Methods for Categorizing and Treating Subjects at Risk for Pulmonary Exacerbation and Disease Progression

Abstract

The present invention is related to novel methods for categorizing and treating a population of subjects that are at risk for increased pulmonary exacerbation and disease progression.

What is claimed: 
     
         1 . A method for categorizing a subject at risk for increased pulmonary exacerbation disease progression wherein the subject has experienced a pulmonary exacerbation, the method comprising
 a. obtaining a biological sample from the subject;   b. detecting the expression level of one or more genes selected from the group consisting of TLR2, ADAM2, PLXND1, CD163, CD36, CD64, CSPG2, IL32, HPSE, HCA112 and combinations thereof;   c. comparing the expression level of the one or more genes from the subject with gene expression profiles of the same genes known to correlate with increased pulmonary exacerbation disease progression; and   d. categorizing the subject as at increased risk for increased pulmonary exacerbation disease progression when the subject's gene expression profile correlates to the gene expression profile for increased pulmonary exacerbation disease progression.   
     
     
         2 . The method of  claim 1 , wherein the subject has been diagnosed as having a disease selected from the group consisting of cystic fibrosis, asthma, chronic pulmonary obstructive disease, emphysema, interstitial lung disease, bronchitis, acute respiratory distress syndrome, and pneumonia. 
     
     
         3 . The method of  claim 1 , wherein the subject has been diagnosed as having cystic fibrosis. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is whole blood, Peripheral Blood Mononuclear Cells (PBMCs), leuokocytes, monocytes, lymphocytes, basophils, or eosinophils. 
     
     
         5 . The method of  claim 1 , wherein the biological sample is whole blood. 
     
     
         6 . The method of  claim 1 , wherein the expression level of the one or more genes is detected by quantitative PCR or flow cytometery. 
     
     
         7 . The method of  claim 1 , wherein the expression level of each of the following genes TLR2, ADAM2, PLXND1, CD163, CD36, CD64, CSPG2, IL32, HPSE, and HCA112 is detected and compared. 
     
     
         8 . The method of  claim 1 , wherein a subject identified as having an increased risk for pulmonary exacerbation disease progression will have an increased risk of morbidity. 
     
     
         9 . The method of  claim 1 , wherein a subject identified as having an increased risk for pulmonary exacerbation disease progression will have an increased risk of mortality. 
     
     
         10 . The method of  claim 1 , wherein a subject identified as having an increased risk for pulmonary exacerbation disease progression will have an increased risk for exacerbation recurrence. 
     
     
         11 . The method of  claim 1 , wherein a subject identified as having an increased risk for pulmonary exacerbation disease progression will have a shorter interval of exacerbation free time. 
     
     
         12 . The method of  claim 1 , further comprising measuring the subject's forced expiratory volume (FEV 1 ) and/or C-reactive protein (CRP) levels. 
     
     
         13 . A method to treat a subject at risk for increased pulmonary exacerbation wherein the subject has experienced a pulmonary exacerbation, the method comprising
 a. obtaining a biological sample from the subject;   b. detecting the expression level of one or more genes selected from the group consisting of TLR2, ADAM2, PLXND1, CD163, CD36, CD64, CSPG2, IL32, HPSE, HCA112 and combinations thereof;   c. comparing the expression level of the one or more genes from the subject with gene expression profiles of the same genes known to correlate with increased pulmonary exacerbation, wherein certain expression profiles identify the subject as at increased risk for increased pulmonary exacerbation; and   d. treating the subject aggressively if the subject is at risk for increased pulmonary exacerbation.   
     
     
         14 . The method of  claim 13 , wherein the subject has been diagnosed as having a disease selected from the group consisting of cystic fibrosis, asthma, chronic pulmonary obstructive disease, emphysema, interstitial lung disease, bronchitis, acute respiratory distress syndrome, and pneumonia. 
     
     
         15 . The method of  claim 13 , wherein the subject has been diagnosed as having cystic fibrosis. 
     
     
         16 . The method of  claim 13 , wherein the biological sample is whole blood, Peripheral Blood Mononuclear Cells (PBMCs), leuokocytes, monocytes, lymphocytes, basophils, or eosinophils. 
     
     
         17 . The method of  claim 13 , wherein the biological sample is whole blood. 
     
     
         18 . The method of  claim 13 , wherein the expression level of the one or more genes is detected by quantitative PCR or flow cytometery. 
     
     
         19 . The method of  claim 13 , wherein the expression level of each of the following genes TLR2, ADAM2, PLXND1, CD163, CD36, CD64, CSPG2, IL32, HPSE, and HCA112 is detected and compared. 
     
     
         20 . The method of  claim 13 , wherein the subject identified as having an increased risk for pulmonary exacerbation will have an increased risk of morbidity, mortality, and/or an increased risk for exacerbation recurrence.