TY - JOUR T1 - Inhaled Granulocyte-Macrophage Colony Stimulating Factor for <strong><em>Mycobacterium Abscessus</em></strong> in Cystic Fibrosis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02127-2017 SP - 1702127 AU - J.P. Scott AU - Yindou Ji AU - Mathur Kannan AU - Mark E. Wylam Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/01/18/13993003.02127-2017.abstract N2 - Nontuberculous mycobacteria (NTM) are an important emerging threat to cystic fibrosis (CF) patients. In North America where the incidence of NTM in CF patients is at least 11.8% Mycobacterium abscessus complex (MABSC), a multidrug-resistant NTM, accounts for about 35% [1] and are notoriously recognised as difficult to eradicate and seriously affect morbidity and mortality in CF [2] as well as lung transplantation outcomes [3, 4]. The mechanisms for the increased incidence of MABSC infection in CF patients are not known. The immune response in CF patients is directed to the Th2 response that is associated with poorer clinical outcome and accelerated decline in lung function. This Th2 pattern is associated with diminished IFNγ production and lesser activation of macrophages. One activator of macrophages is granulocyte macrophage-colony stimulating factor (GM-CSF) whose Toll-like receptor activation includes phagocytosis, bactericidal activity, oxidative burst, and cell adhesion in macrophages [5]. Two experimental findings support the plausibility that reduced GM-CSF-elicited macrophage activation may contribute to NTM and MABSC infection in CF. First, alveolar macrophages from in GM-CSF −/− mice exhibit defective phagocytosis, bacterial killing and reduced H2O2 production [6]. Second, though wild type mouse models of M. abscessus pulmonary infection show limited morbidity and are limited in their usefulness to study NTM therapy GM-CSF knockout models of M. abscessus infection mice either succumbed to the acute infection or the infection persists to a chronic stage in the absence of exogenous GM-CSF [7]. Previously, we [8] and others have reported the successful use of inhaled GM-CSF to treat autoimmune pulmonary alveolar proteinosis (PAP) and metastatic lung metastases [9] without toxicity. Herein, we treated two CF patients with M. abscessus who were experiencing a decline in pulmonary function and clinical stability.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Scott has nothing to disclose.Conflict of interest: Yindou JiConflict of interest: Dr. Kannan has nothing to disclose.Conflict of interest: Dr. Wylam has nothing to disclose.Conflict of interest: Dr. Yi has nothing to disclose. ER -