Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis

Am J Respir Crit Care Med. 2001 Feb;163(2):524-31. doi: 10.1164/ajrccm.163.2.2003146.


Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM-CSF in patients with idiopathic AP. Fourteen patients received 5 microg/kg/d GM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]DO2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 microg/kg/d GM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 microg/kg/d GM- CSF, and one of four patients responded after dose escalation (20 microg/kg/d). The overall response rate was 43% (mean improvement in [A-a]DO2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM- CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Exercise Test / drug effects
  • Female
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Alveolar Proteinosis / diagnosis
  • Pulmonary Alveolar Proteinosis / drug therapy*
  • Pulmonary Diffusing Capacity / drug effects
  • Recombinant Proteins
  • Recurrence
  • Retreatment
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor