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Original Research: Diffuse Lung Disease |

Duration of Benefit in Patients With Autoimmune Pulmonary Alveolar Proteinosis After Inhaled Granulocyte-Macrophage Colony-Stimulating Factor TherapyVital Capacity and Pulmonary Alveolar Proteinosis

Ryushi Tazawa, MD; Yoshikazu Inoue, MD; Toru Arai, MD; Toshinori Takada, MD; Yasunori Kasahara; Masayuki Hojo, MD; Shinya Ohkouchi, MD; Yoshiko Tsuchihashi, MD; Masanori Yokoba, MD; Ryosuke Eda, MD; Hideaki Nakayama, MD; Haruyuki Ishii, MD; Takahito Nei, MD; Konosuke Morimoto, MD; Yasuyuki Nasuhara, MD, FCCP; Masahito Ebina, MD; Masanori Akira, MD; Toshio Ichiwata, MD; Koichiro Tatsumi, MD, FCCP; Etsuro Yamaguchi, MD; Koh Nakata, MD
Author and Funding Information

From the Niigata University Medical and Dental Hospital (Drs Tazawa and Nakata), Niigata; the National Hospital Organization (NHO) Kinki-Chuo Chest Medical Center (Drs Inoue, Arai, and Akira), Osaka; the Niigata University Graduate School of Medical and Dental Sciences (Drs Takada and Nakayama), Niigata; the Department of Respirology (Drs Kasahara and Tatsumi), Graduate School of Medicine, Chiba University, Chiba; the Division of Respiratory Medicine (Dr Hojo), National Center for Global Health and Medicine, Tokyo; the Department of Respiratory Medicine (Drs Ohkouchi and Ebina), Tohoku University Medical School, Sendai; the Juzenkai Hospital (Dr Tsuchihashi), Nagasaki; the Institute of Tropical Medicine (Drs Tsuchihashi and Morimoto), Nagasaki University, Nagasaki; the Kitasato University School of Allied Health Sciences (Dr Yokoba), Kanagawa; the NHO Yamaguchi-Ube Medical Center (Dr Eda), Ube; the Kurashiki Municipal Kojima Hospital (Dr Eda), Kurashiki; the Department of Respiratory Medicine (Dr Nakayama), Tokyo Medical University, Tokyo; the Department of Respiratory Medicine (Dr Ishii), Kyorin University School of Medicine, Tokyo; the Department of Respiratory Medicine (Dr Nei), Nippon Medical University School of Medicine, Tokyo; the First Department of Medicine (Dr Nasuhara), Hokkaido University School of Medicine, Sapporo; the Department of Respiratory Medicine (Dr Ichiwata), Tokyo Medical University Hachioji Medical Center, Tokyo; and the Division of Respiratory Medicine and Allergology (Dr Yamaguchi), Department of Medicine, Aichi Medical University School of Medicine, Aichi, Japan.

Correspondence to: Koh Nakata, MD, Niigata University Medical & Dental Hospital, Bioscience Medical Research Center, 1-754 Asahimachi-dori, Chuo-ku Niigata, Niigata, Japan 951-8520; e-mail: radical@med.niigata-u.ac.jp


Funding/Support: This work was supported in part by grants from the Japanese Ministry of Education and Science, Ministry of Health, Labour, and Welfare of Japan [Grant H14-trans-014 to Dr Nakata, H21-Nanchi-Ippan-161 to Dr Inoue, and H24-Rinkensui-Ippan-003 to Dr Tazawa], Grant-in-Aid for Scientific Research [Category B 18406031 to Dr Inoue and Category C 22590852 to Dr Tazawa], and National Hospital Organization of Japan [Category Network to Dr Inoue].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(4):729-737. doi:10.1378/chest.13-0603
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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.

Trial registry:  ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp

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