Title Outcome of corticosteroid administration in autoimmunepulmonary 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. Conclusion: The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections. Background Pulmonary alveolar proteinosis (PAP) is a rare lung disease in which surfactant materials accumulate abnormally in the terminal bronchioli and alveoli [1, 2]. According to the etiology, PAP can be classified into three forms; hereditary, secondary, and autoimmune PAP [2]. Hereditary PAP are caused by some gene abnormality, for example, granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor α or β insufficiency, in which neither serum GM-CSF autoantibodies nor underlying diseases are confirmed [3–5]. Secondary PAP develops secondary to some underlying diseases that presumably impair surfactant clearance because of abnormal numbers and functions of alveolar macrophages [6]. In patients with autoimmune PAP (aPAP), comprising 90 % of all PAP cases, GM-CSF autoantibody (GMAb) is excessively produced [2, 7, 8]. GMAb interferes with GM-CSF signaling in alveolar macrophages, causing maturation arrest and dysfunction and thus impairing surfactant catabolism [9, 10]. Currently, the standard therapy for PAP is wholelung lavage [11–13]. Alternatively, since the mouse defective in GM-CSF production develops PAP, GM* Correspondence: radical@med.niigata-u.ac. jp Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata 951-8520, Japan Full list of author information is available at the end of the article © 2015 Akasaka et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Akasaka et al. BMC Pulmonary Medicine (2015) 15:88 DOI 10.1186/s12890-015-0085-0