System to be used for the determination of no levels in exhaled air and diagnostic methods for disorders related to abnormal no levels

• US 5,922,610 A
• Filed: 01/05/1996
• Issued: 07/13/1999
• Est. Priority Date: 07/06/1993
• Status: Expired due to Term

• Current Assignee: Aerocrine AB (Circassia Group Plc)
• Original Assignee: Aerocrine AB (Circassia Group Plc)
• Inventors: Lundberg, Jan, Alving, Kjell, Weitzberg, Edward
• Primary Examiner(s): Le, Long V.
• Application Number:
  US08/578,653
• Time in Patent Office: 1,285 Days
• Field of Search: 436/116, 436/117, 436/118, 436/181, 128/716, 128/719, 422/83, 422/84, 422/90, 422/93, 422/98, 600/532
• US Class Current: 436/116
• CPC Class Codes: G01N 2291/0215 Mixtures of three or more gases, e.g. air
• CPC Class Codes: G01N 2291/02845 Humidity, wetness
• CPC Class Codes: G01N 2291/0422 Shear waves, transverse waves, horizontally polarised waves
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 29/02 Analysing fluids using acoustic emission techniques G01N29/14 ; constructional or flow details for analysing fluids G01N29/222; optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/222 Constructional or flow details for analysing fluids optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 33/0026 use of an alternating circulation of another gas calibrating gas analysers G01N33/0006
• CPC Class Codes: G01N 33/0037 for 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 436/17 Nitrogen containing
• CPC Class Codes: Y10T 436/177692 Oxides of nitrogen
• CPC Class Codes: Y10T 436/25875 Gaseous sample or with change of physical state

Abstract

The present invention is drawn to a system to be used for measuring NO levels in exhaled breathing air. The system comprises: (i) a face mask that tightly covers the nose and/or mouth of the individual that the mask is intended to be used on; (ii) an inlet unit for inhaled breathing air, (iii) an outlet unit for exhaled breathing air, (iv) a non-rebreathing valve through which inhaled and exhaled breathing air, respectively, passes, and (v) a measuring unit for NO connected to the outlet unit. The present invention furthers encompasses a method for the diagnosis in mammals of inflammatory conditions in the airways. The characteristic feature is that nitric oxide NO is measured in exhaled breathing air and a found abnormal level is taken as an indication of an inflammatory condition in the airways.

Claims

1. A system for separate measurement of endogenously produced NO in nasally or orally exhaled air, comprising:

(i) a face mask comprising a mouth piece and/or a nose piece, and which face mask covers the nose and/or mouth of the individual that the mask is intended to be used on;

(ii) an inlet unit for inhaled breathing air connected to one of said mouth piece or said nose piece;

(iii) an outlet unit for exhaled breathing air connected to one of said mouth piece or said nose piece;

(iv) a non-rebreathing valve connecting said inlet and outlet units, through which inhaled and exhaled breathing air, respectively, passes;

(v) a flow regulator, through which the exhaled air passes; and

(vi) a measuring unit for endogenously produced NO connected to said outlet unit for measuring endogenously produced NO in nasally exhaled air or in orally exhaled air.

2. The system according to claim 1, wherein said inlet unit for inhaled breathing air comprises tubing having an opening to ambient air, said tubing being equipped with a filter for removal of NO present in ambient air.

3. The system according to claim 1, wherein said inlet unit for inhaled breathing air comprises tubing connected to a pressurized container for breathing air, which contains non-significant levels of NO.

4. The system according to claim 3, wherein an elastic reservoir is connected to the tubing between the pressurized container and the non-rebreathing valve.

5. The system according to any one of claims 2-4, wherein said outlet unit has cubing for exhaled breathing air comprising a T-connection for diverting sample flow air, which is a cart of the exhaled breathing air to the measuring unit.

6. The system according to claim 5, wherein said sample air flow is less than an average breathing flow rate (minute volume) of the individual to whom the system is intended to be applied so that contamination by ambient air is avoided.

