Interferon gamma (IFN?) pathway deficiency and severe NTM disease

Abstract

<b>Background:</b> Non-TB mycobacterium (NTM) infections are increasing in both the UK and Europe. Prevalence in the UK is 6.38/100000, and Mycobacterium avium (MAI) is the commonest species. <b>Aims:</b> To evaluate the characteristics of NTM patients, especially those with severe disease, in a NHS District General Hospital (DGH). <b>Method:</b> A retrospective cohort study, using electronic medical records to study predetermined domains. Inclusion criteria = aged over 18, managed by our services between 2016-2019. <b>Results:</b> We identified 61 patients with a coded diagnosis of NTM; 57 of these were included. Severe NTM disease was classified as B/L pulmonary disease, multiple organ involvement or multiple sites of extra pulmonary disease. The commonest causative organism was MAI (50.9%), followed by M. chimaera (14%). NTM lesions were predominantly reported in the upper lobes. 19.3% patients had prior immunodeficiency; 3 patients were classified as having severe disease. The three patients with severe disease had conditions adversely affecting IFNγ pathway such as Anti-IFNγ antibodies, Chemotherapy and DMARD-induced impaired production of IFNγ. 66.6% (n=38) of patients had pre-existing lung disease. 40.4% of our cohort were taking inhaled corticosteroids prior to diagnosis (n=23); Fluticasone was the commonest. <b>Conclusion/Analysis:</b> IFNγ pathway deficiency related immunosuppression predisposed patients to severe NTM disease, increased chances of requiring IV aminoglycosides as well as prolonged treatment (&gt; 3 years). The prevalence of M. chimaera in our population was higher than expected – 14% (n=8) compared to 6% reported average. An association between NTM and Fluticasone has previously been documented, reflected in our population.