Inhalation of nitric oxide for treating respiratory diseases

Abstract

A method of treating a human subject which is effected by intermittent inhalation of gaseous nitric oxide at a concentration of at least 160 ppm is disclosed. The method can be utilized for treating a human subject suffering from, or prone to suffer from, a disease or disorder that is manifested in the respiratory tract, or from a disease or disorder that can be treated via the respiratory tract. The disclosed method can be effected while monitoring one or more of on-site and off-site parameters such as vital signs, methemoglobin levels, pulmonary function parameters, blood chemistry and hematological parameters, blood coagulation parameters, inflammatory marker levels, liver and kidney function parameters and vascular endothelial activation parameters, such that no substantial deviation from a baseline in seen in one or more of the monitored parameters.

What is claimed is: 
     
         1 . A method of treating a human subject prone to suffer from a disease or disorder that is manifested in the respiratory tract or a disease or disorder that can be treated via the respiratory tract, the method comprising subjecting the subject to intermittent inhalation of gNO at a concentration of at least 160 ppm, thereby treating or preventing the disease or disorder. 
     
     
         2 . The method of  claim 1 , wherein said human subject is selected from the group consisting of an immune-compromised subject human, a subject suffering from chronic asthma, a subject suffering from chronic sinusitis, a subject exposed to an infectious respiratory tract disease or disorder and a subject exposed to a pathogen. 
     
     
         3 . The method of  claim 2 , wherein said immune-compromised human subject is selected from the group consisting of a subject suffering from HIV, a subject suffering from cancer, a subject undergoing or which underwent chemotherapy, and a subject undergoing or which underwent transplantation. 
     
     
         4 . The method of  claim 1 , further comprising monitoring, during and following said subjecting, at least one on-site parameter selected from the group consisting of:
 a methemoglobin level (SpMet);   an oxygen saturation level (SpO 2 );   an end tidal CO 2  level (ETCO 2 ); and   a fraction of inspired oxygen level (FiO 2 ),   and/or at least one off-site parameter selected from the group consisting of:   a serum nitrite level (NO 2   − ); and   an inflammatory cytokine plasma level,   in the subject.   
     
     
         5 . The method of  claim 4 , comprising monitoring at least two of said parameters. 
     
     
         6 . The method of  claim 4 , comprising monitoring all of said parameters. 
     
     
         7 . The method of  claim 4 , wherein a change in said at least one of said parameters following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         8 . The method of  claim 5 , wherein a change in at least two of said parameters following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         9 . The method of  claim 6 , wherein a change in all of said parameters following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         10 . The method of  claim 4 , wherein a change in at least one of said on-site parameters following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         11 . The method of  claim 4 , wherein a change in at least one of said off-site parameters following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         12 . The method of  claim 1 , further comprising monitoring urine nitrite level in the subject. 
     
     
         13 . The method of  claim 12 , wherein a change in said urine nitrite level following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         14 . The method of  claim 4 , further comprising monitoring urine nitrite level in the subject. 
     
     
         15 . The method of  claim 14 , wherein a change in said urine nitrite level following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         16 . The method of  claim 1 , further comprising monitoring in the subject at least one off-site parameter selected from the group consisting of:
 a hematological marker;   a vascular endothelial activation factor;   a coagulation parameter;   a serum creatinine level; and   a liver function marker, in the subject.   
     
     
         17 . The method of  claim 16 , wherein a change in at least one of said off-site parameters following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         18 . The method of  claim 4 , further comprising monitoring at least one off-site parameter selected from the group consisting of:
 a hematological marker;   a vascular endothelial activation factor;   a coagulation parameter;   a serum creatinine level; and   a liver function marker, in the subject.   
     
     
         19 . The method of  claim 18 , wherein a change in said at least one parameter following said subjecting is less than 2 acceptable deviation units from a baseline. 
     
     
         20 . The method of  claim 1 , further comprising monitoring in the subject at least one on-site parameter selected from the group consisting of:
 a vital sign; and   a pulmonary function.   
     
     
         21 . The method of  claim 20 , wherein no deterioration is observed in said at least one parameter during and following said subjecting. 
     
     
         22 . The method of  claim 4 , further comprising monitoring in the subject at least one on-site parameter selected from the group consisting of:
 a vital sign; and   a pulmonary function.   
     
     
         23 . The method of  claim 22 , wherein no deterioration is observed in at said at least one parameter during and following said subjecting. 
     
     
         24 . The method of  claim 1 , wherein said intermittent inhalation comprises at least one cycle of continuous inhalation of said gNO for a first time period, followed by inhalation of no gNO for a second time period. 
     
     
         25 . The method of  claim 24 , wherein said first time period is about 30 minutes. 
     
     
         26 . The method of  claim 24 , wherein said second time period ranges from 3 to 5 hours. 
     
     
         27 . The method of  claim 24 , wherein said inhalation comprises from 1 to 6 of said cycles per day. 
     
     
         28 . The method of  claim 27 , wherein said inhalation comprises 5 of said cycles per day. 
     
     
         29 . The method of  claim 24 , wherein during said first time period, said concentration of gNO in said mixture deviates from said concentration of at least 160 ppm by less than 10%. 
     
     
         30 . The method of  claim 24 , wherein during said first time period, a concentration of NO 2  in said mixture is less than 5 ppm. 
     
     
         31 . The method of  claim 24 , wherein during said first time period, a concentration of O 2  in said mixture ranges from 20% to 25%. 
     
     
         32 . The method of  claim 24 , wherein during said first time period, a fraction of inspired oxygen level (FiO 2 ) in said mixture ranges from 21% to 100%. 
     
     
         33 . The method of  claim 4 , wherein said at least one parameter comprises ETCO 2  and during and following said subjecting, said ETCO 2  is less than 60 mmHg. 
     
     
         34 . The method of  claim 4 , wherein said at least one parameter comprises SpMet and during and following said subjecting, said SpMet is increased by less than 5%. 
     
     
         35 . The method of  claim 4 , wherein said at least one parameter comprises SpO 2  and during said subjecting, a level of said SpO 2  is higher than 89%. 
     
     
         36 . The method of  claim 4 , wherein said at least one parameter comprises serum nitrite/nitrate level and during and following said subjecting, a level of said serum nitrite is less than 2.5/25 micromole per liter respectively. 
     
     
         37 . The method of  claim 1 , wherein said intermittent inhalation of gNO is effected during a time period that ranges from 1 to 7 days.