Diagnosis and treatment for respiratory tract diseases

Abstract

The invention provides methods and compositions for the diagnosis, prognosis and treatment of respiratory tract diseases. Specifically, the invention provides diagnosis, prognosis and treatment of respiratory infections using bitter and sweet taste signal transduction pathways. In one aspect, the invention relates to a method for treating a respiratory infection by administering a composition to the respiratory tract of a subject in an amount capable of activating bitter taste signaling and/or inhibiting sweet taste signaling. The composition comprises at least a bitter receptor agonist and, optionally, a pharmaceutically acceptable carrier for delivering the composition to the respiratory tract. In another aspect, the invention relates to a composition for treatment of a respiratory infection. Such composition comprises at least a bitter receptor agonist and, optionally, a pharmaceutically acceptable carrier for delivering the composition to the respiratory tract.

1 . A method for treating a respiratory infection in a subject, the method comprising:
 administering a composition to the respiratory tract of the subject, wherein the composition comprises an agent capable of activating a bitter taste signal pathway or inhibiting a sweet taste signal pathway in the subject, thereby treating the respiratory infection in the subject.   
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein said composition comprises at least one sweet taste receptor antagonist. 
     
     
         5 . The method of  claim 4 , wherein said at least one sweet taste receptor antagonist is selected from the group consisting of lactisole, a gymnemic acid, ziziphin and hodulcine. 
     
     
         6 . The method of  claim 1 , wherein said composition comprises a combination of at least one bitter taste receptor agonist and at least one sweet taste receptor antagonist. 
     
     
         7 . The method of  claim 1 , wherein said respiratory infection is chronic rhinosinusitis. 
     
     
         8 . The method of  claim 1 , wherein the delivery mode of said composition is selected from the group consisting of an inhalant, nasal sprays, nasal drops, nasal ointments, nasal washes, nasal packings, bronchial sprays, and combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the delivery form of said composition is selected from the group consisting of powders, crystalline substances, gels pastes, ointments, salves, creams, solutions, suspensions, partial liquids, liquid suspensions, sprays, nebulae, mists, atomized vapors, tinctures. 
     
     
         10 . The method of  claim 1 , wherein said composition is formulated for topical application. 
     
     
         11 . The method of  claim 1 , wherein said composition is applied by lavage. 
     
     
         12 . The method of  claim 1 , wherein said composition comprises an ionic strength in the range of 150-200 mEq/L. 
     
     
         13 . The method of  claim 1 , wherein said composition is applied to at least one sinus through endoscopically guided instillation. 
     
     
         14 . The method of  claim 1 , wherein said composition is applied to the respiratory tract. 
     
     
         15 . The method of  claim 1 , wherein said composition is administered to the respiratory tract by a device selected from the group consisting of a bulb, an inhaler, a canister, a sprayer, a nebulizer, a metered-dose sprayer, and a mask. 
     
     
         16 .- 17 . (canceled) 
     
     
         18 . A topical composition for treatment of an infection of the respiratory tract comprising a therapeutically effective amount of an active ingredient selected from the group consisting of 6-n-propylthiouracil (PROP), denatonium, absinthin, phenylthiocarbamide (PTC), a homoserine lactone, and sodium thiocyanate (NaSCN), and a pharmaceutically acceptable topical carrier. 
     
     
         19 . A composition as claimed in  claim 18 , further comprising a sweet taste receptor antagonist selected from the group consisting of lactisole, a gymnemic acid, ziziphin and hodulcine. 
     
     
         20 . (canceled) 
     
     
         21 . A method of determining susceptibility to a respiratory tract infection, comprising the steps of:
 tasting one or more control compounds;   tasting at least one bitter tasting compound at different concentration levels;   rating the intensity of a taste of the control and bitter tasting compounds; and   correlating the rated intensities with susceptibility to a respiratory tract infection.   
     
     
         22 .- 35 . (canceled) 
     
     
         36 . A method for determining a need for a surgical intervention to treat a respiratory infection associated disease or disorder in a subject, the method comprising: conducting a bitter taste test to determine whether said subject is a taster or a non-taster; and based on the determination of said subject being a taster or a non-taster, determining whether said subject is in need of said surgical intervention to treat said respiratory infection associated disease or disorder. 
     
     
         37 . A method for treating a respiratory infection associated disease or disorder in or for stimulating an innate antimicrobial response in the respiratory tract of a subject, the method comprising: administering to said subject a therapeutically effective amount of a taste receptor, type 2, member 38 (T2R38) agonist. 
     
     
         38 . The method of  claim 37 , wherein said agonist is selected from the group consisting of 6-n-propylthiouracil (PROP), denatonium, absinthin, phenylthiocarbamide (PTC), a homoserine lactone, and sodium thiocyanate (NaSCN), and a pharmaceutically acceptable topical carrier. 
     
     
         39 .- 40 . (canceled) 
     
     
         41 . The method of  claim 38  or, wherein said homoserine lactone is C4HSL, C6HSL, or C 12HSL. 
     
     
         42 .- 47 . (canceled)