DE10142911A1 - Determination of human lung diffusion capacity, employs isotopically marked nitrogen oxide - Google Patents

Determination of human lung diffusion capacity, employs isotopically marked nitrogen oxide

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Publication number
DE10142911A1
DE10142911A1 DE2001142911 DE10142911A DE10142911A1 DE 10142911 A1 DE10142911 A1 DE 10142911A1 DE 2001142911 DE2001142911 DE 2001142911 DE 10142911 A DE10142911 A DE 10142911A DE 10142911 A1 DE10142911 A1 DE 10142911A1
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gas
diffusion capacity
determination
human lung
nitrogen oxide
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Ralph Gaebler
Andreas Jentsch
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/08Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/0813Measurement of pulmonary parameters by tracers, e.g. radioactive tracers

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
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  • Engineering & Computer Science (AREA)
  • Physiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

Use of isotopically-marked nitrogen oxide for the determination of human lung diffusion capacity. Use of isotopically-marked nitrogen oxide for the determination of human lung diffusion capacity. The indicator gas is <15>N-marked nitrogen (mon-) oxide, <15>N<16>O. Measurement of its inhaled and exhaled concentrations is carried out using an isotopomer-selective detection procedure for NO, e.g. laser magnetic resonance spectroscopy, Faraday rotation spectroscopy, gas filtration correlation or mass spectrometry. Another isotopomer of NO is employed as the indicator gas, e.g. <14>N<17>O, <14>N<18>O, <15>N<17>O or <15>N<18>O. Exhaled gas is collected in bags and measured later. Only the final gas volume expired is collected and measured.

Description

Damit Messungen der DL tatsächlich die Diffusionseigenschaften der alveolär-kapillären Diffusionsmembran (DM) widerspiegeln, sollte das verwendete Testgas nach seiner Diffusion aus dem Alveolarraum der Lunge in das Blut der Lungenkapillaren von dort nicht wieder in die Gasphase zurückkehren. Hierfür ist eine hinreichend affine Bindung des Indikatorgases im lungenkapillären Blut notwendig. Außerdem sollten biologische Nebeneffekte des Indikatorgases die Untersuchungen nicht beeinträchtigen. Selbstverständlich dürfen von seiner Verwendung keine gesundheitlichen Risiken für die Probandinnen und Probanden ausgehen. So that measurements of the D L actually reflect the diffusion properties of the alveolar-capillary diffusion membrane (D M ), the test gas used should not return to the gas phase from there after its diffusion from the alveolar space of the lungs into the blood of the lung capillaries. Sufficiently affine binding of the indicator gas in the lung capillary blood is necessary for this. In addition, biological side effects of the indicator gas should not affect the investigations. Of course, its use must not pose any health risks for the test subjects.

Seit zwei Jahrzehnten wird 14 N-markiertes Stickstoffmonoxid (14N16O) in klinischen Studien neben dem als Standardgas verwendeten Kohlenmonoxid (CO) zur Messung der DL eingesetzt. Der Vorteil von Stickstoffmonoxid 14N16O gegenüber CO besteht in der größeren Affinität zum lungenkapillären Blut und der schnelleren Reaktionskinetik des Stickstoffmonoxids. For two decades, 14 N-labeled nitrogen monoxide ( 14 N 16 O) has been used in clinical studies to measure D L in addition to carbon monoxide (CO), which is the standard gas. The advantage of nitric oxide 14 N 16 O over CO is the greater affinity for lung capillary blood and the faster reaction kinetics of nitrogen monoxide.

Der Einsatz von CO als Indikatorgas, obwohl es weit in der Anwendung verbreitet ist, weist verschiedene Nachteile auf. Einerseits ist die eingesetzte Konzentration mit ca. 0,2% CO in medizinischer Luft sehr hoch und andererseits setzt die notwendige lange Atemanhaltezeit für die Messung ein gutes Mitwirken des Probanden (Patienten-Compliance) voraus. Desweiteren ist die CO-Diffusionskapazität stark von weiteren Parametern (z. B. Partialdruck Sauerstoff) abhängig. Eine Wiederholung und ein entsprechender Vergleich der aufgenommen Meßwerte ist daher problematisch. Eine genaue Bestimmung der alveolären 14N16O- Konzentration ist nicht möglich, da die endogene Produktion des Körpers von NO den Meßwert verfälscht. Die einzige Möglichkeit diese Fehler zu verringern, besteht im Einsatz von deutlich, höheren Gaskonzentrationen (ca. 40 ppm 14N16O in Luft) des Indikatorgases für den Probanden. Allerdings sind bei diesen hohen Konzentrationen pathologische Veränderungen im Lungengewebe nachweisbar. The use of CO as an indicator gas, although widely used, has several disadvantages. On the one hand, the concentration used with approx. 0.2% CO in medical air is very high and, on the other hand, the long breath-hold time required for the measurement requires good participation of the test person (patient compliance). Furthermore, the CO diffusion capacity is heavily dependent on other parameters (e.g. oxygen partial pressure). A repetition and a corresponding comparison of the recorded measured values is therefore problematic. An exact determination of the alveolar 14 N 16 O concentration is not possible, since the endogenous production of NO by the body falsifies the measured value. The only way to reduce these errors is to use significantly higher gas concentrations (approx. 40 ppm 14 N 16 O in air) of the indicator gas for the test subject. However, pathological changes in the lung tissue are detectable at these high concentrations.

