PULMONARY HOST DEFENSES GET SMOKED: A CASE OF AN OPPORTUNISTIC NONTUBERCULOUS MYCOBACTERIAL INFECTION IN A HABITUAL MARIJUANA USER

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Harmful toxins such as acrolein and phenols are common to tobacco (TS) and marijuana smoke (MS). An important difference is that MS contains delta-9-tetrahydrocabinol (δ9THC). Leukocytes express cannabinoid receptors that bind with δ9THC, diminishing their immune function. MS has been linked to bullous lung disease and chronic bronchitis. MS injures the airway epithelium and impairs mucociliary clearance, which in turn can increase susceptibility to lower respiratory tract infections. Nontuberculous mycobacterial (NTM) infections typically affect older women with predisposing structural or genetic risk factors. An immunocompetent adult male, who was a chronic marijuana smoker with neurofibromatosis-1 (NF-1), treated with Selumetinib, a MEK-1/2 inhibitor, developed a pulmonary NTM infection. Marijuana’s effects on the lung and immune system provide a possible explanation in this case. To date, no opportunistic infections have been reported in similar subjects with NF-1 treated with Selumetinib. Pulmonary manifestations of NF-1 include emphysema, cysts, bullae, and ILD; while pulmonary neoplasms are rare, nervous system tumors tend to metastasize to the lung. CASE PRESENTATION: A 25 year-old white male with NF-1 complicated by plexiform neurofibromas, had been participating in a NIH treatment trial, NCT01362803, with Selumetinib, for 6 years; which was discontinued due to disease stability. An August 2017 CT incidentally showed a 3mm lung nodule with mediastinal lymphadenopathy. Follow up in March 2018 the nodule was 6mm. Workup for infections, endemic mycoses, and HIV were negative. By June 2018 the nodule had increased to 11mm and had cavitated. Electromagnetic navigation bronchoscopic biopsy demonstrated non-necrotizing granulomatous inflammation; and mycobacterium avium complex via DNA probe and culture. He was enrolled in NIH observational study, NCT00018044; and in October 2018 azithromycin, rifampin, and ethambutol were started. Despite 5 months of therapy the cavity enlarged and a satellite nodule formed. DISCUSSION: δ9THC binding to cannabinoid-type 2 receptors on alveolar macrophages (AM) and T-cells adversely affects immune function. Cannabinoids decrease AM phagocytic function, production of reactive oxygen species, and proinflammatory cytokines; the latter are needed for the upregulation of inducible nitric oxide (NO) synthase (iNOS). By decreasing iNOS gene expression, cannabinoids reduce NO production. NO serves as an effector molecule for AM and is important for their microbiocidal function. CONCLUSIONS: We hypothesize that marijuana’s immune-altering effects predisposed this patient to a NTM infection and delayed resolution. If current clinical trials prove effective, exogenous NO or IL-12, could provide important adjunctive therapies; and theoretically restore immune defects associated with MS. Reference #1: Tashkin DP. Effects of marijuana smoking on the lung. Ann Am Thorac Soc. 2013;10(3):239-47. Reference #2: Hoffmann D, Brunnemann KD, Gori GB, Wynder EL. On the Carcinogenicity of Marijuana Smoke. In: Runeckles VC, ed. Recent Advances in Phytochemistry. Springer US; 1975:63-81. Reference #3: Wu T-C, Tashkin DP, Djahed B, Rose JE. Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med. 1988;318(6):347-51. DISCLOSURES: No relevant relationships by Haydar Al-Eid, source=Web Response No relevant relationships by Thomas Carbone, source=Web Response No relevant relationships by Joseph Fontana, source=Web Response No relevant relationships by Andrea Gross, source=Web Response Grant recipient relationship with AIT Therapeutics Please note: $20001 - $100000 Added 03/15/2019 by Kenneth Olivier, source=Web Response, value=Grant/Research Support Grant recipient relationship with Matinas Biopharma Please note: $5001 - $20000 Added 03/15/2019 by Kenneth Olivier, source=Web Response, value=Grant/Research Support no disclosure on file for Bridgette Widemann