Surfactant protein D for the treatment of disorders associated with lung injury
Surfactant protein D (SP-D) is a member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. Described herein are methods and compositions for the treatment of disorders associated with lung injury, including methods and compositions for the treatment of bronchopulmonary disorder (BPD).
1. A method of treating a subject having a pulmonary disorder selected from the group consisting of a pulmonary injury resulting from mechanical ventilation, neonatal respiratory distress syndrome, a pulmonary injury resulting from administration of oxygen, and a bronchopulmonary dysplasia, comprising administering an effective amount of a surfactant in combination with an effective amount of surfactant protein D (SP-D) to the subject, wherein the effective amount of the surfactant is less than the effective amount of the surfactant in the absence of the SP-D, and is sufficient to treat the pulmonary disorder.
2. The method of claim 1 , wherein the pulmonary disorder is a pulmonary injury resulting from administration of oxygen.
3. The method of claim 1 , wherein the pulmonary disorder is a pulmonary injury resulting from mechanical ventilation.
4. The method of claim 1 , wherein the amount of the SP-D) is sufficient to reduce the activity of an endogenous surfactant inhibitor in a lung of the subject.
5. The method of claim 4 , wherein the endogenous surfactant inhibitor comprises a plasma protein.
6. The method of claim 1 , wherein the amount of the SP-D is sufficient to reduce the activity of an endogenous surfactant inhibitor on the surface tension lowering properties of the surfactant in a lung of the subject.
7. The method of claim 1 , wherein the amount of the SP-D is sufficient to reduce the surface tension lowering properties of the surfactant in a lung of the subject by about 4-fold compared to the surface tension lowering properties of the surfactant in the presence of an endogenous surfactant inhibitor in a lung of the subject and in the absence of the SP-D.
8. The method of claim 1 , wherein the SP-D is recombinant human SP-D or a functional fragment thereof.
9. The method of claim 1 , wherein the surfactant and SP-D) are administered in a single pharmaceutical composition.
10. The method of claim 9 , wherein the pharmaceutical composition comprises about 2% SP-D.
11. The method of claim 9 , wherein the pharmaceutical composition comprises a phospholipid selected from the group consisting of dipalmitoylphosphatidylcholine, phosphatidylglycerol, and phosphatidylinositol.
12. The method of claim 9 , wherein the surfactant and SP-D are administered in an aerosolized form.
13. The method of claim 9 , wherein the surfactant and SP-D are administered in a dry powder form.
14. The method of claim 1 , wherein the dose of the SP-D is about 0.1 mg/kg to about 10 mg/kg body weight of the subject.
15. The method of claim 1 , wherein the dose of the SP-D is about 2 mg/kg body weight of the subject.
16. The method of claim 1 , wherein the surfactant is an animal product.
17. The method of claim 1 , wherein the surfactant is bovine surfactant.
18. The method of claim 1 , wherein the surfactant is synthetic surfactant.
19. The method of claim 1 , wherein the subject is a neonate.
20. The method of claim 1 , wherein the subject is a preterm neonate.