BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF.
BACKGROUND
Idiopathic pulmonary alveolar proteinosis (PAP) has recently been recognised as a disease of impaired alveolar macrophage function caused by neutralising anti-granulocyte-macrophage colony-stimulating (anti-GM-CSF) autoantibodies. Subcutaneous recombinant human GM-CSF is a novel treatment for PAP, but its mechanism of action is unclear.


METHODS
Clinical, functional, and bronchoalveolar lavage (BAL) findings were prospectively evaluated in a patient with PAP treated with daily subcutaneous GM-CSF 8 microg/kg for 12 weeks.


RESULTS
Treatment resulted in improvements in dyspnoea, lung function, and peak cycle ergometry performance. In serum and BAL fluid the titre of anti-GM-CSF autoantibodies was raised at baseline and markedly reduced on treatment. At baseline the BAL fluid cellular profile showed a decrease in the absolute number and the percentage of macrophages (50%) and an increase in lymphocytes (45%), predominantly CD4+. This cellular distribution remained unchanged after 6 and 12 weeks of treatment while macrophages became morphologically normal and functionally improved. Extracellular proteinaceous material completely disappeared.


CONCLUSIONS
Clinically successful treatment of PAP with GM-CSF was associated with a profound reduction in GM-CSF neutralising autoantibodies, improvement in alveolar macrophage morphology and function, but persistent BAL lymphocytosis.
Schoch
O D
OD
Division of Pulmonary Medicine, University Hospital, Zurich, Switzerland.
Schanz
U
U
Koller
M
M
Nakata
K
K
Seymour
J F
JF
Russi
E W
EW
Boehler
A
A
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002448:Cell Adhesion / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D016676:Macrophages, Alveolar / Q000473:pathology; D011446:Prospective Studies; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology / Q000628:therapy*
D001323:Autoantibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor