Claims for Patent: 5,485,827

Summary for Patent: 5,485,827

Title:	Methods and devices for treating plumonary vasoconstriction and asthma
Abstract:	A method for treating or preventing bronchoconstriction or reversible pulmonary vasoconstriction in a mammal, which method includes causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide or a therapeutically-effective amount of a nitric oxide-releasing compound, and an inhaler device containing nitric oxide gas and/or a nitric oxide-releasing compound.
Inventor(s):	Zapol; Warren M. (Concord, MA), Frostell; Claes (Danderyd, SE)
Assignee:	The General Hospital Corporation (Boston, MA)
Application Number:	08/384,792
Patent Claims:	1. A method for treating or preventing reversible pulmonary vasoconstriction in a mammal, which method comprises providing gaseous nitric oxide (NO) mixed, immediately prior to inhalation, with an oxygen-containing gas to form a gas mixture containing a therapeutically effective concentration of NO; and causing a mammal in need of such treatment or prevention to inhale a therapeutically effective amount of said NO-containing gas mixture. 2. The method of claim 1, wherein said pulmonary vasoconstriction is acute pulmonary vasoconstriction. 3. The method of claim 1 wherein said mammal has or is at risk of developing a clinical condition selected from the group consisting of pneumonia, traumatic injury, aspiration or inhalation injury, fat embolism in the lung, acidosis, inflammation of the lung, adult respiratory distress syndrome, acute mountain sickness, post cardiac surgery acute pulmonary hypertension, persistent pulmonary hypertension of the newborn, perinatal aspiration syndrome, hyaline membrane disease, acute pulmonary thromboembolism, acute pulmonary edema, heparin-protamine reactions, sepsis, hypoxia, asthma, and status asthmaticus. 4. The method of claim 1, wherein said pulmonary vasoconstriction is chronic pulmonary vasoconstriction which has a reversible component. 5. The method of claim 1, wherein said mammal has or is at risk of developing a clinical condition selected from the group consisting of chronic pulmonary hypertension, bronchopulmonary dysplasia, chronic pulmonary thromboembolism, idiopathic pulmonary hypertension, and chronic hypoxia. 6. The method of claim 1, wherein the concentration of NO in said NO-containing gas mixture is within a predetermined concentration range, and said NO-containing gas mixture is inhaled for at least three minutes. 7. The method of claim 1 wherein said concentration is at least 5 ppm. 8. The method of claim 7 wherein said concentration is 180 ppm or less. 9. The method of claim 1 wherein said concentration is at least 40 ppm. 10. The method of claim 1, wherein said concentration is at least 80 ppm. 11. The method of claim 1, wherein said NO-containing gas mixture comprises nitric oxide, oxygen, and nitrogen gases. 12. The method of claim 11, wherein said No-containing gas mixture comprises between 20-99% oxygen gas by volume. 13. The method of claim 1, wherein said mammal is a human. 14. The method of claim 1, wherein said NO-containing gas mixture is inhaled in the absence of tobacco smoke. 15. A method for diagnosing the reversibility of chronic pulmonary vasoconstriction in a mammal, which method comprises (a) measuring said mammal's PAP, (b) providing gaseous NO mixed, immediately prior to inhalation, with an oxygen-containing gas to form an NO-containing gas mixture; (c) causing said mammal to inhale said NO-containing gas mixture for a period of time, and (d) measuring said mammal's PAP during said period. 16. A method for treating or preventing bronchoconstriction in a mammal, which method comprises providing gaseous NO mixed, immediately prior to inhalation, with an oxygen-containing gas to form a gas mixture containing a therapeutically-effective concentration of NO, and causing a mammal in need of such treatment or prevention to inhale a therapeutically effective amount of said NO-containing gas mixture. 17. The method of claim 16, wherein said mammal is a human. 18. The method of claim 16, wherein said NO-containing gas mixture is inhaled in the absence of tobacco smoke. 19. The method of claim 16, comprising the additional step of, following said inhalation of said NO-containing gas mixture, causing said mammal to inhale a therapeutically-effective dose of a bronchodilator compound in liquid or solid form. 20. The method of claim 19, wherein said bronchodilator compound is inhaled with a gas mixture comprising nitric oxide. 21. The method of claim 19, wherein said bronchodilator compound is a nitric oxide-releasing compound. 22. The method of claim 21, wherein said bronchodilator compound is S-nitroso-N-acetylpenicillamine, S-nitrosocysteine, nitroprusside, nitrosoguanidine, glyceryl trinitrate, isoamyl nitrite, inorganic nitrite, azide, or hydroxylamine. 23. The method of claim 19, wherein said bronchodilator compound is an anticholinergic agent, a .beta..sub.2 agonist, a methyl xanthine, a calcium-channel shocker, a glucocorticoid drug, or cromolyn sodium. 24. The method of claim 16, wherein said bronchoconstriction is associated with asthma. 25. A method of improving gas exchange in the lungs of a mammal, said method comprising providing gaseous NO mixed, immediately prior to inhalation, with an oxygen-containing gas to form a gas mixture containing a therapeutically-effective concentration of NO, and causing said mammal to inhale said NO containing gas mixture. 26. The method of claim 25, wherein said mammal is hypoxic. 27. The method of claim 26, wherein said mammal is a human suffering from a lung injury. 28. The method claim 25, wherein said inhalation is accomplished in the absence of tobacco smoke. 29. The method of claim 25, wherein said NO-containing gas mixture comprises at least 1 ppm NO in air, O.sub.2, or an air/O.sub.2 mixture. 30. An inhaler device comprising a housing defining (a) a chamber containing an inhalable pharmaceutically-active agent and (b) a lumen in communication with said chamber; and a vessel containing pressurized gas comprising at least 1 ppm nitric oxide, said vessel having a mechanism for controllably releasing said gas into said chamber, thereby suspending said agent in said released gas; said lumen being configured to route said released gas into the respiratory system of a patient. 31. The device of claim 30, wherein said pharmaceutically-active agent comprises a bronchodilator compound in liquid or solid form. 32. The device of claim 31, wherein said compound comprises an anticholinergic agent, a .beta..sub.2 agonist, a methylxanthine, a calcium-channel blocker, a glucocorticoid drug, or cromolyn sodium. 33. The device of claim 30, wherein said pharmaceutically-active agent comprises a nitric oxide-releasing compound. 34. The device of claim 33, wherein said compound is selected from the group consisting of S-nitroso-N-acetylpenicillamine, S-nitrosocysteine, nitroprusside, nitrosoguanidine, glyceryl trinitrate, isoamyl nitrite, inorganic nitrite, azide, and hydroxylamine. 35. The device of claim 30, wherein said pharmaceutically-active agent comprises an antimicrobial agent. 36. The device of claim 35, wherein said antimicrobial agent comprises an antibiotic. 37. The device of claim 35, wherein said antimicrobial agent comprises pentamidine. 38. The device of claim 30, wherein said pharmaceutically-active agent comprises a surfactant suitable for the treatment of hyaline membrane disease. 39. The device of claim 30, wherein said vessel also has a mechanism for controllably releasing said gas into said lumen, in a manner that bypasses said chamber.