Document Detail


Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis.
MedLine Citation:
PMID:  11179134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J F Seymour; J J Presneill; O D Schoch; G H Downie; P E Moore; I R Doyle; J M Vincent; K Nakata; T Kitamura; D Langton; M C Pain; A R Dunn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  163     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  524-31     Citation Subset:  AIM; IM    
Affiliation:
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Parkville, Australia. jseymour@petermac.unimelb.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Dose-Response Relationship, Drug
Drug Administration Schedule
Exercise Test / drug effects
Female
Follow-Up Studies
Granulocyte Macrophage Colony-Stimulating Factors, Recombinant / administration & dosage*,  adverse effects
Humans
Male
Middle Aged
Pulmonary Alveolar Proteinosis / diagnosis,  drug therapy*
Pulmonary Diffusing Capacity / drug effects
Recurrence
Retreatment
Tomography, X-Ray Computed
Treatment Outcome
Chemical
Reg. No./Substance:
0/Granulocyte Macrophage Colony-Stimulating Factors, Recombinant

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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