Methods for the Treatment of Lung Diseases with Mast Cell Stabilizers

Abstract

Methods for the treatment of lung diseases with mast cell stabilizers are provided.

1 . A method of treating a patient having a lung disease or condition comprising administering to the patient a composition comprising a mast cell stabilizer with an inhalation device, wherein administration of the composition with the inhalation device produces a systemically effective amount of the mast cell stabilizer and a locally effective amount of the mast cell stabilizer to treat the lung disease or condition. 
     
     
         2 . The method of  claim 1 , wherein administration of the composition with the inhalation device produces in a human subject group an average AUC (0-∞)  of the mast cell stabilizer greater than about 120 ng*hr/mL and/or an average C max  of the mast cell stabilizer greater than about 55 ng/mL, and a deposited lung dose of the mast cell stabilizer greater than about 4 mg. 
     
     
         3 . The method of  claim 1 , wherein the mast cell stabilizer is selected from cromolyn sodium, cromolyn lysinate, ammonium cromoglycate, magnesium cromoglycate, dihydropyridines such as nicardipine and nifedipine, lodoxamide, nedocromil, barnidipine, YC-114, elgodipine, niguldipine, ketotifen, methylxanthines, and quercetin. 
     
     
         4 . The method of  claim 1 , wherein the composition is administered with a metered dose inhaler, nebulizer, soft mist inhaler, a high efficiency nebulizer, or ultrasonic nebulizer. 
     
     
         5 . The method of  claim 1 , wherein the composition is administered with a dry powder inhaler. 
     
     
         6 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition with the inhalation device produces in a human subject group an average AUC (0-∞)  of the cromolyn sodium greater than about 120 ng*hr/mL and an average C max  of the cromolyn sodium greater than about 55 ng/mL, and a deposited lung dose of the mast cell stabilizer greater than about 4 mg. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the composition comprises greater than about 2% cromolyn sodium. 
     
     
         10 . The method of  claim 9 , wherein the composition comprises about 4% to about 6% cromolyn sodium. 
     
     
         11 . The method of  claim 10 , wherein the composition comprises one or more of purified water, sodium chloride, mannitol, and sodium EDTA. 
     
     
         12 . The method of  claim 4 , wherein the composition has a fill volume of about 0.1 mL to about 5 mL. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 4 , wherein the composition comprises about 1 mg to about 120 mg of cromolyn sodium. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 4 , wherein the composition comprises about 40 mg of cromolyn sodium. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the inhalation device provides an RF (≦3.3 μm) of at least about 30% and/or an RF (≦5 μm) of at least about 65%. 
     
     
         24 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the inhalation device provides an RF (≦3.3 μm) of at least about 45% and/or an RF (≦5 μm) of at least about 75%. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition with the inhalation device produces in a human subject group an average AUC (0-∞)  of the cromolyn sodium greater than about 200 ng*hr/mL, and an average C max  of the cromolyn sodium greater than about 80 ng/mL, and a deposited lung dose of cromolyn sodium greater than about 4 mg. 
     
     
         32 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition with the inhalation device produces in a human subject group an average AUC (0-∞)  of the cromolyn sodium greater than about 330 ng*hr/mL, an average C max  of the cromolyn sodium greater than about 150 ng/mL, and a deposited lung dose of the cromolyn sodium greater than about 4 mg. 
     
     
         33 . The method of  claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition with the inhalation device produces in a human subject group an average AUC (0-∞)  of the cromolyn sodium greater than about 525 ng*hr/mL, and an average C max  of the cromolyn sodium greater than about 230 ng/mL, and a deposited lung dose of the cromolyn sodium greater than about 4 mg. 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 1 , wherein the lung disease or condition is selected from the group consisting of idiopathic pulmonary fibrosis, chronic idiopathic cough, pulmonary fibrosis, bronchopulmonary fibrosis, pulmonary artery hypertension, exercise-induced bronchoconstriction, hyperactive airway disorder, respiratory infections, respiratory syncytial virus infection, bronchiolitis obliterans, sarcoidosis, lung fibrosis, cystic fibrosis, chronic cough, steroid resistant pediatric asthma, bronchiectasis, radiation fibrosis, radiation pneumonitis, fibrosing mediastinitis, Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, neurofibromatosis type I, alpha-1 antitrypsin deficiency, elastin mutations, salla disease, familial pulmonary arterial hypertension, pulmonary alveolar proteinosis, pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, hereditary hemorrhagic telangiectasia, pulmonary alveolar microlithiasis, Kartagener syndrome, primary ciliary dyskinesia, central alveolar hypoventilation, narcolepsy, Marfan syndrome, Ehler-Danlos syndrome, ABCA3-related lung disease, SP-A-related lung disease, SP-B-related lung disease, SP-C-related lung disease, Hermansky-Pudlak syndrome, Gaucher disease, Neiman Pick C, Wegener's granulomatosis, Goodpasture syndrome, microscopic polyangiitis, polyarteritis nodosa, Churg-Strauss syndrome, cystic adenomatoid malformation, pulmonary sequestration, neuroendocrine cell hyperplasia, amyotrophic lateral sclerosis, myasthenia gravis, dermatomyositis, polymyositis, sarcoidosis, Langerhans cell histiocytosis, idiopathic pulmonary hemosiderosis, sickle cell anemia, lymphangiomatosis, and refractory chronic cough. 
     
     
         37 . The method of  claim 1 , wherein the lung disease or condition is chronic cough. 
     
     
         38 . The method of  claim 37 , wherein the chronic cough is refractory chronic cough. 
     
     
         39 . The method of  claim 1 , wherein the lung disease or condition is not chronic obstructive pulmonary disease, allergic asthma, non-allergic asthma, wheezing, epistaxis, laryngotracheobronchitis, bronchitis, diffuse bronchiolitis, bronchiolitis obliterans, bronchiectasis, alveolitis, community acquired pneumonia, hospital acquired pneumonia, ventilator associated pneumonia, healthcare associated pneumonia, aspiration pneumonia, lipid pneumonia, eosinophilic pneumonia, chemical pneumonia, atypic pneumonia, severe acute respiratory system disease, pulmonary infection, emphysema, sarcoidosis, tuberculosis, nontuberculous mycobacterial pulmonary diseases, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, interstitial lung disease, pertussis, or graft rejection after lung transplantation. 
     
     
         40 - 55 . (canceled) 
     
     
         56 . The method of  claim 5 , wherein the composition comprises about 1 mg to about 120 mg of cromolyn sodium. 
     
     
         57 . The method of  claim 5 , wherein the composition comprises about 40 mg of cromolyn sodium.