NON-INVASIVE METHOD FOR DIAGNOSING THE SEVERITY OF HEART FAILURE, USE OF A BIOMARKER FOR DIAGNOSING DECOMPENSATED HEART FAILURE, COLLECTOR DEVICE FOR THE HEART FAILURE BIOMARKER FROM EXHALED BREATH AND A DIAGNOSIS KIT

• US 20120011918A1
• Filed: 07/16/2010
• Published: 01/19/2012
• Est. Priority Date: 07/16/2010
• Status: Active Grant

• Current Assignee: Fabiana Goulart Marcondes Braga, Fernando Bacal, Guilherme Lopes Batista, Ivano Gebhardt Rolf Gutz
• Original Assignee: Fundacao De Amparo A Pesquisa Do Estado De Sao Paulo, Universidade De Sã£O Paulo.
• Inventors: Bacal, Fernando, Braga, Fabiana Goulart Marcondes, Gutz, Ivano Gebhardt Rolf, Batista, Guilherme Lopes
• Granted Patent: US 8,747,325 B2
• Time in Patent Office: Days
• US Class Current: 73/23.35
• CPC Class Codes: A61B 5/082 Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath A61B5/083, A61B5/091 take precedence
• CPC Class Codes: A61B 5/091 Measuring volume of inspired or expired gases, e.g. to determine lung capacity
• 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 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant

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

1. A non-invasive method of diagnosing heart failure characterized by comprising:

(a) analysis of acetone in the exhaled air as a biomarker of heart failure wherein the detection and quantification of the acetone can be made by any suitable technique for direct analysis or after sample collection, which may be selected from a group comprising, but not limited to;

chromatography, mass spectrometry, infra-red or ultra-violet-visible spectrophotometry, gas sensors and electronic noses;

(b) indication of the severity of heart failure in accordance with the ranges of acetone in exhaled breath.

2. Non-invasive diagnosis method according to claim 1 characterized by comprising:

a) analysis of acetone in the exhaled air as a biomarker of heart failure wherein the detection and quantification of the acetone can be made by any suitable technique for direct analysis or after sample collection, which may be selected from a group comprising, but not limited to;

chromatography, mass spectrometry, infra-red or ultra-violet-visible spectrophotometry, gas sensors and electronic noses;

(b) indication of the severity of heart failure in accordance with the following ranges;

(b1) acetone concentration with a preferable upper limit of 0.85 mcg/L indicates that the patient does not have a heart failure condition;

(b2) acetone concentration with preferable lower and upper limits of 0.85 up to 2.6 mcg/L indicates compensated heart failure;

(b3) acetone concentration with a preferable lower limit of 2.6 mcg/L indicates decompensated heart failure (heart failure with congestion and/or heart failure with low output).

3. A non-invasive method of diagnosing heart failure characterized by comprising:

(a) means of collecting a sample of exhaled air in a device that extracts one or more biomarkers from gaseous phase to a liquid phase comprising pure water, organic substances with high acetone affinity, chemical reagents or mixtures of substances that increase the retention efficiency of the biomarker of interest.

(b) means of detecting and quantifying the acetone biomarker in the sample of the exhaled air wherein the analytical technique can be selected from a group comprising, but not limited to;

chromatography, mass spectrometry, infra-red or ultra-violet-visible spectrophotometry, gas sensors and electronic noses; and

(c) means of indicating the severity of heart failure in accordance with the ranges of acetone in exhaled breath.

4. Non-invasive diagnosis method according to claim 3 characterized by comprising:

(a) means of collecting a sample of exhaled air in a device that extracts one or more biomarkers from gaseous phase to a liquid phase comprising pure water, organic substances with high acetone affinity, chemical reagents or mixtures of substances that increase the retention efficiency of the biomarker of interest.

(b) means of detecting and quantificating the acetone biomarker in the sample of the exhaled air wherein the analytical technique can be selected from a group comprising, but not limited to;

chromatography, mass spectrometry, infra-red or ultra-violet-visible spectrophotometry, gas sensors and electronic noses; and

(c) means of indicating of the prognosis of the patient suffering from decompensated heart failure comprising the following ranges;

(c1) acetone concentration with a preferable upper limit of 0.85 mcg/L indicates that the patient does not have a heart failure condition;

(c2) acetone concentration with preferable lower and upper limits of 0.85 up to 2.6 mcg/L indicates compensated heart failure;

(c3) acetone concentration with a preferable lower limit of 2.6 mcg/L indicates decompensated heart failure (heart failure with congestion and/or heart failure with low output).

5. A non-invasive method of prognosticating heart failure characterized by comprising:

(a) collection of a sample of exhaled air in a device that extracts one or more biomarkers from gaseous phase to a liquid phase comprising pure water, organic substances with high acetone affinity, chemical reagents or mixtures of substances that increase the retention efficiency of the biomarker of interest.

