for determining an instantaneous fraction of a predetermined component gas and a computation unit having a processor and a memory.
  • the subject inhales atmospheric gas, but it is also disclosed that instead other gas mixtures from a source of respiratory gases can be inhaled Further, it is disclosed that the exhaled air can be provided to other analytical devices for further analysis, e.g. to find indicators of lung disease or cancer.
  • a breath collection device for collecting the breath of a patient for analysis comprising a gas mixture container containing a gas mixture for inhalation by the patient, and a breathing unit containing an inlet connected to said gas mixture container for letting in gas from the gas mixture container, an outlet for letting out gas exhaled by the patient and a breathing element for inhaling gas from the inlet and exhaling gas to the outlet, which is characterized in that said gas mixture container contains a gas mixture containing a predetermined set of volatile organic compounds (VOC) markers.
  • VOC volatile organic compounds
  • a breath collection method for collecting the breath of a patient for analysis comprising the steps of: providing a gas mixture for inhalation by the patient, allowing the patient to inhale the provided gas mixture via an inlet, - passing the gas exhaled by the patient to an outlet, which is characterized in that said provided gas mixture contains a predetermined set of volatile organic compounds (VOC) markers.
  • VOC volatile organic compounds
  • VOCs volatile organic compounds
  • the first suggestion is straightforward but wrong.
  • the second suggestion is difficult to carry out in practice, since filters often appear to be the origin of contaminations (it should be recalled that concentration levels are in the ppt-ppb regime). Therefore, only the latter option is available, which appears to be the most accurate procedure. However, in that case the results will depend on the exact composition of the inhaled air. The latter can vary substantially depending on the location of the measurement: for instance, city versus rural area, hospital area versus regular office area, proximity to highways and airports, proximity to industry plants etc..
  • a second problem is related to the occurrence of so-called negative biomarkers, which can be reasoned as follows.
  • the lung system inhales components from the environment and subsequently these can be absorbed and/or metabolised by the body. Consequently, the concentration of that particular component is higher in the inhaled air then in the exhaled air. In case these components are considered typical for a disease state this can be called negative biomarkers (the differential measurement as discussed earlier will yield negative values).
  • the inhaled air composition needs to be controlled which is the basic idea of the present invention.
  • a breath collection device is proposed by the present invention where the inlet is connected to a container, e.g. a gas cylinder, gas sampling bag etc..
  • the gas container is preferably filled with normal humidified air plus a specific set of VOC markers.
  • the concentration of these VOCs will be very low (ppt-ppb level), and therefore the inhaled air mixture poses absolutely no harm to the patient.
  • ppt-ppb level concentration of these VOCs
  • the present invention makes use of the concept that the absorption and metabolization of inhaled, artificial (i.e. not endogeneous or origin) VOCs depends on disease state.
  • the invention is different from and not just a simple extension of measuring metabolism using oxygen consumption or carbon dioxide generation. To further improve the accuracy of the method and to separate the added
  • VOCs from the natural occurring VOCs labelled compounds with deuterium ( 2 H) and/or stable carbon isotope ( 13 C) can be used as proposed according to a further embodiment.
  • VOC markers are from the group comprising alkanes, aromatics, alcohols, aldehydes, ketones and/or their labelled equivalents. It is to be understood that these marker are examples, the above list is not a complete list)
  • said inlet and said outlet of said breathing unit comprise one-way valves to ensure that the patient is only inhaling the gas mixture from the gas mixture container and is only exhaling via the outlet and not via the inlet.
  • an analysis unit connected to said outlet of said breathing unit for analysis of the exhaled gas is provided.
  • said analysis unit is adapted for performing a differential analysis of the VOC marker profile contained in the gas mixture container versus the VOC marker profile contained in the exhaled gas.
  • a VOC sampling unit for sampling the VOC marker profile contained in the exhaled gas is provided. This enables an offline analysis of the exhaled gas.
  • An appropriate embodiment thus comprises: an air container each containing an air mixture containing no VOC markers and a switching unit having a switching outlet connected to the inlet of said breathing unit and one or more switching inlets connected to said air container and said gas mixture container, respectively, for switching there between so that either the air mixture contained in the air container or the gas mixture contained in the gas mixture container can be inhaled from the patient.
