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 . A method for alleviating the symptoms associated with an asthma attack, said method comprising the step of contacting the airways of an asthmatic patient with a composition comprising an agent selected from the group consisting of albuterol, levalbuterol HCl, ipratroprium bromide and budesonide in a pharmaceutically acceptable basic solution.  
   
   
       2 . The method of  claim 1  wherein the pH of the basic solution ranges from about 7.4 to about 9.5.  
   
   
       3 . A kit for treating asthma, said kit comprising 
 a conventional agent selected from the group consisting of albuterol, levalbuterol HCl, ipratroprium bromide and budesonide; and    a buffered diluent having a pH greater than 7.4.    
   
   
       4 . The kit of  claim 3  further comprising glutamine.  
   
   
       5 . The kit of  claim 3  wherein the pH of the buffered diluent ranges from about 7.5 to about 9.0.  
   
   
       6 . A method for enhancing the therapeutic efficacy of conventional asthmatic agents, said method comprising contacting the airways of a patient with a composition that reduces the proton/hydronium concentration in said airways either simultaneously or prior to administering the conventional asthmatic agent.  
   
   
       7 . The method of  claim 6  wherein the conventional asthmatic agent is selected from the group consisting of albuterol, levalbuterol HCl, and ipratroprium bromide.  
   
   
       8 . The method of  claim 7  wherein said composition comprises a corticosteroid.  
   
   
       9 . The method of  claim 8  wherein said corticosteroid is selected from the group consisting of hydrocortisone or dexamethasone and budesonide.  
   
   
       10 . The method of  claim 7  wherein said composition comprises an inhibitor of V ATP'ase or a stimulant of glutaminase.  
   
   
       11 . The method of  claim 7  wherein said composition comprises a basic solution.  
   
   
       12 . The method of  claim 7  wherein said composition comprises glutamine.  
   
   
       13 . A method of treating asthma, said method comprising the step of administering to a patient a compound that inhibits aldehyde dehydrogenase.  
   
   
       14 . The method of  claim 13  wherein the aldehyde dehydrogenase inhibitor is disulfiram.  
   
   
       15 . The method of  claim 14  wherein the compound is administered by nebulization.  
   
   
       16 . The method of  claim 14  wherein the compound is administered systemically.  
   
   
       17 . A method of treating asthma, said method comprising the step of administering to a patient an antifungal agent.  
   
   
       18 . The method of  claim 17  wherein the antifungal agent is fluconazole or disulfiram.  
   
   
       19 . The method of  claim 18  wherein the compound is administered by nebulization.  
   
   
       20 . The method of  claim 18  wherein the compound is administered systemically.  
   
   
       21 . A method of treating asthma said method comprising the step of administering to a patient a compound selected from the group consisting of CuCl, Cu/Zn SOD, glutathione peroxidase, glutathione-dependent formaldehyde dehydrogenase or gamma glutamyl transpeptidase.  
   
   
       22 . The method of  claim 21  wherein the compound is administered by nebulization.  
   
   
       23 . The method of  claim 21  wherein the compound is administered systemically.  
   
   
       24 . A composition comprising 
 a conventional agent selected from the group consisting of albuterol, levalbuterol HCl, ipratroprium bromide and budesonide; and glutamine.    
   
   
       25 . The composition of  claim 24  further comprising a buffer having a pH greater than 7.4.  
   
   
       26 . The composition of  claim 24  further comprising a compound selected from the group consisting of CuCl, Cu/Zn SOD, glutathione peroxidase, glutathione-dependent formaldehyde dehydrogenase or gamma glutamyl transpeptidase.  
   
   
       27 . The composition of  claim 24  further comprising a corticosteroid.  
   
   
       28 . A method for treating asthma prophylactically, said method comprising the step of scrubbing protons present in the air through the use of environmental filters.  
   
   
       29 . A method for treating asthma, said method comprising the step of administering a nebulized formulation comprising an antibody to gamma interferon.  
   
   
       30 . The method of  claim 29  wherein the antibody in a monoclonal antibody.  
   
   
       31 . A method for treating microbial infection of the airways of a patient, said method comprising the steps of administering a composition that lowers the pH of the airways to a range of about 6.0 to about 6.9.  
   
   
       32 . The method of  claim 31  wherein the microbial infection is a gram negative or mycobacterial infection.  
   
   
       33 . The method of  claim 32  wherein the composition comprises a proton donor.  
   
   
       34 . The method of  claim 33  wherein the proton donor is selected from the group consisting of acetic acid, phosphoric acid and hydrochloric acid.  
   
   
       35 . The method of  claim 32  wherein the composition comprises an S-nitrosothiols.  
   
   
       36 . The method of  claim 32  wherein the composition comprises Diazo-5-oxo-L-norleucine.  
   
   
       37 . A method for treating a viral infection of the airways of a patient, said method comprising the steps of administering a composition that lowers the pH of the airways to a range of about 6.0 to about 6.9.  
   
   
       38 . The method of  claim 37  wherein the composition comprises a proton donor.  
   
   
       39 . The method of  claim 38  wherein the proton donor is selected from the group consisting of acetic acid, phosphoric acid and hydrochloric acid.  
   
   
       40 . The method of  claim 37  wherein the composition comprises an S-nitrosothiols.  
   
   
       41 . The method of  claim 37  wherein the composition comprises Diazo-5-oxo-L-norleucine.