title: Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled granulocyte-macrophage colony-stimulating factor therapy.
abstract: BACKGROUND
  Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized.
  
  
  METHODS
  To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy.
  
  
  RESULTS
  During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, %VC) were higher among those who required additional treatment (P<.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high %VC group (%VC≥80.5) and the low %VC group was seen by a Kaplan-Meier analysis and a log-rank test (P<.0005).
  
  
  CONCLUSIONS
  These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline %VC might be a prognostic factor for disease recurrence.
  
  
  BACKGROUND
  ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp.
authors.affiliation: Niigata University Medical and Dental Hospital, Niigata.
authors.forename: Ryushi
authors.initials: R
authors.lastname: Tazawa
authors.affiliation: National Hospital Organization (NHO) Kinki-Chuo Chest Medical Center, Osaka.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: National Hospital Organization (NHO) Kinki-Chuo Chest Medical Center, Osaka.
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.affiliation: Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Takada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Division of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hojo
authors.affiliation: Department of Respiratory Medicine, Tohoku University Medical School, Sendai.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohkouchi
authors.affiliation: Juzenkai Hospital, Nagasaki; Institute of Tropical Medicine, Nagasaki University, Nagasaki.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tsuchihashi
authors.affiliation: Kitasato University School of Allied Health Sciences, Kanagawa.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yokoba
authors.affiliation: NHO Yamaguchi-Ube Medical Center, Ube; Kurashiki Municipal Kojima Hospital, Kurashiki.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Eda
authors.affiliation: Niigata University Graduate School of Medical and Dental Sciences, Niigata; Department of Respiratory Medicine, Tokyo Medical University, Tokyo.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Respiratory Medicine, Nippon Medical University School of Medicine, Tokyo.
authors.forename: Takahito
authors.initials: T
authors.lastname: Nei
authors.affiliation: Institute of Tropical Medicine, Nagasaki University, Nagasaki.
authors.forename: Konosuke
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, Sapporo.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nasuhara
authors.affiliation: Department of Respiratory Medicine, Tohoku University Medical School, Sendai.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.affiliation: National Hospital Organization (NHO) Kinki-Chuo Chest Medical Center, Osaka.
authors.forename: Masanori
authors.initials: M
authors.lastname: Akira
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical University Hachioji Medical Center, Tokyo.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ichiwata
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Division of Respiratory Medicine and Allergology, Department of Medicine, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Yamaguchi
authors.affiliation: Niigata University Medical and Dental Hospital, Niigata. Electronic address: radical@med.niigata-u.ac.jp.
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000188:drug therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011649:Pulmonary Alveolar Proteinosis / Q000188:drug therapy*; D012138:Respiratory Therapy; D013997:Time Factors
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor