Brian J Day1,2,3,4,5, Jie Huang1, Briana Q Barkes1, May Gillespie1, Li Li1,2, Lisa A Maier6,7,8. 1. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO, USA. 2. Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 3. Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4. Department of Environmental Occupational Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 5. Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 6. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO, USA. maierl@njhealth.org. 7. Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. maierl@njhealth.org. 8. Department of Environmental Occupational Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. maierl@njhealth.org.
Abstract
INTRODUCTION:Chronic beryllium disease (CBD) is characterized by accumulation of macrophages and beryllium-specific CD4+ T cells that proliferate and produce Th1 cytokines. 5-Amino salicylic acid (5-ASA) is currently used to treat inflammatory bowel disease and has both antioxidant and anti-inflammatory actions. We hypothesized that 5-ASA may be a beneficial therapeutic in CBD. METHODS:Seventeen CBD patients were randomized 3:1 to receive 5-ASA 500-mg capsules or placebo four times daily for 6 weeks orally. Primary study endpoints included changes in beryllium lymphocyte proliferation (BeLPT). Secondary endpoints included changes in bronchoalveolar lavage (BAL) fluid, cells, serum, and blood cell glutathione (GSH) levels, BAL cellTNF-α levels, lung function, and quality of life measures. RESULTS:5-ASA decreased BAL cell BeLPT by 20% within the 5-ASA treatment group. No significant changes were observed in serum, PBMCs, BALF, or BAL cell GSH levels in either the 5-ASA or placebo treatment group. 5-ASA treatment decreased ex vivo Be-stimulated BAL cellTNF-α levels within the 5-ASA group and when compared to placebo. Significant improvements were noted in quality of life measurements with 5-ASA treatment. CONCLUSIONS:5-ASA's ability to decrease BAL cell BeLPT and Be-stimulated BAL cellTNF-α levels suggests that 5-ASA may impact the beryllium-specific immune response in CBD. 5-ASA use in other non-infectious granulomatous lung diseases, such as sarcoidosis, may prove to be a useful alternative treatment to corticosteroids for those with mild to moderate disease.
RCT Entities:
INTRODUCTION: Chronic beryllium disease (CBD) is characterized by accumulation of macrophages and beryllium-specific CD4+ T cells that proliferate and produce Th1 cytokines. 5-Amino salicylic acid (5-ASA) is currently used to treat inflammatory bowel disease and has both antioxidant and anti-inflammatory actions. We hypothesized that 5-ASA may be a beneficial therapeutic in CBD. METHODS: Seventeen CBD patients were randomized 3:1 to receive 5-ASA 500-mg capsules or placebo four times daily for 6 weeks orally. Primary study endpoints included changes in beryllium lymphocyte proliferation (BeLPT). Secondary endpoints included changes in bronchoalveolar lavage (BAL) fluid, cells, serum, and blood cell glutathione (GSH) levels, BAL cell TNF-α levels, lung function, and quality of life measures. RESULTS:5-ASA decreased BAL cell BeLPT by 20% within the 5-ASA treatment group. No significant changes were observed in serum, PBMCs, BALF, or BAL cell GSH levels in either the 5-ASA or placebo treatment group. 5-ASA treatment decreased ex vivo Be-stimulated BAL cell TNF-α levels within the 5-ASA group and when compared to placebo. Significant improvements were noted in quality of life measurements with 5-ASA treatment. CONCLUSIONS:5-ASA's ability to decrease BAL cell BeLPT and Be-stimulated BAL cell TNF-α levels suggests that 5-ASA may impact the beryllium-specific immune response in CBD. 5-ASA use in other non-infectious granulomatous lung diseases, such as sarcoidosis, may prove to be a useful alternative treatment to corticosteroids for those with mild to moderate disease.
Authors: Haining Yang; Zeyana Rivera; Sandro Jube; Masaki Nasu; Pietro Bertino; Chandra Goparaju; Guido Franzoso; Michael T Lotze; Thomas Krausz; Harvey I Pass; Marco E Bianchi; Michele Carbone Journal: Proc Natl Acad Sci U S A Date: 2010-06-28 Impact factor: 11.205
Authors: Richard T Sawyer; Brian J Day; Valerie A Fadok; Marina Chiarappa-Zucca; Lisa A Maier; Andrew P Fontenot; Lori Silveira; Lee S Newman Journal: Am J Respir Cell Mol Biol Date: 2004-07-15 Impact factor: 6.914
Authors: S Marchand-Adam; A El Khatib; F Guillon; M W Brauner; C Lamberto; V Lepage; J-M Naccache; D Valeyre Journal: Eur Respir J Date: 2008-09 Impact factor: 16.671