Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study.
BACKGROUND
Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections.


METHODS
For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications.


RESULTS
DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (>18.9 mg/day, n = 16) than treated with low-dose prednisolone (≤18.9 mg/day, n = 15) divided by median daily dose (p < 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p < 0.05). Median serum granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study.


CONCLUSIONS
The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections.
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan. k-akasaka@med.niigata-u.ac.jp.|Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan. k-akasaka@med.niigata-u.ac.jp.
Keiichi
K
Akasaka
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan. belltatnk@gmail.com.
Takahiro
T
Tanaka
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan. nktmr@m12.alpha-net.ne.jp.
Nobutaka
N
Kitamura
Department of Respiratory Medicine, Tohoku University Graduate school of Medicine, Miyagi, Japan. ohkouchi@rm.med.tohoku.ac.jp.
Shinya
S
Ohkouchi
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan. ryushi@med.niigata-u.ac.jp.
Ryushi
R
Tazawa
Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan. ttakada@med.niigata-u.ac.jp.
Toshinori
T
Takada
Department of Pulmonary Medicine, Tokyo Medical School, Tokyo, Japan. ichiwata@tokyo-med.ac.jp.
Toshio
T
Ichiwata
Department of Respiratory and Allergy Medicine, Aichi Medical School, Aichi, Japan. etsuro@aichi-med-u.ac.jp.
Etsuro
E
Yamaguchi
Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan. mhirose@kch.hosp.go.jp.
Masaki
M
Hirose
Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan. to-arai@kch.hosp.go.jp.
Toru
T
Arai
Department of Respiratory Medicine, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan. nakanokentaro@me.com.
Kentaro
K
Nakano
Department of Respiratory Medicine, Nippon Medical University of Medicine, Tokyo, Japan. kneigh@nms.ac.jp.
Takahito
T
Nei
Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan. h141@ks.kyorin-u.ac.jp.
Haruyuki
H
Ishii
Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan. hanta@kuhp.kyoto-u.ac.jp.
Tomohiro
T
Handa
Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan. giichi@kch.hosp.go.jp.
Yoshikazu
Y
Inoue
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata, 951-8520, Japan. radical@med.niigata-u.ac.jp.
Koh
K
Nakata
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage*; D011649:Pulmonary Alveolar Proteinosis / Q000188:drug therapy* / Q000276:immunology; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D001323:Autoantibodies; D005938:Glucocorticoids; D011239:Prednisolone