  • one or more additional gas mixture containers containing a predetermined air mixture containing predetermined set of VOC markers and a switching unit allowing to switch between the different gas mixture containers for inhalation by the patient are provided so that, for instance, a desired step-wise inhalation procedure can be performed, wherein in each step a different gas mixture is provided for inhalation.
  • Fig. 1 schematically shows a first embodiment of a breath collection device according to the present invention
  • Fig. 2 schematically shows a second embodiment of a breath collection device according to the present invention
  • Fig. 3 schematically shows a third embodiment of a breath collection device according to the present invention. DETAILED DESCRIPTION OF THE INVENTION
  • Fig. 1 shows a first embodiment of a breath collection device according to the present invention for collecting the breath of a patient for analysis, e.g. for analysis of biomarker indicating a disease.
  • the device comprises a gas mixture container 1 containing a gas mixture for inhalation by the patient, said gas mixture containing a set of VOC biomarkers.
  • the device further comprises a breathing unit 2 containing an inlet 21 connected to said gas mixture container 1 for letting in gas from the gas mixture container 1 , an outlet 22 for letting out gas exhaled by the patient and a breathing element 23 for inhaling gas from the inlet 21 and exhaling gas to the outlet 22.
  • One-way valves are mounted in the inlet 21 and the outlet 22 to circumvent re-breathing by the patient.
  • the outlet 22 is connected to a VOC sampler 3 wherein the exhaled VOCs are being collected.
  • the arrows depict the air stream when a person is breathing through the breathing element 23, e.g. a mouthpiece or a mask covering mouth and nose.
  • An accurate differential analysis of the VOC profile can be obtained by analysing the VOCs in the gas mixture container 1 and in the VOC sampler 3. This analysis can be performed offline, e.g. using standard gas analysis techniques such as gas chromatography and mass spectrometry.
  • Fig. 2 shows a second embodiment of a breath collection device according to the present invention.
  • the patient can be breathing with the device with an air container 4, e.g. with standardized air without the presence of any biomarker VOCs.
  • the device can switch by a switch 5 to the gas mixture container 1 which has the controlled presence of the biomarker VOCs in the standardized air.
  • the switch comprises a switching outlet 51 connected to the inlet 21 of said breathing unit 2 and one or more switching inlets 52, 53 connected to said air container 4 and said gas mixture container 1 , respectively, for switching there between.
  • the air mixture contained in the air container 4 or the gas mixture contained in the gas mixture container 1 can be inhaled from the patient.
  • Fig. 3 shows a second embodiment of a breath collection device according to the present invention.
  • This embodiment comprises a number n of gas mixture containers 11 , 12, .. ,ln each containing a different gas mixture containing a different predetermined set of VOC markers. This allows to perform a procedures with a number of steps where consecutively the different gas mixtures provided to the patient for inhalation via the switch 5, in case the disease needs to be characterized by such a sequence of operations.
  • the air container 4 shown in Fig. 2 may also be provided in addition for initial use or for use in between the different steps for "neutralizing" the lung content of the patient.
  • an analysis unit 6 is provided for direct analysis of the exhaled gas (preferably online).
  • the shown embodiments are relatively simple embodiments of the breath collection device.
  • the device can be more advanced.
  • the basic idea is the use of at least one container/sampling bag at the inlet, which contains a specific set of VOC bio markers with known concentrations.
  • VOCs are alkanes (pentane, hexane, heptane, cyclohexane), aromatics (toluene, xylene), alcohols (ethanol, propanol, butanol), aldehydes, ketones (butanal, acetone, butanon) and their labelled equivalents.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Physiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Physics & Mathematics (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L’invention concerne un dispositif simple, efficace et précis de prélèvement d’air expiré et un procédé associé de prélèvement d’air expiré par un patient en vue d’une analyse. Ce dispositif comprend : un récipient de mélange de gaz (1) contenant un mélange de gaz destiné à être inhalé par le patient; et une unité de respiration (2) comportant un orifice d’entrée (21) relié au récipient de mélange de gaz (1) pour permettre l’entrée de gaz provenant du récipient (1), un orifice de sortie (22) destiné à évacuer le gaz expiré par le patient, ainsi qu’un élément de respiration (23) permettant l’inhalation de gaz par l’orifice d’entrée (21) et l’expiration de gaz par l’orifice de sortie (22). Le récipient de mélange de gaz (1) contient un mélange de gaz constitué d’un ensemble prédéterminé de marqueurs de composés organiques volatils (COV).
PCT/IB2009/052219 2008-06-02 2009-05-27 Dispositif et procede de prelevement d’air expire Ceased WO2009147576A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08104221.0 2008-06-02
EP08104221 2008-06-02

