IP Library Granted Patent US 8,747,325
Granted Patent B2
US 8,747,325 · App. 12/838,204 · Granted Jun 10, 2014

Non-invasive method for diagnosing the severity of heart failure by extracting and analyzing acetone concentrations in captured exhaled breath

Inventors: Fernando Bacal (São Paulo SP, BR); Fabiana Goulart Marcondes Braga (São José dos Campos SP, BR); Ivano Gebhardt Rolf Gutz (São Paulo SP, BR); Guilherme Lopes Batista (São Paulo SP, BR)
Assignees: Fundacao de Amparo A Pesquisa Do Estado De Sao Paulo (FAPESP); Universidade De Sao Paulo (USP)
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Quick Facts
Patent No.
US 8,747,325
App. No.
12/838,204
Granted
Jun 10, 2014
Kind
B2
Abstract

The invention application presents a fast, efficient, reproductive alternative of a non-invasive method for diagnosing the severity of heart failure based on a specific biomarker. An additional object of the present invention is a collector device for the biomarker from exhaled breath that is portable, simple, low cost and does not need to run on electric power. This invention advantageously permits the replacement of invasive diagnosis methods, favoring the patient's comfort in addition to the agility and speed of medical attention at hospitals, and may become a standard method for all suspected cases of circulatory disease and heart failure and, more specifically, decompensated heart failure.

Claims (59)

1. A non-invasive method of diagnosing heat failure, comprising:

(a) collecting a sample of exhaled air using a capture device comprising:

(i) means for capturing the exhaled air directly from a patient;

(ii) means for extracting and capturing volatile compound(s) from the captured exhaled air of the patient especially a biomarker of interest;

(iii) means of diffusing the captured exhaled air into means for capturing a biomarker;

(iv) means for indirectly cooling the capturing means;

(v) means of insulating said capture device from external conditions; and,

(vi) means for reading total volume of exhaled air collected;

b) analyzing, using a processor, the sample of captured exhaled air for acetone as a biomarker of heart failure, wherein the detection and quantification of the acetone can be made by any suitable technique selected from the group consisting of chromatography, mass spectrometry, infra-red or ultra-violet spectrophotometry, gas sensors and electronic noses; and

c) indicating, using the processor, the severity of heart failure in accordance with the following ranges of acetone in the sample of exhaled air:

(i) acetone concentration with an upper limit of 0.85 mcg/L indicates that the patient does not have a heart failure condition;

(ii) acetone concentration with lower and upper limits of 0.85 mcg/L and 2.6 mcg/L indicates compensated heart failure; and

(iii) acetone concentration with a lower limit of 2.6 mcg/L indicates decompensated heart failure, characterized by heart failure with congestion and/or heart failure with low output.

2. A non-invasive method of prognosticating heat failure, comprising:

(a) collecting a sample of exhaled air using a capture device comprising:

(i) means for capturing the exhaled air directly from a patient;

(ii) means for extracting and capturing volatile compound(s) from the captured exhaled air of the patient especially a biomarker of interest;

(iii) means of diffusing the captured exhaled air into means for capturing a biomarker;

(iv) means for indirectly cooling the capturing means;

(v) means of insulating said capture device from external conditions; and,

(vi) means for reading total volume of exhaled air collected;

b) analyzing, using a processor, the sample of captured exhaled air for acetone as a biomarker of heart failure, wherein the detection and quantification of the acetone can be made by any suitable technique selected from the group consisting of chromatography, mass spectrometry, infra-red or ultra-violet spectrophotometry, gas sensors and electronic noses; and

c) indicating, using the processor, the prognosis of the patient suffering from decompensated heart failure in accordance with the following ranges of acetone in the sample of exhaled air:

(i) acetone concentration with an upper limit of 0.85 mcg/L indicates that the patient does not have a heart failure condition;

(ii) acetone concentration with lower and upper limits of 0.85 mcg/L and 2.6 mcg/L indicates compensated heart failure; and

(iii) acetone concentration with a lower limit of 2.6 mcg/L indicates decompensated heart failure, characterized by heart failure with congestion and/or heart failure with low output.

3. The method according to claim 2 , wherein the collection step (a) is conducted at a temperature of between −10° C. and 15° C., or between −5° C. and 5° C.

4. The method according to claim 2 , wherein the collection step (a) is conducted by the patient blowing air through the mouth into the device, and with an air volume at least 7 liters.

5. The method according to claim 2 , wherein the collection step (a) method according is capable of retaining at least 0.2 μg/L of acetone in the sample of exhaled air.

6. The method according to claim 2 , further comprising a filling and storage step of the sample of exhaled air between steps (a) and (b), said filling and storage step occurring at a temperature between −90° C. and −0° C., or between −80° C. and −20° C.

