Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis.

Abstract

BACKGROUND:

Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. It is plausible that inhaled GM-CSF improves the dysfunction of alveolar macrophages and promotes the clearance of the surfactant. However, effect of the therapy on components in bronchoalveolar lavage fluid (BALF) remains unclear.

OBJECTIVES:

To figure out changes in surfactant clearance during GM-CSF inhalation therapy.

METHODS:

We performed retrospective analyses of BALF obtained under a standardized protocol from the same bronchus in each of 19 aPAP patients before and after GM-CSF inhalation therapy (ISRCTN18931678, JMA-IIA00013; total dose 10.5-21 mg, duration 12-24 weeks). For evaluation, the participants were divided into two groups, high responders with improvement in alveolar-arterial oxygen difference ≥13 mmHg (n = 10) and low responders with that < 13 mmHg (n = 9).

RESULTS:

Counts of both total cells and alveolar macrophages in BALF did not increase during the therapy. However, total protein and surfactant protein-A (SP-A) were significantly decreased in high responders, but not in low responders, suggesting that clearance of surfactant materials is correlated with the efficacy of the therapy. Among 94 biomarkers screened in bronchoalveolar lavage fluid, we found that the concentration of interleukin-17 and cancer antigen-125 were significantly increased after GM-CSF inhalation treatment.

CONCLUSIONS:

GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleukin-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis.

• Authors: Kazumasa Ohashi, Atsuyasu Sato, Toshinori Takada, Toru Arai, Takahito Nei, Yasunori Kasahara, Natsuki Motoi, Masayuki Hojo, Shinya Urano, Haruyuki Ishii, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Yasuyuki Nasuhara, Yoshiko Tsuchihashi, Chinatsu Kaneko, Hiroko Kanazawa, Masahito Ebina, Etsuro Yamaguchi, Jacqueline Kirchner, Yoshikazu Inoue, Koh Nakata, Ryushi Tazawa
• Journal: Respiratory medicine (Respir Med) Vol. 106 Issue 2 Pg. 284-93 (Feb 2012) ISSN: 1532-3064 [Electronic] England
• PMID: 22112784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Autoantibodies
• Interleukin-17
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactants
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Administration, Inhalation
• Autoantibodies (immunology)
• Bronchoalveolar Lavage Fluid (immunology)
• Evidence-Based Medicine
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology, therapeutic use)
• Humans
• Immunohistochemistry
• Interleukin-17 (immunology)
• Lung (immunology, metabolism, pathology)
• Macrophages, Alveolar (drug effects)
• Male
• Middle Aged
• Pilot Projects
• Pulmonary Alveolar Proteinosis (drug therapy, immunology, metabolism, pathology)
• Pulmonary Surfactant-Associated Protein A (immunology, metabolism)
• Pulmonary Surfactants (immunology, metabolism)
• Respiratory Therapy (methods)
• Retrospective Studies
• Treatment Outcome