Bioenergetic profiling of circulating blood cells and systems, devices, and methods relating thereto

Abstract

The invention relates generally to systems and methods of bioenergetic profiling, uses thereof, and systems and devices relating thereto. In particular, methods of the invention are useful in assessing wellness, particularly in elderly subjects. Described are systems and methods of assessing likelihood of subject morbidity, life expectancy, positive clinical outcome, responsiveness to treatment, and certain disease states as well as of selecting treatment strategy, improving outcome to treatment strategy, and treating subjects with low bioenergetic profiles. Also described are devices and systems for measuring respiratory capacity.

1 . A method of assessing the morbidity or mortality of a subject, the method comprising the steps of:
 (a) measuring the respiratory capacity in cells isolated from a blood sample obtained from a subject, and   (b) indicating that the subject has a decreased likelihood of morbidity or death if a relatively high respiratory capacity is measured in the isolated cells compared to a reference population, and that the subject has an increased likelihood of morbidity or diminished life expectancy if a relatively low respiratory capacity is measured in the isolated cells compared to the reference population.   
     
     
         2 . A method of assessing likelihood of a positive clinical outcome for a subject, the method comprising the steps of:
 (a) measuring the respiratory capacity in cells isolated from a blood sample obtained from a subject, and   (b) indicating that the subject has an increased likelihood of a positive clinical outcome if a relatively high respiratory capacity is measured in the isolated cells compared to a reference population, and that the subject has a decreased likelihood of a positive clinical outcome if a relatively low respiratory capacity is measured in the isolated cells compared to the reference population.   
     
     
         3 . A method of selecting treatment strategy for a subject, the method comprising the steps of:
 (a) measuring the respiratory capacity in cells isolated from a blood sample obtained from a subject, and   (b) selecting an aggressive treatment strategy for the subject if a relatively high respiratory capacity is measured in the isolated cells compared to a reference population, and selecting a non-aggressive treatment strategy for the subject if a relatively low respiratory capacity is measured in the isolated cells compared to the reference population.   
     
     
         4 . The method of  claim 1 , wherein the isolated cells comprise isolated peripheral blood mononuclear cells. 
     
     
         5 . The method of  claim 1 , wherein the isolated cells comprise isolated monocytes, isolated lymphocytes, or isolated platelets. 
     
     
         6 . The method of  claim 1 , wherein the respiratory capacity is measured by measuring oxygen consumption rate of the isolated cells. 
     
     
         7 . The method of  claim 6 , wherein oxygen consumption rate is measured by determining basal oxygen consumption rate (Basal OCR) and maximal oxygen consumption rate (Max OCR). 
     
     
         8 . The method of  claim 6 , wherein oxygen consumption rate is measured by determining spare respiratory capacity (SRC) or respiratory control ratio (RCR). 
     
     
         9 . The method of  claim 1 , wherein the subject is human of at least 50 years of age. 
     
     
         10 . The method of  claim 1 , wherein the subject is a human having risk factors for or exhibiting clinical signs of morbidity. 
     
     
         11 . The method of  claim 1 , wherein the subject is a human who has exhibited clinical signs of a cardiac event or coronary heart disease. 
     
     
         12 . The method of  claim 1 , wherein the subject is a human who has cancer. 
     
     
         13 . The method of  claim 1 , wherein morbidity comprises at least one of increased frailty, cognitive impairment, or risk factors for cognitive impairment. 
     
     
         14 . The method of  claim 2 , wherein the positive clinical outcome comprises at least one of responsiveness to treatment with nutraceuticals, benefit from a program of diet and exercise, responsiveness to physical rehabilitation, responsiveness to chemotherapy treatment, or improved recovery in cardiac rehabilitation or intensive care hospitalization treatment. 
     
     
         15 . The method of  claim 2 , wherein the negative clinical outcome comprises at least one of lack of responsiveness to treatment with nutraceuticals, lack of benefit from a program of diet and exercise, lack of responsiveness to physical rehabilitation, lack of responsiveness to chemotherapy treatment, or poor recovery in cardiac rehabilitation or intensive care hospitalization treatment. 
     
     
         16 . The method of  claim 3 , wherein an aggressive treatment strategy comprises surgery, drug or nutraceutical administration, physical rehabilitation, or change in diet or exercise regimen. 
     
     
         17 . The method of  claim 3 , wherein a non-aggressive treatment strategy comprises patient monitoring or palliative care. 
     
     
         18 . A method of treating a subject, the method comprising the steps of:
 (a) measuring the respiratory capacity in cells isolated from a blood sample obtained from the subject; and   (b) administering an aggressive treatment to the subject if a high respiratory capacity compared to a reference population is measured in the isolated cells.   
     
     
         19 . A method of treating a subject, the method comprising the steps of:
 (a) measuring the respiratory capacity in cells isolated from a blood sample obtained from the subject, and   (b) administering a non-aggressive treatment to the subject if a low respiratory capacity compared to a reference population is measured in the isolated cells.   
     
     
         20 . The method of  claim 2 , wherein the isolated cells comprise isolated peripheral blood mononuclear cells. 
     
     
         21 . The method of  claim 2 , wherein the isolated cells comprise isolated monocytes, isolated lymphocytes, or isolated platelets. 
     
     
         22 . The method of  claim 2 , wherein the respiratory capacity is measured by measuring oxygen consumption rate of the isolated cells. 
     
     
         23 . The method of  claim 22 , wherein oxygen consumption rate is measured by determining basal oxygen consumption rate (Basal OCR) and maximal oxygen consumption rate (Max OCR). 
     
     
         24 . The method of  claim 22 , wherein oxygen consumption rate is measured by determining spare respiratory capacity (SRC) or respiratory control ratio (RCR). 
     
     
         25 . The method of  claim 2 , wherein the subject is human of at least 50 years of age. 
     
     
         26 . The method of  claim 2 , wherein the subject is a human having risk factors for or exhibiting clinical signs of morbidity. 
     
     
         27 . The method of  claim 2 , wherein the subject is a human who has exhibited clinical signs of a cardiac event or coronary heart disease. 
     
     
         28 . The method of  claim 2 , wherein the subject is a human who has cancer. 
     
     
         29 . The method of  claim 3 , wherein the isolated cells comprise isolated peripheral blood mononuclear cells. 
     
     
         30 . The method of  claim 3 , wherein the isolated cells comprise isolated monocytes, isolated lymphocytes, or isolated platelets. 
     
     
         31 . The method of  claim 3 , wherein the respiratory capacity is measured by measuring oxygen consumption rate of the isolated cells. 
     
     
         32 . The method of  claim 31 , wherein oxygen consumption rate is measured by determining basal oxygen consumption rate (Basal OCR) and maximal oxygen consumption rate (Max OCR). 
     
     
         33 . The method of  claim 31 , wherein oxygen consumption rate is measured by determining spare respiratory capacity (SRC) or respiratory control ratio (RCR). 
     
     
         34 . The method of  claim 3 , wherein the subject is human of at least 50 years of age. 
     
     
         35 . The method of  claim 3 , wherein the subject is a human having risk factors for or exhibiting clinical signs of morbidity. 
     
     
         36 . The method of  claim 3 , wherein the subject is a human who has exhibited clinical signs of a cardiac event or coronary heart disease. 
     
     
         37 . The method of  claim 3 , wherein the subject is a human who has cancer.