Method for assaying lower respiratory tract infection or inflammation

Abstract

The present invention relates to a reliable method of prediction of lower respiratory tract infection or inflammation in humans, wherein the level of pancreatic stone protein/regenerating protein (PSP/reg) is determined in serum, and a high level is indicative of the development and the severity of the disease, allowing the classification of patients according to risk.

1 . A ex-vivo method of prognosis and/or diagnosis of infections of the airways or lungs in a patient comprising determining a level of pancreatic stone protein/regenerating protein (PSP/reg) in a body fluid sample from said patient, and making a prognosis and/or diagnosis of infections and/or inflammatory diseases of the airways or lungs in the patient, 
       and, optionally, treating said infections and/or inflammatory diseases. 
     
     
         2 . The method of  claim 1 , comprising:
 a) providing a body fluid sample from said patient;   b) determining the level of PSP/reg in said sample;   c) comparing the level of PSP/reg determined in step b) with a reference value;   wherein a higher level of PSP/reg determined in step b), compared to the reference value, is indicative of a severity of said infection and predictive of its outcome.   
     
     
         3 . The method of  claim 1 , wherein said body fluid sample is a serum sample or a plasma sample. 
     
     
         4 . The method of  claim 1 , wherein said patient is a human. 
     
     
         5 . The method of  claim 1 , wherein said PSP/reg protein has an amino acid sequence of SEQ ID NO:1 or SEQ ID NO: 2. 
     
     
         6 . The method of  claim 2 , wherein the reference value is obtained by determining the level of PSP/reg in a body fluid sample from a patient without infection. 
     
     
         7 . The method of  claim 2 , wherein the reference value is below 20 ng/ml. 
     
     
         8 . The method of  claim 1 , wherein the infection of the airways or lungs is selected from the group of low respiratory tract infections. 
     
     
         9 . The method of  claim 2 , wherein a level of PSP/reg equal or higher than the reference value is indicative of an infection of the airways and lungs in said patient. 
     
     
         10 . The method of  claim 1 , wherein a level of PSP/reg equal or higher than 150 ng/ml is indicative of disease severity and predictive of mortality in a ventilator-acquired pneumonia (VAP) patient. 
     
     
         11 . The method of  claim 1 , wherein a level of PSP/reg equal or higher than 25 ng/ml, is indicative of positive sputum microbiology in a COPD patient. 
     
     
         12 . The method of  claim 1 , wherein the level of PSP/reg in said body fluid sample is determined by Enzyme-linked immunosorbent assay (ELISA), Radioimmunoassay (RIA), Enzymoimmunoassay (EIA), mass spectrometry, or microarray analysis. 
     
     
         13 . The method of  claim 1 , wherein the level of PSP/reg is determined by a sandwich ELISA, wherein microtiter plates are coated with one type of antibody directed against PSP/reg, the plates are then blocked and the sample or standard is loaded, a second type of antibody against PSP/reg is applied, a third antibody detecting the particular type of the second antibody conjugated with a suitable label is then added, and the label used to quantify the amount of PSP/reg. 
     
     
         14 . The method of  claim 13 , wherein the label in the sandwich ELISA is an enzyme for chromogenic detection. 
     
     
         15 . A kit of parts for determining PSP/reg for diagnosis/prediction of infection of airways and lungs in a patient comprising apparatus, reagents and standard solutions of PSP/reg. 
     
     
         16 . The method of  claim 7 , wherein the reference value is 10 ng/ml. 
     
     
         17 . The method of  claim 8 , wherein the inflammatory disease of the airways or lungs is selected from the group of acute bronchitis, acute exacerbation of COPD, community or hospital-acquired or ventilator associated pneumonia and interstitial lung disease. 
     
     
         18 . The method of  claim 10 , wherein a level of PSP/reg is higher than 180 ng/ml, or higher than 200 ng/ml. 
     
     
         19 . The method of  claim 19 , wherein based on the level of PSP/reg determined, the patient is grouped with regard to risks regarding severity and outcome of the infection. 
     
     
         20 . The method of  claim 19 , wherein
 (i) ventilator-acquired pneumonia (VAP) patients are grouped as follows:
 PSP/reg level below or equal to 24 ng/ml: good chance of survival, 
 PSP/reg level higher than or equal to 150 ng/ml: high risk of mortality within a variable period between 1 day to 3 years; 
   (ii) chronic obstructive pulmonary disease (COPD) patients are grouped as follows:
 PSP/reg level below 18 ng/ml: low risk of mortality, 
 PSP/reg level above 30 ng/ml: high risk of mortality within a variable period between 1 day to 3 years.