title: 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.
  
  
  OBJECTIVE
  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: Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata 951-8520, Japan.
authors: Kazumasa
authors: K
authors: Ohashi
authors: Atsuyasu
authors: A
authors: Sato
authors: Toshinori
authors: T
authors: Takada
authors: Toru
authors: T
authors: Arai
authors: Takahito
authors: T
authors: Nei
authors: Yasunori
authors: Y
authors: Kasahara
authors: Natsuki
authors: N
authors: Motoi
authors: Masayuki
authors: M
authors: Hojo
authors: Shinya
authors: S
authors: Urano
authors: Haruyuki
authors: H
authors: Ishii
authors: Masanori
authors: M
authors: Yokoba
authors: Ryosuke
authors: R
authors: Eda
authors: Hideaki
authors: H
authors: Nakayama
authors: Yasuyuki
authors: Y
authors: Nasuhara
authors: Yoshiko
authors: Y
authors: Tsuchihashi
authors: Chinatsu
authors: C
authors: Kaneko
authors: Hiroko
authors: H
authors: Kanazawa
authors: Masahito
authors: M
authors: Ebina
authors: Etsuro
authors: E
authors: Yamaguchi
authors: Jacqueline
authors: J
authors: Kirchner
authors: Yoshikazu
authors: Y
authors: Inoue
authors: Koh
authors: K
authors: Nakata
authors: Ryushi
authors: R
authors: Tazawa
mesh_terms: D000280:Administration, Inhalation; D001323:Autoantibodies / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D019317:Evidence-Based Medicine; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011649:Pulmonary Alveolar Proteinosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000276:immunology / Q000378:metabolism*; D012138:Respiratory Therapy / Q000379:methods; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants; D016178:Granulocyte-Macrophage Colony-Stimulating Factor