Respiratory distress syndrome (RDS), also termed hyaline membrane disease, is the leading cause of death and disability among premature infants. Of the 230,000 to 250,000 infants born prematurely each year in the United States, 40,000 to 50,000 develop RDS; and of those who develop this disease, 5,000 to 8,000 die. See generally R. Perelman and P. Farrell, Pediatrics 70, 570 (1982); D. Vidyasagar, in Hyaline Membrane Disease: Pathogenesis and Pathophysiology, 98 (L. Stern Ed. 1984). In addition, RDS can occur in children, adolescents, and adults as a result of trauma or other injury to the lungs. 150,000 cases of adult respiratory distress syndrome (ARDS) are reported annually, with 60-80% mortality. See American Lung Program, Respiratory Diseases, Task Force Report on Problems, Research Approaches, and Needs, National Heart and Lung Institute, DHEW Publn. (NIH) 73-432: 165-80 (1972).
RDS is caused by a primary deficiency in lung surfactant, a material ordinarily secreted onto the surface of lung alveoli. ARDS consists of a secondary deficiency in lung surfactant due to surfactant inhibition and/or decreased secretion. In the absence of surfactant, the alveoli tend to collapse during exhalation. Collapse can be avoided by mechanically ventilating the lungs. A problem with mechanical ventilation, however, is that it can cause damage to the lungs because of high oxygen concentrations and positive pressures.
A number of groups have sought to develop surfactant formulations which can be used to treat or prevent RDS and ARDS. Both human and bovine natural surfactants have been administered into the airways of human subjects. See, e.g., J. Horbar et al., N. Eng. J. Med. 320, 959 (1989); R. Soll et al., Pediatric Res. 23, 425A (1988). Problems with such natural surfactants are, however, potential contamination with microorganisms and potential sensitization of the patient to proteins therein. Accordingly, completely synthetic surfactants have been developed. See, e.g., U.S. Pat. No. 4,826,821 to Clements; U.S. Pat. No. 4,312,860 to Clements.
While the development of surfactant formulations have provided an alternative to mechanical ventilation alone, clinicians are now faced with the difficult problem of how to quickly and efficaciously administer these formulations to the lungs of patients. U.S. Pat. No. 4,832,012 to Raabe and Lee discloses a nebulizing apparatus which may be used to deliver drug-containing liquids to the lungs of patients in the form of an aerosol. It is suggested that the liquid can be heated or cooled prior to nebulization (column 4, lines 47-48). Raabe and Lee do not address the problems involved in administering surfactant formulations to the lungs of a patient. Such formulations are dispersions of lipids in an aqueous carrier solution, rather than single phase solutions.
In view of the foregoing, an object of the present invention is to provide a means for administering surfactant formulations to the lungs of patients in the form of an aerosol.