title: Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune pulmonary alveolar proteinosis: effectiveness, safety, and lowest effective dose.
abstract: OBJECTIVE
  Granulocyte macrophage-colony-stimulating factor (GM-CSF) causes variable improvement in autoimmune pulmonary alveolar proteinosis (aPAP). Upon response to short-term treatment, patients are divided into responders and non-responders. The aim of this study was to test the hypothesis that long-term inhaled GM-CSF (iGM-CSF) is effective in all patients and that attainment of remission permits gradual de-escalation of the dose to the lowest effective safe dose.
  
  
  METHODS
  Patients were treated with iGM-CSF 250 μg once a day given 4 days on and 4 days off for as long as necessary (the "as far as it takes" protocol). Upon remission, defined as absence of symptoms, oxygen desaturation <4 % at the walking test, and significant radiographic reduction of the infiltrates, or at least two of the above, the iGM-CSF dose was de-escalated. In the case of relapse, the patient was repositioned at the previous effective dose. Patients were investigated at 6-month intervals. To detect hematopoietic effects, blood cell counts, CD34+ cells, granulocyte macrophage progenitor colony-forming-units, and burst-forming-unit erythroid were measured.
  
  
  RESULTS
  Six (five female) patients 43.8 ± 15.7 years of age were treated for 14-65 months and all responded to treatment. Remission was achieved after 25.6 ± 10 months. Three patients maintained remission at their lowest effective dose. Two patients relapsed at de-escalating doses. One patient remains on full-dose treatment. iGM-CSF had no impact on any of the hematological parameters tested.
  
  
  CONCLUSIONS
  In aPAP, long-term adherence to the dose schedule permitted remission in all patients. Long-term treatment with iGM-CSF also permitted the definition of lower effective doses, minimizing disease burden and treatment costs safely, since no stimulating activity on hematopoiesis was observed, a fact that is of paramount importance for those aPAP patients needing lifelong treatment.
authors.affiliation: 2nd Pulmonary Medicine Department, "Attikon" University Hospital, Athens Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, 12462, Haidari, Greece, papiris@otenet.gr.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Papiris
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsirigotis
authors.forename: Likurgos
authors.initials: L
authors.lastname: Kolilekas
authors.forename: Georgia
authors.initials: G
authors.lastname: Papadaki
authors.forename: Andriana I
authors.initials: AI
authors.lastname: Papaioannou
authors.forename: Christina
authors.initials: C
authors.lastname: Triantafillidou
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papaporfyriou
authors.forename: Anna
authors.initials: A
authors.lastname: Karakatsani
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kagouridis
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Effrosyni D
authors.initials: ED
authors.lastname: Manali
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000188:drug therapy*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011649:Pulmonary Alveolar Proteinosis / Q000175:diagnosis* / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor