Device and method for collection of exhaled alveolar breath condensate

• US 20040162500A1
• Filed: 02/13/2004
• Published: 08/19/2004
• Est. Priority Date: 02/14/2003
• Status: Active Grant

• Current Assignee: Charlotte Mecklenburg Hospital Authority
• Original Assignee: Charlotte Mecklenburg Hospital Authority
• Inventors: Kline, Jeffrey A.
• Granted Patent: US 7,547,285 B2
• Time in Patent Office: Days
• US Class Current: 600/532
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/0087 Breath samples
• CPC Class Codes: A61B 5/097 Devices for facilitating collection of breath or for directing breath into or through measuring devices
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis

Abstract

A diagnosis method for respiratory disease based on the separation of the expired airway phase in an exhaled breath from the alveolar phase, and a device to accomplish the method. The device includes a cartridge assembly and a disposable condensing chamber carried in a substantially enclosed housing. The cartridge assembly includes a disposable cartridge and a reusable control system that monitors a characteristic of gas passing through the cartridge to determine when to divert the exhaled breath to an exhaust outlet and when to divert the exhaled breath to the condensing chamber. The characteristic is selected as being representative of the transition from the expired airway phase to the alveolar phase. Also included are a refrigeration system, an auxiliary monitoring system for determining when a sufficient volume of gas has been produced, and a built-in analyzer.

Claims

1. A method of diagnosing particular diseases based on expired breath from a mammalian subject, comprising:

providing a breath condensate collection device having condensing chamber, a fluid inlet and a fluid outlet;

cooling the condensing chamber;

receiving, at the fluid inlet, at least one exhaled breath from a mammalian subject;

separating the exhaled breath into an expired airway phase volume and an alveolar phase volume;

condensing portions of either the expired airway phase portion of the exhaled breath or the alveolar phase volume of the exhaled breath, but not both, in the condensing chamber to produce condensate on the inner surfaces of the condensing chamber;

removing the condensate from the condensing chamber;

analyzing the condensate for markers indicative of respiratory disease; and

rendering a diagnosis at least partly on the basis of whether the condensate being analyzed came from the expired airway phase portion of the exhaled breath or the alveolar phase volume of the exhaled breath.

2. The method of claim 1, wherein the separating takes place between the fluid inlet and the condensing chamber.

3. The method of claim 2, wherein the markers include biochemicals.

4. The method of claim 3, wherein the biochemicals include inorganic gases, volatile organic molecules, proteins, nucleic acids, lipids, lipid A, endotoxin and other impervious nonorganic exogenous materials.

5. The method of claim 2, wherein the markers include microbes.

6. The method of claim 5, wherein the microbes include viruses, fungi, mycoplasma, mycobacteria, bacteria, prions and protozoa.

7. The method of claim 2, wherein only the alveolar phase volume of the exhaled breath reaches the condensing chamber.

8. The method of claim 2, wherein only the expired airway phase volume of the exhaled breath reaches the condensing chamber.

9. The method of claim 2, wherein the receiving, separating and condensing steps are repeated in order to increase the amount of condensate produced in the condensing chamber.

10. The method of claim 9, further comprising:

expressing the condensate from the condensing chamber using a piston assembly.

11. A method of collecting breath condensate from a portion of exhaled breath from a mammalian subject by separating the expired airway phase of the breath from the alveolar phase, the method comprising:

providing a cartridge assembly and a condensing chamber, the cartridge assembly having a breathing port and at least two fluid outlets, wherein at least one fluid outlet is in fluid communication with the condensing chamber;

cooling the condensing chamber;

receiving, at the breathing port in the cartridge assembly, at least one exhaled breath from a mammalian subject;

monitoring, in the cartridge assembly, at least one characteristic of the exhaled breath, the characteristic generally capable of distinguishing the expired airway phase of the breath from the alveolar phase of the breath;

based on the state of the monitored characteristic, diverting the flow of the exhaled breath through the cartridge assembly from one fluid outlet to the other fluid outlet; and

upon receiving a diverted portion of the exhaled breath from the cartridge assembly, condensing portions of the exhaled breath to produce condensate on the inner surfaces of the condensing chamber.

12. The method of claim 11, wherein monitoring includes determining when the exhaled breath has transitioned from the expired airway phase to the alveolar phase, and wherein diverting the flow of the exhaled breath based on the state of the monitored characteristic includes diverting the exhaled breath to the condensing chamber once it is determined that the alveolar phase of the exhaled breath has begun.

13. The method of claim 12, wherein cooling the condensing chamber includes cooling the condensing chamber to a temperature of less than 0°

F.

14. The method of claim 13, wherein the diverting step includes adjusting the state of a valve assembly to prevent the exhaled breath from passing into the condensing chamber until the alveolar phase of the exhaled breath has begun and to force the exhaled breath into the condensing chamber once the alveolar phase of the exhaled breath has begun.

15. The method of claim 13, wherein cooling the condensing chamber includes cooling the condensing chamber to a temperature of less than 0°

C.

16. The method of claim 13, further comprising:

expressing the condensate from the condensing chamber using a piston assembly.

17. The method of claim 13, wherein determining when the exhaled breath has transitioned from the expired airway phase to the alveolar phase includes determining when a predetermined level of a particular predetermined gas is reached.

18. The method of claim 17, wherein the particular predetermined gas is selected from the group consisting of CO₂, O₂, N₂, CO and NO.

19. The method of claim 13, wherein the monitoring, diverting and condensing steps are repeated in order to increase the amount of condensate produced in the condensing chamber.

20. The method of claim 19, wherein the monitoring, diverting and condensing steps are repeated for a predetermined period of time.

21. The method of claim 19, wherein the monitoring, diverting and condensing steps are repeated until a predetermined volume of gas has passed into the condensing chamber.

22. The method of claim 12, wherein the monitoring and diverting steps are carried out automatically.

23. The method of claim 11, wherein monitoring includes determining when the exhaled breath has transitioned from the expired airway phase to the alveolar phase, and wherein diverting the flow of the exhaled breath based on the state of the monitored characteristic includes diverting the exhaled breath to the condensing chamber until it is determined that the alveolar phase of the exhaled breath has begun.

24. A breath condensate collection apparatus comprising:

(a) a cartridge assembly including;

a breathing port adapted to permit a mammalian subject to breathe in and out of the cartridge assembly,

at least a first fluid outlet and a second fluid outlet,

a monitoring system adapted to monitor at least one characteristic of a generally gaseous fluid passing through the cartridge assembly, the at least one characteristic generally capable of distinguishing the expired airway phase of an exhaled breath from the mammalian subject from the alveolar phase of the exhaled breath, and

a valve assembly operable to divert the flow of fluid, received via the breathing port, to either the first fluid outlet or the second fluid outlet on the basis of the state of the monitored characteristic; and

(b) a condensing chamber having double side walls and first and second opposing ends, wherein the double side walls include an inner side wall and an outer side wall in spaced relationship to one another, wherein the condensing chamber is in fluid communication with at least one fluid outlet of the cartridge assembly.

25. The breath condensate collection apparatus of claim 24, wherein the condensing chamber includes an outlet and a one-way valve adapted to prevent gas from being drawn into the condensing chamber during an inhalation by the mammalian subject while permitting exhaled breath to be exhausted therethrough during an exhalation by the mammalian subject.

26. The breath condensate collection apparatus of claim 25, wherein the condensing chamber is cooled to a temperature of less than 0°

F.

27. The breath condensate collection apparatus of claim 26, wherein the condensing chamber is cooled to a temperature of less than 0°

C.

28. The breath condensate collection apparatus of claim 26, further comprising a plunger assembly having a piston and a handle, wherein the piston is slidably disposed in the interior of the condensing chamber in snug contact with the inner side wall and wherein the handle extends from the first end of the condensing chamber so as to permit the piston to be moved within the central chamber.

29. The breath condensate collection apparatus of claim 28, wherein the one-way valve is a first one-way valve, wherein the cartridge assembly further includes an inhalation port and a second one-way valve adapted to permit breathing gas to be drawn into the cartridge assembly during an inhalation by the mammalian subject, and the cartridge assembly further includes a third one-way valve in at least one of the at least two fluid outlets adapted to prevent gas from being drawn into the cartridge assembly during an inhalation by the mammalian subject while permitting exhaled breath to be exhausted therethrough during an exhalation by the mammalian subject.

30. The apparatus of claim 25, wherein the actuator device operates the valve assembly to divert the flow of fluid, received via the breathing port, to the second fluid outlet instead of to the first fluid outlet when a predetermined level of a particular predetermined gas is reached.