Der im Patentanspruch angegebenen Erfindung liegt das Problem zugrunde, die physiologischen Vorteile des Stickstoffmonoxids mit den idealen Eigenschaften eines Indikatorgases (keine Verfälschung durch endogene Produktion) zu kombinieren, wobei die Belastung für den Probanden minimal sein soll. The specified in the claim Invention is based on the problem the physiological benefits of Nitric oxide with the ideal Properties of an indicator gas (no falsification by endogenous Production) to combine, the Minimal burden on the test subject should be.

Dieses Problem wird durch die im Patentanspruch aufgeführten Merkmale gelöst. This problem is caused by the im Claim listed Features solved.

Das Wesen der Erfindung liegt in der Verwendung von isotopenmarkiertem Stickstoffmonoxid (z. B. 15N16O) als Indikatorgas. Aufgrund eines natürlichen Anteiles von ca. 0,3% des gesamten Stickstoffmonoxids muß die endogene Produktionsrate von 15N16O mit diesem Faktor gewichtet werden. Die relativen Fehler der Konzentrationsbestimmung sind bei der Verwendung von 15N16O deutlich geringer bzw. die endogene Produktion kann für die Bestimmung der Diffusionskapazität vernachlässigt werden. The essence of the invention lies in the use of isotope-labeled nitrogen monoxide (e.g. 15 N 16 O) as an indicator gas. Due to a natural fraction of approx. 0.3% of the total nitrogen monoxide, the endogenous production rate of 15 N 16 O must be weighted with this factor. The relative errors of the concentration determination are significantly lower when using 15 N 16 O or the endogenous production can be neglected for the determination of the diffusion capacity.

Der Vorteil des erfindungsgemäßen Verfahrens liegt in der Nutzung der idealen chemischen Eigenschaften des Stickstoffmonoxids zur Bestimmung der Lungendiffusionskapazität. Aufgrund der Verwendung eines Isotopomers des Stickstoffmonoxids kann die endogene Produktion von NO in der Lunge vernachlässigt werden. Für den Probanden ergeben sich verschiedene direkte Vorteile. Einerseits kann die eingesetzte Konzentration des Indikatorgas deutlich verringert werden, so daß die Belastung für den Probanden minimal wird. Andererseits kann die Messung aufgrund der geringen Konzentration des Indikatorgases einige Male wiederholt werden, ohne daß es zu einer Belastung des Probanden kommt. The advantage of the invention The procedure lies in the use of the ideal chemical properties of the Nitric oxide for determination the lung diffusion capacity. Because of the use of a Isotopomer of nitric oxide can the endogenous production of NO in of the lungs are neglected. For the subjects surrender various direct benefits. On the one hand can the concentration used of the indicator gas significantly reduced be so that the burden on the Subjects becomes minimal. on the other hand can the measurement due to the low concentration of Indicator gas is repeated a few times without causing a burden on the Subject comes.

Ein Ausführungsbeispiel wird im folgenden näher beschrieben. An embodiment is in following described in more detail.

Das Gasgemisch zur Bestimmung der Lungendiffusionskapazität wird unmittelbar vor der Inhalation aus dem Indikatorgas (z. B. 20 ppm 15N16O in Stickstoff) und einem Gas (z. B. 38% Sauerstoff, 18% Helium, Rest Stickstoff) im Verhältnis 1 : 1 angemischt, so daß die Sauerstoffkonzentration der für den Probanden ungefähr der natürlichen Konzentration entspricht. The gas mixture for determining the lung diffusion capacity is made up of the indicator gas (e.g. 20 ppm 15 N 16 O in nitrogen) and a gas (e.g. 38% oxygen, 18% helium, balance nitrogen) immediately before inhalation : 1 mixed so that the oxygen concentration corresponds approximately to the natural concentration for the test subject.