7. The system according to any one of claims 2-4, wherein at least one filter selected from the group consisting of:

(i) a filter for drying exhaled air;

(ii) a filter for the removal of CO₂ in exhaled breathing air; and

(iii) a particle filter is connected to the tubing or situated in the outlet unit or integrated with the measuring unit, with the provision that the filter or filters are so placed that air targeting the detector will pass said at least one filter before entering the detector.

8. The system according to any one of claims 2-4 further comprising at least one device selected from the group consisting of:

(i) a flow meter; and

(ii) an outlet valve preventing

(a) the build up of pressure in the tubing for inhaled breathing air, and

(b) the leakage of air from the inlet unit to the outlet unit via the non-rebreathing valve.

10. A method for diagnosis of inflammatory conditions in airways of humans, comprising:

separately measuring endogenously produced NO in nasally exhaled air or in orally exhaled air with a system according to any one of claims 2-4 and 9.

34. The system according to claim 1, wherein said inlet unit and said outlet unit are connected to the same one of said mouth piece and said nose piece.

9. A system for measurement of NO in exhaled air, comprising:

(i) a face mask that covers the nose and/or mouth of the individual that the mask is intended to be used on;

(ii) a nasal or oral inlet unit for inhaled breathing air;

(iii) a nasal or oral outlet unit for exhaled breathing air;

wherein if said inlet unit is nasal, said outlet unit is nasal, and if said inlet unit is oral, said outlet unit is oral;

(iv) a non-rebreathing valve through which inhaled and exhaled breathing air passes; and

(v) a measuring unit for NO connected to said outlet unit.

11. A method for diagnosis of inflammatory conditions in the airways of humans, comprising:

measuring endogenously produced NO in nasally exhaled air to obtain a measured value for endogenously produced NO in said nasally exhaled air;

comparing the measured value against a reference value based on values typical for healthy individuals; and

diagnosing a level higher than values typical for healthy individuals as an indication of an inflammatory condition in the upper airways.

12. The method according to claim 11, wherein said inflammatory condition is rhinitis.

24. The method according to any one of claims 11-16, comprising determining the level of NO in nasally exhales air, determining the level of NO in orally exhaled air and determining relative contributions of NO from the lower and upper airways, respectively.

13. A method for diagnosis of inflammatory conditions in airways of humans, comprising:

measuring the level of NO in nasally exhaled air to obtain a measured value for endogenously produced NO in said nasally exhaled air; and

comparing the measured value against a reference value based an values typical for healthy individuals, wherein a level lower than values typical for healthy individuals is taken as an indication of an acute inflammation in the upper airways.

14. The method according to claim 13, further comprising diagnosing an airway epithelial disease or increased susceptibility for developing sinusitis.

15. The method of claim 14, wherein said epithelial disease is Kartagener'"'"'s syndrome.

16. A method for diagnosis of inflammatory conditions in an airway of a human having a mouth, a nasal cavity, an upper airway and a lower airway, comprising:

inhaling through the mouth of said human when an indication of the condition of the lower airways is desired and determining the level of NO in orally exhaled air, and when an indication of thc condition of the upper airways is desired, determining the level of NO in nasally exhaled air or in an air sample taken from the nasal cavity.

19. The method according to claim 16, for the diagnosis of airway epithelial diseases.

30. The method according to claim 19, wherein the airway epithelial disease is Kartagener'"'"'s syndrome or increased susceptibility for developing sinusitis.

17. A method for diagnosis of inflammatory conditions in upper airways of a human having a mouth, a nasal cavity, and upper airway and a lower airway, comprising:

taking a gas sample from the nasal cavity; and

determining the level of NO in said sample, wherein a level higher than values typical for healthy individuals is taken as an indication of an inflammatory condition in the upper airways.

20. The method according to any one of claims 17-19, wherein the gas sample taken from the nasal cavity is a sample aspirated from the nasal cavity or a sample obtained by flushing the nasal cavity with NO-free air.