31. The apparatus of claim 30, wherein the predetermined level is reached by the level of the predetermined gas rising to the predetermined level.

32. The apparatus of claim 30, wherein the predetermined level is reached by the level of the predetermined gas dropping to the predetermined level.

33. The apparatus of claim 30, wherein the particular predetermined gas is selected from the group consisting of CO₂, O₂, N₂, CO and NO.

34. The apparatus of claim 30, wherein the breathing port, the at least two fluid outlets and the valve assembly define a cartridge, and wherein the apparatus further comprises a housing adapted to carry the cartridge, the monitoring system and the condensing chamber.

35. The apparatus of claim 34, wherein the cartridge is adapted to be removable from the housing for disposal after a single use, while the monitoring system is adapted for repeated reuse.

36. The apparatus of claim 30, wherein the actuator device operates, the valve assembly to divert the flow of fluid, received via the breathing port, to the fluid outlet connected to the condensing chamber when the predetermined level of the particular predetermined gas is reached.

37. The apparatus of claim 30, wherein the actuator device operates the valve assembly to divert the flow of fluid, received via the breathing port, away from the fluid outlet connected to the condensing chamber when the predetermined level of the particular predetermined gas is reached.

38. The apparatus of claim 25, wherein the valve assembly includes a valve adjustable between at least two positions, wherein in the first valve assembly state the valve is in a first position diverting fluid received at the breathing port to the first fluid outlet and away from the second fluid outlet, and wherein in the second valve assembly state the valve is in a second position diverting fluid received at the breathing port to the second fluid outlet and away from the first fluid outlet.

39. The apparatus of claim 38, wherein the valve is a directional flap.

40. The apparatus of claim 39, wherein the actuator device is a rotary solenoid.

41. The apparatus of claim 25, wherein the valve assembly includes at least two valves.

42. An apparatus for separating the expired airway phase of breath exhaled by a mammalian subject from the alveolar phase of the exhaled breath, the apparatus comprising:

(a) a fluid inlet;

(b) at least a first fluid outlet and a second fluid outlet;

(c) a valve assembly adjustable between at least two states, the at least two states including a first state wherein fluid received at the fluid inlet is diverted to the first fluid outlet, and a second state wherein fluid received at the fluid inlet is diverted to the second fluid outlet; and

(d) a control system that adjusts the state of the valve assembly, the control system including;

a spectrometer arranged to monitor at least one characteristic of a generally gaseous fluid passing through the separation apparatus, the characteristic generally capable of distinguishing the expired airway phase of an exhaled breath from a mammalian subject from the alveolar phase of the exhaled breath, and

an actuator device, coupled to the spectrometer and the valve assembly, that adjusts the state of the valve assembly on the basis of the state of the monitored characteristic.

43. The apparatus of claim 42, wherein the spectrometer is arranged to measure the partial pressure of a particular predetermined gas in the gaseous fluid passing through the separation apparatus.

44. The apparatus of claim 43, wherein the actuator device adjusts the state of the valve assembly from its first state to its second state when the partial pressure of the particular predetermined gas reaches a predetermined level.

45. The apparatus of claim 44, wherein the partial pressure reaches the predetermined level by rising to the predetermined level.

46. The apparatus of claim 44, wherein the partial pressure reaches the predetermined level by dropping to the predetermined level.

47. The apparatus of claim 44, wherein the particular predetermined gas is selected from the group consisting of CO₂, O₂, N₂, CO and NO.

48. The apparatus of claim 44, wherein the fluid inlet, the at least two fluid outlets and the valve assembly define a cartridge assembly, and wherein the apparatus further comprises a housing adapted to carry the cartridge assembly and the control system.

49. The apparatus of claim 48, wherein the cartridge assembly is adapted to be removable from the housing for disposal after a single use, while the control system is adapted for repeated reuse.

50. The apparatus of claim 44, further comprising a chamber having an inlet connected in fluid communication with one of the at least two fluid outlets and adapted to collect at least a portion of the generally gaseous fluid passing through the separation apparatus.

51. The apparatus of claim 50, wherein the chamber is a condensing chamber adapted to collect liquid condensed out of the generally gaseous fluid.

52. The apparatus of claim 50, wherein the chamber is connected to the second fluid outlet, and wherein the actuator device adjusts the valve assembly from the first state to the second state when the partial pressure reaches the predetermined level.

