Methods and compositions for risk prediction, diagnosis, prognosis, and treatment of pulmonary disorders

Abstract

The invention provides diagnostic and therapeutic targets for pulmonary disease, in particular, fibrotic lung disease. The inventors have found that a genetic variant MUC5B gene is associated with increased expression of the gene, increased risk of developing a pulmonary disease, and an improved prognosis and survival among those developing the pulmonary disease.

1 - 86 . (canceled) 
     
     
         87 . A method of diagnosing a pulmonary disease in a human subject in need thereof, said method comprising:
 obtaining a biological sample from a human subject;   (ii) detecting whether a genetic variant MUC5B gene sequence is present in said biological sample by contacting said sample with a labeled nucleic acid probe capable of hybridizing to a T allele at the rs35705950 single nucleotide polymorphism (SNP) of said genetic variant MUC5B gene sequence, or its complement;   (iii) diagnosing said human subject with a pulmonary disease when a detectable complex is formed by hybridization of said labeled nucleic acid probe to said T allele at the rs35705950 single nucleotide polymorphism (SNP), or its complement.   
     
     
         88 . The method of  claim 87 , further comprising, after said diagnosing of step (iii) administering to said human subject an effective amount of a pulmonary disease treatment. 
     
     
         89 . The method of  claim 88 , comprising administering to said human subject an effective amount of an anti-inflammatory agent, a mucolytic agent, a mucoregulatory agent, a mucokinetic agent or an expectorant. 
     
     
         90 . The method of  claim 89 , wherein said mucolytic agent is N-acetylcysteine, N-acystelyn, erdoseine, dornase alfa, thymosin beta4, dextran, pulmozyme, heparin, or bronchiotol. 
     
     
         91 . The method of  claim 89 , wherein said mucoregulatory agent is carbocysteine, an anticholoinergic agent, a glucocorticoid or a macrolide antibiotic. 
     
     
         92 . The method of  claim 89 , wherein said mucokinetic agent is a bronchodilator, a surfactant or ambroxol. 
     
     
         93 . The method of  claim 89 , wherein said expectorant is hypertonic saline, guaifenesin, dornase/pulmozyme or bronchiotol. 
     
     
         94 . The method of  claim 88 , wherein said pulmonary disease is an interstitial lung disease. 
     
     
         95 . The method of  claim 94 , wherein said interstitial lung disease is a fibrotic interstitial lung disease. 
     
     
         96 . The method of  claim 95 , wherein said fibrotic interstitial lung disease is idiopathic pulmonary fibrosis or familial interstitial pneumonia. 
     
     
         97 . The method of  claim 88 , wherein said biological sample is a pulmonary tissue or a bodily fluid. 
     
     
         98 . The method of  claim 87 , wherein said labeled nucleic acid probe is a fluorescently labeled nucleic acid probe. 
     
     
         99 . The method of  claim 98 , wherein said fluorescently labeled nucleic acid probe has at least 10 nucleotides. 
     
     
         100 . The method of  claim 98 , wherein said fluorescently labeled nucleic acid probe comprises at least 10 contiguous nucleotides of the sequence of SEQ ID NO:24_spanning said SNP, or said complement thereof. 
     
     
         101 . The method of  claim 88 , wherein said human subject has a family history of idiopathic pulmonary fibrosis (IPF) or familial interstitial pneumonia (FIP).