Reagent and method for measuring lung function

• US 20030171687A1
• Filed: 02/26/2003
• Published: 09/11/2003
• Est. Priority Date: 02/27/2002
• Status: Active Grant

• Current Assignee: Cambridge Isotope Laboratories, Inc. (Otsuka Holdings Company Limited)
• Original Assignee: Cambridge Isotope Laboratories, Inc. (Otsuka Holdings Company Limited)
• Inventors: Modak, Anil S., Irie, Yasuo
• Granted Patent: US 6,890,305 B2
• Time in Patent Office: Days
• US Class Current: 600/532
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 51/1206 Administration of radioactive gases, aerosols or breath tests

Abstract

The present invention relates to an assay for evaluating alveolar exchange of oxygen. A ¹³C-labeled substrate, such as ¹³C-sodium bicarbonate is administered to a subject by oral or iv intake, and exhaled ¹³CO₂ is measured. The ¹³CO₂ in expired breath can be collected at various time points following administration of the substrate and measured in Δ per mil with a mass analyzer or photometer, such as an IR spectrometer. This process can be used as a diagnostic test for the indication of, treatment and/or evaluation of the severity of respiratory tract diseases or infections.

Claims

1. A method for evaluating alveolar gas exchange, comprising:

administering a ¹³C-labeled substrate to a subject;

measuring ¹³CO₂ exhaled by the subject; and

determining lung function from the measured ¹³CO₂.

2. The method according to claim 1, wherein the ¹³C-labeled substrate is a ¹³C-labeled carbonate.

3. The method according to claim 2, wherein the ¹³C-labeled carbonate is ¹³C-sodium bicarbonate.

4. The method according to claim 1, wherein the ¹³C-labeled substrate is administered non-invasively.

5. The method according to claim 1, wherein the ¹³C-labeled substrate is administered intravenously.

6. The method according to claim 1, wherein the subject is a human.

7. The method according to claim 1, wherein the exhaled ¹³CO₂ is measured spectroscopically.

8. The method according to claim 7, wherein the exhaled ¹³CO₂ is measured by infrared spectroscopy.

9. The method according to claim 1, wherein the exhaled ¹³CO₂ is measured with a mass analyzer.

10. The method according to claim 1, wherein the exhaled ¹³CO₂ is measured over at least three time periods to generate a dose response curve, and the lung function is determined from the area under the curve.

11. The method according to claim 10, wherein the exhaled ¹³CO₂ is measured over at least two different dosages of the ¹³C-labeled substrate.

12. The method according to claim 1, wherein the exhaled ¹³CO₂ is measured during at least the following time points:

t₀, a time prior to ingesting the ¹³C-labeled substrate;

t₁, a time after the ¹³C-labeled substrate has been absorbed in the bloodstream of the subject; and

t₂, a time during the first elimination phase.

13. The method according to claim 12, wherein the lung function is determined from a slope of Δ

¹³CO₂ at time points t₁ and t₂ calculated according to the following equation;

slope={(Δ

¹³CO₂)₂ −

(Δ

¹³CO₂)₁}/(t₂−

t₁)

wherein Δ

¹³CO₂ is the amount of exhaled ¹³CO₂.

14. A method of treating a respiratory tract disease or infection, comprising:

administering a ¹³C-labeled substrate to a subject suspected of having the respiratory tract disease or infection;

measuring ¹³CO₂ exhaled by the subject;

selecting a treatment for the respiratory tract disease or infection; and

treating the respiratory tract disease or infection.

15. The method according to claim 14, wherein after the measuring and prior to the selecting, the method further comprises determining lung function from the measured ¹³CO₂.

16. The method according to claim 15, wherein the treatment for the respiratory tract disease or infection is selected if the lung function is determined to be below a threshold value.

17. The method according to claim 14, wherein the treatment is selected from administering a drug, selecting a drug dosage, and oxygen therapy.

18. The method according to claim 14, wherein the respiratory tract disease or infection is selected from chronic obstructive pulmonary disease, asthma, cystic fibrosis, silicosis, side effects of lung transplantation, bronchitis, bronchiolitis, emphysema caused by alpha 1-antitrypsin deficiency, the common cold, croup, diphtheria, epiglottitis, influenza, lung cancer, measles, pertussis, pleurisy, pneumonia, pneumonicosis, pneumothorax, pulmonary embolism, pulmonary fibrosis, rubella, rhinitis, sarcoidosis, scarlet fever, sinusitis, sore throat, streptococcal infections, and tuberculosis.

19. The method according to claim 14, wherein the subject is a human.

20. The method according to claim 18, wherein the respiratory tract disease or infection is asthma.

21. The method according to claim 20, wherein the drug is administered via a tablet or an inhaler.

22. A method of determining the presence of a respiratory tract disease or infection, comprising:

administering a ¹³C-labeled substrate to a subject suspected of having the respiratory tract disease or infection;

measuring ¹³CO₂ exhaled by the subject; and

determining lung function from the measured ¹³CO₂;

wherein the lung function is indicative of the presence of the respiratory tract disease or infection.

23. The method according to claim 22, further comprising comparing the lung function to a threshold value.

24. The method according to claim 23, wherein the presence of the respiratory tract disease or infection is indicated if the lung function is below the threshold value.

25. The method according to claim 22, wherein the respiratory tract disease or infection is selected from chronic obstructive pulmonary disease, asthma, cystic fibrosis, silicosis, side effects of lung transplantation, bronchitis, bronchiolitis, emphysema caused by alpha 1-antitrypsin deficiency, the common cold, croup, diphtheria, epiglottitis , influenza, lung cancer, measles, pertussis, pleurisy, pneumonia, pneumonicosis, pneumothorax, pulmonary embolism, pulmonary fibrosis, rubella, rhinitis, sarcoidosis, scarlet fever, sinusitis, sore throat, streptococcal infections, and tuberculosis.

26. The method according to claim 22, wherein the subject is a human.

27. A kit comprising:

a ¹³C-labeled substrate; and

instructions provided with the substrate that describe how to determine lung function.

28. The kit according to claim 27, wherein the ¹³C-labeled substrate is ¹³C-sodium bicarbonate.

29. The kit according to claim 27, further comprising at least three breath collection bags.

30. The kit according to claim 27, wherein the ¹³C-labeled substrate is provided in a form selected from a tablet, powder, and a solution.

31. The kit according to claim 27, further comprising a container for dissolving the ¹³C-labeled substrate.