Die Konzentration des Indikatorgases beträgt ca. 10 ppm. Der Proband atmet maximal tief ein, und hält den Atem für eine Zeit von ca. 1-5 Sekunden an, bevor er maximal ausatmet. Aus dem Verhältnis zwischen inhalierter und end-expiratorischer Konzentration des Indikatorgases kann mit gängigen Methoden (z. B. Three-Equation- Technique) die Lungendiffusionskapazität bestimmt werden. The concentration of the indicator gas is approximately 10 ppm. The subject breathes deep as deep, and holds the breath for a time of about 1-5 seconds, before he exhales maximally. From the Relationship between inhaled and end-expiratory concentration of the Indicator gas can be used with common Methods (e.g. three-equation Technique) the Lung diffusion capacity can be determined.

Claims (2)

1. Verfahren zur Bestimmung der Lungendiffusionskapazität (DL) von Menschen dadurch gekennzeichnet, daß 1. 1.1 als Indikatorgas 15 N-markiertes Stickstoffmonoxid (15N16O) verwendet wird. 2. 1.2 die Messung der inhalierten und exhalierten 15N16O Konzentration mit einem isotopomerenselektiven Nachweisverfahren für Stickstoffmonoxid (Laser- Magnet-Resonanz-Spektroskopie, Faraday-Rotations-Spektroskopie, Gasfilterkorrelationsverfahren, Massenspektrometrie) erfolgt. 3. 1.3 als Indikatorgas ein anderes Isotopomer des Stickstoffmonoxids verwendet wird (14N17O, 14N18O, 15N17O, 15N18O). 1. A method for determining the lung diffusion capacity (D L ) of humans, characterized in that 1. 1.1 15 N-labeled nitrogen monoxide ( 15 N 16 O) is used as the indicator gas. 2. 1.2 the inhaled and exhaled 15 N 16 O concentration is measured using an isotopomer-selective detection method for nitrogen monoxide (laser magnetic resonance spectroscopy, Faraday rotation spectroscopy, gas filter correlation method, mass spectrometry). 3. 1.3 another isotopomer of nitrogen monoxide is used as the indicator gas ( 14 N 17 O, 14 N 18 O, 15 N 17 O, 15 N 18 O). 2. Verfahren zur Bestimmung der Lungendiffusionskapazität (DL) von Menschen nach Anspruch 1 und Anspruch 2, dadurch gekennzeichnet, daß 1. 2.1 das exhalierte Gas in Beuteln gesammelt wird und zu einem späteren Zeitpunkt vermessen wird. 2. 2.2 das nur das end-expiratorische Gasvolumen gesammelt und vermessen wird. 2. A method for determining the lung diffusion capacity (D L ) of humans according to claim 1 and claim 2, characterized in that 1. 2.1 the exhaled gas is collected in bags and is measured at a later time. 2. 2.2 that only the end-expiratory gas volume is collected and measured.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10222750C1 (en) * 2002-05-23 2003-11-06 Walter Schmidt Carbon monoxide inhalation device for testing blood volume and haemoglobin has device for controlled opening of carbon monoxide container positioned between oxygen bag and mouthpiece

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4083367A (en) * 1976-07-28 1978-04-11 Andros Incorporated Method and apparatus for pulmonary function analysis
US5022406A (en) * 1988-08-01 1991-06-11 Tomlinson Harold W Module for determining diffusing capacity of the lungs for carbon monoxide and method
EP0640357A1 (en) * 1993-07-22 1995-03-01 Siemens-Elema AB Gas mixture and device for delivering the gas mixture to the lungs of a living being

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4083367A (en) * 1976-07-28 1978-04-11 Andros Incorporated Method and apparatus for pulmonary function analysis
US5022406A (en) * 1988-08-01 1991-06-11 Tomlinson Harold W Module for determining diffusing capacity of the lungs for carbon monoxide and method
EP0640357A1 (en) * 1993-07-22 1995-03-01 Siemens-Elema AB Gas mixture and device for delivering the gas mixture to the lungs of a living being

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10222750C1 (en) * 2002-05-23 2003-11-06 Walter Schmidt Carbon monoxide inhalation device for testing blood volume and haemoglobin has device for controlled opening of carbon monoxide container positioned between oxygen bag and mouthpiece

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