Use of aerosolized cyclosporine for prevention and treatment of pulmonary disease

Abstract

The present invention relates to methods and compositions for prevention of graft rejection in lung transplant recipients and for treatment of subjects with pulmonary disorders. Specifically, the methods and compositions of the invention provide a means for inhibiting immune response mediated inflammatory processes in the lungs. The method of the invention comprises the administration of aerosolized cyclosporine for prevention of acute and/or chronic refractory rejection in lung transplant patients. The invention further provides for the use of aerosolized cyclosporine to treat subjects having immunologically mediated inflammatory pulmonary disorders including, but not limited to, asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic bronchitis and allergic rhinitis. The present invention, by enabling a method for the use of aerosolized cyclosporine for inhibiting pulmonary inflammation leading to prevention of graft rejection and treatment of pulmonary disorders, provides a safer and less toxic treatment than those methods that utilize systemic administration of cyclosporine.

1 . A method for prevention of graft rejection in a lung transplant recipient comprising administering to the recipient an effective dose of aerosolized cyclosporine directly following transplantation in an amount sufficient to prevent graft rejection. 
     
     
         2 . The method of  claim 1  wherein the dose of cyclosporine is sufficient to achieve deposition levels ranging between 15 and 30 mg in the lung. 
     
     
         3 . The method of  claim 1  wherein the cyclosporine is co-administered with a second immunosuppressive agent. 
     
     
         4 . The method of  claim 1  wherein the cyclosporine is co-administered with a anti-inflammatory reagent. 
     
     
         5 . A method for ameliorating pulmonary inflammation in a subject comprising administering to the subject an amount of aerosolized cyclosporine effective to inhibit or ameliorate pulmonary inflammation. 
     
     
         6 . The method of  claim 5  wherein the pulmonary inflammation is associated with asthma, sarcoidosis, emphysema, cystic fibrosis, isiopathic pulmonary fibrosis, chronic bronchitis, or allergic rhinititis. 
     
     
         7 . The method of  claim 5  wherein the dose of cyclosporine is sufficient to achieve deposition levels ranging between 5 and 30 mg in the lung. 
     
     
         8 . A method for prevention of graft rejection in a non-lung transplant recipient comprising administering to the non-lung transplant recipient an effective dose of aerosolized cyclosporine in an amount sufficient to prevent graft rejection. 
     
     
         9 . The method of  claim 8  wherein the dose of cyclosporine is sufficient to achieve circulating levels ranging between 50-250 ng/ml. 
     
     
         10 . The method of  claim 8  wherein the cyclosporine is co-administered with a second immunosuppressive agent. 
     
     
         11 . A method for inhibiting the immune response associated with a T-cell mediated immune disorder in a subject comprising the administering to the subject an amount of cyclosporine effective to inhibit the immune response associated with the immune disorder. 
     
     
         12 . A composition comprising a suitable carrier and aerosolized cyclosporine in doses sufficient to reduce pulmonary inflammation in subjects having pulmonary disorders. 
     
     
         13 . The composition of  claim 12  wherein the aerosolized cyclosporine has a particle size of between 1 and 5 microns. 
     
     
         14 . The composition of  claim 12  wherein the dose is sufficient to achieve concentration levels of between 5-15 mg of cyclosporine in the lung. 
     
     
         15 . The composition of  claim 12  wherein the carrier is propylene glycol. 
     
     
         16 . A composition comprising aerosolized cyclosporine as a dry powder, having a particle size in the range between 1 and 5 microns. 
     
     
         17 . A composition comprising a suitable carrier and aerosolized cyclosporine in doses sufficient to prevent development of an immune response that would lead to graft rejection in a transplant recipient. 
     
     
         18 . The composition of  claim 17  wherein the cyclosporine has a particle size of between .1 and 2 microns.