title: Inhaled Sargramostim Induces Resolution of Pulmonary Alveolar Proteinosis in Lysinuric Protein Intolerance.
abstract: Pulmonary alveolar proteinosis (PAP) is a potentially fatal complication of lysinuric protein intolerance (LPI), an inherited disorder of cationic amino acid transport. The patients often present with mild respiratory symptoms, which may rapidly progress to acute respiratory failure responding poorly to conventional treatment with steroids and bronchoalveolar lavations (BALs). The pathogenesis of PAP in LPI is still largely unclear. In previous studies, we have shown disturbances in the function and activity of alveolar macrophages of these patients, suggesting that increasing the activity and the number of macrophages by recombinant human GM-CSF (rhuGM-CSF) might be beneficial in this patient group.Two LPI patients with complicated PAP were treated with experimental inhaled rhuGM-CSF (sargramostim) after poor response to maximal conventional therapy. BAL fluid and cell samples from one patient were studied with light microscopy and transmission electron microscopy.Excellent response to therapy was observed in patient 1 with no compliance problems or side effects. Macrophages with myelin figure-like structures were seen in her BAL sample. Slight improvement of the pulmonary function was evident also in patient 2, but the role of sargramostim could not be properly evaluated due to the complicated clinical situation.In conclusion, inhaled rhuGM-CSF might be of benefit in patients with LPI-associated PAP.
authors: Department of Clinical Genetics, Turku University Hospital, PL 52, 20521, Turku, Finland. lamaer@utu.fi.|Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland. lamaer@utu.fi.
authors: Laura M
authors: LM
authors: Tanner
authors: Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
authors: Johanna
authors: J
authors: Kurko
authors: Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.|Functional Foods Forum, University of Turku, Turku, Finland.
authors: Maaria
authors: M
authors: Tringham
authors: Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland.
authors: Heikki
authors: H
authors: Aho
authors: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland.
authors: Juha
authors: J
authors: Mykkänen
authors: Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland.
authors: Kirsti
authors: K
authors: Näntö-Salonen
authors: Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland.
authors: Harri
authors: H
authors: Niinikoski
authors: Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland.
authors: Heikki
authors: H
authors: Lukkarinen
keywords: Lysinuric protein intolerance; aminoaciduria; granulocyte-macrophage colony-stimulating factor; pulmonary alveolar proteinosis; sargramostim