Method and apparatus for determining marker gas concentration in exhaled breath using an internal calibrating gas

• US 7,192,782 B2
• Filed: 01/08/2003
• Issued: 03/20/2007
• Est. Priority Date: 01/11/2002
• Status: Expired due to Fees

• Current Assignee: Ekips Technologies, Inc.
• Original Assignee: Ekips Technologies, Inc.
• Inventors: Roller, Chad, Jeffers, James, Namjou, Khosrow
• Primary Examiner(s): Gakh; Yelena G.
• Application Number:
  US10/338,353
• Publication Number:
  US 20030134427A1
• Time in Patent Office: 1,532 Days
• Field of Search: None
• US Class Current: 436/116
• CPC Class Codes: G01N 21/3504 for analysing gases, e.g. multi-gas analysis
• CPC Class Codes: G01N 33/0037 NOx
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: Y02A 50/20 Air quality improvement or preservation, e.g. vehicle emission control or emission reduction by using catalytic converters
• CPC Class Codes: Y10T 436/177692 Oxides of nitrogen
• CPC Class Codes: Y10T 436/204998 Inorganic carbon compounds

Abstract

A method and an apparatus for measuring the concentration of a specific gas component of a gas mixture including another gas whose concentration is independently known using light absorption spectroscopy are provided. A method and an apparatus for assessing human airway inflammation by measuring the concentration of exhaled NO and CO₂ present in orally exhaled breath using light absorption spectroscopy are also provided. NO concentration is determined at the time during breath sampling corresponding to a known exhaled CO₂ concentration. Methods and apparatus are further provided for measuring NO concentration in orally exhaled human breath that analyze breath emanating from the lower airways and lungs, while excluding breath from the nasal cavity. They include steps and apparatus for discarding initially exhaled breath, flowing breath through an analysis chamber using a vacuum pump and flowing breath through an analysis chamber using a vacuum pump at an initial flow rate and later at a flow rate higher than the initial flow rate.

Claims

1. A method for assessing human airway inflammation comprising steps of;

collecting an orally exhaled human breath sample over an exhalation interval, wherein said orally exhaled human breath sample comprises orally exhaled NO and orally exhaled CO₂;

providing a spectrometer including a spectrometer light source, a spectrometer gas sample cell, a spectrometer detector and a spectrometer computer;

placing said orally exhaled human breath sample in said spectrometer gas sample cell;

illuminating said orally exhaled human breath sample with a spectrometer light source;

detecting a transmitted light beam which has passed through said orally exhaled human breath sample with said spectrometer detector to produce a signal sampling;

generating a human breath sample spectrum from said signal sampling;

analyzing said human breath sample spectrum using said spectrometer computer, said step of analyzing including identifying an absorption characteristic of orally exhaled NO and an absorption characteristic of orally exhaled CO₂, determining an orally exhaled NO absorption intensity and an orally exhaled CO₂ absorption intensity, storing said orally exhaled NO absorption intensity and said orally exhaled CO₂ absorption intensity as a function of time over the exhalation interval;

repeating said analyzing and generating to produce a series of gas mixture spectra, each spectrum having an absorption characteristic of the orally exhaled NO and the orally exhaled CO₂;

identifying a single signal sampling interval wherein a known concentration CO₂ gas absorption which corresponds to an independently known CO₂ gas concentration and a simultaneous NO absorption occur;

calculating a ratio of said simultaneous NO absorption intensity to said known concentration CO₂ gas absorption intensity and multiplying said ratio by a proportionality constant to obtain concentration of said orally exhaled NO thereby providing an assessment of human airway inflammation.

2. The method of claim 1 wherein said collecting step further includes keeping said spectrometer gas sample cell at a pressure selected to reduce line broadening and interference between said exhaled NO absorption and said CO₂ absorption in said orally exhaled human breath sample.

3. The method of claim 1 wherein said step of collecting further includes having a human subject exhale a single breath as said human subject would normally exhale including initial exhaled breath and remaining exhaled breath into said spectrometer gas collection chamber wherein said spectrometer gas collection chamber further includes a spectrometer gas cell for said remaining exhaled breath and a discard container to accept said initial exhaled breath thereby preventing said initial exhaled breath from entering said spectrometer gas sample cell.

4. The method of claim 1 wherein said spectrometer is a mid-infrared tunable laser absorption spectroscopy system.

5. The method of claim 4 wherein said laser is a IV–

VI diode laser further characterized by an emission wavelength in the range of from about 3 μ

m to about 10 μ

m.