(b) detection and quantifying of the acetone biomarker in the sample of the exhaled air wherein the analytical technique can be selected from a group comprising, but not limited to;

chromatography, mass spectrometry, infra-red or ultra-violet-visible spectrophotometry, gas sensors and electronic noses; and

(c) indication of the prognosis of the patient suffering from decompensated heart failure in accordance with the ranges of acetone in exhaled breath.

6. Method according to claim 5 characterized wherein the collection step (a) comprises a substance having affinity with said biomarker and same is preferably water.

7. Non-invasive diagnosis method according to claim 5 characterized wherein the collection step (a) comprises a substance having affinity with said biomarker and same is preferably water.

8. Non-invasive diagnosis method according to claim 5 characterized wherein the collection step (a) comprises a substance having affinity with said biomarker and same is a mixture of water and other compounds.

9. Non-invasive diagnosis method according to claim 5 characterized wherein the temperature in the collection step (a) is preferably between −

10 and 15°

C. preferably between −

10 and 0°

C.

10. Non-invasive diagnosis method according to claim 5 characterized wherein the collection step (a) is conducted preferably by the patient blowing air through the mouth, and with an air volume of preferably at least 7 liters.

11. Non-invasive diagnosis method according to claim 10 characterized wherein the collection step (a) preferably has a volume of air of at least 7 liters.

12. Non-invasive diagnosis method according to claim 10 characterized wherein the collection step (a) is capable of retaining at least 0.2 μ

g/L of acetone in the sample of exhaled air.

13. Method according to claim 5 characterized by comprising a filling and storage step of the sample of exhaled air collected between the steps (a) and (b), occurring at a temperature between −

90 and −

0°

C.

14. Method according to claim 13 characterized by comprising a storage step of the sample of exhaled air collected between steps (a) and (b), occurring at a temperature preferably between −

80 and −

20°

C.

15. A device for collecting exhaled air characterized by comprising:

means for capturing the exhaled air from the patient (1);

means for extracting and capturing (3) volatile compound(s) from the exhaled air of the patient especially a biomarker of interest;

means of diffusing the exhaled air (4) into means for capturing (5) a biomarker;

means for indirectly cooling (6) the capturing means (5);

means of insulating said device from the external conditions (7) and,

means for reading the total volume of exhaled air collected (8).

16. Device according to claim 15 characterized wherein the means of diffusing the exhaled air (4) are preferably constituted of porous material arranged to increase the contact surface between the volatile compounds contained in the air, especially the exposure of the biomarker and capturing means (5).

17. Device according to claim 15 characterized wherein the means for extracting and capturing said biomarker (5) has a high chemical affinity with acetone.

18. Device according to claim 15 characterized wherein the means of extracting and capturing said biomarker (5) comprises a fluid selected from the group water and other compounds.

19. Device according to claim 18 characterized wherein the means of extracting and capturing said biomarker (5) is preferably water.

20. Device according to claim 18 characterized wherein the means of extracting and capturing said biomarker (5) is preferably a mixture of water and 2,4-dinitrophenylhydrazine (DNPH).

21. Device according to claim 18 characterized wherein the fluid (5) occupies a preferred volume of 5 mL inside the collecting means (3) and behind the diffuser means (4) and a temperature lower than ambient temperature as a means of raising between 2 and 4 times Henry'"'"'s constant value.

22. A device for collecting exhaled air characterized by comprising:

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

a connector duct (2) between the element of contact with the patient and a collector element (3);

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;

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

an insulating element (7); and

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

23. Device according to claim 22 characterized wherein said diffuser element (4) is made of porous material arranged to increase the contact surface between the volatile compounds contained in the air.

24. Device according to claim 23 characterized wherein said diffuser element (4) is preferably sintered glass.

25. Device according to claim 22 characterized wherein said fluid element (5) is a substance having high chemical affinity with acetone selected from the group comprising water, organic compounds and a mixture thereof.

26. Device according to claim 25 characterized wherein the fluid (5) is preferably water.

27. Device according to claim 25 characterized wherein the fluid (5) is preferably water or a mixture of water and 2,4-dinitrophenylhydrazine (DNPH).

28. Device according to claim 25 characterized wherein the fluid (5) occupies a preferred 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.

29. Device according to claim 22 characterized by additionally comprising an air volume reader (8).

30. Use of acetone comprised wherein a biomarker is a means for diagnosing the severity of heart failure according to its concentration levels.

31. Use of acetone comprised wherein a biomarker is a means for prognosticating intrahospital mortality according to its concentration levels.

32. Non-invasive prognosis kit comprising the diagnosis of the severity of decompensated heart failure comprising:

a device for collecting exhaled breath air;

a fluid for extracting and capturing the biomarker kept cooled;

an insulating case for housing the sample containing biomarker and fluid after collection;

a biomarker standards kit in different concentrations as a means of calibrating the analytic equipment for guiding the diagnosis based on the analytic technique preferably involving gas chromatography and,

a manual as a means of indicating content ranges of the biomarker for diagnosing the severity of decompensated heart failure in view of the content of the biomarker detected.