Airway Administration of Site-Inactived FVIIA in Inflammatory Conditions Affecting the Respiratory Tract
The present invention provides methods for the local treatment of acute and chronic extravascular pulmonary fibrin deposition and/or reducing unwanted effects associated with systemic administration of natural anticoagulants to a subject via airway administration to the subject by intratracheal, intrabronchial or intraalveolar routes of site-inactivated FVIIa or biologically active derivatives thereof.
1 . A method for treating or preventing extravascular fibrin deposition in the airways, in particular the alveolar or bronchoalveolar spaces, in a human subject comprising administering to the subject human site-inactivated FVIIa or a biologically active derivative thereof, via the airway by means of intratracheal, intrabronchial or intraalveolar administration.
2 . The method of claim 1 , wherein the fibrin deposition is caused by an inflammatory lung disease.
3 . The method of claim 2 , wherein the inflammatory lung disease is selected from the group consisting of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pneumonia, acute bronchoalveolar diseases, chronic bronchoalveolar diseases, fibrosing alveolitis and bronchial asthma.
4 . The method of claim 2 , wherein the inflammatory lung disease is related to a condition selected from the group consisting of direct or indirect pulmonary trauma, pancreatitis, aspiration pneumonitis, sepsis, severe sepsis and septic shock.
5 . The method of claim 1 , wherein the site-inactivated FVIIa is administered by bronchoalveolar lavage with a solution of the site-inactivated FVIIa.
6 . The method of claim 1 , wherein the site-inactivated FVIIa is administered by blind tracheal washing with a solution of the site-inactivated FVIIa.
7 . The method of claim 1 , wherein the site-inactivated FVIIa is administered by causing the inhalation of a nebulized solution of the site-inactivated FVIIa.
8 . The method of claim 1 , wherein the site-inactivated FVIIa is administered by causing the inhalation of the site-inactivated FVIIa in nebulized powder form.
9 . The method of claim 1 , wherein the site-inactivated FVIIa is administered by direct application of the site-inactivated FVIIa during bronchoscopy.
10 . The method of claim 1 wherein the human subject is an adult.
11 . The method of claim 1 wherein the human subject is a child.
12 . The method of claim 1 , wherein the site-inactivated FVIIa is administered in an amount of from 0.1 μg/kg to about 10 mg/kg body weight per day.
13 . The method of claim 1 further comprising administering to the human subject an anticoagulant systemically as an adjuvant therapy.
14 . The method of claim 13 wherein the human subject is an adult.
15 . The method of claim 13 wherein the human subject is a child.
16 . The method of claim 2 , wherein the inflammatory lung disease is acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).