Nontuberculous mycobacterium (NTM) disease has been reported in most developed countries with incidence rates ranging from 1.0 to 1.8 cases per 100,000 persons. Mycobacterium avium complex (MAC) organisms are the most common cause of NTM disease worldwide. These organisms are commonly found in soil and water, including both natural and treated water, as well as wild and domesticated animals. Humans are thought to acquire disease via exposure (e.g., aerosolization) to these sources. There is no evidence that NTM (MAC) is able to be transmitted from animal to human or from human to human. Lung disease is the most common clinical manifestation of NTM (MAC); however lymphatic, skin, and soft tissue, as well as disseminated disease occur. This chapter focuses on pulmonary disease in the non-HIV host.

M. avium complex includes the species M. avium and M. intracellulare. Traditional laboratory characteristics such as physical appearance and biochemical testing cannot distinguish between these species and generally speciation is not clinically relevant; however, DNA probes have been developed for identification and may be useful for epidemiologic study. M. avium is the species more often encountered among patients with disseminated disease, whereas M. intracellulare is more common in respiratory infections.

Patient-specific risk factors for NTM disease include those that predispose to disseminated disease and those that predispose to lung disease. The interactions between the organism, macrophages, and lymphocytes (particularly T helper cells and natural killer cells) are important to protect the host from mycobacterial disease. Detailed discussion of the immunologic response is beyond the scope of this brief chapter; however, interleukin (IL)-12, interferon-gamma (INF-γ), and tumor necrosis factor-alpha (TNF-α) are all important. An immunologic defect, either acquired through disease (HIV or genetic) or through receipt of immunosuppressing medications, which disrupts these pathways, may predispose to disseminated disease. Underlying structural disease predisposes to respiratory infection. This includes chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis, pneumoconiosis, and previous cavitary lung infection from tuberculosis. Additionally, it has been described that women with pulmonary MAC infections with bronchiectasis have a similar body type, sometimes including a thin build, scoliosis, pectus excavatum, and mitral valve prolapse.

IFN-γ and IL-12 protect the host from mycobacteria largely through upregulation of TNF-α and a relationship between the use of TNF-α blocking agents (such as infliximab, adalimumab, and etanercept) and development of active Mycobacterium tuberculosis has been realized among patients with a history of latent tuberculosis; however, the risk associated with receipt of these agents and NTM (MAC) infection is not known. Expert opinion suggests that patients with active NTM disease should receive TNF-α blocking agents only if they are also receiving adequate therapy for NTM.