Airway Alkalinization as Therapy for Airway Diseases

Abstract

The present invention relates to a method of treating asthma by raising the pH of the airways of an individual. The effect can be mediated directly by administering a pharmaceutically acceptable basic solution or alternatively, the effect can be mediated by enhancing the activity of glutaminase.

1 - 41 . (canceled)  
   
   
       42 . A method for therapeutically treating respiratory disease associated with airway acidification comprising alkalinizing the airways of the patient by exposing the airways to an alkaline aerosol.  
   
   
       43 . The method of  claim 42  further comprising: 
 identifying the pH, pKa, buffer capacity and ionic strength best suited for treatment of different, specified levels of acidity in the airways; and    combining at least one base, at least one conjugate acid and at least one salt to produce a separate alkaline aerosol suitable for treatment of each specified level of acidity.    
   
   
       44 . The method of  claim 43  wherein the salt is sodium chloride.  
   
   
       45 . The method of  claim 43  wherein an individualized alkaline aerosol is produced for each patient based on results of non-invasive measurements of airway acidity, pH, and/or redox chemistry in that patient using exhaled breath condensate assays.  
   
   
       46 . The method of  claim 42  wherein the alkaline aerosol includes ammonia (NH3) and conjugate acids of NH3.  
   
   
       47 . The method of  claim 46  wherein the conjugate acid is at least one selected from the group consisting of ammonium acetate, ammonium chloride and ammonium bicarbonate.  
   
   
       48 . The method of  claim 43  wherein the base is at least one selected from the group consisting of glycine (aminoacetic acid), pKa2=9.78), bicine (N,N-Bis(2-hydroxyethyl)glycine (pKa=8.46), tricene (N-[tris(hydroxymethyl)methyl] glycine pKa=8.26), CAPS (3-(Cyclohexamino)-1propanesulphonic acid (10.51), CAPSO (3-(Cyelohexamino)-2-30 hydroxypropanesulphonic acid (pKa=9.71), 2-(Cyclohexamino)-ethenesulphonic acid (pKa=9.41).  
   
   
       49 . The method of  claim 43  wherein the salt is at least one selected from the group consisting of glycine, phosphate buffered saline, bicarbonate or soda ash.  
   
   
       50 . The method of  claim 42  wherein the respiratory disease involves some degree of asthma symptomatology.  
   
   
       51 . The method of  claim 42  wherein the respiratory disease is a viral respiratory tract infection.  
   
   
       52 . The method of  claim 51  wherein the viral respiratory disease is a common cold virus.  
   
   
       53 . The method of  claim 52  wherein the common cold virus is rhinovirus.  
   
   
       54 . The method of  claim 42  wherein the alkalinizing aerosol is in the form of an inhalable aerosol.  
   
   
       55 . The method of  claim 54  wherein the alkalinizing aerosol is delivered to the airways by means of nebulization.  
   
   
       56 . The method of  claim 42  wherein the respiratory disease is acute.  
   
   
       57 . The method of  claim 42  wherein the airway disease is at least one selected from the group consisting of asthma, asthma exacerbations, smooth muscle constriction, airway inflammation, overproduction of mucus, human rhinovirus infection, common cold, allergic rhinitis, tuberculosis, cough, wheeze and airtrapping.