53. The apparatus of claim 50, wherein the chamber is connected to the second fluid outlet, and wherein the actuator device adjusts the valve assembly from the second state to the first state when the partial pressure reaches the predetermined level.

54. The apparatus of claim 43, wherein the valve assembly includes a valve adjustable between at least two positions, wherein in the first valve assembly state the valve is in a first position diverting fluid received at the fluid inlet to the first fluid outlet and away from the second fluid outlet, and wherein in the second valve assembly state the valve is in a second position diverting fluid received at the fluid inlet to the second fluid outlet and away from the first fluid outlet.

55. The apparatus of claim 54, wherein the valve is a directional flap.

56. The apparatus of claim 55, wherein the actuator device is a rotary solenoid.

57. The apparatus of claim 43, wherein the valve assembly includes at least two valves.

58. A breath condensate collection apparatus comprising:

(a) a housing;

(b) a condensing chamber, carried by the housing, having an inlet that receives exhaled breaths from a mammalian subject and an outlet that permits a gaseous, non-condensed portion of the exhaled breaths to escape from the condensing chamber; and

(c) a built-in refrigeration system, carried by the housing, including;

a compressor,

an expansion valve,

an evaporator pipe arranged to cool the condensing chamber, and

a condenser pipe arranged to dissipate heat away from the condensing chamber.

59. The breath condensate collection apparatus of claim 58, wherein the housing includes a cavity correspondingly shaped and sized to carry the condensing chamber, and wherein the evaporator pipe is disposed generally around the cavity.

60. The breath condensate collection apparatus of claim 59, wherein when the condensing chamber is carried in the cavity, the condensing chamber makes contact with a substantial portion of the evaporator pipe.

61. The breath condensate collection apparatus of claim 59, wherein the condensing chamber has walls constructed from a good heat conducting material.

62. The breath condensate collection apparatus of claim 61, wherein the walls of the condensing chamber are constructed from aluminum.

63. The breath condensate collection apparatus of claim 59, further comprising a ventilation system that dissipates heat generated by the refrigeration system.

64. The breath condensate collection apparatus of claim 63, wherein the ventilation system includes one or more vents in the housing.

65. The breath condensate collection apparatus of claim 63, wherein the ventilation system includes one or more fans.

66. The breath condensate collection apparatus of claim 59, further comprising a temperature gauge arranged to provide an indication of the temperature of the condensing chamber.

67. A portable breath condensate collection apparatus comprising:

a housing having at least one compartment adapted to receive and generally enclose a removable cartridge and a removable condensing chamber in fluid communication with one another;

a removable, disposable cartridge, having at least one inlet, at least one outlet and a mouthpiece in fluid communication with at least one inlet, carried in the at least one compartment of the housing such that at least a portion of the mouthpiece is carried externally to the housing; and

a removable condensing chamber, having an inlet and an outlet, carried in the at least one compartment of the housing such that the inlet is in fluid communication with at least one outlet of the cartridge and the outlet is open to the environment.

68. The portable breath condensate collection apparatus of claim 67, wherein the at least one compartment includes a compartment having a first section and a second section, wherein the cartridge is carried in the first compartment section and the condensing chamber is carried in the second compartment section.

69. The portable breath condensate collection apparatus of claim 67, wherein the at least one compartment includes at least a first compartment and a second compartment, wherein the cartridge is carried in the first compartment and the condensing chamber is carried in the second compartment.

70. The portable breath condensate collection apparatus of claim 67, wherein the cartridge includes a valve assembly for alternately permitting or preventing the flow of fluids through the cartridge and into the condensing chamber.

71. The portable breath condensate collection apparatus of claim 70, further comprising a control system, carried by and generally enclosed in the housing, for the valve assembly.

72. The portable breath condensate collection apparatus of claim 71, wherein the control system is adapted to remain in the housing for repeated reuse while the cartridge and the condensing chamber are removed.

73. The portable breath condensate collection apparatus of claim 67, further comprising an analyzer, carried by and generally enclosed in the housing, adapted to provide information regarding the content of breath condensate received therein, and a conduit disposed in sealed fluid communication between the condensing chamber and the analyzer, adapted to guide breathe condensate from the condensing chamber to the analyzer.