Publications (2)

Publication Number Publication Date
WO2009147576A2 true WO2009147576A2 (fr) 2009-12-10
WO2009147576A3 WO2009147576A3 (fr) 2010-05-14

Family

ID=41258495

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2009/052219 Ceased WO2009147576A2 (fr) 2008-06-02 2009-05-27 Dispositif et procede de prelevement d’air expire

Country Status (1)

Country Link
WO (1) WO2009147576A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103330547A (zh) * 2013-06-08 2013-10-02 浙江大学 介入性疾病诊断和监测系统
EP2827773A4 (fr) * 2012-03-19 2015-11-11 Richard C Fuisz Procédé et système pour amplifier et mesurer des substances à analyser dans des gaz respiratoires
WO2017046183A1 (fr) * 2015-09-14 2017-03-23 Freie Universität Berlin Procédé non invasif pur d'identification de maladies touchant des organes ou d'une altération de la fonction d'organes par analyse de substances de marquage dans l'air expiré stimulé par des substances de marquage inhalées
CN108362754A (zh) * 2018-01-19 2018-08-03 北京大学 一种呼出气中生物标志物在线检测系统及方法
CN110198659A (zh) * 2017-01-23 2019-09-03 皇家飞利浦有限公司 用于数据库比较的呼吸样本数据的对齐

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5787885A (en) * 1994-10-13 1998-08-04 Lemelson; Jerome H. Body fluid analysis system
US5962335A (en) * 1997-01-03 1999-10-05 Oridion Medical Ltd. Breath test for detection of drug metabolism
US6899684B2 (en) * 1999-08-02 2005-05-31 Healthetech, Inc. Method of respiratory gas analysis using a metabolic calorimeter
IL148468A (en) * 2002-03-03 2012-12-31 Exalenz Bioscience Ltd Breath collection system

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2827773A4 (fr) * 2012-03-19 2015-11-11 Richard C Fuisz Procédé et système pour amplifier et mesurer des substances à analyser dans des gaz respiratoires
CN103330547A (zh) * 2013-06-08 2013-10-02 浙江大学 介入性疾病诊断和监测系统
WO2017046183A1 (fr) * 2015-09-14 2017-03-23 Freie Universität Berlin Procédé non invasif pur d'identification de maladies touchant des organes ou d'une altération de la fonction d'organes par analyse de substances de marquage dans l'air expiré stimulé par des substances de marquage inhalées
US20180267016A1 (en) * 2015-09-14 2018-09-20 Freie Universität Berlin Pure non-invasive method for identification of organ diseases or impaired organ function by investigation of marker substances in exhaled air stimulated by inhaled marker substances
US11103158B2 (en) 2015-09-14 2021-08-31 Freie Universität Berlin Pure non-invasive method for identification of organ diseases or impaired organ function by investigation of marker substances in exhaled air stimulated by inhaled marker substances
CN110198659A (zh) * 2017-01-23 2019-09-03 皇家飞利浦有限公司 用于数据库比较的呼吸样本数据的对齐
CN108362754A (zh) * 2018-01-19 2018-08-03 北京大学 一种呼出气中生物标志物在线检测系统及方法

Also Published As

Publication number Publication date
WO2009147576A3 (fr) 2010-05-14

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