7. The method according to claim 1 , wherein collection step (a) is conducted at a temperature of between −10° C. and 15° C., or between −5° C. and 5° C.

8. The method according to claim 1 , wherein the collection step (a) is conducted by a patient blowing air through the mouth into the device, and with an air volume of at least 7 liters.

9. The method according to claim 1 , further comprising a filling and storage step of the sample of exhaled air between steps (a) and (b), said filling and storage step occurring at a temperature between −90° C. and 0° C., or between −80° C. and −20° C.

10. The method according to claim 1 , wherein the device comprises:

(i) a sample-receiving element ( 1 ) arranged to conduct the patient's breath;

(ii) a connector duct ( 2 ) between the element of contact with the patient and a collector element ( 3 ), wherein said collector element ( 3 ) comprises a diffuser element ( 4 ) in its output cavity, said diffuser element being submersed in a fluid element ( 5 ), means for extracting and capturing the biomarker;

(iii) a cooling fluid element ( 6 ) indirectly contacting said fluid element ( 5 );

(iv) an insulating element ( 7 ); and

(v) an element for retaining the exhaled air set up to measure the total volume of exhaled air collected ( 9 ).

11. The method according to claim 10 , wherein said diffuser element ( 4 ) is made of porous material arranged to increase a contact surface between the volatile compounds contained in the air.

12. The method according to claim 10 , wherein said diffuser element ( 4 ) is preferably sintered glass or porous polymer.

13. The method according to claim 10 , wherein said fluid element ( 5 ) is a substance having high chemical affinity with acetone selected from the group consisting of water, organic compounds, and a mixture thereof.

14. The method according to claim 13 , wherein the fluid element ( 5 ) is water.

15. The method according to claim 13 , wherein the fluid element ( 5 ) is a mixture of water and 2,4-dinitrophenylhydrazine (DNPH).

16. The method according to claim 10 , wherein the fluid element ( 5 ) occupies a volume of 5 mL inside the collector element ( 3 ) and behind the diffuser element ( 4 ) and a temperature lower than ambient temperature as a means of rising between 2 and 4 times Henry's constant value.

17. The method according to claim 10 , wherein the device further comprises an air volume reader ( 8 ) or delimiter ( 8 ).

18. The method according to claim 2 , wherein the device comprises:

(i) a sample-receiving element ( 1 ) arranged to conduct the patient's breath;

(ii) a connector duct ( 2 ) between an element of contact with the patient and a collector element ( 3 ), wherein said collector element ( 3 ) comprises a diffuser element ( 4 ) in its output cavity, said diffuser element being submersed in a fluid element ( 5 ), means for extracting and capturing the biomarker;

(iii) a cooling fluid element ( 6 ) indirectly contacting said fluid element ( 5 );

(iv) an insulating element ( 7 ); and

(v) an element for retaining the exhaled air set up to measure the total volume of exhaled air collected ( 9 ).

19. The method according to claim 18 , wherein said diffuser element ( 4 ) is made of porous material arranged to increase a contact surface between the volatile compounds contained in the air.

20. The method according to claim 18 , wherein said diffuser element ( 4 ) is preferably sintered glass or porous polymer.

21. The method according to claim 18 , wherein said fluid element ( 5 ) is a substance having high chemical affinity with acetone selected from the group consisting of water, organic compounds, and a mixture thereof.

22. The method according to claim 21 , wherein the fluid element ( 5 ) is water.

23. The method according to claim 21 , wherein the fluid element ( 5 ) is a mixture of water and 2,4-dinitrophenylhydrazine (DNPH).

24. The method according to claim 18 , wherein the fluid element ( 5 ) occupies a volume of 5 mL inside the collector element ( 3 ) and behind the diffuser element ( 4 ) and a temperature lower than ambient temperature as a means of rising between 2 and 4 times Henry's constant value.

25. The method according to claim 18 , wherein the device further comprises an air volume reader ( 8 ) or delimiter ( 8 ).

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2017
From: FUNDACAO DE AMPARO A PESQUISA DO ESTADO DE SAO PAULO (FAPESP); UNIVERSIDADE DE SAO PAULO (USP)
To: BACAL, FERNANDO; BRAGA, FABIANA GOULART MARCONDES; GUTZ, IVANO GEBHARDT ROLF; BATISTA, GUILHERME LOPES
Reel/Frame 044333/0739 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 12, 2011
From: BACAL, FERNANDO; BRAGA, FABIANA GOULART MARCONDES; GUTZ, IVANO GEBHARDT ROLF; BATISTA, GUILHERME LOPES
To: FUNDACAO DE AMPARO A PESQUISA DO ESTADO DE SAO PAULO (FAPESP); UNIVERSIDADE DE SAO PAULO (USP)
Reel/Frame 026576/0039 →
Continuity (1)
Related Publication 20120011918A1 · Jan 19, 2012