Predicting mortality and detecting severe disease

• US 8,617,825 B2
• Filed: 07/08/2011
• Issued: 12/31/2013
• Est. Priority Date: 04/24/2006
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Snider, James V., Jacobson, Sven
• Primary Examiner(s): Cheu, Jacob
• Application Number:
  US13/179,173
• Publication Number:
  US 20110262941A1
• Time in Patent Office: 907 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2333/54 Interleukins [IL]
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/12 Pulmonary diseases
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

Measurement of circulating ST2 and/or IL-33 concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, and the detection of severe disease.

Claims

1. A method of evaluating the efficacy of a treatment of Chronic Obstructive Pulmonary Disorder (COPD), pulmonary embolism, emphysema, lymphoma, or pericarditis in a subject having COPD, pulmonary embolism, emphysema, lymphoma, or pericarditis, the method comprising:

selecting a subject having COPD, pulmonary embolism, emphysema, lymphoma, or pericarditis;

determining a level of soluble ST2 in a biological sample from the selected subject having COPD, pulmonary embolism, emphysema, lymphoma, or pericarditis at a first time point, wherein determining a level of soluble ST2 comprises contacting the biological sample with an antibody that specifically binds to soluble ST2;

identifying a subject that has an elevated level of soluble ST2 at the first time point compared to a reference level of soluble ST2;

administering a treatment to the identified subject;

determining a level of soluble ST2 in a biological sample from the identified subject at second time point following the administration of the treatment;

comparing the level of soluble ST2 in the biological sample at the second time point to the level of soluble ST2 in the biological sample at the first time point; and

identifying the administered treatment as being effective when there is a decrease in the level of soluble ST2 at the second time point compared to the level of soluble ST2 at the first time point.

2. The method of claim 1, wherein the reference level is a threshold level.

3. The method of claim 1, wherein the reference level is a level of soluble ST2 present in a subject who has no disease or no acute disease.

4. The method of claim 1, wherein at least two days pass between the first time point and the second time point.

5. The method of claim 1, wherein the biological samples comprise serum, blood, or plasma.

6. The method of claim 1, wherein the treatment comprises one or more doses or rounds of treatment.

7. The method of claim 1, wherein the treatment includes hospitalization of the identified subject.

8. The method of claim 7, further comprising:

selecting an identified subject having a decrease in the level of soluble ST2 at the second time point compared to the level of soluble ST2 at the first time point; and

discharging the selected subject from the hospital.

9. The method of claim 1, wherein the treatment is an outpatient treatment.

10. The method of claim 9, further comprising:

selecting an identified subject having a decrease in the level of soluble ST2 at the second time point compared to the level of soluble ST2 at the first time point; and

increasing the time interval between outpatient visits for the selected subject.

11. The method of claim 1, further comprising:

determining a level of one or more adjunct biomarkers selected from the group consisting of;

N-terminal (NT)-pro-brain natriuretic peptide (BNP), proBNP, BNP, NT-pro-atrial natriuretic peptide (ANP), proANP, ANP, cardiac troponin I, cardiac troponin T, D-dimers, C-reactive protein, interleukin-6, albumin, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, bacterial endotoxin, and blood urea nitrogen in a biological sample from the selected subject at the first time point;

determining a level of the one or more adjunct biomarkers in a biological sample from the identified subject at the second time point;

comparing the level of the one or more adjunct biomarkers at the second time point to the level of the one or more adjunct biomarkers at the first time point; and

further identifying the administered treatment as being effective when there is a decrease in the level of the one or more adjunct biomarkers at the second time point compared to the level of the one or more adjunct biomarkers at the first time point.

12. The method of claim 11, wherein the selected subject has pericarditis and the one or more adjunct biomarkers are selected from the group consisting of:

cardiac troponin I, BNP, ANP, NT-proBNP, and proBNP.

13. The method of claim 11, wherein the selected subject has pulmonary embolism and the one or more adjunct biomarkers include D-dimers.

14. The method of claim 1, wherein the selected subject has COPD.

15. The method of claim 1, wherein the selected subject has pulmonary embolism.

16. The method of claim 1, wherein the selected subject has emphysema.

17. The method of claim 1, wherein the selected subject has lymphoma.

18. The method of claim 1, wherein the selected subject has pericarditis.