29. The method according to claim 17, wherein said inflammatory condition in the upper airways is rhinitis.

18. A method for diagnosis of inflammatory conditions in upper airways of a human having a mouth, a nasal cavity, and upper airway and a lower airway, comprising:

taking an air sample from the nasal cavity; and

determining the level of NO in said sample wherein a level lower than values typical for healthy individuals is taken as an indication of an acute inflammation in the upper airways.

21. A method for the diagnosis of inflammatory conditions in airways of a human patient having a nasal cavity, comprising:

taking a gas sample from the nasal cavity of the patient while the patient is holding his/her breath; and

determining the level of NO in said gas sample in order to perform the diagnosis of inflammatory conditions in the airways.

22. A method for diagnosis of inflammatory conditions in airways of a human having a nasal cavity, comprising:

exhaling orally against a flow-regulator while a sample is taken from the nasal cavity; and

determining the level of NO in said sample in order to perform the diagnosis of inflammatory conditions in the airways.

23. A method for diagnosis of inflammatory conditions in the airways of a human having lower and upper airways, comprising:

determining the level of NO in nasally exhaled air;

determining the level of NO in orally exhaled air;

comparing said level of NO determined in nasally exhaled air to the level of NO determined in orally exhaled air; and

determining the relative contribution of NO from the lower and upper airways, respectively.

25. A method for diagnosis of inflammatory conditions in the airways of humans, comprising:

passing exhaled breathing air, which is nasally exhaled air or which is orally exhaled air, through at least one filter selected from the group consisting of;

(i) a filter for drying exhaled air;

(ii) a filter for the removal of CO₂ in exhaled breathing air; and

iii) a particle filter; and

thereafter measuring the amount of NO in said exhaled breathing air which has been passed through said filter.

26. A method for diagnosis of gastro-esophageal disorders in humans, comprising:

determining the level of NO in regurgitated air and taking an altered level of NO in relation to a level typical for a healthy population as an indication of a disease associated with altered levels of NO production.

27. A method for diagnosis of gastric reflux in humans, comprising;

determining the level of NO in breathing air, over a predetermined period of time, wherein an occurrence of peak NO levels, compared to a baseline level during said period of tire, is taken as an indication of gastric reflux.

31. The method according to claim 27, which further comprises the steps of:

subjecting said human to fasting conditions to establish said baseline level; and

administering a substance which affects gastric reflux to said human.

32. The method according to claim 31, wherein said substance which affects gastric reflux is food.

33. The method according to claim 32, wherein said substance which affects gastric reflux is a drug.

28. A method for monitoring effects of treatment with drugs inhibiting gastric acid secretion, comprising:

administering a drug to a subject; and

determining the level of NO in regurgitated air of said subject after administration of said drug.

35. A method for diagnosis of inflammatory conditions in lower airways of humans, comprising:

causing a patient to inhale orally through the mouth and thereafter causing said patient to exhale orally through the mouth; and

measuring endogenously produced NO in said orally exhaled air with a system comprising;

(i) a mouth piece;

(ii) an inlet unit for inhaled breathing air connected to said

(iii) an outlet unit for exhaled breathing air connected to said mouth piece;

(iv) a flow regulator, through which the exhaled air passes; and

(v) a measuring unit for endogenously produced NO connected to said outlet unit for measuring endogenously produced NO in orally exhaled air.

36. The method of claim 35, wherein said system further comprises a non-rebreathing valve connecting said inlet and outlet units through which inhaled and exhaled breathing air, respectively, passes.

37. A system for diagnosis of inflammatory conditions in lower airways of humans, comprising:

(i) a mouth piece through which a human can inhale and exhale;

(ii) an inlet unit for inhaled breathing air connected to said mouth piece,

(iii) an outlet unit for exhaled breathing air connected to said mouth piece;

(iv) a flow regulator, through which the exhaled air passes; and

(v) a measuring unit for endogenously produced NO connected to said outlet unit for measuring endogenously produced NO in orally exhaled air.

38. The system of claim 37, which further comprises a non-rebreathing valve connecting said inlet and outlet units through which inhaled and exhaled breathing air, respectively, passes.