Use of inhaled gaseous nitric oxide as a mucolytic agent or expectorant

Abstract

Methods and devices for treating excess mucus accumulation in mammals by administering gaseous inhaled nitric oxide or nitric oxide releasing compounds as a mucolytic agent or expectorant are provided. Delivery of gaseous nitric oxide can be made nasally or orally and is preferably substantially coincident with inhalation of the mammal or based on a synchronous parameter of the mammal's respiratory cycle. Varying therapeutic profiles may be used for the delivery of gaseous nitric oxide depending on the severity of the excess mucus accumulation. Parameters for the therapeutic profiles may include flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways.

1 - 32 . (canceled) 
     
     
         33 . A method of treating inflammatory airway disease, comprising:
 providing a pressurized source of nitric oxide containing gas; and   administering through inhalation a therapeutically effective amount of nitric oxide containing gas to a mammal exhibiting inflammatory airway disease, wherein the nitric oxide containing gas is administered substantially coincident with the inspiration of the mammal, resulting in the reduction of inflammation.   
     
     
         34 . The method of  claim 33 , wherein the inflammatory airway disease is chronic pulmonary disease. 
     
     
         35 . The method of  claim 33 , further comprising the step of regulating a flow rate of the nitric oxide containing gas depending on the mammal's respiratory tidal volume. 
     
     
         36 . The method of  claim 35 , wherein the concentration of nitric oxide gas in the mammal's airway ranges from about 160 ppm to about 220 ppm. 
     
     
         37 . The method of  claim 33 , wherein the administration of the nitric oxide containing gas is timed according to a synchronous parameter of the mammal's respiratory cycle. 
     
     
         38 . The method of  claim 37 , wherein the synchronous parameter is selected from a group consisting of rate of flow of gas directed toward the mammal's airway, pressure change at the initiation of a breath, the synchronous movement of the laryngeal, and the synchronous motion of the chest wall. 
     
     
         39 . The method of  claim 33 , wherein the therapeutically effective amount of nitric oxide containing gas is sufficient to reduce inflammation within thirty minutes. 
     
     
         40 . The method of  claim 33 , wherein the mammal is a horse. 
     
     
         41 . A method of treating inflammatory airway disease in a mammal's airway comprising:
 identifying a mammal exhibiting inflammatory airway disease;   determining the severity of the inflammatory airway disease in the mammal;   providing a source of nitric oxide containing gas; and   administering through inhalation the nitric oxide containing gas using a distinct therapeutic profile corresponding to the severity of the inflammatory airway disease in the mammal, resulting in the flow of non-viscous liquids and mucus reduction.   
     
     
         42 . The method of  claim 41 , wherein the inflammatory airway disease is chronic pulmonary disease. 
     
     
         43 . The method of  claim 41 , wherein the severity of the inflammatory airway disease is scored from 0 to 5, with 5 indicating a most severe condition. 
     
     
         44 . The method of  claim 41 , wherein the distinct therapeutic profile is selected from a pre-determined set of therapeutic profiles. 
     
     
         45 . The method of  claim 44 , wherein the distinct therapeutic profile comprises therapeutic parameters selected from a group consisting of flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways. 
     
     
         46 . A method of treating inflammatory airway disease in a mammal's airway comprising:
 administering through inhalation a therapeutically effective amount of NO-releasing compounds to a mammal exhibiting inflammatory airway disease in the mammal's airway, resulting in the reduction of inflammation.   
     
     
         47 . The method of  claim 46 , wherein the NO-releasing compounds is selected from a group consisting of S-nitrosothiols, S-nitroso-N-acetylpenicillamine, S-nitroso-L-cysteine, NONOates, nitroprusside, NO-ferredoxin, NOheme complex, and nitrosoguanidine. 
     
     
         48 . The method of  claim 46 , wherein the mammal is a horse. 
     
     
         49 . The method of  claim 46 , wherein the therapeutically effective amount of NO-releasing compounds sufficient to reduce inflammation within thirty minutes. 
     
     
         50 . The method of  claim 46 , wherein the inflammatory airway disease is chronic pulmonary disease. 
     
     
         51 . A method of treating inflammatory airway disease in a mammal's airway comprising:
 identifying a mammal exhibiting inflammatory airway disease;   determining the severity of the inflammatory airway disease in the mammal; and   administering through inhalation NO-releasing compounds using a distinct therapeutic profile corresponding to the severity of the inflammatory airway disease in the mammal, resulting in the reduction of inflammation.   
     
     
         52 . The method of  claim 51 , wherein the inflammatory airway disease is chronic pulmonary disease. 
     
     
         53 . The method of  claim 51 , wherein the NO-releasing compounds is selected from a group consisting of S-nitro s othiols, S-nitroso-N-acetylpenicillamine, S-nitroso-L-cysteine, NONOates, nitroprusside, NO-ferredoxin, NO-heme complex, and nitrosoguanidine. 
     
     
         54 . The method of  claim 51 , wherein the severity of the inflammatory airway disease is scored from 0 to 5, with 5 indicating a most severe condition. 
     
     
         55 . The method of  claim 51 , wherein the distinct therapeutic profile is selected from a pre-determined set of therapeutic profiles. 
     
     
         56 . The method of  claim 51 , wherein the mammal is a horse. 
     
     
         57 . The method of  claim 51 , wherein the therapeutically effective amount of NO-releasing compounds sufficient to reduce inflammation within thirty minutes.