6. The method of claim 1 further including placing said exhaled human breath mixture sample in a Herriott cell.

7. The method of claim 1 further including placing said exhaled human breath sample in a multi-pass White cell.

8. The method of claim 1 wherein said step of placing said exhaled human breath in said spectrometer further includes introducing said exhaled human breath sample into said spectrometer gas sample cell and pumping to induce a flow through said spectrometer gas sample cell.

9. The method of claim 1 wherein said human breath sample spectrum is a second harmonic absorption spectrum.

10. The method of claim 1 further comprising performing a running co-average of said NO absorption intensity and a running co-average of the CO₂ gas absorption intensity.

11. The method of claim 1 wherein said exhaled human breath is allowed to flow through said spectrometer gas sample cell at a first flow rate and at a second flow rate.

12. The method of claim 11 wherein said first flow rate is greater than said second flow rate and said first flow rate is used before said second flow rate.

13. The method of claim 1 further including identifying a CO₂ absorption intensity maximum value and a simultaneous NO absorption intensity value obtained simultaneously during a single signal sampling interval and using said CO₂ absorption intensity maximum value and said simultaneous NO absorption intensity value in said calculating a ratio step.

14. The method of claim 13 wherein said CO₂ absorption intensity maximum value is associated with an independently known CO₂ concentration and said independently known CO₂ concentration is in the range of from about 4% to about 5%.

15. The method of claim 1 wherein said concentration of exhaled NO is in the range of from about 5 parts per billion to about 100 parts per billion and indicates airway inflammation.

16. An apparatus for assessing human airway inflammation comprising;

a spectrometer gas sample cell adapted to receive an orally exhaled human breath sample containing exhaled NO and exhaled CO₂, a spectrometer light source for illuminating said orally exhaled human breath sample, a spectrometer detector for detecting light transmitted through said orally exhaled human breath sample to generate a signal sampling characteristic of the orally exhaled human breath sample, and a spectrometer computer wherein said spectrometer computer further includes an executable program for analyzing a human breath sample spectra generated from the signal sampling by identifying an exhaled NO absorption and an exhaled CO₂ absorption, determining an exhaled NO absorption intensity and an exhaled CO₂ absorption intensity, storing said exhaled NO absorption intensity and said exhaled CO₂ absorption intensity as a function of time, generating a series of human breath sample spectra, each spectrum having an absorption characteristic of the exhaled NO and the exhaled CO₂, and to identify a single signal sampling interval wherein a known concentration CO₂ gas absorption which corresponds to an independently known CO₂ gas concentration variable within an acceptable range and a simultaneous NO absorption occur;

calculating a ratio of said simultaneous NO absorption intensity to said known concentration CO₂ gas absorption intensity and multiplying said ratio by a proportionality constant to obtain concentration of said exhaled NO thereby providing an assessment of human airway inflammation.

17. The apparatus of claim 16 further including a mouthpiece for accepting said exhaled human breath sample, a T-piece connected to said mouthpiece, and wherein said T-piece is further connected to a discard container to accept initial exhaled human breath and to a tube for transporting remaining exhaled human breath into said spectrometer gas sample cell.

18. The apparatus of claim 17 further including a one-way flutter valve separating said T-piece from said discard container to keep initial exhaled human breath in said discard container.

19. The apparatus of claim 17 further including a vacuum pump connected to said spectrometer gas sample cell for inducing flow of said remaining exhaled human breath through said tube and spectrometer gas sample cell.

20. The apparatus of claim 16 wherein said spectrometer is a mid-infrared tunable laser absorption spectroscopy system.

21. The apparatus of claim 20 wherein said laser is a IV–

VI diode laser further characterized by an emission wavelength in the range of from about 3 μ

m to about 10 μ

m.

22. The apparatus of claim 16 wherein said spectrometer gas sample cell is a Herriott cell.

23. The apparatus of claim 16 wherein said spectrometer gas sample cell is a multi-pass White cell.

24. The apparatus of claim 16 wherein said executable program further includes instructions for identifying a CO₂ absorption intensity maximum value and a simultaneous NO absorption intensity value obtained simultaneously during a single signal sampling interval and using said CO₂ absorption intensity maximum value and said simultaneous NO absorption intensity value to calculate said ratio.

25. The apparatus of claim 24 wherein said CO₂ absorption intensity maximum value is associated with an independently known CO₂ concentration and said independently known CO₂ concentration is in the range of from about 4% to about 5%.