74. The portable breath condensate collection apparatus of claim 73, wherein the condensing chamber further includes a piston and a handle, wherein the piston is slidably disposed in the interior of the condensing chamber in snug contact with the inside of the condensing chamber and wherein the handle extends from the first end of the condensing chamber so as to permit the piston to be moved within the central chamber.

75. The portable breath condensate collection apparatus of claim 74, wherein the piston is operable to force breath condensate collected in the condensing chamber to the conduit leading to the analyzer.

76. A breath condensate collection apparatus, comprising:

a housing;

a condensing chamber, carried by the housing;

an inlet, carried by the housing, that receives exhaled breath from a mammalian subject;

a conduit disposed in sealed fluid communication between the inlet and the condensing chamber;

a gas flow measurement device, disposed in the conduit, that measures the flow of gas through the conduit; and

a control system, coupled to the gas flow measurement device, that determines when a predetermined volume of gas has passed through the conduit.

77. The breath condensate collection apparatus of claim 76, wherein the conduit, the gas flow measurement device and the control system are carried by the housing.

78. The breath condensate collection apparatus of claim 77, further comprising a signaling device that generates a user-identifiable indication that the predetermined volume of gas has passed through the conduit.

79. The breath condensate collection apparatus of claim 78, wherein the gas flow measurement device is a gas flow transducer and the control system includes a microcontroller that is electrically connected to the gas flow transducer.

80. The breath condensate collection apparatus of claim 78, wherein the signaling device includes a speaker that generates a user-audible signal.

81. The breath condensate collection apparatus of claim 80, wherein the user-audible signal changes, as a mammalian subject breathes through the apparatus, to provide an indication of progress toward reaching the predetermined volume of gas.

82. The breath condensate collection apparatus of claim 78, wherein the signaling device includes at least one user-visible light.

83. The breath condensate collection apparatus of claim 82, wherein the at least one user-visible light includes a plurality of user-visible lights that light sequentially, as a mammalian subject breathes through the apparatus, to provide an indication of progress toward reaching the predetermined volume of gas.

84. A breath condensate collection apparatus for separating the expired airway phase of breath exhaled by a mammalian subject from the alveolar phase of the exhaled breath, the apparatus comprising:

(a) a housing;

(b) a cartridge assembly including;

a breathing port,

at least two fluid outlets,

a valve assembly adjustable between at least two states, the at least two states including a first state wherein gas received at the breathing port is diverted to a first of the at least two fluid outlets, and a second state wherein gas received at the breathing port is diverted to a second of the at least two fluid outlets,

a monitoring system arranged to monitor at least one characteristic of gas passing through the separation apparatus, the characteristic generally capable of distinguishing the expired airway phase of an exhaled breath from a mammalian subject from the alveolar phase of the exhaled breath, and

an actuator device, coupled to the monitoring system and the valve assembly, that adjusts the valve assembly state on the basis of the state of the monitored characteristic;

(c) a condensing chamber, having an inlet and an outlet, carried by the housing such that the inlet is in fluid communication with at least one outlet of the cartridge assembly and the outlet is open to the environment; and

(d) a built-in refrigeration system, carried by the housing.

85. The breath condensate collection apparatus of claim 84, wherein the housing includes at least one compartment adapted to receive and generally enclose the cartridge assembly and the condensing chamber in fluid communication with one another.

86. The breath condensate collection apparatus of claim 84, wherein the condensing chamber is adapted to be removed from the housing after use and replaced by a previously-unused condensing chamber.

87. The breath condensate collection apparatus of claim 84, wherein the cartridge assembly is adapted to be removed from the housing after use and replaced by an unused cartridge assembly.

88. The breath condensate collection apparatus of claim 84, wherein the condensing chamber has double side walls and first and second opposing ends, and wherein the double side walls include an inner side wall and an outer side wall in spaced relationship to one another.

89. The breath condensate collection apparatus of claim 84, wherein the built-in refrigeration system includes a compressor, an expansion valve, an evaporator pipe arranged to cool the condensing chamber, and a condenser pipe arranged to dissipate heat away from the condensing chamber.

90. The breath condensate collection apparatus of claim 84, further comprising:

a conduit disposed in sealed fluid communication between the valve assembly and the condensing chamber;

a gas flow measurement device, disposed in the conduit, that measures the flow of gas through the conduit; and

a control system, coupled to the gas flow measurement device, that determines when a predetermined volume of gas has passed through the conduit.